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.



Kimmel Cancer Center to Host 4th Annual Men’s Event with Special Guest Jay Mohr

Jay Mohr

Jefferson’s Kimmel Cancer Center will host its 4th Annual Men’s Event at the Prime Rib in Philadelphia, with Special Guest Jay Mohr, comedian, actor, radio host, best-selling author and of Saturday Night Live and Jerry Maguire fame.

The event will take place on Thursday, November 15 from 5:30 p.m. to 9:00 p.m at the Prime Rib Restaurant.

It’s an evening of cocktails, dinner, entertainment, auctions and friends to benefit prostate cancer research and awareness at the KCC, a National Cancer Institute Designated Cancer Center.

Honorary Chairs:

Richard Pestell, M.D., Ph.D., Director, Kimmel Cancer Center at Jefferson

Leonard Gomella, M.D., Chair, Department of Urology at Thomas Jefferson University Hospital

Co-Chairs:

Edwin (Tucker) Boynton, KCC Advisory Board Member and Partner at Stradley Ronon Stevens & Young, LLP

Albert Pizzica, M.D., KCC Advisory Board Member, and Owner and CMO, AP Executive Management, LLC

Awards:

Barry E. Bressler, Esquire, Schnader Harrison Segal & Lewis LLP, prostate cancer survivor and Men’s Event Committee member of 4 years, will receive the “Spirit of Courage” award, presented to an individual who has demonstrated great personal courage, strength and dignity while battling cancer and supporting others in their fight against cancer.

The “Spirit of Caring” Award will be awarded to S. Grant Mulholland, M.D., of Jefferson, presented to an individual to recognize outstanding leadership in cancer research and the hope they hold for improving the quality of life in every community.

The “Spirit of Commitment Award” will be given to Men’s Event Co-Chairs, Edwin “Tucker” Boynton and Albert Pizzica, M.D., presented to an individual to recognize outstanding commitment to supporting the work of the Kimmel Cancer Center through personal and professional contributions dedicated to finding a cure.

For more information about event or tickets, please contact Mika Harding, Interim Executive Director of Development, 215.503.1195, Mika.Harding@KimmelCancerCenter.Org or visit http://www.kimmelcancercenter.org/news/mens-event/2012/



Doubling up on Advanced Prostate Cancer with PARP Inhibitors

A newly discovered function of PARP-1 could be the key to more effective therapeutics to treat advanced prostate cancer patients, a recent preclinical study published in Cancer Discovery by Jefferson’s Kimmel Cancer Center researchers suggests.

Karen E. Knudsen, Ph.D., Professor in the Departments of Cancer Biology, Urology, & Radiation Oncology

The team, led by Karen E. Knudsen, Ph.D., Professor in the Departments of Cancer Biology, Urology, & Radiation Oncology at Thomas Jefferson University, found that functions of PARP-1 not only include DNA damage repair but also androgen receptor (AR) regulation in advanced prostate cancer growth and progression.  PARP inhibition in various models was found to suppress AR activity, which fuels prostate growth.

Researchers believe that the dual functions of PARP-1—as both a regulator of AR as well as critical for DNA damage repair—could be leveraged for therapeutic benefit.  PARP inhibitors could slow down advanced-stage prostate cancer and shrink tumors, the team surmises.

“We hope to capitalize on this previously unknown function in PARP-1 in prostate cancer,” said Dr. Knudsen. “Our data show that PARP-1 plays a major role in controlling AR function and that, when suppressed with inhibitors, enhanced anti-tumor effects of castration and delayed onset to castration resistance. “

“This is the basis to support a clinical trial investigating PARP-1 inhibitors in patients with advanced disease,” she added.

Today, PARP-1 is seen as a valuable target because of its involvement in DNA damage repair for cancer cells. The therapy has been successful when combined with DNA-damaging drugs because it heightens the apoptotic activity of these drugs. In other words, it helps halt tumor growth by stopping DNA repair in various cancers.

Prostate cancer is dependent on AR activity for growth and survival, and is largely resistant to standard chemotherapy. AR-directed therapies are the first-line intervention for patients with advanced disease; however, recurrent tumors arise when AR is reactivated, a common occurrence in the castrate-resistant stage of the disease.

