Dr. Pestell seen here at dinner with the Prime Minister of Australia, Julia Gillard, discussing Jefferson’s Kimmel Cancer Center at the Prime Ministerial visit to the USA on March 9, 2011 in New York City.
Dr. Pestell seen here at dinner with the Prime Minister of Australia, Julia Gillard, discussing Jefferson’s Kimmel Cancer Center at the Prime Ministerial visit to the USA on March 9, 2011 in New York City.
It is estimated that more than 70,000 new cases of bladder cancer were diagnosed in 2010, making it the 5th most commonly diagnosed cancer in the U.S.
Please join Dr. Jean Hoffman-Censits, of the Department of Medical Oncology, Solid Tumor Division, and the Kimmel Cancer Center at Jefferson Team in raising awareness of the disease by walking the Radnor Trail, in Wayne, Pa., on Saturday May 7 at 9:00 a.m.
The walk is taking place on the Radnor Trail off Route 30 in Wayne, Pa. Meet at 9 a.m. behind the parking lot of the VIST Financial Bank, 600 West Lancaster Avenue (at the intersection of Sugartown Road and Old Eagle Road) near the sign for the entrance to the trail.
For more information or to join our Jefferson Team, please contact Teresa Bryant at 215-503-5455 or visit http://www.firstgiving.com/fundraiser/thomasjefferson/walkforbladdercancer to sign up for the walk or make a donation.
For more information regarding the Bladder Cancer network visit, WWW.bcan.ORG
Learn more by watching BCAN’s Bladder Cancer Awareness Video.
Edith Mitchell, M.D., clinical professor of Medicine and Medical Oncology at Jefferson Medical College of Thomas Jefferson University, attended the 8th Annual National Summit on Health Disparities Meeting & Awards Dinner in Washington, D.C., on April 11 and 12.
The summit, organized by The National Minority Quality Forum and the Congressional Black Caucus Foundation, in collaboration with the CBC Health Braintrust, brings together members of congress, senior healthcare executives, clinicians, payers, and allied members of the healthcare industry to discuss solutions to disease disparities.
Four consummate Americans were honored for their deep commitment and contributions in the area of health care, including Senator Harry Reid and Former Speaker Nancy Pelosi, who both received the Lifetime Achievement Award.
Dr. Mitchell moderated the “Cancer Biomarkers, Clinical Trials, & New Treatment Options” session, which included Roy Herbst, M.D., Ph.D., Chief of Medical Oncology, Yale Cancer Center and Joseph Sparano, M.D., Associate Chairman, Department of Oncology, Montefiore Medical Center.
Francis Collins, M.D., PhD, Director of the National Institutes of Health, also gave a special address.
The National Minority Quality Forum is a non-profit healthcare research and educational organization dedicated to the elimination of health disparities.
Identifying gene mutations in cancer patients to predict clinical outcome has been the cornerstone of cancer research for nearly three decades, but now researchers at the Kimmel Cancer Center at Jefferson have invented a new approach that instead links cancer cell metabolism with poor clinical outcome. This approach can now be applied to virtually any type of human cancer cell.
The researchers demonstrate that recurrence, metastasis, and poor clinical outcome in breast cancer patients can be identified by simply gene profiling cancer cells that are using ketones and lactate as a food supply.
These findings are reported in the April 15th online issue of Cell Cycle. The investigators are calling this new approach to personalized cancer medicine “Metabolo-Genomics.”
High-energy metabolites have long been suspected to “fuel” aggressive tumor cell behavior. The researchers used this premise to generate a gene expression signature from genetically identical cancer cells, but one cell group was fed a diet of high-energy metabolites. These lactate- and ketone-induced “gene signatures” then predicted recurrence, metastasis, and poor survival.
So, it appears that what cancer cells are eating determines clinical outcome, not necessarily new gene mutations.
Michael P. Lisanti, M.D., Ph.D., Professor and Chair of Stem Cell Biology & Regenerative Medicine at Jefferson Medical College of Thomas Jefferson University and a member of the Kimmel Cancer Center at Jefferson, together with other researchers, found that treatment of human breast cancer cells with high-energy metabolites increases the expression of genes associated with normal stem cells, including genes upregulated in embryonic and neural stem cells.
