PURPOSE Angiogenesis is a critical step in the establishment, growth, and metastasis of solid tumors, and combination of antiangiogenic agents with chemotherapy is an attractive therapeutic option. We investigated the potential of ixabepilone, the first in a new class of antineoplastic agents known as epothilones, to synergize with antiangiogenic agents to inhibit tumor growth. EXPERIMENTAL D...

Androgen-deprivation therapy, usually with combined androgen blockade, is standard initial treatment for advanced prostate cancer. With failure of initial treatment, as indicated by rising prostate-specific antigen (PSA) levels, second-line hormonal therapy is usually instituted. Over the past several years, it has become increasingly clear that systemic chemotherapy has an important role in ho...

Microtubule stabilizing agents (MTSA) are known to inhibit vascular smooth muscle cell (VSMC) proliferation and migration, and effectively reduce neointimal hyperplasia and restenosis. Epothilones (EPOs), non-taxane MTSA, have been found to be effective in the inhibition of VSMC proliferation and neointimal formation by cell cycle arrest. However, effect of EPOs on apoptosis in hyper-proliferat...

Previous studies on the drug content of pelleted tubulin polymers suggest that peloruside A binds in the laulimalide site, which is distinct from the taxoid site. In a tubulin assembly system containing microtubule-associated proteins and GTP, however, peloruside A was significantly less active than laulimalide, inducing assembly in a manner that was most similar to sarcodictyins A and B. Becau...

BACKGROUND Drug-resistance and therapy failure due to drug-drug interactions are the main challenges in current treatment against Human Immunodeficiency Virus (HIV) infection. As such, there is a continuous need for the development of new and more potent anti-HIV drugs. Here we established a high-throughput screen based on the highly permissive TZM-bl cell line to identify novel HIV inhibitors....

Numerous studies have implicated mutations in tubulin or the overexpression of specific tubulin genes in resistance to microtubule-targeted drugs. Much less is known about the role of accessory proteins that modulate microtubule behavior in the genesis of drug resistance. Here, we examine mitotic centromere-associated kinesin (MCAK), a member of the kinesin family of microtubule motor proteins ...