Ovarian, Glioblastoma & Non-Small Cell Lung Cancer: Jefferson Researchers Present at AACR

Several researchers from Jefferson’s Kimmel Cancer Center presented abstracts at the American Association for Cancer Research Annual Meeting 2012 in Chicago. Some of those findings include:

HuR and Ovarian Cancer

Silencing HuR may be a promising therapeutic approach for the treatment of ovarian cancer, according to an abstract presented at AACR by researchers from Thomas Jefferson University, Lankenau Institute for Medical Research, the Geisinger Clinic and the Massachusetts Institute of Technology.

HuR is a RNA-binding protein that post-transcriptionally regulates genes involved in the normal cellular response to cancer-associated stressors, like DNA damage, nutrient depletion and therapeutic agents.  When triggered by stress, HuR translocates from the nucleus to the cytoplasm where it potently influences translation of key tumor promoting mRNAs by mRNA stabilization and direct facilitation of translation.

Previously, it has been shown that HuR expression is a prognostic marker in ovarian cancers. Thus, researchers tested the effects of manipulating HuR expression levels on ovarian tumor growth characteristics and tested the hypothesis that silencing HuR through delivery of an HuR siRNA would be effective in suppressing the growth of ovarian tumors.

Following treatment of ovarian cancer cells in culture with an adenovirus containing the HuR coding sequence, HuR expression was increased by about 40% above control cells.

In the patient cohort, researchers also detected HuR activation (i.e., cytoplasmic HuR positivity) in twenty-four of thirty four patients (71 percent), providing evidence that the majority of patients have activated HuR.

“These data provide evidence that silencing HuR, even as a monotherapeutic strategy, may be a promising therapeutic approach for the treatment of ovarian cancer,” wrote the authors.

Authors of the paper include Janet A. Sawicki and Yu-Hung Huang, of Lankenau Institute for Medical Research, Charles J. Yeo, Agnieszka K. Witkiewicz, Jonathan R. Brody, of Thomas Jefferson University, Radhika P. Gogoi, of Geisinger Clinic, Danville, Pa., and Kevin Love and Daniel G. Anderson, of Massachusetts Institute of Technology, Cambridge, Mass.

This work was supported by the Marsha Rivkin Center for Ovarian Cancer Research.

Radiotherapy and Glioblastoma

Radiotherapy’s effect on glioblastoma (GBM) is enhanced in the presence of a heat shock protein and a P13K inhibitor, researchers from the Department of Radiation Oncology reported at AACR.

Glioblastoma tumors frequently contain mutations in the tumor suppressor gene, PTEN, leading to loss of PTEN activity, which causes overactivation of the PI3K pathway, inducing inhibition of apoptosis and radioresistance.

Heat-shock protein 90 (HSP90) is a molecular chaperone that is over-expressed in GBM and that has among its client proteins, PI3K and Akt.

It was hypothesized that dual inhibition of HSP90 and PI3K signaling would additively or synergistically radiosensitize GBM through inhibition of radiation-induced PI3K/Akt signaling, leading to enhanced apoptosis.

Confirming their theory, the researchers found that the response of glioblastoma to radiotherapy was enhanced in the presence of BKM120 and HSP990. Enhanced apoptosis also contributed to the mechanism of cell death.

Authors of the study include Phyllis Rachelle Wachsberger, Yi Liu, Barbara Andersen, and Adam P. Dicker, of the Department of Radiation Oncology at Thomas Jefferson University Hospital and Richard Y. Lawrence, of Jefferson and the Sheba Medical Center, Tel Hashomer, Israel.

This work was supported by a grant from Novartis Pharmaceuticals.

Non-Small Lung Cancer and DACH1

Researchers from the Kimmel Cancer Center at Jefferson have identified a protein relationship that may be an ideal treatment target for non-small cell lung cancer (NSCLC).  They presented their findings at AACR.

DACH1, a cell fate determination factor protein, appears to be a binding partner to p53, a known tumor suppressor, which inhibits NSCLC cellular proliferation.

