Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Friend leukemia was used as an experimental model to study the action of a ribofuranosyl derivative of nitrosourea : RPCNU. This new product was known to be active in L 1210 leukemia and immunosuppressive. RPCNU significantly decreases the splenomegaly induced in DBA2 mice by Friend virus when it is given at a time ranging from 7 days before to 14 days after virus inoculation. The survival time in leukemic treated groups is also greatly increased. However, viral content of the spleen extracts of the leukemic treated mice is not reduced. Therefore, RPCNU cannot be considered as an antiviral agent. A comparison between survival of leukemic and non leukemic mice treated with different doses show that the effectiveness of RPCNU is correlated with its toxicity. The effect of RPCNU on Friend leukemia by cytotoxicity on hematopoietic stem cells is discussed in this paper.
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PMID:Effect of the nitrosourea derivative rpcnu (ICIG 1163) on the development of Friend leukemia in mice. 89 12

2-Chloroethyl nitrosocarbamoylcystamine or ICIG-1325 (CNCC) is a lipid-soluble isomeric mixture of nitrosoureas. Its dose-effect relationship on L1210 leukaemia is characterized by a large maximally efficient dose-range (MEDR), greater than that of other nitrosoureas. CNCC also demonstrated significant therapeutic activity on intracerebrally (i.c.) transplanted L1210 leukaemia and on six transplanted solid tumours, TM2 mammary carcinoma, M555 ovarian carcinoma, B16 melanoma, glioma 26, 3LL, Lewis lung carcinoma and colon 26 carcinoma. It was inactive on fibrosarcoma ICIG-Ci4. Its antitumour activity spectrum is wider than that of the related compounds 2-[3-(2-chloroethyl) 3-nitrosoureido]D-glucopyranose (CZT), (chloro-2-ethyl)-1(ribofuranosyl-isopropylidene-2'-3' paranitrobenzoate-5')-3 nitrosourea (RFCNU), and (chloro-2-ethyl)-1 (ribopyranosyl triacetate-2'-3'-4')-3 nitrosourea (RPCNU). A study of its metabolic disposition in animals has shown that CNCC undergoes extensive first-pass metabolism leading to the formation of four main plasma metabolites. These metabolites are water-soluble nitrosoureas that arose from the bioreduction of the disulphide bridge followed by the methylation and the oxidation of the thiol groups. Experimental screening was performed with these chemically synthesized metabolites. Both N'-(2-chloroethyl)-N-[2-(methylsulphinyl)ethyl]-N'-nitrosourea (CMSOEN2) and N'-(2-chloroethyl)-N-[2-(methylsulphonyl)ethyl]-N'-nitrosourea (CMSO2EN2) are very active on L1210 leukaemia grafted intraperitoneally (i.p.) and i.c., L40 leukaemia, B16 melanoma, glioma 26 and Lewis lung carcinoma. Their effectiveness is better than that of the parent compound CNCC. In addition,the percentage of mice cured after CMSOEN2 or CMSO2EN2 treatment is increased especially on B16 melanoma and glioma 26. 6 Haematological toxicity of both active metabolites is lower than that of CNCC, particularly on platelets which is the main toxicity location due to nitrosoureas.
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PMID:Cytostatic action of two nitrosoureas derived from cysteamine. 380 87

The results of three phase II clinical trials with three new analogues belonging to the family of nitrosoureas are reported. One of the studied agents, chlorozotocine (CZT) is American, while the other two, RFCNU and RPCNU, are French. All three drugs have a sugar radical. CZT proved effective mainly in a few cases of leukemia and in one case of blastic transformation of chronic myelocytic leukemia. RFCNU was shown to be effective in 8% of digestive tumors, in 1 out of 7 pancreatic cancers and in 3 out of 10 hepatic and pulmonary metastases from an undiscovered primary adenocarcinoma. As for RPCNU, it's action resembles that of RFCNU: tumor regression lasting for over three years was obtained in a patient with hepatic metastases from a digestive carcinoma; in another patient a regression rate exceeding 50% was seen in pulmonary metastases from a rectal tumor. One of the significant results of our study is the apparent tissular specificity of responses according to the agent given: CZT is more often efficient on the lymphatic localizations of the studied tumors (4/5 responses); RFCNU and RPCNU often proved active on hepatic metastases (17% responses). Digestive tolerance was excellent with CZT and RFCNU and not quite as satisfactory for RPCNU. As predicted by our experimental study, platelet toxicity is both less common and less severe with RFCNU than with CZT and RPCNU.
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PMID:[Phase II study of 3 new nitrosoureas, 1 American (chlorozotocin) and 2 French (RFCNU and RPCNU)]. 629 62