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News Article | May 4, 2017
Site: www.eurekalert.org

(New York, NY - May 4, 2017) -- Immunotherapy, which has achieved remarkable results in late-stage lung cancer patients, can also hold great hope for newly diagnosed patients, cutting the deadly disease off before it has the chance to take hold and offering a potential cure, according to a new Mount Sinai study published today in Cell. Researchers at The Tisch Cancer Institute at Mount Sinai discovered that some of the same immune cells that allow immunotherapy to turn around some late-stage lung cancers are also present just as the disease takes hold. Before now, little was known about the immune response in early lung cancer, said Miriam Merad, MD, PhD, Professor of Oncological Sciences and of Medicine (Hematology and Medical Oncology) at The Tisch Cancer Institute at Mount Sinai. Dr. Merad and a multidisciplinary team of thoracic surgeons, pathologists, and scientists devised a comprehensive study that began when patients went into surgery to have cancerous lesions removed. The patients' lung tumor samples, samples of surrounding healthy lung tissue, and blood samples were immediately analyzed on a cellular level to map out the immune system components present. The team of researchers crafted a barcoding method that attaches cells in each sample to a different metal isotope, allowing the samples to be pooled for a simultaneous analysis of cells from all three tissue types. The scientists combined this barcoding approach with high-dimensional profiling to map the complete immune landscape to search for tumor-driven changes that would be vulnerable to targeted immunotherapy. The analysis of the samples showed that stage I lung cancer lesions already harbor immune system components that likely compromise anti-tumor T cells' ability to fend off cancer. These single-cell analyses offered unprecedented detail of tumor-driven immune changes, providing a powerful tool for the future design of immunotherapies such as checkpoint inhibitors, particularly those that target the PD-1 and PD-L1 proteins that shield cancer from the immune system; these checkpoint inhibitors have shown great promise in later-stage cancers. "Immunotherapy has mostly been used in advanced or metastatic lung cancer, but its benefit in early-stage tumors remains unknown," Dr. Merad said. "The standard treatment for early lung cancer is normally surgical removal of the lesions--sometimes with chemotherapy and radiation. Our study reveals that early lung lesions are heavily infiltrated with many different immune cells, suggesting that immunotherapy could also work on very early lesions and potentially lead to a cure by heading cancer off at the pass before it really takes root in the lungs." This new research also identified a multitude of additional immunotherapy targets to increase the number of patients that would significantly benefit from immunotherapy, which at the moment remains fairly small. This research is being used to develop immunotherapy trials with early lung cancer patients. "About 50 percent of patients with small lung cancer lesions relapse," Merad said. "And when lung cancer is advanced, chemotherapy does not have a great success rate, so knowing how to attack the cancer at an early stage could have huge impacts on the number of patients relapsing and their overall survival. Our research further corroborates the belief that immunotherapy agents are most efficient at early stages of cancer, particularly in patients who have never been treated with chemotherapy." Raja M. Flores, MD, Chair of the Department of Thoracic Surgery at Mount Sinai Health System, and his team contributed significantly to the study by identifying patients and providing their tissue samples. Mount Sinai's Human Immune Monitoring Center (HIMC) also played an integral role, by providing a platform to analyze patient samples using quality control assays and cutting-edge technology. Through the HIMC, Dr. Merad plans to build a portal to share the results of this study and of other HIMC research to collaborate with colleagues at other cancer centers in the hopes of promoting further cancer and immunology research. This study was funded by Foundation pour la Recherche Medicale DEA20150633125 and NIH grants R01, R01 CA173861, U19AI128949, U24 AI 118644, U19 AI 117873-01. The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is on the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. or find Mount Sinai on Facebook, Twitter and YouTube.


