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)

The complexes of 2-aminomethyl benzimidazole, 2-(beta-aminoethyl)benzimidazole, and 2-(alpha-aminoethy-l)benzimidazole with Pt(II) and Pd(II) have been prepared. The molecular structure of the free ligands and their complexes were studied by IR and 1H NMR. It was concluded that the substituted benzimidazole derivatives behave as bidentate ligands, being bound to the metal atoms via the nitrogen of the -N = group and the amino group of the side chain of the benzimidazole ring. The metal complexes were tested for antineoplastic activity both in cultures of neoplastic cells (MEL-745, K-562, Colon 205, IMP-32, SK-N-SH) and in vivo in rodents bearing L-1210 leukemia. The antiproliferative activity of these agents was compared to that of cis-platin.
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PMID:Synthesis, molecular structure determination, and antitumor activity of platinum(II) and palladium(II) complexes of 2-substituted benzimidazole. 325 11

FK973, a new, substituted dihydrobenzoxazine (11-acetyl-8-carbamoyloxymethyl-4-formyl-14-oxa-1,11- diazatetracyclo[7.4.1.0.0]tetra-deca-2,4,6-trien-6,9-diyl diacetate), was obtained by chemical modification of a novel antibiotic which was isolated from the fermentation products of Streptomyces sandaensis No. 6897. FK973 had cytotoxic effects against in vitro cultured human and murine tumor cells. FK973 in doses of 0.032-5.6 mg/kg (i.p.) had stronger antitumor activities and higher chemotherapeutic ratio than mitomycin C against such murine ascitic tumors as P388 and L1210 leukemia, B16 melanoma, M5076 reticulum cell sarcoma of ovarian origin, Colon 26 carcinoma, Ehrlich carcinoma, and MH134 hepatoma. In tests against murine and human solid tumors implanted s.c. in normal mice and nude mice, respectively, FK973 (i.v.) inhibited growth of murine tumors (M5076 sarcoma, Colon 38 carcinoma, B16 melanoma, and Lewis lung carcinoma) by 66-100% and human tumors (LX-1 lung, MX-1 mammary, and SC-6 stomach carcinoma) by 84-99%. In studies with drug-resistant P388 leukemia, FK973 was also effective against vincristine-resistant P388, moderately effective against mitomycin C (MMC)- and adriamycin-resistant P388, and partially effective against cyclophosphamide-resistant P388 cells in mice. Leukopenic effects of FK973 and MMC in mice were comparable at doses which gave antitumor activity almost equally. FK973 had no effect on the numbers of platelets and red blood cells, whereas MMC markedly decreased both. FK973 decreased the numbers of colony forming units in spleen and in culture and the effect was less than that of MMC. Therefore, FK973 may give weaker myelosuppression than MMC. The results suggest that FK973 will be a beneficial drug for the treatment of cancer.
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PMID:Antitumor activity and hematotoxicity of a new, substituted dihydrobenzoxazine, FK973, in mice. 334 97

Flavone acetic acid, given on Days 2 and 9 at a dose of 267 mg/kg, inhibited tumor growth completely in 60%-80% of mice with early-stage Colon Adenocarcinoma 38. The therapeutic efficacy of the flavone against this tumor was retained when the sites of tumor implantation and drug administration were separated. Flavone acetic acid also caused regression of advanced (500-mg) Colon 38 tumors, with greatest efficacy observed following administration of high individual dose rather than high total dose. Unlike many previous potential anticancer agents, only modest activity was observed for this compound against either P388 or L1210 leukemia.
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PMID:Flavone acetic acid: a novel agent with preclinical antitumor activity against colon adenocarcinoma 38 in mice. 370 11

This research note discusses the China cancer mortality data and the methodological problems involved in spatial analysis of these data. Some of the research findings produced by mapping and analyses of the cancer data at the provincial level are also summarized. The two most common cancers in China, stomach and esophagus, were found to have no significant correlation with some selected physical variables and population density, suggesting the need to examine other socio-economic variables such as dietary habit. The study also suggests that the type of diet which may be responsible for these two cancers could be very different from each others. Colon and rectum, leukemia, and breast cancers were found to have very high positive spatial autocorrelation and high correlation with population density--a result contrary to previous findings in the West. Future research using a geographic information system approach and county data is suggested.
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PMID:Geographical patterns of cancer mortality in China. 376 83

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

Proportional mortality of actors and actresses was studied because cancers of many sites have been linked to hair dyes and cosmetics of which actors have been frequent users. Death records (1950-1978) for 2,618 white male and 838 white female members of Actors Equity and the Screen Actors Guild were compared with the U.S. mortality rats. Among males, significantly elevated proportional mortality ratios (PMR) were found for suicide (1.58), cirrhosis of the liver (1.99), all malignancies (1.15), and cancers of the colon/rectum (1.32), pancreas (1.51), and testes (2.37). Colon/rectum and pancreas cancers were not significantly elevated by proportional cancer mortality. Among females, significantly elevated PMRs were found for suicide (2.02) and lung cancer (2.20). Suicide in either sex was much more common in California than in New York. The elevated lung cancer in females was confined to Equity members. No elevations were found for cancers that have been related to hair dye or cosmetic use--ie, breast, ovary, bladder, leukemia, and lymphomas.
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PMID:A proportional mortality study of the acting profession. 402 39

