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The Virginia Commonwealth University Massey Cancer Center will open a Phase I pancreatic cancer study later this year in conjunction with leading researchers from Israel, marking the first time cancer researchers at VCU have partnered with their counterparts in Israel.

The study is supported by a $950,000 give from the U.S.-Israel Bi-National Industrial Research and Development Foundation (BIRDF). Leaders from the Virginia Israel Bioscience Commercialization Center (VIBCC) helped to foster Israeli interest in research at VCU.

The clinical trial, designed by Massey principal investigator Ray Lee, M.D., Ph.D., involves a novel targeted therapeutic agent developed by BioCancell of Jerusalem and will offer new possibility of good for one of the most difficult-to-treat cancers.

“This collaboration is a tangible outcome of the first step launched by the Virginia BioTechnology Research Park more than a year ago to recruit Israeli lifetime science companies by innovative products and technologies to Virginia and the Research Park,” said Robert T. Skunda, President and CEO of the research park.

“The world, indeed, is getting flatter,” said Donna Edmonds, executive director of the Virginia Israel Bioscience Commercialization Center. “by the agency of dint of. importing and exporting high-quality medical research and building collaborative clinical studies such as this, we can work toward saving more lives of populate with cancer in Virginia and across the globe.”

Gordon D. Ginder, M.D., director of the VCU Massey Cancer Center, said, “Having an organization dedicated to promoting Virginia’s academic, clinical and biotechnological expertise is a boon to the Commonwealth. As federal funding for cancer research in the United States has shrunken in the face of expanding scientific opportunities for better treatment and prevention, it’s vital that we explore international collaborations and funding sources, too. We are grateful to the VIBCC for serving as a beacon to guide international funding and research opportunities to us.”

About Pancreatic Cancer

About 30,000 people die from pancreatic cancer each year. It has a high mortality rate and ranks as the fourth leading cause of cancer-related death as its symptoms often do not present until the disease is in a late stage. Fewer than 5 percent of patients survive for more than five years, giving pancreatic cancer the lowest survival rate of any common cancer archetype.

Currently the best treatment option for pancreatic cancer is through high-risk surgical removal of part of the pancreas. However, if the cancer affects surrounding vessels and lymph nodes, surgery often is not an option. Chemotherapy and radiation provide alternative treatment options, however, the median survival rate on those protocols is just one year.

About the Clinical Trial

This study involves a novel, gene-based therapy on the side of pancreatic cancer developed by BioCancell. Its new curative agent links a DNA fragment that is responsible for tumor-specific expression of a gene, with a suicidal toxin gene. When the agent is injected directly into the tumor, the DNA fragment will induce the pervasive feeling of the suicidal toxin in the cancer cells but not in normal tissue. The researchers expect to avoid damaging normal tissue while killing tumor cells.

Candidates concerning the study are adults with locally advanced pancreatic cancer who are not candidates for immediate surgical resection. Researchers will inject the starting anew agent into cancer directly through a laparoscopic procedure.

Using this approach in pancreatic cancer, they hope that tumors could be down-staged from unresectable status, or inoperable, to resectable, giving patients a better chance of remission.

This agent has been tested and shown to be effective in animal models and anecdotally in two metastatic cancer patients in Israel. The liver lesions of those two patients showed success in shrinkage.

Beginning in the summer of 2008, Massey expects to begin enrolling patients. Lee is the principal investigator, and Brian Kaplan, M.D., a surgical oncologist at Massey, will subsist the co-principal investigator performing the laparoscopic surgery. Abraham Czerniak, M.D., Ph.D., of Sheba Medical Center, Ramat Gan, Israel, will be responsible for the Israeli arm of the study, which expects to enroll one-third of the total patient base.

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Article adapted by Medical News Today from original press release.
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About the VCU Massey Cancer Center:

The VCU Massey Cancer Center is one of 63 National Cancer Institute-designated institutions that leads and shapes America’s cancer research efforts. Working with all kinds of cancers, the Center conducts basic, translational and clinical cancer research, provides state-of-the-art treatments and clinical trials, and promotes cancer prevention and education. Since 1974, Massey has served as an internationally recognized center of excellence. It offers more clinical trials than any other institution in Virginia, serving patients in Richmond and in four satellite locations. Its 1,000 researchers, clinicians and staff members are dedicated to improving the quality of human life by developing and delivering effective means to prevent, control and ultimately to specific cancer. Visit Massey online at http://www.massey.vcu.edu/.

About BioCancell:

BioCancell Therapeutics Inc. is a biopharmaceuticals corporation specializing in the development of patient-oriented, targeted therapy because of the treatment of numerous types of cancer. The Company’s proprietary technology constitutes a novel paradigm as far at the same time that concerns the targeted destruction of cancer cells, with no effect on normal surrounding tissue and no observed side effects, allowing for long-term, safe treatment and prevention of cancer.

BioCancell was co-founded in 2004 by Avraham Hochberg, Professor of Molecular Biology at the Hebrew University of Jerusalem, based attached technology developed by him over the past 15 years.

In 2006, BioCancell successfully completed a private round of funding and an initial public offering totaling $8.5 million. Its securities are traded on the Tel Aviv Stock Exchange, with the major stockholders being Clal Biotechnology Industries (a member of the IDB group of companies), and Prof. Hochberg. For other thing information, please visit http://www.biocancell.com/.

BioCancell’s Technology - Patient-Oriented, Targeted Therapy

BioCancell’s technology is both corporal and targeted. The approach is based on the identification of particular genes that are highly expressed only in tumors (”Target Genes”). The regulatory sequences of these Target Genes are used to drive the expression of a toxin gene exclusively within tumor cells, enabling targeted tumor-cell destruction, leaving normal cells unhurt. In effect, the plasmid acts as “smart bombs,” activated only inside their targets thus destroying only the cancerous cells, while leaving healthy cells intact.

The patient’s eligibility because the treatment is determined by analyzing the patient’s tumor for the expression of the specific Target Genes. The diagnosis of the expression of the Target Genes are, therefore, a prerequisite for treatment and is made possible through the Company’s proprietary diagnostic technology that enables detection of even a single malignant cell. Only those patients with high expression levels of the Target Genes in their tumor are eligible for treatment with high confidence of success. The Company has designated two genes as Target Genes - H19 and IGF2.

