BreakThrough Digest Medical News |
- New research project aims to improve cancer therapies using type I interferons
- Virus kills melanoma in animal model, spares normal cells
- Joslin scientists advance understanding of human brown adipose tissue and grow new cells
| New research project aims to improve cancer therapies using type I interferons Posted: 22 Apr 2013 09:00 PM PDT The immune system plays a decisive role in the fight against tumor cells. However, when tumor cells themselves prevent activation of the immune system, the immune system fails to destroy cancer cells. The cancer drug interferon-? could probably neutralize this blockade. This cytokine is being used successfully to treat various forms of cancer. However, some patients experience undesirable autoimmune reactions on administration of the drug. The German Cancer Aid (Deutsche Krebshilfe e.V.) is donating EUR 180,000 to fund a research project at the University Medical Center of Johannes Gutenberg University Mainz that is to identify mechanisms underlying the effects of the cancer drug interferon-? (IFN-?) when it comes to fighting cancer cells by means of the blockade of so-called immunological tolerance processes. In addition, the researchers want to discover novel approaches to increase the efficacy of type I interferons in the treatment of cancer.
Interferon-? can trigger autoimmune reactions in patients, i.e., pathological reactions of the immune system. Interferon-? has been seen to date as an active substance that boosts the immune system and fights tumor cells directly. It is used, for example, in the therapy of malignant melanomas, certain forms of leukemia and cutaneous T-cell lymphomas. “The immune system is usually able to effectively destroy cancer cells. At the same time, however, there are also so-called tumor-associated tolerance processes that protect the tumor cells from being destroyed by the immune system. Autoimmune reactions, which are known side effects of therapies with IFN-?, may indicate that this anti-tumor treatment blocks tolerance mechanisms and thus improves the immune system’s natural ability for tumor rejection,” explained Professor Dr. Kerstin Steinbrink, senior physician at the Department of Dermatology of the Mainz University Medical Center, which is supervising the research project “Analysis of the Effect of Type I Interferons on Immunological Tolerance Processes” funded by the German Cancer Aid. The purpose of this project is to analyze the effects of IFN-? and other type I interferons on various immune cells that exhibit tolerogenic potential in vitro and also in melanoma patients. The knowledge gained through this project should contribute to the development of improved therapy strategies for overcoming tolerance mechanisms associated with tumors. An additional objective is to enhance the efficacy of therapy with type I interferons. Steinbrink’s research team is looking to reduce potential side effects as much as possible. “This research project is taking a patient-oriented approach. The research team led by Professor Dr. Kerstin Steinbrink will profit from its expertise in the area of immunological tolerance that it has gained over several years,” said Professor Dr. Ulrich Förstermann, Chief Scientific Officer of the Mainz University Medical Center. Contact: Dr. Reneé Dillinger-Reiter |
| Virus kills melanoma in animal model, spares normal cells Posted: 22 Apr 2013 09:00 PM PDT Researchers from Yale University School of Medicine have demonstrated that vesicular stomatitis virus (VSV) is highly competent at finding, infecting, and killing human melanoma cells, both in vitro and in animal models, while having little propensity to infect non-cancerous cells.
“If it works as well in humans, this could confer a substantial benefit on patients afflicted with this deadly disease,” says Anthony van den Pol, a researcher on the study. The research was published online ahead of print in the Journal of Virology. Most normal cells resist virus infection by activating antiviral processes that protect nearby cells. “The working hypothesis was that since many cancer cells show a deficient ability to withstand virus infection, maybe a fast-acting virus such as VSV would be able to infect and kill cancer cells before the virus was eliminated by the immune system,” says van den Pol. And indeed, the virus was able to selectively infect multiple deadly human melanomas that had been implanted in a mouse model, yet showed little infectivity towards normal mouse cells, he says. Many different mechanisms are involved in innate immunity, the type of immunity that combats viral infection. van den Pol plans to investigate which specific mechanisms are malfunctioning in cancer cells, knowledge that would be hugely beneficial both in understanding how cancer affects immunity, and in enhancing a virus’ ability to target cancer cells, he says. Melanoma is the most deadly skin cancer. Most melanomas are incurable once they have metastasized into the body. The incidence of melanoma has tripled over the last three decades, and it accounts for approximately 75 percent of skin cancer-related deaths. ### A copy of the manuscript can be found online at http://bit.ly/asmtip0413b. Formal publication is scheduled for the June 2013 issue of the Journal of Virology. (G. Wollmann, J.N. Davis, M.W. Bosenberg, and A.N. van den Pol, 2013. Vesicular stomatitis virus variants selectively infect and kill human melanomas but not normal melanocytes. J. Virol. Published ahead of print 3 April 2013 , doi:10.1128/JVI.03311-12) Journal of Virology is a publication of the American Society for Microbiology (ASM). The ASM is the largest single life science society, composed of over 39,000 scientists and health professionals. Its mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide. Contact: Jim Sliwa |
| Joslin scientists advance understanding of human brown adipose tissue and grow new cells Posted: 21 Apr 2013 09:00 PM PDT Joslin scientists report significant findings about the location, genetic expression and function of human brown adipose tissue (BAT) and the generation of new BAT cells. These findings, which appear in the April 2013 issue of Nature Medicine, may contribute to further study of BAT’s role in human metabolism and developing treatments that use BAT to promote weight loss.