What’s more, lactate and ketones were found to promote the growth of normal stem cells, which has critical applications for stem cell transplantation and for a host of different human diseases. It appears that these metabolites increase “stemness” in cancer cells, which drives poorer outcomes.
“Tumors that are using the body’s own nutrients (lactate and ketones) as “fuel” have a poorer outcome for patient survival, a behavior that now can be used to predict if a patient is at a high-risk for recurrence or metastasis,” Dr. Lisanti said. “This is getting to the heart of personalized cancer medicine. Now, we have identified a panel of biomarkers that directly links cancer metabolism with targeted cancer therapy.”
These findings suggest, according to the authors, that high-risk cancer patients (those whose cancer cells use high-energy metabolites) can be treated with new therapeutics that target oxidative mitochondrial metabolism, such as the antioxidant metformin, a drug that is also used to treat diabetes.
“Knowing the gene signatures of patients whose cancer cells are “eating” these metabolites for fuel is a pivotal piece of new information that we can use to diagnose and treat cancer patients,” said Martinez-Outschoorn, M.D., of the department of Medical Oncology at Thomas Jefferson University, and the lead author of the paper. “It’s not just that we know those patients will have poor survival; we know that those patients are using mitochondrial metabolism, which is the type of energy metabolism that we should be targeting with new anti-cancer drugs.”
The researchers propose that this new approach to diagnosis and subsequent treatment be called “Metabolo-Genomics” since it incorporates both cell metabolism and gene transcriptional profiling. This strategy could now be used to direct which patients receive a particular “tailored” anti-metabolic therapy.
Genetic markers, like expression of the mutationally activated HER2 gene, provide biomarkers that can be used to identify breast cancer patients at high-risk for recurrence or metastasis, and to modify their subsequent treatment with targeted therapies (i.e., herceptin, a drug used in aggressive breast cancers). But with “Metabolo-Genomics,” it is now about using “global” cancer cell metabolism for these predictions.
“Just by feeding cancer cells a particular energy-rich diet, it changes their character, without introducing mutations or altering their genetic profile,” Dr. Lisanti said. “We’ve only fed them high energy nutrients that help them to use their mitochondria, and this changes their transcriptional profile. It’s a new biomarker for “lethal” cancers that we can now treat with the right drugs, such as the antioxidant metformin.
Dr. Lisanti and his colleagues believe that tumor metabolism is the new big picture for understanding how cancers undergo recurrence and metastasis.
Several researchers from Thomas Jefferson University’s Department of Radiation Oncology will participate in this year’s American Brachytherapy Society Annual Meeting in San Diego, Calif.
Laura Doyle, M.S., a medical physicist at the Bodine Center for Cancer Treatment, will be moderating a session called “Clinical Advancements in Microbrachytherapy” on Friday, April 15 from 4:30 to 5:00 pm
Three abstracts have also been accepted for the moderated and general poster sessions:
1. “Usage of mixed seed technique for permanent seed implants: a feasibility study”
Ivan Buzurovic, Tarun Podder, K. Huang, and Yan Yu.
2. “Can the number of leftover seeds be reduced? A study of prostate volume, nomogram, and delivered activity for ultrasound-guided I-125 prostate seed implant”
Yunfeng Cui, Laura Doyle, Tarun Podder, Timothy N. Showalter, Adam Dicker, Ying Xiao,
Yan Yu, Haisong Liu
3. “Intraoperative planning increases feasibility of prostate seed implantation for small (<20cc) and large (>500cc) glands”
Laura A. Doyle, Katherine L. Chapman, Yan Yu, Adam Dicker, Timothy N. Showalter
A widely-available yet expensive radiotherapy technique used to treat prostate cancer patients after surgery has promising benefits—higher dose and less damage to the rectum and bladder—compared to a less precise technique, Thomas Jefferson University researchers document for the first time in a new study published in Practical Radiation Oncology.
A team of radiation oncologists and medical physicists, including lead author Amy Harrison, M.S., the medical physics clinical supervisor at Jefferson, show that intensity-modulated radiotherapy (IMRT) allows a higher dose to be delivered to the area after their glands have been removed while maintaining the same dose to the rectum and bladder compared to 3D conformal radiation therapy.
Higher doses to the prostate bed have been shown to be more effective in that setting for controlling prostate-specific antigen (PSA) levels.
