Jefferson Radiation Oncology Resident Looks to Improve Prostate Cancer Outcomes in Ghana

Kosj Yamoah, M.D., Ph.D.

A new study published in January in the journal BMC Cancer, led by Kosj Yamoah, M.D., Ph.D., a resident in the Department of Radiation Oncology at Thomas Jefferson University and Hospital, takes aim at the issue by investigating prostate cancer diagnoses and treatment delivery in black men living in the West African region, in order to devise research strategies to help improve health outcomes.

Overall, many men are diagnosed at a later stage, with more than half opting out of treatment, they found. The researchers point to stigmas about cancer as a root of the problem.

“Cancer could eclipse infectious diseases as an epidemic if more awareness and intervention doesn’t come about,” said Dr. Yamoah, who grew up in Ghana until age 20, when he came to the United States. “Cancer can be very hush-hush because of cultural and financial issues and social stigmas associated with the disease. We need to bring awareness and address the needs of the population and barriers to care.”

“Cancer is still perceived as a death sentence,” he added. “People are scared to go to their doctor to find out if they have it, let alone to follow through with treatment.”

In a retrospective analysis of 379 patients referred for treatment at the National Center for Radiotherapy and Nuclear Medicine at the Korle Bu Teaching Hospital (KBTH) from 2003 to 2009, the team found that 33 percent were diagnosed with metastatic disease and 70 percent had a prostate-specific antigen (PSA) score four times higher than men in the United States or Europe at time of diagnosis.

PSA screening rates in Ghana are low, the authors explain, and many men opt out of radiation therapy and other therapies after diagnosis. Out of the 251 patients eligible for radiation therapy, only 141 patients actually received external beam radiation therapy.

Among patients with at least two years of follow up after external beam radiation therapy, three- and five-year PSA-failure free survival was 73.8 percent and 65.1 percent respectively. In the U.S., those percentages are 90 percent and 85 percent, respectively.

Reasons recognized by KBTH clinicians for patients declining radiation therapy included: the prohibitive cost of treatment, fear of radiation, and a state of denial based on their perception of disease originating solely from spiritual causes rather than biologic processes.

The data, which to date provides the largest source of published information on outcomes for prostate cancer treatment in the West African region, is a call to action, according to the authors.

The research team plans to develop treatment regimens tailored to the needs of Ghanaian men, which may differ from guidelines currently utilized in the Unites States and Europe in order to better address the disease burden and improve mortality rates in Ghana. That could mean more frequent PSA screening.

“There is controversy in the United States with PSA testing, but in a country like Ghana, there may be a role for PSA screening, even infrequent screening, because of all the late stage cancers we are finding,” said Dr. Yamoah.

The team has established collaboration between two institutions with the hope of improving prostate cancer treatment and plan to start more clinical trials to develop novel, shorter course treatments for locally-advanced prostate cancer.

“Based on these results, our group has proposed a plan for future research aimed at identifying an appropriate role for PSA screening in this population, developing radiation therapy treatment schedules that better fulfill the needs of Ghanaian prostate cancer patients, and contributing to understanding genetic factors associated with prostate cancer risk and treatment response,” the authors write.

Sarah E. Hegarty, a statistical analyst in the Department Pharmacology & Experimental Therapeutics at Jefferson, and Terry Hyslop, Ph.D., also of the Department Pharmacology & Experimental Therapeutics at Jefferson, were also part of the study.



Phone and Mailed Interventions Significantly Increase Colorectal Cancer Screening Rates

Ronald Myers, Professor of Medical Oncology

A mailing or phone call to help patients get screened for colorectal cancer significantly increases their chances of actually getting tested, according to a study published in the January issue of Cancer Epidemiology, Biomarkers and Prevention by researchers at the Kimmel Cancer Center at Jefferson.

The research team, led by Ronald E. Myers, Ph.D., Professor and Director of Division of Population Science, Department of Medical Oncology at Thomas Jefferson University, performed a randomized, controlled trial of 945 people aged 50-79 to test the impact of a new, preference-based navigation intervention, as opposed to standard mailing or usual care, on screening rates.

A third of the patients received a “tailored” phone call to encourage them to perform their preferred screening test (colonoscopy vs. at-home blood stool test), plus a mailing of preferred information; another third were sent information on colonoscopy and a stool blood test kit; while the last third received no intervention.

Patients who received a phone call and/or mailing were almost three times as likely to undergo screening six months later compared to those who had no intervention. However, there was no significant difference between the phone and mailed interventions versus mailings only on screening rates.

While colorectal cancer screening rates are increasing in the United States, rates lag behind those for breast and cervical cancer screening. Screening and early detection of colon and rectal cancer holds tremendous promise for reducing the toll of colon and rectal cancer.

Colorectal cancer is the third leading cause of cancer death in this country with more than 140,000 new cases diagnosed each year. Late diagnoses will account for many of the colorectal cancer related deaths.

The study, which was conducted between 2007 and 2011, included 10 primary care practices affiliated with the Christiana Care Health System in Delaware that used a comment medical record system.

The research team searched for patients who had no prior diagnosis of colorectal neoplasia or inflammatory bowel diseases, had visited one of the participating practices within the previous two years, and were not compliant with American Cancer Society colorectal cancer screening guidelines.

For the study, 312 patients received a tailored intervention, where they were informed about both colonoscopy and blood stool tests and then were sent information on colonoscopy or the actual blood test performed, based on their preference. Another group, consisting of 316 patients, was mailed information about both colonoscopy and stool blood test performed.  The remaining 317 were sent no information or tests and did not receive any phone calls.

