Suchergebnisse

[EN] Objective: Determine whether Radiofrequency ablation (RFA) of the pancreas and subsequent transection of the main pancreatic duct may avoid the risk of both necrotizing pancreatitis and postoperative pancreatic fistula (POPF) formation. Methods: Thirty-two rats were subjected to RFA and section of the pancreas over their portal vein. Animals were killed at 3, 7, 15 and 21 days (Groups 0-3, respectively). Two additional control groups (sham operation and user manipulation only, respectively) of 15 days of postoperative period were considered. Postoperative complications, histological changes (including morphometric and immunohistochemical analysis) and incidence of POPF were evaluated. Results: A significant increase in serum amylase levels (p 0.05) on the 3rd postoperative day which return to baseline levels in the following weeks was noted in groups 0-3. Those groups showed a rapid atrophy of the distal pancreas by apoptosis with no signs of necrotizing pancreatitis or POPF. The distal pancreas in groups 1-3 compared to group 0 and control groups showed a significant increase of small islets ( 1000 μm 2 ). Conclusions: The rapid acinar atrophy of the distal pancreas after RFA and section of the pancreatic ducts in this model does not lead to necrotizing pancreatitis. ; This research has been supported by grant TEC2011-27133-C02-02 from the Spanish Government and the European Economic Community. ; Quesada, R.; Burdío, F.; Iglesias, M.; Dorcaratto, D.; Cáceres, M.; Andaluz, A.; Poves, I. (2014). Radiofrequency pancreatic ablation and section of the main pancreatic duct does not lead to necrotizing pancreatitis. Pancreas. 43(6):931-937. doi:10.1097/MPA.0000000000000156 ; S ; 931 ; 937 ; 43 ; 6

Background. Spread hepatic tumours are not suitable for treatment either by surgery or conventional ablation methods. The aim of this study was to evaluate feasibility and safety of selectively increasing the healthy hepatic conductivity by the hypersaline infusion (HI) through the portal vein. We hypothesize this will allow simultaneous safe treatment of all nodules by irreversible electroporation (IRE) when applied in a transhepatic fashion. Material and methods. Sprague Dawley (Group A, n = 10) and Athymic rats with implanted hepatic tumour (Group B, n = 8) were employed. HI was performed (NaCl 20%, 3.8 mL/Kg) by trans-splenic puncture. Deionized serum (40 mL/ Kg) and furosemide (2 mL/Kg) were simultaneously infused through the jugular vein to compensate hypernatremia. Changes in conductivity were monitored in the hepatic and tumour tissue. The period in which hepatic conductivity was higher than tumour conductivity was defined as the therapeutic window (TW). Animals were monitored during 1-month follow-up. The animals were sacrificed and selective samples were used for histological analysis. Results. The overall survival rate was 82.4% after the HI protocol. The mean maximum hepatic conductivity after HI was 2.7 and 3.5 times higher than the baseline value, in group A and B, respectively. The mean maximum hepatic conductivity after HI was 1.4 times higher than tumour tissue in group B creating a TW to implement selective IRE. Conclusions. HI through the portal vein is safe when the hypersaline overload is compensated with deionized serum and it may provide a TW for focused IRE treatment on tumour nodules. ; This work received financial support from the Spanish Government (Ministry of Economy and Competitiveness) under Grant TEC2014-52383-C3. The authors disclose no conflicts of interests.

Background. Spread hepatic tumours are not suitable for treatment either by surgery or conventional ablation methods. The aim of this study was to evaluate feasibility and safety of selectively increasing the healthy hepatic conductivity by the hypersaline infusion (HI) through the portal vein. We hypothesize this will allow simultaneous safe treatment of all nodules by irreversible electroporation (IRE) when applied in a transhepatic fashion. Material and methods. Sprague Dawley (Group A, n = 10) and Athymic rats with implanted hepatic tumour (Group B, n = 8) were employed. HI was performed (NaCl 20%, 3.8 mL/Kg) by trans-splenic puncture. Deionized serum (40 mL/Kg) and furosemide (2 mL/Kg) were simultaneously infused through the jugular vein to compensate hypernatremia. Changes in conductivity were monitored in the hepatic and tumour tissue. The period in which hepatic conductivity was higher than tumour conductivity was defined as the therapeutic window (TW). Animals were monitored during 1-month follow-up. The animals were sacrificed and selective samples were used for histological analysis. Results. The overall survival rate was 82.4% after the HI protocol. The mean maximum hepatic conductivity after HI was 2.7 and 3.5 times higher than the baseline value, in group A and B, respectively. The mean maximum hepatic conductivity after HI was 1.4 times higher than tumour tissue in group B creating a TW to implement selective IRE. Conclusions. HI through the portal vein is safe when the hypersaline overload is compensated with deionized serum and it may provide a TW for focused IRE treatment on tumour nodules. ; This work received financial support from the Spanish Government (Ministry of Economy and Competitiveness) under Grant TEC2014-52383-C3. The authors disclose no conflicts of interests.

Phosphorylated IKKalpha(p45) is a nuclear active form of the IKKalpha kinase that is induced by the MAP kinases BRAF and TAK1 and promotes tumor growth independent of canonical NF-¿B signaling. Insights into the sources of IKKalpha(p45) activation and its downstream substrates in the nucleus remain to be defined. Here, we discover that IKKalpha(p45) is rapidly activated by DNA damage independent of ATM-ATR, but dependent on BRAF-TAK1-p38-MAPK, and is required for robust ATM activation and efficient DNA repair. Abolishing BRAF or IKKalpha activity attenuates ATM, Chk1, MDC1, Kap1, and 53BP1 phosphorylation, compromises 53BP1 and RIF1 co-recruitment to sites of DNA lesions, and inhibits 53BP1-dependent fusion of dysfunctional telomeres. Furthermore, IKKalpha or BRAF inhibition synergistically enhances the therapeutic potential of 5-FU and irinotecan to eradicate chemotherapy-resistant metastatic human tumors in vivo. Our results implicate BRAF and IKKalpha kinases in the DDR and reveal a combination strategy for cancer treatment. ; This work was funded by grants from Instituto de Salud Carlos III FEDER (PIE15/00008 and PI16/00437), Generalitat de Catalunya 2017SGR135, and the "Xarxa de Bancs de Tumors" sponsored by Pla Director d'Oncologia de Catalunya (XBTC). C.C. is supported by FPI BES-2014-068451 and the EMBO Short-Term Fellowship (na7084). P.M. is supported by funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement #702430. The Boulton lab is supported by The Francis Crick Institute, which receives its core funding from Cancer Research UK (FC0010048), the UK Medical Research Council (FC0010048), and the Wellcome Trust (FC0010048). S.J.B. is funded by European Research Council (ERC) Advanced Investigator Grants (TelMetab) and a Wellcome Trust Senior Investigator Grant. The Centre de Regulació Genòmica/Universitat Pompeu Fabra Proteomics Unit is part of the "Plataforma de Recursos Biomoleculares y Bioinformáticos (ProteoRed)" supported by grant PT13/0001 of Instituto de Salud Carlos III from the Spanish government and "Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement de la Generalitat de Catalunya" (2014SGR678). We acknowledge support from the Spanish Ministry of Economy and Competitiveness and "Centro de Excelencia Severo Ochoa 2013-2017" (SEV-2012-0208).