Therefore, there is a dire need to develop means to suppress the AR function in these patients. With this new role defined, PARP inhibitors targeting both functions could sensitize prostate cancer cells to DNA damage, and potentially improve the efficacy of AR-directed therapies in these patients, the researchers suggest in the paper.

Almost 40 percent of men with prostate cancer progress into an advanced stage, termed castrate-resistant prostate cancer, where chemotherapy and other therapies have little to no effect.

Using various in vitro and in vivo model systems, the researchers found that PARP-1 activity is required for AR function and is increased in castrate-resistant prostate cancer.  Additionally, inhibiting PARP-1 suppressed proliferation of cultured, primary human tumor specimens in a state-of-the-art system.

“These findings introduce a paradigm shift with regard to PARP-1 in prostate cancer,” said Dr. Knudsen, “and provide the basis for new therapies that could help a whole population of cancer patients who have little options.”

Dr. Knudsen recently received a two-year Challenge Award worth $1 million from the Prostate Cancer Foundation (PCF) for her work with PARP-1 and prostate cancer, and attended PCF’s 10th annual fundraiser in Philadelphia.

The study from Dr. Knudsen’s laboratory was a result of an inter-institutional team effort, including the contributions of lead author and postdoctoral fellow Dr. Matthew Schiewer, of the Department of Cancer Biology at Thomas Jefferson University, as well as key collaborators: Dr. Felix Feng (University of Michigan), Drs. Wayne Tilley and Lisa Butler (University of Adelaide), Dr. Ganesh Raj (UT Southwestern), Dr. Peter McCue, Dr. Leonard Gomella, Dr. Adam Dicker, Dr. Jonathan Brody, and Dr. John Pascal of Thomas Jefferson University.

##

This work was supported by NIH grants (R01 CA099996-09, and R01 ES016675-11), the Commonwealth of Pennsylvania grant, a Prostate Cancer Foundation Creativity award, a Prostate Cancer Foundation Young Investigator Award grants from the National Health and Medical Research Council of Australia, a Cancer Council of South Australia Senior Research Fellowship, and Pre-doctoral Fellowships from the DOD.



KCC’s New Magazine “Milestones” is Now Available

Jefferson’s Kimmel Cancer Center announces its first issue of “Milestones,” an online magazine covering breakthrough research, faculty, clinical updates, events and all things KCC.

This issue’s cover story delves into the latest advances in cancer genomics and how researchers are transforming cancer treatment with focused genomics.

“The work of Dr. Paolo Fortina and the staff in the Cancer Genomics Shared Facility allow the cancer center to provide the highest quality genomic analysis using Next Generation Sequencing (NGS). The technology allows us to determine the molecular drivers of an individual patient’s tumor. With NGS, we will provide more specific therapy, targeting the molecular mechanisms driving an individual patient’s tumor. In this way, we will provide the most specific and least toxic therapies for all patients who come to our door,” writes Richard G. Pestll, M.D., Ph.D., Director of the KCC, in this issue’s “Director’s Perspective.”

Look for Q&A sections on researchers and clinical staff, the latest in melanoma and breast cancer research, the phase I clinical trial program, and past and future events, including November’s Men’s Event with comedian Jay Mohr.

To read the online version of the 2012 Fall/Winter “Milestones” magazine, please visit
http://www.kimmelcancercenter.org/about/Fall-Winter-2012-Milestones.pdf



Tissue around tumor holds key to fighting triple negative breast cancer

Renato V. Iozzo, M.D., Professor of Pathology, Anatomy and Cell Biology, at Thomas Jefferson University

A natural substance found in the surrounding tissue of a tumor may be a promising weapon to stop triple negative breast cancer from metastasizing.

A preclinical study published in PLOS ONE September 19 by Thomas Jefferson University researchers found that decorin, a well-studied protein known to help halt tumor growth, induces a series of tumor suppressor genes in the surrounding tissue of triple negative breast cancer tumors that help stop metastasis.

