Penn Presbyterian Medical Center

Philadelphia, PA, United States

Penn Presbyterian Medical Center

Philadelphia, PA, United States
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News Article | May 8, 2017
Site: www.eurekalert.org

PHILADELPHIA - A newly identified molecular chain of events in a mouse model of prostate cancer highlights novel targets to treat it and other cancers. A team led by Marcelo Kazanietz, PhD, a professor of Systems Pharmacology and Translational Therapeutics, published in Cell Reports that the overexpression of a protein called PKCε with the loss of the tumor suppressor Pten causes the progression of prostate cancer. This deadly combination produces an uptick in the levels of the cancer-promoting molecule CXCL13. When the team purposely disrupted CXCL13, or CXCR5, the cell-surface receptor it attaches to, the metastatic and tumor-forming characteristics of the mouse prostate cancer cells were impaired. "In addition to providing evidence for a vicious cancer cycle driven by PKCε, our studies identified a compelling rationale for blocking the CXCL13-CXCR5 molecules as a new cancer treatment," Kazanietz said. He and colleagues plan to identify compounds to block CXCR5 or CXCL13 with potential to be developed as anti-cancer agents. The researchers also suggested that CXCL13 levels in blood could be used as a biomarker to measure the precise state of prostate cancer progression in a patient. The team's next step will be to interfere with CXCR5/CXCL13 signals not only from the cancer cells but also from other cells in the tumor microenvironment that contribute to cancer growth. Pulmonologists and oncologists have also observed that PKCε is overexpressed in lung cancer patients, but they do not fully understand its exact molecular consequences. In general, a high level of PKCε is associated with a poor prognosis. "We are in the midst of extending these findings to lung cancer," said Kazanietz, who is collaborating with Penn Medicine researchers David Feldser, PhD, an assistant professor of Cancer Biology, Steven M. Albelda, MD, a professor of Pulmonary, Allergy and Critical Care, and Evgeniy Eruslanov, PhD, a research assistant professor of Thoracic Surgery. This research was funded in part by the National Institutes of Health (R01-CA089202, R01-CA189765, R01-CA196232), the Department of Defense (PC130641, W81XWH-12-1-0009). Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.


News Article | May 26, 2017
Site: www.eurekalert.org

PHILADELPHIA -- Irene Hurford, MD, an assistant professor in the department of Psychiatry, has received a 2017 Exemplary Psychiatrist Award from the National Alliance on Mental Illness (NAMI). Hurford is one of only five recipients of the award nationally, which is presented to "honor the exceptional contributions that ... psychiatrists make to improve the lives of people living with mental health conditions." Her research focuses on measuring cognition in psychosis, treatment outcomes in early-episode psychosis, interventions to improve functioning in early psychosis, and program evaluation. In addition to her faculty role at Penn, Hurford developed and directs the Psychosis Education, Assessment, Care, and Empowerment (PEACE) Program through Horizon House, Inc. PEACE helps people in the early stages of psychosis learn to manage their symptoms and meet their life goals. It works to support the entire person towards recovery from, and resiliency to, psychosis. Hurford's philosophy behind PEACE is to treat psychosis as a barrier, not an insurmountable illness that has to define who people are. She and her team take a hopeful approach. The goal is to keep clients in work or school. Hurford educates and engages family members of clients in the PEACE program by including them in the counseling sessions. By participating, they learn about the illness as well as how to help their family members cope. They also come to realize that their loved ones can truly recover from psychosis and lead lives of their own choosing. Also, Hurford has been the coordinated specialty team trainer for three pilot first-episode psychosis projects throughout Pennsylvania, providing training and guidance based on her experience in establishing PEACE. She is the principal investigator for statewide program evaluation of first episode psychosis programs in Pennsylvania. She received her medical degree from McMaster University in Hamilton, Ontario, Canada and BSc in psychology from the University of Toronto. She completed her residency in psychiatry and post-doctoral training at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA) as well as an advanced fellowship in psychiatry at San Diego VA Medical Center. Her awards include the Brain & Behavior Research Foundation's NARSAD Young Investigator Award and designation as a Top Psychiatrist by the Consumer's Research Council of America. NAMI, the nation's largest grassroots mental health organization, offers education programs to individuals, families, and professionals; advocates for public policy in support of people with mental illness and their families; staffs a national help line; and works to increase public awareness of mental illness. Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.


