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Archives for Cancer

Expert in Immune Responses in Stem Cell Transplantation Joins UPCI

PITTSBURGH, Dec. 17, 2014 – Warren Shlomchik, M.D., a leading expert in investigating the immunologic mechanisms underlying graft-versus-host-disease (GVHD), a common complication for some stem cell transplant patients, has been named director of stem cell transplantation and cell therapies for the University of Pittsburgh’s Division of Hematology-Oncology and University of Pittsburgh Cancer Institute (UPCI), a partner with UPMC CancerCenter, and UPCI’s scientific director of hematopoietic malignancies.

Dr. Shlomchik’s appointment is effective March 1, 2015. He will also serve as a professor of medicine and immunology at the University of Pittsburgh School of Medicine. He comes to Pittsburgh from Yale Cancer Center at the Yale University School of Medicine, where he had been on the senior faculty for 16 years.

“Warren’s work has been invaluable in helping researchers understand more about the mechanisms of GVHD. His main priorities here in Pittsburgh will be to continue to conduct innovative, ground-breaking lab-based science and to oversee the translation of that science into investigator-initiated clinical trials, which will be a huge advance for our transplant and hematopoietic malignancies clinical research program,” said Edward Chu, M.D., chief of the Division of Hematology/Oncology and deputy director of UPCI.

Dr. Shlomchik is a leading expert in GVHD, a well-established complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted donor cells attack the transplant recipient’s body. At Pitt, Dr. Shlomchik will continue his research on GVHD mechanisms as well as work to develop novel immunologic-based and cell therapy approaches to circumvent and/or overcome the development of GVHD.

“We’ve been very fortunate at UPCI this year to add several renowned researchers to our ranks, including Dr. Shlomchik,” said Nancy E. Davidson, M.D., director of UPCI and UPMC CancerCenter. “The decision of these researchers to come here shows that we are serious about the work we are doing to unravel the mysteries of cancer and take those findings directly to our patients.”

Dr. Shlomchik earned his bachelor of arts at Harvard University and his medical degree at the University of Pennsylvania. He completed his residency in internal medicine at New York Hospital/Cornell Medical Center and was a fellow at the University of Pennsylvania in hematology-oncology.

Newly-Identified Gene Mutation Could Help Explain How Breast Cancer Spreads

SAN ANTONIO, Dec. 9, 2014 – A newly-identified genetic mutation could increase our understanding of how breast cancer spreads and potentially guide treatment options for women with the disease, according to a study from Magee-Womens Research Institute (MWRI) and the University of Pittsburgh Cancer Institute (UPCI) presented today at the 2014 San Antonio Breast Cancer Symposium.

This research represents the most comprehensive analysis to date of genomic changes that occur in breast cancer progression and indicate the extensive changes that happen during the spread of the disease.

Researchers from MWRI and UPCI sequenced frozen breast tumor samples from six patients, beginning with the primary tumor when the cancer was first diagnosed through the progression of metastatic disease.  Using multiple sequencing techniques, the team identified a new gene created by two separate genes that fused together as a result of unstable DNA.  This fusion gene was identified in a metastatic tumor sample and is believed to play a part in the spread of the original breast cancer.

“We applied all of our sequencing technologies to the tumors in order to understand the changes that occur between the first breast cancer occurrence and late-stage disease,” said Ryan Hartmaier, a research instructor at the University of Pittsburgh and lead author of the study.

Since several types of breast cancer are fueled by the hormone estrogen, estrogen blocking treatment is often recommended to prevent the disease from spreading. However, the fusion gene identified did not  respond to estrogen blocking treatment, contributing to the breast cancer’s spread.

“This research helps us further understand the genomic landscape of metastatic breast cancer,” said Adrian Lee, Ph.D., the study’s senior author, director of the Women’s Cancer Research Center and professor of pharmacology, chemical biology and human genetics Pitt. “The new class of genetic changes identified take us another step further in personalized medicine and could change the way we treat certain patients if we are able to identify who will develop this genetic mutation.”

New Drug Therapy A Safe, Effective Option for Elderly Patients with Acute Myeloid Leukemia

PITTSBURGH, Dec. 8, 2014 – Seventy percent of elderly patients with acute myeloid leukemia (AML) who were treated with a combination of drugs aimed to make chemotherapy treatments effective and less toxic achieved remission or a slowing of disease progression, according to research at the University of Pittsburgh Cancer Institute (UPCI), partner with UPMC CancerCenter. The findings were presented Sunday at the 56th American Society of Hematology Annual Meeting in San Francisco.

