Read about “Direct detection and quantification of abasic sites for in vivo studies of DNA damage & repair”

Use of chemotherapeutic agents to induce cytotoxic DNA damage and programmed cell death is a key strategy in cancer treatments. However, the efficacy of DNA-targeted agents such as temozolomide is often compromised by intrinsic cellular responses such as DNA base excision repair (BER). Previous studies have shown that BER pathway resulted in formation of abasic or apurinic/apyrimidinic (AP) sites, and blockage of AP sites led to a significant enhancement of drug sensitivity due to reduction of DNA base excision repair. Since a number of chemotherapeutic agents also induce formation of AP sites, monitoring of these sites as a clinical correlate of drug effect will provide a useful tool in the development of DNA-targeted chemotherapies aimed at blocking abasic sites from repair. Here we report an imaging technique based on positron emission tomography (PET) that allows for direct quantification of AP sites in vivo. For this purpose, positron-emitting carbon-11 has been incorporated into methoxyamine ([(11)C]MX) that binds covalently to AP sites with high specificity. The binding specificity of [(11)C]MX for AP sites was demonstrated by in vivo blocking experiments. Using [(11)C]MX as a radiotracer, animal PET studies have been conducted in melanoma and glioma xenografts for quantification of AP sites. Following induction of AP sites by temozolomide, both tumor models showed significant increase of [(11)C]MX uptake in tumor regions in terms of radioactivity concentration as a function of time, which correlates well with conventional aldehyde reactive probe (ARP)-based bioassays for AP sites.

Read the full article on CWRUmedicine.org

Read about “Non-Hodgkin’s lymphoma in the elderly”

The expansion of older population segments and the continuous increase in the incidence of non-Hodgkin’s lymphoma (NHL) makes this group of neoplasms an important and growing problem. Older NHL patients have increased risk of therapy-related toxicity as a result of age-related physiological changes and frequent co-morbidities. A functional assessment of the elderly patient is necessary to determine the likelihood of tolerating and responding to therapy. The comprehensive geriatric assessment (CGA) is one multidisciplinary tool that has been applied successfully to older cancer patients and aids in identification of subjects who will or will not benefit from anti-neoplastic treatment. Although indolent lymphomas present more frequently at advanced stage, randomized trials do not show better outcomes with early therapy, supporting close observation until specific therapeutic indications arise. Use of the monoclonal antibody rituximab as a single agent or in combination with chemotherapy improves survival and has become the standard of care in first-line treatment. Radioimmunoconjugates, bendamustine, and other monoclonal antibodies as well as novel targeted agents also are active against indolent lymphomas. Diffuse large B-cell lymphoma is an aggressive but potentially curable disease. Several trials performed exclusively in elderly patients have demonstrated improved response rates and survival with the addition of rituximab to CHOP (cyclophosphamide, doxorubicin [adriamycin], vincristine, prednisone) chemotherapy in the front-line setting. Salvage chemotherapy followed by autologous haematopoietic cell transplant (autoHCT) has been shown to have better failure-free and overall survival in randomized trials involving younger patients. Highly selected individuals up to age 70 years may attain long-term survival benefit from autoHCT, although transplant-related mortality is higher than in younger patients.

Read the full article on CWRUmedicine.org

Dr. Afshin Dowlati discusses a new way to predict effectiveness of chemotherapy

Doctors often have trouble knowing who might respond to certain cancer treatments. “We kind of give chemotherapy and wish for a good result,” says Dr. Afshin Dowlati. That could change.

Dowlati led a study that revealed lung cancer patients with low levels of a molecule that controls cellular interaction have twice the chance of responding to chemotherapy than those with high levels. Those levels can also predict how likely a patient is to live a year after diagnosis. The difference could help patients decide whether to try chemotherapy, drugs or pursue alternative therapies, Dowlati says.

Learn more at CWRUmedicine.org

New test developed by CWRUmedicine researchers may reduce colon cancer

Colon cancer is the second most deadly cancer in the U.S. despite being the most preventable. The American Gastroenterological Association (AGA) recently announced concern that people will neglect colon cancer screening during this economic climate.

Screening is recommended in both sexes over age 50 and earlier if a patient has a family history of this disease. However, some people put it off due to fear of having a colonoscopy, which can be both invasive and expensive. As more people lose health insurance coverage, the high cost of this procedure may lead many more people to forego screening.