News Article | May 5, 2017
Site: www.eurekalert.org

(New York - May 5, 2017) - Much is known about flu viruses, but little is understood about how they reproduce inside human host cells, spreading infection. Now, a research team headed by investigators from the Icahn School of Medicine at Mount Sinai is the first to identify a mechanism by which influenza A, a family of pathogens that includes the most deadly strains of flu worldwide, hijacks cellular machinery to replicate. The study findings, published online today in Cell, also identifies a link between congenital defects in that machinery -- the RNA exosome -- and the neurodegeneration that results in people who have that rare mutation. It was by studying the cells of patients with an RNA exosome mutation, which were contributed by six collaborating medical centers, that the investigators were able to understand how influenza A hijacks the RNA exosome inside a cell's nucleus for its own purposes. "This study shows how we can discover genes linked to disease -- in this case, neurodegeneration -- by looking at the natural symbiosis between a host and a pathogen," says the study's senior investigator, Ivan Marazzi, PhD, an assistant professor in the Department of Microbiology at the Icahn School of Medicine at Mount Sinai. Influenza A is responsible in part not only for seasonal flus but also pandemics such as H1N1 and other flus that cross from mammals (such as swine) or birds into humans. "We are all a result of co-evolution with viruses, bacteria, and other microbes, but when this process is interrupted, which we call the broken symmetry hypothesis, disease can result," Dr. Marazzi says. The genes affected in these rare cases of neurodegeneration caused by a congenital RNA exosome mutation may offer future insight into more common brain disorders, such as Alzheimer's and Parkinson's diseases, he added. In the case of Influenza A, the loss of RNA exosome activity severely compromises viral infectivity, but also manifests in human neurodegeneration suggesting that viruses target essential proteins implicated in rare disease in order to ensure continual adaptation. Influenza A is an RNA virus, meaning that it reproduces itself inside the nucleus. Most viruses replicate in a cell's cytoplasm, outside the nucleus. The researchers found that once inside the nucleus, influenza A hijacks the RNA exosome, an essential protein complex that degrades RNA as a way to regulate gene expression. The flu pathogen needs extra RNA to start the replication process so it steals these molecules from the hijacked exosome, Dr. Marazzi says. "Viruses have a very intelligent way of not messing too much with our own biology," he says. "It makes use of our by-products, so rather than allowing the exosome to chew up and degrade excess RNA, it tags the exosome and steals the RNA it needs before it is destroyed. "Without an RNA exosome, a virus cannot grow, so the agreement between the virus and host is that it is ok for the virus to use some of the host RNA because the host has other ways to suppress the virus that is replicated," says the study's lead author, Alex Rialdi, MPH, a graduate assistant in Dr. Marazzi's laboratory. Co-authors include investigators from the University of California-San Francisco, Columbia University, Regeneron Pharmaceuticals and Regeneron Genetics Center, Burnham Institute for Medical Research, and the University of California-Los Angeles. The study was supported by NIH grants 2RO1AI099195 and DP2 2OD008651 (U.B.), and partially supported by HHSN272201400008C - Center for Research on Influenza Pathogenesis (CRIP) a NIAID-funded Center of Excellence for Influenza Research and Surveillance (A.G.S, H.v.B., R.A., and I.M.). Other support includes the Department of Defense W911NF-14-1-0353 (to I.M.) NIH grant 1R56AI114770-01A1 (to I. M.), NIH grant 1R01AN3663134 (I.M. and H.v.B), and NIH grant U19AI106754 FLUOMICS (I.M., R.A., S.C., N.K., A.G.S.). The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services -- from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. , or find Mount Sinai on Facebook, Twitter and YouTube.