IMRT is currently being used at some centers in the United States, including the Kimmel Cancer Center, to treat men after they’ve had their prostate glands removed, but detailed data are limited evaluating the advantages of this approach compared to 3D conformal radiation therapy. In other words, documented justification for the approach was lacking.
“This is the first contemporary study to look at IMRT versus 3D radiation therapy for post-op patients using consensus guidelines,” said Timothy Showalter, M.D., assistant professor of Radiation Oncology at Thomas Jefferson University, and an expert in image-guided therapy of prostate cancer. “This is also filling a gap for information that no one supplied before to show that this radiotherapy is beneficial in the postoperative setting, similar to its role in non-surgical approaches.”
“The reason that it’s more and more relevant now is that there are emerging data to support doing adjuvant radiation therapy after prostatectomy for high risk patients,” he added.
There a variety of toxicities associated with radiation therapy after a prostatectomy, including late gastrointestinal bleeds, loose stools and painful bowel moments, but IMRT can minimize damage that can lead to such side effects.
“The biggest benefit for our patients who have a PSA failure after radical prostatectomy is to be able to deliver high dose radiation while sparing normal tissue,” said Dr. Showalter.
Future studies, the researchers report, should determine whether these advantages translate into improved clinical outcomes for prostate cancer patients.
Cancer Registrars throughout the United States and abroad will join their colleagues, community leaders, and other medical professionals to observe the 15th annual National Cancer Registrars Week, April 11th-15th. Quality cancer data is central to the nation’s fight against cancer, and cancer registrars are the first link in capturing these data.
Our Cancer Registry works with physicians, administrators, researchers, and health care planners. We manage a wide range of demographic and medical data on those with cancer. The information is both submitted and utilized by state and national cancer registries to enable cancer programs to accurately determine cancer patient populations, measure outcomes of treatment, survival, and formulate plans for improvement.
According to the National Cancer Registrars Association, cancer treatment is improving-saving lives and extending survival for cancer patients. This demonstrates the important work carried out by Cancer Registrars has resulted in better information that is being used to manage a wide variety of cancers. Cancer Registrars pave the way to a cure!
“It is my distinct honor to recognize and give my support to Pennsylvania Cancer Registrars during Cancer Registrars Week, April 11-15, 2011,” said Governor Tom Corbett said in a statement. “As more than 70,000 Pennsylvanians will be diagnosed with cancer this year and nearly 29,000 will lose their lives due to cancer, it is vitally important that data are available on which to base cancer research and prevention programs. By providing some of this key information, Cancer Registrars are helping to make a difference in the lives of those affected by this disease.”
For more information, contact Fran Guiles at 215-955-0042 or email@example.com. TJUH’s Oncology Data Services Department (Cancer Registry) is located at 1015 Chestnut Street – Suite 608.
The latest advances in both breast cancer treatment and research – including innovations in diagnostic, surgical, chemotherapy and radiation approaches – will be discussed Friday, April 8, 2011, at a breast cancer symposium at the Kimmel Cancer Center at Jefferson in Philadelphia.
The all-day, breast cancer symposium, part of an annual series at the Kimmel Cancer Center, will be held at the Bluemle Life Sciences Building, 233 S. 10th Street, beginning at 8:30 a.m.
“Treating breast cancer is a multidisciplinary effort, with input from a variety of specialists, such as pathologists, surgeons, radiation oncologists, and medical oncologists, who make decisions about patient treatment and care,” says Richard Pestell, M.D., Ph.D., director of the Kimmel Cancer Center at Jefferson and professor and chair of cancer biology at Jefferson Medical College of Thomas Jefferson University.
“This symposium is an opportunity for those players to come together and highlight the innovative discoveries we believe will be important for the next generation of therapeutics in breast cancer patients,” he adds.
A range of topics will be covered by top experts here at Jefferson and other institutions in the United States.
Michael Lisanti, M.D., professor of cancer biology at Jefferson Medical College, will discuss his recent work with new models for cancer, “The Reverse Warburg Effect” and “The Autophagic Tumor Stroma Model of Cancer.” His studies have shown how mitochondrial oxidative stress plays a role in cancer development and how cancer metabolism can be used to predict clinical outcomes.
“High-risk breast cancer patients—those whose cancer cells use high-energy metabolites—can be treated with new therapeutics that target oxidative mitochondrial metabolism,” Dr. Lisanti said. “We should re-consider using antioxidants and autophagy inhibitors as anti-cancer agents.”