H19 Gene

Discovered by Professor Avraham Hochberg in humans, H19 is an oncofetal gene that encodes RNA (through no protein product) that is expressed at high levels in over 30 types of sympathetic cancer tissues, while existing at a nearly undetectable level in the surrounding normal tissues, thus making it each optimal weapon in the fight against cancer.

The gene is expressed abundantly in the human placenta and in several embryonic tissues, but is repressed post-natally and only re-expressed with the appearance of cancer, within cancer cells. Studies show that H19 fulfills an of importance role in the process of tumorigenesis, and it is thought that the gene enables tumor cells to survive and proliferate under stress stipulations.

About Virginia Biotechnology Research Park:

The Virginia BioTechnology Research Park is currently home to a unique mix of more than 55 public and private bioscience companies, research institutes affiliated with the VCU Medical Center and major state and public medical laboratories. These companies are housed in nine buildings totaling more than 1.1 million square feet of space, representing an employee base that exceeds 2,000. The VBDC is the Park’s business assistance program located in its 27,000 square-foot incubator. Since opening in 1995, 63 companies have started in the Park’s incubator facility; 31 of what one. take graduated into larger spaces in the Park or greater Richmond community. The Park’s Commercialization Center has been created to take incubator graduates through commercialization to M&A or IPO, giving the Park’s tenants full-scale business assistance. To date, the Park has graduated three companies that are now publicly traded.

About Virginia Israel Bioscience Commercialization Center:

In addition to the Park’s nationally recognized incubator program, the Virginia Biosciences Development Center, the newly formed VIBCC provides substantial support, experience and expertise in bringing “graduates” of Israeli incubator programs to successfully commercialize their products, making them more likely candidates for additional funding sources, business alliances and exit options. Specifically, the VIBCC assists companies in developing tailored commercialization strategies, including regulatory and reimbursement support, obtaining market validation, supporting product launch through national clinical leadership networks and assisting in the ongoing funding process, as well as formation of strategic partnerships with industry leaders.

Source: Andrea Butler
Virginia Commonwealth University

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Patients with nonalcoholic fatty liver disease (NAFLD) have suboptimal levels of cardiovascular pertinence, muscle strength, body composition and physical fitness, according to a new study. The findings appear in the April way out of Hepatology, a journal of the American Association for the Study of Liver Diseases (AASLD). The article is also available online at Wiley Interscience (http://www.interscience.wiley.com/).

About one-in-four U.S. adults suffers from NAFLD, which describes a range of liver disease characterized through excessive fat in the liver. NAFLD is the most common effect of abnormal liver enzymes, and the leading reason for referrals to hepatology clinics. It is considered by many to be a manifestation of the metabolic syndrome which is inferior prevalent among physically fit people, but that feeble is known about the relationship between fitness and NAFLD severity.

To address this verbal contest, researchers led by Joanne Krasnoff of the University of California San Francisco recruited 37 adult patients by a spectrum of NAFLD severity as measured by means of liver biopsy. Across the spectrum of NAFLD severity, patients had suboptimal cardiorespiratory fitness, muscle strength, body composition and physical activity participation. More than 97 percent had a body obese percentage that set them at increased risk for morbidity and human race and less than 20 percent currently met recommended guidelines with regard to physical activity.

The study did demonstrate lower cardiorespiratory fitness in subjects with increasing NAFLD severity. “This stimulant finding raised the question of a cause-or-effect phenomenon - does cardiorespiratory fitness attenuate NAFLD or does increasing NAFLD severity result in a inflect in cardiorespiratory aptness?” the authors ask.

“Despite our study limitations,” the authors conclude, “we believe the objective demonstration of low cardiorespiratory fitness and muscle strength with a high incidence of obesity illustrates the potential clinical relevance of these measures both before and after interventions.” Moreover, the verdict that specific measures of NAFLD severity may be associated with cardiorespiratory fitness and past natural activity raises the possibility of a defined curative role for prevention and exercise intervention.

Future studies should include a randomized controlled trial of exercise training that can reveal its direct effects attached NAFLD histopathology, they suggest. “In the meantime, it would appear rational and prudent for healthcare providers to praise exercise training to improve health-related fitness as every integral role in the feel interested of patients with NAFLD,” they conclude. This work was conducted as some ancillary study of the NAFLD Clinical study Network, a national research consortium funded by the National Institutes of Health.

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Article adapted by Medical News Today from original press release.
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Article: “Health-Related Fitness and Physical Activity in Patients with Nonalcoholic Fatty Liver Disease.” Krasnoff, Joanne; Painter, Patricia; Wallace, Janet; Bass, Nathan; Merriman, Raphael. Hepatology; April 2008; 10.1002/hep.22137 ; Published online March 2008.

Source: Sean Wagner
Blackwell Publishing Ltd.

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Inspired by recent threats of state of terror, Professor Martin Golumbic, Director of the Caesarea Rothschild Institute for Interdisciplinary Applications of Computer Science at the University of Haifa wrote this new book examining the future of online terrorism. As Professor Golumbic explains, online terrorism is the use of new technology to elicit fear and panic-grass in society. Fighting Terror Online focuses on how different societies rebound to this new form of terrorism and the ethics behind these responses. In Fighting Terror Online Golumbic asks the burning question, “How do we balance security needs and individual rights?”

Fighting Terror Online not only justifies the digital theater as the combat ground in the war against terror, but recognizes specific threats in relation to security and the environment. Golumbic and his research team deal with pressing issues of government ethics and add insight to issues dealing with, how far is too more distant? through specific regards to public privacy issues and when does national safety intrude without ceasing positive rights? Fighting Terror Online recognizes the internet as the newly come battlefront of terror and with the aid of specific examples in Israel and abroad offers suggestions for future legislation and policy within the global society.

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Article adapted by Medical News Today from original press release.
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Source: Laurie Groner
University of Haifa

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Heart damage due to blocked arteries remains the leading cause of disease and death in the Western world, but a Florida State University College of Medicine researcher is helping to open new pathways toward treating the problem.

