Wr-1065 dose toxicity

This study tested the effect of amifostine's active metabolite, the free thiol, WR, on the cytotoxicity of standard anticancer drugs against human A WR was clearly radioprotective when assessed by colony formation and incorporation of [3H]thymidine. However, when the number of adherent cells was evaluated, radioprotection appeared to be slight and evident only in logarithmically growing cells. Alone, WR demonstrated an antiproliferative effect that was related to dose ( mM) and was evident by lowered counts of adherent cells 48 h after exposure. 50% inhibitory concentration (IC50) values were determined for each of 16 different anticancer drugs in the presence and absence of the highest nontoxic dose of. Second, because. First, at doses necessary for optimal radioprotection there are toxic side effects in humans including hypotension and nausea. WR was clearly radioprotective when assessed by colony formation and incorporation of [3H]thymidine. However, when the number of adherent cells was evaluated, radioprotection appeared to be slight and evident only in logarithmically growing cells. Alone, WR demonstrated an antiproliferative effect that was related to dose ( mM) and was evident by lowered counts of adherent cells 48 h after exposure. However, when the number of adherent cells was evaluated, radioprotection appeared to be slight and evident only in logarithmically growing cells. Alone, WR demonstrated an antiproliferative effect that was related to dose ( mM) and was evident by lowered counts of adherent cells 48 h after exposure. WR was clearly radioprotective when assessed by colony formation and incorporation of [3H]thymidine. Normal tissue toxicity limits radiation therapy and could depend on the extent of damage to the vascular endothelium Aminothiols such as WR [N- (2-mercaptoethyl)-1,3-diaminopropane] provide radioprotection for normal tissues, but little is known about how the aminothiols specifically affect the endothelium. These studies also suggest that WR might be . Mar 01,  · These findings are consistent with the hypothesis that WR is a catalytic inhibitor of topo II in mammalian cells. WR was active against both an acute infection of HIV-1 and a chronic infection of SIV. The data suggest that the non-toxic drug amifostine. Sept Lower, non-toxic concentration of WR did not protect cells from death, however it was effective in significantly decreasing delayed genomic.

  • Exposure of CHO cells to microM of WR for 30 min did not effect cell c . The effects of WR (2-((aminopropyl)amino)ethanethiol) on cell cycle progression, topoisomerase (topo) II alpha activity, and topo II alpha phosphorylation in Chinese hamster ovary (CHO) cells have been investigated.
  • Exposure of CHO cells to microM of WR for 30 min did not effect cell c . The effects of WR (2-((aminopropyl)amino)ethanethiol) on cell cycle progression, topoisomerase (topo) II alpha activity, and topo II alpha phosphorylation in Chinese hamster ovary (CHO) cells have been investigated. These studies also suggest that WR might be expected to reduce the toxicity and clastogenicity in clinical applications of etoposide or quinolone antibiotics in dose-limiting normal tissues. Publication types. These findings are consistent with the hypothesis that WR is a catalytic inhibitor of topo II in mammalian cells. Alone, WR demonstrated an antiproliferative effect that was related to dose ( mM) and was evident . exposed to WR for 2 h before irradiation (Cs y rays, 1 Gy/min). Nov A lower dose, μM WR, completely inhibited SIV replication in 2 of The data suggest that the non-toxic drug amifostine may be a. As seen in Figure 1, the dose-response curve for MCF7 cells incubated with WR prior to paclitaxel (Taxol tends to fall below that of paclitaxel alone. Jan 01, · WR had no statistically significant effect on the cytotoxicites of any of the anticancer agents tested in either cell line. As seen in Figure 1, the dose-response curve for MCF7 cells incubated with WR prior to paclitaxel (Taxol tends to fall below that of paclitaxel alone. WR had no statistically significant effect on the cytotoxicites of any of the anticancer agents tested in either cell line. Cells exposed to 4 mM WR immediately following the first 4 Gy radiation dose and then washed free h before exposure to a second Gy dose, which was also followed by a 30 min exposure to WR, increased the surviving fraction by 80% over the value obtained for cells not exposed to WR during their split-dose radiation treatment. Amifostine thiol (WR) dihydrochloride can protect normal tissues from the toxic effects of certain cancer drugs and activate p53 through a JNK-dependent signaling . Customer Review. (WR) were tested for toxicity and radioprotective effect in cultured human cells using viability (reproductive death) as an indicator. lular drug toxicity was not significant for cells in suspension at RADIOPROTECTION OF V79 CELLS BY WR UNDER AEROBIC CONDITIONS incubation with amifostine or WR en-. patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Free Radic Biol Med. Author manuscript; available in PMC Dec Free Radic Biol Med. Author manuscript; available in PMC Dec The result showed that WR attenuated the severity of 6-OHDA-induced catalepsy (P <) when compared with 6-OHDA-lesioned rats. Four groups of 6-OHDA-lesioned rats received vehicle or one of the three different doses of WR (20, 40 and 80 μg/2 μl/rat), respectively for 3 days before 6-OHDA administration. These studies also suggest that WR might be . Apr 01,  · These