The research is important because most elderly patients diagnosed with AML can’t tolerate the aggressive chemotherapy needed and tend to have more aggressive disease than younger patients, making prognosis poor. So researchers, led by UPCI’s Annie Im, M.D., an assistant professor of medicine in Pitt’s Division of Hematology/Oncology, examined whether an epigenetic strategy using the drugs decitabine followed by cytarabine would help make other treatments more tolerable by reactivating genes that had previously been silenced by the malignancy.

“Outcomes are really poor in elderly patients who have AML because the only therapies we have are often too toxic to offer as treatment options, and the unmet need for novel therapies is dire,” Dr. Im said. “But we have shown that using this therapy in this patient population is safe and effective.”

In the study, 23 patients were evaluated after receiving what’s called an induction therapy of decitabine intravenously for five days followed by a standard dose of cytarabine intravenously for five days. Fourteen patients had complete remission and five patients had a complete remission with delayed bone marrow recovery. All patients except for two received two cycles of induction.

Researchers believe the drugs work because they help reactivate genes that had been silenced by the malignancy. In addition, evidence suggests that epigenetic priming by decitabine enhances the efficacy of cytarabine. The next phase of the trial will examine overall survival and the rate of adverse events, and include epigenetic correlative studies.

NSAIDs Prevent Colon Cancer by Inducing Death of Intestinal Stem Cells That Have Gene Mutation

PITTSBURGH, Nov. 3, 2014 – Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) protect against the development of colorectal cancer by inducing cell suicide pathways in intestinal stem cells that carry a certain mutated and dysfunctional gene, according to a new study led by researchers at the University of Pittsburgh Cancer Institute (UPCI) and the School of Medicine. The findings were published online today in the Proceedings of the National Academy of Sciences.

Scientists have long known from animal studies and clinical trials that use of NSAIDs, such as aspirin and ibuprofen, lowers the risk of developing intestinal polyps, which can transform into colon cancer. But they have not known why, said senior investigator Lin Zhang, Ph.D., associate professor, Department of Pharmacology and Chemical Biology, Pitt School of Medicine, and UPCI, a partner with UPMC CancerCenter.

“Our study identifies a biochemical mechanism that could explain how this preventive effect occurs,” he said. “These findings could help us design new drugs to prevent colorectal cancer, which is the third leading cause of cancer-related deaths in the country.”

The research team performed experiments in animal models and examined tumor samples from patients who had taken NSAIDs and those who hadn’t. They found that NSAIDs activate the so-called death receptor pathway, which selectively triggers a suicide program in intestinal stem cells that have a mutation in the APC gene that renders the cells dysfunctional. Healthy cells lack the mutation, so NSAIDs cause them no harm. In that manner, the drugs instigate the early auto-destruction of cells that could lead to precancerous polyps and tumors.

“We want to use our new understanding of this mechanism as a starting point to design better drugs and effective cancer prevention strategies for those at high risk of colon cancer,” Dr. Zhang said. “Ideally, we could harness the tumor-killing traits of NSAIDs and avoid possible side effects that can occur with their chronic use, such as gastrointestinal bleeding and ulcers.”

The research team included lead author Brian Leibowitz, Ph.D., and Jian Yu, Ph.D., of UPCI and the Pitt’s Department of Pathology, as well as others from UPCI and Pitt School of Medicine; Sichuan University, China; INCELL Corp, San Antonio, Texas; and Indiana University School of Medicine.

The project was funded by National Institutes of Health grants CA106348, CA121105, CA172136, CA129829 and DK085570, and the American Cancer Society.

Never Giving Up: UPMC, Pitt Researchers Receive Grants Totaling $800,000 from V Foundation

PITTSBURGH, Oct. 21, 2014 – Researchers from the University of Pittsburgh Cancer Institute (UPCI), partner with UPMC CancerCenter, have been awarded a grant from the V Foundation for Cancer Research to study gene mutations in patients whose head and neck cancer was caused by human papillomavirus (HPV) in hopes of finding a more effective, less toxic therapy for this often painful, disfiguring disease.