Overall screening adherence at six months was significantly higher in both invention groups compared to the control group, the researchers found. Thirty-eight percent of patients who received the tailored phone interventions and 33 percent of patients who received mailings completed screening tests. Only 12% of patients in the control group completed screening tests.

In terms of the intervention groups, the researchers found that preference-based navigation did not significantly boost overall adherence to a level that was significantly higher than that achieved by mail, but increased participant performance of their preferred screening test in comparison to the mailed intervention, especially colonoscopy use.

“The study showed that both strategies were superior to usual care, and that there is not a one-size fits all approach to screening,” said Dr. Myers. “The next step is to determine if an intervention strategy that maximizes screening test access, incorporates patient preference, and engages providers can achieve higher screening rates compared to just mailings.”



Radiation Oncology Services Expanding at Riddle Hospital

Jefferson Radiation Oncology at Riddle Memorial Hospital is pleased to announce that the expansion of Radiation Oncology services has begun.

In the next few months, the Department will begin installing a new True –Beam linear accelerator, Brachytherapy High Dose Rate machine and a CT scanner.

Construction is expected to be completed by December 2013.

The acquisition of this new technology at Riddle Hospital will allow Jefferson physicians to offer the latest cancer treatment techniques, while utilizing state-of-the-art equipment.

Riddle Hospital offers a wide variety of cancer services including support groups, free cancer screenings, diagnostic techniques, treatments and educational programs, to name a few.

For more information, visit http://www.kimmelcancercenter.org/jkccn/members/riddle-memorial-hospital.html



Karen Knudsen, Ph.D., Appointed Deputy Director of Basic Science at Thomas Jefferson University

Thomas Jefferson University and the Kimmel Cancer Center are pleased to announce that Karen E. Knudsen, Ph.D., has accepted the position as Deputy Director of Basic Science, and will hold the prestigious Hilary Koprowski Chair in the Department of Cancer Biology.

Dr. Knudsen received her Ph.D. from the University of California at San Diego in 1996, focusing on cell cycle checkpoint control.  Her postdoctoral studies with Dr. Webster K. Cavenee at the Ludwig Institute for Cancer Research cultivated a program centered on the mechanisms underlying hormone-dependent cell cycle control.

Dr. Knudsen was recruited to Thomas Jefferson University in 2007 (now a Professor in the Departments of Cancer Biology, Urology, & Radiation Oncology) after a successful career at the University of Cincinnati College of Medicine, where she was a tenured Associate Professor.  In addition to her duties as the Deputy Director, Dr. Knudsen also serves as Leader of the Kimmel Cancer Center Biology of Prostate Cancer Program, and Director of the Greater Philadelphia Prostate Cancer Working Group.

Dr. Knudsen’s research interests are dedicated to understanding the mechanisms by which hormone receptor and cell cycle deregulation lead to prostate cancer progression and therapeutic bypass.  The overall goal of Dr. Knudsen’s laboratory is to utilize this information for successful development of precision medicine, so as to improve therapeutic outcome and patient care through rational therapy delivery.  Her studies identifying tumor suppressor and hormone receptor alterations have uncovered new targets for treating advanced disease, and led to development of biomarker-driven clinical trials.

Dr. Knudsen serves on a multitude of national boards and committees, including those for the American Association for Cancer Research, the Endocrine Society, and the Prostate Cancer Foundation.  She has been a Senior Editor for Cancer Research since 2007, is an Associate Editor for Endocrine-Related Cancer, and sits on the editorial boards of Molecular Cancer Therapeutics, the American Journal of Pathology, Molecular Endocrinology, and Oncogene. Most recently, Dr. Knudsen was appointed Editor-in-Chief of Molecular Cancer Research by the American Association for Cancer Research.  Dr. Knudsen has received numerous awards for her research, including the Ronald Ross Award for Excellence in Hormone-dependent malignancies from the Pacific Rim Breast and Prostate Cancer Research Organization, and the Richard E. Weitzman Laureate Award from the Endocrine Society.



Bench to Bedside: How to Fast Track Targeted Cancer Drugs with Radiation into the Clinic

Researchers from the translational research program of the National Cancer Institute and the Radiation Therapy Oncology Therapy Group have developed new guidelines to help fast track the clinical development of targeted cancer drugs in combination with radiation therapy.

The suggested strategic guidelines, published in the Journal of the National Cancer Institute in a recent commentary with lead author Yaacov Richard Lawrence, MRCP, an adjunct Assistant Professor in the Department of Radiation Oncology at Thomas Jefferson University and Director of the Center for Translational Research in Radiation Oncology at Sheba Medical Center in Israel, offers specific steps in the preclinical and early phase clinical trial process to get well-studied and novel targeted agents into the clinic more quickly.

Over the last decade, molecular agents that target cellular survival and growth, like Erlotinib and Sunitinib, have been developed but alone have had modest effect on improved survival. Combining such targeted agents with radiation therapy, however, has the potential to improve cure rates and long-term overall survival.

“There’s a missed opportunity in today’s cancer care treatment,” says Dr. Lawrence. “There is very promising laboratory data out there, but the clinical development of these new drugs with radiation has been limited. Here, we have put together a road map to help overcome obstacles and speed the development of new pipeline drugs with radiation.”

Adding radiation therapy to existing chemotherapy agents to radiation therapy has improved survival, and the authors of the commentary, which includes Adam P. Dicker, Chair of the Department of Radiation Oncology at Jefferson, believe new targeted therapies can follow in the same path.

