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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(European Association of Urology) Patients with prostate, bladder or kidney cancers are at greater risk of dying if they have had psychiatric care prior to the cancer treatment. In addition, patients with these cancers show greater suicide risk than the general population, even once the data is corrected for previous psychiatric care. These are the findings of a study presented at the European Association of Urology congress in Barcelona, highlighting the need for psychiatric care to be integrated into cancer treatment.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Authors: Kim GS, Hwang KA, Choi KC Abstract Gestational trophoblastic disease (GTD) is an unusual disease occurring in pregnancy that originates from abnormal trophoblastic cells and comprises a group of diseases with different properties of invasion, metastasis and recurrence. The GTD group includes hydatidiform moles and gestational trophoblastic neoplasms (GTNs), with GTNs being divided into invasive moles, choriocarcinoma, placental site trophoblastic tumors and epithelioid trophoblastic tumors. The present review focuses on current effective treatments for GTD, including conventional and novel promising direct...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
In itslist of the top 10 global health threats for 2019, the World Health Organization (WHO) identified noncommunicable diseases such as diabetes, cancer, and heart disease as a grave danger, causing more than 70% of deaths worldwide and disproportionately affecting low- and middle-income countries. The WHO noted that these illnesses sometimes exacerbate mental health issues among young people, which can lead to suicide.
Source: JAMA - Category: General Medicine Source Type: research
 We all have habits we’d rather not have, whether it’s smoking, emotional eating, or any of a hundred other things. And it’s likely that we’ve all, at one point or another, tried to break one or more of them, only to have the break be only temporary. What’s the secret to permanent habit change? Listen to this episode and find out! Subscribe to Our Show! And Remember to Review Us! About Our Guest Judson Brewer, MD, PhD is a thought leader in the field of habit change and the “science of self-mastery,” having combined over 20 years of experience with mindfu...
Source: World of Psychology - Category: Psychiatry & Psychology Authors: Tags: General Habits Mindfulness The Psych Central Show breaking habits Gabe Howard Vincent M. Wales Source Type: blogs
We present data on 12 main disease groups in all countries, with breakdown by communicable and nutritional diseases, non-communicable diseases, injuries, and ill-defined causes. To calculate age-specific and sex-specific death rates for each cause, we applied the national cause of death distribution to the UN mortality envelopes for 2005–16 for each country.FindingsUnlike Brazil, China, and Mexico, communicable diseases still account for nearly half of deaths in India in children aged 5–14 years (73 920 [46·1%] of 160 330 estimated deaths in 2016). In 2016, India had the highest death rates in nearly...
Source: The Lancet - Category: General Medicine Source Type: research
President Donald Trump’s proposed 2020 budget includes nearly $300 million meant to “defeat the HIV/AIDS epidemic” in the U.S. — even as it calls for a 12% reduction in total funding to the Department of Health and Human Services (HHS). During his February State of the Union address, Trump announced an ambitious plan to “eliminate the HIV epidemic in the United States within 10 years.” During a subsequent call with reporters, health officials said the initiative would focus on 48 at-risk counties across the country and would involve promoting early HIV treatment and diagnosis, expanding ...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized HIV/AIDS Source Type: news
 Suicide is something that most people think they understand, but there are many misconceptions about it. We say it’s a serious problem, yet will mention it casually and insensitively in certain settings. In this episode, our hosts openly discuss suicide and their personal stories with trying to end their own lives.   SUBSCRIBE &REVIEW “I thought about suicide every day for as far back as I can remember.” – Gabe Howard   Highlights From ‘Suicide’ Episode [1:00] Frankly discussing suicide. [3:00] Don’t belittle a person’s suicide attempt. [7:00] Why ...
Source: World of Psychology - Category: Psychiatry & Psychology Authors: Tags: A Bipolar, A Schizophrenic, and a Podcast Depression Schizophrenia Suicide Source Type: blogs
Discussion “[Cannabis] is a genus of flowering plant with three main varieties: sativa, indica and ruderalis.” It has been used for hundreds of years for hemp or fiber and also for psychoactive and medicinal effects. The active compounds are collectively called cannabinoids, of which delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most abundant. The floral buds or calyxes of the plant have the most cannabinoids, but other parts of the plant are also used such as leaves. Hash oil, hashish (or resin) and marijuana (dried leaves) are the common products from strongest to least strongest products. ...
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Hyperhidrosis is defined as abnormally excessive sweating unrelated to heat or exercise. If you have this condition you might find yourself sweating so much that it soaks through your clothes or drips off your hands. Hands, feet, underarms and the face are areas that are typically affected, and the sweating usually occurs on both sides of the body. The most common form of hyperhidrosis is known as primary focal (essential) hyperhidrosis. The nerves responsible for signaling sweat glands become overactive, even though they haven’t been triggered by physical activity or a rise in temperature. It’s interesting to ...
Source: World of Psychology - Category: Psychiatry & Psychology Authors: Tags: Mental Health and Wellness Dehydration Hyperhidrosis Sweat sweating Source Type: blogs
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