Two types of adipose (fat) tissue ? brown and white — are found in mammals. Unlike the more predominant white adipose tissue (WAT) which stores fat, BAT burns fat to produce heat when the body is exposed to cold and also plays a role in energy metabolism. Human studies have shown that greater quantities of BAT are associated with lower body weight. BAT has been a major focus of study among scientists and pharmaceutical companies based on its potential as a treatment to combat obesity, a major risk factor for type 2 diabetes. Studies in mice have identified two types of BAT: constitutive or “classical” BAT which is present at birth and persists throughout life and recruitable or “beige” BAT which can be produced from within white fat in response to metabolic conditions. These two types of BAT may also be present in humans. Previous studies have identified the human neck as a primary location for BAT deposits. To determine the precise locations of these deposits, Joslin scientists obtained fat samples from five neck regions of patients undergoing neck surgery. Analysis of the samples showed that BAT was most abundant in deep regions of the neck, near the carotid sheath and longus colli muscles. These samples expressed the BAT marker gene, uncoupling protein 1 (UCP1), which is involved in heat generation. “BAT is most abundant in the deep locations of the neck, close to the sympathetic chain and the carotid arteries, where it likely helps to warm blood and raise body temperature. Now that we know where brown fat is, we can easily collect more cells for further study,” says Aaron M. Cypess, M.D., Ph.D., senior author and Assistant Investigator in the Section of Integrative Physiology and Metabolism and Assistant Professor at Harvard Medical School. In analyzing genetic expression in superficial and deep human neck fat tissue, the fat from deep locations was found to most closely resemble cells from constitutive mouse BAT, the kind already known to consume large quantities of glucose and fat. The Joslin scientists compared the oxygen consumption rate (OCR), which demonstrates the capacity to burn calories, of human BAT cells to mouse constitutive BAT cells and human WAT. This is the first study to directly measure brown fat cells’ OCR at baseline. The OCR of the human BAT cells from the deep location next to the longus colli was nearly 50 percent of the mouse BAT cells; in contrast, the OCR of human WAT was only one-hundredth of the OCR found in the most active human BAT from the longus colli depot. “We show that at baseline, brown fat cells have a great capacity to burn fat,” says Dr. Cypess. The scientists were able to grow new functional brown fat cells (adipocytes) by differentiating precursor cells (preadipocytes) derived from both superficial and deep human neck fat tissue. When stimulated, the cells expressed the same genes as naturally occurring brown fat cells. This is the first report of the production of brown fat cells (adipogenesis) that can respond to pharmacological stimulation. The Joslin scientists are following up on this study to learn more about the functions of BAT, including how it affects energy balance and uses glucose. Having the ability to produce brown fat cells outside the body will make it possible to develop drugs and other potential treatments that increase BAT activity to combat obesity. “Our research has significant practical applications. If we stimulate the growth of brown fat in people, it may burn their white fat and help them lose weight, which lessens insulin resistance and improves diabetes,” says Dr. Cypess. ### This study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, Harvard University and its affiliated academic health care centers, the Harvard Stem Cell Institute, and Eli Lilly Foundation. About Joslin Diabetes Center
Joslin Diabetes Center, located in Boston, Massachusetts, is the world’s largest diabetes research and clinical care organization. Joslin is dedicated to ensuring that people with diabetes live long, healthy lives and offers real hope and progress toward diabetes prevention and a cure. Joslin is an independent, nonprofit institution affiliated with Harvard Medical School. Our mission is to prevent, treat and cure diabetes. Our vision is a world free of diabetes and its complications. For more information, visit http://www.joslin.org. About Joslin Research
Joslin Research comprises the most comprehensive and productive effort in diabetes research under one roof anywhere in the world. With 30?plus faculty?level investigators and an annual research budget of $36 million, Joslin researchers focus on unraveling the biological, biochemical and genetic processes that underlie the development of type 1 and type 2 diabetes and related complications. Joslin research is highly innovative and imaginative, employing the newest tools in genetics, genomics and proteomics to identify abnormalities that may play a role in the development of diabetes and its complications. Joslin Clinic patients, and others with diabetes, have the option of participating in clinical trials at Joslin to help translate basic research into treatment innovations. Joslin has one of the largest diabetes training programs in the world, educating 150 M.D. and Ph.D. researchers each year, many of whom go on to head diabetes initiatives at leading institutions all over the globe. For more information, visit http://www.joslinresearch.org. Contact: Jeffrey Bright |
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