Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tissue levels of two proteolytic enzymes, plasminogen activator and cathepsin B - like cysteine proteinase, which were found to be increased in malignant tumors and to be proportional to tumor metastatic potential in some instances, have been determined in a panel of solid metastasizing tumors in mice. The examination of B16 melanoma, MCa mammary carcinoma and of two lines of Lewis lung carcinoma with widely different potential to spontaneously metastasize, showed no correlation between metastatic potential and the tissue content of the proteinases considered. The treatment of the animals with cytotoxic antitumor drugs (CCNU, GANU, cisplatin, and cyclophosphamide) or with antimetastatic drugs acting with a mechanism unrelated with cytotoxicity (ICRF 159 and DM-COOK) caused only marginal inhibition in some instances, whereas no meaningful pattern of inhibition either based in terms of metastatic potential of the tumor or on drug mechanism of action was recognizable. A direct involvement of the two proteinases examined in the process of metastasis in the tumor panel used is thus not apparent, although a more complex interaction with other latent proteinases and inhibitors might be operative.
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PMID:Proteinases and proteinase inhibition by cytotoxic and antimetastatic drugs in transplantable solid metastasizing tumors in mice. 389 94

The antitumor effects of GANU have been examined in a panel of mouse tumors for which data appear to be lacking in the literature. GANU has significant activity against P388 leukemia and TLX5 lymphoma, and also against the solid tumors B16 melanoma and Lewis lung carcinoma; pulmonary metastases of this tumor are particularly sensitive to the effects of GANU. The effects of GANU on TLX5 lymphoma and Lewis lung carcinoma are less pronounced than those of BCNU and CCNU, as already reported for L1210 leukemia. In contrast with other results obtained with this tumor, chlorozotocin has a less pronounced effect than GANU, and virtually none in lung metastases of Lewis lung carcinoma.
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PMID:Antitumor effects of GANU and other nitrosourea derivatives against transplantable leukemias and solid tumors in mice. 622 44

A new water-soluble nitrosourea derivative, methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), was tested for antitumor activity against murine tumors (L1210 and P388 leukemias, B16 melanoma, and Lewis lung carcinoma) and BC-47 rat bladder carcinoma, and the results were compared with those for four other nitrosourea derivatives; chlorozotocin, 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (GANU), 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1- nitrosourea hydrochloride (ACNU), and 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU). MCNU was shown not only to have a broad antitumor spectrum against all the tumors tested, but also to be effective over a wide range of dosages. The antitumor activity of MCNU was superior to those of GANU and chlorozotocin and similar to those of ACNU and methyl-CCNU. Furthermore, MCNU and other nitrosoureas were evaluated for toxicity in BDF1 female mice with respect to body weight changes. Weight loss in mice given MCNU at a dose lethal to 10% of the mice was relatively mild and the treated mice regained body weight most rapidly to the pretreatment level among all groups receiving the above drugs at equitoxic doses. These results may suggest that MCNU is a new nitrosourea derivative worthwhile to perform clinical trials.
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PMID:Antitumor activity and toxicity of methyl 6-[3-(2-chloroethyl)- 3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside in experimental animals. 651 Jun 39

Sugar alcohols, such as mannitol, sorbitol, galactitol, and inositol, selectively reduced the acute lethal toxicity of 1-(2-chloroethyl)-3-(methyl alpha-D-glucopyranos-6-yl)-1-nitrosourea (MCNU) without reducing its antitumor activity. Fifty mg MCNU/kg killed all CD2F1 mice within about 10 days, while the administration of 3,000 mg sugar alcohols/kg immediately prior to MCNU protected mice from the lethal toxicity and all survived. The amelioration of MCNU toxicity by sugar alcohols was dose-dependent. Pretreatment with mannitol 1 day before MCNU administration was effective. In addition, a series of five daily treatments with lower doses of mannitol was also effective. This protection was accompanied by the reduction of both body weight loss and myelosuppression. The antitumor effects of MCNU on P388 leukemia and Lewis lung carcinoma were not significantly altered by mannitol treatment. These phenomena were not limited to MCNU, the lethal toxicity of GANU, ACNU, Me-CCNU, and mitomycin C also being reduced by mannitol treatment.
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PMID:Reduction of lethal toxicity of chloroethylnitrosoureas by sugar alcohols without loss of antitumor activity. 680 55