interacciones entre lípidos poliinsaturados nutricionales...
TRANSCRIPT
Interacciones entre liacutepidos poliinsaturados nutricionales
(PUFAs) urolitiasis inflamaciograven crogravenica de bajo grado y riesgo de
tumores de vigraveas urinaria
Aldo R Eynard Profesor Titular Plenario de Biologiacutea Celular Histologiacutea y
Embriologiacutea FCM Investigador Principal del CONICET
Objetivos de esta Charla
Compartir a grandes trazos nuestra experiencia y principales conclusiones de la integracioacuten en investigacioacuten ldquobaacutesica-epidemiologravegicardquo respecto a Tumores de Vias Urinarias (TVU)con aspectos nutricionales (liacutepidos poli -insaturados PUFA) e inflamaciograven crogravenica de bajo grado (LGCI) desarrollada ininterrumpidamente a lo largo de mas de 3 deacutecadas
Hipogravetesis manipulaciograven de los liacutepidos dietarios modificarigravean diferencialmente la estructura funcioacuten y composicioacuten quiacutemica de las membranas celulares En particular los restos azugravecares
del glicoacagraveliz urotelial azugravecares que luego forman la glicoproteigravena de Tam y Horsffal involucrada en litiasis de vigraveas
urinarias (VU)
La deficiencia en agravecidos grasos esenciales (EFAD) perturba la ultraestructura del plasmalema urotelial y de su glicocagraveliz
Observamos en animales EFAD longevos alta incidencia de tumorigenesis micro- litiasis e inflamaciograven en Viacuteas
Urinarias
J Natl Canc Inst 6473-79 l980
La inmunohistoquimica ultraestructural confirmograve perturbaciones en los restos azuces (glicocagraveliz) del plasmalema urotelial y en sus propiedades de fluidez cuando las ratas se estagraven en carencia crogravenica de EFA (fat-free diet) pero no en los Controles (+aceite de maigravez ) que era reversible (realimentacion con dieta Control)con caracterigravesticas pre- neoplagravesicas
Family n-7 n-9 n-6 n-3
Carbohidrates-Carbohidrates-
Diet Diet Diet Diet
ograve ograve ograve ograve
160 180
palmitic stearic
r-9-desaturaseeth ograve ograve ograve ograve
161n-7 181n-9 182n-6 183n-3
palmitoleic oleic linoleic -linolenic
(LA) (AA)
r-6-desaturaseeth ograve ograve ograve ograve
elongation 162n-7 182n-9 183n-6 184n-3
ograve ograve (-linolenic
(GLA) ograve
ograve
182n-7 202n-9 203n6 204n3
dihomo-(-
linolenic
(DGLA)
r-5-desaturaseeth ograve ograve ograve ograve
elongation 183n7 203n9 204n-6 205n-3
ograve ograve arachidonic (EPA)
(AA) ograve
ograve
203n-7 223n9 224n-6 225n-3
adrenic
$-Oxidation ograve ograve ograve ograve
204n-7 224n-9 225n-6 226n3
clupanodonic
La CG nos indicograve altos porcentajes de w3 en varios tejidos de estas ratas EFAD iquestporquegrave Veamos un resumen del metabolismo de UFAs
CITOSOL
EICOSANOIDES
LA (182 n-6) ALA (183 n-3) ALIMENTOS
ESPACIO
EXTRACELULAR
PLA2
MEMBRANA PLASMAacuteTICA MEMBRANA PLASMATICA
AG
COXs LOXs CP-450
9
PUFA ω-3 PUFA ω-6
desaturasa (en vegetales)
Das 2006 Comba et al 2011
Asigrave en base a hallazgos propios y de otros Grupos toma forma un ldquoproblemardquo y planteamos una hipogravetesis sobre el
papel de los PUFAs dietarios y LGCI en el riesgo de desarrollar TVU
1La mucosa de las vias urinarias de los mamigraveferos es impermeable al agua y asigrave evita ingresos de togravexicos y mutagravegenos
que se excretan por la orina hacia el organismo La ldquobarrerardquo estagrave localizada en el plasmalema luminal de las umbrella cells
2Dicho plamalema (iquestcon PL muy ricos en w3 203 ) se dantildearigravea si le faltan AGE (w6 y w3) dietarios tanto en su ultraestructura
sus PUFAs como en sus restos azugravecares (glicoproteigravenas glicocagraveliz) y en sus propiedades biofigravesiscas
3 Alimentacion crogravenica (16-30 meses) con dieta experimental litogegravenica (causante de ICBJ) y carente en EFAS w3 y w6 induce
hiperplasia ldquotransicionalrdquo en ratas controles (reversible) pero progresa a TVU (invasores) en rats EFAD
iquestLos PUFAs dietarios que juegan un papel importante en las membranas plasmaacuteticas luminales de las Viacuteas Urinarias base morfologravegica funcional de la
barrera a la permeabilidad y sus perturbaciograven junto a irritaciograven crogravenica puede ldquomodularrdquo el riesgo de desarrollar TVU
Nutrition 14 208-211 1998
El ldquodogmardquo sobre el proceso tumoral vagravelido para TVU
bull Es un complejo proceso multicausal en multi-etapas ldquosilenciosordquo al comienzo que se inicia con la transformacioacuten maligna de una ceacutelula que prolifera y trasmite esa mutacioacuten a su descendencia Si progresa hay una proliferacioacuten celular atiacutepica y anaacuterquica que no responde a los controles del organismo invade tejidos vecinos (invasioacuten) seguido muchas veces de metaacutestasis
In Vitro Nos preguntamos sabiendo que E-Cadherinas (CAMs) marcadores de adecuada diferenciaciograven tumoral y desmocolina proteina del citoesqueleto incrementan su expresiograven por incubaciograven con w6 183 (GLA) en ligraveneas cancerosas humanas (vejiga colon epidermis mama) iquest ese efecto deseable podrigravea ser bloqueado por el PUFA w9 203 (5811 Meadrsquos acid)
bull
WB efecto antagogravenico de concentraciones y course time de w6 GLA y w9 203 sobre expresiograven de e-cadherina y desmogleina (ligravenea de
cancer epidermoide humano)
iquestPero nos preguntabamos quegrave pasa con la gente y los TUV
ENFOQUE DE INVESTIGACION INTEGRADO DESARRROLLADO DESDE 1990 RESPECTO A TVU Y NUTRICION (LIPIDOS)
Epidemiologiacutea (casos amp controles y ldquoecoloacutegicosrdquo)
Patologiacutea Experimental (Modelos animales)
Biologiacutea Celular y Molecular (liacuteneas tumorales en cultivos
celulares biomembranas )
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
Objetivos de esta Charla
Compartir a grandes trazos nuestra experiencia y principales conclusiones de la integracioacuten en investigacioacuten ldquobaacutesica-epidemiologravegicardquo respecto a Tumores de Vias Urinarias (TVU)con aspectos nutricionales (liacutepidos poli -insaturados PUFA) e inflamaciograven crogravenica de bajo grado (LGCI) desarrollada ininterrumpidamente a lo largo de mas de 3 deacutecadas
Hipogravetesis manipulaciograven de los liacutepidos dietarios modificarigravean diferencialmente la estructura funcioacuten y composicioacuten quiacutemica de las membranas celulares En particular los restos azugravecares
del glicoacagraveliz urotelial azugravecares que luego forman la glicoproteigravena de Tam y Horsffal involucrada en litiasis de vigraveas
urinarias (VU)
La deficiencia en agravecidos grasos esenciales (EFAD) perturba la ultraestructura del plasmalema urotelial y de su glicocagraveliz
Observamos en animales EFAD longevos alta incidencia de tumorigenesis micro- litiasis e inflamaciograven en Viacuteas
Urinarias
J Natl Canc Inst 6473-79 l980
