To define prognostic impact of EpsteinBarr virus (EBV) infection in diffuse large

The excision repair cross-complementation group 1 (ERCC1) enzyme plays a rate-limiting role in the nucleotide excision repair pathway and is associated with resistance to platinum-based chemotherapy. The purpose of this study was to evaluate the role of ERCC1 expression as a predictive marker of survival in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) treated with cisplatin-based concurrent chemoradiotherapy (CCRT). ERCC1 expression was assessed by immunohistochemical staining. The median age of the 45 patients analysed was 56 years (range 27–75 years), and 82% were men; 73% of all specimens showed high expression of ERCC1. The overall tumour response rate after CCRT was 89%. The median follow-up was 53.6 months (95% CI, 34.5–72.7 months). The 3-year progression-free survival (PFS) and overall survival (OS) rates were 58.7 and 61.3%, respectively. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 3-year PFS (83.3 vs 49.4%, P=0.036) and OS (91.7 vs 45.5%, P=0.013) rates. Multivariate analysis showed that low expression of ERCC1 was an independent predictor for prolonged survival (HR, 0.120; 95% CI, 0.016–0.934, P=0.043). These results suggest that ERCC1 expression might be a useful predictive marker of locally advanced SCCHN in patients treated with cisplatin-based CCRT.

Background: Gastric cancer with bone marrow metastases is known to pursue a rapidly deteriorating clinical course. We conducted a retrospective analysis to evaluate clinical manifestations and prognosis of gastric cancer patients with bone marrow metastases. Methods: Between September 1994 and February 2006, 39 gastric cancer patients with pathologically confirmed bone marrow dissemination were selected. Results: The majority of the patients showed younger age, poorly differentiated adenocarcinoma or signet ring cell carcinoma, thrombocytopenia, anemia, elevated lactate dehydrogenase and alkaline phosphatase. Poor prognostic factors for survival were serum sodium ≤133 mmol/l [relative risk (RR) 4.57; 95% CI 1.99–10.52; p < 0.001], the presence of lung metastasis (RR 3.47; 95% CI 1.48–8.15; p = 0.007) and the presence of peritoneal seeding (RR 2.17; 95% CI 1.06–4.43; p = 0.036). Median survival durations after bone marrow metastases for patients without any adverse factors (n = 19, 48.7%) and those with 1–3 adverse factors (n = 20, 51.3%) were 67 and 23 days, respectively (p = 0.013). Patients without any adverse factors did benefit from palliative chemotherapy (p = 0.048). Conclusion: We suggest that gastric cancer patients with bone marrow metastases should receive more tailored therapies according to different risk factors in order to enhance survival.

To characterize the radiation-enhancing effects on human cancer cells and underlying mechanisms of celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, and to ascertain whether its effects are COX-2 dependent. Clonogenic cytotoxicity assays and radiation survival assays after treatment with celecoxib F radiation were done on four human cancer cell lines that expressed differential COX-2 levels. Stably COX-2 knocked down or overexpressed cell lines were developed, and clonogenic assays, apoptosis assays, or cell cycle change measurements were conducted after treatment with celecoxib F radiation. Prostaglandin E 2 (PGE 2 ) was applied to medium after treatment with celecoxib F radiation to determine whether the radiation-enhancing effect associated with celecoxib results from reduced generation of prostaglandin. Celecoxib's radiation-enhancing effect was observed in COX-2-expressing A549 and NCI-H460 cells but was not observed in the COX-2 nonexpressing MCF-7 and HCT-116 cells. Celecoxib's radiation-enhancing effects in A549 cells were shown to disappear after the administration of COX-2 knocked down. In contrast, the HCT-116 cells were radiosensitized by celecoxib after being transfected with COX-2 expression vector. The addition of PGE 2 after treatment with celecoxib F radiation had no significant effects on celecoxib's radiation-enhancing effects in A549 and COX-2 transfected HCT-116 cells. Radiation-induced G 2 -M arrest was enhanced and sustained in the COX-2-overexpressing cells compared with that seen in COX-2 low-expressing cells. Celecoxib or NS-398 effected no changes or attenuated radiation-induced G 2 -M arrest in the COX-2-overexpressing cells but further enhanced the radiation-induced G 2 -M arrest in the COX-2 low-expressing cells. Celecoxib's radiation-enhancing effects seem to occur in a COX-2 expression-dependent manner in the cancer cells. This effect does not seem to be the result of reduced PGE 2 generation. Celecoxib may exert an inhibitory effect on enhanced radiation-induced G 2 -M arrest in the COX-2-overexpressing cells, which may allow the arrested cells to enter mitosis and die after radiation, but may also further enhance radiation-induced G 2 -M arrest in the COX-2 low-expressing cells, by virtue of another mechanism. (Cancer Res 2005; 65(20): 9501-9)