The paper describes the antitumor activity of a newly-developed hormonocytostatic drug testiphenon--a complex ether of 5 alpha-dihydrotestosterone and chlorphenacyl (17 beta-[n-di/2-chloroethyl/aminophenylacetate]-5 alpha-androstan-17 beta-ol-3-on). Its antitumor properties were studied in 15 models of transplantable solid tumors and systemic neoplasms of mice and rats such as sarcoma 298, sarcoma 37, sarcoma-180, Lewis lung epidermoid carcinoma, carcinoma of the forestomach-5, large bowel adenocarcinoma, Harding-Passey's melanoma, cervical cancer-5, mammary adenocarcinoma Ca-755, hemoblastosis La, plasmacytoma MOPC-406, Rauscher's erythroblastosis, Walker's carcinosarcoma 256, sarcoma 45, alveolar carcinoma of the mammary gland and DMBA-induced mammary tumors of mice. The spectrum of antitumor activity of testiphenon proved wider than those of its components or other estrogeno-cytostatic drugs--phenestrol and estracyt. The drug is specifically intended for selective action upon target tissues for androgens and tumors developing from the said tissues.

AbstractThe ureas (I) and (IV) are synthesized from the alkylisocyanates (II) and the dimethylaminoethylamine (III) and nitrosated to give the corresponding nitrosoalkylureas (V).

The effect of methylcobalamin on 3H-methotrexate uptake by tumor and normal tissues of mice with mammary adenocarcinoma (Ca-755) was studied. Methylcobalamin stimulated the rate of 3H-methotrexate influx into the tumor and small intestine but did not change its influx into the spleen. The effect was dependent on the dose of methylcobalamin. Comparative analysis of the kinetic differences in 3H-methotrexate influx and efflux in tumor and susceptible host tissues revealed the optimal dose of methylcobalamin 0.01 mg/kg to improve the antitumor drug action.

Chemischer InformationsdienstVolume 16, Issue 17 Natural Products ChemInform Abstract: SYNTHESIS AND STUDY OF DERIVATIVES OF 5-BROMO-, 6-NITRO-, AND 5-BROMO-6-NITRO-1-GLYCOSYLISATINS L. V. EKTOVA, L. V. EKTOVASearch for more papers by this authorV. N. TOLKACHEV, V. N. TOLKACHEVSearch for more papers by this authorI. V. YARTSEVA, I. V. YARTSEVASearch for more papers by this authorT. D. PARAMONOVA, T. D. PARAMONOVASearch for more papers by this authorN. A. LESNAYA, N. A. LESNAYASearch for more papers by this authorZ. P. SOFYINA, Z. P. SOFYINASearch for more papers by this authorS. S. MARENNIKOVA, S. S. MARENNIKOVASearch for more papers by this authorE. V. CHEKUNOVA, E. V. CHEKUNOVASearch for more papers by this authorM. N. PREOBRAZHENSKAYA, M. N. PREOBRAZHENSKAYASearch for more papers by this author L. V. EKTOVA, L. V. EKTOVASearch for more papers by this authorV. N. TOLKACHEV, V. N. TOLKACHEVSearch for more papers by this authorI. V. YARTSEVA, I. V. YARTSEVASearch for more papers by this authorT. D. PARAMONOVA, T. D. PARAMONOVASearch for more papers by this authorN. A. LESNAYA, N. A. LESNAYASearch for more papers by this authorZ. P. SOFYINA, Z. P. SOFYINASearch for more papers by this authorS. S. MARENNIKOVA, S. S. MARENNIKOVASearch for more papers by this authorE. V. CHEKUNOVA, E. V. CHEKUNOVASearch for more papers by this authorM. N. PREOBRAZHENSKAYA, M. N. PREOBRAZHENSKAYASearch for more papers by this author First published: April 30, 1985 https://doi.org/10.1002/chin.198517299AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume16, Issue17April 30, 1985 RelatedInformation

The lipid-bound sialic acid (LSA) levels increased in the metastasizing Lewis lung carcinoma (3LL) and significantly decreased in blood plasma of the tumour-bearing mice after cyclophosphamide treatment correlating with the drug therapeutic effect. 5-fluorouracil that was less active in the used therapeutic doses did not cause similar changes in the LSA levels. No correlation was found between the LSA levels in adenocarcinoma 755 and the drug antitumour activity. It was observed that the content of hematoside, GM1 and GD1b sharply increases and GD3 and GD1a levels significantly decrease under the cyclophosphamide treatment of the Lewis tumour.

