Clin Cancer Res
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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.