Researchers comparing leading treatment approaches for patients with severe uveitis have discovered that systemic therapy with oral corticosteroids and immunosuppression can preserve or improve vision in the long term better than regional implant therapy can. The results, published in the May 6, 2017 issue of JAMA, should reassure physicians about the relative safety of this approach, and may lead ophthalmologists to change their treatment protocol for better and safer outcomes. Douglas Jabs, MD, MBA, Director of the Eye and Vision Research Institute, New York Eye and Ear Infirmary of Mount Sinai, and Professor of Ophthalmology and Medicine, Icahn School of Medicine at Mount Sinai, chaired an international team of researchers as they examined the long-term effects of two treatment approaches for patients with vision-threatening uveitis. Uveitis, the fifth leading cause of vision loss in the United States, is a collection of more than 30 diseases characterized by inflammation inside the eye that damages the tissues; without appropriate treatment, it will often lead to visual impairment or blindness. For more severe cases, treatment generally calls for taking oral corticosteroid and immunosuppressive medications. The alternative is regional therapy, either with repetitive corticosteroid injections or with a surgically placed fluocinolone acetonide implant that releases corticosteroid medication over three years. Since most of the more severe uveitis cases are chronic, long-term therapy is typically needed. The Multicenter Uveitis Steroid Treatment (MUST) Trial Follow-up Study followed 215 patients from the original MUST Trial for seven years. The MUST Trial and Follow-up Study were conducted at 21 medical centers across the United States, along with two sites in the United Kingdom and Australia. Patients in the Trial had been randomized to receive either systemic treatment with oral corticosteroids and immunosuppression or regional therapy with the fluocinolone acetonide implant. At the seven-year mark, the findings showed that patients taking oral medications had better vision on average, compared to those in the implant group. The results differ from the initial MUST Trial findings and from the earlier five-year results of the MUST Follow-up Study, in which the same patients had similar visual outcomes at both time points. The MUST Trial and Follow-up Study also showed that there was no significant increase in the risks of systemic side effects for the systemic therapy group compared to implant therapy, with one exception: patients in the systemic group were more likely to receive antibiotics for infections. These outcomes suggest that systemic treatment, if used properly, may be given relatively safely for up to seven years. "The implication of these data is that oral corticosteroids and immunosuppression may be a preferable initial choice for therapy of the more severe uveitides," explained Dr. Jabs. "They have better visual outcomes long-term, fewer ocular side effects, and no apparent significant increase in the risk of systemic side effects, except for the greater use of antibiotics." While the large majority of both groups maintained good vision at the end of seven years, some patients with the fluocinolone acetonide implant did worse in terms of visual acuity. Results of the follow-up study show vision loss occurred more often in the implant group due to damage from inflammatory lesions in the back of the eye, which occurred at the time of relapse of the uveitis. Even though the implant is designed to release corticosteroid medication for three years, the study found that the benefit lasted approximately five years, with relapses beginning at that time. Relapses can be treated with an implant exchange or by switching to systemic therapy. "Although both treatment approaches control the inflammation in the large majority of patients, for the first five years the implant was better than systemic therapy at controlling inflammation. Hence it has value for those patients where systemic therapy cannot control the inflammation or for those patients who cannot tolerate the oral medications," said Dr. Jabs. He notes the implant has an important role to play in the management of these diseases. "The visual loss that occurred in the implant group with relapse of the uveitis emphasizes the need of sustained control of inflammation in order to optimize visual outcomes in patients. These patients need close follow-up for reactivation of the inflammation, so that appropriate adjustments to treatment can be made." The National Eye Institute (NEI), which is part of the National Institutes of Health, supported the MUST Trial and MUST Trial Follow-up Study. The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. , or find Mount Sinai on Facebook, Twitter and YouTube.