There will also be presentations by Hallgeir Rui, M.D., Ph.D, also of the department of cancer biology at Jefferson Medical College, who will discuss therapy-relevant stratification of breast cancer, and Paula Ryan, M.D., Ph.D., of Fox Chase Cancer Center’s department of medical oncology, who will present a clinical update on patients with triple negative breast cancer, a high-risk disease that is characterized as more aggressive and less responsive to standard treatment.
Hyman B. Muss, M.D., of the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill School of Medicine, will lead a session titled “Geriatrics: Treating the Elderly with Breast Cancer.”
Sixty percent of cancer in the United States occurs in persons aged 65 and older. At the same time, senior patients may have acute or chronic diseases that make treating their cancer challenging. That’s why the Kimmel Cancer Center at Jefferson established the new, multidisciplinary Senior Adult Oncology Center to provide a comprehensive consultation for senior patients in order to meet those special challenges.
The Kimmel Cancer Center held it’s quarterly “All Hands” meeting on March 29, 2011. Dr. Richard Pestell, Director of the Kimmel Cancer Center, delivered his quarterly “State of the Cancer Center” address. Awards were presented in four categories. The Nursing Award was presented to Carole Muto, RN, MSN, CPAN. The Clinical Award was presented to Andrew Chapman, DO. The Basic Science Award was presented to Marja Nevalainen, MD, PhD. The Administration Award was presented to Mildred Harden.
On March 25th, the Jefferson School of Population Health and Philadelphia Department of Health hosted a seminar featuring Rosemarie Henson, MSSW, MPH.
Ms. Henson is the Senior Advisor to the Assistant Secretary for Health at the Department of Health and Human Service (DHHS). Prior to her position at DHHS, Ms. Henson directed multiple disease prevention and health promotion programs at the Center for Disease Control and Prevention (CDC).
For many years Ms. Henson directed the CDC’s Office on Smoking and Health (OSH) where she launched the state-based National Network of Tobacco Cessation Quitlines, which provided access to telephone counseling and follow-up for all US smokers. She also played a pivotal role in leading the CDC’s efforts to establish youth tobacco surveillance activities globally; she led the successful CDC tobacco-free campus initiative; and the national strategy for the release of two landmark Surgeon General’s reports.
As part of the Philadelphia Department of Public Health Get Healthy Philly Tobacco Policy and Control Series, Ms. Henson will present on the National Tobacco Control Strategy of DHHS.
Edith Mitchell, M.D., clinical professor of Medicine and Medical Oncology at Jefferson Medical College of Thomas Jefferson University, will be honored by the Philadelphia County Medical Society (PCMS). Dr. Mitchell will be the recipient of the PCMS 2011 Practitioner of the Year Award. Dr. Mitchell will receive the award on June 11 at the PCMS President’s Ball.
The work of Michael P. Lisanti, Professor and Chair of Stem Cell Biology and Regenerative Medicine & Leader of the KCC Molecular Biology & Genetics Program was recently highlighted on the NCI’s Physical Sciences-Oncology Centers Research News Website in an article entitled “Tumors Acts As Parasites, Sucking Energy From Surrounding Cells “ (article link). The article describes Dr. Lisanti’s recent publications on cancer cell metabolism and the “Reverse-Warburg Effect.”
Thomas Jefferson University has started recruiting patients for a new National Cancer Institute (NCI)-sponsored clinical trial to test whether the cholesterol-reducing drug rosuvastatin is effective in the prevention of recurrent colon cancer.
Previous laboratory research and population studies have shown that patients taking statins, the class of drugs that lowers cholesterol, had fewer colon polyps, which can lead to cancer if left untreated. However, those findings come largely from retrospective, observational studies originally designed to investigate lipid-lowering or cardiovascular endpoints in the short term rather than tumor endpoints.
“The jury is still out, and we need to get definitive answers,” said Bruce Boman, M.D., Ph.D, professor of medical oncology at Thomas Jefferson University and principal investigator for the national clinical trial. “This prospective design comparing a statin against a placebo is what is needed to address the question: Are statins effective chemoprevention agents or not?”
This five-year, nationwide study will be the first randomized, prospective, placebo-controlled, double-blind study to evaluate the drug’s role in preventing colon cancer and will involve 1,740 patients in total.
