Altered expression of FAS system is related to adverse clinical outcome in stage I-II breast cancer patients treated with adjuvant anthracycline-based chemotherapy
ABSTRACT To determine the prognostic value of Fas receptor and Fas ligand (FasL) as apoptosis-related biomarkers in the context of chemoresponsiveness in breast cancer (BC) patients submitted to anthracycline-based adjuvant therapy.
Fas and FasL were investigated by immunohistochemistry in surgical samples collected from 167 stage I-IIa-b BC patients enrolled in a prospective clinical trial using epirubicin plus cyclophosphamide in the adjuvant setting.
Fas and FasL were significantly associated with tumor stage (P < 0.0001). Multivariate analysis indicated that stage, loss of Fas (relative risk, 8.5 and 9.12; P < 0.0001) and FasL up-regulation (relative risk, 2.38 and 2.88; P = 0.01) were independent prognostic variables influencing both disease-free survival (DFS) and overall survival (OS). A Cox analysis using a four-category Fas/FasL phenotype (+/-, +/+, -/+, -/-) as a stratification factor evidenced a highly positive association between Fas/FasL phenotype and the cumulative hazard of relapse and death in the entire series of patients. We also estimated the DFS and OS for different combinations of the pathological-tumor-node-metastasis (TNM) stage and Fas/FasL by using the K sample log-rank exact test demonstrating that significantly shorter DFS and OS were observed in Fas-negative and FasL-positive patients in both stage I-IIa and IIb.
Data presented herein demonstrated that, according to a number of in vitro studies, the prognosis for BC patients receiving adjuvant anthracycline-based chemotherapy strongly depends on the Fas/FasL status. Therefore, a concomitant altered pattern of Fas/FasL expression seems to configure an aggressive tumor phenotype linked to disease progression.
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Article: 5Fluorouracil[Show abstract] [Hide abstract]
ABSTRACT: 5-Fluorouracil (5-FU) has been the mainstay of colorectal cancer treatment for over 40 years. However, response rates for 5-FU in advanced colorectal cancer are modest. Although combining 5-FU with the newer chemotherapeutic agents oxaliplatin and irinotecan has improved response rates, new therapeutic strategies are necessary. Understanding the molecular mechanism by which tumors become resistant to 5-FU is needed if drug resistance is to be overcome. Tumor drug resistance is often due to insufficient chemotherapy-induced cell death. In this chapter, we describe the mechanisms of action of 5-FU, focusing on 5-FU-induced cell death. In the future, strategies aimed at increasing the effectiveness of 5-FU may target the cell death and cell survival pathways that are activated by this drug.
- Biochemical Journal 01/1991; 272(2):281-95. · 4.78 Impact Factor