Clin Cancer Res
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The purpose of this research was to develop a quantitative real-time reverse transcription-PCR (RT-PCR) for CK19-mRNA and evaluate its clinical potential for the molecular detection of occult carcinoma cells in the peripheral blood of breast cancer patients. ⋯ The developed method is highly sensitive and specific, and can be used for high-throughput continuous monitoring and quantification of circulating epithelial cells in the peripheral blood of breast cancer patients.
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The spicamycin analogue KRN5500 is a nucleoside-like antibiotic with broad spectrum activity against human solid tumor models. It appears to possess a novel mechanism of action directed against the endoplasmic reticulum and Golgi apparatus with effects on protein processing. A Phase I trial was undertaken to determine the maximum tolerated dose (MTD), dose-limiting toxicities, and pharmacokinetic behavior of KRN5500 given as a 1-h i.v. infusion for 5 consecutive days every 3 weeks. ⋯ The MTD of KRN5500, when given as a 1-h i.v. infusion for 5 consecutive days, was 2.9 mg/m(2)/day. The only suggestion of therapeutic activity observed in this study was disease stabilization in three patients with chemorefractory colorectal cancer. Administering KRN5500 as a continuous i.v. infusion with the objective of prolonging systemic exposure to potentially cytotoxic concentrations of the drug should be considered.
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The purpose of this study was to establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and preliminary activity of BMS-188797 administered weekly. ⋯ The MTD and the recommended Phase II dose of weekly BMS-188797 is 50 mg/m(2). The drug demonstrates antitumor activity in taxane-refractory solid tumors and is now being evaluated in combination with carboplatin.
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Comparative Study
Endometriosis and its treatment with danazol or lupron in relation to ovarian cancer.
It has been hypothesized that circulating androgens may be involved in the development of ovarian cancer. The androgenic medication, danazol, and the antiandrogenic medications, leuprolide and nafarelin, are commonly used in the treatment of endometriosis. We assessed the associations between the use of these medications and ovarian cancer. ⋯ Danazol, but not leuprolide/nafarelin, increased the risk of ovarian cancer. This supports the hypothesis that androgen excess may be associated with the development of ovarian cancer.
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Apicidin, a histone deacetylase inhibitor, is a novel cyclic tetrapeptide that exhibits potent antiproliferative activity against various cancer cell lines. The aim of this study was to examine the potential of apicidin to induce apoptosis in human Bcr-Abl-positive leukemia cells and to assess the mechanism of apicidin-induced apoptosis. ⋯ These results indicate that apicidin effectively induces the apoptosis of Bcr-Abl-positive leukemia cells through the activation of the mitochondrial pathway-dependent caspase cascades. The down-regulation of Bcr-Abl mRNA might also be one of the mechanisms implicated in the apicidin-mediated apoptosis in the K562 cells. This study provides the rationale to additionally investigate apicidin as a potential therapeutic agent for the drug-resistant Bcr-Abl-positive leukemia cells.