La inmunohistoquimica ultraestructural confirmograve perturbaciones en los restos azuces (glicocagraveliz) del plasmalema urotelial y en sus propiedades de fluidez cuando las ratas se estagraven en carencia crogravenica de EFA (fat-free diet) pero no en los Controles (+aceite de maigravez ) que era reversible (realimentacion con dieta Control)con caracterigravesticas pre- neoplagravesicas
Family n-7 n-9 n-6 n-3
Carbohidrates-Carbohidrates-
Diet Diet Diet Diet
ograve ograve ograve ograve
160 180
palmitic stearic
r-9-desaturaseeth ograve ograve ograve ograve
161n-7 181n-9 182n-6 183n-3
palmitoleic oleic linoleic -linolenic
(LA) (AA)
r-6-desaturaseeth ograve ograve ograve ograve
elongation 162n-7 182n-9 183n-6 184n-3
ograve ograve (-linolenic
(GLA) ograve
ograve
182n-7 202n-9 203n6 204n3
dihomo-(-
linolenic
(DGLA)
r-5-desaturaseeth ograve ograve ograve ograve
elongation 183n7 203n9 204n-6 205n-3
ograve ograve arachidonic (EPA)
(AA) ograve
ograve
203n-7 223n9 224n-6 225n-3
adrenic
$-Oxidation ograve ograve ograve ograve
204n-7 224n-9 225n-6 226n3
clupanodonic
La CG nos indicograve altos porcentajes de w3 en varios tejidos de estas ratas EFAD iquestporquegrave Veamos un resumen del metabolismo de UFAs
CITOSOL
EICOSANOIDES
LA (182 n-6) ALA (183 n-3) ALIMENTOS
ESPACIO
EXTRACELULAR
PLA2
MEMBRANA PLASMAacuteTICA MEMBRANA PLASMATICA
AG
COXs LOXs CP-450
9
PUFA ω-3 PUFA ω-6
desaturasa (en vegetales)
Das 2006 Comba et al 2011
Asigrave en base a hallazgos propios y de otros Grupos toma forma un ldquoproblemardquo y planteamos una hipogravetesis sobre el
papel de los PUFAs dietarios y LGCI en el riesgo de desarrollar TVU
1La mucosa de las vias urinarias de los mamigraveferos es impermeable al agua y asigrave evita ingresos de togravexicos y mutagravegenos
que se excretan por la orina hacia el organismo La ldquobarrerardquo estagrave localizada en el plasmalema luminal de las umbrella cells
2Dicho plamalema (iquestcon PL muy ricos en w3 203 ) se dantildearigravea si le faltan AGE (w6 y w3) dietarios tanto en su ultraestructura
sus PUFAs como en sus restos azugravecares (glicoproteigravenas glicocagraveliz) y en sus propiedades biofigravesiscas
3 Alimentacion crogravenica (16-30 meses) con dieta experimental litogegravenica (causante de ICBJ) y carente en EFAS w3 y w6 induce
hiperplasia ldquotransicionalrdquo en ratas controles (reversible) pero progresa a TVU (invasores) en rats EFAD
iquestLos PUFAs dietarios que juegan un papel importante en las membranas plasmaacuteticas luminales de las Viacuteas Urinarias base morfologravegica funcional de la
barrera a la permeabilidad y sus perturbaciograven junto a irritaciograven crogravenica puede ldquomodularrdquo el riesgo de desarrollar TVU
Nutrition 14 208-211 1998
El ldquodogmardquo sobre el proceso tumoral vagravelido para TVU
bull Es un complejo proceso multicausal en multi-etapas ldquosilenciosordquo al comienzo que se inicia con la transformacioacuten maligna de una ceacutelula que prolifera y trasmite esa mutacioacuten a su descendencia Si progresa hay una proliferacioacuten celular atiacutepica y anaacuterquica que no responde a los controles del organismo invade tejidos vecinos (invasioacuten) seguido muchas veces de metaacutestasis
In Vitro Nos preguntamos sabiendo que E-Cadherinas (CAMs) marcadores de adecuada diferenciaciograven tumoral y desmocolina proteina del citoesqueleto incrementan su expresiograven por incubaciograven con w6 183 (GLA) en ligraveneas cancerosas humanas (vejiga colon epidermis mama) iquest ese efecto deseable podrigravea ser bloqueado por el PUFA w9 203 (5811 Meadrsquos acid)
bull
WB efecto antagogravenico de concentraciones y course time de w6 GLA y w9 203 sobre expresiograven de e-cadherina y desmogleina (ligravenea de
cancer epidermoide humano)
iquestPero nos preguntabamos quegrave pasa con la gente y los TUV
ENFOQUE DE INVESTIGACION INTEGRADO DESARRROLLADO DESDE 1990 RESPECTO A TVU Y NUTRICION (LIPIDOS)
Epidemiologiacutea (casos amp controles y ldquoecoloacutegicosrdquo)
Patologiacutea Experimental (Modelos animales)
Biologiacutea Celular y Molecular (liacuteneas tumorales en cultivos
celulares biomembranas )
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
Hipogravetesis manipulaciograven de los liacutepidos dietarios modificarigravean diferencialmente la estructura funcioacuten y composicioacuten quiacutemica de las membranas celulares En particular los restos azugravecares
del glicoacagraveliz urotelial azugravecares que luego forman la glicoproteigravena de Tam y Horsffal involucrada en litiasis de vigraveas
urinarias (VU)
La deficiencia en agravecidos grasos esenciales (EFAD) perturba la ultraestructura del plasmalema urotelial y de su glicocagraveliz
Observamos en animales EFAD longevos alta incidencia de tumorigenesis micro- litiasis e inflamaciograven en Viacuteas
Urinarias
J Natl Canc Inst 6473-79 l980
La inmunohistoquimica ultraestructural confirmograve perturbaciones en los restos azuces (glicocagraveliz) del plasmalema urotelial y en sus propiedades de fluidez cuando las ratas se estagraven en carencia crogravenica de EFA (fat-free diet) pero no en los Controles (+aceite de maigravez ) que era reversible (realimentacion con dieta Control)con caracterigravesticas pre- neoplagravesicas
Family n-7 n-9 n-6 n-3
Carbohidrates-Carbohidrates-
Diet Diet Diet Diet
ograve ograve ograve ograve
160 180
palmitic stearic
r-9-desaturaseeth ograve ograve ograve ograve
161n-7 181n-9 182n-6 183n-3
palmitoleic oleic linoleic -linolenic
(LA) (AA)
r-6-desaturaseeth ograve ograve ograve ograve
elongation 162n-7 182n-9 183n-6 184n-3
ograve ograve (-linolenic
(GLA) ograve
ograve
182n-7 202n-9 203n6 204n3
dihomo-(-
linolenic
(DGLA)
r-5-desaturaseeth ograve ograve ograve ograve
elongation 183n7 203n9 204n-6 205n-3
ograve ograve arachidonic (EPA)
(AA) ograve
ograve
203n-7 223n9 224n-6 225n-3
adrenic
$-Oxidation ograve ograve ograve ograve
204n-7 224n-9 225n-6 226n3
clupanodonic
La CG nos indicograve altos porcentajes de w3 en varios tejidos de estas ratas EFAD iquestporquegrave Veamos un resumen del metabolismo de UFAs
CITOSOL
EICOSANOIDES
LA (182 n-6) ALA (183 n-3) ALIMENTOS
ESPACIO
EXTRACELULAR
PLA2
MEMBRANA PLASMAacuteTICA MEMBRANA PLASMATICA
AG
COXs LOXs CP-450
9
PUFA ω-3 PUFA ω-6
desaturasa (en vegetales)
Das 2006 Comba et al 2011
Asigrave en base a hallazgos propios y de otros Grupos toma forma un ldquoproblemardquo y planteamos una hipogravetesis sobre el
papel de los PUFAs dietarios y LGCI en el riesgo de desarrollar TVU
1La mucosa de las vias urinarias de los mamigraveferos es impermeable al agua y asigrave evita ingresos de togravexicos y mutagravegenos
que se excretan por la orina hacia el organismo La ldquobarrerardquo estagrave localizada en el plasmalema luminal de las umbrella cells
