UPMC Physician Resources

Archives for UPMC

Pitt CVR and Sanofi Pasteur Collaborate to Assess the Effectiveness of a Dengue Vaccine

PITTSBURGH, April 15, 2014 – The University of Pittsburgh Center for Vaccine Research (CVR) and Sanofi Pasteur, the vaccines division of Sanofi, have entered a scientific collaboration to help assess the effectiveness of a dengue vaccine once introduced for immunization programs.

Pitt’s CVR is creating the new test to help assess the effectiveness of Sanofi Pasteur’s dengue vaccine candidate, which aims to reduce cases of dengue and the circulation of the virus in the population. The new test will tell if a person’s immunity to the mosquito-borne virus is due to a previous natural infection or from vaccination.

“Distinguishing whether a person’s immune response is from the vaccine or from infection by a mosquito can play an important role in the assessment of a candidate vaccine,” said Ernesto Marques, M.D., Ph.D., associate professor of infectious diseases and microbiology at Pitt’s CVR. “The goal of this test is to provide additional support in assessing the effectiveness of the vaccine after introduction.”

Dengue disease is caused by four types of dengue virus. It occurs mostly in tropical and subtropical countries, putting about half the world’s population at risk. It is endemic in Puerto Rico and locally acquired cases re-emerged recently in the Florida Keys and Texas. There is no treatment for dengue and no vaccine to prevent it.

It is estimated that around 100 million clinical cases of dengue occur annually, but a larger number of additional cases are so mild that the people who are infected don’t even realize it. Each year 500,000 people, including children, develop severe dengue, characterized by high fever, uncontrolled bleeding, respiratory distress and organ failure.

For every symptomatic case of dengue, there could be as many as three asymptomatic, or “silent” cases, according to recent international research. The new dengue test will be important to fully understand the impact of vaccination by providing additional support in assessing symptomatic versus silent infections, ultimately helping officials gauge how much a vaccine reduces disease transmission,” said Nicholas Jackson, Ph.D., head of dengue research and development for Sanofi Pasteur.

“This test also could be used by the government and health agencies to manage an immunization program,” added Dr. Marques. “It will give evidence that the vaccine works and could allow doctors to determine which populations still need vaccination so they can most effectively target their immunization outreach efforts.”

The Sanofi Pasteur dengue vaccine candidate was found to be safe and demonstrated protection against three of the four dengue virus types in the first efficacy clinical study, with results reported in 2012 in The Lancet, a medical journal. The study, which included 4,002 children, was conducted in a region of Thailand where dengue is highly endemic, and it was the first time a dengue vaccine candidate showed protection against the virus.

Data from Sanofi Pasteur’s ongoing phase III clinical studies with over 31,000 volunteers are expected to be available later this year and will document efficacy of their vaccine in a broader population and different epidemiological environments.

Pitt has a strong history in dengue research, most notably the first isolation and characterization of two of the four types of dengue virus in 1958 by William M. Hammon, M.D., Ph.D., then a professor of microbiology and epidemiology at Pitt’s Graduate School of Public Health. In 1980, Donald S. Burke, M.D., currently the CVR co-director and dean of Pitt Public Health, isolated dengue type 2 viruses in Bangkok.

Children’s Brain Care Institute Physicians Awarded Grant for Study on Brain Damage After Cardiac Arrest

PITTSBURGH, April 11, 2014 – Two critical care physicians, both members of the Brain Care Institute at Children’s Hospital of Pittsburgh of UPMC and associate directors of the Safar Center for Resuscitation Research, were recently awarded an R01 grant from the National Institutes of Neurological Disorders and Stroke to fund a study focused on brain damage after cardiac arrest in infants and children.

Hülya Bayir, MD, professor of critical care medicine, environmental and occupational health, and pediatrics at the University of Pittsburgh, and Robert Clark, MD, chief of pediatric critical care medicine at Children’s Hospital of Pittsburgh of UPMC, will conduct multidisciplinary research for the study called “Mitochondria-Targeted Redox Therapy for Cerebral Ischemia in Developing Brain.” The goal is to synthesize, develop, and test novel mitochondria-targeting therapeutics to meaningfully improving neurological outcome and quality of life in infants and children who suffer from brain damage caused by cardiac arrest, which can cause long-term disability.

