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Evaluation of Bystander Cell Killing Effects in Suicide Gene Therapy of Cancer: Engineered Thymidylate Kinase (TMPK)/AZT Enzyme-Prodrug Axis

Suicide gene therapy of cancer (SGTC) entails the introduction of a cDNA sequence into tumor cells whose polypeptide product is capable of either directly activating apoptotic pathways itself or facilitating the activation of pharmacologic agents that do so. The latter class of SGTC approaches is of the greater utility in cancer therapy owing to the ability of some small, activated cytotoxic compounds to diffuse from their site of activation into neighboring malignant cells, where they can also mediate destruction. This phenomenon, termed “bystander killing”, can be highly advantageous in driving significant tumor regression in vivo without the requirement of transduction of each and every tumor cell with the suicide gene. We have developed a robust suicide gene therapy enzyme/prodrug system based on an engineered variant of the human thymidylate kinase (TMPK), which has been endowed with the ability to drive azidothymidine (AZT) activation. Delivery of this suicide gene sequence into tumors by means of recombinant lentivirus-mediated transduction embodies an SGTC strategy that successfully employs bystander cell killing as a mechanism to achieve significant ablation of solid tumors in vivo. Thus, this engineered TMPK/AZT suicide gene therapy axis holds great promise for clinical application in the treatment of inoperable solid tumors in the neoadjuvant setting. Here we present detailed procedures for the preparation of recombinant TMPK-based lentivirus, transduct...
Source: Springer protocols feed by Cancer Research - Category: Cancer & Oncology Source Type: news

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As a retired physician who has written a book about end-of-life issues for elderly patients, I have placed myself in an awkward position. According to most guidelines, at age 67, I am elderly. How will I approach the end of my life? Not only do my personal medical concerns career around in the echo chamber of my own mind, but I have the added challenge of trying to follow my own advice regarding end-of-life decision making. And, there are multiple examples of physicians who did not do that. Witness the example of Francis Warren, Harvard’s most famous surgeon of the 20th century, renowned for heroic cancer surgeries a...
Source: Kevin, M.D. - Medical Weblog - Category: General Medicine Authors: Tags: Physician Palliative Care Source Type: blogs
[Abstract unavailable] Language: en...
Source: SafetyLit - Category: International Medicine & Public Health Tags: Suicide and Self-Harm Source Type: news
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Source: EurekAlert! - Social and Behavioral Science - Category: International Medicine & Public Health Source Type: news
Listen to part one of the first ever LIVE Psych Central Show, recorded on location at HealtheVoices 2018, an annual event that brings together online advocates from across various health conditions for an opportunity to learn, share and connect. In this show, you will meet four advocates who join our hosts on stage for a panel discussion on a variety of advocacy issues, including lupus, inflammatory bowel disease, HIV, and breast cancer. You’ll hear about how being diagnosed affected their lives in ways they didn’t expect, and what made them become advocates. The second half of this show will be posted next wee...
Source: World of Psychology - Category: Psychiatry & Psychology Authors: Tags: General Interview Mental Health and Wellness The Psych Central Show Advocacy Source Type: blogs
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This article reviews those aspects of MAiD that are of particular relevance to psychologists, as seen through the perspective of the author’s research. It includes a brief overview of the major legal cases that led the Supreme Court of Canada to overturn the laws against assisted suicide. It addresses such issues as the prevalence of the desire for death in the terminally ill, reasons for requesting MAiD, the concept of “intolerable suffering,” and the association between MAiD, depression, and suicide. Findings from the Canadian National Palliative Care Survey are highlighted, which document the attitudes...
Source: Canadian Psychology - Category: Psychiatry & Psychology Source Type: research
Authors: Hao S, Du X, Song Y, Ren M, Yang Q, Wang A, Wang Q, Zhao H, Du Z, Zhang G Abstract The incidence of lung cancer and lung cancer-associated mortality have markedly increased worldwide, and gene-targeted therapy has emerged as a promising treatment strategy. The present study aimed to explore the targeted antitumor effect of the herpes simplex virus-thymidine kinase/human interleukin-12 (HSV-TK/hIL-12) fusion gene regulated by the human secretory leukocyte protease inhibitor (hSLPI) promoter of human non-small cell lung cancer (hNSCLC). There were four recombinant eukaryotic expression vectors: pcDNA3.1-CMV-...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
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Source: Wheat Belly Blog - Category: Cardiology Authors: Tags: Wheat Belly Lifestyle autoimmune bowel flora diabetes gluten-free grain-free grains Inflammation joint pain undoctored Source Type: blogs
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Source: blog.bioethics.net - Category: Medical Ethics Authors: Tags: Health Care syndicated Source Type: blogs
Abstract Gene therapy has demonstrated effectiveness in many genetic diseases as evidenced by recent clinical applications. Viral vectors have been extensively tested in clinical gene-therapy trials, but nonviral vectors such as cationic polymers or lipids are much less used due to their lower gene-transfection efficiencies. However, the advantages of nonviral vectors, such as easily tailored structures, nonimmunogenetics, and relatively low cost, still drive great efforts to improve their transfection efficiencies. A reverse question asks if nonviral vectors with current gene transfection efficiency can find appl...
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research
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