“We know we want to repeat that success with new biological drugs,” says Dr. Lawrence. “In order to do that, we need direction, which is sorely lacking. These guidelines explicitly explain how much evidence is needed to go forward from the lab into the clinic, and furthermore how to design the clinical trials in humans.”

The guidelines discuss key questions when investigating specific targeted agents and tumor types, designing new clinical trials, such as the ‘time-to-event continual reassessment method design’ for phase I trials, and randomized phase II “screening” trials, and the use of surrogate endpoints, such as pathological response.

It also discusses the role and purpose of preclinical studies in radiation oncology drug development and how to identify new, radiation response agents.

There are challenges to drug development with radiation, the authors explain. A major problem is the limited interest from the pharmaceutical industry in developing drugs with radiation, which is of special importance since the pharmaceutical industry fund a large amount of clinical cancer research. Furthermore, significant individual skills and institutional commitments are also required to ensure a successful program. The situation has been extenuated by the decrease in radiation biologists in recent years.

It is hoped that by providing a clear pathway, the guidelines will help the field overcome these barriers and create a focus and interest in drug development.
Some new approaches, the researchers say, include combining radiosensitizers with hypofractionated (high daily dose) radiation schedules and integrating immunomodulators with radiation therapy.

“We feel passionate that a a good way to push clinical care forward for cancer patients is by combining these two types of treatment: advanced radiation treatment together with the new generation of anticancer drugs,” says Dr. Lawrence. “We know where the future lies, and guidelines provide the path to bring us there.”

The full guidelines in the JNCI can be found here: http://jnci.oxfordjournals.org/content/early/2012/12/07/jnci.djs472.full



More Designated Time Equals More Published Research for Radiation Oncology Residents

What helps radiation oncologist residents publish more academic research?

Giving them more time to do it, physicians in the Department of Radiation Oncology at Thomas Jefferson University Hospital conclude in a study published recently in the Journal of American College of Radiology.

Based on results from a web-based survey completed by 97 radiation oncologists and current senior residents from academic medical centers across the country, the biggest factor contributing to more first-author publications for residents is the amount of designated research time given during residency.

Anecdotally, there seems to be much variability in the productivity of radiation oncology residents. Some publish numerous articles, whereas others produce less. However, what leads to this variability remains undefined.

It appears that previous individual accomplishments or values among residents—often thought of as critical factors—seem to play less of a role than time and structure of a program.

To determine the predictors, researchers from Jefferson and Drexel University College of Medicine, invited 232 radiation oncologists and senior residents to partake in the web-based survey.

The survey addressed demographic factors, previous academic accomplishments, and residency program structure. The end point—research productivity—was defined as the number of first-author papers produced or research grants awarded on the basis of work initiated during residency.

There was a 42 percent response rate, most of whom were women. The median number of publications produced on the basis of work during residency was three. The average amount of dedicated research time was six months. 16 percent had less than three months. The more time a resident had, the more papers they published.

The results imply that academic success is not simply the result of innate ability but rather the structural aspects of residency programs.

“Medical research by residents is an important part of training, contributes to the academic growth of the radiation oncology field, and ideally makes them better physicians,” said Robert B. Den, M.D., Assistant Professor of Radiation Oncology at Jefferson and author of the paper.  “The structure of a program highly influences resident research capability,” he added.

Other authors on the paper includes Jordan M. Gutovich of Drexel University, Maria Werner-Wasik, M.D., Associate Professor of Radiation Oncology at Jefferson, Adam P. Dicker, M.D., Ph.D., Chair of Radiation Oncology at Jefferson, and Yaacov Richard Lawrence, MRCP, an adjunct Assistant Professor in the Department of Radiation Oncology at Jefferson University and director of the Center for Translational Research in Radiation Oncology at Sheba Medical Center in Israel.

The full study can be found here: http://www.jacr.org/article/S1546-1440%2812%2900386-9/abstract



Game changing diagnostic & prognostic prostate cancer genetic tests revealed by KCC researchers

Richard Pestell, M.D., Ph.D.

Researchers at the Kimmel Cancer Center at Jefferson (KCC) have developed potentially game-changing diagnostic and prognostic genetic tests shown to better predict prostate cancer survival outcomes and distinguish clinically-relevant cancers.

The team, led by Richard G. Pestell, M.D., Ph.D., Director of the KCC and the Chair of the Department of Cancer Biology at Thomas Jefferson University, report their preclinical findings from a blinded, retrospective analysis of over 350 patients and mouse study in a recent issue of the journal of Cancer Research.

Using an oncogene-specific prostate cancer molecular signature, the researchers were able to separate out men who died of prostate cancer versus those who lived, and more specifically, identifying men who died on average after 30 months (recurrence free survival). The diagnostic test distinguished patients with clinically relevant prostate cancer from normal prostate in men with elevated prostate-specific antigen (PSA) levels.

The researchers worked with three oncogenes previously associated with poorer outcomes in prostate cancer: c-Myc , Ha-Ras, and v-Src.

The test, the researchers say, is superior to several previously published gene tests and to the Gleason scale, which is a rating given to prostate cancer based upon its microscopic appearance and currently used to help evaluate the prognosis of men with the disease.

Given the diversity of prostate cancer outcomes—some men live two years after diagnosis, others live for more than 20 more years— a new oncogene-specific signature like this could not only help better identify prostate cancer risk but also test targeted therapies—by way of a new prostate cancer cell line.

These studies describe the first isogenic prostate cancer cell lines that metastasize reliably in immune competent mice. Previous studies were in immune deficient mice.

