Lomustine (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea; CCNU) is a synthetic orally active nitrosourea marketed in the past few years for the chemotherapy of carcinoma, particularly of the brain. The major toxic effects are bone marrow suppression with leucopenia and thrombocytopenia and gastrointestinal effects with nausea and vomiting. Progressive lung changes resulting from cytotoxic drugs ...

N,N'-Bis(2-chloroethyl)-N-nitrosourea (BCNU) is a sub strate for a microsomal enzyme of mouse liver. The reaction requires NADPH, and the product is 1,3-bis(2-chloro ethyl)urea. This activity is also found in mouse lungs but not in several other tissues. With reaction conditions under which BCNU is not chemically degraded, the Km for BCNU with liver microsomes is 1.7 mM; nicotine is a competiti...

A dose-response relation for the cytotoxic activity of chloroethylnitrosourea cancer chemotherapeutic agents in cell culture has been developed. Data for the activity of 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea, and 1-(2-chloroethyl)-3-(piperidine-3,6-dion-3-yl)-1-nitrosourea against 9L rat b...

In quantitative therapeutic studies 1,3-bis(2-chloroethyl)-1-nitrosourea (NSC 409962) and 1-(2.-chloroethyl)-1-nitrosourea (NSC-47547) have been shown to have marked activity against intraperitoneal (I.P.) L1210 leukemia when administered by the I.P., subcutaneous, or oral route. This class of compounds is the first to be ob served to possess an encouraging degree of activity against intracereb...

1. The intraperitoneal injection of N-methyl-N-nitrosourea (100mg/kg) caused a partial inhibition of protein synthesis in several organs of the rat, the maximum effect occurring after 2-3h. 2. In the liver the inhibition of protein synthesis was paralleled by a marked disaggregation of polyribosomes and an increase in ribosome monomers and ribosomal subunits. No significant breakdown of polyrib...

Bifunctional alkylating agents are known to cross-link DNA by simultaneously alkylating two guanine residues located on opposite strands. Despite this apparent requirement for bifunctionality, 1-(2-chloroethyl)-1-nitrosoureas bearing a single alkylating function were found to cross-link DNA in vitro. Cross-linking was demonstrated by showing inhibition of alkali-induced strand separation. Exten...

The possibility was examined that the carbamoylating activity of some chloroethylnitrosoureas could interfere with the activity of normal human cells to survive treatment with these drugs; 1-(2-chloroethyl)-3-(frans-4-hydroxycyclohexyl)-1 -nitrosourea, which has strong carbamoylating activity, inhibited the rejoining of drug or X-ray-induced DMA strand breaks in IMR-90 cells, whereas the noncar...

Two human colon tumor cell lines were examined for their responses to 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea treatment when maintained as cultured cell lines and xenograft tumors in nude mice. One tumor line, HT, was resistant to 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea treatment both in tissue culture and in vivo. The other tumor line, BE, was sensitive to 1-(2-ch...

Incubation at approximately physiological conditions of amino acids, peptides, and proteins with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea or cyclohexyl isocyanate resulted in carbamoylation of the alpha-amino groups of amino acids, the terminal amino groups of peptides and proteins and the epsilon-amino groups of lysine moieties. Carbamoylation of the alpha-amino groups and the terminal ami...

BACKGROUND A meta-analysis of chemotherapy for glioblastoma multiforme (GBM) was performed. We sought to update prior analyses by focusing exclusively on GBM, including new trials of novel treatments, assessing effectiveness of individual treatment categories and presenting data in a clinically useful format. METHODS A search of MEDLINE and EMBASE was conducted for randomised controlled trial...