News Article | February 23, 2017
Site: www.eurekalert.org

Diabetes is a leading cause of kidney disease, a serious, often fatal complication that is difficult to diagnose in early, potentially treatable stages. Now, a research team at the Icahn School of Medicine at Mount Sinai has revealed biological pathways involved in diabetic kidney disease, providing hope that both early diagnostic tests and targeted treatment can be designed. The study, published in Diabetes, shows that oxidative stress in the "power plants" within a population of kidney cells progressively impairs the ability of the bean-shaped organs to strain blood for waste products and produce urine. The research team also found a cellular receptor that can be blocked to modulate that stress reaction. Blocking that receptor saved the kidneys in mice genetically destined to develop diabetic kidney failure. About 30 percent of patients with type 1 (juvenile onset) diabetes and 10 to 40 percent of those with type 2 (adult onset) diabetes eventually will suffer from kidney failure, according to the National Kidney Foundation. When that happens, patients must turn to dialysis or kidney transplantation, if available. "Diabetic kidney disease is one of the major causes of death in diabetic patients, and is also the leading single cause of end-stage renal disease in the United States," says the study's senior investigator, Ilse S. Daehn, PhD, Assistant Professor of Medicine (Nephrology) at the Icahn School of Medicine at Mount Sinai. "Our findings open new diagnostic opportunities for early detection and potential therapeutic strategies to protect against further renal damage in patients." The study's findings essentially offer a "fundamental paradigm shift in our understanding of the development and treatment of diabetic kidney disease," says Dr. Daehn, who is also a member of The Charles Bronfman Institute for Personalized Medicine. Investigators focused on the kidney's glomerulus -- globular bodies, full of capillaries and other structures, that serve as the first stage and the key unit in the filtration of blood for waste products to be expelled in urine. The research team studied three different cell types that interact within the glomerulus, using two sets of mice. One group naturally develops diabetic kidney disease and the other group is naturally resistant to the disorder. They discovered that in mice prone to kidney disease, endothelial cells were affected. In these wafer-like cells, which form the inner lining of blood vessels, the mitochondria -- cellular subunits that act like power plants, producing energy -- were stressed, and so made excess amounts of reactive oxygen species (ROS). These are molecules that have important roles in cell signaling but, when overproduced, can damage cell proteins and DNA. This process begins to destroy podocytes, cells that wrap around and work with capillaries and the other cell types in the glomerulus. The glomerulus eventually becomes brittle, the capillaries collapse, and kidneys become leaky, shedding essential body proteins. Progressive damage leads to kidney failure, resulting in end-stage kidney disease. The research team was able to measure, in susceptible mice, molecules linked to excess ROS, suggesting that a biomarker could be developed that signals early development of kidney disease in humans. And knowing that ROS excess leads to kidney disease implies that agents that collect ROS molecules within the kidney might provide a potential therapy, Dr. Daehn says. Investigators then looked for "upstream" regulators of mitochondrial stress within the endothelium in the glomerulus and discovered a pathway that helps manage this oxidative stress. This pathway produced excess quantities of a cell receptor, endothelium receptor-A, as well as its ligand -- the protein that binds to the receptor. This discovery means that a small molecule that blocks the ligand from binding to its receptor might tamp down production of mitochondrial ROS, thus halting damage to the glomerulus, Dr. Daehn says. The researchers used an experimental small molecule, BQ-123, to specifically block this receptor and found that mice that were destined to develop diabetic kidney disease were spared from the disorder. Researchers tested their hypothesis by looking at urine and kidney biopsies from patients with diabetic kidney disease. They found molecules in the urine linked to oxidative stress and rapid disease progression, and biopsies that showed increased mitochondrial DNA damage and increased endothelium receptor-A expression. "These findings in human samples go a long way to substantiate our hypotheses, which is exciting because it represents a new way forward to understanding and treating diabetic kidney disease," Dr. Daehn says. Among other researchers from the Icahn School of Medicine who co-authored the study was senior investigator Erwin Böttinger,, MD, Professor of Medicine (Nephrology). The research team also includes investigators from Columbia University in New York and the University of Gothenberg in Sweden. The study was supported by National Institutes of Health Grants 5U01DK060995, 5R01DK056077 and R01DK097253. The authors report no conflicts of interest. The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. , or find Mount Sinai on Facebook, Twitter and YouTube.