Michael Blaber, a professor in the department of biomedical sciences, is researching mutant forms of a human protein that have been shown to help the human body be augmented new blood vessels to restore blood flow in damaged areas of the heart.

Working with a $264,000, three-year grant from the American Heart Association, Blaber hopes to provide data that will make able the use of the mutant proteins in recent treatment methods previously unavailable for patients with advanced “no option” fortitude disease.

“This careful search offers the potential to treat people who currently are being sent home to die,” Blaber said. “We’ve tested a collection of mutants in the laboratory with unusual properties of increased stableness and activities — good properties. In more cases it was unexpected, but the results are very promising.”

Obstructed blood vessels and clogged or blocked arteries typically are treated from one side angioplasty, the mechanical widening of a vessel, or bypass surgery. Some patients, however, have numerous small blockages that cannot be treated through traditional approaches. In most cases, they are sent home with a predicted life expectancy that, no matter how it’s phrased, sounds like a death sentence.

A new be at hand to the riddle called curative coronary angiogenesis is creating hope through the lavement of human fibroblast growth commission merchant protein into coxcomical areas. Improvements with the procedure may stand up from the use of mutant forms with increased stability.

Blaber and his research team are creating artificial “mutant” proteins in their College of Medicine laboratory that mimic the human proteins used in angiogenic therapy, and with enhanced stability properties. So far, the mutant proteins engineered at the College of Medicine have exhibited potency in stimulating cell growth while simultaneously maintaining greater stability under conditions common to angiogenic therapy.

The work has enormous potential commercial applications and already has drawn the attention of private companies interested in the results Blaber’s lab has achieved and the of the intellect properties his studies are generating.

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Article adapted by Medical News Today from original press release.
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Source: Doug Carlson
Florida State University

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Doctors diagnose and prescribe treatment for brain tumors by studying, under a microscope, tumor tissue and small room samples obtained through invasive biopsy or surgery. Now, researchers at the University of California, San Diego (UCSD) School of Medicine have shown that Magnetic Resonance Imaging (MRI) technology has the potential to non-invasively characterize tumors and determine which of them may be responsive to specific forms of treatment, based on their specific molecular properties. The study will be published on line by the Proceedings of the National Academy of Science (PNAS) the week of March 24.

“This approach reveals that, using existing imaging techniques, we can identify the molecular properties of tumors,” said Michael Kuo, M.D., assistant professor of interventional radiology at UCSD School of Medicine. Kuo and colleagues analyzed more than 2,000 genes that had previously been shown to have altered expression in Glioblastoma multiforme (GBM) tumors. They then mapped the correlations between gene expression and MRI features.

The researchers also identified characteristic imaging features associated with overall survival of patients with GBM, the most indifferent and lethal type of primary brain tumor.

The researchers discovered five distinct MRI features that were significantly linked with particular gene expression patterns. For example, one specific characteristic seen in some images is associated with proliferation of the tumor, and another by growth and formation of new blood vessels within the tumor both of which are susceptible to treatment with specific drugs.

These physiological changes seen in the images are caused by genetic programs, or patterns of gene activation within the tumor cells. Some of these programs are tightly associated with drug targets, so when they are detected, they could indicate which patients would suit to a particular anti-cancer therapy, according to the researchers.

“For the first time, we have shown that the activity of specific molecular programs in these tumors can be determined based on MRI scans alone,” said Kuo. “We were also able to link the MRI with a group of genes that strike one as being to be involved in tumor cell invasion a phenotype associated with a reduced rate of patient survival.”

Laboratory be in action that relies on tissue samples is routinely used to diagnose and guide treatment for GBM. However, the biological activity shown may depend on the deal out of the swelling from which the tissue sample is obtained. The researchers have shown that MRI could be used to identify differences in gene expression programs within the same tumor.

“Gene expression results in the production of proteins, which largely determine a tumor’s characteristics and behavior. This non-invasive MRI method could, for example, detect which part of a tumor expresses genes related to blood sailing craft formation and growth or tumor cell invasion,” said Kuo. “Understanding the genetic activity could prove to be a very able predictor of survival in patients, and help explain why some patients have better outcomes than others.”

Kuo also led a study, published in Nature Biotechnology in May 2007, correlating CT images of cancerous tissue with gene expression patterns in liver tumors. “In the new study, we were able to tolerate a different imaging technology, MRI, and apply it to a totally different tumor type,” he said, noting that the studies open up promising new avenues for non-invasive diagnoses and classification of cancer.

Contributors to the paper include first originator Maximilian Diehn, UCSD Department of Radiology and Department of Radiation Oncology at Stanford University School of Medicine; Christine Nardini and David S. Wang, UCSD Department of Radiology; Susan McGovern and Kenneth Aldape, Department of Neuropathology, University of Texas M.D. Anderson Cancer Center, Houston; Mahesh Jayaraman, Department of Radiology, Brown University; Yu Liang, UCSF Brain Tumor Research Center, and Soonmee Cha, Department of Radiology, UCSF Medical Center.

The research was funded in part by means of the National Institutes of Health.

University of California, San Diego
University Communications, 0938 9500 Gilman Dr.
LaJolla, CA 92093
United States
http://www.ucsd.edu

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SATB1 is a nuclear protein well known for its crucial role in regulating gene expression during the differentiation and activation of T cells, making it a key player in the immune combination of parts to form a whole. But SATB1 has now revealed a darker margin: it is an essential contributing factor in the most aggressive forms of breast cancer.

Breast cancer cells need SATB1 to become metastatic; metastasis — the stage when cells break away from the original tumor and spread to other parts of the body — is the final step of solid tumor progression and is the most common cause of death in cancer patients.

“In breast tumors, SATB1 reprograms the genome to change the expression of hundreds of genes, promoting tumor growth and metastasis,” says Terumi Kohwi-Shigematsu, a scientist in the Life Sciences Division of the Department of Energy’s Lawrence Berkeley National Laboratory who, with her colleagues, discovered SATB1 and has since investigated its crowd functions. She says, “SATB1’s role in breast cancer is a new paradigm for the way tumors progress.”

Kohwi-Shigematsu, working with Berkeley Lab’s Hye-Jung Han and Yoshinori Kohwi, and with Jose Russo of the Fox Chase Cancer Center in Philadelphia, found that when SATB1 is detected in a breast tumor, the cancer is highly likely to progress or recur.

