BreakThrough Digest Medical News |
- Researchers discover breakthrough in ovarian cancer
- Scientists find calcium is the initial trigger in our immune response to healing
- Spanish scientists develop a pioneering technique to effectively treat mucositis
- Scientists identify new therapeutic target for coronary heart disease
- Cure in sight for kissing bug’s bite
| Researchers discover breakthrough in ovarian cancer Posted: 13 Feb 2013 09:00 PM PST Researchers at The University of Arizona Cancer Center at St. Joseph’s Hospital and Medical Center in Phoenix have discovered that many women with low-grade serous carcinoma of the ovary or peritoneum have seen their tumors stabilize or shrink after taking a regular dose of the compound selumetinib.
The findings, published in the Feb. 14 edition of The Lancet Oncology, show that selumetinib targets a mutation in the MAPK pathway for patients with low-grade serous carcinoma, allowing for treatment on previously chemoresistant tumors. “This is a potentially important breakthrough for the Gynecologic Oncology Group,” said John Farley, MD, a gynecologic oncologist in the Division of Gynecologic Oncology and the Department of Obstetrics and Gynecology at the Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center, a Dignity Health Member. The Gynecologic Oncology Group is a non-profit international organization with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of gynecologic malignancies. Dr. Farley is part of the University of Arizona Cancer Center at St. Joseph’s and is board certified in obstetrics and gynecology with a subspecialty certification in gynecologic oncology. He is a retired decorated Army colonel who completed a residency in obstetrics and gynecology and a fellowship in gynecologic oncology at Walter Reed Army Medical Center. He is the first author on this study. This study was initially developed in 2007, with 52 patients enrolled for the Phase II clinical trial between December 2007 and November 2009. Patients were given 50 milligrams of selumetinib orally twice daily. Of those participants, eight had a measurable decrease in tumor size, seven had partial responses and 34 patients saw their tumors stabilize. The findings suggest that inhibitors of the MAPK pathway warrant further investigation in patients with low-grade ovarian cancer. “There just aren’t very good treatments for low-grade ovarian cancer, so this discovery opens up a lot of new exciting possibilities for us,” Dr. Farley said. He added that Phase III of this trial is scheduled to begin in the next few weeks, with that trial to be the “definitive test” before the treatment becomes available to the general population. ### This study is registered with ClinicalTrials.gov, number NCT00551070. About The University of Arizona Cancer Center The University of Arizona Cancer Center is the only National Cancer Institute-designated Comprehensive Cancer Center headquartered in Arizona. The UACC is supported by NCI Cancer Center Support Grant number CA023074. With primary locations at the University of Arizona in Tucson and at St. Joseph’s Hospital and Medical Center in Phoenix, the Cancer Center has more than a dozen research and education offices in Phoenix and throughout the state and 300 physician and scientist members work together to prevent and cure cancer. For more information, go to http://www.arizonacancercenter.org About St. Joseph’s Hospital and Medical Center Located in the heart of Phoenix, Ariz., St. Joseph’s Hospital and Medical Center is a 607-bed, not-for-profit hospital that provides a wide range of health, social and support services with special advocacy for the poor and underserved. St. Joseph’s is a nationally recognized center for quality tertiary care, medical education and research. It includes the internationally renowned Barrow Neurological Institute, the Heart & Lung Institute, the Muhammad Ali Parkinson Center, and a Level I Trauma Center verified by the American College of Surgeons. U.S. News & World Report routinely ranks St. Joseph’s among the best hospitals in the United States for neurology and neurosurgery. Contact: Lynne Reaves |
| Scientists find calcium is the initial trigger in our immune response to healing Posted: 13 Feb 2013 09:00 PM PST For the first time scientists studying the cellular processes underlying the body’s response to healing have revealed how a flash of calcium is the very first step in repairing damaged tissue. The findings, published in Current Biology, could lead to new therapies that speed up the healing process following injury or surgery.
