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

Nine patients with intracerebral metastasis from lung carcinoma were treated with intracarotid and intravertebral artery infusion of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Four of these patients considered definite responders showed unequivocal clinical improvement and definite decreases in the size of tumors evaluated by neurologic examination, computerized tomographic (CT) scan and radionuclide brain scan (RBS). One patient's clinical condition stabilized with doubtful improvement of diagnostic tests (probable responder). The remaining four patients had further unfavorable progression of the clinical and scan findings and were clearly nonresponders. Complications were transient and included: local pain in the eye, orbit, and occipital-nuchal area during infusion in 7 patients, focal seizure in 3 patients, mild confusion with disorientation in 2 patients, and nausea in 2 patients. Our findings suggest that intra-arterial BCNU therapy may be effective and may be used as an adjuvant to surgery and/or radiotherapy for the treatment of metastatic brain tumor from lung carcinoma.
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PMID:Intra-arterial BCNU therapy in the treatment of metastatic brain tumor from lung carcinoma: a preliminary report. 50 86

The synthesis of approximately 80 cyclic or acyclic analogs of cyclophosphamide, isophosphamide, triphosphamide, and phosphoramide mustard is outlined briefly. All of the analogs contain at least one 2-chloroethyl or bis(2-chloroethyl)-amino group bound to phosphorus. Representatives of some of the various classes of analogs were evaluated against murine L1210 leukemia in vivo. Some of the cyclic oxidized derivatives and a phosphorodiamidic chloride yielded long-term survivors. 4-Peroxycyclophosphamide was also active against ic implanted L1210 leukemia and against two other murine tumors, Lewis lung carcinoma and C3H mammary tumor.
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PMID:Synthesis and structure-activity relationships of pre-activated analogs of cyclophosphamide (NSC-26271). 94 26

FCE 24157 (chemically (beta-[1-methyl-4-(1-methyl-4--[1-methyl-4-(4-N,N- bis(2-chloroethyl) amino-benzene-1-carboxy-amido) pyrrole-2-carboxiamido]pyrrole-2-carboxyamido)pyrrole-2-c arboxyamido]) propionamidine, hydrochloride) is a distamycin A (Dista A) derivative bearing a benzoyl mustard moiety instead of the formyl group at the N-terminal. Contrary to Dista A, FCE 24517 has been found to display potent cytotoxic activity on human and murine tumour cell lines. The compound maintains activity on melphalan (L-PAM)-resistant cells, whereas cross-resistance is observed on doxorubicin-(DX)-resistant cells. In vivo, FCE 24517 was found to possess evident antineoplastic activity on a series of murine transplanted solid tumours and human tumour xenografts. The following neoplasms were in fact found to be sensitive to FCE 24517 treatment: M14 human melanoma xenograft, N592 human small cell lung carcinoma, MTV murine mammary carcinoma, Colon 38 murine carcinoma, PO2 murine pancreatic carcinoma and M5076 murine reticulosarcoma. Lower effectiveness was observed against the murine P388 and Gross leukaemia, Lewis lung murine carcinoma, LoVo human colon carcinoma xenografts and A459 human lung adenocarcinoma. Against the murine L1210 leukaemia, FCE 24517 displayed a clear activity only when the tumour was transplanted i.p. and treatment was given i.p., whereas only marginal activity was seen against this leukaemia if transplanted i.v. and the drug was given i.v. As true also in vitro, FCE 24517 was effective against i.p. implanted L1210 leukaemia resistant to L-PAM. The mode(s) of action of this new compound is under active investigation.
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PMID:Biological profile of FCE 24517, a novel benzoyl mustard analogue of distamycin A. 176 67

