2011 Ladies of Port Richmond Breakfast Fundraiser

On Saturday, October 22nd, the Ladies of Port Richmond held a Breakfast Fundraiser to support breast canceer research at AppleBee’s located at Caster and Aramingo Avenue.  Thank you to all who participated and made donations to the Ladies of Port Richmond supporting their efforts to aid in the fight against breast cancer.



Ulrich Rodeck receives Ben Franklin-PCF Creativity Award

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

Ulrich Rodeck, M.D., Ph.D., a professor in the Department of Dermatology and Cutaneous Biology, at Jefferson Medical College, Thomas Jefferson University, received the Ben Franklin-Prostate Cancer Foundation Creativity award for his work in improving the therapeutic window of radiation therapy for prostate cancer.

Radiation therapy of locally advanced prostate cancer is associated with severe toxicity limits. Dr. Rodeck will test the hypothesis that modulators of inflammation will preferentially protect normal tissues, but not tumor tissues against radiation-associated toxicity. A series of novel radioprotective compounds have been selected to test this hypothesis in models of prostate cancer and in patients.

This radiobiology proposal will allow higher doses of external beam radiation to be administered, resulting in improved cancer control with reduced side effects to normal adjacent tissue.

Dr. Rodeck received the award on October 4 during the Prostate Cancer Foundation award ceremony and auction at the Union League.

Philadelphia Magazine also featured photos from the Prostate Cancer Foundation event on October 11.



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.



Eagles-Jefferson Prostate Cancer Awareness Campaign

From Left to Right: Eagles wide receiver Riley Cooper, Eagles safety Kurt Coleman, Dr. Leonard Gomella, Dr. Costas Lallas, Eagles alumni Bill Bergey and Eagles alumni Gary Cobb

The Philadelphia Eagles and Thomas Jefferson University Hospital are excited to announce they are teaming up in the 2011 season to promote Prostate Cancer Awareness.

The two organizations have worked together since 2006 on the Tackling Breast Cancer initiative, and are launching the new prostate cancer campaign at the Eagles home-opener this Sunday against the Giants, designed to raise awareness of the disease and urge men to get screened.

To kick off their partnership,  the Eagles and Jefferson held a VIP event at the Lincoln Financial Field’s West Club on September 22.

Eagles president Joe Banner and Dr. Leonard Gomella, the Bernard W. Godwin, Jr. Professor of Prostate Cancer and Chairman of the Department of Urology at Jefferson Medical College and Thomas Jefferson University Hospital, addressed the a group of invited Premium and Corporate Clients.

On display was Jefferson’s surgical robot, the daVinci Si Surgical System. Physicians use the technology to perform a minimally invasive prostatectomy (removal of part or all of the prostate gland). With the robot-assisted surgery, patients get smaller incisions, shorter hospital stays, and faster recoveries.

Dr. Gomella explains Jefferson’s new surgical robot, the daVinci Si Surgical System




Dr. Robert Den Featured in PCF Video

Radiation oncologist Robert B. Den, M.D., who recently joined Thomas Jefferson University Hospital as an attending physician, was featured in a Prostate Cancer Foundation video highlighting his prostate cancer research and clinical work, as well as the importance of providing support for young investigators.

Dr. Den is a clinical scientist who specializes in the treatment of prostate cancer, combining his laboratory research that investigates novel anticancer agents in combination with radiation and hormonal therapy for locally advanced and high risk prostate cancer.Dr.

Den was awarded the Ben Frankin – PCF Young Investigator Award in 2010. That work is examining the importance of the retinoblastoma tumor suppressor gene, RB, in the response of prostate cancer cells to radiation and hormonal therapy. The research begins to address the ability to personalize therapy based on RB status.

Watch the video by clicking on this link: Robert Den – YI Interview from PCF on Vimeo.




Article By Dr. Nitin Ohri in Uro Today

Nitin Ohri, M.D.

Radiation Oncology’s Nitin Ohri, M.D., wrote a piece in Uro Today for its “Beyond the Abstract” section for a paper published in the International Journal of Radiation Oncology, Biology and Physics titled “Physician beliefs and practices for adjuvant and salvage radiation therapy after prostatectomy.”

In the study, researchers surveyed United States prostate cancer specialists to assess post-prostatectomy radiotherapy practice patterns and the opinions on which they are based.