“These findings provide a new paradigm for decorin, with great implications for curbing tumor growth by inducing new tumor suppressor genes within the tumor microenvironment, and for the discovery of novel gene signatures that could eventually help clinical assessment and prognosis,” said senior author Renato V. Iozzo, M.D., Professor of Pathology, Anatomy and Cell Biology, at Thomas Jefferson University.

Triple negative breast cancer is the most deadly of breast cancers, with fast-growing tumors, that disproportionately affect younger and African-American women. Today, no such marker is applied in care of triple negative breast cancer, and as a result, patients are all treated the same.

“Originally, we thought that decorin was affecting the tumor, but, surprisingly, decorin affects the so-called tumor microenvironment, where malignant cells grow and invade, igniting genes to stop such growth,” said Dr. Iozzo, who is also a member of Jefferson’s Kimmel Cancer Center. “Absence of decorin in the microenvironment could explain metastasis in some patients, where higher levels of the protein may keep cancer from spreading.”

In the study, 357 genes were found to be induced by the increased presence of decorin, but more interestingly, the researchers discovered that three of these genes, which were previously unlinked to triple negative breast cancer, were tumor suppressor genes affecting the tumor microenvironment, including Bmp2K, Zc3hav1, and PEG3.

Decorin is a naturally occurring substance in the connective tissue where, among other roles, it helps regulate cell growth by interacting with growth factors and collagen. A decade ago, Dr. Iozzo and his team discovered that decorin, a cell protein, and specifically, a proteoglycan, is increased in the matrix surrounding tumor cells. They also discovered that decorin causes production of a protein, p21, which also can arrest cell growth. However, decorin’s role in breast cancer and the mechanism behind its anti-tumor properties remained elusive.

For this study, researchers aimed to investigate the impact of decorin in triple negative breast cancer tumors using human cell lines in mice, as well analyze gene expression activity in the tumor microenvironment.

Tumors treated with decorin were found to have a decreased volume of up to 50 percent after 23 days. Using a sophisticated microarray technique, the researchers then analyzed the mouse tumor microenvironment, finding increased expression of 357 genes, three of which are the tumor suppressor genes of interest.

These results demonstrate a novel role for decorin in reduction or prevention of tumor metastases that could eventually lead to improved therapeutics for metastatic breast cancer.

“Here, we have a molecule that can turn a tumor microenvironment from a bad neighborhood to a clean neighborhood by inducing genes in that neighborhood to stop growth and prevent the tumor from metastasizing,” said Dr. Iozzo.



Jefferson and the Eagles Team Up for Prostate Health and Cancer Awareness

Eagles player Jason Avant and Dr. Leonard Gomella, Chair of Urology at Jefferson

September is Prostate Cancer Awareness month, and Thomas Jefferson University Hospitals has again teamed up with the Philadelphia Eagles to educate fans and others about prostate health and to raise cancer awareness.

To help kick off the campaign, Jefferson will serve as the presenting partner at the Sunday, September 16 game versus the Baltimore Ravens, with Edouard Trabulsi, M.D., Director of Multidisciplinary Genitourinary Oncology Center of the Kimmel Cancer Center at Jefferson (KCC),  and David P. McQuaid, FACHE, President, Thomas Jefferson University Hospitals, Inc., receiving Eagles jerseys on the field before kickoff.

“The KCC and our Departments of Urology, Medical Oncology and Radiation Oncology are deeply honored and grateful to once again have the Eagles as our partners,” said Leonard Gomella, MD, chair of the Department of Urology at Thomas Jefferson University Hospitals and director of clinical affairs at the KCC. “Prostate cancer is the second leading cause of cancer death among men, and over 200,000 will be diagnosed this year alone.  That’s why it’s so important for men to take their prostate health seriously.”

Prostate cancer is the most common type of cancer among men, with one in six men being diagnosed in his lifetime, and most treatable if caught early.

“In the months ahead, Jefferson and the Eagles look forward to more victories on the field and in raising prostate cancer awareness,” Dr. Gomella said.

Eagles wide receiver Jason Avant is also joining forces with Jefferson to help spread prostate health awareness, participating in several community events and a public service announcement with Dr. Gomella on the importance of prostate health and screening.