As cancer develops and becomes more invasive, the expression of DACH1 decreases. Clinical studies have demonstrated a reduced expression of the DACH1 in breast, prostate and endometrial cancer.

In a previous study of more than 2,000 breast cancer patients, Jefferson researchers found that a lack of DACH1 expression was associated with a poor prognosis in breast cancer patients. Patients who did express DACH1 lived an average of 40 months longer.

Genetic studies have identified several oncogenes activated in lung cancer, including K-Ras and EGFR. Given the importance of the EGFR in human lung cancer, researchers examined the role of DACH1 in lung cancer cellular growth, migration and DNA damage response.

For this study, endogenous DACH1 was reduced in human NSCLC, with expression levels of DACH1 correlating inversely with clinical stage and pathological grade.

Re-expression of DACH1 also  reduced lung cancer cell colony formation and cellular migration. Cell cycle analyses demonstrated that G2/M block by ectopic expression of DACH1 occurs synergistically with p53.

Fluorescent microscopy demonstrated co-localization of DACH1 with p53, and immunoprecipitation and western blot assay showed DACH1 association with p53.

“DACH1 enhanced the cytotoxcity of cisplatin and doxorubicin, two commonly used drugs for NSCLC,” the authors write in the abstract. “Together, our studies demonstrate that p53 is a DACH1 binding partner that inhibits NSCLC cellular proliferation.”

Authors of the study include Ke Chen, Kongming Wu, Wei Zhang, Jie Zhou, Timothy Stanek, Zhiping Li, Chenguang Wang, L. Andrew Shirley, Hallgeir Rui, Steven McMahon, Richard G. Pestell, of  Thomas Jefferson University, Kimmel Cancer Center and Huazhong University of Science and Technology, Wuhan, China.



Dr. Bo Lu to Lead the Radiation Therapy Oncology Group’s Lung Cancer Translational Research Program

The Radiation Therapy Oncology Group (RTOG) announced that Bo Lu, M.D., Ph.D., of Thomas Jefferson University and the Kimmel Cancer Center at Jefferson, has been appointed chair of the group’s Translational Research Program (TRP) Committee’s Lung Cancer Subcommittee. The RTOG TRP Committee supports the integration of new scientific discoveries into the design of multi-center clinical trials.

Bo Lu, M.D., Ph.D., of Thomas Jefferson University Hospital and the Kimmel Cancer Center at Jefferson

Dr. Lu is professor in the Department of Radiation Oncology at Jefferson, where he also serves as director of the department’s Division of Molecular Radiation Biology.  Prior to joining Jefferson in early 2011, Dr. Lu was associate professor in the Departments of Radiation Oncology and Cancer Biology at Vanderbilt University School of Medicine and director of the Department of Radiation Oncology’s translational research program.  He is also a visiting professor of radiation oncology at Tianjin Medical University Cancer Hospital, in Tianjing, China.

“As a member of RTOG’s Translation Research Program Committee since 2009, it has been exciting to be part of research efforts incorporating novel cancer treatment strategies into the design of early phase, multicenter clinical trials,” says Dr. Lu. Among Dr. Lu’s basic science research interests are the development of drugs that cause tumor cells to be more sensitive to radiation therapy and that target lung cancer stem cells.

“Dr. Lu is internationally renowned for his work in translational radiation oncology, and I am enthusiastic about his leadership role with regard to guiding the RTOG’s translational research agenda in lung cancer,” says Adam Dicker, M.D., Ph.D, Professor and Chairman of Radiation O­ncology at Thomas Jefferson University and RTOG’s Translational Research Program Chair. “He has demonstrated talent for applying findings from the laboratory into clinical research,” remarks Dr. Dicker.

“Dr. Lu’s extensive basic science background and insight about promising new agents will be a tremendous asset to RTOG’s Lung Cancer Committee,” says committee chair and radiation oncologist Jeffrey Bradley, M.D., Associate Professor of Radiation Oncology at Washington School of Medicine. Dr. Bradley adds, “I anticipate an exciting and productive collaboration.”

“The opportunity to work with RTOG colleagues to advance new treatment options and improve clinical care for lung cancer patients is very rewarding,” says Dr. Lu, “and I am pleased to assume an expanded role within a research organization that promotes the robust evaluation of new therapeutic approaches in radiation oncology.”