Significant discordance was identified. An online survey found that urologists were less likely to recommend radiation therapy immediately after a radical prostatectomy than radiation oncologists. Instead, those clinicians most likely opt to perform frequent PSA tests to monitor cancer, recommending salvage therapy if levels become elevated.

Read the entire article in Uro Today by Dr. Ohri here:

Post-prostatectomy Management of Patients with Adverse Pathologic Features: Why is there no Consensus?



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.



The Royal Australasian College of Physicians President, Professor John Kolbe Visits The KCC


Professor John Kolbe, MBBS, FRACP visited the Kimmel Cancer Center and Thomas Jefferson University on September 26, 2011.

John Kolbe is a graduate of the University of Queensland.  After working in Adelaide, he completed his clinical
training in Auckland and then undertook a research fellowship at Johns Hopkins Medical Institutions.  He is
currently a respiratory physician at Auckland City Hospital and Professor of Medicine and Head of the
Department of Medcine, Faculty of Medical and Health Sciences, University of Auckland.

He is a past‐President of the Thoracic Society of Australia and New Zealand.  Previous positions in the College
include Chair of Specialities Board, President of Adult Medicine Division and Chair of College Policy &
Advocacy Committee. He is currently President of The Royal Australasian College of Physicians.



Kimmel Cancer Center “All Hands Meeting”

The Kimmel Cancer Center held it’s quarterly “All Hands” meeting on September 15, 2011. Dr. Richard Pestell, Director of the Kimmel Cancer Center, delivered his quarterly “State of the Cancer Center” address.  Awards were presented in three categories. The Administration Award was presented to Andrea M. Kahn-Kothmann, ESQ. The Nursing Award was presented to Mary Ann McGinley, PhD, RN. The Clinical Award was presented to Takami Sato, MD.

Ms. Andrea M. Kahn-Kothmann receives Administration Award from Mr. Richard Haldeman

Dr. Mary Ann McGinley receives Nursing Award from Dr. Richard Pestell


Dr. Takami Sato recieves Clinical Award from Dr. Wm. Kevin Kelly with an assist from Dr. Michael Mastrangelo





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.”



Half-Match Bone Marrow Transplant Procedure Yields Promising Outcomes for Cancer Patients

Dolores Grosso, DNP, Co-Principal Investigator and lead author of the article

Half-matched bone marrow or stem cell transplants for blood cancer patients have typically been associated with disappointing clinical outcomes. However, a clinical trial conducted at the Kimmel Cancer Center at Jefferson testing its unique, two-step half-match procedure has produced some promising results: the probability of overall survival was 45 percent in all patients after three years and 75 percent in patients who were in remission at the time of the transplant.

Reporting in the journal Blood in a published-ahead-of-print article dated August 25, Neal Flomenberg, M.D., Chair of the Department of Medical Oncology at Thomas Jefferson University Hospital, Dolores Grosso, DNP, Co-Principal Investigator and lead author of the article, and colleagues discuss the results of 27 patients treated on this phase I/II trial who had diagnoses that included leukemia, lymphoma and myelodysplasia.

The patients received their transplant in two steps. First, after receiving radiation therapy to further treat their disease, the patients were given a specified dose of T cells (a type of immune cell that fights infection) from their half-matched family donor. The donors were parents, siblings or children of the patient. The patients next received the drug cyclophosphamide to help the newly infused donor T cells to be more tolerant to the patient’s body. The second step of the transplant occurred when the patients received a dose of their donors’ stem cells to help their blood counts return to normal and further strengthen their new immune system.

Dr. Flomenberg and his team found that after a follow-up of 28-56 months, overall survival for the patients after one year was 54 percent and 48 percent at three years. Patients in remission at the time of the transplant fared better with an overall survival of 75 percent. Seventeen of the 27 patients—with a median age of 52 years old—were alive six months after their transplant, which was the official end point of the trial.

While more recent studies have shown promising increases in overall survival for patients undergoing half-match transplants, historically, clinical outcomes for these types of transplants have been poor, which has limited the use of this type of procedure.

The results of the Jefferson trial represent a very promising improvement in this area.

Bone marrow or stem cell transplants are performed in order to replace a patient’s diseased immune system with that of a healthy donor. Traditionally, the use of a genetically fully matched donor has been associated with the best results in bone marrow transplant, but many patients lack a fully-matched related or unrelated donor. Almost every patient will have a half-matched donor (also known as a haploidentical donor) in their family, however.