National Survey Links Teen Binge Drinking and Alcohol-Brand References in Pop Music

PITTSBURGH, April 8, 2014 – Binge drinking by teenagers and young adults is strongly associated with liking, owning and correctly identifying music that references alcohol by brand name, according to a study by the University of Pittsburgh and Norris Cotton Cancer Center.

Based on a national, randomized survey of more than 2,500 people ages 15 to 23, the findings suggest that policy and educational interventions designed to limit the influence of alcohol-brand references in popular music could be important in reducing alcohol consumption in teens and young adults. The results are published online in the journal Alcoholism: Clinical & Experimental Research.

“Every year, the average adolescent is exposed to about 3,000 references to alcohol brands while listening to music,” said lead author Brian A. Primack, M.D., Ph.D., associate professor of medicine and pediatrics and director of the Program for Research on Media and Health in Pitt’s School of Medicine. “It is important that we understand the impact of these references in an age group that can be negatively affected by alcohol consumption.”

Alcohol is considered the third-leading, lifestyle-related cause of death in the U.S., according to the Centers for Disease Control and Prevention.

“Brand references may serve as advertising, even if they are not paid for by the industry,” said senior author James D. Sargent, M.D., co-director of the Cancer Control Research Program at Norris Cotton Cancer Center in New Hampshire and professor of pediatrics in the Geisel School of Medicine at Dartmouth College. “This is why it is useful to examine the influence of brand mentions.”

Of the 2,541 participants who completed the survey, 1,488, or 59 percent, reported having had a complete alcoholic drink, defined as 12 ounces of beer, 5 ounces of wine or 1.5 ounces of hard liquor at one time. Of those, 18 percent reported binging — or drinking heavily over a short period of time — at least monthly, and 37 percent reported having had problems, such as injuries, due to alcohol.

In the survey, which could be completed either online or on paper, participants were given the titles of popular songs that include alcohol mentions and asked if they liked or owned the song. They also were tested to determine if they could spontaneously recall what brand of alcohol was mentioned in the lyrics.

Survey participants who could correctly recall alcohol brands in songs had more than twice the odds of having had a complete alcoholic drink, compared to those who could not recall the brand, even after adjusting for factors including age, socioeconomic status, and alcohol use by friends or parents. The participants who could identify the alcohol brands in songs also had greater odds of having ever binged on alcohol.

“A surprising result of our analysis was that the association between recalling alcohol brands in popular music and alcohol drinking in adolescents was as strong as the influence of parental and peer drinking and an adolescent’s tendency toward sensation-seeking,” said Dr. Primack. “This may illustrate the value that this age group places on the perceived opinions and actions of music stars.”

Dr. Primack said that one possible solution could be to empower adolescents with critical thinking skills. “Media literacy is a growing educational methodology that may be successful in helping young people make healthier decisions,” he said. “In the case of alcohol, it may be valuable to help them understand how alcohol-brand references in music may manipulate their thoughts and emotions to sell them a product.”

Additional authors on this research are Auden McClure, M.D., M.P.H., and Zhigang Li, Ph.D., both of the Geisel School of Medicine at Dartmouth College.

This work was supported by National Cancer Institute grants K07-CA114315 and R01-CA077026, and a SYNERGY Scholars Award from the Dartmouth Center for Clinical and Translational Research.

Women Seeking Emergency Contraception More Likely to Use IUDs if Offered Counseling and ‘Same-Day Service,’ Pitt Study Finds

PITTSBURGH, April 3, 2014 – Health care clinics should routinely offer same-day placement of intrauterine devices (IUDs) to women seeking emergency contraception, according to researchers at the University of Pittsburgh School of Medicine. The study findings, published online in the journal Contraception, demonstrate that providing patient education along with same-day placement service increases both knowledge and use of IUDs three months and a year after women seek emergency contraception.

“Women seeking emergency contraception, who are at very high risk of undesired pregnancy, deserve clear information about the most effective contraceptives available,” explained Eleanor Bimla Schwarz, M.D., M.S., director of the women’s health services research unit at the Center for Research on Health Care, Pitt School of Medicine, and lead author of the study.