“This oncogene signature shows further value over current biomarkers of prediction and outcomes,” said Dr. Pestell. “Such a signature and cell line may also enable the identification of targets for therapies to better treat prostate cancer, which takes the lives of over 27,000 men a year.”

In breast cancer, the identification of tumor subsets with various gene signatures has improved clinical care for patients because of targeted therapies.

The work here by the KCC aims to identify gene patterns and subsequent tests in prostate cancer that could serve similar purposes. But to help develop such therapies, model systems that closely resemble human disease are required. To date, there have been several limitations with currently available cell lines.

Although important transplantation experiments have been conducted using human prostate cancer cell lines in immune deficient animals, the immune system plays an important role in prostate cancer onset and progression making it imperative to develop prostate cancer cell lines that can be studied in immune competent animals.

Also, although the transgenic mouse has been an effective model to study the molecular basis of human cancers, the prostate cancer mouse models have long latency and often unpredictable metastasis.

Here, the researchers succeeded in overcoming these issues.

The oncogene-specific prostate cancer molecular signatures were recapitulated in human prostate cancer and validated in distinct populations of patients as a prognostic and diagnostic test.

What’s more, the researchers demonstrated how the isogenic prostate cancer cell lines metastasized in immune-competent mice.

“Identification of gene signatures in breast cancer has allowed for a deeper understanding of the disease, and this paper moves us steps closer to being able to follow a similar trajectory with prostate cancer. Today, such an understanding and a formidable testing ground for new therapies is lacking for this disease,” Dr. Pestell said. “With this new oncogene-specific prostate cancer molecular signature, we have a valuable prognostic and diagnostic resource that could help change the way we manage and treat prostate cancer.”

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Other researchers in the study include Xiaoming Ju, Adam Ertel, Mathew Casimiro, Zuoren Yu, Hui Meng, Peter A. McCue, Rhonda Walters, and Paolo Fortina.



KCC researchers discover new pathways that drive metastatic prostate cancer

Karen Knudsen, Ph.D.

Elevated levels of Cyclin D1b could function as a novel biomarker of lethal metastatic disease in prostate cancer patients, according to a pre-clinical study published ahead of print on December 21 in the Journal of Clinical Investigation by researchers at the Kimmel Cancer Center at Jefferson.

The group, headed by Karen E. Knudsen, Ph.D., Professor and Hilary Koprowski Chair, Departments of Cancer Biology, Urology, and Radiation Oncology at Thomas Jefferson University and Deputy Director for Basic Science at the KCC, found that Cyclin D1b, a variant of the cell cycle regulator Cyclin D1a, functions independently of the cell cycle to promote metastasis in both early and late stage prostate cancer.

Rather, Cyclin D1b, but not Cyclin D1a, regulates a large gene network, the researchers found, which was shown to cooperate with androgen receptor (AR) signaling to fuel metastatic progression in multiple models of prostate cancer.

Studies have shown that Cyclin D1b expression is elevated in early stages of prostate cancer (in up to 30% of primary disease), and researchers have now demonstrated that this occurs more frequently in late stage castration-resistant prostate cancer: up to 80%.

Cyclin D1b expression is also highly correlated with that of the pro-metastatic gene SNAI2 (Slug), which the group identified as regulated by cooperative signaling between Cyclin D1b and AR.

“Numerous clinical and pre-clinical studies have effectively demonstrated that AR signaling is critical for progression to metastatic disease, but our knowledge of AR targets which can induce metastatic phenotypes is limited,” said Dr. Knudsen. “Our data describe how cross talk between the cell cycle and AR can rewire the AR signaling axis to enhance the expression of genes which elicit metastasis in both early and castration resistant prostate cancer models.”

“We found that Cyclin D1b can directly promote AR dependent expression of the gene SNAI2 (Slug), which dramatically increased metastatic events to soft tissues in animal models,” she added.

Metastatic castration resistant prostate cancer represents the most lethal form of the disease, which arises when AR is reactivated despite continued hormone therapy.

Soft tissue metastasis to the liver and lung represents a particularly aggressive form of prostate cancer, whose presence predicts for decreased survival time in prostate cancer patients.

Currently, there is little knowledge as to how these metastatic events occur, and identification of pathways and biomarkers of this lethal event could greatly benefit prostate cancer patients.

Using various in vitro and in vivo models, researchers found that Slug enhances the ability of cells to colonize soft tissues, which resulted in a higher incidence of metastasis in the liver and lung.

Given the inability to manage AR signaling in metastatic castration resistant prostate cancer, Slug driven pathways could be leveraged to dramatically limit the incidence of soft tissue metastasis and improve patient morbidity and mortality, researchers believe.

“Identification of AR driven pathways which mediate metastatic progression represents a significant leap forward in our attempts to effectively manage prostate cancer progression,” said Dr. Knudsen. “Cyclin D1b and Slug can likely be used as biomarkers to identify patients with an increased risk of metastasis, and will eventually provide us with novel “druggable” targets downstream of AR and Slug which can be exploited to dramatically reduce the incidence of these lethal metastatic tumors.”

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This study was completed as a result of an inter-institutional team effort, including the contributions of the lead author and graduate student Michael A. Augello of the Department of Cancer Biology at Thomas Jefferson University, as well as key collaborators: Dr. Felix Feng (University of Michigan), Dr. Alessandro Fatatis (Drexel University), Dr. Tapio Visakorpi (University of Tampere), Dr. Donald McDonnell (Duke University), Dr. C. Burd (University of Ohio), Dr. D E. Frigo (University of Houston) and Dr. Ruth Birbe of Thomas Jefferson University.