The successful use of haploidentical donors would greatly expand the number of donors available to a patient, extending this therapy to almost everyone who would benefit from receiving a transplant.  This would include minority patients, including patients with sickle cell anemia, who do not have as many fully-matched unrelated donors available to them.

“Our half-match bone marrow transplant results open up many doors for different types of patients who can’t find an exact match,” said Dr. Flomenberg. “It also justifies recommending that patients at high risk for relapse should consider having a half-match transplant early in the treatment of their disease.”

“Jefferson’s two-step procedure provides promising results that could serve as the basis for further exploration and optimization of the technique,” he added.

Jefferson medical oncologists’ approach is unique in that the dosage, timing and treatment of donor T cells was carefully controlled and optimized. No other transplant regimen controls the exact amount of donor T cells given.  The investigators believe that dosing the T cells in this way helped avoid many of the life-threatening side effects of this type of transplant.

“We believe the dosage and timing of T cells from the donor into the patient is essential for success. In fact, it’s equally as important as prescribing specific doses of radiation and chemotherapy to initially treat the disease,” said Dr. Grosso. “The goal of this two-step regimen was to develop a better technique for half-matched patients with relapsed blood cancers initially, but we also showed that it can be appropriate for high risk patients earlier in their disease who lacked fully matched donor options.”



Edith Mitchell Talks to WHYY Radio about African American Doctors in Medicine

Edith Mitchell, M.D., associate director of Diversity Services for the Kimmel Cancer Center

Jefferson medical oncologist Edith Mitchell, M.D., FACP, works on diversity efforts as associate director of Diversity Services for the Kimmel Cancer Center at Jefferson.

In a recent WHYY Radio interview, Dr. Mitchell shares some of her experiences with African American patients and gives her perspective on race and medicine today. She believes that listening to patients is crucial and says that patients are more likely to follow doctor’s orders and stick with a care plan when they’re comfortable with their physician.

See the full “In the Gap: African American Doctors” article.



Robert B. Den, M.D., Joins the Department of Radiation Oncology at Jefferson

Robert M. Den, M.D., Department of Radiation Oncology

Radiation oncologist Robert B. Den, M.D., recently joined Thomas Jefferson University Hospital as an attending physician, and was also named an assistant professor at Jefferson Medical College of Thomas Jefferson University in the Department of Radiation Oncology.

Dr. Den is a clinical scientist who specializes in the treatment of prostate cancer, combining his laboratory research that investigates novel anticancer agents in combination with radiation and hormonal therapy for locally advanced and high risk prostate cancer.

A graduate of Yale University with a B.S. in chemistry, Dr. Den received his medical degree from Harvard University in 2006. Dr. Den’s postgraduate training began at Massachusetts General Hospital in Boston as an intern of medicine before becoming a resident in radiation oncology at Thomas Jefferson University Hospital from 2007 to 2010, and ultimately serving as chief resident (2010-2011).

Dr. Den will serve as a radiation oncologist in the Bodine Center for Radiation Therapy at the Kimmel Cancer Center at Jefferson.

“I’m looking forward to continuing my prostate cancer research with my colleagues here at Jefferson, including the department’s chair, Dr. Adam Dicker, and Dr. Karen Knudsen,” said Dr. Den. “What’s equally important is taking that research to bedside so patients may benefit.”

“Our goal is to personalize the care for each man with prostate cancer, to effectively eradicate the disease,” he added.

Dr. Den is the 2010 recipient of the prestigious Prostate Cancer Foundation Ben Franklin Young Investigator Award. That work is examining the importance of the retinoblastoma tumor suppressor gene, RB, in the response of prostate cancer cells to radiation and hormonal therapy. The research begins to address the ability to personalize therapy based on RB status.

Expanding on that research, Dr. Den is also the principal investigator for a Department of Defense Physician Research Training Award to study whether RB can be used to determine which therapeutic modalities should be administered to patients with locally advanced prostate cancer.  He is also working towards opening a clinical trial to study preoperative radiation for high risk prostate cancer patients.

Dr. Den is member of several professional societies including the American Society for Therapeutic Radiology and Oncology and the American Society of Clinical Oncology, and has co-authored over 25 scientific papers, abstracts and book chapters.



