Untitled - Red TemÃ¡tica de investigaciÃ³n cooperativa en cÃ¡ncer

More documents

Recommendations

Info

P-14 AICAR INDUCES BAK/BAK-DEPENDENT APOPTOSIS THROUGH UP-REGU- LATION OF THE BH3-ONLY PROTEINS BIM AND NOXA IN MOUSE EMBRYO FIBROBLASTS MONCUNILL-MASSAGUER C 1 , GONZÁLEZ-GIRONÈS D 1 ,IGLESIAS-SERRET D 1 , COSIALLS AM 1 PÉREZ-PERARNAU A 1 , MARIELA-PALMERI C 1 , RUBIO-PATIÑO C 1 , VIOLLET B 2 , PONS G 1 , VILLUNGER A 3 , GIL J 1 1 DEPARTAMENT DE CIÈNCIES FISIOLÒGIQUES II, INSTITUT D’INVESTIGACIÓ BIOMÈDICA DE BELLVITGE (IDIBELL)–UNIVERSITAT DE BARCELONA, L’HOSPITALET DE LLOBREGAT, CATALUNYA, (RD06/0020/0097) 2 INSTITUT COCHIN, UNIVERSITÉ PARIS DESCARTES, CENTRE NATIONAL DE LA RECHERCHE SCIENTI- FIQUE (CNRS), PARIS, FRANCE 3 DIVISION OF DEVELOPMENTAL IMMUNOLOGY, BIOCENTER, INNSBRUCK MEDICAL UNIVERSITY, INNBRUCK, AUSTRIA AICAR triggers apoptosis independently of AMPK and p53 through the upregulation of the BH3-only proteins BIM and NOXA in chronic lymphocytic leukemia (CLL) cells. However, it remains unknown how AICAR treatment modulates the expression of these BH3-only proteins. Here we propose mouse embryonic fibroblasts (MEFs) as a useful model to analyze the mechanism of AICAR-induced apoptosis. ZMP formation is required for AICAR-induced apoptosis and it activates its main target Ampk. Nevertheless, direct Ampk activation with A-769662 failed to induce apoptosis in MEFs, and AICAR also potently induced apoptosis in Ampkα1-/-/α2-/- MEFs, demonstrating an Ampk-independent mechanism of cell death. Notably, MEFs double knockouot for Bax and Bak were completely resistant to the apoptosis triggered by AICAR, confirming the involvement of the mitochondrial pathway in its mechanism of action. Apoptosis was preceeded by ZMP-dependent but Ampk-independent modulation of mRNA levels of different Bcl-2 family members, including Noxa, Bim and Bcl-2. Bim protein levels are accumulated by AICAR treatment of MEF cells, suggesting its role in the apoptotic process. Strikingly, MEFs lacking both Bim and Noxa display high resistance to AICAR, in concordance with their requirement for AICAR-induced cell death B lymphocytes. Overall, we demonstrate that AICAR mechanism of apoptosis is highly similar in MEFs, mouse B lymphocytes and CLL cells and thus MEFs will be used for the complete elucidation of AICAR-induced apoptosis mechanism. P-15 DETERMINATION OF SNAIL1 PARACRINE FUNCTIONS: IMPLICATION IN PRO-TUMOROGENIC ABILITIES ON COLORECTAL EPITHELIAL CELLS LINES HERRERA-TEJERO A 1 , HERRERA-TORRES M 1 ,GARCÍA DE HERREROS A 1 , BONILLA-VELASCO F 1 , PEÑA-MAROTO 1 1 HOSPITAL UNIV. PUERTA HIERRO-MAJADAHONDA (RD06/0020/0020) Experimental data support the idea that the active recruitment of stromal cells by tumor cells is essential for the generation of a microenvironment that actively fosters tumor growth. Snail1 is a transcriptional factor that plays an important role in epithelial-mesenchymal transition (EMT)-mediated metastasis through the regulation of E-Cadherin expression. E-Cadherin is downregulated in human colon epithelial cells when co-cultured with Snail1 expressing cells. Moreover, expression of Snail1 in the tumor stroma correlates with lower specific survival of cancer patients. The aim of this study was to determine the possible pro-tumorogenic paracrine functions of Snail1 expressing cells. Cancer-Associated Fibroblasts (CAFs) and Normal Fibroblasts (NFs) were isolated from 15 primary human colon tumors and 5 normal mucosa