By a News Reporter-Staff News Editor at Cancer Gene Therapy Week -- Investigators publish new report on Biotechnology. According to news reporting originating in Miyagi, Japan, by NewsRx journalists, research stated, "We previously described a novel suicide (or 'cell fate control') gene therapy enzyme/prodrug system based on an engineered variant of human thymidylate kinase (TMPK) that potentiates azidothymidine (AZT) activation. Delivery of a suicide gene sequence into tumors by lentiviral transduction embodies a cancer gene therapy that could employ bystander cell killing as a mechanism driving significant tumor regression in vivo."
The news reporters obtained a quote from the research from Tohoku University, "Here we present evidence of a significant bystander cell killing in vitro and in vivo mediated by the TMPK/AZT suicide gene axis that is reliant on the formation of functional gap-junctional intercellular communications (GJICs). Potentiation of AZT activation by the engineered TMPK expressed in the human prostate cancer cell line, PC-3, resulted in effective bystander killing of PC-3 cells lacking TMPK expression--an effect that could be blocked by the GJIC inhibitor, carbenoxolone. Although GJICs are mainly formed by connexins, a new family of GJIC molecules designated pannexins has been recently identified. PC-3 cells expressed both connexin43 (Cx43) and Pannexin1 (Panx1), but Panx1 expression predominated at the plasma membrane, whereas Cx43 expression was primarily localized to the cytosol. The contribution of bystander effects to the reduction of solid tumor xenografts established by the PC-3 cell line was evaluated in an animal model. We demonstrate the contribution of bystander cell killing to tumor regression in a xenograft model relying on the delivery of expression of the TMPK suicide gene into tumors via direct intratumoral injection of recombinant therapeutic lentivirus."
According to the news reporters, the research concluded: "Taken together, our data underscore that the TMPK/AZT enzyme-prodrug axis can be effectively utilized in suicide gene therapy of solid tumors, wherein significant tumor regression can be achieved via bystander effects mediated by GJICs."
For more information on this research see: The engineered thymidylate kinase (TMPK)/AZT enzyme-prodrug axis offers efficient bystander cell killing for suicide gene therapy of cancer. Plos One, 2013;8(10):e78711. (Public Library of Science - www.plos.org; Plos One - www.plosone.org)
Our news correspondents report that additional information may be obtained by contacting T. Sato, Molecular Pharmacology, Tohoku University, Sendai, Miyagi, Japan. Additional authors for this research include A. Neschadim, A. Lavie, T. Yanagisawa and J.A Medin (see also Biotechnology).
Keywords for this news article include: Asia, Biotechnology, Japan, Miyagi, Kinase, Oncology, Engineering, Therapeutics, Cancer Gene Therapy, Enzymes and Coenzymes.
Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC