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.



Scott Waldman Awarded CURE Grant to Move Colon Cancer Test Closer to Commercialization

Scott Waldman, M.D., Ph.D.

Scott Waldman, M.D., Ph.D., Chair of the Department of Pharmacology and Experimental Therapeutics at Thomas Jefferson University, has been awarded a Commonwealth Universal Research Enhancement (CURE) grant for almost $750,000 to help advance a molecular diagnostic test for colon cancer into commercialization.

Such a test would better detect recurrence in a group of colon cancer patients whose metastases are hidden, and help reduce racial disparities, particularly in the African-American community, who are at higher risk of dying from metastatic disease.

The nonformula grant was awarded competitively from the Pennsylvania Department of Health. One of this year’s priorities for the Department’s Health Research Advisory Committee is Cancer Diagnostics or Therapeutics with Commercialization Potential.

About 25 percent of colon cancer patients who are deemed node-negative, or pN0, (meaning the cancer has not spread to the lymph nodes) after treatment end up recurring with metastatic disease.  Known as occult tumors, these hidden metastases often escape detection, be it imaging modalities or histopathology.

Today, no such test exists to distinguish these colon cancer patients, and as a result, they are often treated the same.

To better stratify this group, Dr. Waldman and colleagues have developed a diagnostic test that uses the hormone receptor guanylyl cyclase C (GCC) as a biomarker.

Previous research shows that a quantitative, molecular analysis of lymph nodes in patients deemed colorectal cancer-free was found to be an effective predictor of recurrence. Expression of GCC in the nodes, they found, is associated with an increased risk.

“This approach can improve prognostic risk stratification and chemotherapeutic allocation for these colon cancer patients,” said Dr. Waldman, a member of Jefferson’s Kimmel Cancer Center. “With this CURE grant, we can now move a much-needed technology closer to commercialization, meaning closer to patients.”

The test will ultimately determine who can benefit from adjuvant chemotherapy, which is designed to eradicate whatever occult disease is left after surgery and other treatments.

This test would benefit the African-American community, in particular. Beyond the general population risk, there is an established stage-specific difference in outcomes in pN0 African Americans, who are 40 percent more likely to die from the metastatic colon cancer than whites.

Stratifying these patients could ultimately reduce related racial disparities in mortality and survival.

The primary purpose of this nonformula grant is to support research activities that commercialize and bring to market new cancer diagnostics and therapeutics for which proof of concept has previously been demonstrated and has the capability to solve or diminish a specific problem related to the diagnosis or treatment of one or more malignant diseases.



You Can Help Save PA Research Funding

For more than a decade, Pennsylvania’s Commonwealth Universal Research Enhancement Program (CURE) has supported a broad range of biomedical research at 39 institutions across Pennsylvania. These funds have led to research advances in cancer, cardiovascular disease, diabetes, infectious diseases, and other health areas and improvements in public health.

In his budget for fiscal year 2013, Governor Corbett proposes defunding the CURE program created by Act 77 in 2001, diverting almost $60 million in research funds from the tobacco settlement into the general budget for other purposes.

If the defunding takes place, Jefferson stands to lose $2 to $4 million per year in research funding.

Left intact with sustained funding, the CURE program will advance promising medical discoveries, support the hiring and retention of skilled workers, leverage federal and private research funding, and catalyze the formation of biotechnology companies.

Please voice your support of the CURE program by taking a moment to send a note (see suggested letter HERE) to your PA State representative. You can find your representative on this website.

Jefferson’s Kimmel Cancer Center is a member of the Pennsylvania Cancer Alliance.



Kimmel Cancer Center Founding Directors Portrait Unveiled


Dr. Richard G. Pestell, Martha Mayer Erlebacher, Dr. Carlo M. Croce, Dr. Richard L. Davidson

A portrait of Dr. Carlo Croce, the founding Director of the Jefferson Kimmel Cancer Center, painted by Philadelphia artist Martha Erlebacher, was unveiled on Tuesday, April 10, 2012, at 4:00 PM in the Bluemle Life Sciences Building.

Martha Mayer Erlebacher has been recognized as one of the leading representational figurative and still-life artists in America who has shown her work nationally and internationally. A number of books and periodicals feature her work, much of which “examines the deep metaphorical and social themes of contemporary culture through her painterly and aesthetic images.”

Dr. Croce is world-renowned for his contributions involving the genes and genetic mechanisms implicated in the pathogenesis of human cancer. He is a member of the National Academy of Sciences and Institute of Medicine in the United States and the Accademia Nazionale delle Scienze detta deiXL in Italy. He has earned a plethora of awards in recognition of his hard work and dedication including two Outstanding Investigator awards from the National Cancer Institute and most recently, an Elected Membership to The American Academy of Arts and Sciences.

Dr. Joesph S. Gonnella and Dr. Carlo M. Croce

Dr. Croce is a principal investigator on eleven federal research grants and has more than 950 peer-reviewed, published research papers. A native of Milan, Italy, Dr. Croce earned his medical degree, summa cum laude, in 1969 from the School of Medicine, University of Rome. He began his career in the United States the following year as an associate scientist at the Wistar Institute of Biology and Anatomy in Philadelphia. In 1980, he was named Wistar Professor of Genetics at the University of Pennsylvania and Institute Professor and Associate Director of the Wistar Institute, titles he held until 1988. From 1988-91, he was Director of the Fels Institute for Cancer Research and Molecular Biology at Temple University School of Medicine in Philadelphia.

In 1991 Dr. Croce was named Director of the Kimmel Cancer Institute at Thomas Jefferson University.  While here, Dr. Croce discovered the role of microRNAs in cancer pathogenesis and progression, implicating a new class of genes in cancer causation.  After thirteen years as Director of the Kimmel Cancer Center, Dr. Croce moved to Ohio State University in 2004.  Under his direction at OSU, faculty within the Human Cancer Genetics Program conduct both clinical and basic research.  Basic research projects focus on how genes are activated and inactivated, how cell-growth signals are transmitted and regulated within cells, and how cells interact with the immune system. Clinical research focuses on discovering genes linked to cancer and mutations that predispose people to cancer.



Jefferson Graduate Student Receives Joanna M. Nicolay Melanoma Foundation ‘Research Scholar Award’

From left to right: Dr. Andrew Aplin of Jefferson's Department of Cancer Biology, JMNMF's Denise Safko, Awardee Kevin Basile, JMNMF President Greg Safko, and Dr. Richard Pestell, Director of the KCC

Kevin Basile, a Thomas Jefferson University graduate student in the Genetics Ph.D. Program, was one of nine students from leading cancer centers across the U.S. to receive a $10,000 “Research Scholar Award” from the Joanna M. Nicolay Melanoma Foundation (JMNMF) for his exceptional research work.

Two members of the board of directors for JMNMF, including Secretary Denise Safko and President Greg Safko, presented the award to Mr. Basile at the Kimmel Cancer Center’s Bluemle Life Sciences Building on March 26.

Mr. Basile was also accompanied by Dr. Richard Pestell, Director of the Kimmel Cancer Center, and Andrew Aplin, Ph.D., an Associate Professor in the Department of Cancer Biology.

The stop was part of a “road-show” of sorts for JMNMF committee and board members, who are traveling up the Northeast from Baltimore to Boston for RSA ceremonies.

Mr. Basile’s research focuses on resistance to RAF inhibitors in melanoma and methods to enhance the efficacy of those inhibitors.

The JMNMF is a nonprofit public charity founded in January 2004 to foster melanoma education, advocacy and research. In just eight years, the Foundation has grown dramatically to become an influential voice in the melanoma community and is now established as a national, and international, “voice for melanoma prevention, detection, care and cure.”

The nationally competitive grants increased dramatically by nearly 30 percent in 2012 (following a 40 percent funding increase in 2011) to significantly enhance the potential for advancements in the melanoma cancer field and encourage a larger number of students to choose melanoma research as their professional career path.

The 2012 RSA applicant pool and cancer research centers represented grew to include 42 of the country’s most promising young melanoma researchers, and 28 prominent National Cancer Institute (NCI)-Designated Cancer Centers or members of the Association of American Cancer Institutes (AACI).

This represents a dramatic 60 percent increase in students and 75 percent growth in research institutions participating, respectively. As first in the U.S. to fund graduate student melanoma researchers, the JMNMF program is celebrating the program’s sixth anniversary.

“Our Foundation’s ‘Research Scholar Awards’ are invaluable at the grassroots level, to specifically grow interest in melanoma research, at qualified cancer centers across the country,” said Robert E. Nicolay, JMNMF Chairman. “If we can attract the brightest minds that are considering, or are already within, the nation’s cancer research pipelines, to pursue a career in melanoma research – we’re that much closer to better understanding the disease, identifying the means for effective treatments and, most importantly, finding a cure for this deadly and very prevalent disease.”

For more information about JMNMF, please visit: http://www.melanomaresource.org/



Stronger Intestinal Barrier May Prevent Cancer in the Rest of the Body, New Study Suggests

Scott Waldman, M.D., Ph.D., chair of the Department of Pharmacology and Experimental Therapeutics at Jefferson and director of the Gastrointestinal Cancer Program at Jefferson’s Kimmel Cancer Center

A leaky gut may be the root of some cancers forming in the rest of the body, a new study published online Feb. 21 in PLoS ONE by Thomas Jefferson University researchers suggests.

It appears that the hormone receptor guanylyl cyclase C (GC-C)—a previously identified tumor suppressor that exists in the intestinal tract—plays a key role in strengthening the body’s intestinal barrier, which helps separate the gut world from the rest of the body, and possibly keeps cancer at bay. Without the receptor, that barrier weakens.

A team led by Scott Waldman, M.D., Ph.D., chair of the Department of Pharmacology and Experimental Therapeutics at Jefferson and director of the Gastrointestinal Cancer Program at Jefferson’s Kimmel Cancer Center, discovered in a pre-clinical study that silencing GC-C in mice compromised the integrity of the intestinal barrier.  It allowed inflammation to occur and cancer-causing agents to seep out into the body, damaging DNA and forming cancer outside the intestine, including in the liver, lung and lymph nodes.

Conversely, stimulating GC-C in intestines in mice strengthened the intestinal barrier opposing these pathological changes.

A weakened intestinal barrier has been linked to many diseases, like inflammatory bowel disease, asthma and food allergies, but this study provides fresh evidence that GC-C plays a role in the integrity of the intestine.  Strengthening it, the team says, could potentially protect people against inflammation and cancer in the rest of the body.

“If the intestinal barrier breaks down, it becomes a portal for stuff in the outside world to leak into the inside world,” said Dr. Waldman. “When these worlds collide, it can cause many diseases, like inflammation and cancer.”

The role of GC-C outside the gut has remained largely elusive. Dr. Waldman and his team have previously shown its role as a tumor suppressor and biomarker that reveals occult metastases in lymph nodes. They’ve used to it better predict cancer risk, and have even shown a possible correlation with obesity.

Reporting in the Journal of Clinical Investigation, Dr. Waldman colleagues found that silencing GC-C affected appetite in mice, disrupting satiation and inducing obesity. Conversely, mice who expressed the hormone receptor knew when to call it quits at mealtime.

However, its role in intestinal barrier integrity, inflammation, and cancer outside the intestine is new territory in the field.

A new drug containing GC-C is now on the verge of hitting the market, but its intended prescribed purpose is to treat constipation.

This study helps lays the groundwork, Dr. Waldman said, for future pre-clinical and clinical studies investigating GC-C’s abilities beyond those treatments in humans, including prevention and treatment of inflammatory bowel disease and cancer.

“We’ve shown that when you pull away GC-C in animals, you disrupt the intestinal barrier, putting them at risk for getting inflammatory bowel disease and cancer.  And when you treat them with hormones that activate GC-C it helps strengthen the integrity of the intestinal barrier,” Dr. Waldman said.  “Now, if you want to prevent inflammation or cancer in humans, then we need to start thinking about feeding people hormones that activate GC-C to tighten up the barrier.”



Jefferson’s Kimmel Cancer Center Establishes Center to Eliminate Cancer Disparities

Dr. Edith Mitchell, director of newly-established Center to Eliminate Cancer Disparities, and Robin Evans, a patient.

PHILADELPHIA—In an effort to reduce and eventually eliminate cancer disparities among adults in the Philadelphia region, the Kimmel Cancer Center at Jefferson has established the Center to Eliminate Cancer Disparities.

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, will serve as its Director.

Despite the decline in cancer incidence and mortality rates in the United States, disparities in cancer burdens continue to exist among certain population groups and the gap continues to widen.  The Philadelphia region in particular has a disproportionately high number of residents suffering from cancers, many of which are preventable and treatable.

Such disparities include differences in incidence, prevalence, mortality and burden of cancer and related adverse health conditions. Disparate population groups may be characterized by gender, age, race and ethnicity, income, social class, disability, geographic location or sexual orientation.

“I have dedicated my career to the treatment of cancer patients and have had the opportunity to experience, as a physician and as a researcher, the significance cancer disparities can have on the outcome of a patient’s treatment,” said Dr. Mitchell. “The first step in the elimination of these disparities is to raise awareness through public and professional education about what resources are available to groups in their fight against cancer.”

The Center aims to accomplish its mission through the facilitation of disparities-focused research, researcher and clinician education, training and teaching, and increased patient access to quality supportive services, such as palliative care, cancer screening and prevention, and survivorship programs.

Dr. Mitchell and her fellow clinicians and researchers at Jefferson are dedicated to the ongoing study of cancer and other health disparities among patients of diverse ethnic and socioeconomic backgrounds. They have created strategic priorities for eliminating such disparities through innovative research, education and training, advocacy, community outreach, and quality medical care.

The need for research into cancer, and other health care disparities, has become increasingly evident in recent years as doctors and scientists learn more about how slight variations in genetic makeup can have drastic effects on the way cancer invades an individual’s body.  Knowing that these disparities exist can improve how screening processes are established and help doctors understand which treatments will and will not be effective.

Dr. Mitchell has spent her medical career helping individuals in medically underserved areas to realize that simple changes in lifestyle can have a dramatic impact on cancer care. Through her work, Dr. Mitchell has demonstrated the importance of community service and outreach especially to those individuals who may not have the means to seek out more conventional medical advice.

She holds board certifications in both Internal Medicine and Medical Oncology and is a Fellow in the American College of Physicians. She has also served as the Program Leader in gastrointestinal oncology for more than 15 years and has a focused research effort in aggressive breast cancers.

“We want all researchers and clinicians to be aware of the disparities that exist in cancer diagnoses among diverse ethnic groups so that they can incorporate these important factors into their research efforts and clinical practice,” said Dr. Mitchell.

“The Center will also provide patients with contact information for cancer advocacy and support groups both locally and nationally that serve the needs of their demographic background. We are proud to host and sponsor several annual events where patients can come together to share their stories and plan for a future free of cancer disparities,” she said.



Jefferson appoints Administrator, Radiation Oncology

Thomas Jefferson University Hospital has selected Alex Khariton to become its Administrator for the Department of Radiation Oncology.

Previously, Mr. Khariton had been the Administrative Director for the Department of Radiation Oncology at Cooper University Hospital in Camden, N.J., for the past eight years.

“I”m looking forward to working for an  NCI-designated cancer center that provides excellent clinical car, partakes in innovative research, and has a well-respected medical school,” says Alex.

Alex is also Co-Chair of the Reimbursement and Economic committee for the SROA (Society of Radiation Oncology Administrators) and a member of  the American Society for Therapeutic Radiology and Oncology (ASTRO).

The new hire announcement was featured online in the Philadelphia Business Journal’s “People on the Move” section:

http://www.bizjournals.com/philadelphia/potmsearch/detail/submission/511141



Drugs targeting chromosomal instability may fight a particular breast cancer subtype

Richard Pestell, M.D., Ph.D, Director of the KCC

Another layer in breast cancer genetics has been peeled back.

A team of researchers at Jefferson’s Kimmel Cancer Center (KCC) led by Richard G. Pestell, M.D., PhD., FACP, Director of the KCC and Chair of the Department of Cancer Biology, have shown in a study published online Feb. 6 in the Journal of Clinical Investigation that the oncogene cyclin D1 may promote a genetic breakdown known as chromosomal instability (CIN). CIN is a known, yet poorly understood culprit in tumor progression.

The researchers used various in vitro and in vivo model systems to show that elevated levels of cyclin D1 promotes CIN and correlate with CIN in the luminal B breast cancer subtype. Cyclin D1 protein is elevated in breast, prostate, lung and gastrointestinal malignancies.

The findings suggest that shifting towards drugs targeting CIN may improve outcomes for patients diagnosed with luminal B subtype. Luminal B breast cancer has high proliferation rates and is considered a high grade malignancy.

Estrogen or progesterone receptor positive and HER2 positive cancers indicate luminal B, and about 10 percent of patients are diagnosed with it every year, though many do not respond well to treatment. The identification of CIN in luminal B provides a new therapeutic opportunity for these patients.

“Cyclin D1 has a well defined role in cell proliferation through promoting DNA replication,” says Dr. Pestell. “My team was the first to discover that cyclin D1 also has alternate functions, which include regulating gene transcription at the level of DNA. We were interested in discovering the function of DNA associated cyclin D1.”

To help answer this, the researchers, including lead author Mathew C. Casimiro, Ph.D., of the Department of Cancer Biology at Thomas Jefferson University, first needed to directly access cyclin D1′s role in gene regulation.

They applied an analysis known as ChIP sequencing to study the protein’s interactions with genes that comprise the entire mouse genome, and found it occupied the regulatory region of genes governing chromosomal stability with high incidence.

They went on to show cyclin D1 promoted aneuploidy and chromosomal rearrangements typically found in cancers.

Faulty chromosomes—either too many or too few, or even ones that are the wrong shape or size—have been shown to be the crux of many cancers. However, a major question of cancer genetics is the mechanisms of CIN. What causes the breakdown in chromosomal stability?

As cyclin D1 expression is increased in the early phases of tumorigenesis, cyclin D1 may be an important inducer of CIN in tumors.

To analyze the association between CIN and cyclin D1 expression in the context of breast cancer, the team aligned an expression of a 70-gene set with the highest CIN score against over 2,000 breast cancer samples. They stratified the samples based on previously described subtypes and aligned them with cyclin D1 expression profiled across the dataset.

A significant correlation among CIN, cyclin D1 and the luminal B subtype was identified, and it was apparent that the relationship between these levels was subtype specific.

“Interestingly, previous studies have presented contradictory results,” Dr. Pestell says. “Many studies have suggested a positive correlation between cyclin D1 expression and outcomes, while others have shown reduced survival. Here, we’ve dug deep, using a genome-wide analysis, and found that overexpression of the protein appears to be directly associated with the genes involved in CIN and this correlates with the luminal B subtype.”

Drugs targeting chromosomal instability for cancer therapy have been explored, but a sub-stratification rationale for the luminal B subtype has not been established. The research presented in this study suggests such a target is worthy of further investigation.

“There is a big drive towards using targeting therapies for stratified breast cancers,” says Dr. Casimiro. “What we are thinking is that there are a growing number of drugs that target aneuploidy, like AICAR and 17-AAG, that may be used as an adjuvant therapy in patients with luminal B breast cancer.”



Marja Nevalainen Talks to ‘Cancer Discovery’ About Science Careers

In a Dec. 1 news article  published in the American Association for Cancer Research journal Cancer Discovery,  Marja Nevalainen, M.D., Ph.D., an associate professor of cancer biology, medical oncology, and urology, offers up her insight for a story focusing on the challenges and opportunities postdocs face in an increasingly tight job market.

KCC's Dr. Marja Nevalainen

“Typically, postdoctoral training is overseen by one mentor,” says Nevalainen, who also oversees junior faculty and graduate education at the KCC. Nevalainen suggests an advisory committee of 2 or 3

members for each postdoctoral trainee, especially if the postdoc is supported by an institutional training grant (T32).

In addition, “If you have a strong basic scientist as one mentor, input from a physician–scientist may facilitate thinking about research designs in the lab that have translational applications such as therapy and biomarker development.”

Read the full article here:

“Jobs Wanted: Cancer Research”



Richard Pestell Named AAAS Fellow

Richard Pestell, M.D., Ph.D., FACP, Director of the Kimmel Cancer Center at Jefferson (KCC), has been named a 2011 Fellow of the American Association for the Advancement of Science (AAAS).

As part of the Section on Medical Sciences, Dr. Pestell was elected as an AAAS Fellow for his distinguished contributions to cancer care as director of two National Cancer Institute cancer centers, including the KCC and Lombardi Cancer Center at the Georgetown University Medical Center, and research identifying new molecular targets (cyclins, acetylation) and light activated gene therapy.

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

Dr. Pestell is an internationally renowned expert in oncology and endocrinology, who also currently serves as Chairman of the Department of Cancer Biology, Associate Dean of Cancer Programs at Jefferson Medical College (JMC), and Vice President of Oncology Services at Thomas Jefferson University Hospital.

Election as a AAAS Fellow is an honor bestowed upon AAAS members by their peers.

Dr. Pestell, who was named Director of the KCC in November 2005, is a highly respected researcher and clinician whose current work is focused on developing new cancer therapies that specifically target tumors, and reduce the side effects that are associated with commonly used cancer treatments such as chemotherapy and radiation.

He has made significant contributions to our understanding of cell cycle regulation and the disturbances that can lead to the malignant transformation of cells. Dr. Pestell has particular expertise in hormonally-responsive tumors, such as those of the breast and prostate, and his work is directed toward the eventual discovery of novel therapies for these cancers.

This year 539 members have been awarded this honor by AAAS because of their scientifically or socially distinguished efforts to advance science or its applications. New Fellows will be presented with an official certificate and a gold and blue (representing science and engineering, respectively) rosette pin on Saturday, February 18 at the AAAS Fellows Forum during the 2012 AAAS Annual Meeting in Vancouver, B.C., Canada.

This year’s AAAS Fellows will be formally announced in the AAAS News & Notes section of the journal Science on Dec. 23.

Also, as part of the Section on Medical Sciences, Hideko Kaji, Ph.D., of the Department of Biochemistry and Molecular Biology of Thomas Jefferson University, was named a AAAS fellow for her distinguished contributions to biology by discovering specific tRNA binding to mRNA-ribosome complexes, N-terminal protein modification by arginine, and ribosome recycling, the last step of protein synthesis.

Fellows elected in previous years include Eric Wickstrom, Ph.D., a Professor of Biochemistry and Molecular Biology at JMC and member of the KCC, and Charlene J. Williams, Ph.D., of the Department of Medicine at JMC.



New “Achilles’ Heel” in Breast Cancer: Tumor Cell Mitochondria

Researchers at the Kimmel Cancer Center at Jefferson have identified cancer cell mitochondria as the unsuspecting powerhouse and “Achilles’ heel” of tumor growth, opening up the door for new therapeutic targets in breast cancer and other tumor types.

Reporting in the online Dec.1 issue of Cell Cycle, Michael P. Lisanti, M.D., Ph.D., Professor and Chair of Stem Cell Biology & Regenerative Medicine at Thomas Jefferson University, and colleagues provide the first in vivo evidence that breast cancer cells perform enhanced mitochondrial oxidative phosphorylation (OXPHOS) to produce high amounts of energy.

“We and others have now shown that cancer is a ‘parasitic disease’ that steals energy from the host—your body,” Dr. Lisanti said, “but this is the first time we’ve shown in human breast tissue that cancer cell mitochondria are calling the shots and could ultimately be manipulated in our favor.”

Mitochondria are the energy-producing power-plants in normal cells. However, cancer cells have amplified this energy-producing mechanism, with at least five times as much energy-producing capacity, compared with normal cells.  Simply put, mitochondria are the powerhouse of cancer cells and they fuel tumor growth and metastasis.

The research presented in the study further supports the idea that blocking this activity with a mitochondrial inhibitor—for instance, an off-patent generic drug used to treat diabetes known as Metformin—can reverse tumor growth and chemotherapy resistance. This new concept could radically change how we treat cancer patients, and stimulate new metabolic strategies for cancer prevention and therapy.

Investigating the Powerhouse

Whether cancer cells have functional mitochondria has been a hotly debated topic for the past 85 years. It was argued that cancer cells don’t use mitochondria, but instead use glycolysis exclusively; this is known as the Warburg Effect. But researchers at the Jefferson’s KCC have shown that this inefficient method of producing energy actually takes place in the surrounding host stromal cells, rather then in epithelial cancer cells.  This process then provides abundant mitochondrial fuel for cancer cells. They’ve coined this the “Reverse Warburg Effect,” the opposite or reverse of the existing paradigm.

To study mitochondria’s role directly, the researchers, including co-author and collaborator Federica Sotgia, Assistant Professor in the Department of Cancer Biology, looked at mitochondrial function using COX activity staining in human breast cancer samples. Previously, this simple stain was only applied to muscle tissue, a mitochondrial-rich tissue.

Researchers found that human breast cancer epithelial cells showed amplified levels of mitochondrial activity. In contrast, adjacent stromal tissues showed little or no mitochondrial oxidative capacity, consistent with the new paradigm.  These findings were further validated using a computer-based informatics approach with gene profiles from over 2,000 human breast cancer samples.

It is now clear that cancer cell mitochondria play a key role in “parasitic” energy transfer between normal fibroblasts and cancer cells, fueling tumor growth and metastasis.

“We have presented new evidence that cancer cell mitochondria are at the heart of tumor cell growth and metastasis,” Dr. Lisanti said. “Metabolically, the drug Metformin prevents cancer cells from using their mitochondria, induces glycolysis and lactate production, and shifts cancer cells toward the conventional ‘Warburg Effect’.  This effectively starves the cancer cells to death”.

Personalized Treatment

Although COX mitochondrial activity staining had never been applied to cancer tissues, it could now be used routinely to distinguish cancer cells from normal cells, and to establish negative margins during cancer surgery. And this is a very cost-effective test, since it has been used routinely for muscle-tissue for over 50 years, but not for cancer diagnosis.

What’s more, it appears that upregulation of mitochondrial activity is a common feature of human breast cancer cells, and is associated with both estrogen receptor positive (ER+) and negative (ER-) disease. Outcome analysis indicated that this mitochondrial gene signature is also associated with an increased risk of tumor cell metastasis, particularly in ER-negative (ER-) patients.

“Mitochondria are the ‘Achilles’ heel’ of tumor cells,” Dr. Lisanti said. “And we believe that targeting mitochondrial metabolism has broad implications for both cancer diagnostics and therapeutics, and could be exploited in the pursuit of personalized cancer medicine.”



KCC’s 3rd Annual Men’s Event

Another successful year! The Kimmel Cancer Center hosted its 3rd annual Men’s Event at the Prime Rib in Philadelphia on November 15.

About 150 people joined Richard Pestell, M.D., Ph.D., Director, Kimmel Cancer Center at Jefferson, Leonard Gomella, M.D., Chair, Department of Urology at Jefferson and 2011 Men’s Event Co-Chairs Edward Glickman, President of Pennsylvania Real Estate Investment Trust, and Joseph Weiss, Chairman, Electronic Ink, for an evening of cocktails, dinner, entertainment, auctions and friends.

The dinner and auction raised more than $100,000 to build awareness about prostate cancer and benefit research at Jefferson’s National Cancer Institute Designated Cancer Center.

At this year’s event, John W. Buehler, Jr., a prostate cancer survivor and KCC patient, received the “Symbol of Courage” award, and Kenny Boone was recognized for his support of prostate cancer research and awareness with a “Symbol of Caring” award.

Here’s a glimpse of the night.

Dr. Richard Pestell, director of the KCC

Men's Event auction raised over $100,000

Co-chair Joe Weiss

Eagles long snapper Jon Dorenbos emceed the event

Prostate cancer survivor John Buehler received the "Symbol of Courage" award

Drs. Adam Dicker and Neal Flomenberg

Jessica Soens, Guy Galcerno, Ellen Doubet, and Don Seitz






Kimmel Cancer Center Hosts Interurban Clinical Club

On Friday, October 28, the Kimmel Cancer Center at Jefferson hosted the 204th meeting of the Interurban Clinical Club at Jefferson Medical College of Thomas Jefferson University.

Drs. Michael Lisanti, Richard Pestell, Carrie Sims and Michael Root at the 204th meeting of the Interurban Clinical Club at the Union League of Philadelphia.

The Interurban Clinical Club is a prestigious club founded by Sir William Osler in 1905 for the purpose of exchanging ideas and fellowship among medical teachers in some of the leading Eastern medical schools.

Several prominent physicians and researchers from institutions in the Philadelphia region presented the latest in their cancer research and other disciplines.

Many KCC researchers spoke at the all-day event, including opening remarks by Richard Pestell, M.D., Ph.D., director of the KCC, Steven McMahon, Ph.D., Erik Knudsen, Ph.D., Michael Lisanti, M.D., Ph.D, and Michael Root, M.D., Ph.D.

That night, a black tie cocktail reception and dinner were held at the Union League of Philadelphia, with a special performance by “The Arrhythmia, a capella group made up of a dozen students in such fields as medicine, pharmacy, and doctoral studies at Jefferson Medical College.

This year, the Sir William Osler Young Investigator Award was given to Jordan Orange, M.D., Ph.D., an Associate Professor of Pediatrics at the University of Pennsylvania School of Medicine.

Dr. Mark Zeidel, the ICC President, also presented Dr. Alfred Knudson, of Fox Chase Cancer Center, with a gift as a “thank you” and in recognition of his extensive accomplishments in cancer research.

There are five to nine active members of the ICC  from each city, including Baltimore, Boston, New Haven, New York and Philadelphia. Existing members of the ICC from the Kimmel Cancer Center at Jefferson include Richard Pestell, M.D., Ph.D., Barry J. Goldstein, M.D., Scott Waldman, M.D., Ph.D, and Michael Lisanti, M.D., Ph.D.

See below for photographs from the event:

The Arrhythmias performing at the Union League of Philadelphia before the dinner and lecture

Dr. Wafik El-Deiry (ICC Secretary/Treasurer), Dr. Michael Levine, Dr. Jordan Orange, Dr. Steven Douglas, Dr. Richard Pestell. Dr. Orange is being presented with the 2011 Sir William Osler Young Investigator Award

Dr. Rochelle Hirschhorn and Dr. Kurt Hirschhorn at the Union League of Philadelphia

Dr. Pestell, Dr. Mark Zeidel (ICC President), and special guest speaker Dr. Alfred Knudson. Dr. Zeidel was presenting Dr. Knudson with a gift as a thank you and in recognition of his extensive accomplishments in cancer research




Gordon Schwartz, M.D., Nominated to National Accreditation Program for Breast Centers Board

Gordon F. Schwartz, MD, MBA, FACS, director of the Jefferson Breast Care Center

Gordon F. Schwartz, MD, MBA, FACS, director of the Jefferson Breast Care Center, will represent the American Society of Breast Disease on the board of the National Accreditation Program for Breast Centers (NAPBC).

The NAPBC is a consortium of national, professional organizations dedicated to the improvement of the quality of care and the monitoring of outcomes for patients with diseases of the breast.

Dr. Schwartz attended his first meeting as a member of the board in San Francisco the week of October 24 during the 2011 Clinical Congress of the American College of Surgeons.

Dr. Schwartz is an internationally renowned expert in breast diseases and a professor of surgery and medical oncology at Thomas Jefferson University Hospital.  His practice has been dedicated to treating breast diseases, both benign and malignant, for more than 30 years.

In 2009, Dr. Schwartz became director of the Jefferson Breast Care Center—one of the first Academic Medical Institutions receiving full accreditation by NAPBC.



Surgeons Cut Whipple Procedure Wound Infections in Half with New Measures

Harish Lavu, M.D., Department of Surgery

Thomas Jefferson University Hospital surgeons found that a carefully-selected surgical care check list of 12 measures reduced Whipple procedure wound infections by nearly 50 percent.

Smoking cessation at least two weeks prior to surgery, gown and glove change prior to skin closure, and using clippers over razors to shave the surgical area are some of the measures that helped reduced infection rates, according to the study published in the October 26 online issue of the Journal of Surgical Research.

In a retrospective study, Harish Lavu, M.D., assistant professor in the Department of Surgery at Thomas Jefferson University, and colleagues analyzed clinical data from 233 consecutive Whipple procedures—also known as a pancreaticoduodenectomy, an operation to treat benign and malignant diseases of the pancreas—from October 2005 to May 2008 on patients who underwent routine preoperative preparation (RPP). That preparation is less comprehensive than the 12 measure surgical care bundle. For instance, it uses a razor for hair removal and iodine skin preparation and does not include smoking cessation.

They compared those rates to 233 consecutive Whipple procedures performed from May 2008 to May 2010 following the implementation of the surgical care bundle.

The researchers found a 49 percent reduction in wound infections in the surgical care bundle group (7.7 percent) compared to the RPP group (15 percent). The difference was statistically significant.

“It is typically quite difficult to achieve a 50 percent reduction in an adverse outcome,” Dr. Lavu says. “We can make a significant impact on lowering wound infection in patients undergoing this surgery by using this set of guidelines.”

Wound infection rates for Whipple procedures are historically higher and more common than in other procedures. Infections can be painful and require reopening the incision, which can ultimately leave scarring. Also, if an infection is not identified quickly, it can spread and patients can become very ill.

Two standout measures, Dr. Lavu says, are the gown and glove change prior to skin closure and intraoperative wound edge protection, which separates edges of the incision from contact with visceral contents, instruments and gloves during the procedure. And, like past studies have shown, using chlorhexidine-alcohol for skin preparation, instead of iodine, helps lower the risk of wound infections.

“The preoperative and post operative briefings alone, which are now being instituted in many American hospitals, reduce complications simply by improving  communication among members of the health care team,” Dr. Lavu says.

“While some procedures at certain hospitals include a similar surgical bundle care, Jefferson’s is the first one, to the author’s knowledge, that has been implemented for pancreatic surgery.”

“Now it is the standard of care here, and we are trying to move the surgical care bundle as it applies to other kinds of surgery, even in other departments at Jefferson,” Dr. Lavu says.

The 12 measures that were implemented at Jefferson in 2008 include:

  • Absence of remote infection
  • Preoperative smoking cessation
  • Pre-admission chlorhexidine-alcohol skin preparation
  • Preoperative clipper hair removal
  • Preoperative chlorhexidine-alcohol skin preparation
  • Preoperative antibiotic administration
  • Intraoperative would edge protection
  • Intraoperative glycemic control
  • Intraoperative temperature control
  • Gown and glove change prior to skin closure
  • Deep venous thrombosis prophylaxis and beta-blocker administration
  • Pre and post-operative briefings



Jefferson-Eagles Breast Health Floor Dedication Event

Ribbon Cutting at Jefferson Breast Care Center for Eagles floor and donor wall: Dr. Richard Pestell, director of KCC, Caity Buck, breast cancer survivor, Eagles owner Christina Lurie, Eagles safety Kurt Coleman, and Tom Lewis, president & CEO of TJUH

On October 11, the Jefferson Breast Care Center unveiled the Jefferson-Philadelphia Eagles Breast Health floor with a ribbon-cutting ceremony.

The speakers were Jefferson President and CEO Tom Lewis, Director of the Kimmel Cancer Center at Jefferson Dr. Richard Pestell, Eagles owner Christina Lurie, Eagles safety Kurt Coleman and breast cancer survivor Caity Buck.

Earlier this year, renovations were completed on the 3rd floor of the Jefferson Breast Care Center, thanks to the $1.04 million raised through the Philadelphia Eagles’ “Tackling Breast Cancer” campaign. Because of the team, its fans and partners, Jefferson patients can now benefit from a true multidisciplinary clinical team in this newly renovated space.

The Center gives the patient a comprehensive experience where surgery, medical oncology, radiation oncology, radiology, pathology risk assessment/genetics, social work and a breast care navigator are all working together with the patient at the center of care.

Fox 29 and Comcast SportsNet covered the dedication event.



Kimmel Cancer Center at Jefferson Celebrates 20 Years of Patient Care and Cancer Discovery

October 2011 marks 20 years of exceptional cancer care and research at KCC

From October forward, the Kimmel Cancer Center at Jefferson (KCC), a National Cancer Institute-designated cancer center, is celebrating 20 years of service to the community and the groundbreaking cancer research from the scientists and physicians who’ve provided an invaluable contribution to medical science and healthcare.

“This is truly a milestone for the Kimmel Cancer Center—it’s two decades of caring and collaborating to beat cancer,” says Richard Pestell, M.D., Ph.D., director of the KCC and Chair of the Department of Cancer Biology at Thomas Jefferson University.

“With our multidisciplinary approach, KCC’s team of clinicians and researchers has continued to put their best feet forward to provide excellent, stand-out personalized care for cancer patients in the Philadelphia region and beyond and uncover new pathways to better prevent, diagnose and treat the disease,” he added.

Today, the KCC offers up an experienced team of medical and radiation oncologists, surgeons, pathologists, urologists, neurosurgeons, nurses and other specialists for patients as they fight against cancer. With the Jefferson Breast Care Center, the Bodine Center for Radiation Therapy, the Myrna Brind Center of Integrative Medicine, and Jefferson Pancreatic, Biliary Tract and Related Cancer Center, to name a few, patients have access to the best facilities, providers and technologies for cancer screening and treatment.

It was October 1991 when the Jefferson Cancer Institute opened, with the dedication of the Bluemle Life Science Building on the Thomas Jefferson University campus. Four years later, with the awarding of a Cancer Center Support Grant, the National Institutes of Health National Cancer Institute (NCI) officially recognized it as one of only 54 NCI-designated cancer centers in the U.S. at the time. The institute took its current name in 1996 when businessman and philanthropist Sidney Kimmel made a generous donation to the institute to expand its research activities.

The donation to Jefferson is not a “gift,” but “an investment for humanity,” Mr. Kimmel told the Philadelphia Inquirer in 1996. “I really believe we’re going to have a breakthrough” in cancer research.

Living up to his expectations, KCC cancer researchers have made significant contributions over the last two decades, including better care in prostate cancer (Leonard Gomella, M.D.); new targets and diagnostics for prostate and breast cancer (Hallgeir Rui, M.D., Ph.D., Dr. Pestell); discoveries in colon cancer (Scott Waldman, M.D., Ph.D); pioneering discoveries in cancer metabolism and stem cells (Michael Lisanti, M.D. Ph.D., Dr. Pestell); better bone marrow transplants (Neal Flomenberg, M.D.); more selective radiation treatment (Adam Dicker, M.D.); and new areas of the human genome to treat (Isidore Rigoutsos, Ph.D., and  Paolo M. Fortina, M.D., Ph.D.).

Dr. Pestell, who became director in 2005, has made significant contributions to understanding cell cycle regulation and the aberrations that can lead to cells turning cancerous. His work identified new molecular markers, and new targets for cancer treatment. An internationally renowned expert in oncology and endocrinology, Dr. Pestell’s record of research funding is outstanding, securing substantial National Institutes of Health grants for the KCC.

Today, KCC’s well-funded basic science programs include cell biology, immunology and structural biology, developmental therapeutics, melanoma, leukemia/lymphoma, prostate and breast cancers, and gastrointestinal and genitourinary cancers. KCC also conducts numerous cancer clinical trials each year aimed at prevention and treatment of cancer.

Two recent clinical trials have resulted in the addition of new procedures at Thomas Jefferson University Hospital.  For example, in the Department of Urology, under chairman Leonard Gomella, M.D, a bladder cancer diagnostic tool using an imaging agent and blue light technology is now helping physicians better detect tumors along the bladder lining. Also, a new, two-step approach to half-match bone marrow transplants (where a patient can use a sibling or parent as a donor) developed by Chair of Medical Oncology Neal Flomenberg, M.D., is proving to be a success for blood cancer patients whose options were otherwise limited.  Jefferson is the only hospital in the region performing half-match procedures.

Since being appointed as chair of the Department of Radiation Oncology in 2010, Adam Dicker, M.D., Ph.D., has led extensive clinic renovations and the ongoing addition of new technologies. That includes Bodine’s recently acquired radiation therapy equipment for head and neck and prostate cancer patients and an upcoming radiosurgey instrument designed to deliver higher doses of radiation to smaller areas. Bodine’s state-of-the-art brachytherapy suite is also set to open in early 2012.

Last year, Charles J. Yeo, M.D., Chair of Surgery, performed his 1,000th Whipple procedure.  The Whipple procedure is a major surgical operation involving removal of portions of the pancreas, bile duct and duodenum, and is typically performed to treat malignant tumors involving the pancreas, common bile duct or duodenum.  Jefferson’s surgery department treats more pancreatic cases than anywhere in the region.

Thomas Jefferson University Hospital is consistently ranked in the top 50 best hospitals for treating cancer in America (#31 in 2011) in U.S. News and World Report. What’s more, the hospital has moved up more than 20 places in the past five years for cancer.



Dr. Michael Lisanti’s Cancer Research Featured in New Scientist

Michael Lisanti, M.D., Ph.D.

New cancer research suggests that we have misunderstood the feeding habits of cancer for decades, wrongly believing that cancer cells produce the bulk of their energy by breaking down glucose in the absence of oxygen, known as the Warburg effect.

Dr. Michael Lisanti of the Kimmel Cancer Center at Jefferson proposes that when a cell turns cancerous it begins to release hydrogen peroxide. The resulting free radicals cause oxidative damage that prompt support cells in the surrounding connective tissues, known as fibroblasts, to digest themselves.

In a New Scientist article, Dr. Lisanti explains, “It’s the Warburg effect, but in the wrong place. Cancer cells can feed off normal cells as a parasite.”

Dr. Lisanti and his team found that treating cancer cells with catalase, an enzyme that destroys hydrogen peroxide, triggered a five-fold increase in cancer cell death. The article also goes on to say that Dr. Lisanti is now gathering evidence to find out whether his ideas can be applied to many cancers or just a few.



New Half-Match Bone Marrow Transplant Procedure Featured in Philadelphia Inquirer

Neal Flomenberg, M.D., chair of the Department of Medical Oncology at Jefferson and Dolores Grosso, DNP, co-principal investigator of the study, have developed a way to make stem-cell transplants work, even when only half the immune markers are matched.

Featured in the “Check Up” section of The Philadelphia Inquirer, this research has major implications. Half-match transplants would triple the pool of suitable donors, giving new hope to patients with terminal leukemia, lymphoma, sickle-cell anemia and other blood diseases. “You could help almost everybody,” said Grosso.

Learn more by reading “Check Up: Innovation in stem-cell donation.”