The three-year, $600,000 grant was awarded to principal investigator Julie Bauman, M.D., M.P.H., associate professor of medicine and director of the Head and Neck Cancer Section in the Division of Hematology-Oncology at the University of Pittsburgh School of Medicine and co-director of the UPMC Head and Neck Cancer Center of Excellence. The V Foundation, formed by ESPN and former college basketball coach Jim Valvano who is known for challenging people to never give up, also recognized Pitt’s Kara Bernstein, Ph.D., with a V Scholar award, worth $200,000 over two years.

“Coach Valvano established the V Foundation in 1993, the same year he lost his own battle with cancer. His dream was to find a cure for cancer, and we share in that dream here at the University of Pittsburgh Cancer Institute,” said Nancy E. Davidson, M.D., director UPCI and UPMC CancerCenter. “These are highly competitive grants, and we are so pleased that Pitt investigators were recognized.”

Dr. Bauman said the grant will help researchers build on existing scientific knowledge and pioneer new treatments for head and neck cancer, which affects more than 50,000 people in the U.S. and 600,000 people worldwide each year. The primary cause of head and neck cancer in North America and Europe is becoming oral infection with HPV. Although HPV-related cancer responds well to intensive treatment, combinations of surgery, radiation and chemotherapy can result in permanent changes to uniquely human functions: facial expression, speech and swallowing.

“We’ve already learned that half of HPV-related head and neck cancers demonstrate abnormalities in a gene known as PIK3CA,” Dr. Bauman said. “We’re now learning how alterations in this gene cooperate with the virus to transform benign HPV infections into cancer. In addition, we are conducting a clinical trial to see whether a new drug that targets PIK3CA improves response in patients with HPV-related cancer. Ultimately, we aim to identify more effective and less toxic treatments, and even to prevent the transformation of HPV infection into cancer.”

Dr. Bauman is collaborating on the study with Jennifer Grandis, M.D., F.A.C.S., Pitt’s vice chair for research, professor of otolaryngology and pharmacology, and program leader for UPCI’s Head & Neck Cancer Program; Michelle Ozbun, Ph.D., the Maralyn S. Budke Endowed Professor of Viral Oncology at the University of New Mexico Cancer Center; Uma Duvvuri, M.D., Ph.D., Pitt assistant professor of otolaryngology; Andrew Cowan, M.D., Ph.D., assistant professor of surgery, Division of Otolaryngology, University of New Mexico Cancer Center; and Simion Chiosea, M.D., of the UPMC Anatomic Pathology Department.

The V Foundation has awarded more than $100 million for cancer research to more than 100 facilities nationwide since its inception. The translational research grants are designed to accelerate laboratory findings with the goal of benefiting patients more quickly. The V Scholar grants are designed to help early career cancer investigators develop into promising future research talents.

As a V Scholar, Dr. Bernstein will use her award to investigate why people who have mutations in proteins known as RAD51 paralogues are more susceptible to getting cancer – particularly breast and ovarian – and to identify methods for treating their specific cancers.

“Our goal is to uncover individualized cancer treatment for these particular tumors so these patients will have the best outcomes possible,” Dr. Bernstein said.

Pitt/McGowan Institute Team Discovers Stem Cells in the Esophagus

PITTSBURGH, Oct. 16, 2014 – Despite previous indications to the contrary, the esophagus does have its own pool of stem cells, said researchers from the University of Pittsburgh School of Medicine in an animal study published online today in Cell Reports. The findings could lead to new insights into the development and treatment of esophageal cancer and the precancerous condition known as Barrett’s esophagus.

According to the American Cancer Society, more than 18,000 people will be diagnosed with esophageal cancer in the U.S. in 2014 and almost 15,500 people will die from it. In Barrett’s esophagus, the lining of the esophagus changes for unknown reasons to resemble that of the intestine, though gastro-esophageal reflux disease or GERD is a risk factor for its development.

“The esophageal lining must renew regularly as cells slough off into the gastrointestinal tract,” said senior investigator Eric Lagasse, Pharm.D., Ph.D., associate professor of pathology, Pitt School of Medicine, and director of the Cancer Stem Cell Center at the McGowan Institute for Regenerative Medicine. “To do that, cells in the deeper layers of the esophagus divide about twice a week to produce daughter cells that become the specialized cells of the lining. Until now, we haven’t been able to determine whether all the cells in the deeper layers are the same or if there is a subpopulation of stem cells there.”

The research team grew pieces or “organoids” of esophageal tissue from mouse samples, and then conducted experiments to identify and track the different cells in the basal layer of the tissue. They found a small population of cells that divide more slowly, are more primitive, can generate specialized or differentiated cells, and have the ability to self-renew, which is a defining trait of stem cells.