2Dicho plamalema (iquestcon PL muy ricos en w3 203 ) se dantildearigravea si le faltan AGE (w6 y w3) dietarios tanto en su ultraestructura
sus PUFAs como en sus restos azugravecares (glicoproteigravenas glicocagraveliz) y en sus propiedades biofigravesiscas
3 Alimentacion crogravenica (16-30 meses) con dieta experimental litogegravenica (causante de ICBJ) y carente en EFAS w3 y w6 induce
hiperplasia ldquotransicionalrdquo en ratas controles (reversible) pero progresa a TVU (invasores) en rats EFAD
iquestLos PUFAs dietarios que juegan un papel importante en las membranas plasmaacuteticas luminales de las Viacuteas Urinarias base morfologravegica funcional de la
barrera a la permeabilidad y sus perturbaciograven junto a irritaciograven crogravenica puede ldquomodularrdquo el riesgo de desarrollar TVU
Nutrition 14 208-211 1998
El ldquodogmardquo sobre el proceso tumoral vagravelido para TVU
bull Es un complejo proceso multicausal en multi-etapas ldquosilenciosordquo al comienzo que se inicia con la transformacioacuten maligna de una ceacutelula que prolifera y trasmite esa mutacioacuten a su descendencia Si progresa hay una proliferacioacuten celular atiacutepica y anaacuterquica que no responde a los controles del organismo invade tejidos vecinos (invasioacuten) seguido muchas veces de metaacutestasis
In Vitro Nos preguntamos sabiendo que E-Cadherinas (CAMs) marcadores de adecuada diferenciaciograven tumoral y desmocolina proteina del citoesqueleto incrementan su expresiograven por incubaciograven con w6 183 (GLA) en ligraveneas cancerosas humanas (vejiga colon epidermis mama) iquest ese efecto deseable podrigravea ser bloqueado por el PUFA w9 203 (5811 Meadrsquos acid)
bull
WB efecto antagogravenico de concentraciones y course time de w6 GLA y w9 203 sobre expresiograven de e-cadherina y desmogleina (ligravenea de
cancer epidermoide humano)
iquestPero nos preguntabamos quegrave pasa con la gente y los TUV
ENFOQUE DE INVESTIGACION INTEGRADO DESARRROLLADO DESDE 1990 RESPECTO A TVU Y NUTRICION (LIPIDOS)
Epidemiologiacutea (casos amp controles y ldquoecoloacutegicosrdquo)
Patologiacutea Experimental (Modelos animales)
Biologiacutea Celular y Molecular (liacuteneas tumorales en cultivos
celulares biomembranas )
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
La deficiencia en agravecidos grasos esenciales (EFAD) perturba la ultraestructura del plasmalema urotelial y de su glicocagraveliz
Observamos en animales EFAD longevos alta incidencia de tumorigenesis micro- litiasis e inflamaciograven en Viacuteas
Urinarias
J Natl Canc Inst 6473-79 l980
La inmunohistoquimica ultraestructural confirmograve perturbaciones en los restos azuces (glicocagraveliz) del plasmalema urotelial y en sus propiedades de fluidez cuando las ratas se estagraven en carencia crogravenica de EFA (fat-free diet) pero no en los Controles (+aceite de maigravez ) que era reversible (realimentacion con dieta Control)con caracterigravesticas pre- neoplagravesicas
Family n-7 n-9 n-6 n-3
Carbohidrates-Carbohidrates-
Diet Diet Diet Diet
ograve ograve ograve ograve
160 180
palmitic stearic
r-9-desaturaseeth ograve ograve ograve ograve
161n-7 181n-9 182n-6 183n-3
palmitoleic oleic linoleic -linolenic
(LA) (AA)
r-6-desaturaseeth ograve ograve ograve ograve
elongation 162n-7 182n-9 183n-6 184n-3
ograve ograve (-linolenic
(GLA) ograve
ograve
182n-7 202n-9 203n6 204n3
dihomo-(-
linolenic
(DGLA)
r-5-desaturaseeth ograve ograve ograve ograve
elongation 183n7 203n9 204n-6 205n-3
ograve ograve arachidonic (EPA)
(AA) ograve
ograve
203n-7 223n9 224n-6 225n-3
adrenic
$-Oxidation ograve ograve ograve ograve
204n-7 224n-9 225n-6 226n3
clupanodonic
La CG nos indicograve altos porcentajes de w3 en varios tejidos de estas ratas EFAD iquestporquegrave Veamos un resumen del metabolismo de UFAs
CITOSOL
EICOSANOIDES
LA (182 n-6) ALA (183 n-3) ALIMENTOS
ESPACIO
EXTRACELULAR
PLA2
MEMBRANA PLASMAacuteTICA MEMBRANA PLASMATICA
AG
COXs LOXs CP-450
9
PUFA ω-3 PUFA ω-6
desaturasa (en vegetales)
Das 2006 Comba et al 2011
Asigrave en base a hallazgos propios y de otros Grupos toma forma un ldquoproblemardquo y planteamos una hipogravetesis sobre el
papel de los PUFAs dietarios y LGCI en el riesgo de desarrollar TVU
1La mucosa de las vias urinarias de los mamigraveferos es impermeable al agua y asigrave evita ingresos de togravexicos y mutagravegenos
que se excretan por la orina hacia el organismo La ldquobarrerardquo estagrave localizada en el plasmalema luminal de las umbrella cells
2Dicho plamalema (iquestcon PL muy ricos en w3 203 ) se dantildearigravea si le faltan AGE (w6 y w3) dietarios tanto en su ultraestructura
sus PUFAs como en sus restos azugravecares (glicoproteigravenas glicocagraveliz) y en sus propiedades biofigravesiscas
3 Alimentacion crogravenica (16-30 meses) con dieta experimental litogegravenica (causante de ICBJ) y carente en EFAS w3 y w6 induce
hiperplasia ldquotransicionalrdquo en ratas controles (reversible) pero progresa a TVU (invasores) en rats EFAD
iquestLos PUFAs dietarios que juegan un papel importante en las membranas plasmaacuteticas luminales de las Viacuteas Urinarias base morfologravegica funcional de la
barrera a la permeabilidad y sus perturbaciograven junto a irritaciograven crogravenica puede ldquomodularrdquo el riesgo de desarrollar TVU
Nutrition 14 208-211 1998
El ldquodogmardquo sobre el proceso tumoral vagravelido para TVU
bull Es un complejo proceso multicausal en multi-etapas ldquosilenciosordquo al comienzo que se inicia con la transformacioacuten maligna de una ceacutelula que prolifera y trasmite esa mutacioacuten a su descendencia Si progresa hay una proliferacioacuten celular atiacutepica y anaacuterquica que no responde a los controles del organismo invade tejidos vecinos (invasioacuten) seguido muchas veces de metaacutestasis
In Vitro Nos preguntamos sabiendo que E-Cadherinas (CAMs) marcadores de adecuada diferenciaciograven tumoral y desmocolina proteina del citoesqueleto incrementan su expresiograven por incubaciograven con w6 183 (GLA) en ligraveneas cancerosas humanas (vejiga colon epidermis mama) iquest ese efecto deseable podrigravea ser bloqueado por el PUFA w9 203 (5811 Meadrsquos acid)
bull
WB efecto antagogravenico de concentraciones y course time de w6 GLA y w9 203 sobre expresiograven de e-cadherina y desmogleina (ligravenea de
cancer epidermoide humano)
iquestPero nos preguntabamos quegrave pasa con la gente y los TUV
ENFOQUE DE INVESTIGACION INTEGRADO DESARRROLLADO DESDE 1990 RESPECTO A TVU Y NUTRICION (LIPIDOS)
Epidemiologiacutea (casos amp controles y ldquoecoloacutegicosrdquo)
Patologiacutea Experimental (Modelos animales)
Biologiacutea Celular y Molecular (liacuteneas tumorales en cultivos
celulares biomembranas )