News Article | February 28, 2017
Site: www.prweb.com

The Colon Cancer Foundation, a New York-based nonprofit dedicated to the fight against colorectal cancer, today announced a massive new public awareness campaign called “Protect Your Butt!” The new campaign will focus on the Colon Cancer Foundation’s commitment to saving lives through colon cancer awareness, prevention, and translational research programs focused on a cure and optimal care for those most affected by this disease. The campaign also will break through all stigmas and fears around colon cancer and screening, and significantly increase awareness of the disease. Over 50,000 Americans die from colon cancer each year making colon cancer the #2 cancer in the USA. The kickoff event for the Protect Your Butt! Campaign is the “World’s Largest Booty Shake,” scheduled for Wednesday, March 1, in Central Park. The World’s Largest Booty Shake is expected to draw thousands of colon cancer survivors, those passionate about the cause, and more. “Our kick-off booty shake event is just the beginning,” said Dr. Thomas Weber, the foundation’s founder. “Too many people avoid talking about colon cancer because they are unaware or scared. Our new multifaceted Protect Your Butt! Campaign will reach millions of Americans through large events, social media, email marketing, and television. We are literally going to shake this up, raise money for the cure, and save lives.” The World’s Largest Booty Shake is sponsored by the Mount Sinai Health System, and partners of the Colon Cancer Foundation, Epigenomics and Bracco. These three leading health providers focus on colon cancer prevention, screening, and research. “We are proud to be the presenting sponsor for the World’s Largest Booty Shake,” said David Greenwald, MD, Director of Clinical Gastroenterology and Endoscopy at The Mount Sinai Hospital. “Colon cancer is the No. 2 cancer killer in the United States. By raising awareness and encouraging screening, we can save more lives and change this statistic.” The World’s Largest Booty Shake event starts at noon on Wednesday, March 1, at the Central Park Band Shell, south of Bethesda Terrace between 66th and 72nd streets. Headlining the World’s Largest Booty Shake will be rising R&B star Mark MK and DJ Theo, who will debut the new R&B single: “PYB – Protect Your Butt!” The new single can be downloaded on iTunes, Spotify, Tidal, Amazon, and other services, and part of the proceeds will go towards colon cancer research. All money raised during the Protect Your Butt! Campaign helps to raise awareness of the nation’s second leading cancer killer and provides funds for colorectal cancer research, education, and prevention programs for the underserved. For more information about the Colon Cancer Foundation, visit http://www.coloncancerchallenge.org. The Colon Cancer Foundation (coloncancerchallenge.org) is a 501(c)(3) not-for-profit organization registered in New York state and listed by the Federal IRS as a public charity dedicated to reducing colorectal cancer incidence and death. Its mission includes supporting research into the causes and cures for colorectal cancer, increasing public awareness, educating the public about the importance of early detection and forming strategic partnerships in the fight against colorectal cancer. The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services—from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the “Honor Roll” of best hospitals in America, ranked No. 15 nationally in the 2016-2017 “Best Hospitals” issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation’s top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai’s Kravis Children’s Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www.mountsinai.org, or find Mount Sinai on Facebook, Twitter and YouTube. Epigenomics is a molecular diagnostics company focused on blood-based detection of cancers using its proprietary DNA methylation biomarker technology. The company develops and commercializes diagnostic products across multiple cancer indications with high medical need. Epigenomics' lead product, Epi proColon, is a blood-based screening test for the detection of colorectal cancer. Epi proColon has received approval from the U.S. Food and Drug Administration (FDA) and is currently marketed in the United States, Europe, and China and selected other countries. Epigenomics’ second product, Epi proLung®, is in development as a blood-based test for lung cancer detection. Bracco Imaging S.p.A., part of the Bracco Group, is one of the world’s leading companies in the diagnostic imaging business. Headquartered in Milan, Italy, Bracco Imaging develops, manufactures and markets diagnostic imaging agents and solutions that meet medical needs. Bracco Imaging offers a product and solution portfolio for all key diagnostic imaging modalities: X-ray Imaging (including Computed Tomography-CT, Interventional Radiology, and Cardiac Catheterization), Magnetic Resonance Imaging (MRI), Contrast Enhanced Ultrasound (CEUS), and Nuclear Medicine through radioactive tracers. The diagnostic imaging portfolio is completed by a range of medical devices and advanced administration systems for contrast imaging products.


News Article | March 2, 2017
Site: www.eurekalert.org

(New York, NY - March 2, 2017) --Mount Sinai researchers have discovered that a rheumatoid arthritis drug can block a metabolic pathway that occurs in tumors with a common cancer-causing gene mutation, offering a new possible therapy for aggressive cancers with few therapeutic options, according to a study to be published in Cancer Discovery. Ramon Parsons, MD, PhD, Ward-Coleman Chair in Cancer Research and Chair of the Department of Oncological Sciences at the Icahn School of Medicine at Mount Sinai, led a team that studied how a mutation of the PTEN gene rewires a metabolic pathway in tumors, channeling increased amounts of the amino acid glutamine into the pathway, speeding up DNA production, and causing uncontrolled growth of the tumor. The team discovered that leflunomide, an oral rheumatoid arthritis drug approved by the U.S. Food and Drug Administration, blocks an enzyme in this pathway and damages the DNA created through the pathway, killing PTEN mutant cancer cells while leaving healthy cells untouched. Parsons and his team transplanted human breast cancer cells into mice to test leflunomide's efficacy. Leflunomide drastically reduced the breast cancer tumors in the mice. "Finding successful targeted therapies for cancer is a challenging but important goal in the face of insufficient treatment options," said Dr. Parsons, who discovered the PTEN gene. "Targeted therapies that are tumor-specific are much needed, and identifying changes based on specific tumor suppressor or oncogene alterations will facilitate this effort. Due to the high mutation rate of PTEN in cancer, the effects of PTEN could be at the heart of targeted therapy." This discovery has implications in aggressive cancers with the PTEN mutation and few treatment options such as triple negative breast cancer, prostate cancer, endometrial cancer, and glioblastoma, a brain cancer. Dr. Parsons hopes to create a clinical trial to further test leflunomide in patients with breast and colon cancer. This research was funded by NCI R01CA082783, R01CA155117, and P01CA97403 (R.P.), and partially supported by NIH grants 5P01CA120964 and 5P30CA006516 (J.MA.), and R01 GM041890 and the Breast Cancer Research Foundation (L.C.). The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is on the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. or find Mount Sinai on Facebook, Twitter and YouTube.