Dr. Lu received his Ph.D. in cell and molecular biology from Baylor School of Medicine and his doctorate in medicine from Shanghai Medical University in China. He completed his residency in radiation oncology at the University of Southern California. Dr. succeeds Quynh Le, M.D., Ph.D. from Stanford University who recently was named chair of RTOG’s Head and Neck Cancer Committee.

“An important goal at the Kimmel Cancer Center is to foster translational medicine—taking basic science research and moving it closer to clinical practice,” said Richard Pestell, M.D., Ph.D., FACP, Director of the Kimmel Cancer Center at Jefferson. “With his lab investigations focusing on just that, and now this appointment to RTOG’s lung cancer subcommittee, Dr. Lu will no doubt help us discover safer and more effective treatments for patients suffering from this disease.”

For more information about RTOG and the group’s Translational Research Program: www.rtog.org

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The Radiation Therapy Oncology Group (RTOG) is administered by the American College of Radiology (ACR), and located in the ACR Center for Clinical Research in Philadelphia, PA. RTOG is a multi-institutional international clinical cooperative group funded primarily by National Cancer Institute grants CA21661, CA32115 and CA37422. RTOG has 40 years of experience in conducting clinical trials and is comprised of over 300 major research institutions in the United States, Canada, and internationally. The group currently is currently accruing to 40 studies that involve radiation therapy alone or in conjunction with surgery and/or chemotherapeutic drugs or which investigate quality of life issues and their effects on the cancer patient.

The American College of Radiology (ACR) is a national professional organization serving more than 32,000 radiologists, radiation oncologists, interventional radiologists and medical physicists with programs focusing on the practice of radiology and the delivery of comprehensive health care services.



Bernadette E. Garofola Named ASRT Fellow

Bernadette E. Garofola, chief radiation therapist at Thomas Jefferson University Hospital

Bernadette E. Garofola, M.Ed., R.T.(R)(T)(CT), chief radiation therapist at Thomas Jefferson University Hospital, has been named a Fellow of the American Society of Radiologic Technologists.

Ms. Garofola was honored at a ceremony on June 18 at the ASRT Annual Governance and House of Delegates Meeting in Albuquerque, N.M.

The honorary Fellow category was established by ASRT in 1956 to recognize members who have made outstanding contributions to the profession and to ASRT. Fellows have volunteered in leadership positions at the national and local levels, written articles for publication, presented at professional meetings and helped advance the radiologic science profession.

Backed by a radiologic science career that spans nearly 30 years, Ms. Garofola has participated in ASRT volunteer activities since she joined the association in 1986. In addition to serving terms as a delegate for the Radiation Therapy and Management Chapters, she has been a member of a number of ASRT communities including the Committee on R.T. Advocacy, Committee on Bylaws and Committee on Nominations. She also is a member of the Philadelphia Society of Radiologic Technologists and served as its president in 2001.

For more information about ASRT and the radiologic science profession, visit www.asrt.org.



Radiation Oncology Announcements and Appointments

New faculty:

Thomas Jefferson University welcomes two new, seasoned clinicians and researchers to its Department of Radiation Oncology: Nicole Simone, M.D., from the National Institutes of Health’s National Cancer Institute (NCI) and Bo Lu, M.D., Ph.D, from Vanderbilt University.

Nicole Simone, M.D.

Dr. Simone is a board-certified Radiation Oncologist who has treated mostly patients with breast and head and neck cancers, while her research involves radiation’s effect on microRNAs in breast cancer and caloric restriction and radiation therapy—and the ability of both to delay breast cancer tumor growth.

“Dr. Simone is rapidly being recognized as one of the rising stars in the field,” said Adam Dicker, M.D, Ph.D, Professor and Chairman of the Department of Radiation Oncology. “Her research cuts across a number of cutting edge fields, including breast and prostate cancer biology, metabolism, microRNAs and computational biology.  The connection between diet and cancer treatment is very relevant for patients.”