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
Observamos en animales EFAD longevos alta incidencia de tumorigenesis micro- litiasis e inflamaciograven en Viacuteas
Urinarias
J Natl Canc Inst 6473-79 l980
La inmunohistoquimica ultraestructural confirmograve perturbaciones en los restos azuces (glicocagraveliz) del plasmalema urotelial y en sus propiedades de fluidez cuando las ratas se estagraven en carencia crogravenica de EFA (fat-free diet) pero no en los Controles (+aceite de maigravez ) que era reversible (realimentacion con dieta Control)con caracterigravesticas pre- neoplagravesicas
Family n-7 n-9 n-6 n-3
Carbohidrates-Carbohidrates-
Diet Diet Diet Diet
ograve ograve ograve ograve
160 180
palmitic stearic
r-9-desaturaseeth ograve ograve ograve ograve
161n-7 181n-9 182n-6 183n-3
palmitoleic oleic linoleic -linolenic
(LA) (AA)
r-6-desaturaseeth ograve ograve ograve ograve
elongation 162n-7 182n-9 183n-6 184n-3
ograve ograve (-linolenic
(GLA) ograve
ograve
182n-7 202n-9 203n6 204n3
dihomo-(-
linolenic
(DGLA)
r-5-desaturaseeth ograve ograve ograve ograve
elongation 183n7 203n9 204n-6 205n-3
ograve ograve arachidonic (EPA)
(AA) ograve
ograve
203n-7 223n9 224n-6 225n-3
adrenic
$-Oxidation ograve ograve ograve ograve
204n-7 224n-9 225n-6 226n3
clupanodonic
La CG nos indicograve altos porcentajes de w3 en varios tejidos de estas ratas EFAD iquestporquegrave Veamos un resumen del metabolismo de UFAs
CITOSOL
EICOSANOIDES
LA (182 n-6) ALA (183 n-3) ALIMENTOS
ESPACIO
EXTRACELULAR
PLA2
MEMBRANA PLASMAacuteTICA MEMBRANA PLASMATICA
AG
COXs LOXs CP-450
9
PUFA ω-3 PUFA ω-6
desaturasa (en vegetales)
Das 2006 Comba et al 2011
Asigrave en base a hallazgos propios y de otros Grupos toma forma un ldquoproblemardquo y planteamos una hipogravetesis sobre el
papel de los PUFAs dietarios y LGCI en el riesgo de desarrollar TVU
1La mucosa de las vias urinarias de los mamigraveferos es impermeable al agua y asigrave evita ingresos de togravexicos y mutagravegenos
que se excretan por la orina hacia el organismo La ldquobarrerardquo estagrave localizada en el plasmalema luminal de las umbrella cells
2Dicho plamalema (iquestcon PL muy ricos en w3 203 ) se dantildearigravea si le faltan AGE (w6 y w3) dietarios tanto en su ultraestructura
sus PUFAs como en sus restos azugravecares (glicoproteigravenas glicocagraveliz) y en sus propiedades biofigravesiscas
3 Alimentacion crogravenica (16-30 meses) con dieta experimental litogegravenica (causante de ICBJ) y carente en EFAS w3 y w6 induce
hiperplasia ldquotransicionalrdquo en ratas controles (reversible) pero progresa a TVU (invasores) en rats EFAD
iquestLos PUFAs dietarios que juegan un papel importante en las membranas plasmaacuteticas luminales de las Viacuteas Urinarias base morfologravegica funcional de la
barrera a la permeabilidad y sus perturbaciograven junto a irritaciograven crogravenica puede ldquomodularrdquo el riesgo de desarrollar TVU
Nutrition 14 208-211 1998
El ldquodogmardquo sobre el proceso tumoral vagravelido para TVU
bull Es un complejo proceso multicausal en multi-etapas ldquosilenciosordquo al comienzo que se inicia con la transformacioacuten maligna de una ceacutelula que prolifera y trasmite esa mutacioacuten a su descendencia Si progresa hay una proliferacioacuten celular atiacutepica y anaacuterquica que no responde a los controles del organismo invade tejidos vecinos (invasioacuten) seguido muchas veces de metaacutestasis
In Vitro Nos preguntamos sabiendo que E-Cadherinas (CAMs) marcadores de adecuada diferenciaciograven tumoral y desmocolina proteina del citoesqueleto incrementan su expresiograven por incubaciograven con w6 183 (GLA) en ligraveneas cancerosas humanas (vejiga colon epidermis mama) iquest ese efecto deseable podrigravea ser bloqueado por el PUFA w9 203 (5811 Meadrsquos acid)
bull
WB efecto antagogravenico de concentraciones y course time de w6 GLA y w9 203 sobre expresiograven de e-cadherina y desmogleina (ligravenea de
cancer epidermoide humano)
iquestPero nos preguntabamos quegrave pasa con la gente y los TUV
ENFOQUE DE INVESTIGACION INTEGRADO DESARRROLLADO DESDE 1990 RESPECTO A TVU Y NUTRICION (LIPIDOS)
Epidemiologiacutea (casos amp controles y ldquoecoloacutegicosrdquo)
Patologiacutea Experimental (Modelos animales)
Biologiacutea Celular y Molecular (liacuteneas tumorales en cultivos
celulares biomembranas )
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
La inmunohistoquimica ultraestructural confirmograve perturbaciones en los restos azuces (glicocagraveliz) del plasmalema urotelial y en sus propiedades de fluidez cuando las ratas se estagraven en carencia crogravenica de EFA (fat-free diet) pero no en los Controles (+aceite de maigravez ) que era reversible (realimentacion con dieta Control)con caracterigravesticas pre- neoplagravesicas
Family n-7 n-9 n-6 n-3
Carbohidrates-Carbohidrates-
Diet Diet Diet Diet
ograve ograve ograve ograve
160 180
palmitic stearic
r-9-desaturaseeth ograve ograve ograve ograve
161n-7 181n-9 182n-6 183n-3
palmitoleic oleic linoleic -linolenic
(LA) (AA)
r-6-desaturaseeth ograve ograve ograve ograve
elongation 162n-7 182n-9 183n-6 184n-3
ograve ograve (-linolenic
(GLA) ograve
ograve
182n-7 202n-9 203n6 204n3
dihomo-(-
linolenic
(DGLA)
r-5-desaturaseeth ograve ograve ograve ograve
elongation 183n7 203n9 204n-6 205n-3
ograve ograve arachidonic (EPA)
(AA) ograve
ograve
203n-7 223n9 224n-6 225n-3
adrenic
$-Oxidation ograve ograve ograve ograve
204n-7 224n-9 225n-6 226n3
clupanodonic
La CG nos indicograve altos porcentajes de w3 en varios tejidos de estas ratas EFAD iquestporquegrave Veamos un resumen del metabolismo de UFAs
CITOSOL
EICOSANOIDES
LA (182 n-6) ALA (183 n-3) ALIMENTOS
ESPACIO
EXTRACELULAR
PLA2
MEMBRANA PLASMAacuteTICA MEMBRANA PLASMATICA
AG
COXs LOXs CP-450
9
PUFA ω-3 PUFA ω-6
desaturasa (en vegetales)
Das 2006 Comba et al 2011
Asigrave en base a hallazgos propios y de otros Grupos toma forma un ldquoproblemardquo y planteamos una hipogravetesis sobre el
papel de los PUFAs dietarios y LGCI en el riesgo de desarrollar TVU
1La mucosa de las vias urinarias de los mamigraveferos es impermeable al agua y asigrave evita ingresos de togravexicos y mutagravegenos
que se excretan por la orina hacia el organismo La ldquobarrerardquo estagrave localizada en el plasmalema luminal de las umbrella cells
2Dicho plamalema (iquestcon PL muy ricos en w3 203 ) se dantildearigravea si le faltan AGE (w6 y w3) dietarios tanto en su ultraestructura
sus PUFAs como en sus restos azugravecares (glicoproteigravenas glicocagraveliz) y en sus propiedades biofigravesiscas
3 Alimentacion crogravenica (16-30 meses) con dieta experimental litogegravenica (causante de ICBJ) y carente en EFAS w3 y w6 induce
hiperplasia ldquotransicionalrdquo en ratas controles (reversible) pero progresa a TVU (invasores) en rats EFAD
