Clin Cancer Res
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Cyclooxygenase-2 (COX-2) has been suggested to be associated with carcinogenesis. In hepatocellular carcinoma (HCC), the expression pattern of COX-2 protein has been well correlated with the differentiation grade, suggesting that abnormal COX-2 expression plays an important role in hepatocarcinogenesis. We investigated the expression pattern and clinical significance of COX-2 in HCC tissues. ⋯ The inhibitory effect on each cell line was identified in 10 microM NS-398 and was significantly strong in 100 microM NS-398. All cell lines exhibited apoptosis, which was identified by 4'-6-diamidino-2-phenylindole staining. In conclusion, COX-2 may be a determinant of the differentiation grade of HCC, and the inhibition of COX-2 can induce growth suppression of hepatoma cell lines via induction of apoptosis.
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Randomized Controlled Trial Clinical Trial
Role of tumor necrosis factor on toxicity and cytokine production after isolated hepatic perfusion.
Isolated limb or liver perfusion with tumor necrosis factor (TNF) and melphalan results in regression of advanced cancers in the majority of treated patients. However, the contribution of TNF to the efficacy of isolation perfusion with melphalan has not been demonstrated conclusively in random assignment trials. Furthermore, TNF is an inflammatory cytokine and may be associated with significant systemic and regional toxicity. This study was conducted to characterize the toxicity and secondary cytokine production attributable to TNF by comparing these parameters in patients undergoing isolated hepatic perfusion (IHP) using melphalan with or without TNF. ⋯ Addition of TNF to melphalan during IHP results in significant differences in post-IHP production of IL-6 and IL-8 with associated changes in mean arterial blood pressure and greater regional toxicity, as reflected in higher levels of serum bilirubin. However, these measurable differences were transient and did not appear to be of major clinical consequence. Prior to its routine use, the benefit of TNF in isolation perfusion should be demonstrated in random assignment trials.
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The lack of a standardized methodology for quantifying DNA ploidy and S-phase fraction (SPF) by flow cytometry is hindering routine use of these markers in breast cancer management. In a retrospective clinical multicenter study, we validated a standardized flow cytometry protocol. We tested 633 frozen T(1)T(2), N(0)N(1), M(0) breast tumors obtained in four institutions. ⋯ In node-negative patients, SPF was the only predictor of DFS (P = 0.01), whereas in node-positive patients, the risk of relapse increased with both high SPF (P = 0.003) and estrogen receptor negativity (P = 0.004). Low SPF values distinguished grade II tumors with a particularly good outcome. Our results strongly support the use of SPF in multicenter studies and clinical trials and suggest that node-negative patients with slowly proliferating tumors do not require systemic adjuvant therapy.
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Angiogenesis is essential for tumor growth and metastasis. It is a complex, dynamic process that is coordinated by several classes of angiogenic factors. One candidate family is the Tie2 tyrosine kinase, whose expression is restricted largely to endothelial cells. Tie2 has three known ligands, angiopoietin (Ang)-1, Ang-2, and Ang-4, that have different functional effects but play a requisite role in embryonic vessel remodeling. Because there are only limited data on the Tie2 pathway in human breast cancer, and our previous data have suggested that breast tumors establish a blood supply by vascular remodeling, we have investigated the expression of Ang-1, Ang-2, Ang-4, and Tie2 in a series of normal and neoplastic human breast tissues. ⋯ These findings suggest that the Ang/Tie2 pathway plays a significant role in human breast tumor angiogenesis but provide no initial evidence for direct regulation of the pathway by estrogen.
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Although rare, the morbidity and mortality from brain tumors are significant. Chemotherapy has made only a small impact on these tumors. The human T98G glioblastoma multiforme cell line was used as a brain tumor model. ⋯ In the tumor growth delay determination of the s.c. tumor, the sequential treatment regimen was more effective than the simultaneous treatment regimen. However, when the same treatments were administered to animals bearing intracranial T98G tumors, the survival of animals receiving the simultaneous treatment regimen increased from 41 days for those treated with BCNU alone to 102 days for animals treated with the combination, whereas animals receiving the sequential treatment regimen survived 74 days. Treatment with the protein kinase Cbeta inhibitor decreased T98G glioblastoma multiforme angiogenesis and improved treatment outcome with BCNU.