respectively. Colon cancer cell lines SW480-ADH or LIM1215 were co-cultured with a panel of Snail1 expressing colon and fibroblasts cell lines, or primary CAFs, to study migration and proliferation changes. Coculture analyses were developed using trans-well culture system. Proliferation assays were also analyzed with conditioned medium from fibroblasts and CAFs. The Snail1 expressing cell lines induced higher cell migration of SW480-ADH or LIM1215 compared with Mock cells. Moreover, increase of proliferation index in SW480-ADH cells were observed when co-cultured with Snail1 expressing cells. In both migration and proliferation, the effect was higher when Snail1 was expressed by fibroblasts, regarding tumor colon cells. Analysis of primary CAFs showed higher Snail expression levels in CAFs compared with NFs. Interestingly, co-culture of CAFs with LIM1215 or SW480-ADH cells induced a significant increase in epithelial cell migration, as well as in proliferation, associated with Snail expression. Together, these experiments demonstrate the Snail1-dependent paracrine pro-tumorogenic effects of fibroblasts on colon cancer cells. Future analysis will include cytokine profile study of Snail1 expressing cells, as well as primary CAFs and NFs, to characterize the cross-talk between colorectal cancer cells and fibroblasts. 58 59
P-16 MEAT CONSUMPTION AND OESOPHAGEAL ADENOCARCINOMA RISK IN THE EPIC COHORT LUJAN-BARROSO L 1 , JAKSZYN P 1 , AGUDO A 1 , GONZÁLEZ SVATETZ CA 1 1 ICO/IDIBELL, BARCELONA (RD06/0020/0091) Background: Previous analysis from our group based on only 65 oesophageal adenocarcinomas cancer (OAC) cases suggest a positive association with processed meat and an unexpected positive association with poultry. Very little information is available regarding different types of meat intake and OAC in prospective studies. Objetive: To assess the association between meat intake (red, white and processed meat) and OAC. Estimate the substitution effect of different types of meat. Methods: The EPIC study is a study designed to investigate the relationships between diet, lifestyle, and environmental factors and the incidence of cancer carried-out in 23 centres from 10 European countries. Meat intake was estimated based on country-specific food questionnaires. The hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) for the development of OAC cancer were estimated using the Cox proportional hazards model. Meat intake is presented as 25g/2000kcal. All models were adjusted for BMI, sex, smoking status, educational level, total fruits and vegetables, alcohol and energy intake. Additive model was constructed to evaluate: 1. additive effect (the risk associated with to adding the amount of red meat while white meat remains constant). 2. Substitution effect (the effect of substitution red meat for white meat while keeping total meat intake constant). Results: The association between total meat intake and OAC was statically significant (HR: 1.16, 95%CI=1.07-1.27). Additive models shows a positive significant effect of white meat (HR: 1.22, 95%CI=1.03- 1.45) and processed meat (HR: 1.18, 95%CI= 1.02-1.37). None substitution effect were found for any meat-type. Conclusion: We have found a positive significant association between processed meat intake and OAC and a non significant association with red meat intake. An unexpected statically significant increase of the risk due to white meat intake was observed. Further studies with large sample size