A Tumor Suppressor May Also Fight Obesity

The hormone receptor guanylyl cyclase C (GCC) has been established as a suppressor of colorectal cancer tumors, but new evidence from Thomas Jefferson University suggests it may also help fight one of the country’s biggest pandemics: obesity.

Reporting in the August 25 online issue of the Journal of Clinical Investigation, Scott Waldman, M.D., Ph.D., chairman of the Department of Pharmacology and Experimental Therapeutics at Jefferson, and colleagues 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.

Revealing a never-before-shown endocrine axis between the intestine and hypothalamus, the research could provide novel therapeutic targets to control appetite, obesity and the metabolic syndrome, a promising notion, given that one-third of the U.S. population is considered obese.

Until now, the role of GCC outside the gut has remained elusive. Dr. Waldman and his team have previously shown its role as a tumor suppressor and biomarker that reveals occult metastases in lymph nodes. But its role in appetite is new and surprising territory.

“We were working with GCC-deficient mice to look at its role in tumorigenesis in the intestine,” said Dr. Waldman.  “Then the mice grew up, and we noticed something: They got fatter.

“We couldn’t understand why it was happening, because GCC is expressed predominantly in intestine, and there was no indication that it regulated any function that had to do with metabolism and nutrient uptake.”

To investigate this, Dr. Waldman, who also leads the Gastrointestinal Malignancies Program at the Kimmel Cancer Center at Jefferson, and his colleagues raised both GCC mice and GCC deficient mice, tracking their weight, satiation responses, hepatic and serum triglyceride measurements, hormone receptor expression, and physical activity.

When food was digested by the mice, they found, the gut released hormones into the blood stream, not just within the intestines, and up into the brain, where the hormone receptors were triggered. Mice with GCC knew when to stop, but hormone receptor-deficient mice never got the message that their stomachs were full. They simply kept eating and became obese.

“They got to be diabetic and developed the metabolic syndrome, fatty livers, etc.” Dr. Waldman said. “We ruled out usual suspects: gastroenterology function was normal. They weren’t more sedentary than wild type mice. And they did not have abnormal metabolism. We realized they just have a different appetite.”

The research offers up a new neural-gut axis that explains appetite more, but it still begs some questions: Do obese people possess little to no GCC? And if so, does that mean obese people have a genetic disposition to gain weight?

It’s possible, said Dr. Waldman, but it’s still unclear. There is the possibility that obese people do not have the receptor or they do not release enough hormones to trigger the receptor. More studies are needed to better explain this, he added.

“Obesity could be biological, and not behavioral,” said Dr. Waldman. “But there is no evidence here that confirms that; however, knowing this new information opens that possibility.”



ADVANCE for Nurses Magazine Features KCC’s Senior Adult Oncology Center

The multidisciplinary staff at the Center assesses the many health challenges confronting senior adults and recommends a personalized cancer treatment plan for each patient. Jefferson staff members Pat Dugan, Vicki Squire and Barb Daulerio were interviewed for the article.

The nursing magazine, ADVANCE for Nurses, put the spotlight recently on the Senior Adult Oncology Center at Jefferson’s Kimmel Cancer Center, and its unique approach to senior cancer care. The multidisciplinary staff assesses the many health challenges confronting senior adults and recommends a personalized cancer treatment plan for each patient.

Cancer care coordinator for the Jefferson Senior Adult Oncology Center, Barbara Daulerio, BSN, RN, explains in an Advance for Nurses story, “This clinic examines what cancer treatment means to a specific person. Age alone does not determine functional capacity; our comprehensive geriatric assessment is able to give us a much clearer idea of what sort of cancer treatments a patient can or cannot tolerate.”

Learn more by reading “Tailored Treatment: Senior Cancer Care Personalizes Healing at the Kimmel Cancer Center.”

Also, see the photo gallery of the center and our staff —  “Senior Oncology Care: A Personalized Approach to Special Patient Population” — featured on the magazine’s website.

ADVANCE for Nurses provides concise, practical information on clinical, management, professional and career development issues for nurses practicing in all areas of the profession. The magazine is in print serving five regions that cover all 50 states, and online with regional websites serving nurses across the country.



The Great Walk

Ms. Olivia Newton-John and Dr. Richard G. Pestell

Ms. Olivia Newton-John and Dr. Richard G. Pestell

Dr. Richard Pestell joins Olivia Newton-John to recognize donations received from grateful donors as part of The Great Walk to Beijing international fundraising effort.Olivia Newton-John is delighted to accept these funds, raised from over 830 donors, for her Olivia Newton-John Cancer & Wellness Centre in Victoria, Australia.



Blocking Receptor in Key Hormone Fires Up Enzyme to Kill Pancreatic Cancer Cells

Hwyda Arafat, M.D., Ph.D., associate professor of Surgery at Jefferson Medical College of Thomas Jefferson University

Pancreatic cancer researchers at Thomas Jefferson University have shown, for the first time, that blocking a receptor of a key hormone in the renin-angiotensin system (RAS) reduces cancer cell growth by activating the enzyme AMPK to inhibit fatty acid synthase, the ingredients to support cell division.

With that, a new chemopreventive agent that inhibits the angiotensin II type 2 receptor—never before thought to play a role in tumor growth—could be developed to help treat one of the fastest-moving cancers that has a 5-year survival rate of only 5 percent.

Hwyda Arafat, M.D., Ph.D., associate professor of Surgery at Jefferson Medical College of Thomas Jefferson University and the co-director of the Jefferson Pancreatic, Biliary and Related Cancers Center, and her fellow researchers, including the chair of the Department of Surgery at Jefferson, Charles J. Yeo, M.D., FACS, present their findings in the August issue of Surgery.

Angiotensin II (AngII) is the principal hormone in the RAS that regulates our blood pressure and water balance; it has two receptors: type 1 and type 2. AngII is also generated actively in the pancreas and has been shown to be involved in tumor angiogenesis.

Previous studies have pointed to the hormone’s type 1 receptor as the culprit in cancer cell proliferation and tumor inflammation; however, the idea that type 2 had any effect was never entertained.

By looking at pancreatic ductal adenocarcinoma (PDA) cells in vitro, Jefferson researchers discovered that the type 2 receptor, not just type 1, mediates the production of fatty acid synthase (FAS), which has been shown to supply the cell wall ingredients necessary for cancer cells to multiply.

FAS was previously identified as a possible oncogene in the 1980s. It is up-regulated in breast cancers and is indicator of poor prognosis, and thus believed to be a worthwhile chemopreventive target.

“AngII is not just involved in cell inflammation and angiogenesis; it’s involved in tumor metabolism as well,” said Dr. Arafat, a member of the Kimmel Cancer Center at Jefferson. “It promotes FAS with both receptors, which makes the tumor grow.”

“Blocking the type 2 receptor reduces PDA cell growth with the activation of AMPK, revealing a new mechanism by which chemoprevention can exploit,” she added. “In fact, maybe combined blocking of the two receptors would be more efficient than just blocking one receptor.”

AMPK, or adenosine monophosphate-activated protein kinase, is the focus of several agents today, including ones for diabetes and related metabolic diseases. It is a master metabolic regulator for cells that is activated in times of reduced energy availability, like starvation. Activation of AMPK has been shown to improve energy homeostasis, lipid profile and blood pressure. The enzyme also activates a well-known tumor suppressor, p53.

“The main thing is activation of AMPK in tumor cells,” said Dr. Arafat. “AMPK is the perfect candidate as it regulates multiple targets that both halt tumor cell division and activate programmed cell death. Although it is yet to be determined how the type 2 receptor imposes deregulation of AMPK activity, identification of the type 2 receptor as a novel target for therapy is very exciting”

Next, Dr. Arafat and fellow researchers are proposing to take this research into animal studies. They hope to target the receptors early on in the disease to better understand its prevention capabilities and also study its treatment potential. Considering pancreatic cancer is typically detected in later stages, finding better ways to treat cases that have progressed further along would be of great benefit to patients.



Leukemia Drug Reverses Tamoxifen-Resistance in Breast Cancer Cells

Researchers at the Kimmel Cancer Center at Jefferson demonstrate drug combination’s “antioxidant effect” on cancer cells and fibroblasts

Taking a leukemia chemotherapy drug may help breast cancer patients who don’t respond to tamoxifen overcome resistance to the widely-used drug, new research from the Kimmel Cancer Center at Jefferson suggests.

Interestingly, researchers found that tamoxifen combined with dasatinib, a protein-tyrosine kinase inhibitor, reverses the chemo-resistance caused by cancer-associated fibroblasts in the surrounding tissue by normalizing glucose intake and reducing mitochondrial oxidative stress, the process that fuels the cancer cells.

Previous animal studies have confirmed that combining tyrosine kinase inhibitors with anti-estrogen therapies, like tamoxifen, can prevent drug resistance, but none have suggested that the target of the inhibitors is the cancer-associated fibroblasts.

The researchers report their findings in the August 1 issue of Cell Cycle.

About 70 percent of women diagnosed with breast cancer will have estrogen receptor positive (ER(+)) disease, which indicates that the tumor may respond to tamoxifen. However, a large percentage of these tumors—up to 35 percent—have little to no response to the drug or eventually develop resistance to it.

In this study, researchers sought to better understand drug resistance by looking at the metabolic basis in an ER (+) cell line and cancer-associated fibroblasts. The researchers have previously established a relationship between the two, where cancer cells induce aerobic glycolysis by secreting hydrogen peroxide in adjacent fibroblasts via oxidative stress. In turn, these fibroblasts provide nutrients to the cancer cells to proliferate, a process that ultimately makes tumors grow.

Here, they investigated and then demonstrated that this interaction was also the basis of tamoxifen resistance.

In a sense, the drug combination had an “antioxidant effect” in these types of cancer cells, according to Michael P. Lisanti, M.D., Ph.D., Professor and Chair of Stem Cell Biology and Regenerative Medicine at Jefferson Medical College of Thomas Jefferson University and a member of the Kimmel Cancer Center.

“The fibroblasts are what make ER (+) cancer cells resistant to the tamoxifen,” said Dr. Lisanti. “But the tamoxifen plus dasatinib maintained both fibroblasts and cancer cells in a ‘glycolytic state,’ with minimal oxidative stress and more cell death, most likely because of an absence of metabolic coupling. The supply between the two was cut.”

“This suggests resistance to chemotherapeutic agents is a metabolic and stromal phenomenal,” he added.

Researchers showed that ER (+) cancer cells alone responded to tamoxifen but when co-cultured with human fibroblasts had little to no effect. Similarly, dasatinib, a chemotherapy drug used to treat leukemia patients who can no longer benefit from other medications, had no effect on fibroblasts alone or cancer cells. Together, however, the drugs prevented the cancer cells co-cultured with the fibroblasts from using high-energy nutrients from the fibroblasts.

This combination resulted in nearly 80 percent cell death, the team reported—a two to three fold increase when compared with tamoxifen alone.

“The drugs have no effect when they are used alone—it’s in unison when they effectively kill the cancer cells in the presence of fibroblasts,” said Dr. Lisanti. “This opens up the door for possible new treatment strategies. This ‘synthetic lethality’ may help patients overcome resistance in the clinic.”

##

Researchers involved in the study include Ubaldo E. Martinez-Outschoorn, of the Jefferson Stem Cell Biology and Regenerative Medicine Center and Department of Medical Oncology; Zhao Lin, of the Departments of Stem Cell Biology & Regenerative Medicine and Cancer Biology;Ying-Hui Ko, of the Departments of Stem Cell Biology & Regenerative Medicine and Cancer Biology; Allison F. Goldberg, of the Department of Surgery; Neal Flomenberg, chair of the Department of Medical Oncology; Chenguang Wang, of the Departments of Stem Cell Biology & Regenerative Medicine and Cancer Biology; Stephanos Pavlides, of the Departments of Stem Cell Biology & Regenerative Medicine and Cancer Biology; Richard G. Pestell, director of the Kimmel Cancer Center at Jefferson and Chair of the Department of Cancer Biology; Anthony Howell, of the Manchester Breast Centre & Breakthrough Breast Cancer Research Unit; and Federica Sotgia, of the Departments of Stem Cell Biology & Regenerative Medicine and Cancer Biology.



Dr. Greenbaum to co-organize International Conference on Liver Biology

Dr. Linda Greenbaum

Dr. Linda Greenbaum will co-organize, (along with Dr. Jessica Zucman-Rossi (Professor of Medicine (Oncology), University of Paris Descartes), the 2012 FASEB Summer Research Conference  on “Liver Biology: Fundamental Mechanisms & Translational Applications.  The conference will take place in Snowmass, Colorado July 29-August 3, 2012 and will bring together 150- 200 outstanding basic and translational scientists dedicated to the study of liver diseases.