Dr. Schwarz and colleagues compared knowledge and use of IUDs and contraceptive implants among women seeking emergency contraception at an inner-city clinic eight months before and 21 months after it began providing structured counseling and offering same-day IUD or implant placement. A total of 186 women between the ages of 15 and 45 who wanted to avoid pregnancy for at least six months completed surveys immediately and three and 12 months after their clinic visit. Data from the clinic’s electronic medical record provided additional information about contraceptive initiation during the course of the study.

Researchers found that after the clinic began offering structured counseling, more women had accurate knowledge of the effectiveness of IUDs and started to use either an IUD or implant. Thus, this change in clinic policy dropped the number of women using no form of contraception from 17 percent to 3 percent. Data obtained from the electronic medical records indicated that when the option of same-day placement was offered, 11 percent of women received a same-day IUD, and according to survey data, of those who received this service, 88 percent and 80 percent reported continued use at a three- and 12-month follow-up, respectively.

“The results of our study demonstrate that we can make ‘same-day service with a smile’ our standard of care,” concluded Dr. Schwarz. “By fully educating our patients about their contraceptive options and providing convenient access to desired services, we empowered women to effectively avoid undesired pregnancies.”

Additional co-authors of this study include Melissa Papic and Erin Baldauf, both of the University of Pittsburgh School of Medicine; Sara M. Parisi, of the University of Pittsburgh Graduate School of Public Health, Department of Epidemiology; and Rachel Rapkin and Glenn Updike, of the University of Pittsburgh, Department of Obstetrics, Gynecology and Reproductive Sciences.

The study was funded by the Department of Health and Human Services Office of Population Affairs.

Pitt Center for Vaccine Research Joins Global Task Force to Address Urgent Viral Threat

PITTSBURGH, April 7, 2014 – Causing victims to suffer severe fever and pain, chikungunya virus has reached the Caribbean and South America — and is predicted to soon cause outbreaks in the United States. For many years the mosquito-borne virus has remained primarily in Africa, the Indian subcontinent and Southeast Asia. In response to the arrival of the virus in the Western Hemisphere, the University of Pittsburgh Center for Vaccine Research announced today that it will be part of the new Global Virus Network (GVN) Chikungunya Task Force, composed of top virologists from around the world.

The announcement of the new task force coincides with World Health Day 2014 on April 7. This year’s theme is vector-borne diseases, which are infections spread to humans through mosquitos, ticks and other insects. Chikungunya is a vector-borne disease that is quickly spread by mosquitoes.

“Viruses are among the leading causes of death and disability in the world. Being able to quickly bring together the most knowledgeable researchers without regard to borders and political agendas to address viral threats such as chikungunya is paramount,” said GVN co-founder and scientific director Robert Gallo, M.D., who also is director of the Institute of Human Virology at the University of Maryland School of Medicine.

There is no specific antiviral drug treatment for chikungunya, which can resemble dengue fever, another threatening mosquito-borne infection. Treatment of those infected with chikungunya is directed primarily at relieving symptoms, which include a very high fever and joint pain. The joint pain often is debilitating and, in some cases, persists for several months or years. While chikungunya does not cause death directly, it can contribute to a fatal outcome in people who become infected and have other medical problems.

The GVN Chikungunya Task Force is composed of 16 virologists representing nine countries. William B. Klimstra, Ph.D., and Kate D. Ryman, Ph.D., associate professors at Pitt, along with others, will represent the United States. The additional participating countries include the United Kingdom, France, Ireland, Sweden, Grenada, Estonia, South Africa and Thailand. All of the participating members are affiliated with GVN Centers of Excellence. Much of the group’s effort will focus on issues related to more rapid identification of infections, improved treatment options and development of an effective vaccine.

“By being part of this new global collaboration, we will have to the opportunity to exchange information that will help in developing not only an effective response to chikungunya, which may begin to be seen in the U.S. within the next few years, but also an improved response to other emerging viruses,” said Dr. Klimstra.

Chikungunya was first described following an outbreak in southern Tanzania in 1952. Since then, the virus has been identified in dozens of countries across Asia, Europe, Africa and now the Americas.