findings are consistent with the hypothesis that WR is a catalytic inhibitor of topo II in mammalian cells. Feb Here, we demonstrate that oral WR is an effective radioprotector against otherwise lethal doses of radiation directed to the upper abdomen. Here we describe the effects of WR and WR on the toxicity induced by CDDP and 5FU as single agents and in combination. Jan 01, · The maximal tolerated dose (MTD) for CDDP in the combination is approximately 1/3 of the dose without 5FU. To protect against toxicity induced by an increased CDDP dose, a chemoprotector such as WR may be used. Here we describe the effects of WR and WR on the toxicity induced by CDDP and 5FU as single agents and in combination. The maximal tolerated dose (MTD) for CDDP in the combination is approximately 1/3 of the dose without 5FU. To protect against toxicity induced by an increased CDDP dose, a chemoprotector such as WR may be used. incubation with amifostine or WR en-. patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. The phosphorylated parent compound of WR, WR, has been demonstrated in one study. tissue toxicity induced by irradiation (), most studies have examined the effects on non-endothelial cells. One such drug, the aminothiol WR [N-(2-mercaptoethyl)- 1,3-diaminopropane], is an effective radioprotector and anti-mutagen (9). It is demonstrated that WR strongly inhibits the clastogenesis of the topo II poisons etoposide and clinafloxacin at clinically attained exposure levels. In non-tumor-bearing mice toxic deaths . In this paper we show results of preliminary studies indicating that CC caused lethal delayed hepatotoxicity at therapeutic antineoplastic doses. Oral mucositis evaluation included WHO toxicity grading, a validated oral. WR was administered during the second and third cycle as an oral rinse. The U.S. Department of Energy's Office of Scientific and Technical Information. The U.S. Department of Energy's Office of Scientific and Technical Information. Higher apparent volumes of distribution (Vc and Vss) and higher mean residence time (MRT. The pharmacokinetics of WR [S(3-aminopropylamino)ethanethiol] were investigated following iv, intraduodenal, and intraportal administrations in the rhesus monkey. Pharmacokinetic parameters were estimated by compartmental modeling of plasma concentration data from min and min iv infusions. When amifostine is converted to an active metabolite (WR), appear to improve survival or lung injury due to PQ toxicity at the doses administered. However, it is toxic when administered at high doses required for cysteamine, and WR, for finding an optimal radioprotective agent for ARS. 50% inhibitory concentration (IC50) values were determined for each of 16 different anticancer drugs in the presence and absence of the highest nontoxic dose of WR from concentration-response curves constructed in triplicate. This study tested the effect of amifostine's active metabolite, the free thiol, WR, on the cytotoxicity of standard anticancer drugs against human A ovarian and MCF7 breast cancer cell lines in vitro, using the well-characterised sulphorhodamine B assay.
  • In non-tumor-bearing mice toxic deaths were delayed ca 50 days after a single iv dose of micrograms/kg and as much as 70 days after 10 micrograms/kg was given ip. In this paper we show results of preliminary studies indicating that CC caused lethal delayed hepatotoxicity at therapeutic antineoplastic doses.
  • We do not sell to patients. Amifostine thiol dihydrochloride Chemical Structure CAS No.: Get it tomorrow October 12 by noon. For research use only. Amifostine thiol (WR) dihydrochloride can protect normal tissues from the toxic effects of certain cancer drugs and activate p53 through a JNK-dependent signaling pathway. Initial single-dose toxicity and pharmacokinetic studies were performed in and tumor cells being both less able to convert amifostine to WR Purpose: N-(2-mercaptoethyl)1,3-diaminopropane (WR), is the active metabolite of amifostine, a broad spectrum cytoprotective agent used in conjunction. 50% inhibitory concentration (IC50) values were determined for each of 16 different anticancer drugs in the presence and absence of the highest nontoxic dose of WR from concentration-response curves constructed in triplicate. This study tested the effect of amifostine's active metabolite, the free thiol, WR, on the cytotoxicity of standard anticancer drugs against human A ovarian and MCF7 breast cancer cell lines in vitro, using the well-characterised sulphorhodamine B assay. Department of Energy Office of Scientific and Technical Information. Search terms: Advanced search options. U.S. Mesna has been given in combination with ifosfamide in different doses and alkaline phosphatase is necessary to form its active metabolite, WR CDDP at 7 mg/kg enhanced leukopenia caused by 5FU at mg/kg to 20% and thrombocytopenia to 40%; WR reduced leukopenia and prevented thrombocytopenia induced by the combination. WR failed to prevent 5FU toxicity, but the maximum tolerated dose of CDDP in the combination with 5FU (at mg/kg) could be increased from 3 to 7 mg/kg. Protection by WR of the toxicity induced by the combination of cisplatin and 5-fluorouracil We evaluated the effects of WR and its metabolite WR on in vitro growth inhibition by 5-fluorouracil (5FU) and cisplatin (CDDP) and the effect of WR on in vivo toxicity and antitumor effect of 5FU and CDDP. three doses of amifostine (56, and mg/Kg) after a cisplatin single injection (10 brane bound alkaline phosphatase, resulting in WR and other.