PURPOSE Second mitochondria-derived activator of caspase (Smac) regulates chemotherapy-induced apoptosis. Smac mimetics have been tested in clinical trials as chemosensitizers. We determined the role of Smac in modulating the chemosensitivity of esophageal squamous cell carcinoma (ESCC). EXPERIMENTAL DESIGN Smac expression was evaluated in tissues from ESCC patients with differential chemothe...

One hundred patients with non-small cell lung cancer were entered by members of the Northern California Oncology Group into a randomized Phase II trial of i.v. melphalan versus i.v. melphalan with concomitant oral misonidazole. The patients had not received prior chemotherapy. Eighty-five patients were evaluable for assessment of response and 89 were evaluable for toxicity analysis. The melphal...

Disruption of fungal cell wall should be an effective intervention strategy. However, the cell wall-disrupting echinocandin drugs, such as caspofungin (CAS), cannot exterminate filamentous fungal pathogens during treatment. For potency improvement of cell wall-disrupting agents (CAS, octyl gallate (OG)), antifungal efficacy of thirty-three cinnamic acid derivatives was investigated against Sacc...

Chloroquine was a cheap, extremely effective drug against Plasmodium falciparum until resistance arose. One approach to reversing resistance is the inhibition of chloroquine efflux from its site of action, the parasite digestive vacuole. Chloroquine accumulation studies have traditionally relied on radiolabelled chloroquine, which poses several challenges. There is a need for development of a s...

In addition to the fungal cellular membrane, the cellular antioxidant system can also be a viable target in the antifungal action of amphotericin B (AMB). Co-application of certain redox-potent natural compounds with AMB actually increases efficacy of the drug through chemosensitization. Some redox-potent chemosensitizers and AMB perturb common cellular targets, resulting in synergistic inhibit...

RNA interference is a post-transcriptional mechanism by which double-stranded RNA specifically silence expression of a corresponding gene. Small interfering double-stranded RNA (siRNA) of 21-23 nucleotides can induce the process of RNA interference. Studies from our laboratory have shown that translation of thymidylate synthase (TS) mRNA is controlled by its own protein end-product TS in a nega...

Epidemiological studies suggested that trans-resveratrol, a wine grape component, could prevent malignant tumor development. This compound also demonstrated cytostatic and cytotoxic effects on tumor cells in vitro. To obtain trans-resveratrol derivatives with a better cellular uptake and enhanced antiproliferative effects, we synthesized a triacetate derivative as well as an oligomer, epsilon-v...

Inhibitors of the breast cancer resistance protein (BCRP/ABCG2) multidrug transporter are of interest as chemosensitizers for clinical drug resistance, for improving the pharmacokinetics of substrate chemotherapeutic drugs, and in functional assays of BCRP activity for tailoring chemotherapy. The fungal toxin fumitremorgin C (FTC) is a potent and specific inhibitor of BCRP, but its neurotoxic e...

NSAIDs (non-steroidal anti-inflammatory drugs) have potential use as anticancer agents, either alone or in combination with other cancer therapies. We found that NSAIDs including celecoxib (CCB) and ibuprofen (IBU) significantly potentiated the cytotoxicity of Hsp90 inhibitors in human multidrug-resistant (MDR) cells expressing high levels of mutant p53 (mutp53) protein and P-glycoprotein (P-gp...

Development of multidrug resistance against antitumor agents is a major limiting factor for the successful chemotherapy. Currently, both amphiphilic polymeric micelles and chemosensitizers have been proposed to overcome MDR during chemotherapy. Herein, the redox-responsive polymeric micelles composed of dextran and indomethacin (as chemosensitizer) using a disulfide bond as the linker are prepa...