A vaccine against chikungunya does not yet exist; however, it is a focus of work at Pitt in both Drs. Klimstra’s and Ryman’s laboratories. Dr. Ryman recently was lead author on a publication in PLOS Neglected Tropical Diseases describing a new method for creation of live-attenuated chikungunya vaccines and identification of a promising vaccine candidate. Both researchers also are developing animal disease models for testing of vaccines, as well as therapeutic interventions for chikungunya disease.

The Caribbean’s first cases of chikungunya occurred last October. It is estimated that in those few months, approximately 15,000 cases have occurred. With the area’s high level of tourism, the virus would have many opportunities to quickly spread to other locations. In addition, the type of mosquito connected to the Caribbean cases is common in the United States, Mexico and parts of South America.

“The GVN Chikungunya Task Force will help speed the process of creating vaccines and much-needed diagnostic tools,” said GVN President Sharon Hrynkow, Ph.D. “We look forward to working with public health agencies, including the Pan American Health Organization, to prevent the spread of chikungunya and mitigate human suffering.”

More information about the Global Virus Network’s Chikungunya Task Force is available by visiting www.gvn.org.

Common Breast Cancer Subtype May Benefit From Personalized Treatment Approach, UPCI Finds

SAN DIEGO, April 4, 2014 – The second-most common type of breast cancer is a very different disease than the most common and appears to be a good candidate for a personalized approach to treatment, according to a multidisciplinary team led by scientists at the University of Pittsburgh Cancer Institute (UPCI), a partner with UPMC CancerCenter.

Invasive lobular carcinoma, characterized by a unique growth pattern in breast tissue that fails to form a lump, has distinct genetic markers which indicate drug therapies may provide benefits beyond those typically prescribed for the more common invasive ductal carcinoma. The results recently were published in Cancer Research and will be expanded upon on Tuesday at the American Association for Cancer Research (AACR) Annual Meeting 2014.

Patients with invasive lobular carcinoma typically are treated through surgical removal of the cancer, followed by chemotherapy or hormone therapy or both, usually with the estrogen-mimicking drug tamoxifen or estrogen-lowering aromatase inhibitors, the same as patients with invasive ductal carcinoma.

“However, recent analyses suggest that a subset of patients with lobular carcinoma receive less benefit from adjuvant tamoxifen than patients with ductal carcinoma,” said lead author Matthew Sikora, Ph.D., postdoctoral associate at UPCI, and recipient of this year’s AACR-Susan G. Komen Scholar-in-Training Award for this research. “Our study, the largest of its kind, indicates an issue with the estrogen receptors inside lobular carcinoma cells and points to potential targets for drug therapy in future clinical trials, which we are developing.”

Early studies in developing these potential targets are the topic of Dr. Sikora’s AACR presentation, with a focus on a unique signaling pathway regulated by estrogen specifically in lobular carcinoma cells.

Additional researchers on this study include Steffi Oesterreich, Ph.D., and Amir Bahreini, B.S., both of UPCI.

This research was supported by the Breast Cancer Research Foundation, Department of Defense Breast Cancer Research Program and Pennsylvania Department of Health.

Combining Cell Replication Blocker with Common Cancer Drug Kills Resistant Tumor Cells, UPCI Researchers Find

SAN DIEGO, April 4, 2014 – Researchers from the University of Pittsburgh Cancer Institute (UPCI), a partner with UPMC CancerCenter, have found that an agent that inhibits mitochondrial division can overcome tumor cell resistance to a commonly used cancer drug, and that the combination of the two induces rapid and synergistic cell death. Separately, neither had an effect. These findings will be presented Monday at the annual meeting of the American Association for Cancer Research Annual Meeting 2014.

“In our earlier work, we found that blocking production of a protein called Drp1 stopped mitochondria, known as the powerhouses of the cell, from undergoing fission, which is necessary for the cellular division process called mitosis,” said Bennett Van Houten, Ph.D., the Richard M. Cyert Professor of Molecular Oncology, Pitt School of Medicine, and leader of UPCI’s Molecular and Cell Biology Program. “The loss of this critical mitochondrial protein caused the cells to arrest in mitosis and to develop chromosomal errors, and eventually led the tumor cell into the cell death pathway known as apoptosis.”