Edith Mitchell Appointed to NCI’s Clinical Trials & Translational Research Advisory Committee

Edith P. Mitchell, M.D., FACP, a medical oncologist at Thomas Jefferson University Hospital and Clinical Professor of Medicine and Medical Oncology in the Department of Medical Oncology at Jefferson Medical College of Thomas Jefferson University, has been appointed to the National Cancer Institute’s Clinical Trials and Translational Research Advisory Committee.

Dr. Edith Mitchell

The committee makes recommendations on the NCI-supported national clinical trials enterprise to build a strong scientific infrastructure by bringing together a broadly developed and engaged coalition of stakeholders involved in the clinical trials process. This encompasses oversight of all trials both extramural and intramural.

The committee will also provide broad scientific and programmatic advice on the investment of tax payer dollars in clinical trials and supportive science. This will lead to enormous potential for more specific cancer treatment, coupled with the complexity of evaluating new, highly specific agents integrating knowledge, insights, and skills of multiple fields into a new kind of cross-disciplinary, scientifically-driven, cooperative research endeavor.

The Committee will consist of 25 members.

Congratulations to Dr. Mitchell on this appointment.



ACS-IRG Pilot Projects Awarded for 2012

The Kimmel Cancer Center at Jefferson hosted the Annual ACS-IRG Luncheon on November 11. The 2012 Pilot Project recipients are S. Onder Alpdogan, MD; Amy Leader, DrPh, MPH; and Jianqing Lin, MD; all of the Department of Medical Oncology; Scott Keith, PhD; from the department of Pharmacology & Experimental Therapeutics; Nicole Simone, MD; department of Radiation Oncology; and Christopher Snyder, PhD; department of Microbiology & Immunology. They briefly explained their research projects to Lynne Ayres, MBA, Director of Research Communications, and Larry Slagle, Distinguished Giving Director, of the East Central Division of the American Cancer Society. Ms. Ayres and Mr. Slagle explained the ACS mission and offered ways in which the Pilot Project recipients would be able to assist them in that mission.

Left to Right: Nicole Simone, Jianqing Lin, Marja Nevalainen, Larry Slagle, Lynne Ayres, Christopher Snyder, Amy Leader, and Scott Keith.




Kimmel Cancer Center “All Hands Meeting”

The Kimmel Cancer Center held it’s quarterly “All Hands” meeting on December 12, 2012. Dr. Richard Pestell, Director of the Kimmel Cancer Center, delivered his quarterly “State of the Cancer Center” address. Awards were presented in 3 categories. The Administration Award was presented to the KCC Post-Award Administration Group (Dina Liebowitz, Melissa McDaid Dyer, Melanie Elliott, Karen Gosik, Tracey Kajkowski, Kathy Wyszynski, Rick Yellis and Pam Bachman). The Nursing Award was presented to Bone Marrow Transplant Unit (Patricia Cornett Farley, Michael Sun, Ngoc Bao Ho, Minh Duc Tran, Brendan McGuire and Barbara Stanback). The Clinical Award was presented to Matthew Carabasi, MD. There were also special presentations about upcoming Consortium-wide Pilot/Special Project Funding opportunities. Dr. Richard Davidson discussed the American Cancer Society – Institutional Research Grant. Drs. Andrew Quong and Noreen Robertson discussed the KCC Pilot Project Program (funding provided by TJU and Drexel). Dr. Banu Onaral and Mr. Davood Tashayyod discussed the Wallace H. Coulter Foundation Translational Research Partnership Program.

Dr. Matthew Carabasi receives the Clinician Award from Drs. Neal Flomenberg and Richard Pestell

The Bone Marrow Transplant Unit receives the Nursing Award from Drs. Neal Flomenbger and Richard Pestell



Kimmel Cancer Center “All Hands Meeting”

The Kimmel Cancer Center held it’s quarterly “All Hands” meeting on September 12, 2012. Dr. Richard Pestell, Director of the Kimmel Cancer Center, delivered his quarterly “State of the Cancer Center” address. Awards were presented in 4 categories. The Administration Award was presented to Janene Palidora. The Nursing Award was presented to Cheryl Santosusso. The Clinical Award was presented to Vochita Bar Ad, MD. The Basic Science/”Discovery of the Year” Award was presented to George Prendergast, PhD. In addition to the KCC Awards, the “Distinguished Mentor” Award was presented to Karen Knudsen. PhD by the Jefferson College of Graduate Studies Office of Postdoctoral Affairs and the Jefferson Postdoctoral Association. Dr. Renato Iozzo also received the “Distinguished Mentor” award. See JCGS Page for more

Dr. Noreen Robertson receives the Administration Award from Drs. Richard Pestell and Richard Davidson

Ms. Janene Palindora receives Administration Award from Mr. Richard Haldeman

Ms. Cheryl Santosusso receives Nursing Award from Dr. Neal Flomenberg

Ms. Cheryl Santosusso receives Nursing Award from Dr. Neal Flomenberg

Dr. Vochita Bar Ad receives the Clinicican Award from Dr. Neal Floimenberg

Dr. George Prendergast receives Basic Science/"Discovery of the Year" Award from Dr. Richard Pestell

Dr. Karen Knudsen receives JCGS "Distinguished Mentor" Award from Dr. Lisa Kozlowski




Kimmel Cancer Center “All Hands Meeting”

The Kimmel Cancer Center held it’s quarterly “All Hands” meeting on June 19, 2012. Dr. Richard Pestell, Director of  the Kimmel Cancer Center, delivered his quarterly “State of the Cancer Center” address. Awards were presented in 3 categories. The Administration Award was presented to Rita Genovese, CPC, PCS. The Basic Science Award was presented to Adam Ertel, PhD. The Nursing Award was presented to Susan Krick, RN. The Clinical Award was presented to Edith Mitchell, MD.

