Posts Tagged ‘chemotherapy’

Read about “A Segregation Analysis of Barrett’s Esophagus and Associated Adenocarcinomas”

March 30, 2010

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”

March 30, 2010

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

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

March 29, 2010

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

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

March 1, 2010

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