• Parasites, Hosts and Diseases
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• v.28 no.2
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• pp.79-84
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• 1990

Metabolic inhibitors which act in the process of pyrimidine salvage influenced on the uracil incorporation into nucleic acids of Toxoplasma. Inhibitors of dihydrofolate reductase, pyrimethamine and methotrexate, and inhibitors of thymidylate synthase, fluoro-uridine, fluoro·dUMP and fluoro-uracil, diminished isotopic uracil uptake in dose-dependent manners. Azauridine which suppresses do novo pyrimidine biosynthesis did not affect the salvage even in a relatively high dose. These results suggested that the activation of uracil salvage should be closely related with the function of TMP biosynthetic enzymes. The pattern of thymidine uptake had no differences between control HL-60 cells and Toxoplasma infected cells, which did not reject the specific proliferation of Texoplasma. It can be exploited to characterize the elects of various compounds related with the proliferation of Toxoplasma, especially its DNA synthesis. Key words: Toxoplasma gondii, uracil salvage, dihydrofolate reductase, thymidylate synthase TMP biosynthesis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1845-1849
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• 2014

Background: There is no standard treatment for patients with colorectal cancer (CRC) progressing after irinotecan and oxaliplatin treatment. Here we aimed to retrospectively evaluate the efficacy and tolerability of raltitrexed in combination with oral 5-fluoropyrimidine (uracil tegafur-UFT) or mitomycin C as salvage therapy in mCRC patients. Materials and Methods: A total of 62 patients who had received raltitrexed combined with UFT or mitomycin C were identified between December 2008 and June 2013. They were given raltitrexed 2.6 $mg/m^2$ (max 5 mg) i.v. on day 1 in combination with either oral UFT 500 mg/day on days 1-14 every 3 weeks (group A) or mitomycin C 6 $mg/m^2$ i.v. on day every 3 weeks (group B). Results: Forty-two patients (67.7%) were in group A and 20 (32.2%) in group B. In 15 patients (24%) grade 3/4 toxicity was observed, resulting in dose reduction, and in 13 patients (20.9%) dose delay was necessary. The median progression free survival (PFS) was 3 months (95%CI 2.65-3.34) and median overall survival (OS) was 6 months (95%CI 2.09-9.90) in the whole group. Median PFS was 3 months (95%CI 2.60-3.39) in group A vs 3 months (95%CI 1.64-4.35) in group B (p=0.90). Median OS was 6 months (95%CI 2.47-9.53) in group A vs 12 months (95%CI 2.83-21.1) in group B (p=0.46). Conclusions: The combination of raltitrexed with UFT or mitomycin C seem to be a salvage therapy option due to safety profile and moderate clinical activity in heavily-pretreated mCRC patients.

• Parasites, Hosts and Diseases
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• v.32 no.1
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• pp.19-26
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• 1994

An in uipo culturing to examine the cyst stage of ToxopLQsma gondii (ME49 strain) was Investigated using murine peritoneal macrophages, and we also examined the effect of CAMP or DHFR Inhibitors on the growth of bradyzoltes. For experiments ICR mice were Injected 1.p. with 1,500 brain cysts. At 1, 3, 5 and 7 days, peritoneal exudates were Isolated and then adherent peritoneal macrophages were cultured for 1,3,5 and 10 days. Growth pattern of bradyzoltes was measured by (3H)-uracil uptake assay and morphological pattern of pseudocysts formed in macrophages was observed Uth Glemsa stain. Mostly bradyzoites were observed In the macrophages extracted at 3 and S days post Infection. After 3 days in vitro, a number of pseudocysts were formed in the macrophages and the size of pseudocysts was increased during further 5 and 10 days in vitro culture. CAMP stimulated the growth of bradyzoltes when in uiuo 3 and 5 days and then in vitro 5 and 10 days conditions were applied. In case of.DHFR Inhibitors, pynmethamlne produced a linearly decremental effect with a cont.-dependent mode but methotrexate was not effective against Intracellular bradyzoltes or pseudocysts In this system. It was suggested that cyst-forming strain of T gondii (ME49 strain) could be maintained and cultivated in uitro by use of murine peritoneal macrophages. In uivo 3 and 5 days and then in uiko 5 and 10 days conditions appeared to be suitable for culturing of bradyzoltes. CAMP and pyrimethamine had an effect of stimulation and inhibition on the growth of bradyzolte, respectively.