5% Triton X 100 in PBS, and finally rinsed twice with PBS. For H2AX determinati

It is the fourth most common cancer and second leading cause of death from cancer throughout the world. The incidence varies up to 10 fold across the world with the greatest percentage in China, followed by South Korea, South American countries and Japan. Irinotecan is an S phase specific, semisynthetic derivative of camptothecin which interferes with ARN-509 分子量 DNA replication and cell division through its potent inter action with the enzyme topoisomerase I. CPT 11 is fre quently used in the treatment of gastric cancer, and showes a good response rate varying from 14% to 23% as single agent and 45% to 70% in combination, with a median time to progression of 3 months in single agent and 4 6 months in combination.<br><br> Recent studies suggested that the methylation of the heparan sulfate 6 O endosulfatase promoter is associated with better survival of lung adenocarcinoma patients, and silencing SULF2 through methylation could increase sensitivity to topoisomerase 1 inhibitors such as camptothecin chemotherapy. WRN gene is a RecQ family member with both exo nuclease and helicase activities. AUY922 分子量 WRN CpG island hypermethylation is a common event in epithelial and mesenchymal tumorigenesis. Besides, WRN hypermethy lation in colorectal tumors is a predictor of good clinical response to irinotecan, which is commonly used in the treatment in colorectal cancer. However, up to now, the correlation between SULF2, WRN promoter methy lation and the chemosensitivity of irinotecan in gastric cancer has not been studied yet. In the present work, we collected 102 fresh tissues from pathologically diagnosed gastric carcinoma patients to evaluate the potential correlation.<br><br> We used methyla Alvocidib Flavopiridol tion specific PCR to detect the promoter methylation of SULF2 and WRN, and adopted the HDRA method to test the chemosensitivity of irinotecan. Also the associ ation of patients clinicopathological parameters and methylation status of SULF2 and WRN was analyzed. Methods Patients and samples preparation All specimens and relevant clinical data were obtained from the Department of Oncology and General Surgery of Drum Tower Hospital, from 2009 through 2011. There were 75 men and 27 women with a median age of 62 years. Demographic variables in cluding age, gender and stage of gastric cancer are com pleted. Tumors were staged according to the criteria of the 2003 AJCC staging system for gastric cancer.<br><br> Each tumor was considered suitable for the study based on the presence of 80% tumor cells. The patients did not undergo chemotherapy or radiotherapy prior to surgery. Informed consent was obtained from all patients and the protocols for our study were approved by the Human Research Protective Committee of Drum Tower Hospital. This may elicit functional synergy between PARP 1 and ATM, consistent with the embryonic lethality observed in the double ATM PARP 1 knockout. Conclusions Substantial differences in PARP 1 activation by ionizing radiation and alkylating agents have been reported and our data suggest that PARP 1 is not a major determi nant of cell survival to DNA double strand breaks as long as the level of oxidative stress is limited.