Conducted by a network of cancer research professionals from the National Surgical Adjuvant Breast and Bowel Project (NSABP) at 400 medical centers across North America, including Jefferson, the study involves patients who have recently been diagnosed with early stage colon cancer, and who were not already taking statins for high cholesterol. Those recruited have been surgically treated for stage I and II colon cancers previously.
Patients will be randomly assigned to one of two groups. Each group will take one pill a day for five years. One group will receive rosuvastatin, while the other group will receive a placebo.
The cumulative incidence for developing colorectal adenomas three years after surgery/treatment for early stage colon cancer is 50 percent. Thus, the benefit/risk ratio for chemoprevention intervention is potentially very positive in this high-risk population.
“There will be an estimated 102,900 new cases of colon cancer in the United States this year,” said Norman Wolmark, M.D., NSABP’s chairman. “In fact, colorectal cancer is the third most common cancer found in men and women in this country. We hope this trial will be an important step in reducing these numbers.”
The principal investigator for the trial at Jefferson is Scott Goldstein, M.D, director of the Division of Colon and Rectal Surgery at Thomas Jefferson University.
People recently diagnosed with a Stage I or II colon cancer and interested in the study should contact Vicki Squire of Thomas Jefferson University at Vicki.Squire@jeffersonhospital.org or 215-503-5641.
A list of other sites in North America that are participating in the study may be found at http://www.nsabp.pitt.edu/P5_Sites.asp
Reporting in Nature, scientists from Thomas Jefferson University have determined that a single protein called FADD controls multiple cell death pathways, a discovery that could lead to better, more targeted autoimmune disease and cancer drugs.
Twelve years ago, internationally-known immunologistan associate professor in the Department of Microbiology and Immunology at Thomas Jefferson University, realized FADD, which stands for Fas-Associated protein with Death Domain, played an important role in embryonic development and the onset of some diseases, but he didn’t know exactly why until now.
In the paper published online March 2, Dr. Zhang and researchers show this protein regulates not one but two types of cell deaths pivotal for embryo and disease development. It is now known that FADD causes apoptosis, the “healthy” cell death, while keeping necrosis, the “toxic” one, at bay.
Understanding this pathway is instrumental in developing drugs with selectivity and fewer side effects, said Dr. Zhang, a member of the Kimmel Cancer Center at Jefferson.
“This work has direct impact on our understanding of diseases: cancer, autoimmune disease, immune-deficiency disease,” he said. “This is the one gene that regulates these two processes in cells, so now we can find targeted drugs to control the cell death process.”
The research suggests that with the absence or variation in expression of this one protein, an embryo may not develop properly or a person may develop disease later in life.
“This breakthrough is a testimony to Dr. Zhang’s research acumen and dogged determination to solve a longstanding mystery regarding the regulation of cell death pathways,” said Tim Manser, Ph.D., professor and chair of the Department of Microbiology and Immunology at Jefferson. “It is gratifying to know that Thomas Jefferson University provides the research infrastructure that allows outstanding researchers like Dr. Zhang to make seminal discoveries, such as those reported in the Nature paper.”
FADD’s importance in embryogenesis and lymphocyte death response has been known, but the mechanism that underlies these functions in FADD has remained elusive.
Researchers found that mice that did not express FADD contained raised levels of RIP1, Receptor-Interacting Protein 1, an important protein that mediates necrosis and the apoptotic processes, and their embryonic development failed due to massive necrosis.
“When the FADD-mediated death process is deregulated, we will produce white bloods cells that will attack our own tissue, which is the cause of auto-immune diseases, such as arthritis and lupus,” said Dr. Zhang. “And without the necessary cell deaths that are required for tumor surveillance, humans could develop cancer.”
There are drugs currently under development today that activate TNF-a-related apoptosis-inducing ligand (TRAIL) death receptor signaling, which induces apoptosis through FADD in cancer cells specifically, but its mechanisms are not well understood and the treatment not perfected. There are also tumor cells that are resistant to TRAIL-induced apoptosis for unknown causes.
“The killing of these tumor cells is not efficient, and this paper actually figured out why,” said Dr. Zhang. “We now know that the FADD protein, while required for apoptotic death, is inhibiting necrotic death in tumor cells.”