For the 23rd consecutive year, Jefferson Hospitals will also offer free prostate health and cancer screenings on September 19 and 25 from 9 a.m. to 3 p.m. (registration required). Call 1-800-JEFF-NOW to make an appointment.



KCC Becomes Provisional ECOG Member

In August, The Eastern Cooperative Oncology Group (ECOG) voted to approve Jefferson’s Kimmel Cancer Center and Thomas Jefferson University Hospital as a Provisional Member.

ECOG is one of the largest clinical cancer research organizations in the United States, and conducts clinical trials in all types of adult cancers. It constitutes a large network of private and public medical institutions that work toward developing various protocols for effective cancer treatments.

It was established in 1955 as one of the first cooperative groups launched to perform multi-center cancer clinical trials.

Funded primarily by the National Cancer Institute (NCI), ECOG has evolved from a five member consortium of institutions on the East Coast to one of the largest clinical cancer research organizations in the U.S. with almost 6000 physicians, nurses, pharmacists, statisticians, and clinical research associates (CRAs) from the U.S., Canada, and South Africa.

Institutional members include universities, medical centers, Community Clinical Oncology Programs (CCOPs), and Cooperative Group Outreach Programs (CGOPs). These institutions work toward the common goal of controlling, effectively treating, and ultimately curing cancer. Research results are provided to the worldwide medical community through scientific publications and professional meetings.

Currently, ECOG has more than 90 active clinical trials in all types of adult malignancies. Annual accrual is 6,000 patients, with more than 20,000 patients in follow-up.

For more information, please visit http://www.ecog.org/



Dr. Karen Knudsen Led Group Receives Million Dollar Prostate Cancer Foundation Award

Karen Knudsen, Ph.D.

A group of investigators led by Dr. Karen Knudsen was awarded a 2-year challenge grant of one million dollars by the Prostate Cancer Foundation.  The details of this award (from the PCF web site) are:

2012 Movember-PCF Challenge Award

Lead Investigator:
Karen Knudsen, PhD
Thomas Jefferson University

Title
Interrogation of Aberrant DNA Repair in Sporadic Prostate Cancer

Co-investigators: Johann De Bono, MD, PhD, Royal Marsden Hospital; Felix Feng, MD, University of Michigan; Mark Rubin, MD, Weill Cornell Medical College.

What this means to patients: Understanding the extent and impact of alterations in DNA Damage Response pathways in prostate cancer patients will target specific DNA repair problems and allow effective Precision Medicine (tailored treatment regimens) based on molecular subtyping of patient DDR alterations matched to drug therapy.

Synopsis: DNA Damage Response (DDR) pathway alterations are changes in DNA repair mechanisms that promote genomic instability and have been associated with local and advanced prostate cancer. Dr. Knudsen and team will identify and comprehensively determine the frequency of abiraterone in DDR pathways at different stages of prostate cancer progression. They will determine the clinical relevance of these DNA repair defects in prostate cancer patients and their role in the development and progression of treatment-resistant prostate cancer. Previous studies showed that the DNA repair protein PARP1 is elevated in tumors of advanced prostate cancer patients. PARP1 is recruited to sites of androgen receptor function and is required for AR activity in both hormone-dependent and treatment refractory disease. PARP inhibition therefore has dual effects on cancerous cells; 1) impairs DNA repair in tumors and, 2) suppresses AR signaling—halting cancer progression. Dr. Knudsen and colleagues will evaluate effects of combination therapy with PARP inhibitors and next generation anti-androgens in treatment-resistant prostate cancer patients.



Dr. Onder Alpdogan and Dr. Jianqing Lin Granted ACS-IRG Awards

Congratulations to Dr. Onder Alpdogan and Dr. Jianqing Lin for each being selected recipients of an ACS-IRG award.

The American Cancer Society-Institutional Research Grants (ACS-IRG) are designed to provide seed money to support junior faculty members with an interest in cancer research. The ACS defines junior faculty as investigators at the rank of assistant professor or equivalent who are eligible to apply as a principal investigator for grant support from national agencies.