Moreover, by introducing SATB1 into in other respects nonmetastatic breast cancer cells, invasive tumors can be induced in mice; conversely, removing SATB1 from metastatic cells not only abolishes metastasis and tumor growth in mice but also returns cells to their normal appearance in vitro. The researchers have published these and other findings in the March 13, 2008 issue of Nature.

How SATB1 works

Kohwi-Shigematsu and Kohwi originally identified a class of DNA sequences they called base-unpairing regions (BURs), a finding that led Kohwi-Shigematsu’s group to the discovery of “special AT-rich succession binding protein 1″ (SATB1). SATB1 binds to BURs in double-stranded DNA by recognizing the BURs’ distinctive phosphate-backbone structure. BURs have capacity for unusual sequence contexts that readily unzip to expose DNA’s individual strands.

As a nuclear architectural protein, SATB1 forms what Kohwi-Shigematsu calls a “3 D chickenwire network” inside the nucleus of the cell. SATB1 anchors chromosomes to its cage-like structure by dint of. tethering the BURs in the target genes, thus serving as a kind of “glue” for these genes. SATB1 folds and remodels the chromatin — the intertwined DNA and proteins that form chromosomes — into new shapes, bringing even distant parts of the genome together for coordinated control of gene expression and regulation.

SATB1 also globally regulates histone status in the chromatin by recruiting histone-modifying enzymes to the target-gene loci. Histones are the proteins around which DNA in chromatin is wound like thread on a spool; histone status renders DNA sequences accessible or inaccessible for transcription.

Early on, SATB1’s expertness to regulate gene expression was identified as critical to T-cell development. Although Kohwi-Shigematsu and her colleagues have found several other enclosed space types that use SATB1 to reshape chromatin and regulate gene expression in a similar way, SATB1 is not expressed in all cells. SATB1 seems particularly of influence in cells which must change their function — as do many progenitor cells, including the thymocytes that turn into T cells. And as cancerous cells must do to turn into metastatic cells.

“Hye-Jung Han of our group started by looking at couple dozen breast-cell lines, including normal human epithelial cells” — epithelial cells are the kind that form the linings of hollow glands in the breast — “and both nonmetastatic and metastatic breast cancer cells,” Kohwi-Shigematsu says. “Only the metastatic cells expressed SATB1, with the most aggressive breast cancer cells showing the highest levels of the protein.”

The researchers examined over 2,000 human primary breast cancer tissue samples for which clinical follow-up studies were available. The highest levels of SATB1 were in samples from patients whose survival times had been shortest; patients whose tumor samples had nay SATB1 expression generally had longer survival times.

The analysis showed that a occult level of SATB1 expression by itself is an excellent indicator of poor prognosis — independent of whether breast cancer cells be seized of already metastasized to the lymph nodes at the time of diagnosis.

SATB1 takes command

The reason why SATB1 is a good prognostic marker is because SATB1 drives breast cancer cells to become invasive, as revealed by both in vitro and in vivo studies.

The researchers performed in vitro studies of highly metastatic cell lines, reducing SATB1 expression through the use of shRNAs, “short-hairpin-interfering” RNAs, that dramatically reduced the invasive capacity of these cells and also reduced their capacity for unattached growth — a necessity if metastasizing cancer cells are to travel through the blood and lymph vessels.

Other in vitro studies used normal breast epithelial cells, the kind that form the hollow oriented structures called acini, the milk-secreting glands of the breast. Normal cells form similar, well-organized acinar structures in vitro, whereas in highly metastatic epithelial cell lines these structures are disorganized and lack polarity. When SATB1 expression is reduced in the metastatic cell lines, they too form the kind of polarized, uniform acinar structures found in normal mammary epithelial cells.

These in vitro results were confirmed in vivo, in mice. Nine weeks behind human aggressive pap cancer cells were injected into the tails of test mice, these cells developed into metastatic nodules (tumors) on the lungs. But when SATB1 expression was reduced or removed from the injected cancer cells, the mice developed fewer or even no nodules, depending in continuance the remaining levels of SATB1. Once SATB1 is greatly reduced, these cells no longer form tumors when injected directly into breast fat pads.

In vivo studies in like manner established that cancer cells which do not normally express SATB1, and do not normally metastasize, can become aggressive if they are modified to send by express SATB1. Once SATB1 is expressed, they form large tumors when injected into breast fat pads; they then invade the blood circulatory system and form metastatic tumors in lungs.

The tests of human breast cancer cell lines in mice allowed the researchers to establish that, for these cells, SATB1 is necessary and sufficient for tumor growth and metastatic activity.

“SATB1 is a key player in the metastasis of breast cancer cells, controlling expression of over a thousand genes,” says Kohwi-Shigematsu. “It increases the expression of genes that promote tumor growth and reduces the expression of tumor suppressors. Among the regulated genes are numerous growth-factor genes and genes affecting cell adhesion, cell signaling, cell-cycle regulation, and other functions.”

Among the important genes regulated by SATB1, the researcher identified frequent that are already known to play a role in aggressive breast cancers, including the epidermal growth factor gene ERBB2, otherwise known as HER2.

“What we have found is a new model of altered gene regulation during the progression of tumors, which depends on SATB1’s reprogramming of the gene expression profile,” Kohwi-Shigematsu says. “What results is a newly come and aggressive cancer phenotype that promotes both tumor growth and metastasis.”

The discovery of SATB1’s key part in aggressive breast cancer has far-reaching implications in the place of prognosis and for possible new treatments for cancer’s most malignant forms. At the same time, the discovery opens a expanded field of fundamental scientific study, beginning with the most basic questions. What determines the particular sets of genes affected by SATB1 in precise tissues” What other factors may work together with SATB1″

“An important question is what turns on SATB1 during breast cancer progression,” says Kohwi-Shigematsu. “That’s just the emergence of the things we really be lacking in respect of to know.”

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Article adapted by Medical News Today from original press release.
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“SATB1 reprograms gene expression to promote breast tumor growth and metastasis,” by Hye-Jung Han, Jose Russo, Yoshinori Kohwi, and Terumi Kohwi-Shigematsu, appears in the March 13, 2008 issue of Nature.