Until recently, very little was known about how damaged tissue activates and attracts the first white blood cells to the wound ? the first stage in the healing process. However, researchers from the University of Bristol’s School of Biochemistry in collaboration with a team from the University of Bath, have shown that the very first trigger in this process is a flash of calcium which spreads like a wave back from the wound edge through gap junctions that connect all the cells. This flash of calcium signal goes on to activate an enzyme known as DUOX that synthesises hydrogen peroxide, which, in turn, attracts the first white blood cells to the wound. This white blood cell invasion, which is initiated during our inflammatory responses, is needed to kill off invading microbes and stop the onset of septicaemia following tissue damage. The findings indicate that the wound-induced calcium flash represents the earliest identified signal following wounding and might therefore orchestrate the rapid recruitment of immune cells. To assess the impact of a reduced calcium flash upon the inflammatory response the team used Drosophila (fruit fly) embryos because they are translucent which makes it easy to image the inflammatory response and because of their simple genetics. The team found that blocking the calcium flash inhibited H2O2 release at the wound site leading to a reduction in the number of immune cells migrating to the wound. Paul Martin, Professor of Cell Biology and an expert in wound healing at the University, said: “White blood cells are a little like ‘Jeckyll and Hyde’ in that they help us heal but are also the reason behind why we scar so we really need to know how they are regulated at wounds in order to learn how to control their behaviours for future therapeutic intervention.” Will Razzell, the lead PhD researcher on this study, added: “We are more than ever understanding the pathways that lead to immune cell attraction to wounds. As calcium represents the immediate inflammatory signal, we now have a good foundation to investigate this complicated process further.” Contact: Caroline Clancy |
| Spanish scientists develop a pioneering technique to effectively treat mucositis Posted: 13 Feb 2013 09:00 PM PST Investigators at the University of Granada have patented a melatonin gel that is 100% effective against this inflammatory reaction. Scientists from the University of Granada have patented a compound made from melatonin that is effective in the treatment and prevention of mucositis, one of the most unpleasant side effects of chemotherapy and radiotherapy in cancer patients. It is an easily applied gel that “is believed to be the first product developed anywhere in the world to combat mucositis”, according to investigators from the Biomedical Research Centre in Granada. There is currently no treatment for this problem because its physiopathology is still not understood.
Mucositis is an inflammatory reaction that affects the mucous membranes throughout the digestive tract from the mouth to the anus, and is one of the principle adverse effects resulting from chemotherapy, radiotherapy and bone marrow transplants. This problem severely complicates the treatment of cancer as patients frequently have to be admitted to hospital, naso-gastric tubes and opiates must be used and, most seriously, radiotherapy treatment against the cancer is interrupted. On some occasions, the results can be fatal. Radiotherapy and Mucositis.
It is estimated that 40% of patients who receive radiotherapy and up to 70% of bone marrow transplant patients will develop mucositis. In patients with cancer of the head and neck, 97% develop this condition to some degree, while 100% of those who receive staged radiotherapy over a prolonged period also suffer from mucositis. At the moment no effective treatment for mucositis exists, which is why the product developed at the University of Granada is of such enormous interest to the medical world and the pharmaceutical industry, given that it could greatly enhance the quality of life of cancer patients. This patented compound is the fruit of more than twenty years of research into the properties of melatonin at the University of Granada, which has shown that mitochondrial damage is present in cases of mucositis. “Melatonin alleviates the inflammatory reaction and protects the mitochondria,´ says Germaine Escames Rosa, the principal author of the study, “and for this reason we think it could be useful for treating mucositis.” The success of the treatment developed at the University of Granada is due to the type of gel used in the pharmaceutical formulation, and the amount of melatonin used. “The oral application of this melatonin gel at a specific concentration, impregnates the mucous membranes and reverses the mitochondrial damage, preventing the appearance of mucositis in 100% of cases.” Any other type of melatonin application, such as different concentrations, would not have the same effect. National Patent
Via the University of Granada Research Results Transfer Office, the product has already been patented at national level, and an international patent has also been applied for. In addition, the microbiological and stability tests that are required in order to apply for registration as a health product are currently being undertaken, while the research team are involved in preparing for its launch as a commercial product. The studies undertaken for the manufacture of this gel have been financed by CEI BioTic of Granada and the Ministry of Economy and Competitiveness. Contact: Germaine Escames Rosa 958-241-000 x20197 |
| Scientists identify new therapeutic target for coronary heart disease Posted: 13 Feb 2013 09:00 PM PST Scientists investigating how certain genes affect an individual’s risk of developing coronary heart disease have identified a new therapeutic target, according to research published today in The American Journal of Human Genetics.