News Article | February 22, 2017
Site: www.eurekalert.org

An early-stage clinical trial has found that, compared to a placebo, a novel medication significantly reduces potentially life-threatening episodes of swelling of the airway as well as the hands, feet, and abdomen of patients affected by a rare genetic disorder. The findings were published in the New England Journal of Medicine. Although the small study was designed to test safety of the drug, the findings were so obviously promising that an expedited phase III clinical study has just started enrolling patients at the Icahn School of Medicine at Mount Sinai and other locations. The study's co-lead author, Paula Busse, MD, is an allergist-immunologist at Mount Sinai and an associate professor at the Icahn School of Medicine. The disorder, hereditary angioedema (HAE), causes recurrent and unpredictable attacks of swelling throughout the body. What triggers these attacks is not known. The multicenter, double-blind, placebo-controlled phase 1b study of 37 patients with type 1 or 2 HAE found that all participants that used a 300-mg dose of the drug, lanadelumab, were attack-free, as were 82 percent who took 400 mg. Only 27 percent of participants who used a placebo were incident-free. "Lanadelumab appears to stop attacks of HAE before they start, and this prophylactic approach may represent an exciting new advance for patients," says Dr. Busse, who treats dozens of patients with the disorder. "Given the uncertainty of when an attack may happen, some HAE patients don't want to travel," she says. "The disease can produce such swelling for three to five days that a face is disfigured, hands can't be used, it is difficult to walk, and the abdomen can become very painful. Having a drug that can provide an ongoing buffer against HAE will be wonderful." Current therapies for preventing HAE attacks work, but there are some drawbacks, Dr. Busse adds. A drug known as a C-1 inhibitor needs to be given intravenously every three or four days, and another approach, the use of pills called androgens (a modified testosterone), can produce unwanted hair growth in women, affect mood, cause weight gain, affect lipid levels and liver function, and inhibit growth in children. Lanadelumab, on the other hand, is a monoclonal antibody that is injected every two weeks and was found to be well tolerated by patients in this trial. HAE is an autosomal, dominantly inherited blood disorder caused by a deficiency or dysfunction of a regulatory gene known as the C1 inhibitor. The C1 inhibitor protein normally suppresses the production of another protein called bradykinin, which is the cause of swelling. Without a C1 inhibitor that functions properly, a person produces more bradykinin and consumes less of it. Bradykinin causes the swelling (angioedema) by making vessels dilate and leak fluid. The study included extensive blood analysis, which closely tracked how the drug successfully suppressed production of bradykinin. "If the phase III clinical study confirms the benefit we have seen, lanadelumab will make life much easier for HAE patients," says Dr. Busse. "Many patients who don't like and therefore don't use current treatments will likely opt for this new therapy, which will hopefully reduce morbidity and mortality, and improve the quality of life of patients with HAE." Dr. Busse worked with researchers from a number of universities nationally, and with a research team from Dyax, the developer of Lanadelumab and supporter of the trial. The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. , or find Mount Sinai on Facebook, Twitter and YouTube.