Bo Lu, M.D., Ph.D

Dr. Bo Lu is also a board-certified Radiation Oncologist who comes to Jefferson from Vanderbilt University in Nashville, Tenn., where he was an Ingram associate professor with tenure in the Department of Radiation Oncology and Cancer Biology of the University’s School of Medicine.  He was also an attending radiation oncologist at the Vanderbilt University Medical Center, member of the Ingram Cancer Center, and director of the Translational Research Program and Lung Cancer Research Program.

“I am delighted that Dr. Lu has joined our faculty,” said Dr. Dicker. “He is internationally renowned for his work in clinical and translational radiation oncology, and I have received numerous congratulatory calls and emails from Chairs of Departments of Radiation Oncology around the world recognizing his numerous achievements.”

Dr. Lu’s focus is on radiation-induced cell death in lung patients, among other basic science areas. His clinical interests include the integration of novel targeted agents in the treatment of lung cancer, radiosurgery for lung cancer, and reductionof toxicities from thoracic radiation. More recently, Dr. Lu has looked at cancer stem cells for enhancing radiotherapy in a setting of lung cancer.

Appointments:

Congratulations to Maria Werner-Wasik, M.D., professor in the department of radiation oncology, and radiation oncology residency program director, who was elected as the Radiation Therapy Oncology Group Vice-Chair for Publications. (www.rtog.org)

Maria Werner-Wasik, M.D.

Dr. Werner-Wasik is a member of the RTOG Lung Cancer Steering Committee.  She succeeds William Sause, M.D., of Intermountain Medical Center in Salt Lake City, Utah, who has served as the RTOG publications vice-chair since 1999.

Dr. Werner-Wasik will chair the RTOG Publications Committee which is responsible for the oversight ofpublication quality and timeliness of the results of the group’s trials.

Drs. Timothy Showalter and Robert Den have been selected as recipients of the American Brachytherapy Society sponsored High Dose Rate fellowship program (1 week) for 2011.




Dr. Eric Wickstrom Elected AAAS Fellow

Dr. Eric Wickstrom

Dr. Eric Wickstrom

Eric Wickstrom, Ph.D., of Jefferson Medical College, Kimmel Cancer Center, recognized for creating new methods to see cancer gene activity from outside the body

Exemplary work in genetic imaging and therapy have earned  Eric Wickstrom, Ph.D., a Professor of Biochemistry & Molecular Biology at Jefferson Medical College of Thomas Jefferson University and member of the Kimmel Cancer Center at Jefferson, recognition by his peers as a 2010 Fellow of the American Association for the Advancement of Science (AAAS).

AAAS is honoring Dr. Wickstrom for his “distinguished contributions to genetic imaging and genetic therapy by design and application of modified oligonucleotides.”

Dr. Wickstrom will be recognized, along with the other 502 members elected, at the AAAS Fellows Forum during the 2011 AAAS Annual Meeting in Washington, D.C. on February 19.  A tradition that began in 1874, AAAS names Fellows every year for their scientifically or socially distinguished efforts to advance science or its applications.

As part of the Jefferson Medical College and Kimmel Cancer Center, Dr. Wickstrom, along with his co-workers, create new methods to see cancer gene activity from outside the body, and to capture cancer cells flowing through the blood.

More specifically, his laboratory is developing cancer gene-specific oligonucleotides and siRNAs against cancer genes in the signal transduction pathway for use as diagnostics and therapeutics for cancers.

This year’s AAAS Fellows will also be announced in the AAAS “News & Notes” section of the journal Science on January 28, 2011.

AAAS Fellows elected in previous years include Charlene J. Williams, Ph.D., of the Department of Medicine at Jefferson Medical College of Thomas Jefferson University

Media Only Contact: Steve Graff
Thomas Jefferson University Hospital
Phone: (215) 955-6300



Reception to Celebrate Dr. Dicker’s Appointment as Chairman

A reception to celebrate Dr. Adam Dicker’s appointment as Chairman of Radiation Oncology was held in the Hamilton Building on Wednesday May 26, 2010. For more about Dr. Dicker’s appointment please go here

Dicker_Party

Reception Attendees