iquestLos PUFAs dietarios que juegan un papel importante en las membranas plasmaacuteticas luminales de las Viacuteas Urinarias base morfologravegica funcional de la
barrera a la permeabilidad y sus perturbaciograven junto a irritaciograven crogravenica puede ldquomodularrdquo el riesgo de desarrollar TVU
Nutrition 14 208-211 1998
El ldquodogmardquo sobre el proceso tumoral vagravelido para TVU
bull Es un complejo proceso multicausal en multi-etapas ldquosilenciosordquo al comienzo que se inicia con la transformacioacuten maligna de una ceacutelula que prolifera y trasmite esa mutacioacuten a su descendencia Si progresa hay una proliferacioacuten celular atiacutepica y anaacuterquica que no responde a los controles del organismo invade tejidos vecinos (invasioacuten) seguido muchas veces de metaacutestasis
In Vitro Nos preguntamos sabiendo que E-Cadherinas (CAMs) marcadores de adecuada diferenciaciograven tumoral y desmocolina proteina del citoesqueleto incrementan su expresiograven por incubaciograven con w6 183 (GLA) en ligraveneas cancerosas humanas (vejiga colon epidermis mama) iquest ese efecto deseable podrigravea ser bloqueado por el PUFA w9 203 (5811 Meadrsquos acid)
bull
WB efecto antagogravenico de concentraciones y course time de w6 GLA y w9 203 sobre expresiograven de e-cadherina y desmogleina (ligravenea de
cancer epidermoide humano)
iquestPero nos preguntabamos quegrave pasa con la gente y los TUV
ENFOQUE DE INVESTIGACION INTEGRADO DESARRROLLADO DESDE 1990 RESPECTO A TVU Y NUTRICION (LIPIDOS)
Epidemiologiacutea (casos amp controles y ldquoecoloacutegicosrdquo)
Patologiacutea Experimental (Modelos animales)
Biologiacutea Celular y Molecular (liacuteneas tumorales en cultivos
celulares biomembranas )
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
Family n-7 n-9 n-6 n-3
Carbohidrates-Carbohidrates-
Diet Diet Diet Diet
ograve ograve ograve ograve
160 180
palmitic stearic
r-9-desaturaseeth ograve ograve ograve ograve
161n-7 181n-9 182n-6 183n-3
palmitoleic oleic linoleic -linolenic
(LA) (AA)
r-6-desaturaseeth ograve ograve ograve ograve
elongation 162n-7 182n-9 183n-6 184n-3
ograve ograve (-linolenic
(GLA) ograve
ograve
182n-7 202n-9 203n6 204n3
dihomo-(-
linolenic
(DGLA)
r-5-desaturaseeth ograve ograve ograve ograve
elongation 183n7 203n9 204n-6 205n-3
ograve ograve arachidonic (EPA)
(AA) ograve
ograve
203n-7 223n9 224n-6 225n-3
adrenic
$-Oxidation ograve ograve ograve ograve
204n-7 224n-9 225n-6 226n3
clupanodonic
La CG nos indicograve altos porcentajes de w3 en varios tejidos de estas ratas EFAD iquestporquegrave Veamos un resumen del metabolismo de UFAs
CITOSOL
EICOSANOIDES
LA (182 n-6) ALA (183 n-3) ALIMENTOS
ESPACIO
EXTRACELULAR
PLA2
MEMBRANA PLASMAacuteTICA MEMBRANA PLASMATICA
AG
COXs LOXs CP-450
9
PUFA ω-3 PUFA ω-6
desaturasa (en vegetales)
Das 2006 Comba et al 2011
Asigrave en base a hallazgos propios y de otros Grupos toma forma un ldquoproblemardquo y planteamos una hipogravetesis sobre el
papel de los PUFAs dietarios y LGCI en el riesgo de desarrollar TVU
1La mucosa de las vias urinarias de los mamigraveferos es impermeable al agua y asigrave evita ingresos de togravexicos y mutagravegenos
que se excretan por la orina hacia el organismo La ldquobarrerardquo estagrave localizada en el plasmalema luminal de las umbrella cells
2Dicho plamalema (iquestcon PL muy ricos en w3 203 ) se dantildearigravea si le faltan AGE (w6 y w3) dietarios tanto en su ultraestructura
sus PUFAs como en sus restos azugravecares (glicoproteigravenas glicocagraveliz) y en sus propiedades biofigravesiscas
3 Alimentacion crogravenica (16-30 meses) con dieta experimental litogegravenica (causante de ICBJ) y carente en EFAS w3 y w6 induce
hiperplasia ldquotransicionalrdquo en ratas controles (reversible) pero progresa a TVU (invasores) en rats EFAD
iquestLos PUFAs dietarios que juegan un papel importante en las membranas plasmaacuteticas luminales de las Viacuteas Urinarias base morfologravegica funcional de la
barrera a la permeabilidad y sus perturbaciograven junto a irritaciograven crogravenica puede ldquomodularrdquo el riesgo de desarrollar TVU
Nutrition 14 208-211 1998
El ldquodogmardquo sobre el proceso tumoral vagravelido para TVU
bull Es un complejo proceso multicausal en multi-etapas ldquosilenciosordquo al comienzo que se inicia con la transformacioacuten maligna de una ceacutelula que prolifera y trasmite esa mutacioacuten a su descendencia Si progresa hay una proliferacioacuten celular atiacutepica y anaacuterquica que no responde a los controles del organismo invade tejidos vecinos (invasioacuten) seguido muchas veces de metaacutestasis
In Vitro Nos preguntamos sabiendo que E-Cadherinas (CAMs) marcadores de adecuada diferenciaciograven tumoral y desmocolina proteina del citoesqueleto incrementan su expresiograven por incubaciograven con w6 183 (GLA) en ligraveneas cancerosas humanas (vejiga colon epidermis mama) iquest ese efecto deseable podrigravea ser bloqueado por el PUFA w9 203 (5811 Meadrsquos acid)
bull
WB efecto antagogravenico de concentraciones y course time de w6 GLA y w9 203 sobre expresiograven de e-cadherina y desmogleina (ligravenea de
cancer epidermoide humano)
iquestPero nos preguntabamos quegrave pasa con la gente y los TUV
ENFOQUE DE INVESTIGACION INTEGRADO DESARRROLLADO DESDE 1990 RESPECTO A TVU Y NUTRICION (LIPIDOS)
Epidemiologiacutea (casos amp controles y ldquoecoloacutegicosrdquo)
Patologiacutea Experimental (Modelos animales)
Biologiacutea Celular y Molecular (liacuteneas tumorales en cultivos
celulares biomembranas )
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
CITOSOL
EICOSANOIDES
LA (182 n-6) ALA (183 n-3) ALIMENTOS
ESPACIO
EXTRACELULAR
PLA2
MEMBRANA PLASMAacuteTICA MEMBRANA PLASMATICA
AG
COXs LOXs CP-450
9
PUFA ω-3 PUFA ω-6
desaturasa (en vegetales)
Das 2006 Comba et al 2011
Asigrave en base a hallazgos propios y de otros Grupos toma forma un ldquoproblemardquo y planteamos una hipogravetesis sobre el
papel de los PUFAs dietarios y LGCI en el riesgo de desarrollar TVU
1La mucosa de las vias urinarias de los mamigraveferos es impermeable al agua y asigrave evita ingresos de togravexicos y mutagravegenos
que se excretan por la orina hacia el organismo La ldquobarrerardquo estagrave localizada en el plasmalema luminal de las umbrella cells
2Dicho plamalema (iquestcon PL muy ricos en w3 203 ) se dantildearigravea si le faltan AGE (w6 y w3) dietarios tanto en su ultraestructura
sus PUFAs como en sus restos azugravecares (glicoproteigravenas glicocagraveliz) y en sus propiedades biofigravesiscas
3 Alimentacion crogravenica (16-30 meses) con dieta experimental litogegravenica (causante de ICBJ) y carente en EFAS w3 y w6 induce