Leukemia L1210 cells with acquired resistance to 1-methyl-1-nitrosourea (MNU) (L1210/MNU) and 1.3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (L1210/BCNU) were developed from leukemia L1210 cells sensitive to these drugs (L1210/0). The modal chromosome number of leukemia L1210/MNU and L1210/BCNU cells increases from 40 (L1210/0) to 41. It was shown that in leukemia L1210/MNU cells the inhibition of DNA synthesis after MNU administration in a therapeutic dose (80 mg/kg) is lasted within 24 hours, while that in leukemia L1210/0 cell--within 96 hours. After administration of BCNU (20 mg/kg) inhibition of DNA synthesis in leukemia L1210/BCNU cells reached of 50% of control in comparison with practically complete inhibition of DNA synthesis in leukemia L1210/0 cells. Centrifugation on alkaline sucrose density gradients revealed no differences in the rate of sedimentation of leukemia L1210/0, L1210/MNU and L1210/BCNU cell lysates. After 1 hour treatment with MNU of mice bearing L1210/MNU and L1210/0 leukemia cells single-strand breaks in DNA were determined. After 4 hours these strand-breaks retained in leukemia L1210/0 cells, but were eliminated in leukemia L1210/MNU cells. Administration of BCNU to mice with leukemia L1210/0 and L1210/BCNU cells resulted in both cases in the production of DNA aggregates. There is no complete cross-resistance between MNU and BCNU which allows a substitution of these drugs providing for the increase in their therapeutic efficiency.

The results of an experimental evaluation of a prolonged action antitumor drug--prolotestone are presented. The drug is a mixture of steroids of the androstane series, 2 alpha-methylhydrotestosterone and its three esters. The preparation has been approved for medication. Prolotestone treatment in the dose of 14 mg once in two weeks produced a high antiblastogenic effect in rats with hormone-dependent cancer of the mammary gland induced by dimethylbenz(a)anthracene. It was shown in tests involving the use of a number of transplantable tumors that prolotestone potentiates the antitumor effect of sarcolysin and mitigates its untoward side-effects. The preparation is practically non-toxic, possesses a high anabolic index, has a beneficial effect on hepatic function and lowers the glucocorticoid function of the adrenals. It is thought that application of the drug should not be limited to the treatment of breast cancer.

AbstractMan erhält das Bis‐chJorethyl‐aminoprolinesterdihydrochlorid (V) ausgehend von 1‐Tosy1‐4‐amino‐L‐prolinester(I) über die Zwischenstufen (II)‐(IV) auf dem skizzierten Weg.

The mechanism of the stimulant effect of methylcobalamine on the growth of mouse adenocarcinoma 755 was studied. More rapid growth of adenocarcinoma 755 under the cobalamine coentzyme effect is consequent on an increased proliferative pool with the stable parameters of the mitotic cycle and minimal death of tumour cells. Apparently, inhibition of DNA synthesis in the greater S-phase cell subpopulation potentiated the antitumour effect of methotrexate combined with methylcobalamine.

The rate of metastasization was estimated by calculating the coefficients of the metastases involved lung mass and the number of metastatic nocules. The experiments with melanoma B-16 and Lewis carcinoma have shown a marked stimulating effect of removing the primary tumor node on metastases growth, the number of metastatic nodules in the lung being less compared with control, but these were larger. In experiments with carcinoma RL-67 the removal of the primary node would not stimulate the growth of metastases. Adenocarcinoma 755 showing no metastases in routine percutaneous inoculation would not give metastases too after the removal of the primary tumor.

Extraction in low salt concentration followed by centrifugation allows rat liver nuclear chromatin to be divided into two fractions: the supernatant chromatin and matrix chromatin. The former fraction contains about 60-70% of initial DNA and about 15% of initial protein along with all five histones, and an insignificant amount of non-histone proteins. RNA synthesis in the matrix chromatin fraction is 2-3 times more intense than that in the original nuclei. The data on gradient centrifugation do not suggest the elongation of RNA molecules synthesized in the matrix fraction. The results obtained as compared with the literature data suggest that the matrix chromatin fraction is enriched with active genes.