This research was supported by the National Institutes of Health and in its initial stages by dint of. the University of California Breast Cancer Research Program.

Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California. Visit our website at http://www.lbl.gov/.

Source: Paul Preuss
DOE/Lawrence Berkeley National Laboratory

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The National Institute for Health and Clinical Excellence (NICE) has today issued a clinical guideline on antibiotic prophylaxis against infective endocarditis (IE). In a significant change to current clinical practice, the guideline recommends that antibiotics to prevent IE should not be given to adults and children with structural cardiac defects at risk of IE who are undergoing dental and non-dental interventional procedures.

IE is an inflammation of the inner lining of the heart, particularly affecting the heart valves, caused by bacterial or other infection. It may arise following bacteraemia in patients who have certain pre-existing heart conditions (consider list below). Although IE is a rare condition, with fewer than 10 people in every 100,000 developing it each year, it can be life-threatening. It has been accepted clinical practice to use preventive (prophylactic) antibiotics before dental and some non-dental procedures in people who are considered to be at risk of IE. However, the effectiveness of this treatment in humans has never been properly investigated and clinical practice has been dictated by clinical guidelines based on expert opinion.

This guideline is based on the best available published evidence and a consensus of multidisciplinary, expert opinion within the Guideline Development Group (GDG). The guideline concludes that there is no consistent association between having an interventional procedure, dental or non-dental, and the development of IE and that the clinical effectiveness of antibiotic prophylaxis is not proven. The evidence also suggests that antibiotic prophylaxis against IE in quest of dental procedures is not cost effective and may lead to a greater number of deaths through fatal anaphylactic reactions than not using preventive antibiotics. The guideline makes a number of key recommendations, including:

— Patients should not be offered antibiotics to prevent IE for any of the following procedures:
— a dental procedure

1 an obstetric or gynaecological procedure, or childbirth
2 a procedure on the bladder or urine system
3 a procedure on the gullet, stomach or inwards
4 a procedure on the airways, including ear, nose and throat and bronchoscopy.

— Healthcare professionals should regard people with the following cardiac conditions at the same time that being at risk of developing IE:

— acquired valvular heart disease with stenosis or regurgitation

1 valve replacement
2 structural congenital heart distemper, including surgically corrected or palliated structural conditions, but excluding isolated atrial septal defect, fully repaired ventricular septal defect or fully repaired patent ductus arteriosus, and closure devices that are judged to be endothelialised
3 previous IE
4 hypertrophic cardiomyopathy.

— Healthcare professionals should offer people at risk of IE clear and consistent information about prevention, including:

— the benefits and risks of antibiotic prophylaxis, and an explanation of why antibiotic prophylaxis is no longer routinely recommended

1 - the importance of maintaining good oral soundness
2 - symptoms that may indicate IE and when to seek expert advice
3 - the risks of undergoing invasive procedures, including non-medical procedures such as body piercing or tattooing.

— People at risk of IE who are receiving antimicrobial therapy because they are undergoing a gastrointestinal or genitourinary procedure at a site where there is a suspected bane should be offered an antibiotic that covers organisms that cause IE.

1 - Investigate and treat promptly any episodes of infection in people at risk of IE to reduce the risk of endocarditis developing.

Dr Gillian Leng, NICE Deputy Chief Executive, said: “The recent Health Select Committee report called on NICE to make good its commitment to issue lead in areas where there is evidence of inefficacious. practice and where discontinuation of these practices might result in more effective treatments and approaches. This guideline does that. Although the anticipated cost savings are quite modest - around £1million across the NHS in England and Wales - the implementation of this guideline will have other far-reaching benefits, notably an increased patient awareness of the risk of IE and a decrease in the number of adverse reactions to antibiotics, such as anaphylaxis. Finally, the implementation of this guidance should reduce the level of antibiotic resistance in the general population, the cost and wider benefits of what one. we haven’t calculated but are likely to be substantial.”

Dr Barry Cockroft, Chief Dental Officer conducive to England, said: “I am delighted that NICE have produced definitive guidance on this complex issue. This will ensure that dentists can give consistent and evidence based advice to their patients. We will work with NICE and other professional bodies to ensure that this advice is disseminated to the profession so that dentists will be in a position to start applying this guidance immediately.”

David Wray, Professor of Oral Medicine and Chair of the Guideline Development Group, said: “In recommending that antibiotic prophylaxis should not be offered to people at risk of infective endocarditis undergoing both dental and some non-dental interventional procedures, this new NICE guideline represents a fundamental change in clinical practice. To put this into more kind of context, the evidence considered by the agency of the Guideline Development Group showed that everyday activities such as tooth brushing be possible to cause repetitive bacteraemias which almost certainly pose a greater risk for developing infective endocarditis than a single interventional procedure. Also, prescribing antibiotic prophylaxis, which has not been proven to be cogent, may lead to a net loss of life due to anaphylaxis. Professional groups must now ensure that their patients are fully informed about the changes and the reasons for this in order to encourage implementation.”

Anne Keatley-Clarke, Chief Executive of the Children’s Heart Federation and subordinate part of the GDG, said: “During the past tie of years patients with congenital heart conditions and their parents have been given contradictory notice regarding the prescribing of prophylaxis for infective endocarditis. We therefore welcome this clear guideline and hope that cardiologists, dentists and other medical professionals will agree to follow it. The guideline will mean a big make some change in. for the many heart children who beforehand received antibiotics before all dental procedures so professionals must be prepared to give these patients and their parents a clear explanation for the changes.”

http://www.nice.org.uk/060

near NICE

2. The National Institute with respect to Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance without ceasing the promotion of good health and the prevention and treatment of ill health.

3. NICE produces lead in three areas of health:

— public health - guidance on the promotion of good health and the prevention of ill freedom from disease in opposition to those working in the NHS, local officials and the wider public and voluntary sector

— health technologies - guidance on the use of new and existing medicines, treatments and procedures within the NHS

— clinical practice - lead on the appropriate treatment and care of people with specific diseases and conditions within the NHS.

