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The cellular response to the antitumor drug cisplatin is complex, and resistance is widespread. To gain insights into the global transcriptional response and mechanisms of resistance, we used microarrays to examine the fission yeast cell response to cisplatin. In two isogenic strains with differing drug sensitivity, cisplatin activated a stress response(More)
ATP-binding cassette (ABC) transporters are a large family of proteins implicated in physiological cellular functions. Selected components of the family play a well-recognized role in extruding conventional cytotoxic antitumor agents and molecularly targeted drugs from cells. Some lines of evidence also suggest links between transporters and tumor cell(More)
BACKGROUND Topoisomerase I is required for DNA relaxation during critical cellular functions. The identification of camptothecins as specific enzyme inhibitors and their clinical efficacy have stimulated extensive efforts to exploit topoisomerase I as a tumor target and explain the putative mechanisms of antitumor-specific action. OBJECTIVE This review(More)
Camptothecins are potent antitumor agents that stabilize the covalent binding of topoisomerase I to DNA forming a reversible ternary complex which, following collision with the replication forks, converts the single-strand breaks into lethal double-strand breaks. This cytotoxic mechanism has been originally ascribed to the closed lactone form, because(More)
The camptothecins are among the most promising antitumor agents endowed with a unique mechanism of action, because they act through inhibition of DNA topoisomerase I, an enzyme involved in regulating critical cellular functions including DNA replication, transcription and recombination. On the basis of the pharmacological interest of camptothecins in cancer(More)
In an attempt to synthesize potential anticancer agents acting by inhibition of topoisomerase I (Topo I) a new series of oxyiminomethyl derivatives in position 7 of camptothecin (CPT) was prepared. The synthesis relied on the condensation of 20S-CPT-7-aldehyde or 20S-CPT-7-ketones with alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl O-substituted(More)
The molecular mechanism of cisplatin uptake remains poorly defined and impaired drug accumulation may be implicated in the acquisition of resistance to cisplatin. Thus, we used cell lines of different tumor types (ovarian carcinoma A2780 and IGROV-1, osteosarcoma U2-OS, cervix squamous cell carcinoma A431) and stable cisplatin-resistant sublines, exhibiting(More)
The role of HER2 in predicting response to doxorubicin (DXR) therapy in breast cancer was evaluated in vivo in a series of breast carcinomas from 220 patients with tumors larger than 2.5 cm and treated with 3 cycles of DXR (75 mg/m(2)) as neoadjuvant chemotherapy. Patients with HER2-positive tumors were more frequently responsive to DXR treatment compared(More)
ST1968 is a novel hydrophilic camptothecin (CPT) derivative of the 7-oxyiminomethyl series. Because ST1968 retained ability to form remarkably stable cleavable complexes, this study was done to investigate its preclinical profile of antitumor activity in a large panel of human tumor models, including irinotecan-resistant tumors. Although less potent than(More)
Atypical retinoids are potent inducers of apoptosis, but activation of the apoptotic pathway seems to be independent of retinoid receptors. Previous studies with a novel adamantyl retinoid, ST1926, have shown that apoptosis induction is associated with an early genotoxic stress. To better understand the relevance of these events, we have selected a subline(More)