hiperplasia ldquotransicionalrdquo en ratas controles (reversible) pero progresa a TVU (invasores) en rats EFAD
iquestLos PUFAs dietarios que juegan un papel importante en las membranas plasmaacuteticas luminales de las Viacuteas Urinarias base morfologravegica funcional de la
barrera a la permeabilidad y sus perturbaciograven junto a irritaciograven crogravenica puede ldquomodularrdquo el riesgo de desarrollar TVU
Nutrition 14 208-211 1998
El ldquodogmardquo sobre el proceso tumoral vagravelido para TVU
bull Es un complejo proceso multicausal en multi-etapas ldquosilenciosordquo al comienzo que se inicia con la transformacioacuten maligna de una ceacutelula que prolifera y trasmite esa mutacioacuten a su descendencia Si progresa hay una proliferacioacuten celular atiacutepica y anaacuterquica que no responde a los controles del organismo invade tejidos vecinos (invasioacuten) seguido muchas veces de metaacutestasis
In Vitro Nos preguntamos sabiendo que E-Cadherinas (CAMs) marcadores de adecuada diferenciaciograven tumoral y desmocolina proteina del citoesqueleto incrementan su expresiograven por incubaciograven con w6 183 (GLA) en ligraveneas cancerosas humanas (vejiga colon epidermis mama) iquest ese efecto deseable podrigravea ser bloqueado por el PUFA w9 203 (5811 Meadrsquos acid)
bull
WB efecto antagogravenico de concentraciones y course time de w6 GLA y w9 203 sobre expresiograven de e-cadherina y desmogleina (ligravenea de
cancer epidermoide humano)
iquestPero nos preguntabamos quegrave pasa con la gente y los TUV
ENFOQUE DE INVESTIGACION INTEGRADO DESARRROLLADO DESDE 1990 RESPECTO A TVU Y NUTRICION (LIPIDOS)
Epidemiologiacutea (casos amp controles y ldquoecoloacutegicosrdquo)
Patologiacutea Experimental (Modelos animales)
Biologiacutea Celular y Molecular (liacuteneas tumorales en cultivos
celulares biomembranas )
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
Asigrave en base a hallazgos propios y de otros Grupos toma forma un ldquoproblemardquo y planteamos una hipogravetesis sobre el
papel de los PUFAs dietarios y LGCI en el riesgo de desarrollar TVU
1La mucosa de las vias urinarias de los mamigraveferos es impermeable al agua y asigrave evita ingresos de togravexicos y mutagravegenos
que se excretan por la orina hacia el organismo La ldquobarrerardquo estagrave localizada en el plasmalema luminal de las umbrella cells
2Dicho plamalema (iquestcon PL muy ricos en w3 203 ) se dantildearigravea si le faltan AGE (w6 y w3) dietarios tanto en su ultraestructura
sus PUFAs como en sus restos azugravecares (glicoproteigravenas glicocagraveliz) y en sus propiedades biofigravesiscas
3 Alimentacion crogravenica (16-30 meses) con dieta experimental litogegravenica (causante de ICBJ) y carente en EFAS w3 y w6 induce
hiperplasia ldquotransicionalrdquo en ratas controles (reversible) pero progresa a TVU (invasores) en rats EFAD
iquestLos PUFAs dietarios que juegan un papel importante en las membranas plasmaacuteticas luminales de las Viacuteas Urinarias base morfologravegica funcional de la
barrera a la permeabilidad y sus perturbaciograven junto a irritaciograven crogravenica puede ldquomodularrdquo el riesgo de desarrollar TVU
Nutrition 14 208-211 1998
El ldquodogmardquo sobre el proceso tumoral vagravelido para TVU
bull Es un complejo proceso multicausal en multi-etapas ldquosilenciosordquo al comienzo que se inicia con la transformacioacuten maligna de una ceacutelula que prolifera y trasmite esa mutacioacuten a su descendencia Si progresa hay una proliferacioacuten celular atiacutepica y anaacuterquica que no responde a los controles del organismo invade tejidos vecinos (invasioacuten) seguido muchas veces de metaacutestasis
In Vitro Nos preguntamos sabiendo que E-Cadherinas (CAMs) marcadores de adecuada diferenciaciograven tumoral y desmocolina proteina del citoesqueleto incrementan su expresiograven por incubaciograven con w6 183 (GLA) en ligraveneas cancerosas humanas (vejiga colon epidermis mama) iquest ese efecto deseable podrigravea ser bloqueado por el PUFA w9 203 (5811 Meadrsquos acid)
bull
WB efecto antagogravenico de concentraciones y course time de w6 GLA y w9 203 sobre expresiograven de e-cadherina y desmogleina (ligravenea de
cancer epidermoide humano)
iquestPero nos preguntabamos quegrave pasa con la gente y los TUV
ENFOQUE DE INVESTIGACION INTEGRADO DESARRROLLADO DESDE 1990 RESPECTO A TVU Y NUTRICION (LIPIDOS)
Epidemiologiacutea (casos amp controles y ldquoecoloacutegicosrdquo)
Patologiacutea Experimental (Modelos animales)
Biologiacutea Celular y Molecular (liacuteneas tumorales en cultivos
celulares biomembranas )
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
iquestLos PUFAs dietarios que juegan un papel importante en las membranas plasmaacuteticas luminales de las Viacuteas Urinarias base morfologravegica funcional de la
barrera a la permeabilidad y sus perturbaciograven junto a irritaciograven crogravenica puede ldquomodularrdquo el riesgo de desarrollar TVU
Nutrition 14 208-211 1998
El ldquodogmardquo sobre el proceso tumoral vagravelido para TVU
bull Es un complejo proceso multicausal en multi-etapas ldquosilenciosordquo al comienzo que se inicia con la transformacioacuten maligna de una ceacutelula que prolifera y trasmite esa mutacioacuten a su descendencia Si progresa hay una proliferacioacuten celular atiacutepica y anaacuterquica que no responde a los controles del organismo invade tejidos vecinos (invasioacuten) seguido muchas veces de metaacutestasis
In Vitro Nos preguntamos sabiendo que E-Cadherinas (CAMs) marcadores de adecuada diferenciaciograven tumoral y desmocolina proteina del citoesqueleto incrementan su expresiograven por incubaciograven con w6 183 (GLA) en ligraveneas cancerosas humanas (vejiga colon epidermis mama) iquest ese efecto deseable podrigravea ser bloqueado por el PUFA w9 203 (5811 Meadrsquos acid)
bull
WB efecto antagogravenico de concentraciones y course time de w6 GLA y w9 203 sobre expresiograven de e-cadherina y desmogleina (ligravenea de
cancer epidermoide humano)
iquestPero nos preguntabamos quegrave pasa con la gente y los TUV
ENFOQUE DE INVESTIGACION INTEGRADO DESARRROLLADO DESDE 1990 RESPECTO A TVU Y NUTRICION (LIPIDOS)
Epidemiologiacutea (casos amp controles y ldquoecoloacutegicosrdquo)
Patologiacutea Experimental (Modelos animales)
Biologiacutea Celular y Molecular (liacuteneas tumorales en cultivos
celulares biomembranas )
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
El ldquodogmardquo sobre el proceso tumoral vagravelido para TVU
bull Es un complejo proceso multicausal en multi-etapas ldquosilenciosordquo al comienzo que se inicia con la transformacioacuten maligna de una ceacutelula que prolifera y trasmite esa mutacioacuten a su descendencia Si progresa hay una proliferacioacuten celular atiacutepica y anaacuterquica que no responde a los controles del organismo invade tejidos vecinos (invasioacuten) seguido muchas veces de metaacutestasis
