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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OBJECTIVE: Vast efforts are directed toward curing or prolonging the life of patients with cancer. However, less attention is given to mental health aspects of cancer care, and there is elevated incidence of death by suicide in this population. Evaluating ...
Source: SafetyLit - Category: International Medicine & Public Health Tags: Suicide and Self-Harm Source Type: news
Thread Starter Will voluntary detainment in a mental hospital affect becoming a medic? Follow 30 minutes ago 30m ago I haven’t been hospitalised but I have overdosed. As others have said it’s confidential and won’t affect you application or acceptance so that shouldn’t stop you fr...
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(Wiley) In addition to focusing on curing or prolonging the life of patients with cancer, it is important to also address mental health aspects of cancer care, especially because there is an elevated incidence of death by suicide in this patient population. A new Psycho-Oncology analysis uncovers opportunities to mitigate the risk of death by suicide among patients with cancer.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Psycho-Oncology, EarlyView.
Source: Psycho-Oncology - Category: Cancer & Oncology Authors: Source Type: research
Astha Koolwal Kapoor, Sushma BhatnagarIndian Journal of Palliative Care 2018 24(3):381-383Suicide risk is very high in the patients suffering from advanced cancer. Around 60% of patients with advanced cancer suffer from cancer related pain and this further accentuates the risk of psychiatric disorders as well as suicide. A fifty year old male who was a known case of carcinoma of floor of mouth, post chemotherapy and post radiotherapy came in the outpatient clinic with complains of throat pain which increased on swallowing. On further probing, it was revealed, that he consumed poison in the recent past while being agita...
Source: Indian Journal of Palliative Care - Category: Palliative Care Authors: Source Type: research
We presently forget 98% of everything we experience. That will go away in favor of perfect, controllable, configurable memory. Skills and knowledge will become commodities that can be purchased and installed. We will be able to feel exactly as we wish to feel at any given time. How we perceive the world will be mutable and subject to choice. How we think, the very fundamental basis of the mind, will also be mutable and subject to choice. We will merge with our machines, as Kurzweil puts it. The boundary between mind and computing device, between the individual and his or her tools, will blur. Over the course of the ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Suicide rates are high and have only been increasing over the years. Over 800,000 people die all over the world by suicide each year. A proportion of the suicides are murder suicides resulting in additional loss of life. Attempts at suicide occur more frequently and we have about one million suicide attempts occurring each year. Suicide is a heart-breaking problem that is growing and needs to be addressed in as many ways as is possible. Understanding the risk factors, knowing the warning signs and what to do about them, is a crucial step. The more the awareness the greater the impact on suicide prevention. Risk Factors f...
Source: Psych Central - Category: Psychiatry Authors: Tags: Depression General Suicide Source Type: news
Authors: Parker Kerrigan BC, Hossain A, Yamashita S, Lang FF Abstract Stem cells (SC) are the seeds of tissue repair and regeneration that have been extensively investigated as tumor-tropic vectors for gene delivery to solid cancers. SC have an inherent glioma tropism that supports their use as reliable vehicles to deliver therapeutic gene products to brain neoplasms. Several types of adult SC (ASC) have been used to carry antiglioma agents, and neural SC (NSC) and mesenchymal SC (MSC) are the most studied. The therapeutic cargoes that have been tested include secreted proteins, converting enzyme/prodrug suicide co...
Source: Progress in Neurological Surgery - Category: Neurosurgery Tags: Prog Neurol Surg Source Type: research
Lung cancer patients have an increased risk for committing suicide. But no comprehensive study about the suicide issues among non-small-cell lung cancer (NSCLC) patients has been published. We aimed to estimate the trend of suicide rate and identify the hi...
Source: SafetyLit - Category: International Medicine & Public Health Tags: Suicide and Self-Harm Source Type: news
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