News Article | May 25, 2017
Site: www.eurekalert.org

PHILADELPHIA -- There are more than 98,000 people currently awaiting a kidney transplant in the United States. But the organs are in short supply: only about 17,000 patients will receive transplants each year. For sicker patients and those facing the longest wait times -- five to seven years or more on the waiting list -- a new study finds there may be a benefit to accepting a kidney from a deceased diabetic donor. In a study published today in the Clinical Journal of the American Society of Nephrology, researchers from the Perelman School of Medicine at the University of Pennsylvania, have found that the best chance of survival, for older patients, those who live in areas with long waits for transplantation, or those who already have diabetes, may come from accepting a kidney from a deceased donor who had diabetes. "Most often, these organs are considered 'high-risk' as diabetes is a risk factor for kidney disease, and there may be underlying kidney damage that is not detected in initial organ screenings prior to transplantation," said lead author Jordana Cohen, MD, MSCE, an instructor of Medicine in the division of Renal-Electrolyte and Hypertension. "However, there are many patients on the wait list who will die before they receive a kidney transplant. For these patients, based on this study, their best chance of survival and of having a better quality of life may come from accepting this kind of organ." Researchers performed an observational study of 437,619 kidney transplant candidates using data from the Organ Procurement and Transplantation Network database. They identified 8,101 recipients of diabetic donor kidneys and 126,560 recipients of nondiabetic donor kidneys. The team assessed the risk an adverse event after accepting a diabetic donor kidney as compared to remaining on the waitlist or receiving a nondiabetic donor kidney. "Our goal was to evaluate the mortality risk of transplantation with diabetic donor kidneys compared to remaining on the kidney transplant waitlist, and to determine which patients would benefit most from transplantation with these organs," said senior author Deirdre L. Sawinski, MD, assistant medical director of Kidney Pancreas Transplantation, and an assistant professor of medicine in the division of Renal-Electrolyte and Hypertension. "In this analysis, we were able to determine that kidney transplant candidates who are at highest risk of dying on the waitlist, such as the elderly, patients with diabetes themselves, and those at centers with the longest average waiting times, benefit most from transplantation with diabetic donor kidneys, with a nearly 10 percent improvement in long term survival." The team also found that poor quality diabetic donor kidneys, as determined by a donor index that takes into account factors such as donor age and kidney function, provide no survival benefit, and that younger kidney transplant candidates--those under age 40 years old--do not benefit from transplantation with diabetic donor kidneys. While kidneys from diabetic donors may not last as long or work as well as kidneys from non-diabetic donors, the initial survival benefits seem to outweigh these risks. Sawinski added that "patients, who are over the age of 40 or those who already have diabetes, should consider accepting a kidney from a deceased diabetic donor when available, in order to increase their chances of being transplanted sooner, and increasing their survival." Additional Penn authors on this study include Kimberly Forde and Peter Reese. This study was supported in part by the National Institutes of Health (K23-HL133843), (K23-DK103918) and (K23-DK090209). Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.


News Article | May 25, 2017
Site: www.prweb.com

Doctors in Pennsylvania have released their report on the potential therapeutic value of combining immunotherapy drugs with radiotherapy in the treatment of malignant pleural mesothelioma. Their study is the subject of a new article at Surviving Mesothelioma. Click here to read it now. The University of Pennsylvania analysis looked at studies that combined immunotherapy drugs like Keytruda (pembrolizumab), avelumab, and nivolumab with radiation treatments to positively impact mesothelioma survival. “The combination of immunotherapy and radiation therapy may allow for complimentary immunologic effects that can enhance antitumor response,” writes Dr. Evan W. Alley of the Hematology and Oncology Division at Penn Presbyterian Medical Center. The article in Translational Lung Cancer Research recommends that more clinical trials be conducted on the combined effects of these two immunomodulatory therapies in the treatment of mesothelioma. “If it can be shown that these two therapies can enhance one another’s effectiveness and boost mesothelioma survival, it could open up a new set of treatment options for patients who currently have few viable choices,” says Alex Strauss, Managing Editor for Surviving Mesothelioma. To read more about the synergistic effects of immunotherapy drugs and radiation on mesothelioma tumors, see Immunotherapy and Radiation: A Powerful Mesothelioma Combo, now available on the Surviving Mesothelioma website. Alley, EW, et al, “Immunotherapy and radiation therapy for malignant pleural mesothelioma”, April 2017, Translational Lung Cancer Research, pp. 212-219, http://tlcr.amegroups.com/article/view/13139/10997#B39 For more than a decade, Surviving Mesothelioma has brought readers the most important and ground-breaking news on the causes, diagnosis and treatment of mesothelioma. All Surviving Mesothelioma news is gathered and reported directly from the peer-reviewed medical literature. Written for patients and their loved ones, Surviving Mesothelioma news helps families make more informed decisions.


