Ted isophosphoramide bromo mustard. Fraction 2 nitroimidazole TH 302 acts as a sensor of the oxygen concentration, the release LY2109761 of the DNA alkylating Br IPM in hypoxic regions of tumors. TH 302 is st Aerobic to more strongly under hypoxic conditions compared with conditions in cancer cell lines in vitro and in vivo tumor xenograft targeted hypoxic tumor cells. The combination of a professional normoxic selective chemotherapeutic agent with a classical hypoxia compartmentselective as TH 302 should complement one Eliminate Ren approach for all subpopulations of tumor cells without a corresponding increase in the systemic toxicity of t. However, the combination of a classic chemotherapeutic agent and TH 302 independent effect on tumor subcompartments Of one another. The sequence and timing of administration of both agents k Can under certain circumstances Attach the therapeutic index of the combination.
If the cans are moved, then put The pharmacological effects of the first agent on the activity t of the second agent, either pharmacokinetic or pharmacodynamic. Peculiar to this particular approach to cancer therapy, k nnte One of the agents affecting the F-specific Books of other agents, compared to administration alone. For example, an effect can on the Tumorgef System obtained Hen or reduce the Ausma and the distribution of tumor hypoxic regions. Cytostatic or cytotoxic effects in normoxic chamber k Nnte the rate of oxygen consumption in cells and on the size E or volume of hypoxic chamber. Here, we investigated the efficacy of combination therapy of TH 302 in xenograft models of different companies with different chemotherapy drugs. We also examined whether the sequence and dose dependence Observed dependence of the regime of the efficacy and toxicity of t in the groups of combination therapy.
There have been studies to guide decisions about what to study diseases and combinations of chemotherapy in future clinical trials to help. Criteria for the prioritization of disease and chemotherapy in combination with TH 302 are by adults Conditions with unmet medical needs and attitudes, in which chemotherapy drugs are approved as a single agent. Materials and methods of human cancer cell lines H460 and Calu 6 non-small cell lung cancer, cancer cells, c Lon HT29 cells, PC3 prostate cancer, cancer cells HT1080 fibrosarcoma Hs766t, the SU. 86.86, BxPC 3 and MIA PaCa 2 pancreatic cancer cells and A375 melanoma cells were obtained from American Type Culture Collection. All cell lines were used as monolayer cultures in normal ATCC recommended media with 10% f Fetal K Calf serum in a humidified atmosphere at 37 ° C re erg Complements under 95% air and cultured for 5% CO 2. Stew2 melanoma cancer cells were from Dr. Lee Cranmer f Arizona Cancer Center and in RPMI 1640 with 10% Fetal K Calf serum erg Complements was. Irinotecan and cisplatin chemotherapy and were was from Sigma Chemical Co., docetaxel, Sanofi Aventis, gemcitabine was Synchem OHG was doxorubicin from the deck Bioservice LLC, temazolomide and pemetrexed were from AK Scientific Inc. TH 302 was synthesized at Syngene. Docetaxel was dissolved in 5% ethanol St and 5% Cremophor EL water. All other drugs were in saline Gel solution St. TH 302 dosage.