Dr. Jianke Zhang’s research team in Microbiology and Immunology Department at Thomas Jefferson University includes Haibing Zhang, Ph.D., Research Associate and Jinghe Li, M.D.; Candidate for Ph.D. and are also affiliated with the Kimmel Cancer Center, and declare no conflicts of interest.
Thomas Jefferson University welcomes two new, seasoned clinicians and researchers to its Department of Radiation Oncology: Nicole Simone, M.D., from the National Institutes of Health’s National Cancer Institute (NCI) and Bo Lu, M.D., Ph.D, from Vanderbilt University.
Dr. Simone is a board-certified Radiation Oncologist who has treated mostly patients with breast and head and neck cancers, while her research involves radiation’s effect on microRNAs in breast cancer and caloric restriction and radiation therapy—and the ability of both to delay breast cancer tumor growth.
“Dr. Simone is rapidly being recognized as one of the rising stars in the field,” said Adam Dicker, M.D, Ph.D, Professor and Chairman of the Department of Radiation Oncology. “Her research cuts across a number of cutting edge fields, including breast and prostate cancer biology, metabolism, microRNAs and computational biology. The connection between diet and cancer treatment is very relevant for patients.”
Dr. Bo Lu is also a board-certified Radiation Oncologist who comes to Jefferson from Vanderbilt University in Nashville, Tenn., where he was an Ingram associate professor with tenure in the Department of Radiation Oncology and Cancer Biology of the University’s School of Medicine. He was also an attending radiation oncologist at the Vanderbilt University Medical Center, member of the Ingram Cancer Center, and director of the Translational Research Program and Lung Cancer Research Program.
“I am delighted that Dr. Lu has joined our faculty,” said Dr. Dicker. “He is internationally renowned for his work in clinical and translational radiation oncology, and I have received numerous congratulatory calls and emails from Chairs of Departments of Radiation Oncology around the world recognizing his numerous achievements.”
Dr. Lu’s focus is on radiation-induced cell death in lung patients, among other basic science areas. His clinical interests include the integration of novel targeted agents in the treatment of lung cancer, radiosurgery for lung cancer, and reductionof toxicities from thoracic radiation. More recently, Dr. Lu has looked at cancer stem cells for enhancing radiotherapy in a setting of lung cancer.
Congratulations to Maria Werner-Wasik, M.D., professor in the department of radiation oncology, and radiation oncology residency program director, who was elected as the Radiation Therapy Oncology Group Vice-Chair for Publications. (www.rtog.org)
Dr. Werner-Wasik is a member of the RTOG Lung Cancer Steering Committee. She succeeds William Sause, M.D., of Intermountain Medical Center in Salt Lake City, Utah, who has served as the RTOG publications vice-chair since 1999.
Dr. Werner-Wasik will chair the RTOG Publications Committee which is responsible for the oversight ofpublication quality and timeliness of the results of the group’s trials.
Drs. Timothy Showalter and Robert Den have been selected as recipients of the American Brachytherapy Society sponsored High Dose Rate fellowship program (1 week) for 2011.
Researchers from the Kimmel Cancer Center at Jefferson and two other institutions have discovered new evidence that suggests the “longevity” protein SIRT1, known for its life-spanning effects in different species, can inhibit the development of a known precursor to prostate cancer, prostatic intraepithelial neoplasia (PIN).
“Prostate cancer is one of the malignancies that has a very direct relationship to aging,” says Richard G. Pestell, M.D., Ph.D., Director, Kimmel Cancer Center and Chairman of Cancer Biology at Thomas Jefferson University. “And these results provide a direct link for the first time between the onset of prostate cancer and the Sirt1 gene that regulate aging.”
Dr. Leonard G. Gomella, chair of the Department of Urology and director of Clinical Affairs at the Kimmel Cancer Center at Jefferson, co-chaired the American Society of Clinical Oncology (ASCO) 2011 Genitourinary (GU) Cancers Symposium meeting in Orlando on Feb. 17 though Feb. 19.
The “2011 Genitourinary Cancers Symposium: An Evidence-based Multidisciplinary Approach,” was a three-day Symposium that offered educational sessions and oral and poster abstract presentations focused on genitourinary cancers of the prostate, penis, urethra, testis, bladder and kidney.
Over 1,800 physicians, researchers, care givers and survivors attended the meeting sponsored by ASCO, the American Society for Radiation Oncology (ASTRO) and the Society of Urologic Oncology (SUO).