Ms. Rita Genovese receives Administrative Award from Mr. Richard Haldeman

Ms. Susan Krick receives Nursing Award from Dr. Adam Dicker

Dr. Adam Ertel receives the Basic Science Award from Dr. Richard Davidson

Dr. Adam Ertel receives the Basic Science Award from Dr. Richard Davidson




Jefferon’s Kimmel Cancer Center Holds 4th Annual Men’s Event

Jefferson’s Kimmel Cancer Center hosted its 4th Annual Men’s Event to benefit prostate cancer research and awareness at the Prime Rib Restaurant on November 15.

Guests enjoyed cocktails, dinner, auctions, and entertainment from special guest Jay Mohr. The event grossed over $200,000.

Below are some photos of the night, award ceremony and stand up act by Jay Mohr.

Nataliia Pestell and Richard Pestell, Director of the Kimmel Cancer Center at Jefferson

Leonard Gomella, MD, Chair of the Department of Urology, Jay Mohr, and Tricia Gomella

Recipients of the “Spirit of Commitment Award” Edwin "Tucker" Boyton and Albert Pizzica and Richard Pestell (middle)

Andrew Quong, Albert Pizzica, Leonard Gomella, Tricia Gomella, Jay Mohr, Nataliia Pestell, Richard Pestell, Edwin "Tucker" Boynton, and Mika Harding

Recipient of the "Spirit of Caring" Award S. Grant Mulholland, M.D., and Albert Pizzica

Mark Hurwitz, Professor and Vice Chair for Quality, Safety, and Performance Excellence and Director of Thermal Oncology of the Department of Radiation Oncology and Jane Hurwitz

Anne and Matt Hamilton

Jay Mohr

President of Thomas Jefferson University Hospitals, David McQuaid and Richard Webster, Chief Operating Officer

Auction items

David McQuaid and Robert Den, M.D., Department of Radiation Oncology

Leonard Gomella

Recipient of "Spirit of Courage" Award Barry E. Bressler, Esquire, and Albert Pizzica

Jay Mohr



Karen E. Knudsen Named New Editor-in-chief of AACR Journal Molecular Cancer Research

Karen Knudsen, PhD

The American Association for Cancer Research is pleased to announce Karen E. Knudsen, Ph.D., professor and Hilary Koprowski chair in the departments of cancer biology, urology and radiation oncology at Thomas Jefferson University in Philadelphia, and deputy director for basic science of the NCI-designated Kimmel Cancer Center as the new editor-in-chief of Molecular Cancer Research, one of its seven major peer-reviewed journals.

“I am honored and excited for the opportunity to lead Molecular Cancer Research,” said Knudsen, who will serve as the journal’s editor-in-chief for five years. “I hope to establish the journal as the seat of outstanding basic research related to cancer.”

Knudsen will officially begin her term in January 2013.

Molecular Cancer Research is an online and print journal that publishes original, novel and well-designed studies on the molecular and cellular aspects of cancer biology. Papers selected for publication represent new information in basic research that has implications for cancer therapeutics in angiogenesis, metastasis or genomics. The first issue of the journal was published in November 2002.

“Dr. Knudsen brings a wealth of expertise to the position of editor-in-chief of Molecular Cancer Research,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “We are confident that her experience with the peer review process, coupled with her extensive knowledge of basic cancer research, will build on the journal’s success and impact in the field.”

Knudsen’s scientific accomplishments include the authorship of more than 80 peer-reviewed publications in cancer and biomedical science journals. In addition, she has authored numerous book chapters focusing on transcription and cell cycle regulation in hormone-dependent cancers. Knudsen’s research interest is predominantly prostate cancer and the molecular mechanisms that underlie tumor progression.

Throughout her career, Knudsen has been involved in both national and international scientific committees, and has held numerous leadership roles in scientific publishing, including Cancer Research. She recently received the Excellence in Mentoring Award from Thomas Jefferson University, the Richard E. Weitzman Laureate Award from the Endocrine Society and the Ron Ross Award from the Pacific Rim Breast and Prostate Cancer Foundation.

Knudsen received her doctorate from the University of California, San Diego in 1996. She trained as a postdoctoral fellow at the Ludwig Institute for Cancer Research with Webster K. Cavenee, Ph.D.

Knudsen served as assistant professor in the department of cell and cancer biology at the University of Cincinnati College of Medicine for five years and was promoted to associate professor with tenure in 2005. Two years later she joined Thomas Jefferson University as an associate professor in the departments of cancer biology and urology. In 2010, Knudsen was promoted to professor, and in addition to her duties as the deputy director of the Kimmel Cancer Center, she currently serves as the program leader for the Kimmel Cancer Center Program in Biology of Prostate Cancer.

Knudsen succeeds Michael B. Kastan, M.D., Ph.D., executive director of the Duke Cancer Institute, as editor-in-chief of the journal.



New Ocular Melanoma Research Grant in Honor of David Eschelman

David Eschelman, M.D.

The Community United for Research and Education of Ocular Melanoma, or CURE OM, recently announced a new research grant in honor of Dr. David Eschelman of Thomas Jefferson University’s Department of Radiology specifically for the study of ocular melanoma.