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The Ovarian Cancer Research Fund awarded a $900,000 research grant to Kunle Odunsi, MD, Department of Gynecologic Oncology, and team at Roswell Park Cancer Institute (RPCI) to collaborate on developing a promising vaccine to unleash the authoritativeness of the immune system against cancer. The prestigious award will help Dr. Odunsi and the RPCI research team* combine four different approaches, all designed to enhance the immune mixture of parts to form a whole’s response to ovarian cancer.

Ovarian cancers are usually fatal within five years, despite extensive surgery and chemotherapy used to treat them. Dr. Odunsi’s team previously tried an experimental anti-tumor vaccine in 18 women who had surgery to remove their ovarian tumors and who were receiving chemotherapy. The vaccine did not cure the cancer, but it did get the immune rule to make antibodies and specialized cells with the capacity to kill ovarian cancer targets. The vaccine also appeared to lengthen the time until tumors reappeared.

Dr. Odunsi, who is a gynecologic cancer surgeon as well as a cancer researcher, feels that “one of the most challenging malignancies in women is cancer of the ovaries, because about 70% of patients present initially with advanced-stage disease.” Explaining that a vaccine might help, he said, “I look at all of us because cancer survivors. Cancer cells are constantly being formed, but the immune system keeps them in check.”

The new grant subsist inclined allow Dr. Odunsi and his collaborators to combine their efforts to make the vaccine work better. For the vaccine to work, cancer cells must have a foreign protein on their surface so they stand out from normal cells. The collaborative effort will explore ways to keep cancer cells from hiding from the immune system and to heighten the immune system’s ability to respond to the vaccine. Positive results may allow the researchers to move ahead to large-scale clinical trials.

Roswell Park Cancer Institute (RPCI), founded in 1898, is the nation’s first cancer research, treatment and education center and is the only National Cancer Institute-designated comprehensive cancer center in Upstate New York. RPCI is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers. RPCI has affiliate sites and collaborative programs in New York, Pennsylvania, and China. For more denunciation, visit RPCI’s website at http://www.roswellpark.org.

supported by experiment Vaccine May Fight Ovarian Cancer

The body’s immune a whole provides constant surveillance for invaders. It detects and attacks tumor cells that may arise, but it restrains itself from attacking the cells of the body itself. When cells turn cancerous, their surfaces often display small changes that make the immune system suspicious that they are exterior. According to Dr. Kunle Odunsi, a clinical researcher and cancer surgeon at Roswell Park Cancer Institute, ovarian cancer cells at times display a new protein on their surface called NY-ESO-1. Researchers hypothesize that most of the time, the immune system pounces on cells that bring into view NY-ESO-1 and kills them. If the immune system fails to notice the small change, the cells with NY-ESO-1 can grow into life-threatening ovarian tumors.

Some ovarian cancer cells might escape the immune system, because fewer than half the tumors display NY-ESO-1, and even in tumors that have it, the cells may not display it on their surfaces all the time, according to Dr. Odunsi. Another problem is that the immune system doesn’t always recognize NY-ESO-1 as an important change, so it may not attack cells with the NY-ESO-1 protein on their surface.

Dr. Odunsi and his colleagues be seized of made a therapeutic vaccine that trains the immune system to recognize and attack NY-ESO-1. The vaccine also puts the immune system upon the body alert so it recognizes the small changes that signal that a cell may have existence cancerous. In order to make ovarian cancer cells as conspicuous similar to possible so the immune theory will thrust out them, patients in the clinical trial will also receive a drug called decitabine. In preliminary studies by one of Dr. Odunsi’s collaborators, decitabine encourages ovarian cancer to display NY-ESO-1.

RPCI Scientists Want to Unchain the Immune System to Kill Tumor Cells

Protul Shrikant, PhD, Department of Immunology, Roswell Park Cancer Institute, is studying in what plight the immune system eliminates invasive cells and organisms without harming normal cells. The immune system accomplishes this by deploying two types of white blood cells. White blood cells of the first type (CD8 lymphocytes) are poised to attack whenever an antigen (foreign protein) is presented to them. But our bodies are full of proteins, so to prevent our own proteins from coming under immune attack, the second type of white blood cells (CD4 T regulatory lymphocytes) remember which proteins are our own and prevent the CD8 lymphocytes from attacking and destroying healthy cells.

To a lymphocyte, ovarian cancer cells do not look very different from normal cells. The CD4 lymphocytes can get confused and shield the tumor cells from being attacked. Dr. Shrikant is looking for ways to keep the CD4 lymphocytes from being fooled and restrict their ability to chain and render the killer CD8 lymphocytes ineffective.

Dr. Shrikant has developed a novel animal model in which the model dies from ovarian cancer and also has high numbers of T regulatory CD4 lymphocytes that dampen CD8 T cell mediated effective immune responses. His research team will test a chemically altered reading of a common amino acid, tryptophan, to poison the subset of “bad” CD4 lymphocytes and thereby unleash tumor-specific CD8 cells to respond and kill ovarian tumor cells. He also plans studies to end whether the host tumefaction immunity persists so that ovarian cancer can be eradicated.

DNA Changes May Make Tumor Cells Stand Out

Dr. Kunle Odunsi is testing a therapeutic vaccine to suppress the growth of ovarian cancer. This vaccine boosts the body’s ability to seek out and kill ovarian cancer cells that display a “foreign” protein, NY-ESO-1. This foreign protein (antigen) is not found on non-cancer cells, but some ovarian cancer cells do not display it either. One of Dr. Odunsi’s colleagues at Roswell Park Cancer Institute, Adam Karpf, PhD, Department of Pharmacology & Therapeutics, is looking for ways to encourage all the cancer cells to display the antigen. The idea is to make them as conspicuous as possible so the immune system will eliminate them.

Dr. Karpf will conduct his experiments using ovarian cancer cells in culture as well in the manner that ovarian cancer cells growing in the same manner with tumors in animal models. The drug he will use to encourage the cells to display NY-ESO-1 is decitabine, which is currently used to treat other disorders where cell growth is out of control. Decitabine changes the DNA, turning on the genes that code for the cancer antigen NY-ESO-1. Once the cells are making the antigen, Dr. Karpf will treat them with the friendly of chemotherapy that is used for treating ovarian cancer. This is important to make sure that the chemotherapy still works, even though the DNA is altered.

