Irreversible electroporation shows efficacy against pancreatic carcinoma without systemic toxicity in mouse models
ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) therapies show limited success. Irreversible electroporation (IRE) is an innovative loco-regional therapy in which high-voltage pulses are applied to induce plasma membrane defects leading to cellular death. In the present study we evaluated the feasibility of IRE against PDAC. IRE treatment exhibited significant antitumor effects and prolonged survival in mice with orthotopic xenografts. Extensive tumor necrosis, reduced tumor cell proliferation and disruption of microvessels were observed at different days post-IRE. Animals had transient increases in transaminases, amylase and lipase enzymes that normalized at 24h post-IRE. These results suggest that IRE could be an effective treatment for locally advanced pancreatic tumors.
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ABSTRACT: Tissue ablation is an essential procedure for the treatment of many diseases. In the last decade, a non-thermal tissue ablation using intensive pulsed electric fields, called non-thermal irreversible electroporation (NTIRE), has rapidly emerged. The exact mechanisms responsible for cell death by NTIRE, however, are currently unknown. Nevertheless, the techniques remarkable ability to ablate tissue in the proximity of larger blood vessels, to preserve tissue architecture, short procedure duration, and shortened post-operative recovery period rapidly moved NTIRE from bench to bed side. This article provides an overview on the development of NTIRE, its current state of the art, challenges and future needs.IEEE transactions on bio-medical engineering 01/2013; 60(3). DOI:10.1109/TBME.2013.2238672 · 2.23 Impact Factor
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ABSTRACT: Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p〈0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors.Oncotarget 01/2012; · 6.63 Impact Factor
- Archives of surgery (Chicago, Ill.: 1960) 11/2012; 147(11):1061. DOI:10.1001/jamasurg.2013.493 · 4.30 Impact Factor