Aliphatic triazenes, such as 1,3-dimethyltriazene, are potent biological alkylating agents because they form alkyldiazonium ions. They are also subject to very rapid proteolytic decomposition, even at physiological pH. The acylated analogues 1,3-dialkyl-3-acyltrizenes are much more stable in aqueous solution, but they also give rise to alkyldiazonium ions. Four acylated 1,3-dimethyltriazenes, where the acyl groups were diethylphosphoryl (DMP), carbethoxy (DMC), acetyl (DMA), and N-methylcarbamoyl (DMM), were studied kinetically. Rate-pH profiles indicated that the acyl group had a profound effect on the mechanism of decomposition. The cytotoxic potential of all four compounds was studied in vitro by using the MTT-tetrazolium assay. The compounds had fair-to-good activity against some cell lines, particularly those deficient in methylation repair. In vivo assays of DMC and DMM against several tumor xenografts in nude mice showed promising activity for some cancers, particularly in the case of DMM. In vitro assays were also carried out on three 1-(2-chloroethyl)-3-methyl-3-acyltriazenes. The acyl groups were carbethoxy (CMC), acetyl (CMA), and N-methylcarbamoyl (CMM). The activity of these compounds largely paralleled that of bis(2-chloroethyl)-N-nitrosourea (BCNU), except for those cell lines which exhibited the Rem phenotype; triazenes were more active in those lines than BCNU. The in vivo activity of CMC, CMA, and CMM was tested in the P388 leukemia assay. All three were active but CMC and CMA proved to be rather toxic. CMM was well tolerated and was examined in several tumor xenografts in nude mice. Significant activity was found against MX-1 mammary carcinoma, against LX-1 small cell lung carcinoma, and particularly against LOX amelanotic melanoma, where complete cures were effected. The antineoplastic activity of the acyltriazenes is well-correlated with their chemical behavior.
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PMID:1,3-Dialkyl-3-acyltriazenes, a novel class of antineoplastic alkylating agents. 239 96

Clomesone was evaluated for antitumor activity against a spectrum of animal tumor models. Clomesone exhibited significant antitumor activity against the murine L1210 leukemia implanted i.p., s.c., and intracerebrally (i.c.). Activity against s.c.-implanted tumor was largely independent of schedule and route of administration. Therapeutically optimal single-dose treatment (for tumored mice) was less toxic to nontumored mice than therapeutically optimal prolonged treatment. Clomesone also exhibited activity against other murine tumors (P388 leukemia, B16 melanoma, Lewis lung carcinoma, and M5076 sarcoma). It was active against P388 leukemia sublines resistant to cyclophosphamide, L-phenylalanine mustard, and cis-diamminedichloroplatinum(II). No activity was observed against a P388 subline resistant to N,N'-bis(2-chloroethyl)-N-nitrosourea or against Ridgway osteogenic sarcoma, a nitrosourea-resistant murine solid tumor. Clomesone is generally as effective as the chloroethylnitrosoureas against experimental tumor models. Since clomesone does not have the hydroxyethylating and carbamoylating activities of the chloroethylnitrosoureas (which do not appear to contribute to antitumor activity), it would likely be a more toxicologically selective compound. It may prove to be less carcinogenic than the chloroethylnitrosoureas, and it may contribute less target organ toxicity and less interference with the actions of other drugs when used in combinations.
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PMID:Antitumor activity of 2-chloroethyl (methylsulfonyl)methanesulfonate (clomesone, NSC 33847) against selected tumor systems in mice. 253 44

The effect of an antimetastatic agent plus intratumor chemotherapy was evaluated in mice bearing Lewis-lung carcinoma by measuring survival time and by histological examination. Polymeric flavan-3,4-diol (APF) from avocado seeds, Persea gratissima, administered alone directly into the tumor did not change survival time, although it partially destroyed the primary tumor. However, the drug administered in combination with an antimetastatic, 1,2-bis(3,5-dioxopiperazin-1-yl)ethane (ICRF-154), resulted in an increase in survival time. When 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was used in place of polymeric flavanadiol as an intralesional drug, a significant increase in survival was also achieved. The effect of each drug alone and of their combination was evaluated by "responder analyses". Animals "cured" by the combination and rechallenged with 2 X 10(6) tumor cells showed that immunization could occur.
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PMID:Intratumor chemotherapy in combination with a systemic antimetastatic drug in the treatment of Lewis-lung carcinoma. 383 80

8-Carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H) -one (mitozolomide) demonstrates curative action against a range of murine tumor model systems. At single doses of between 20 and 40 mg/kg, the latter of which approximates the 10% lethal dose value in mice, the compound elicited cures against the L1210 and P388 leukemias irrespective of the route of tumor and/or drug administration; in these tests, animals receiving 10(5) cells i.p. survived greater than 60 days after treatment. Potent effects were also observed against the TLX5 lymphoma (s.c.) and B16 melanoma (i.p.). In other experiments, 7 of 10 animals implanted with 2 X 10(5) Lewis lung carcinoma cells survived greater than 60 days while 10 of 10 animals survived greater than 60 days after implantation of the Colon 26 tumor. Potent inhibition of the solid tumor models was also observed with complete cures of the Colon 38, M5076 sarcoma, and ADJ/PC6A plasmacytoma. In cross-resistance studies, the compound was ineffective against an L1210 leukemia made resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea and against a TLX5 lymphoma resistant to dimethyltriazenes but cured animals bearing the L1210 leukemia with derived resistance to cyclophosphamide.
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PMID:Experimental antitumor activity against murine tumor model systems of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3 H)-one (mitozolomide), a novel broad-spectrum agent. 400 40