They have discovered that an enzyme known as ADAMTS7 plays a crucial role in the build-up of cells in the coronary arteries which lead to coronary heart disease. Coronary heart disease (also known as coronary artery disease) is the nation’s biggest killer, with around 94,000 deaths in the UK each year*. The condition happens when the blood supply to the heart is blocked by a build-up of fatty deposits ? called atherosclerotic plaques ? within the walls of one or more of the coronary arteries. Lifestyle factors ? including smoking, a bad diet and lack of exercise ? contribute to an individual’s risk of heart disease, but a number of genes have also been found to play a role. The research was led by Shu Ye, Professor of Molecular Medicine and Genetics at Queen Mary, University of London. Professor Ye said: “Recent studies have identified a number of genetic regions that are associated with coronary heart disease. However, to translate these findings into new therapeutics which could benefit patients, we need to understand how these genetic variants are influencing the disease.” In this study the scientists focused on a genetic region associated with coronary heart disease which contained the ADAMTS7 gene. This gene governs the production of an enzyme, also called ADAMTS7, which breaks down a structural protein called thrombospondin-5 in the arterial wall. This breakdown allows cells in the wall of the artery to move about more freely, and to migrate into the atherosclerotic plaques, making them larger and the affected artery narrower. By analysing genetic data from an earlier study which involved 787 people in Italy, together with ultrasound scans of their arteries, the researchers found that a particular variant of the ADAMTS7 gene was associated with a 50 per cent reduction in risk of atherosclerosis. Professor Ye said: “Through analysing arterial cells from 18 individuals, we found that this ADAMTS7 gene variant reduces the ability of the ADAMTS7 enzyme to break down the structural protein thrombospondin-5. As a result, arterial cells are less able to migrate and consequently we found that individuals carrying this genetic variant are less likely to develop atherosclerotic plaques and, even if they do, the plaques tend to be smaller. “Further research is needed but this indicates that ADAMTS7 would be a promising target against which new medicines could be designed to act.” ### Contact: Katrina Coutts |
| Cure in sight for kissing bug’s bite Posted: 12 Feb 2013 09:00 PM PST Chagas disease, a deadly tropical infection caused by the protozoan parasite Trypanosoma cruzi and transmitted by biting insects called “kissing bugs,” has begun to spread around the world, including the U.S. Yet current treatment is toxic and limited to the acute stage.
In The Journal of Infectious Diseases (JID), Galina Lepesheva, Ph.D., and her colleagues at Vanderbilt University and Meharry Medical College report curing both the acute and chronic forms of the infection in mice with a small molecule, VNI. VNI specifically inhibits a T. cruzi enzyme essential for cell multiplication and integrity. In mouse models of Chagas disease, VNI achieved cures with 100 percent survival and without toxic side effects. The discovery “represents a possible new way to combat a serious worldwide threat, for which there are currently few good therapeutic options,” said Richard Okita, Ph.D., of the National Institute of General Medical Sciences, part of the National Institutes of Health (NIH), which helped support the research. About 8 million people have been infected by T. cruzi, mostly in Latin America, but kissing bugs have been found across the southern United States, according to a recent report. Because the parasite is in the insect’s feces, it can also be transmitted through contaminated food and drink, through blood and from mother to child. The most common symptom of the acute phase of the infection is fever, but the parasite also can trigger inflammation of the heart and brain, which can be fatal. In the chronic phase, Chagas disease most severely affects the heart and gastrointestinal tract. ### Fernando Villalta, Ph.D., chair of Microbiology and Immunology at Meharry, is first author on the paper published in JID. Lepesheva, research associate professor of Biochemistry at Vanderbilt and a member of the Vanderbilt Institute for Global Health, is corresponding author. Other senior authors from Vanderbilt are Jeffrey Johnston, Ph.D., Stevenson Professor of Chemistry, and Michael Waterman, Ph.D., professor of Biochemistry, emeritus, and former chair of the department. The research was supported by NIH grant GM067871, by a pilot project grant from the Vanderbilt Institute of Chemical Biology, and in part by NIH grants GM084333 and AI080580. *Attached photo of kissing bug courtesy of the Centers for Disease Control and Prevention Contact: Bill Snyder |
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