Jianqing Lin, M.D., assistant professor of medical oncology


Dr. Lin’s Research Overview
The current proposal is a continuation of the concept that digoxin is an inhibitor of HIF-1a that will subsequently slow the growth of prostate cancer progression. Since the drug has minimal toxicity, it would be an ideal therapy to explore in other disease states in prostate cancer. With the awareness of over-treatment and treatment related complications in men with low-risk localized prostate cancer patients are willing to be on active surveillance. This current proposal is to examine the effects of digoxin to delay or reverse prostate cancer progression, with significant effort on tissue acquisition and to understand the molecular pathway affected with the treatment of digoxin. This study will shed light on the effects of future HIF-1a inhibitors for the treatment of prostate cancer and the foundation for future NIH funding.

Dr. Alpdogan’s Research Overview

Onder Alpdogan, M.D., assistant professor of medical oncology

Use of haploidentical HSCT in the treatment of advanced/relapsed RCC is a novel idea and has never been studied in preclinical models. We believe that haploidentical transplant model is a better platform to develop immunotherapy to solid tumors specificall renal cell carcinoma. Immunological response would be faster than other transplant models because of MHC disparity. This innovative new approach might give us an opportunity to develop new treatment strategies for patients with resistant/relapsed RCC after exhausting standard therapy including cytokine (IL-2) and Tyrosine Kinase Inhibitors (TKIs). These studies will not only generate new information about clinically relevant treatment strategies, but also provide substantial new findings about stem cell biology and transplantation.



Voichita Bar-Ad, M.D., Named Residency Program Director in Jefferson’s Radiation Oncology Department

Voichita Bar-Ad, M.D., an associate professor in the Department of Radiation Oncology at Thomas Jefferson University Hospital

Voichita Bar-Ad, M.D., an associate professor in the Department of Radiation Oncology at Thomas Jefferson University Hospital and Jefferson’s Kimmel Cancer Center, has been named Residency Program Director.

Dr. Bar-Ad is a board-certified radiation oncologist who treats primarily head and neck and gastrointestinal cancer cases. Her research focuses on treatment-related side effects and toxicities, patient quality of life and symptom management. She has paid specific attention to radiation-induced oral mucositis for head and neck cancer patients treated with radiotherapy or concurrent chemoradiotherapy, using the intensity- modulated radiation therapy technique.

“I am devoted to my patients and immersed in my research projects, but teaching is my joy, my passion,” Dr. Bar-Ad said last fall when she was named an “Educator of the Year” by the Association of Residents in Radiation Oncology (ARRO).

“This new role as Program Director enables me to continue what I love to do, guiding and teaching residents,” said Dr. Bar-Ad. “I’m greatly honored, and feel fortunate to lead a program that trains the radiation oncologists of tomorrow to have excellent clinical and research skills.”

Radiation oncology residency at Jefferson is a four-year training program, with resident having already completed one year of post-graduate training in medicine, surgery, or a transitional program.

The residency in radiation oncology trains residents broadly in cancer management and emphasizes interdisciplinary care.  Faculty members provide instruction in all modes of radiation oncology:  megavoltage photon- and electron-beam therapy, interstitial and intracavitary radioactive-source implantations, stereotactic radiosurgery and radiotherapy, intensity modulated radiation therapy and the diagnostic and therapeutic uses of radioactive isotopes.

In addition to the residents unanimously selecting Dr. Bar Ad for the ARRO 2011 Teacher of the Year Award, they also selected her to receive the 2012 Department of Radiation Oncology’s “Teacher of the Year Award,” an honor bestowed every June by the residents to the one faculty member who has helped them the most in their educational experience.

Jefferson’s Residency Program became accredited in 1973, but has been in existence since 1960.  The first resident, Dr. Carl Mansfield, went on to become a Chair of the Department, a position he maintained until May 1995, when he went to the National Cancer Institute to serve as a director of the Radiation Research Program

“Thomas Jefferson University Hospital has created one of the nation’s most outstanding residency programs in radiation oncology, and it is with great honor to have such a distinguished physician, researcher and teacher help continue that tradition,” said Adam P. Dicker, M.D., Ph.D., Chair of the Department of Radiation Oncology. “A strong residency program is essential for the successes of an academic medical center, and I look forward to having Dr. Bar-Ad’s leadership bring significant benefits to our residents and patients.”



