AACR: New Biomarker to Identify Hepatitis B-Infected Patients at Risk for Liver Cancer

CHICAGO— Hepatitis B-infected patients with significantly longer telomeres—the caps on the end of chromosomes that protect our genetic data— were found to have an increased risk of getting liver cancer compared to those with shorter ones, according to findings presented by researchers at Jefferson’s Kimmel Cancer Center at the American Association for Cancer Research (AACR) Annual Meeting 2012.

The relative telomere length in hepatitis B-infected cases with liver cancer was about 50 percent longer than the telomere length of the cancer-free hepatitis B-infected controls.

A strong correlation between telomere length and non-cirrhotic hepatocellular carcinoma (HCC), a liver cancer commonly caused from hepatitis B and C viral infections, could help physicians better stratify the hepatitis B population in an effort to better prevent and treat the disease.

Previous reports have suggested telomere length plays a role in cancer prediction; however, there have been conflicting results and the majority of the studies measured telomere length in liver cells (hepatocytes) and white blood cells.

Here, Hushan Yang, Ph.D., of the Division of Population Science at the Department of Medical Oncology at Thomas Jefferson University and Jefferson’s Kimmel Cancer Center, and colleagues used circulating cell-free serum DNA from an existing and ongoing clinical cohort at the Liver Disease Prevention Center at Thomas Jefferson University Hospital.

Tapping into a cohort of almost 2,600 Korean Americans, a population disproportionately infected with hepatitis B, the team analyzed blood samples from over 400 hepatitis B-infected patients to compare relative telomere length using quantitative real-time polymerase chain reaction (qRT-PCR).

This nested case-control study included 140 hepatitis B-HCC cases and 280 cancer-free hepatitis B controls. Demographic and clinical data were obtained for each patient through medical chart review and consulting with treating physicians.

All participants were restricted to Korean hepatitis B patients to control the confounding effects of ethnicity and HCC etiology. The large majority of the patients were infected at birth or childhood, making this population an ideal resource to study the long-term outcome of hepatitis B infection at the population level.

The hepatitis B-HCC cases were found to have a relative telomere length about 50 percent longer than the cancer-free controls (0.31 versus 0.20, P=0.003), a statistically significant difference.

The difference, however, was also only evident in males and in non-cirrhotic patients, and not cirrhotic patients, possibly because that the effect conferred by telomere length was overshadowed by the strong association between cirrhosis and HCC. There were also no statistical differences between cohorts with respect to age and smoking status.

“This is the first study to demonstrate that relative telomere length in circulating cell-free serum DNA could potentially be used as a simple, inexpensive and non- invasive biomarker for HCC risk,” said Dr. Yang. “This sets the stage for further retrospective and prospective investigations, in-depth molecular characterizations, and other assessments to determine the clinical value of serum DNA telomere length in risk prediction and early detection of HCC.”

Co-authors of the study were Shaogui Wan, Xiaoying Fu, Ronald Myers, Ph.D., Division of Population Science, Department of Medical Oncology, Thomas Jefferson University; Hie-Won Hann, M.D., Richard Hann, Jennifer Au, M.D., Division of Hepatology and Gastroenterology, Department of Medicine, Thomas Jefferson University; and Jinliang Xing, Department of Cell Biology, Fourth Military Medical University in China.

This study was supported by two grants from the National Cancer Institute, a Tobacco Grant from the Pennsylvania Department of Health, an American Cancer Society grant, and a Research Scholar Award from the V Foundation for Cancer Research.



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. 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.



Dr. Greenbaum selected as Chair of AASLD/ALF Joint Grant Review Committee

Dr. Linda Greenbaum

Dr. Linda Greenbaum was selected as the  Chair of the  American Association for the Study of Liver Diseases (AASLD)/ American Liver Foundation (ALF) joint grant review committee for the term 2011-14.



New Tumor Tracking Technique for Radiotherapy Spares Healthy Tissue, Could Improve Cancer Treatment

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.



Vitamin K and Sorafenib Combination Demonstrated Anti-Tumor Effects in Pancreas Cancer and Hepatocellular Carcinoma

Dr. Brian Carr

Dr. Brian Carr

A combination of Sorafenib and Vitamin K had an effect in vitro on both human pancreas cancer and hepatocellular carcinoma, according to researchers from the Kimmel Cancer Center at Jefferson. Data from the two studies were presented at the AACR 100th Annual Meeting 2009 in Denver. (Abstract #5470 and #5483)

Vitamin K1 or Vitamin K2, plus Sorafenib (Nexavar) each have shown activity against the growth of human cancer cells by inhibiting the extracellular signal-regulated kinase (ERK) pathway according to Brian Carr, M.D., Ph.D., a professor of Medical Oncology at the Jefferson Medical College of Thomas Jefferson University. ERK plays a major role in cell growth of cancers.

Although Sorafenib has demonstrated success at extending survival in patients with hepatocellular carcinoma (HCC, or primary liver cancer), hand-foot syndrome is a common adverse effect that affects approximately 20 percent of patients who receive the drug. It typically manifests as painful sores on the soles of patients’ feet that can prevent the patients from walking, Dr. Carr said. Profound tiredness and weight loss is also seen in at least 30 percent of patients.

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New Jefferson Trial to Test Radiation-Emitting Beads Against Advanced Liver Cancer

Dr. Brian Carr

Dr. Brian Carr

Liver cancer specialists at Jefferson’s Kimmel Cancer Center in Philadelphia are beginning an 18-month study of a new treatment for liver cancer. The therapy entails injecting tiny beads that emit small amounts of radiation into the liver’s main artery while also blocking the blood supply feeding the cancer’s growth.

The technique, called radioembolization, has been approved by the federal Food and Drug Administration for use in inoperable liver cancer. This is the first time that the particular technology, called SIR-Spheres microspheres, which is FDA-approved for treating colon cancer that has spread to the liver, is being studied in patients with hepatocellular carcinoma, or primary liver cancer (cancer that originates in the liver). The trial, which is led by Brian Carr, M.D., FRCP, Ph.D., professor of Medical Oncology at Jefferson Medical College of Thomas Jefferson University, includes patients from the University of Texas’ M.D. Anderson Cancer Center in Houston and the University of Pittsburgh.

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