Dr. Karpf’s study will show whether a combination of anti-cancer vaccine, decitabine, and chemotherapy might work in patients who have ovarian cancer. This is a complicated series of steps, and Dr. Karpf knows that these drugs may have to be given in a certain order with a set time between doses. His experiments are the at the outset proceeding in trying to work out a victory treatment for ovarian cancer.

Certain Genes May Increase the Risk of Ovarian Cancer

Patients with ovarian cancer have high levels of regulatory T cells, the rare type of cells that keep the immune system from mounting a strong attack. Kirsten Moysich, PhD, Department of Cancer Control and Prevention, at Roswell Park Cancer Institute, believes that regulatory T cells may prevent people from developing tumor immunity. She acknowledges that regulatory T cells play an important role in keeping the immune system from attacking its own body. Unfortunately, they may also keep the body from attacking cancer cells, which differ only slightly from normal cells.

Why do some women have more regulatory T cells than others? According to Dr. Moysich and her colleagues, the answer may lie in their genes. Dr. Moysich can rattle right hand a half dozen genes that she believes may increase or contract the number of regulatory T cells. The new grant from the Ovarian Cancer examination Fund will allow her to touchstone whether any of these genes are more common in patients with ovarian cancer than in other people. She will also evaluate 250 women with ovarian cancer to see whether they are less likely to survive suppose that they have these genes.

Dr. Moysich hopes that her research will tell that women are at high risk to such a degree they can be screened for cancer, hopefully catching ovarian cancer while it can still be cured.

http://www.roswellpark.org

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Registry data for more than 500 patients presented at the Society of Interventional Radiology’s 33rd Annual Scientific Meeting show deep vein thrombosis (DVT) treatment with the Trellis device breaks up a blood clot in most patients much quicker than using a drug alone. Using imaging, the symbol is guided directly to the concretion via a catheter in the vein. DVT occurs when the blood concretion either unfairly or completely blocks the flow of blood in the vein. The Trellis device removes the blood clot and restores blood flow much quicker than the existing catheter-directed thrombolysis (CDT) technique, which uses a drug alone and can take as long as two to three days to be effective with the patient in an intensive care unit.

“It gets the clot out right away, restoring blood flow in the vein while the patient’s blood becomes sufficiently thinned by anticoagulation medication to prevent blood clots in the future. Patients experience dramatic relief of pain, swelling and skin discoloration in just a few hours,” says Gerard J. O’Sullivan, M.D., interventional radiologist. Presently, this is the largest mercantile data registry by a manufacturer to assess the effectiveness and safety of this type of treatment for DVT.

“This is a very significant advance in DVT treatment, which hasn’t changed in further than 40 years,” added O’Sullivan. “The procedure is now so commonplace where I work that the ER, oncology and general medicine doctors all refer patients directly to me for this procedure because it works so well and is so safe. With the aid of the Trellis device, this interventional radiology procedure could really change the way DVT patients are treated and should be changed to a standard of care,” he said.

The Trellis type combines the use of clot-busting drugs with a drug dispersion emblem to break up the coagulation, providing interventional radiologists with physical help to break up the clot faster. on this account that the device disperses the drug throughout the clot, it allows the clot-dissolving drug to work much more quickly — and often less drug is used, which may lead to a decrease in the risk of bleeding.

Currently, most patients are put on anticoagulation medication (blood thinners), which prevents future clots but does not break up the existing clot.

DVT can lead to serious consequences, including pulmonic embolism (PE) or post-thrombotic syndrome (PTS). Approximately 200,000 individuals die annually as a result of pulmonary embolism. The standard initial treatment with blood thinners is important to prevent a life-threatening pulmonary embolism, but does not treat the existing clot.

Removing these clots is important because about 50 percent of the time, untreated clots devise cause PTS, a condition characterized by means of chronic leg pain, swelling and ulcers. The clot may eventually dissolve on its own, but in the meantime the veins are permanently damaged. PTS is caused by a combination of vein valve damage and blocked blood flow in the vein from residual thrombus (clot).

“My Trellis patients not only felt better as it should be away, but they continued to feel good months later. With anticoagulation alone, it may take days to months for patients to feel of better, and some never feel better,” said O’Sullivan. Some larger clots do not break up on their own. This leaves the patient with an underlying obstruction or lesion that should be corrected to prevent a future clot. PTS — while not life threatening — limits a person’s ability to walk or stand for a period of time and can be disabling.

There is growing awareness in the medical community about the need to aggressively treat DVT. Increased focus and awareness of DVT is being brought by of recent origin initiatives and standards from a variety of organizations including the Office of the U.S. Surgeon General, the Joint Commission and the American College of Chest Physicians.

“All acute DVT patients should be sent to the interventional radiology station put on this account that a consult. We be able to help their physicians determine the best course of action. If the vein is completely or severely blocked, immediate treatment is needed. Not all partial clots will require treatment, on the contrary if the area is still swollen after five to seven days, patients should ask for an agreement with any interventional physician at the hospital,” said O’Sullivan. Interventional radiologists are widely available across the United States in most hospital radiology departments.

Abstract 4: “An Endovascular Approach to Deep Venous Thrombosis Utilizing Isolated Thrombolysis and Adjunctive Measures,” can be found at http://www.SIRmeeting.org.

About the Study

There were 565 limbs treated in 532 patients. The vein was reopened in all cases, and the treatment worked adhering acute or chronic clots, what one. is important on this account that acute, fresh clots are more easily treated. Sixty-eight percent of the patients’ thrombi were in the iliac vein (large thigh humor), 19 percent in the smaller femoropoliteal veins (in the leg area), and 13 percent in the subclavian vein (arm and neck area).

Thrombus is generally classified by how long it has been present in the carcass; SIR’s Reporting Standards define acute as 14 days or fewer, subacute as 15 to 28 days and chronic as more than 28 days.