News Article | February 16, 2017
Site: www.eurekalert.org

(New York, NY - February 16, 2017) --Mount Sinai researchers have created a novel model that shows the step-by-step progression from normal blood cells to leukemia and its precursor diseases, creating replicas of the stages of the disease to test the efficacy of therapeutic interventions at each stage, according to a study to be published in Cell Stem Cell. This research marked the first time scientists have been able to transplant leukemia from humans to a test tube and then into mice for study, a landmark feat that will allow for valuable research to help find therapies for blood cancer patients in the future. "The new model will empower investigation into the cellular and molecular events underlying the development of leukemia in ways that were not possible before," said Eirini P. Papapetrou, MD, PhD, Associate Professor of Oncological Sciences, Medicine, Hematology, and Medical Oncology at the Icahn School of Medicine at Mount Sinai. "These findings provide a framework to aid investigation into disease mechanisms, drug responses, and the cellular and molecular events driving leukemia progression." Scientists used CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat), a new, cutting-edge genome editing technology, to convert blood cells from patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) to particular stem cells (called induced pluripotent stem cells) that can mimic all stages of disease progression, from a healthy state to pre-malignancy and finally full-blown leukemia. Though scientists believe that cancer develops through a step-by-step process by which a normal cell transforms to a fully malignant cell through intermediate stages, recreating the steps was challenging with previous tools. Scientists were able to manipulate the leukemia in a test tube environment, both by genetically modifying the disease-ridden stem cells at certain stages to revert to a pre-cancerous state, and by altering them so they would either progress to a severe or mild form of MDS. The ability to manipulate the leukemia to regress or progress will allow future researchers to test therapies that may be most potent at a particular stage, thus saving or extending a patient's life. Memorial Sloan Kettering Cancer Center was a valuable collaborator in this research. The lab of Michael G. Kharas, PhD, performed some of the mouse transplantation experiments in the study. "We are encouraged by the discovery that it was possible to generate potent engraftable leukemia derived from AML induced pluripotent stem cells," said Dr. Kharas, the co-corresponding author. "This work shows that integrated patient cell reprogramming and cancer genetics is a powerful way to dissect cancer progression." The progression model created through this research could also be used to develop models for more complex cancers, including solid tumors, the researchers said. The research was funded by grants from the National Institutes of Health from the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases (R01HL121570 and R00DK087923); the Damon Runyon Cancer Research Foundation, the Edward P. Evans Foundation, the Ellison Medical Foundation, the Henry and Marilyn Taub Foundation, the Babich Family Foundation and Alex's Lemonade Stand Foundation. The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is on the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. or find Mount Sinai on Facebook, Twitter and YouTube.


