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5-fluorouracil (5-FU) is widely used in the treatment of cancer. Over the past 20 years, increased understanding of the mechanism of action of 5-FU has led to the development of strategies that increase its anticancer activity. Despite these advances, drug resistance remains a significant limitation to the clinical use of 5-FU. Emerging technologies, such(More)
Resistance to chemotherapy and molecularly targeted therapies is a major problem facing current cancer research. The mechanisms of resistance to 'classical' cytotoxic chemotherapeutics and to therapies that are designed to be selective for specific molecular targets share many features, such as alterations in the drug target, activation of prosurvival(More)
PURPOSE We studied the prognostic value of thymidylate synthase (TS) expression in primary colorectal cancer (CRC) and the role of TS expression as a predictor of chemotherapeutic benefit in patients treated with adjuvant chemotherapy. PATIENTS AND METHODS TS expression was immunohistochemically assessed on tumor sections from 862 patients with CRC Dukes'(More)
Polyamines have been shown to play a role in the growth and survival of several solid tumors, including colorectal cancer. We identified the polyamine catabolic enzyme spermidine/spermine N(1)-acetyltransferase (SSAT) as being one of the most highly inducible genes in two DNA microarray screens to identify novel determinants of response to chemotherapeutic(More)
Chemotherapy-induced interleukin-8 (IL-8) signaling reduces the sensitivity of prostate cancer cells to undergo apoptosis. In this study, we investigated how endogenous and drug-induced IL-8 signaling altered the extrinsic apoptosis pathway by determining the sensitivity of LNCaP and PC3 cells to administration of the death receptor agonist tumor necrosis(More)
We have evaluated the role played by BRCA1 in mediating the phenotypic response to a range of chemotherapeutic agents commonly used in cancer treatment. Here we provide evidence that BRCA1 functions as a differential mediator of chemotherapy-induced apoptosis. Specifically, we demonstrate that BRCA1 mediates sensitivity to apoptosis induced by(More)
BACKGROUND BRCA1-mutant breast tumors are typically estrogen receptor alpha (ER alpha) negative, whereas most sporadic tumors express wild-type BRCA1 and are ER alpha positive. We examined a possible mechanism for the observed ER alpha-negative phenotype of BRCA1-mutant tumors. METHODS We used a breast cancer disease-specific microarray to identify(More)
PURPOSE To define the value of thymidylate synthase (TS), Ki-67, and p53 as prognostic markers in patients with stage II and III colon carcinoma. PATIENTS AND METHODS We retrospectively analyzed the prognostic value of TS, Ki-67, and p53 in 706 patients with Dukes' B (291 patients) or Dukes' C (415 patients) colon carcinoma who were treated with either(More)
Isolated central nervous system (CNS) relapse involving the brain parenchyma is a rare complication of systemic non-Hodgkin lymphoma. We retrospectively analyzed patient characteristics, management, and outcomes of this complication. After complete response to initial non-Hodgkin lymphoma treatment, patients with isolated CNS relapse with the brain(More)
PURPOSE Hodgkin's lymphoma (HL) has no standard of care for patients who are relapsed or refractory to autologous stem-cell transplantation (ASCT). This phase II study examined safety and activity of panobinostat in this population. PATIENTS AND METHODS Panobinostat 40 mg was administered orally three times per week. The primary end point was objective(More)