PM01183 is a novel marine-derived covalent DNA binder in clinical development. PM01183 is structurally similar to trabectedin (yondelis, ecteinascidin-743) except for the C subunit, and this modification is accompanied by different pharmacokinetics in cancer patients. We here characterize the interaction of PM01183 with the nucleotide excision repair (NER) pathway in comparison with trabectedin...

To investigate the possibility that anticancer drugs combined with cytokines may show increased activity, human tumor cells were treated with combinations of human recombinant interleukin 1 alpha (rIL-1 alpha) and etoposide (VP-16). The cytotoxicity of these combinations was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay using rIL-1 alpha-sensitive A375-C6 ...

The effects of vincristine (VCR) in combination with methotrexate (MTX) and other antitumor agents were evaluated by cell growth inhibition assay using a human acute lymphoblastic leukemia cell line (MOLT-3). The data were analyzed with the aid of an isobologram using the concept of an envelope of additivity (G. G. Steel and M. J. Peckman, Int. J. Radiat. Oncol., 5:85-91, 1979). Simultaneous ex...

The area method for Euclidean constructive geometry was proposed by Chou, Gao and Zhang in the early 1990’s. The method can efficiently prove many non-trivial geometry theorems and is one of the most interesting and most successful methods for automated theorem proving in geometry. The method produces proofs that are often very concise and human-readable. In this paper, we provide a first compl...

PURPOSE c-Src inhibition in cancer cells leads to an abrogation of invasion but a variable effect on apoptosis. The pathways downstream of c-Src promoting survival are not well characterized. Because cancer therapy that both decreases invasion and induces significant apoptosis would be ideal, we sought to characterize the mechanisms of resistance to c-Src inhibition. EXPERIMENTAL DESIGN c-Src...

The effects of vincristine (VCR) in combination with methotrexate (MTX) and other antitumor agents were evaluated by cell growth inhi bition assay using a human acute lymphoblastic leukemia cell line (MOLT-3). The data were analyzed with the aid of an isobologram using the concept of an envelope of additivity (G. G. Steel and M. J. Peckman, Int. J. Radiât.Oncol., 5: 85-91, 1979). Simultaneous ...

Erlotinib is a tyrosine kinase inhibitor approved for the treatment of patients with advanced non–small cell lung cancer (NSCLC). In these patients, erlotinib prolongs survival but its benefit remains modest because many tumors expresswild-type (wt) EGFRor develop a second-site EGFRmutation. To test drug combinations that could improve the efficacy of erlotinib, we combined erlotinib with quina...

PURPOSE The Src family of kinases (SFKs) regulate multiple signal transduction cascades and influence proliferation, motility, survival, and angiogenesis. Dasatinib inhibits SFKs, which leads to cytotoxicity, cell cycle arrest, apoptosis, and decreased invasion of cancer cells. Signal transducer and activator of transcription 3 (STAT3) is a latent transcription factor that regulates survival an...

Elevated serum levels of hepatocyte growth factor (HGF) and high tumor expression of c-Met are both indicators of poor overall survival from ovarian cancer (OVCA). In the present study, we evaluated the role of the HGF signaling pathway in OVCA cell line chemoresistance and OVCA patient overall survival as well as the influence of HGF/c-Met signaling inhibition on the sensitivity of OVCA cells ...

BACKGROUND/AIM Somatostatin (SST) analogs are mainstay for controlling tumor proliferation and hormone secretion in carcinoid patients. Recent data suggest that extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation may potentiate the anti-tumor effects of SST analogs in carcinoids. Additionally, ERK1/2 phosphorylating agents have been shown to suppress biomarker expression in carci...