In an attempt to evaluate whether the radiation sensitizer misonidazole (MISO) could enhance the responsiveness of chemoresistant tumors, MISO was combined with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) for the treatment of BALB/c X DBA/2 F1 (hereafter called CD2F1) and C3H/HeJ mice bearing nitrosourea-resistant L1210/BCNU or KHT/CCR ...

BACKGROUND CCNU and other treatment protocols are commonly offered to owners for the treatment of dogs diagnosed with cutaneous (epitheliotropic) T-cell lymphoma (CTCL). Chemotherapy protocols provide variable benefits; they have different side-effects, and they typically require monitoring to detect drug toxicity at a non-negligible cost to the owner. At this time, even though CCNU is most oft...

The DNA sequenceselectivitiesof guanine-N7alkylation producedby three chloroethylating antitumor agents, I-(2-chloroethyl)-3-(cis-2-hy droxy)cyclohexyl-l-nitrosourea(cis-2-OH CCNU), 2-chloroethyl(meth ylsulfonyl)methanesulfonate,and 8-carhamoyl-3-(2-chloroethyl)imidazo 15,l-dl-l,2,3,5-tetrazin-4(3H)-one (mitozolomide), were examined using a modification of the Maxam and Gilbert sequencing techn...

The effect of treatment with the thymic factor thymostimulin (TP-1 ) on the survival rate of tumor-bearing mice was studied, using C57BL/6 mice inoculated with 1 x 105 Lewis lung carcinoma (3LL) cells. TP-1 given from inoculation day (4 mg/ kg, twice weekly) caused a delay in the appearance of primary tumor [14.4 ±1.1 (S.E.) days in control; 18.5 ±1.4 days in TP-1-treated animals; p < 0.05], ...

Recent studies in mouse tumor systems have indicated a potential therapeutic advantage in combining the radiosensitizer misonidazole (MISO) with cancer chemotherapy drugs. One agent the antitumor activity of which has been enhanced to a greater extent than its hematological or gastrointestinal toxicities is the nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1nitrosourea (CCNU). Recently, sensitize...

Recent studies in mouse tumor systems have indicated a potential therapeutic advantage in combining the radiosensitizer misonidazole (MISO) with cancer chemotherapy drugs. One agent the antitumor activity of which has been enhanced to a greater extent than its hematological or gastrointestinal toxicities is the nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). Recently, sensitiz...

Cediranib is an orally available, pan-VEGFR tyrosine kinase inhibitor. A previous Phase III study of patients with recurrent glioblastoma treated with this drug did not meet the primary end of progressive-free survival (PFS). We identified one patient, a 57-year-old Caucasian female who, following surgery in October 2008 and concurrent temozolomide and radiation therapy from November 8, 2008, t...

The lethal and bone marrow toxicity and antitumor activity of the cis- and trans-2-hydroxylated metabolites of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) have been correlated with their relative in vitro alkylating and carbamoylating activities. Both the isomers have considerably greater alkylating activity and shorter chemical half-lives than the parent compound and on a molar basis h...

Poly(adenosine diphosphate ribose) polymerase, a chromatin-bound enzyme, was stimulated 150 to 200% after treatment of HeLa cells with methylnitrosourea (MNU). In contrast, a slight inhibitory effect on enzyme activity was observed after treatment of cells with various concentrations of chloroethylnitrosoureas. To define precisely the differential effects of nitrosoureas on the enzyme activity,...

Two human colon carcinoma cell lines which differ greatly in their content of O'-alkylguanine-DNA alkyltransferase were analyzed for their response to l-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) and 2chloroethyl(methylsulfonyl)methanesulfonate (ClEtSoSo) before and after treatment with O6-alkyIguanines. HT29 cells contained about 17 times more alkyltransferase activity than BE cells. Th...