arc111 and Weight-Loss

arc111 has been researched along with Weight-Loss* in 1 studies

Other Studies

1 other study(ies) available for arc111 and Weight-Loss

ArticleYear
Bone marrow and tumor cell colony-forming units and human tumor xenograft efficacy of noncamptothecin and camptothecin topoisomerase I inhibitors.
    Molecular cancer therapeutics, 2008, Volume: 7, Issue:10

    Topoisomerase I (TopoI), an established anticancer target, is an enzyme producing a single-strand DNA break during transcription. Several noncamptothecin TopoI inhibitors have been identified. One of these, ARC-111, was compared with two clinically used camptothecins, topotecan and irinotecan/SN-38. In mouse and human bone marrow colony formation [colony-forming units granulocyte-macrophage (CFU-GM)] assays, the IC(90) values were 519 and 331 nmol/L for topotecan and SN-38 mouse CFU-GM and were 19 and 26 nmol/L for human CFU-GM, giving mouse to human differentials of 28- and 13-fold. ARC-111 produced IC(90) values of 28 nmol/L in mouse and 6.2 nmol/L in human CFU-GM, thus only a 4.5-fold differential between species. Human bone marrow CFU-GM was more sensitive to topotecan than were several human cancer cell lines, but ARC-111 cytotoxicity was similar for human bone marrow CFU-GM and the seven human tumor cell lines tested. In HCT-116 xenografts, tumor growth delays (TGD) were 17 days for irinotecan and 20 days for ARC-111. In HT-29 xenografts, the TGD was 9 days for both irinotecan and ARC-111. Both ARC-111 and docetaxel had a TGD of 21 days in NCI-H460 xenografts, and both ARC-111 and gemcitabine had a TGD of 7 days in MiaPaCa2 xenograft. Current TopoI inhibitors have broad antitumor activity in human tumor xenografts that is not achieved in the clinic. This may be due to greater sensitivity of human bone marrow than mouse to the cytotoxicity of these agents. It may be possible to achieve similar levels of ARC-111 in patients as in mice allowing improved antitumor activity.

    Topics: Animals; Antineoplastic Agents; Body Weight; Bone Marrow; Camptothecin; Cell Line, Tumor; Cell Proliferation; Confidence Intervals; Dose-Response Relationship, Drug; Flow Cytometry; Humans; Inhibitory Concentration 50; Irinotecan; Male; Mice; Mice, Inbred BALB C; Naphthyridines; Neoplastic Stem Cells; Topoisomerase I Inhibitors; Topotecan; Weight Loss; Xenograft Model Antitumor Assays

2008