The researchers blocked Drp1 in breast cancer cell lines with an agent called mitochondrial division inhibitor-1 (mdivi-1) and found that when mdivi-1 and the cancer drug cisplatin were given together, they caused DNA damage, DNA replication stress, and greater than expected apoptosis rates. The synergistic drug combination acted through two independent biochemical pathways that caused the mitochondrial membrane to swell, increasing its permeability and allowing the leak of chemical signals that trigger apoptosis.

“Cisplatin is one of the most widely used cancer drugs today, but some tumors are inherently resistant to it, and many others become resistant, leading to treatment failure,” Dr. Van Houten said. “In our studies, this combination overcame cisplatin resistance and caused cancer cell death, which is very encouraging.”

The team is testing the regimen’s effectiveness in a mouse model of ovarian cancer, a disease that often recurs and no longer responds to cisplatin treatment.

Screening Reveals Additional Link Between Endometriosis and Ovarian Cancer

SAN DIEGO, April 4, 2014 – Some women with endometriosis, a chronic inflammatory disease, are predisposed to ovarian cancer, and a genetic screening might someday help reveal which women are most at risk, according to a University of Pittsburgh Cancer Institute (UPCI) study, in partnership with Magee-Womens Research Institute (MWRI).

Monday at the American Association for Cancer Research (AACR) Annual Meeting 2014, UPCI and MWRI researchers will present the preliminary results of the first comprehensive immune gene profile exploring endometriosis and cancer.

“A small subset of women with endometriosis go on to develop ovarian cancer, but doctors have no clinical way to predict which women,” said senior author Anda Vlad, M.D., Ph.D., assistant professor of obstetrics, gynecology and reproductive sciences at MWRI. “If further studies show that the genetic pathway we uncovered is indicative of future cancer development, then doctors will know to more closely monitor certain women and perhaps take active preventative measures, such as immune therapy.”

Endometriosis is a painful, often invasive and recurrent condition that happens when the tissue that lines the uterus grows outside of the uterus, causing inflammation. It affects approximately one in 10 women.

By screening tissue samples from women with benign endometriosis, endometriosis with precancerous lesions and endometriosis-associated ovarian cancer, Dr. Vlad and her colleagues identified the complement pathway, which refers to a series of protein interactions that trigger an amplified immune response, as the most prominent immune pathway that is activated in both endometriosis and endometriosis-associated ovarian cancer.

“If, as our study indicates, a problem with the immune system facilitates cancer growth through chronic activation of the complement pathway, then perhaps we can find ways to change that and more effectively prime immune cells to fight early cancer, while controlling the complement pathway,” said lead author Swati Maruti Suryawanshi, Ph.D., a post-doctoral research fellow at MWRI.

Instrumental to this multidisciplinary study were Robert P. Edwards, M.D., and Esther Elishaev, M.D., both of Magee-Womens Hospital of UPMC, and Xin Huang, Ph.D., MWRI. Additional contributors are Raluca Budiu, Ph.D., SungHwan Kim, Ph.D., and George Tseng, Ph.D., all of Pitt; and Marcia Klein-Patel, M.D., Ted Lee, M.D., Suketu Mansuria, M.D., all of UPMC.

This research was funded by UPMC grant 02.93530.

Genetic Testing Beneficial in Melanoma Treatment, UPCI Study Shows

SAN DIEGO, April 4, 2014 – Genetic screening of cancer can help doctors customize  treatments so that patients with melanoma have the best chance of beating it, according to the results of a clinical trial by researchers at the University of Pittsburgh Cancer Institute (UPCI), a partner with UPMC CancerCenter.

The trial, funded by the National Institutes of Health (NIH), will be presented Monday at the American Association for Cancer Research (AACR) Annual Meeting 2014. It showed that the cancer immune therapy drug ipilimumab appears most likely to prevent recurrence in patients whose cancer shows high expression of immune-related genes.

