The hydroxymethylglutaryl-CoA reductase inhibitor lovastatin is used widely to treat hypercholesterolemia and has been shown to have cell cycle-specific effects. In these studies, we have examined the effects of combining lovastatin and paclitaxel (Taxol), a microtubule-stabilizing agent, in the human leukemia K562 and HL-60 cell lines. Isobologram analysis of cytotoxicity assays revealed that ...

The cytokinetic and cytotoxic interactions involved in combining tamoxifen, methotrexate, and 5-fluorouracil were studied in two hormone-dependent human breast cancer cell lines, 47-DN and MCF-7. These cells had measurable cytosol and nuclear estrogen receptor and cytosol progesterone receptor. Growth of the MCF-7 cells in medium containing gelding serum was stimulated maximally by addition of ...

Multidrug-resistance (MDR) represents a major cause of failure in cancer chemotherapy. The need for a reduction in MDR by natural-product-based drugs of low toxicity led to the current investigation of applying medicinal herbs in future cancer adjuvant therapy. Carthami Flos (CF), the dried flower of safflower (Carthamus tinctorius L.), is one of the most popular traditional Chinese medicinal h...

Isobolographic analysis provides a fundamental basis for assessing whether biological responses induced by mixtures of agents are greater, equal or smaller than would have been expected on the basis of the individual activities of the component agents and the concept of dose additivity. Limited in its direct application to binary mixtures, isobolographic analysis provides a conceptual framework...

We have observed the selective toxicity of mitomycin C toward hypoxic as compared to aerobic cells in vitro for three established cell lines (Chinese hamster ovary, Chinese hamster V-79, and human HeLa) and for cells from the transplantable KHT murine tumor. The magnitude of the selective toxicity was cell line dependent. We have studied the in vivo effects of mitomycin C against aerobic and hy...

We have performed isobologram analyses of the ability of tamoxifen (TAM) to alter the response to Adriamycin (ADR) and vinblastine (VBL) in human breast cancer cells. MCF-7 cells express functional receptors for estrogen and progesterone but do not express detectable levels of M(r) 170,000 glycoprotein (gp170). CL 10.3 and MCF-7ADR cells are MCF-7 variants which express gp170. CL 10.3 but not M...

Nasopharyngeal carcinoma is a rare but highly invasive cancer. As options of agents for effective combination chemoradiotherapy for advanced nasopharyngeal carcinoma are limited, novel therapeutic approaches are desperately needed. The ubiquitin ligase CHFR is known to target PARP1 for degradation and is epigenetically inactivated in nasopharyngeal carcinoma. We present evidence that PARP1 prot...

BACKGROUND Drug interactions may reveal mechanisms of drug action: additive interactions suggest a common site of action, and synergistic interactions suggest different sites of action. We applied this reasoning in a review of published data on anesthetic drug interactions for the end-points of hypnosis and immobility. METHODS We searched Medline for all manuscripts listing propofol, etomidat...

The human malaria parasite, Plasmodium falciparum, degrades nearly all its host cell hemoglobin during a short segment of its intraerythrocytic development. This massive catabolic process occurs in an acidic organelle, the digestive vacuole. Aspartic and cysteine proteases have been implicated in this pathway. We have isolated three vacuolar proteases that account for most of the globin-degradi...

Expression of the TUSC2/FUS1 tumor suppressor gene in TUSC2 deficient EGFR wildtype lung cancer cells increased sensitivity to erlotinib. Microarray mRNA expression analysis of TUSC2 inducible lung cancer cells treated with erlotinib uncovered defects in the response to oxidative stress suggesting that increasing reactive oxygen species (ROS) would enhance therapeutic efficacy. Addition of the ...