In Vitro Nos preguntamos sabiendo que E-Cadherinas (CAMs) marcadores de adecuada diferenciaciograven tumoral y desmocolina proteina del citoesqueleto incrementan su expresiograven por incubaciograven con w6 183 (GLA) en ligraveneas cancerosas humanas (vejiga colon epidermis mama) iquest ese efecto deseable podrigravea ser bloqueado por el PUFA w9 203 (5811 Meadrsquos acid)
bull
WB efecto antagogravenico de concentraciones y course time de w6 GLA y w9 203 sobre expresiograven de e-cadherina y desmogleina (ligravenea de
cancer epidermoide humano)
iquestPero nos preguntabamos quegrave pasa con la gente y los TUV
ENFOQUE DE INVESTIGACION INTEGRADO DESARRROLLADO DESDE 1990 RESPECTO A TVU Y NUTRICION (LIPIDOS)
Epidemiologiacutea (casos amp controles y ldquoecoloacutegicosrdquo)
Patologiacutea Experimental (Modelos animales)
Biologiacutea Celular y Molecular (liacuteneas tumorales en cultivos
celulares biomembranas )
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
In Vitro Nos preguntamos sabiendo que E-Cadherinas (CAMs) marcadores de adecuada diferenciaciograven tumoral y desmocolina proteina del citoesqueleto incrementan su expresiograven por incubaciograven con w6 183 (GLA) en ligraveneas cancerosas humanas (vejiga colon epidermis mama) iquest ese efecto deseable podrigravea ser bloqueado por el PUFA w9 203 (5811 Meadrsquos acid)
bull
WB efecto antagogravenico de concentraciones y course time de w6 GLA y w9 203 sobre expresiograven de e-cadherina y desmogleina (ligravenea de
cancer epidermoide humano)
iquestPero nos preguntabamos quegrave pasa con la gente y los TUV
ENFOQUE DE INVESTIGACION INTEGRADO DESARRROLLADO DESDE 1990 RESPECTO A TVU Y NUTRICION (LIPIDOS)
Epidemiologiacutea (casos amp controles y ldquoecoloacutegicosrdquo)
Patologiacutea Experimental (Modelos animales)
Biologiacutea Celular y Molecular (liacuteneas tumorales en cultivos
celulares biomembranas )
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
WB efecto antagogravenico de concentraciones y course time de w6 GLA y w9 203 sobre expresiograven de e-cadherina y desmogleina (ligravenea de
cancer epidermoide humano)
iquestPero nos preguntabamos quegrave pasa con la gente y los TUV
ENFOQUE DE INVESTIGACION INTEGRADO DESARRROLLADO DESDE 1990 RESPECTO A TVU Y NUTRICION (LIPIDOS)
Epidemiologiacutea (casos amp controles y ldquoecoloacutegicosrdquo)
Patologiacutea Experimental (Modelos animales)
Biologiacutea Celular y Molecular (liacuteneas tumorales en cultivos
celulares biomembranas )
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
iquestPero nos preguntabamos quegrave pasa con la gente y los TUV
ENFOQUE DE INVESTIGACION INTEGRADO DESARRROLLADO DESDE 1990 RESPECTO A TVU Y NUTRICION (LIPIDOS)
Epidemiologiacutea (casos amp controles y ldquoecoloacutegicosrdquo)
Patologiacutea Experimental (Modelos animales)
Biologiacutea Celular y Molecular (liacuteneas tumorales en cultivos
celulares biomembranas )
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
ENFOQUE DE INVESTIGACION INTEGRADO DESARRROLLADO DESDE 1990 RESPECTO A TVU Y NUTRICION (LIPIDOS)
Epidemiologiacutea (casos amp controles y ldquoecoloacutegicosrdquo)
Patologiacutea Experimental (Modelos animales)
Biologiacutea Celular y Molecular (liacuteneas tumorales en cultivos
celulares biomembranas )
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
OMEGA-6 (ω-6)
Aacutec Linoleico (LA)
Aacutec Araquidoacutenico (AA)
OMEGA-3 (ω-3)
Aacutec Linolenico (ALA) Aacutec Eicosapentaenoico (EPA) Aacutec Docosahexaenoico (DHA)
OMEGA-9 (ω-9)
Aacutec Oleico (OA)
Aacutec Laurico (LA)
Aacutec Palmitico (PA)
Aacutec Estearico (EA)
18
iquestPorquegrave el enfoque de la investigaciograven debe incluir la Epidemiologigravea respuestahellip la gente no come molegraveculas hellip ingiere alimentos y comidas
Das 2006 Eynard et al 2013
cadena hidrocarbonada
bull grupo carboxilo
bull grupo metilo
= PUFAs
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
Comunicamos que los PUFA nutricionales modulan diferencialmente la Biologiacutea Celular del Urotelio (propiedades biofigravesicas de la Membrana Plasmagravetica) e
incremento de w9 dietario favorece el efecto pro-cancerigeno del Arsenico (As)
bull Calderon RO and Eynard AR ldquoFatty acids specifically related to the anisotropics properties of plasma membrane from rat urotheliumrdquo BBActa 1483 174-184 2000
bull Bongiovanni G Eynard AR and RO Calderoacuten Altered lipid profile and changes in uroplakin properties of rat urothelial plasma membrane with diets of different lipid composition Mol Cell Biochem 271 69-75 2005
bull Pre-cancerous changes in urothelial endocytic vesicle leakage fatty acid composition and As and associated element concentrations after arsenic exposure Grasso EJ Bongiovanni GA Peacuterez RD Calderoacuten RO Toxicology 2011 284(1-3)26-33
bull Grasso EJ Calderoacuten RO ldquoUrothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane compositionrdquo Histochem Cell Biol 2013 139(2)249-65
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
Comprobamos que la melamina un irritante de la mucosa urinaria que es proneoplaacutesico y urolitogravegenico a dosis bajas y prolongadas favorece incidencia de Ca in situ y TVU si es antildeadido a dietas rica en w9 (olegraveina) inhibido por dieta w3
(aceite pescado) (ldquoNSrdquo con dieta w6 maigravez)
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
Nos preguntamos iquestcual es la incidencia (izq 2009) y de la mortalidad (derecha) por TVU en poblaciograven de Cograverdoba
y resultograve que no era homogegravenea
Eur J Cancer Prev 18259-2662009
Aballay LR1 Diacuteaz Mdel P Francisca FM Muntildeoz SE ldquoCancer incidence and pattern of arsenic
concentration in drinking water wells in Coacuterdoba Argentinardquo Int J Environ Health
Res 201222220-31
colon mujeres
[000 ndash 410]
(410 - 1270]
(1820 ndash 2890]
(2890 ndash 8510]
(8510ndash 28570]
colon varones
000
[001 - 1820]
(1820 - 2770]
(2770 ndash 5890]
(5890 ndash 163950]
vejiga mujeres
[000 ndash 070]
(070 - 250]
(250 - 430]
(430 ndash 570]
(570 ndash 5000]
vejiga varones
000
(000 - 710]
(710 - 1420]
(1420 - 2440]
(2440 - 24930]
mama
[000 ndash 3100]
(3100 - 5390]
(5390 ndash 7810]
(7810 ndash 13950]
[13950 ndash 83040]
proacutestata
[1400 ndash 2030]
[2030 - 3790]
(3790 ndash 5260]
(5260 ndash 10360]
[10360-152880]
a)
b)
c)
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
iquestTiene que ver zonas con alta incidencia de riesgo de TVU en Coacuterdoba (no muy diferente a otras agravereas de Argentina) en
relaciograven con los haacutebitos dietarios yo contaminantes ambientales