“We’ve reached a point in the treatment of melanoma — and cancer in general — where we’re making major improvements in the outcomes of patients through personalized medicine,” said lead investigator Ahmad Tarhini, M.D., Ph.D., associate professor of medicine and translational science in Pitt’s Department of Medicine and Clinical and Translational Science Institute. “Anti-cancer therapy can be associated with significant side effects and economic costs. Therefore, we have a major interest in the development of tests that may allow us to predict which treatment regimen is most likely to help certain patients, while sparing others the unwanted side effects and cost of medications that are unlikely to work.”

Before and after ipilimumab treatment, Dr. Tarhini and his colleagues obtained tumor biopsies used to run genetic tests on the tumors of 32 patients with advanced, stage 3 melanoma who were treated by UPMC. All patients were given standard-of-care surgery, which included complete surgical removal of an advanced tumor.

Patients with tumors that had higher levels of expression of a group of immune-related genes, either before or soon after treatment with ipilimumab, had 63 percent lower risk of cancer recurrence after surgery.

“By validating these findings in a large national trial that also will allow us to investigate other significant biomarker data, we’ll seek to develop ‘biomarker signatures’ that doctors can use to customize melanoma treatment plans. The ultimate goals of therapy are to best treat the cancer in an individualized approach, while avoiding the unnecessary exposure of patients to severe side effects,” said Dr. Tarhini.

Additional researchers on this study are Yan Lin, Ph.D., Hui-Min Lin, M.S., Cindy Sander, B.S., William A. La Framboise, Ph.D., and John M. Kirkwood, M.D., all of UPCI.

This research was supported by NIH award P50CA121973 and Bristol-Myers Squibb.

Plant-Derived Anti-Cancer Compounds Explained at National Conference

SAN DIEGO, April 4, 2014 – Compounds derived from plant-based sources — including garlic, broccoli and medicine plants — confer protective effects against breast cancer, explain researchers at the University of Pittsburgh Cancer Institute (UPCI), partner with the UPMC CancerCenter.

In multiple presentations Sunday at the American Association for Cancer Research (AACR) Annual Meeting 2014, UPCI scientists will update the cancer research community on their National Cancer Institute (NCI)-funded findings, including new discoveries about the mechanisms by which the plant-derived compounds work.

“In recent years, we’ve made some very encouraging discoveries indicating that certain plants contain cancer-fighting compounds,” said Shivendra Singh, Ph.D., UPMC Chair in Cancer Prevention Research and professor in Pitt’s Department of Pharmacology & Chemical Biology. “By understanding the molecular mechanisms by which these plant-derived compounds work against breast cancer, we hope to find efficient ways to use them to prevent and fight cancer in patients.”

At the AACR poster session “Mechanisms of Chemoprevention,” Dr. Singh will oversee four presentations by Pitt pharmacology & chemical biology researchers on plant-derived compound discoveries in his laboratory.

  • Dr. Singh will discuss how withaferin A, derived from an Indian medicine plant, binds to tubulin, a well-known target for drug treatment in breast and other cancers. This compound binds tubulin in the cancer at a site distinct from those affected by other clinically used tubulin targeting agents. Notably, this effect of withaferin A is selective for cancerous breast cells.
  • Eun-Ryeong Hahm, Ph.D., will discuss how diallyl trisulfide, an oil-soluble molecule created by chewing of allium vegetables, such as garlic, decreases levels of the estrogen receptor-alpha protein in breast cancer cells and inhibits growth of breast cancer stem cells by decreasing levels of two other proteins.
  • Su-Hyeong Kim, Ph.D., will discuss how benzyl isothiocyanate, a molecule found in edible cruciferous vegetables, such as garden cress, works in breast cancer cells to decrease levels of Bmi-1, a protein that controls genes responsible for cell proliferation.
  • Anuradha Sehrawat, Ph.D., will discuss how breast cancer stem cell growth is inhibited when a protein called Ron sensitizes the stem cells to the benzyl isothiocyanate molecule in cruciferous vegetables. The molecule then induces breast cancer stem cell death.

This work was supported by NCI grants RO1 CA142604-04, P30 CA047904, RO1 CA113363-09 and RO1 CA129347-07.

Page 1 of 33:1 2 3 4 »Last »