“It was thought that there were no stem cells in the esophagus because all the cells were dividing rather than resting or quiescent, which is more typical of stem cells,” Dr. Lagasse noted. “Our findings reveal that there indeed are esophageal stem cells, and rather than being quiescent, they divide slowly compared to the rest of the deeper layer cells.”

In future work, the researchers will examine human esophageal tissues for evidence of stem cell dysfunction in Barrett’s esophagus disease.

“Some scientists have speculated that abnormalities of esophageal stem cells could be the origin of the tissue changes that occur in Barrett’s disease,” Dr. Lagasse said. “Our current and future studies could make it possible to test this long-standing hypothesis.”

The project’s co-investigators are Aaron DeWard, Ph.D., and Julie Cramer, Ph.D., both of Pitt’s Department of Pathology and the McGowan Institute.

The research was funded by grants from the Commonwealth of Pennsylvania, National Institutes of Health grant DK08571, the McGowan Institute and the University of Pittsburgh Department of Pathology Postdoctoral Research Training Program.

UPMC Partners with GK Klinika to Develop and Co-Manage Cancer Hospital in Lithuania

 PITTSBURGH, Oct. 7, 2014 GK Klinika Group, a private health care company in the Baltic region, is partnering with UPMC for its help in developing and co-managing a new, 100-bed cancer hospital in Vilnius, Lithuania.

Scheduled to open in 2017 and funded by GK Klinika, the hospital is expected to care for patients covered by both private and public insurance to enhance the quality of oncology care throughout the Baltic region. Under the 15-year agreement, UPMC will assist with project planning, construction and training, and will co-manage all clinical and administrative activities after the facility opens.

The prime minister of Lithuania, Algirdas Butkevicius, will participate in a signing ceremony at UPMC’s headquarters today. The Lithuanian government is actively working to encourage foreign business expansion in that country, particularly in its highly advanced life sciences sector, and expects that this partnership with UPMC will foster U.S.-Lithuania relations and geopolitical stability in the region. 

“As an international leader in health care and medical research — and one that has proven that its model of care can be adapted to other countries and cultures — UPMC was the logical choice to be our partner in creating a world-class cancer facility,” said Karapet Babaian, M.D., chief executive officer of GK Klinika and of Baltijos Medicinos Tyrimu Institutas (BMTI), the unit that is working with UPMC. “The scope and length of this agreement is a testament to our faith in this new partnership.”

GK Klinika is one of the leading private clinics in the Baltic region, with more than 15 years of experience and a reputation for promoting innovative medical technology to achieve better patient outcomes. 

“GK Klinika and UPMC share the same vision: to give patients access to the best cancer care in the world close to home. We look forward to working with our partner to make that dream a reality in Lithuania,” said Charles Bogosta, president of UPMC’s International and Commercial Services Division.

UPMC’s wide-ranging assistance to GK Klinika will include hiring and training of staff in Pittsburgh and Vilnius, information technology planning, developing early cancer detection programs, conducting a genomics-testing pilot project and providing disease-specific treatment algorithms. UPMC physicians also will periodically provide consults related to advanced surgeries performed at the new hospital and second opinions via telemedicine.

The chief executive officer of the new hospital will be appointed by mutual agreement of both partners. 

Starting with its partnership to create a transplant center in Italy 18 years ago, UPMC has expanded its international footprint to include operations or services in countries that now include Ireland, India, China, Singapore, Japan and Kazakhstan. Through its international growth and commercialization efforts with industry partners, UPMC is diversifying its sources of revenue, fueling economic development in its local communities, and strengthening its ability to recruit and retain the best clinicians to improve health care outcomes globally.

Pitt Researchers Awarded $4.2 Million to Continue Cancer Studies in Chinese Populations

PITTSBURGH, Oct. 6, 2014 – Cancer epidemiologist Jian-Min Yuan, M.D., Ph.D., has been awarded a five-year grant of more than $4.2 million from the National Cancer Institute (NCI) to support the continued work of two studies examining how environmental and lifestyle exposures and genetics have affected the incidence, mortality and age-related outcomes of cancer in more than 81,000 Chinese men and women.