bull Previamente para hacer egraveste estudio epidemiologravegico y para preguntarles a los cordobeses sobre sus haacutebitos alimentarios hubo que desarrollar probar y validar un Instrumento de Encuesta (FFQ) que no existiacutea y que es ahora ampliamente usado en el paigraves y en el extranjero
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
Observamos que en un concepto mas amplio que ldquola dietardquo que el riesgo de TUV estaacute asociado a nuestros ldquopatrones alimentariosrdquo Patrograven ldquoPrudenterdquo diminuye riesgo aceites vegetales (girasol maigravez soja) carnes magras legumbres frutas moderado alcohol ( vino tinto) 4 comidas diarias poco o no tabaco Predomina en Controles
Patrograven ldquoCono Surrdquo u ldquoOccidentalrdquo incrementa riesgo carnes grasas cagraverneos procesados ( embutidos) mayor consumo alcohol (vino y destilados) amilaceos papa fritas mate bebidas colas endulzantes artificiales tabaquismo Predomina en Casos
Andreatta MM Navarro A Muntildeoz SE Aballay L Eynard AR ldquoDietary patterns and food groups are linked to the risk of urinary tract tumors in Argentinardquo Eur J Cancer Prev 19 478 -4842010
Pou SA Niclis C Eynard AR and MP Diacuteaz ldquoDietary patterns and risk of urinary tract tumors a multilevel analysis of individuals in rural and urban contextrdquo Eur J Nutr 53 1247-12532014
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
Hay resultados que apoyan lo propuesto en 1998 Los hallazgos de otros laboratorios rol de PUFAs y TVU
bull Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat
multi-organ carcinogenesis model Toriyama-Baba H et al Jpn J Cancer
Res 2001921175ndash83
bull Various dietary polyunsaturated fatty acids modulate acrylamide-induced
preneoplatic urothelial proliferation and apoptosis in mice Zhang X et al
Exp Toxicol Pathol 2010 629-16
bull Tissue fatty acid composition in human urothelial carcinoma
Miryaghoubzadeh J et al Br J Biomed Sci 201370(1)1-5
bull Docosahexaenoic acid inhibits invasion of human
RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-
modulation of granzyme B expression DEliseo D et al J Nutr Biochem
2012 23452-7
bull Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer
bull Parada B et al Biomed Res Int2013368178 doi 1011552013368178
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
Perturbaciones en las Uroplaquinas Glicoproteigravecas (glicocaliz) y TVU
bull Glycosylation in bladder cancer Ohyama C Int J Clin
Oncol 2008 13308-13
bull Levels of acyl-coenzyme A synthetase 5 in urothelial cells and
corresponding neoplasias reflect cellular differentiationGaisa
NT et al Histol Histopathol 2013 Mar28(3)353-64
bull
bull Glycosylation of uroplakins Implications for bladder
physiopathology Iwona Kątnik-Prastowska et al Glycoconj J
2014 31(9) 623ndash636
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
Desbalance en Eicosanoides PGsInflamacion y TVU
bull Aberrant PGEmetabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells Eruslanov Eet al Int Immuno pharmacol 201111848ndash55
bull Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections Oberbach A et al PLoS ONE 20105e10882
bull Influence of polyunsaturated fatty acids on urologic inflammation Tamma SM et al Int Urol Nephrol 201547(11)1753-61
bull ldquoUrothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar a PPAR alphagamma agonist evidence for urolithiasis as the inciting event in the mode of actionrdquo Dominick MAet al Toxicol Pathol 2006 34903ndash20
bull Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance Kurtova AV et al Nature 2015 8517(7533)209-13
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
TVU y Epidemiologia
bull Intake of a-linolenic acid and other fatty acids in relation to the risk of bladder cancer results from the New Hampshire casendashcontrol study Brinkman MT et al Br J Nutr 20111061070ndash7
bull Meat consumption animal products and the risk of bladder cancer a case-control study in Uruguayan menRonco AL et al Asian Pac J Cancer Prev 201415(14)5805-9
bull Urinary calculi and risk of cancer a nationwide population-based study Shih CJ Medicine (Baltimore) 2014 Dec93(29)e342 doi 101097
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
Nuestros resultados e hipogravetesis ldquoacadegravemicardquo se tornan verosimigraveles
bull hellipEstalla el affaire de antildeadido maliciosos de melamina a formulas lagravecteas en China
bull Xin H Stone R Tainted milk scandal Chinese probe unmasks high-tech bull adulteration with melamine Science 20083221310ndash1 bull bull Bhalla V Grimm PC Chertow GM Pao AC Melamine nephrotoxicity
an emerging epidemic in an era of globalization Kidney Int 200975 774-9
bull hellip ello nos llevograve a poner una nota de advertencia para el seguimiento bull de esos nintildeos y del eventual beneficio de suplementaciograven con 3w en la
siguiente publicaciograven
bull Vara-Messler M Cremonezzi DC Soria EA Eynard AR ldquoNutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents Risk for UTT in children exposed to melamine-contaminated milk formulaerdquo J Env Sci Hlth Part C Env Carcino Ecotox Reviews 30 174-1872012
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
Agente litogegravenico melamina y dantildeo renal en seres humanos
bull Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up a multi-center retrospective analysis He Q et al Ren Fail 2014 36(9)1366-70
bull Increased detection rate of melamine-containing calcium urolithiasis by using matrix-assisted laser desorptionionization time-of-flight mass spectrometry technique in clinical practice Wu CF et al Chim Acta 2014 Apr 20431294-8
bull Melamine contamination in nutritional supplements--Is it an alarm bell for the general consumer athletes and Weekend Warriors Gabriels G et al Nutr J 20151469 doi 101186s12937-015-55-7
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
bull ldquoCrosstalk among dietary polyunsaturated fatty acids urolithiasis chronic inflammation and urinary tract tumor riskrdquo Eynard AR Navarro A Nutrition 29 930-938 2013
bull ldquo Downregulation of the transcription factor GLI1 underlies the growth inhibitory properties of arachidonic acid Andrea Comba12 Maria E Pasqualini2 Marianela Vara Messler2 Renata Silva2 Maite G Fernandez-Barrena1 Anne Vrabel1 Luciana L Almada1 David L Marks1 Volker Ellenrieder3 Aldo R Eynard2 Martin E Fernandez-Zapico1 (revisado JBC)
bull ldquoAntitumoral effects of chia oil in a syngenic murine model of mammary gland carcinomardquo Marianela Vara-Messler12 Maria E Pasqualini1 Andrea Comba1 Silva Renata1 Carola Buccelatti3 Annalisa Trenti2 Lucia Trevisi2 Aldo R Eynard1 Angelo Sala34
Chiara Bolego2 Mirta A Valentich1 (revisadoEur J Nutr)
MUCHAS GRACIAS POR SU ATENCIOacuteN
MUCHAS GRACIAS POR SU ATENCIOacuteN