News Article | May 26, 2017
Site: www.eurekalert.org

PHILADELPHIA -- For years, the common narrative in human developmental neuroimaging has been that gray matter in the brain - the tissue found in regions of the brain responsible for muscle control, sensory perception such as seeing and hearing, memory, emotions, speech, decision making, and self-control -- declines in adolescence, a finding derived mainly from studies of gray matter volume and cortical thickness (the thickness of the outer layers of brain that contain gray matter). Since it has been well-established that larger brain volume is associated with better cognitive performance, it was puzzling that cognitive performance shows a dramatic improvement from childhood to young adulthood at the same time that brain volume and cortical thickness decline. A new study published by Penn Medicine researchers this month and featured on the cover of the Journal of Neuroscience may help resolve this puzzle, revealing that while volume indeed decreases from childhood to young adulthood, gray matter density actually increases. Their findings also show that while females have lower brain volume, proportionate to their smaller size, they have higher gray matter density than males, which could explain why their cognitive performance is comparable despite having lower brain volume. Thus, while adolescents lose brain volume, and females have lower brain volume than males, this is compensated for by increased density of gray matter. "It is quite rare for a single study to solve a paradox that has been lingering in a field for decades, let alone two paradoxes, as was done by Gennatas in his analysis of data from this large-scale study of a whole cohort of youths," said Ruben Gur. "We now have a richer, fuller concept of what happens during brain development and now better understand the complementary unfolding processes in the brain that describe what happens." The study was led by Ruben Gur, PhD, professor of Psychiatry, Neurology, and Radiology in the Perelman School of Medicine at the University of Pennsylvania, Raquel Gur, MD, PhD, a professor of Psychiatry, Neurology, and Radiology, and Efstathios Gennatas, MBBS, a doctoral student of neuroscience working in the Brain Behavior Laboratory at Penn. According to Gur, the study findings may better explain the extent and intensity of changes in mental life and behavior that occur during the transition from childhood to young adulthood. "If we are puzzled by the behavior of adolescents, it may help to know that they need to adjust to a brain that is changing in its size and composition at the same time that demands on performance and acceptable behavior keep scaling up," Gur added. In the study, the researchers evaluated 1,189 youth between the ages of 8 and 23 who completed magnetic resonance imaging as part of the Philadelphia Neurodevelopmental Cohort, a community-based study of brain development that includes rich neuroimaging and cognitive data, to look at age-related effects on multiple measures of regional gray matter, including gray matter volume, gray matter density, and cortical thickness. Neuroimaging allowed the researchers to derive several measures of human brain structure in a noninvasive way. Observing such measures during development allowed the researchers to study the brain at different ages to characterize how a child's brain differs from an adult's. "This novel characterization of brain development may help us better understand the relationship between brain structure and cognitive performance," Gennatas said. "Our findings also emphasize the need to examine several measures of brain structure at the same time. Volume and cortical thickness have received the most attention in developmental studies in the past, but gray matter density may be as important for understanding how improved performance relates to brain development." Further study is required to fully characterize the biological underpinnings of different MRI-derived measures by combining neuroimaging and brain histology. The study's findings in healthy people can also help researchers understand the effects of brain disorders in males and females as they evolve during adolescence. This work was supported by the National Institutes of Health (NIH) grants (MH107235), (MH089983), (MH096891), and the Dowshen Neuroscience fund. Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.