Uveal melanoma, also known as ocular melanoma (OM), is diagnosed in about 2,000 people a year in this country. Though rare, it is the most common eye cancer in adults.

CURE OM was created by the Melanoma Research Foundation (MRF).

At a time when there was a major shortage of a specific liver-directed treatment for people with OM, Dr. Eschelman went to bat for patients as a fierce advocate, CURE OM stated in a recent newsletter.

Dr. Eschelman collaborated with Guerbet USA, Congress and the FDA to find a permanent new source for this drug. As a result of his perseverance, a new source of the therapy was approved in a very short time.

Because of his dedication to bringing life-changing treatments to people with OM, Guerbet USA created the second CURE OM research grant in his honor to aid research and inspire others to continue important work.

While the grant was created in Dr. Eschelman’s name, CURE OM will be accepting research proposals and decide on the recipient of the research award based on a peer-reviewed process. More information about the grant will be posted on the CURE OM website soon.

“The MRF extends sincere appreciation to Dr. Eschelman for his work and dedication, and to Guerbet USA for its support of the OM community,” the newsletter stated.



Dr. Renato Iozzo appointed as Editor-In-Chief of Matrix Biology

Renato V. Iozzo, M.D., Ph.D.

Renato Iozzo, M.D., Ph.D.,  a Professor of Pathology, Anatomy and Cell Biology at Thomas Jefferson University, has recently been appointed as Editor-in-Chief of the journal Matrix Biology beginning January 2013.

This flagship journal is published by Elsevier and is affiliated with both the International Society for Matrix Biology and the American Society for Matrix Biology. Dr. Iozzo served as president of both societies between 2007 and 2010.  Dr. Iozzo’s  efforts follow those of Dr. Bjorn Olsen from Harvard Medical School.

Dr. Iozzo is als  a long-standing member of the graduate program in Cellular and Developmental Biology.  He is also Professor of Biochemistry and Molecular Biology and a member of Jefferson’s Kimmel Cancer Center since its foundation.

His research interest is focused on the biology of proteoglycans and their roles in cancer and angiogenesis. He has published over 280 peer-reviewed articles, numerous reviews and edited two books on proteoglycans. His work is one of the most cited in the Proteoglycan and Matrix Biology fields, with over 18,000 citations and an h-index of 76



NCI Awards ‘Provocative Questions’ Grant to Thomas Jefferson University Researcher Scott Waldman

Scott Waldman, M.D., Ph.D., chairman of the Department of Pharmacology and Experimental Therapeutics

Scott Waldman, M.D., Ph.D., chairman of the Department of Pharmacology and Experimental Therapeutics at Thomas Jefferson University, has been awarded one of the prestigious “Provocative Questions”  grants from the National Cancer Institute (NCI) , as part of the Institute’s ambitious program to tackle the “important but not obvious” questions in cancer to ensure no stone was left unturned  after decades of promising research.

Scientists have known for a long time that obesity contributes to cancer risk, but they don’t know why.

That’s one of the questions set forth by the NCI—24 in total—that Dr. Waldman will help answer with a four-year grant for almost $1.2 million. Out of 700 applicants, just 57 recipients from institutions nationwide were chosen.

For Dr. Waldman, the answers behind cancer and obesity may lie in a hormone receptor known as guanylyl cyclase C (GCC), found mostly in the intestinal tract.

GCC has been established as a suppressor of colorectal cancer tumors and a useful tool to better predict colon cancer risk and recurrence by Dr. Waldman and his team. Preclinical and clinical studies found that lower levels of GCC were associated with an increased risk for colorectal cancer. They also discovered administering GCC reversed that trend.

More recent studies have revealed GCC’s role in appetite. The researchers found that silencing GCC affected appetite in mice, disrupting satiation and inducing obesity. Conversely, mice who expressed the hormone receptor knew when to call it quits at mealtime.

Now, under the “Provocative Questions” program, Dr. Waldman will further explore the relationship between cancer and the hormones regulating GCC to get a deeper understanding of the mechanisms of the risk posed by obesity—and a possible therapeutic target to treat it.

This is a promising notion, given that one-third of the U.S. population is considered obese, and that obese people have a 50 percent increased risk of being diagnosed with colorectal cancer.

“We are proposing that obesity increases colorectal cancer risk by suppressing the expression of those hormones, and silencing GCC,” said Dr. Waldman, “which is an effect that can be reversed by dietary calorie restriction or oral GCC hormone replacement therapy.”

There is potential for immediate translation of results to help reduce colorectal cancer risk in obese patients, given that an oral GCC drug to treat constipation just received regulatory approval, added Dr. Waldman, who is a member of Jefferson’s Kimmel Cancer Center.

The Provocative Questions project emerged from discussion among a number of veteran cancer researchers that noticed there were many questions — some important but not very obvious, some that had been asked but abandoned in the past because there were no ways to study or address them, some sparked by new discoveries or novel technologies — that could stimulate the NCI’s research communities to use laboratory, clinical, and population sciences in especially effective and imaginative ways.

More than 50 grants, attempting to answer 20 of the 24 proposed questions, with $22 million are being funded this year from that set of applications.

This research is supported by the National Cancer Institute of the National Institutes of Health under award number R01CA170533-01.



The Kimmel Cancer Center Remembers the Late Sen. Arlen Specter

The Kimmel Cancer Center at Jefferson is remembering longtime proponent of cancer research Senator Arlen Specter, who passed away on Oct. 14 at the age of 82, after a battle with non-Hodgkin lymphoma.