Nicole Simone, M.D., Receives ASTRO Research Award

Nicole L. Simone, M.D., Department of Radiation Oncology

The American Society for Radiation Oncology (ASTRO) has awarded five physicians with research grants to promote the continued advancement of radiation therapy.

One of this year’s recipient for the Junior Faculty Career Research Training Award is Nicole L. Simone, M.D., of the Department of Radiation Oncology at Thomas Jefferson University Hospital.

The Junior Faculty Award provides $100,000 annually for two years to help develop the careers of promising junior faculty by allowing them dedicated time to work on research relevant to radiation oncology and cancer treatment.

It is presented each year to board-eligible physicians or physicists in radiation oncology or radiobiologists who are within the first three years of their junior faculty appointment.

The Residents/Fellows in Radiation Oncology Research Seed Grant Award was established to support residents or fellows who are planning a career focused on basic science or clinical research to support a pilot project related to radiation therapy. The grants are awarded each year for a one-year project and are in the amount of $25,000 each.

Recipients were selected by ASTRO’s Research Evaluation Committee.

‘Providing these leaders of tomorrow with the necessary funding for their valuable research is essential for the radiation oncology field,” said Leonard L. Gunderson, MD, MS, FASTRO, chairman of the ASTRO Board of Directors, said in a release. “It is very rewarding to know that these grants are going to physicians whose research will make a lasting impact on our field.”

For more on the ASTRO awards, visit https://www.astro.org/News-and-Media/News-Releases/2012/ASTRO-awards-five-research-grants.aspx



Breast Cancer Patients Who Lack RB Gene Respond Better to Neoadjuvant Chemotherapy

Breast cancer patients whose tumors lacked the retinoblastoma tumor suppressor gene (RB) had an improved pathological response to neoadjuvant chemotherapy, researchers at Thomas Jefferson University Hospital and the Kimmel Cancer Center at Jefferson report in a retrospective study published in a recent online issue of Clinical Cancer Research.

Many breast cancer patients undergo neoadjuvant therapy to reduce the size or extent of the cancer before surgical intervention.   Complete response of the tumor to such treatment signifies an improved overall prognosis.  Today, no marker is applied to identify tumors which will respond to such treatment, and as a result, only a subset of patients exhibit benefit from it.

“We found that loss of RB was associated with better pathological response rates in breast cancer patients—at various stages and representing multiple molecular subtypes—who were administered neoadjuvant chemotherapy,” said Agnieszka Witkiewicz, M.D., Associate Professor of Pathology, Anatomy and Cell Biology at Thomas Jefferson University.

Erik Knudsen, Ph.D, Professor of Cancer Biology and the Hilary Koprowski Chair in Cancer Biology, was excited that discoveries from his life-long research on the RB-pathway were making their way into the clinic. “This represents a potential new biomarker that could be used to tailor treatment plans for women considering neoadjuvant therapy and is a testament to the importance of cancer research,” he said.

For the study, researchers, including Gordon Schwartz, M.D., Director of the Jefferson Breast Care Center and Adam Ertel, Ph.D., Bioinformatics Specialist, Department of Cancer Biology, performed a combination of gene expression profiling to identify those with RB loss and direct histological analysis in over 1,000 breast cancer patients who had undergone neoadjuvant therapy.   These patients represented distinct subtypes of breast cancer and were treated with multiple different therapeutic regimens.

RB loss was associated, the team found, with an improved response to all the neoadjuvant regimens investigated in the major subtypes of breast cancer.

“Together, these data indicate that the loss of RB, which occurs relatively frequently in locally advanced disease, could be a useful tool for defining patients who experience an improved response to neoadjuvant chemotherapy,” said Dr. Witkiewicz. “Based on these findings, we have initiated a prospective clinical trial at Jefferson, evaluating the association of RB and another marker, PTEN, with the response to neoadjuvant chemotherapy.”