News Article | December 14, 2016
Site: www.eurekalert.org

(New York, NY - December 12, 2016) -- Even before tumors develop, breast cancer cells with a few defined molecular alterations can spread to organs, remain quiet for long periods of time, and then awaken to form aggressive, deadly breast cancer metastasis, says a team of investigators led by researchers at Icahn School of Medicine at Mount Sinai and the University of Regensburg in Germany. They say their finding, published in two papers in the journal Nature, and conducted in animal models and tested in human samples, now solves the mystery of how breast cancer metastasis forms without a primary tumor in this new model of early dissemination and metastasis. Furthermore, a clinical primary tumor may never develop, investigators say. The University of Regensburg team had discovered that cancer cells could spread not only from a highly mutated, overtly evolved and pathologically-defined invasive tumors, but also from early stage cancers commonly considered incapable of spreading cells. However, how these early cancer lesions could spawn cells with traits of malignant tumors was unknown. In two papers published in the journal Nature, and conducted in animal models and tested in human samples, the two teams now have identified the first mechanisms that allow cells to spread early in cancer progression and contribute to metastasis. In the study from Mount Sinai, two changes in mammary cancer cells -- a switched-on oncogene and a turned-off tumor suppressor-- motivated cells to travel from breast tissue to the lungs and other parts of the body. There, the cells stayed quiet until a growth switch was activated and metastases developed in lungs. "This research provides insight into the mechanisms of early cancer spread and may shed light into unexplained phenomena -- among them, why as many as 5 percent of cancer patients worldwide have cancer metastases but no original tumor, and most importantly, why it is so difficult to treat cancer that has spread," says the study's senior investigators, Julio A. Aguirre-Ghiso, PhD, Professor of Medicine, Hematology and Medical Oncology, Maria Soledad Sosa, PhD, Assistant Professor of Pharmacological Sciences, and graduate student Kathryn Harper of The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. "Biologically, this new model of early metastasis challenges everything we thought we knew about how cancer spreads and forms metastasis. It feels like we are going to have to adjust our ideas about the subject of metastasis," he says. "Our hope is that these findings will reshape the way we think about how metastasis should be treated." An important finding from the Mount Sinai team is that most early spread cells remain dormant and most chemotherapy and targeted therapies are aimed at those cells that are proliferative. So early spread cancer cells would escape these conventional therapies even if it kills a primary tumor, Dr. Aguirre-Ghiso says. The work also poses new questions on how early spread cancer cells support metastasis development. Do they do it on their own, do they set the soil for later arriving cells from tumors not caught early, or do they cooperate with later arriving cells? This study reveals a new biological mechanism of early dissemination that must be explored to fully understand how to target the seeds of metastasis. The companion paper headed by Dr. Christoph Klein at the University of Regensburg in Germany, published in the same issue of Nature and co-authored by Dr. Aguirre-Ghiso and members of his team provides additional key mechanistic clues on how early spread is controlled and proof in human cancer cells and tumors of the preclinical findings in this study. Researchers from both teams arrived at their findings independently and then collaborated on the project. Researchers from both teams studied very early stages of breast cancer including DCIS (ductal carcinoma in situ), a noninvasive breast lesion, since 2-3 percent of women who have been treated for DCIS die of metastasis without ever developing a primary tumor. "The best explanation for this phenomenon is that early metastasis occurs before or as DCIS develops. A key finding from this second paper is that in the mouse models, 80% of metastasis originated from the early spread cells and not from the large tumors. In fact, the Klein group identified a mechanism by which spread is more efficient in early lesions than in large tumors. In both studies, investigators found that early cancer cell spread is an extension of the normal process of creating a branching tree of breast milk ducts in females. Two major pathways are activated in this ancient process -- p38, a tumor suppressor, and HER2, an oncogene. Switching off p38 and turning on HER2 activates a module of the EMT (epithelial to mesenchymal transition) signaling pathway. EMT promotes movement of cells during embryogenesis and tissue development. The Klein paper also shows that progesterone receptor signaling, which controls branching of the mammary tree, is important for this early spread by regulating cues involved in EMT and growth programs, a mechanism that was hinted in his earlier studies. As a mammary tree develops, p38, HER2, and EMT are alternatively turned on and off. This, in cooperation with progesterone signaling, allows mammary cells to move through the mammary gland, hollow out a tubular, branching network of milk ducts that flow to the nipple. "Tweaking these pathways are a normal way of forming hollow branching tubes," Dr. Aguirre-Ghiso says. But in their experiments, they found that if HER2 is over-activated (not switched off) or mutated, and p38 is permanently turned off, EMT was continually activated, allowing cells to move out of the mammary gland and into the animal's body through the blood. "We were able to use organoids in three-dimensional cultures, and high resolution imaging directly in the live animal models to actually see these cells enter the blood stream from the mammary tree and travel to the lung, the bone marrow, and other places," he says. "We hadn't thought about oncogenes and tumor suppressors in this way before. This is a new function for these pathways." John S. Condeelis, PhD, co-Director of the Gruss Lipper Biophotonics Center and its Integrated Imaging Program at Einstein, where the high resolution intravital imaging was performed, noted that "We were surprised to learn that cancer cells from DCIS-like lesions could show such robust dissemination using similar machinery found in tumor cells from invasive carcinoma. This is a new insight with implications beyond our expectations." Also David Entenberg MSc, Director of Technological Development and Intravital Imaging who led the imaging efforts within the same Center said, "A few years ago, it would not have been possible to image these disseminating cells inside a living animal with this level of detail. We're pleased that Einstein's imaging technology could, through this collaboration, contribute to the definitive proof of early dissemination." And while both studies focus on the mechanisms of early dissemination in breast cancer, similar processes could control early dissemination and metastasis in other human cancers, including melanoma and pancreatic cancer. In fact, pancreatic cancer early dissemination has also been linked to an EMT process, Dr. Aguirre-Ghiso says. Among the critical avenues they are investigating, Mount Sinai researchers are looking for the growth switch that pushes early spread of dormant cancer cells to form metastases. "While our findings add a whole new level of complexity to the understanding of cancer, they also add energy to our efforts to finally solve the big issue in cancer -- stop the metastasis that kills patients," Dr. Aguirre-Ghiso says. Study contributors include lead co-authors Kathryn L. Harper, PhD, Maria Soledad Sosa, PhD, Julie F. Cheung, BSc, Rita Nobre MSc, Alvaro Avivar-Valderas, PhD, Chandandaneep Nagi, MD, and Eduardo F. Farias, PhD, from Icahn School of Medicine at Mount Sinai; Christoph Klein, MD and Hedayatollah Hosseini, PhD from the University of Regensburg, Germany; Nomeda Girnius, PhD and Roger J. Davis, PhD from Howard Hughes Medical Institute at the University of Massachusetts Medical School; and David Entenberg, MSc and John Condeelis, PhD from Albert Einstein College of Medicine in New York. The study was supported by grants SWCRF, CA109182, CA196521, CA163131, CA100324, F31CA183185, BC132674, BC112380, NIH 1S10RR024745 Microscopy CoRE at ISMMS, the Integrated Imaging Program at Einstein, HHMI, DFG KL 1233/10-1 and the ERC (322602). For a video on this release: https:/ The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is on the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. or find Mount Sinai on Facebook, Twitter and YouTube.

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