are needed in order to clarify these findings P-17 ΔNP73 UPREGULATION CORRELATES WITH POOR PROGNOSIS OF COLON CANCER PATIENTS SAN MILLÁN BLANCO C 1 , SOLDEVILLA NAVARRO B 1 , GIL CALDERÓN B 1 , BONILLA VELASCO F 1 , DOMÍNGUEZ MUÑOZ G 1 1 HOSPITAL UNIV. PUERTA DE HIERRO-UAM, MADRID (RD06/0020/0020) Cumulative data support the role of ∆TAp73 variants in tumorigenic processes such as drug resistance. We evaluate the impact of TP73 isoforms and their putative target genes ABCB1, HMGB1 and CASP1 on the survival of colon cancer patients and the correlation between their expressions. We determined in 77 colon cancer patients the expression of Ex2p73, Ex2/3p73, ΔNp73, TAp73, ABCB1, HMGB1 and CASP1 by RT-PCR. Tumor characteristics, disease-free survival (DFS) and overall survival (OS) were examined in each patient. Additionally, functional experiments were performed to check whether ectopic expression of ∆Np73 modifies the proliferation, drug resistance, migration and invasion properties of colon tumor cells and the expression of ABCB1, HMGB1 and CASP1. Positive correlations were observed between the expression levels of ∆TAp73 variants and HMGB1. A trend was also observed for ABCB1. Over-expression of ΔEx2/3p73 and ΔNp73 isoforms significantly associated with advanced stages (p = 0.04 and p = 0.03, respectively) and predicted shortened OS (p = 0.04 and p = 0.05, respectively). Similarly, high levels of ABCB1 and HMGB1 associated with shorter OS (p = 0.04 and p = 0.05, respectively). Multivariate analysis showed that, in addition to the tumor stage, ABCB1 and HMGB1 had independent relationships with OS (p = 0.008). Ectopic expression of ∆Np73 associated with an increase in proliferation and drug resistance. The positive correlation between ∆TAp73 variants and HMGB1 and ABCB1 expression supports them as TP73 targets. The fact that upregulation of ∆TAp73 isoforms associated with shortened OS, increase in proliferation and drug resistance confirms their oncogenic role and plausible value as prognostic markers. ABCB1 and HMGB1, putative ∆TAp73 target genes, strongly predict OS in an independent manner, making clear the importance of studying downstream TP73 targets that could predict the outcome of colon cancer patients better than ∆TAp73 themselves do. 60 61
Page 3 and 4: Programa Científico 7 Resumenes de
Page 5 and 6: 10:00 h Recepción de los Participa
Page 7: 11:10 h O-19. “PAPEL DEL CORREPRE
Page 10 and 11: O-02 p21 LOSS INDUCES AN INFLAMMATO
Page 12 and 13: O-06 CCND2 REARRANGEMENTS ARE THE M
Page 14 and 15: O-10 INFLUENCE OF LKB1/STK11 IN GEN
Page 16 and 17: O-14 ANALYSIS OF NEW GENES DIRECTLY
Page 18 and 19: O-18 PIK3CA ALTERATIONS IN BLADDER
Page 20 and 21: P-01 “HOMEOBOX NKX2-3 PROTEIN IND
Page 22 and 23: , 43
Page 24 and 25: P-03 TETRACHLORODIBENZO-P-DIOXIN DI
Page 26 and 27: P-07 DIOXIN RECEPTOR KNOCK-DOWN PRO
Page 28 and 29: P-10 MOLECULAR PATHWAYS REGULATED B
Page 32 and 33: P-18 DIFFERENT EXOSOME CARGO FROM P
Page 34 and 35: P-22 ÍNDICE DE RIESGO BASADO EN GE
Page 36 and 37: P-26 SECUENCIACIÓN DE ALTO RENDIMI
Page 38 and 39: P-30 GENETIC VARIANTS IN MIRNAS: NE
Page 40 and 41: P-34 CARACTERIZACIÓN CLÍNICA Y BI
Page 42 and 43: P-37 IDENTIFICATION OF PROTEIN BIOM
Page 44 and 45: P-41 LA FOSFORILACIÓN DE eIF4E AUM
Page 46: P-45 METHODS FOR RNA AND miRNA PURI
Page 49 and 50: Apellidos Nombre E-mail Grupo RTICC

Untitled - Red TemÃ¡tica de investigaciÃ³n cooperativa en cÃ¡ncer

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?