Dr. Yuan, associate director for Cancer Control and Population Sciences at the University of Pittsburgh Cancer Institute (UPCI), partner with the UPMC CancerCenter, and co-leader of UPCI’s Cancer Epidemiology and Prevention Program, is the principal investigator of the Shanghai Cohort Study and the Singapore Chinese Health Study. For the two population-based prospective studies, researchers examine cancer and other major health outcomes by evaluating blood, urine and other samples collected from participants for more than 25 years. These studies already have yielded important findings about the causes and prevention of cancer and have led to chemoprevention trials underway in the U.S.

“We anticipate that the two Asian study groups will become even more scientifically valuable over the next five years as the younger members of these groups get older and have a greater risk of developing cancer, thereby increasing the number of pre-disease, biomarker-based research opportunities,” said Dr. Yuan, who also is Pitt’s Arnold Palmer Endowed Chair in Cancer Prevention.

With the new award, Dr. Yuan and his collaborators hope to accrue 2,700 new cancer cases over the next five years. They also hope to:

  • Gather data to maintain and enhance the two Asian study databases, including follow-up for cancer, non-cancer and death outcomes; maintenance of the biorepositories; and management of the databases.
  • Conduct in-person and telephone interviews among participants to update exposure and medical information.
  • Collect blood and urine samples from participants with cancer diagnoses.
  • Engage in collaborative research projects of the NCI and the Asia Cohort Consortium. 

“Having the ability to examine diseases in large populations is reshaping the way we approach diagnosis and treatment. We’re excited about the possibilities this research holds and what we’ll learn next,” said Nancy E. Davidson, M.D., director of UPCI and UPMC CancerCenter.

This research is supported by the NCI under award number UM1CA182876.

Renowned Robotic Thoracic and Esophageal Surgeon Joins UPMC

PITTSBURGH, Sept. 25, 2014 – A thoracic surgeon who specializes in the minimally invasive treatment of malignant and benign diseases of the chest has joined the Department of Cardiothoracic Surgery under the direction of James D. Luketich, MD.

Inderpal S. Sarkaria, MD, FACS, joined the Department of Cardiothoracic Surgery at UPMC as Director of Thoracic Robotic Surgery, Vice Chairman for Clinical Affairs, and Co-Director of the Esophageal Surgery Institute.

Dr. Sarkaria has extensive expertise and experience in minimally invasive and Video Assisted Thoracic Surgical (VATS) approaches including esophagectomy for esophageal cancer, VATS lobectomy for lung cancer, VATS thymectomy, laparoscopic anti-refux surgery for GERD, laparoscopic surgery for achalasia, laparoscopic repair of giant paraesophageal hernias (GPEH), and robotic-assisted approaches to these conditions.

Dr. Sarkaria is also a member of and has lectured extensively at several major national and international thoracic surgical societies, and has been involved with committees for resident and fellow education, health care policy, and neuroendocrine lung tumors.

Adding Chemotherapy to Radiation Treatment Not Effective in Treating Vulvar Cancer, UPMC Study Shows

SAN FRANCISCO, Sept. 18 - The addition of chemotherapy to post-surgical radiation treatment is not effective in treating vulvar cancer, according to Magee-Womens Hospital of UPMC research presented this week in San Francisco at the 56th annual meeting of the American Society for Radiation Oncology (ASTRO).

Vulvar cancer is extremely rare, accounting for just 4 percent of gynecologic cancers and 0.6 percent of cancers women face in the U.S. each year. Led by Sushil Beriwal, M.D., associate professor with the department of radiation oncology at the University of Pittsburgh School of Medicine and radiation oncologist at Magee, this study identified patients diagnosed with vulvar cancer between 1998 and 2011 who had undergone surgery to remove the cancer and required adjuvant radiation therapy because the disease had spread to their lymph nodes.

The study utilized the National Cancer Database, a nationwide oncology outcomes database, to identify 1,087 patients who underwent chemotherapy treatment in addition to radiation therapy after their initial surgery to remove the cancer. The study took into account factors including age, race, insurance coverage, tumor size and spread of the disease.

“Our study found that overall, the addition of chemotherapy to adjuvant radiation therapy did not improve patient survival,” said Dr. Beriwal. “While retrospective studies do impose some limits on our conclusion, we found that at the very least, use of concurrent chemotherapy should be carefully evaluated on an individual basis.”

While the study didn’t confirm a benefit of the addition of adjuvant chemotherapy to treatment, Dr. Beriwal said it is important to share the findings because they move researchers one step closer to understanding how to most effectively treat vulvar cancer.

 

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