PHILADELPHIA--A new strategy - an injectable antibody - for lowering blood lipids and thereby potentially preventing coronary artery disease and other conditions caused by the build-up of fats, cholesterol, and other substances on the artery walls, is supported by findings from two new studies from researchers in the Perelman School of Medicine at the University of Pennsylvania. The new approach targets a protein called ANGPTL3, a regulator of enzymes that clear triglycerides and other fat molecules from the blood. Research in recent years has hinted that inherited mutations in the ANGPTL3 gene that disable its function can decrease triglyceride, LDL cholesterol and HDL cholesterol levels. As reported in a paper published today online in the New England Journal of Medicine, researchers from Penn Medicine, Regeneron Pharmaceuticals, and a group of international collaborators studied ANGPTL3 in both humans and mice. They found that blocking ANGPTL3 activity with an investigative injectable antibody, known as evinacumab, reduced triglycerides by up to 76 percent and lowered LDL cholesterol 23 percent in human study participants, and largely reversed signs of atherosclerosis in a mouse models. Researchers also included a human genetics study of approximately 188,000 people, which found that carriers of mutations that disable ANGPTL3 had nearly 40 percent fewer incidents of coronary artery disease as compared to those with fully functioning ANGPTL3. "In the clinic, I treat many patients with very high triglycerides, but our current medications aren't lowering triglycerides enough in many cases. I'm delighted at the prospect of a new treatment that's a lot more potent, all the more because it lowers LDL at the same time," said study co-author Richard L. Dunbar, MD, assistant professor of Cardiovascular Medicine and member of Penn's Division of Translational Medicine and Human Genetics. "It's very reassuring to see that people with this genetic defect actually seem to be protected from heart disease. I think that really bodes well for a therapeutic that's targeting the ANGPTL3 pathway." In a separate study, published in the March issue of the Journal of the American College of Cardiology (JACC) researchers from Penn Medicine, Harvard Medical School, Washington University in St. Louis, and nine other institutions, who also studied humans and mice, reported on a similar set of findings. Among these was the discovery from another large population sample that carriers of ANGPTL3-inactivating mutations had a 34 percent lower rate of coronary artery disease compared to non-carriers. "We used different lines of evidence to show that ANGPTL3 deficiency is associated with a reduced risk of coronary artery disease," said study co-author Kiran Musunuru, MD, PhD, MPH, an associate professor of Cardiovascular Medicine at Penn. "But ultimately we were able to identify that fact that carriers of this genetic mutation did in fact experience a benefit - with little other health risk." The trial of research on ANGPTL3 as a potential target for atherosclerosis prevention began over a decade ago when scientists reported on two cases of familial hypolipidemia, a rare inherited condition involving abnormally low blood levels of cholesterol and triglycerides. Most cases of familial hypolipidemia are linked to other gene mutations that cause liver and digestive problems, but in members of this American family with the condition, Musunuru found mutations in the gene for ANGPTL3, and no associated health problems. In the NEJM study from Dunbar and colleagues, the antibody had similar effects in an initial clinical trial in 83 people, lowering the blood levels of triglycerides measured after fasting by about 75 percent at the highest dose, and lowering LDL cholesterol by about 30 percent. Statins and other drugs are already widely used to lower LDL cholesterol, but there are fewer options for lowering triglycerides. "For treating high triglyceride levels there's really nothing out there that's quite this potent, so that's where I expect this new approach to have its greatest therapeutic benefit," Dunbar said. Hypertriglyceridemia, a condition in which fasting triglyceride levels are greater than 150 mg/dL, is estimated to affect at least tens of millions of American adults. It is associated with coronary artery disease and other forms of atherosclerosis, and can lead to potentially fatal inflammation of the pancreas. In principle, the strategy of targeting ANGPTL3 could have an even broader use in treating atherosclerosis in the general population. The researchers found that in a mouse model of atherosclerosis, treatment with evinacumab reduced the area of atherosclerotic lesions by 39 percent. The population study findings, including those from the JACC study, suggest that even the partial inactivation of ANGPTL3--carriers typically have one mutant copy of the gene and one working copy--may be powerfully protective against coronary artery disease, which has long been one of the leading causes of death in developed countries. In the JACC study, for example, carriers of inactivating ANGPTL3 mutations had only a 17 percent reduction in triglycerides on average. But that modest reduction was associated with a 34 percent reduction in coronary artery disease risk. Moreover, Musunuru and his colleagues found that the people in their sample with the lowest blood levels of ANGPTL3 had a 35 percent lower rate of heart attacks compared to those with the highest ANGPTL3 levels. Dunbar noted that the population study findings probably have lain to rest a lingering concern about targeting ANGPTL3, namely its effect in lowering not just LDL and triglycerides but also the so-called "good cholesterol," known as HDL cholesterol. "If lowering HDL were a major concern, then I don't think we would have seen the evidence of overall benefit that we did in this study," he said. The two studies together suggest that single copies of inactivating ANGPTL3 mutations are found in roughly one of every 250 people of European descent, whereas people with mutations in both copies of the gene--as in the family studied by Musunuru and colleagues--are much rarer. According to Dunbar, the next logical step would be to take evinacumab into larger clinical trials to study its safety, effectiveness, and optimal dosing. "The effect of even a single dose lasts for several months, and it's plausible that with multiple doses we would see an even deeper and more sustained effect," he said. Additional Penn authors on the NEJM study include Scott Damrauer, MD, Aeron Small, and Daniel J. Rader MD, and the Journal of the American College of Cardiology study include Xiao Wang, PhD, Daniel J. Rader, MD, and Danish Saleheen, MBBS, PhD. Funding sources for the studies detailed in this press release included grants from the National Heart, Lung, and Blood Institute (NHLBI) (R01HL131961), (K08HL114642), (R01HL118744), (R01HL127564) and (R21HL120781) and Regeneron Pharmaceuticals. Editor's Note: Dunbar has received grant support from and consulted for Regeneron Pharmaceuticals, Inc. Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.

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