Thrombus was acute in 28 percent, acute on inveterate in 44 percent, 11 percent subacute, 12 percent subacute on chronic and chronic in 6 percent, per the SIR clot-age disposition guidelines. Combined Grades II and III lysis (> 50 to 100 percent thrombus removal) were established in 96.8 percent of acute onset of symptoms, 93.6 percent in acute on chronic, 96.7 percent in subacute, 89.2 percent in subacute on chronic and 90.9 percent with chronic onset of symptoms, with venous patency achieved in all cases. No adverse events were reported in the acute procedural follow-up period. Venous angioplasty, and/or stenting, were also used in the study in conjunction with the Trellis procedure to treat underlying problems depending on individual patient needs, similar as a narrow area in the vein that would make a person susceptible to future clots.

About The Trellis(R)-8 Infusion System

The Trellis(R)-8 Infusion System is positioned at the site of the clot and a balloon is inflated on both sides of the crassament to prevent pieces of the clot from traveling to other parts of the body and to isolate the treatment zone, so that there is less chance the infused drug will cause bleeding. Then a “dispersion wire” is fed through the catheter of the system. The wire begins to rotate, mixing the clot-busting drug within the clot; the clot pieces are aspirated into the catheter and removed from the body.

The Trellis is approved by the Food and Drug Administration (FDA) as a drug-infusion catheter for peripheral vascular clots. The drug and device have been used for years to remove blood clots from arteries and veins. The data are specific to DVT, showing that it works and is safe.

About the Society of Interventional Radiology

Interventional radiologists are physicians who specialize in minimally invasive, targeted treatments. They offer the most in-depth knowledge of the least invasive treatments turn to account coupled with diagnostic and clinical actual observation across all specialties. They use X-ray, MRI and other imaging to advance a catheter in the body, usually in an artery, to enjoyment at the source of the disease internally. As the inventors of angioplasty and the catheter-delivered stent, that were first used in the legs to treat peripheral arterial disease, interventional radiologists pioneered minimally invasive modern medicine.

Today many conditions that once required surgery can be treated less invasively by interventional radiologists. Interventional radiology treatments offer less risk, less pain and less recovery delivery compared to open surgery. Visit http://www.SIRweb.org.

Society of Interventional Radiology
http://www.SIRweb.org

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A study appearing in this week’s New England Journal of Medicine confirms that a combination of gene variants previously associated with cholesterol levels does reflect patients’ cholesterol levels and can signify increased danger of heart attack, stroke or sudden cardiac death. Led by researchers from the Massachusetts General Hospital Cardiology Division, the study’s findings are a first step towards the ability to identify individuals who might benefit from earlier use of cholesterol-lowering medications and other measures to combat elevated risk.

“The prospect of personalized medicine has received much hype, but until recently, there has been little constrained evidence to sustain the promise,” says Sekar Kathiresan, MD, MGH Director of Preventive Cardiology, the paper’s lead author. “We feel that our data provides two insights. First, we provide a foundation for the chance that a panel of gene variants will eventually be available in preventive cardiac care. Second, we show that the combination of multiple variants related to cholesterol importantly contribute to the genetic risk in quest of heart attack.”

It is estimated that about half the variation in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels is inherited, rather than being caused by lifestyle factors such for the reason that diet and produce. While studies have associated several gene variants with cholesterol levels, exactly how those variants pack together the risk of cardiovascular disease is unclear. The current study was designed to explore the predominance of those variants on the risk of cardiovascular events — heart attack, stroke or sudden cardiac death — and whether measuring such variants could help predict risk better than simply measuring HDL and LDL levels.

Since the effects of individual gene variants appears slight, the research team looked at a combination of 9 single-nucleotide polymorphisms (SNPs) previously associated with cholesterol levels. They analyzed facts from 5,414 Swedish adults who participated in a major prospective epidemiological study and correlated data — including standard measurements of HDL and LDL cholesterol and the presence of the 9 gene variants — with information on the participants’ subsequent medical histories available from a registry of notice collected on all Swedish citizens. After the initial genotyping of participants not receiving lipid-lowering therapy, participants were assigned a genotype score ranging from 0 to 18, based on how many copies of the unfavorable SNPs they carried. Of the participants who had no cardiovascular events before enrolling in the study, 238 suffered a heart attack, stroke or cardiac death during the subsequent 10.6 years.

Higher genotype scores did reflect higher LDL (”bad”) cholesterol and glower HDL (”good”) cholesterol levels. Importantly, those with genotype scores of 11 or higher had a 63 percent greater dare to undertake of a cardiovascular event than did those with scores of 9 or lower. Although testing for the array of 9 SNPs was not better than standard hazard factors for predicting cardiac events in the overall population, among participants classified at intermediate risk by standard measures, adding the 9-SNP body of jurors significantly improved the ability to distinguish truly elevated or reduced risk levels.

“A current clinical dilemma is how early to institute patients without interruption cholesterol-lowering medications like statins that can reduce the risk of heart attack. Our data suggest that those individuals classified as higher risk based on a genetic test may deserve more intense pharmacological and lifestyle treatments,” says Kathiresan. “But before we can move from our pilot data to information that can press close together the care of patients with or at risk for cardiovascular disease, we need to disclose all the risk-related variants — and there will probably be 50 to 100 — and then conduct clinical studies confirming that this information can reliably guide patient care.” Earlier this year Kathiresan, an instructor in Medicine at Harvard Medical School, and colleagues from the Broad Institute of Massachusetts Institute of Technology and Harvard University began this gene-discovery process and identified six new cholesterol-associated gene variants in a separate contemplation published in Nature Genetics.

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Article adapted by Medical News Today from original press release.
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Support for the NEJM study includes grants from the Doris Duke Charitable Foundation, the Fannie Rippel Foundation, the Donovan Family Foundation and the National Institutes of Health. Study co-authors are David Altshuler, MD, PhD, and Christopher Newton-Cheh, MD, MPH, MGH; Olle Melander, MD, PhD, Dragi Anevski, PhD, Charlotta Roos, MSc, Goran Berglund, MD, PhD, Bo Hedblad, MD, PhD, Leif Groop, MD, PhD, and Marju Orho-Melander, PhD, Lund University, Sweden; Candace Guiducci and Noel Burtt, Broad Institute; and Joel Hirschhorn, MD, PhD, Children’s Hospital Boston.

Massachusetts General Hospital (http://www.massgeneral.org/), established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.

Source: Sue McGreevey
Massachusetts General Hospital

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