Sanford Markowitz, MD, CWRUmedicine oncologist and colon cancer researcher of the University Hospitals Ireland Cancer Center at University Hospitals Case Medical Center, has developed a less expensive, non-invasive test for this disease.

About the test:

• The non-invasive test detects DNA markers for colon cancer using a stool sample that is taken at home
• The DNA Stool Test is available now at the doctor’s office, or can be easily ordered by the doctor
• Although the test isn’t covered by insurance, the cost is significantly lower
• Patients with negative results will not need to commit time and money to having a colonoscopy; patients with positive results will move forward with  colonoscopy to provide more information
• It is 80 percent effective and while colonoscopy is still the most effective test, it is not useful if patients are avoiding it altogether
• The American Cancer Society added the test to its screening guidelines last year

Learn more at CWRUmedicine.org

CWRUmedicine’s Marvin T. Nieman, Ph.D. awarded The American Society of Hematology 2010 Scholar Award

The program is designed to support hematologists who have chosen a career in research by providing partial salary or other support during that critical period required for completion of training and achievement of status as an independent investigator.

The awards are for two years at $50,000 per year for fellows and $75,000 per year for junior faculty.

Read more at CWRUmedicine.org

WVIZ PBS Ideastream talk with CWRUmedicine faculty about “confronting colon cancer”

According to the American Cancer Society, colon cancer is the second-leading cause of cancer-related deaths in the United States. Tonight at 7:30 p.m. on WVIZ/PBS Ideastream, several CWRUmedicine’s Hematology Oncology specialists are featured in “Confronting Colon Cancer” – an in-depth look at the disease from detection and diagnosis through treatment. Tune in tonight or watch the special online below.

To learn more about cancer research, visit CWRUmedicine.org

Dr. Neal Meropol discusses how To Decipher the Health Care Debate

Rising unemployment, escalating health plan costs and 50 million uninsured Americans can’t be ignored. That’s why the House and Senate have outlined bills to increase the number of insured people, improve care quality and outlaw denial of health care for risk reasons. We caught up with Dr. Neal Meropol, section chief of hematology and oncology at University Hospitals, to learn where to get the latest facts on the health care debate.

Use reputable sources. Meropol suggests looking to Web sites such as the Kaiser Family Foundation, PBS or The New York Times — all offer side-by-side comparisons of the House and Senate bills, from eligibility to prescription drug issues.

But be objective. “You’ve got to be careful because a lot of [articles] are going to be colored by politics,” Meropol says. Read newspapers rather than one-sided outlets such as blogs. Or check out educational resources such as The New England Journal of Medicine.

Stay flexible. Keep an open mind while the debate outcome is being decided, Meropol says. “Neither of these plans calls for anybody to alter their current health plan. Both plans on the table will protect individuals.”

Read more at Cleveland Magazine

Dr Afshin Dowlati discusses a new way to predict effectiveness of chemotherapy

Doctors often have trouble knowing who might respond to certain cancer treatments. “We kind of give chemotherapy and wish for a good result,” says Dr. Afshin Dowlati of CWRUmedicine’s Hematology Oncology. That could change. Dowlati led a study that revealed lung cancer patients with low levels of a molecule that controls cellular interaction have twice the chance of responding to chemotherapy than those with high levels. Those levels can also predict how likely a patient is to live a year after diagnosis. The difference could help patients decide whether to try chemotherapy, drugs or pursue alternative therapies, Dowlati says.

Read more at Cleveland Magazine ::
http://tiny.cc/ssiZv

DNA Screening for Colon Cancer Video

Download now or watch on posterous

DNA Screening for Colon Cancer.flv (5669 KB)

It is estimated that colon cancer will kill 50,000 people in the United States this year. But found early, that number could be lowered substantially. So why do so many still die from it? The answer and the solution can be found in a medical laboratory in Cleveland, Ohio.

A team of researchers led by Sanford Markowitz, M.D., Ph.D. at the Case Western Reserve University Department of Medicine has found a way to detect colon cancer quickly and non-invasively.
Learn more at CWRUmedicine.org

Med City News:: Tour of new Cancer Hospital

Plain Dealer editors and reporters recently toured University Hospitals Case Medical Center’s 375,000-square-foot, 120-bed cancer hospital that’s going up at the corner of Euclid Avenue and Cornell Drive, according to the Cleveland newspaper. Although the structure was topped out some months ago, much work remains to be done on the interior. The $250 million building is scheduled to open in spring 2011.

Read more on Med City News