Dr. Gomella’s talk during the opening remarks was titled “Decision Making Based on Predictors of Clinical Progression.”
To learn more about this symposium, visit http://gucasymposium.org/Home.aspx
A quantitative, molecular analysis of lymph nodes in patients deemed colorectal cancer-free was found to be an effective predictor of recurrence, according to a study from researchers at the Kimmel Cancer Center at Jefferson and published online Feb 9. in Clinical Cancer Research.
Recurrence occurs in about 25 percent of node-negative patients (pN0), suggesting that occult metastases escaped detection, be it imaging modalities or histopathology.
To better predict recurrence and accurately stage these patients, Terry Hyslop, Ph.D. and Scott A. Waldman, M.D., Ph.D. of the Department of Pharmacology and Experimental Therapeutics of Thomas Jefferson University and the Kimmel Cancer Center at Jefferson, and colleagues explored a novel molecular approach, using the biomarker GUCY2C for metastatic colorectal cancer cells.
Using 291 colorectal cancer patients who were node-negative, the researchers analyzed lymph nodes by histopathology and GUCY2C quantitative qRT-PCR. They were followed for a median of 24 months and categorized as having either low, intermediate or high tumor burdens.
The researchers had previously concluded that expression of GUCY2C increased risk of recurrence. However, it is apparent that nodal metastases do not assure recurrence; rather they indicate risk.
The researchers found that patients with greater occult tumor burden have a greater risk of recurrence compared to patients with less burden. Thus, molecular tumor burden in lymph nodes are independently associated with time to recurrence and disease-free survival in patients with node-negative colorectal cancer.
“This approach can improve prognostic risk stratification and chemotherapeutic allocation in pN0 patients,” the authors write. “More generally, this study reveals a previously unappreciated paradigm to advance cancer staging, clinically translating emerging molecular platforms that complement histopathology, laboratory diagnostic, and imaging modalities.”
Researchers from Jefferson’s Kimmel Cancer Center have genetic evidence suggesting the antioxidant drugs currently used to treat lung disease, malaria and even the common cold can also help prevent and treat cancers because they fight against mitochondrial oxidative stress—a culprit in driving tumor growth.
For the first time, the researchers show that loss of the tumor suppressor protein Caveolin-1 (Cav-1) induces mitochondrial oxidative stress in the stromal micro-environment, a process that fuels cancer cells in most common types of breast cancer.
“Now we have genetic proof that mitochondrial oxidative stress is important for driving tumor growth,” said lead researcher Michael P. Lisanti, M.D., Ph.D., professor of cancer biology at Jefferson Medical College of Thomas Jefferson University and member of the Kimmel Cancer Center at Jefferson. “This means we need to make anti-cancer drugs that specially target this type of oxidative stress. And there are already antioxidant drugs out there on the market as dietary supplements, like N-acetyl cysteine.”
These findings were published in the online February 15 issue of Cancer Biology & Therapy.
Lisanti’s lab previously discovered Cav-1 as a biomarker that functions as a tumor suppressor and is the single strongest predictor of breast cancer patient outcome. For example, if a woman has triple negative breast cancer and is Cav-1 positive in the stroma,
her survival is greater than 75 percent at 12 years, versus less than 10 percent at 5 years if she doesn’t have the Cav-1 protein, according to Dr. Lisanti.
The researchers also established Cav-1’s role in oxidative stress and tumor growth; however, where that stress originates and its mechanism(s) were unclear.
To determine this, Jefferson researchers applied a genetically tractable model for human cancer associated fibroblasts in this study using a targeted sh-RNA knock-down approach. Without the Cav-1 protein, researchers found that oxidative stress in cancer associated fibroblasts leads to mitochondrial dysfunction in stromal fibroblasts. In this context, oxidative stress and the resulting autophagy (producton of recycled nutrients) in the tumor-microenvironment function as metabolic energy or “food” to “fuel” tumor growth.
The researchers report that the loss of Cav-1 increases mitochondrial oxidative stress in the tumor stroma, increasing both tumor mass and tumor volume by four-fold, without any increase in tumor angiogenesis.
“Antioxidants have been associated with cancer reducing effects—beta carotene, for example—but the mechanisms, the genetic evidence, has been lacking,” Dr. Lisanti said. “This study provides the necessary genetic evidence that reducing oxidative stress in the body will decrease tumor growth.”
