Department of Medicine

Case Western Reserve University School of Medicine & UH Case Medical Center

Prostate Cancer at CWRUmedicine

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Worldwide, prostate cancer is one of the most common types of cancer found in men. Learning more about prostate cancer and treatment options can help you and your loved ones take an active part in making choices about care.

* Click here to read about new research conducted by the Division of Hematology Oncology at Case Western Reserve University.

The prostate is a chestnut-sized gland below the bladder, which contributes most of the fluid that combines with a man’s sperm to make semen.

Prostate cancer is the most common cancer other than skin cancer in American men and is the second leading cause of cancer death in men.

The American Cancer Society estimates that more than 234,000 men will be diagnosed with prostate cancer in 2006. Incidence rates for the disease are higher for African-American men than for white men.

Other Prostate Cancer Survivors ::

Harry Belafonte
Musician, actor and social activist Harry Belafonte

Robert De Niro
Actor Robert De Niro

Rudy Giuliani
Former New York City Mayor Rudy Giuliani

John Kerry
U.S. Senator & 2004 Presidential candidate John Kerry

Nelson Mandela
Former President of South Africa Nelson Mandela

Read about "Gab2 Promotes Hematopoietic Stem Cell Maintenance & Self-Renewal with STAT5"

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BACKGROUND ::
Grb2-associated binding (Gab) adapter proteins play major roles in coordinating signaling downstream of hematopoietic cytokine receptors. In hematopoietic cells, Gab2 can modulate phosphatidylinositol-3 kinase and mitogen associated protein kinase activities and regulate the long-term multilineage competitive repopulating activity of hematopoietic stem cells (HSCs). Gab2 may also act in a linear pathway upstream or downstream of signal transducer and activator of transcription-5 (STAT5), a major positive regulator of HSC function. Therefore, we aimed to determine whether Gab2 and STAT5 function in hematopoiesis in a redundant or non-redundant manner.

METHODOLOGY & PRINCIPAL FINDINGS ::
To do this we generated Gab2 mutant mice with heterozygous and homozygous deletions of STAT5. In heterozygous STAT5 mutant mice, deficiencies in HSC/multipotent progenitors were reflected by decreased long-term repopulating activity. This reduction in repopulation function was mirrored in the reduced growth response to early-acting cytokines from sorted double mutant c-Kit(+)Lin(-)Sca-1(+) (KLS) cells. Importantly, in non-ablated newborn mice, the host steady-state engraftment ability was impaired by loss of Gab2 in heterozygous STAT5 mutant background. Fetal liver cells isolated from homozygous STAT5 mutant mice lacking Gab2 showed significant reduction in HSC number (KLS CD150(+)CD48(-)), reduced HSC survival, and dramatic loss of self-renewal potential as measured by serial transplantation.

CONCLUSIONS & SIGNIFICANCE ::
These data demonstrate new functions for Gab2 in hematopoiesis in a manner that is non-redundant with STAT5. Furthermore, important synergy between STAT5 and Gab2 was observed in HSC self-renewal, which might be exploited to optimize stem cell-based therapeutics.

Read the full article on CWRUmedicine.org

Read about "A Segregation Analysis of Barrett's Esophagus and Associated Adenocarcinomas"

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Familial aggregation of esophageal adenocarcinomas, esophagogastric junction adenocarcinomas, and their precursor Barrett’s esophagus (BE) has been termed familial BE (FBE). Numerous studies documenting increased familial risk for these diseases raise the hypothesis that there may be an inherited susceptibility to the development of BE and its associated cancers. I

n this study, using segregation analysis for a binary trait as implemented in S.A.G.E. 6.0.1, we analyzed data on 881 singly ascertained pedigrees to determine whether FBE is caused by a common environmental or genetic agent and, if genetic, to identify the mode of inheritance of FBE. The inheritance models were compared by likelihood ratio tests and Akaike’s A Information Criterion. Results indicated that random environmental and/or multifactorial components were insufficient to fully explain the familial nature of FBE, but rather, there is segregation of a major type transmitted from one generation to the next (P < 10(-10)). An incompletely dominant inheritance model together with a polygenic component fits the data best.

For this dominant model, the estimated penetrance of the dominant allele is 0.1005 [95% confidence interval (95% CI), 0.0587-0.1667] and the sporadic rate is 0.0012 (95% CI, 0.0004-0.0042), corresponding to a relative risk of 82.53 (95% CI, 28.70-237.35) or odds ratio of 91.63 (95% CI, 32.01-262.29). This segregation analysis provides epidemiologic evidence in support of one or more rare autosomally inherited dominant susceptibility allele(s) in FBE families and, hence, motivates linkage analyses.

Read the full article on CWRUmedicine.org

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

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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"

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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

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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

DNA Screening for Colon Cancer

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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. Watch and learn as CWRUmedicine Hematology Oncology’s, Dr Sanford Markowitz speaks about this new breakthrough.
Learn more at CWRUmedicine.org

New test developed by CWRUmedicine researchers may reduce colon cancer

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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

Study shows soy is not only safe for breast cancer survivors, it may also be beneficial

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Cleveland Plain Dealer – Despite soy’s healthy profile, many women who have had breast cancer are reluctant to eat soy foods. And many cancer doctors caution their patients against doing so.

The concern stems from substances in soy called isoflavones, which behave like weak estrogen in the body. Estrogen, a hormone that controls the menstrual cycle, has been shown to increase the risk of breast cancer in women.

Here’s how: Estrogen stimulates cells to divide. Cancer arises from DNA mutations in cells — errors that occasionally happen during cell division. If one of these spontaneous mutations occurs in a gene that controls cell growth and division, it could lead to the development of cancer.

Another worry is the interaction between isoflavones and tamoxifen, a breast cancer drug that blocks estrogen from cells.

But a study published in the December issue of the Journal of the American Medical Association may set those fears aside.

The study, by researchers at Vanderbilt University, says soy foods are safe — and possibly beneficial — for breast cancer survivors. They looked at 5,042 women in China who were breast cancer survivors and divided them into four groups based on how much soy they ate. Women who ate low amounts of soy consumed an average of about a half-cup of soy milk a day, while the high-soy-consumption group had about three cups a day.

After four years, 10.3 percent of those who consumed the least soy died, compared with 7.4 percent of those who had the most, leading researchers to theorize that soy did not increase breast cancer occurrence and may have had some protective effect.

CWRUmedicine’s breast cancer specialist, Dr. Paula Silverman, often gets questions from her patients about whether it’s safe to eat soy. Her answer: Go ahead and enjoy.

“I don’t think there was good data about that, ever,” says Silverman, medical director of the Breast Cancer Program at University Hospitals Case Medical Center. “I’ve always felt that soy was probably safe.” Some years ago, Silverman heard a lecture by a physician who made a compelling argument that plant estrogens and human estrogens are not the same. Silverman thinks the weak estrogens in soy may act more like tamoxifen than like human estrogen. “The bottom line is dietary soy is safe for breast cancer survivors,” Silverman says.

The National Institutes of Health says it remains unclear what role dietary soy or soy isoflavone might play in cancer risk. While several large population studies have reported that higher soy intake is associated with a decreased risk of developing various types of cancers, including breast, prostate and colon cancer, other research suggests soy does not have this effect.

Read the Full Story on CWRUmedicine.com

WVIZ PBS Ideastream talk with CWRUmedicine faculty about "confronting colon cancer"

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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

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