Nitrosourea derivatives 18-22 which utilize either a piperidine or pyridine ring as a carrier group were synthesized and evaluated for anticancer activity. N'-(1-Benzyl-4-piperidinyl)-N-(2-chloroethyl)-N-nitosourea hydrogen maleate (19) exhibited good activity against intracranial L1210 leukemia as well as the mouse ependymoblastoma brain tumor system. Compound 19 exhibited comparable activity in the Lewis lung carcinoma system to N,N'-bis(2-chloroethyl)-N-nitrosourea. Replacement of the N-benzyl group in both the 3-piperidinyl- and 4-piperidinylnitrosoureas resulted in less active compounds in all tumor systems tested. The 3-pyridylnitrosourea 22 was inactive in the L-1210 leukemia system.
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PMID:Synthesis of nitrosourea derivatives of pyridine and piperidine as potential anticancer agents. 740 Nov 13

Local chemotherapy with biodegradable polymers prolongs survival with minimal morbidity in patients with intracranial high-grade gliomas. However, use of local chemotherapy for metastatic brain tumors has not been defined. We studied the safety and the efficacy of locally delivered chemotherapy with and without concurrent radiation therapy in treating tumors that frequently metastasize to the brain. The chemotherapeutic agents 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), carboplatin, and camptothecin were incorporated into controlled-release polymers and tested individually against intracranial challenges with one of four tumors (lung carcinoma, renal cell carcinoma, colon carcinoma, and melanoma). For each combination of drug and tumor type, four groups were tested: (a) empty polymer (no drug); (b) external beam radiotherapy (XRT) alone; (c) local chemotherapy from biodegradable polymer alone; and (d) local chemotherapy and XRT together. Polymers were implanted 5 days after tumor inoculation; XRT was given on days 7-9 (300 cGy/day). BCNU and XRT together were effective against all four tumors. BCNU polymer alone significantly prolonged survival in mice with intracranial melanoma or renal cell carcinoma. Carboplatin alone was effective against both melanoma and colon carcinoma and in combination with XRT against colon and renal cell carcinomas. Camptothecin was effective only with XRT against melanoma. These studies demonstrate that local delivery of chemotherapy with concurrent radiation therapy is safe and can significantly prolong survival in models of common intracranial metastatic tumors. Concurrent use of local chemotherapy with standard XRT appears to be more effective than either treatment alone. Local chemotherapy may also be of benefit to patients who have previously received maximal cranial irradiation but suffer an intracranial recurrence.
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PMID:Local delivery of chemotherapy and concurrent external beam radiotherapy prolongs survival in metastatic brain tumor models. 891 60

Our laboratory has synthesized and evaluated the anticancer activity of a number of sulfonylhydrazine DNA modifying agents. As a class, these compounds possess broad spectrum antitumor activity, demonstrating significant activity against a variety of experimental murine tumors, including the P388 and L1210 leukemias, B16 melanoma, M109 lung carcinoma, and M5076 reticulum cell sarcoma, as well as against the human LX-1 lung carcinoma xenograft. The current report describes the activity of a more recently synthesized member of this class, 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-(methylamino)carbonylhydrazine (101M). 101M was active in mice against the i.p. implanted L1210 leukemia over a wide range of doses and produced long-term survivors when administered as a single i.p. bolus of 10, 20, 40, 60, or 80 mg/kg, demonstrating a wider margin of safety than the nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Curative therapy was achieved with doses of 101M that did not produce depression of the bone marrow. 101M was also highly effective against the L1210 leukemia when administered by the oral route. The ability of 101M to penetrate the blood-brain barrier and eradicate leukemia cells in the brain was remarkable (>6 log kill). This agent was also curative against L1210 variants resistant to cyclophosphamide, BCNU, or melphalan. Mice implanted with the murine C26 colon carcinoma were also cured by two injections of 10 or 20 mg/kg of 101M. Administration of 101M by two different well-tolerated regimens caused complete regression of established human glioblastoma U251 xenografts in 100% of treated mice, and significant responses were also obtained with 101M against advanced murine M109 lung carcinomas in mice. The broad spectrum of anticancer activity of the sulfonylhydrazine prodrug 101M coupled with the wide range of therapeutic safety exhibited by this agent, makes 101M particularly attractive for further development and clinical evaluation.
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PMID:1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-(methylamino)carbonylhydrazine (101M): a novel sulfonylhydrazine prodrug with broad-spectrum antineoplastic activity. 1130 84


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