Currently, anti-cancer drugs targeting oxidative stress are not used because is it commonly thought they will reduce the effectiveness of certain chemotherapies, which increase oxidative stress.
“We are not taking advantage of the available drugs that reduce oxidative stress and autophagy, including metformin, chloroquine and N-acetyl cysteine,” Dr. Lisanti said. “Now that we have genetic proof that oxidative stress and resulting autophagy are important for driving tumor growth, we should re-consider using antioxidants and autophagy inhibitors as anti-cancer agents.”
The diabetic drug metformin and chloroquine, which is used for the prevention and treatment of malaria, prevent a loss of Cav-1 in cancer associated fibroblasts (which is due to oxidative stress), functionally cutting off the fuel supply to cancer cells.
This research also has important implications for understanding the pathogenesis of triple negative and tamoxifen-resistance in ER-positive breast caner patients, as well as other epithelial cancers, such as prostate cancers.
“Undoubtedly, this new genetically tractable system for cancer associated fibroblasts will help identify other key genetic ‘factors’ that can block tumor growth,” Dr. Lisanti said.
Medical physicists at Thomas Jefferson University and Jefferson’s Kimmel Cancer Center have demonstrated a new real-time tumor tracking technique that can help minimize the amount of radiation delivered to surrounding healthy tissue in a patient—up to 50 percent less in some cases—and maximize the dose the tumor receives.
Respiratory and cardiac motions have been found to displace and deform tumors in the lung, pancreas, liver, breast, and other organs. Because of this, radiation oncologists must expand the margin during radiotherapy, and consequently a large volume of healthy tissue is irradiated, and critical organs adjacent to the tumor are sometimes difficult to spare.
In an effort to shrink that margin, Jefferson researchers developed a new 4D, robotic technique that better predicts and continuously tracks tumors during radiotherapy, preventing unnecessary amounts of radiation from being administered to unnecessary areas. Thus, critical organs and tissues are spared; cancer treatment is potentially improved; and side effects are decreased.
Published in the online February 1 issue of Physics in Medicine and Biology journal, the study was co-authored by Ivan Buzurovic, Ph.D., a medical physics resident and researcher in the Department of Radiation Oncology at Jefferson Medical College at Thomas Jefferson University, and Yan Yu, Ph.D., director of Medical Physics at Thomas Jefferson University.
In this technique, the robotic system—programmed with the proposed algorithms developed by Jefferson researchers—is automatically adjusted so that the position of the tumor remains stationary during treatment.
“The advantage of this novel approach in radiation therapy is that the system is able to predict and track tumor motion in three-dimensional space,” said Dr. Buzurovic. The technique can compensate both tumor motion and residual errors during patient treatment, he added.
When active tracking was applied and tumor motion was up to 1.5 cm, irradiated planning target volume (PTV) was 20 to 30 percent less for medium size tumors and more than 50 percent for small size tumors. For tumor motion range up to 2.5 cm, irradiated PTV was two times smaller when tracking is applied.
“The proposed robotic system needs 2 seconds to start tracking with the high precision level. The tracking error was less than 0.5 mm for regular breathing patterns and less than 1 mm for highly irregular respiration,” said Dr. Buzurovic. “Prediction algorithms were developed to predict tumor motion and to compensate errors due to delay in the system response.”
The study findings suggest that the use of tumor tracking technology during radiotherapy treatment for lung cancer would result in significant reduction in dose to the healthy tissue, potentially decreasing the probability or severity of side effects, co-author Dr. Yu said.
With this new technique, radiation oncologists would be able to administer more radiation and faster to the tumor than conventional methods, said Adam P. Dicker, M.D, Ph.D., professor and chairman of the Department of Radiation Oncology at Thomas Jefferson University.
“If we shrink our margin by this new robotic technique, then we can bring larger doses to tumors,” Dr. Dicker said. “And a higher dose means a better cure in lung cancer, for instance.”
Researchers from Department of Radiation Oncology at the University of Michigan Hospital in Ann Arbor, Mich., and Brody School of Medicine at East Carolina University, Greenville, N.C., were also involved in the study.
The researchers’ method, demonstrated in extensive computer simulation, can be applied to two commercially available robotic treatment couches.
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