The clinical trial is open to patients who have a diagnosis of triple negative breast cancer and are eligible for neoadjuvant chemotherapy. (clinicaltrials.gov/ct2/show/NCT01514565).



Thomas Jefferson University Hospital Ranked Among Best for Cancer by U.S. News & World Report

Thomas Jefferson University Hospital has again been ranked as one of the nation’s best hospitals for cancer care by the U.S. News & World Report, coming in at No. 20 in the 2012 Best Hospitals survey.

Last year, Jefferson ranked 31st in the nation for cancer.

In addition, the hospital was ranked number three in the state of Pennsylvania and number two in the Philadelphia metro area.

This year, the institution ranked among the best in the nation in 11 specialty areas, including cancer. What’s more, there was a dramatic improvement in nine of those 11 ranked specialties.

U.S. News & World Report this year named Thomas Jefferson University Hospital 7th in the nation in orthopedics, 12th in pulmonology, and 14th for rehabilitation medicine.  Jefferson was also nationally ranked in diabetes and endocrinology (25), ear nose and throat (16), gastroenterology (22), geriatrics (31), gynecology (40), nephrology (39), and urology (27).

The urology ranking is 21 places higher than last year.

“Jefferson University Hospital is again honored to be among the top hospitals across so many specialties.  This recognition is a reflection of our commitment to our patients and providing a standard of care that is among the very best in the nation and the region.  Our clinicians and staff work tirelessly to move us forward and provide the high-quality care the community has come to expect from Jefferson,” said David P. McQuaid, FACHE, President, Thomas Jefferson University Hospitals, Inc.

Since its establishment in 1825, this academic medical center has provided nationally recognized care intended to improve the health of all the communities it serves. Jefferson accomplishes its mission in partnership with Thomas Jefferson University and as a member of the Jefferson Health System.



ATP: From Bystander to Actor in Kinase Regulation

Tung O. Chan, Ph.D.

A new function of ATP—beyond its passive roles as an energy source and a phosphate donor for phosphorylation reactions—was unraveled by Jefferson researchers.

Their studies revealed a new model of kinase regulation, whereby ATP modulates an “on-off-switch” mechanism in Akt by inducing conformational changes in the Akt kinase domain.

The three members of the Akt protein kinase family play key roles in multiple cellular processes, including glucose metabolism, cell survival and proliferation, and cell migration. The Jefferson team’s data was reported in the Proceedings of the National Academy of Sciences (PNAS) and was the subject of a perspective in Science Signaling in their May issue, entitled “Uncaging Akt.”

Jefferson paper’s senior author Tung O. Chan, Ph.D., assistant professor at Jefferson’s Center for Translational Medicine and Ulrich Rodeck, M.D., Ph.D., professor at the Department of Dermatology and Cutaneous Biology, indicate that their work, together with a complimentary study by Genentech researchers, describes a new mechanism with high translational appeal.

Ulrich Rodeck, M.D., Ph.D.

A molecular switch that affects the activation state of specific Akt isoforms may be exploited to modulate Akt signal strength in malignant diseases, as well as in diabetes and diseases of the heart and the central nervous system.

The Jefferson studies were conducted by a team of investigators at the Center for Translational Medicine, Department of Medicine and Kimmel Cancer Center, in collaboration with colleagues in the Departments of Dermatology and Cutaneous Biology, Radiation Oncology, Molecular Biology and Biochemistry, and Pharmaceutical Sciences.



Dr. Karen Knudsen and Dr. Renato Iozzo receive Distinguished Mentor Awards.

On Monday, June 11, 2012, at the Annual Jefferson Postdoctoral Research Symposium, Dr. Karen Knudsen and Dr. Renato Iozzo were honored with The Distinguished Mentor Award. The Distinguished Mentor Award was established to recognize Jefferson faculty members that excel in the mentoring of postdoctoral fellows. The award also serves to highlight the importance of positive and effective mentoring of postdoctoral fellows. A good mentor not only teaches his/her mentees but serves as an advocate, advisor and positive role model during the period of direct training and most often, in the following years. It is our hope that the Distinguished Mentor will serve as a model for the entire university and help to enhance the culture of mentoring at Jefferson.