On the Senate Appropriations Committee, Sen. Specter led the fight to increase funding for the National Institutes of Health from $12 to $30 billion to expand medical research to find cures for cancer and other maladies.  He also supported expanding health care for seniors and children and proposed legislation to cover the almost 50 million Americans who do not have health insurance.

“Despite his own battles with cancer, Sen. Specter fought tirelessly through much of his 30-year Senate career on behalf of biomedical research and the special needs of cancer patients and their families,” the Association of American Cancer Institutes (AACI)  said in a statement. The KCC is a member of the AACI, along with 5 other Pennsylvania institutions.

“Sen. Specter was a dedicated friend to the cancer research community and he will be remembered for his unwavering support of programs that ease the burden of cancer on all Americans,” added AACI President William S. Dalton, PhD, MD.

Sen. Specter’s fights did not go unnoticed at the KCC.

In 2009, Sen. Specter was honored at the Kimmel Cancer Center Inaugural Ball  with the “Spirit of Courage Award,” which is presented to an individual who has demonstrated great personal courage, strength and dignity while battling cancer and supporting others in their fight against cancer.

Also, on Monday, Elena Gitelson, M.D., assistant professor in the Department of Medical Oncology at Thomas Jefferson University, spoke to CBS3′s Pat Ciarrocchi to provide insight on both non-Hodgkin’s lymphoma and Hodgkin’s lymphoma, another cancer Sen. Specter battled in the mid- 2000′s. Dr Gitelson was not involved in the medical care of Sen. Specter.

“Lymphomas are a large spectrum of different diseases,” Dr. Gitelson told CBS. It’s a condition that begins when lymphocytes that normally fight infection in the body’s system go haywire, she said, noting that in some cases, the Hodgkin’s variety can transform into the non-Hodgkin’s type, with both requiring specific chemotherapies.

Alternatively, non-Hodgkin’s lymphoma may develop as a new disease.

“A very important factor is how strong your spirit is when you fight cancer,” said Dr. Gitelson. “And I have been admiring his.”



Stat5 Predicts Outcomes for Prostate Cancer Patients after Radical Prostatectomy

Marja Nevalainen, M.D., Ph.D., associate professor of Cancer Biology, Medical Oncology and Urology at Jefferson Medical College of Thomas Jefferson University and Jefferson’s Kimmel Cancer Center

Men who had high levels of the activated Stat5 protein in their prostate cancer after a radical prostatectomy were more likely to have a recurrence or die from the disease compared to men who had little to no presence of the growth protein, according to a recent study published in Human Pathology by Jefferson’s Kimmel Cancer Center researchers.

This suggests, Stat5, a protein that when activated signals cancer cells to grow and survive, could be an ideal biomarker to help guide patients and physicians for future treatment.

The research team, led by Marja Nevalainen, M.D., Ph.D., associate professor of Cancer Biology, Medical Oncology and Urology at Jefferson Medical College of Thomas Jefferson University and Jefferson’s Kimmel Cancer Center, examined prostate cancer biopsies and tumor tissues obtained from 562 men who underwent a radical prostatectomy, comparing Stat5 levels with outcome.

They also looked at prostate tumor tissue in 106 patients who were under a “watchful waiting” or active surveillance treatment plan and had no neoadjuvant therapy. Samples were taken at the time of diagnosis.

“In both cohorts, if the patient had increased Stat5 in their prostate cancer, that patient was more likely to experience prostate recurrence or die from his disease compared to patients who had very low levels of Stat5,” said Dr. Nevalainen.

More specifically, patients without detectable nuclear Stat5a/b expression had recurrence-free survival of 72 percent at eight years. In contrast, patients with high nuclear Stat5a/b score had a recurrence-free survival rate of 42 percent at eight years. This indicates an approximately 30 percent benefit in recurrence-free survival at eight years associated with negative status for nuclear Stat5a/b expression in prostate cancer.

For those on active surveillance, patients with low nuclear Stat5a/b scores had a lower probability of prostate cancer specific death. There was an approximate 50 percent benefit in prostate cancer specific survival at 10 years associated with a negative status for Stat5.

The findings support a series of past and ongoing studies investigating Stat5 and its predictive capabilities led by Dr. Nevalainen.

A study from 2005, published in the journal Clinical Cancer Research, showed similar findings to this current study. Activated Stat5 in prostate cancer predicted outcome; however, there were differences in the cohorts. The key limitation of the previous study was the heterogeneous cohort of the patients, who received different adjuvant therapies at the time / after radical prostatectomy.  In the present study, the patients received a single mode of surgical intervention with no neoadjuvant therapies.

In 2008, in a another study published in Clinical Cancer Research, researchers showed that they can effectively kill prostate cancer cells in both the laboratory and in experimental animal models by blocking Stat5. That provided a proof of principle that Stat5 is a therapeutic target protein for prostate cancer.

Next, the group will be investigating Stat5’s predictive response after radiation therapy.

“There is an urgent need for reliable biomarkers to identify prostate cancer patients whose cancer is most likely to recur after the initial therapy and progress to advanced disease,” said Dr. Nevalainen. “The data presented here supports the initiation of prospective studies to determine the clinical utility of Stat5 as a prognostic and predictive marker in prostate cancer.”

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number R01CA113580.

Several media outlets covered the study, including Urology Times and Prostate Cancer Foundation news section. Links to those article are below.

“Protein predicts post-RP cancer recurrence, death”

“Stat5 Predicts Early Disease Recurrence and Prostate Cancer Specific Deaths in Patients After Radical Prostatectomy”

The release was picked up by  Science Daily, Medical News Today, and Yahoo! News.