Tallysomycin S10b (TLM S10b), a structural analog of bleomycin (BLM), was evaluated and compared with BLM for antitumor activity in several murine tumor systems and for toxic effects in mice and rats. Neither TLM S10b nor BLM was effective against IP P388 and L1210 leukemias, whereas both drugs were active against IP P388/J leukemia (a BLM-sensitive subline). TLM S10b and BLM were both active against murine solid tumors, including SC B16 melanoma, IV Lewis lung carcinoma, SC Madison 109 lung carcinoma, SC CD8F1 mammary carcinoma and SC Colon 38 carcinoma. In human tumor xenograft models, TLM S10b was active against a colon tumor and had slight activity against breast and lung tumors. Compared with TLM S10b, BLM had less activity against the colon tumor, comparable activity against the breast tumor, and no effect against the lung tumor. A consensus of the antitumor data indicated that compared with BLM, TLM S10b had comparable or greater activity and was about twice as potent. TLM S10b and BLM had approximately equivalent LD50 values in mice. TLM S10b had minimal effects on WBC counts, blood urea nitrogen levels, and serum glutamic pyruvic transaminase levels in mice during the time periods monitored. These effects were comparable to or less pronounced than those of BLM. Both drugs caused dose-related increases in the whole-lung hydroxyproline content in mice, but the dose-response curves were not parallel. TLM S10b caused a larger increase than BLM at the lower doses and a smaller increase than BLM at the highest doses. In rats, TLM S10b and BLM caused comparable, significant decreases in lung mechanics; however, histopathological examination of the lungs indicated that TLM S10b caused less evidence of pulmonary toxicity than did BLM at comparable dose levels. TLM S10b was, therefore, generally comparable to BLM in causing pulmonary toxicity in mice and showed possibly less pulmonary toxicity in rats, while demonstrating approximately equivalent to four-fold greater potency, depending on the test system. It also appeared that TLM S10b caused less pulmonary toxicity than BLM in both mice and rats at doses approaching maximally tolerated levels. TLM S10b is currently undergoing phase I clinical evaluation.
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PMID:Tallysomycin S10b: experimental antitumor activity and toxicity. 620 48

The experimental antitumor activity of a new mitomycin derivative, 7-cysteaminomitosane (RR-150), was evaluated in mice. When administered i.p. to mice bearing i.p.-implanted tumors, RR-150 was superior to mitomycin C (MMC) in increasing the life span of animals bearing P388 leukemia, B16 melanoma, and a line of L1210 leukemia partially resistant to MMC. RR-150 appeared comparable to MMC in increasing life span of mice bearing Madison 109 lung carcinoma, Colon 26 carcinoma, or parental (nonresistant) L1210 leukemia. Mice immunosuppressed with 550 rads whole-body irradiation prior to i.p. implantation of B16 still benefited (e.g., 40% cure rate) following optimal RR-150 therapy when compared to nonirradiated, B16-implanted mice given RR-150 (e.g., 70% cure rate). RR-150 had inconsistent activity in the treatment of s.c.-implanted tumors. In toxicity evaluations, RR-150 was comparable to MMC in suppression of total while blood cell counts but appeared to be less neutropenic. RR-150 also caused less cumulative leukopenia than did MMC in a weekly chronic dose experiment. Based on serum chemistries, RR-150 did not have significant nephrotoxicity, but there was evidence of possible liver toxicity at doses near the 50% lethal dose. Because of the balance of favorable antitumor and toxicity properties of RR-150, work is under way to prepare a more bioavailable form for advanced evaluation.
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PMID:Antitumor activity and toxicity in animals of RR-150 (7-cysteaminomitosane), a new mitomycin derivative. 643 70

A 37-year-old man was found to have classic malacoplakia of the rectum after three courses of chemotherapy for stage IV Hodgkin's disease. Sigmoidoscopy with excisional biopsy was performed because of rectal bleeding. The biopsy specimen of the rectal lesion showed focal extensive granulomatous changes with large macrophages containing round, dense Michaelis-Gutmann bodies. Electromicroscopy demonstrated calcifying spheres with laminated concertric structures (Michaelis-Gutmann bodies) and coliform bacillus in the cytoplasm of macrophages (Von Hansemann bodies). Review of the literature revealed that association of malacoplakia with Hodgkin's disease has never been documented, although it has been reported to be associated with conditions such as malignancy, organ transplantation, collagen disease, and leukemia. The possible role of immune disturbance as an underlying cause of malacoplakia is discussed.
Dis Colon Rectum 1983 Feb
PMID:Rectal malacoplakia in a patient with Hodgkin's disease. Report of a case and review of the literature. 660 Apr 25

The modified steroidal alkylating agent, 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstane-17-oic-13,17-lactam[p-[bis(2-chloroethyl)amino]-phenyl]acetate showed excellent activity in treatment of there murine solid tumors. Colon 26-bearing CD2F1 mice lived twice as long as controls with tumor free survivors at the end of the 70-day observation period. CD8F1 mammary tumor growth was suppressed greater than 90% compared to controls. B16 melanoma-bearing B6D2F1 mice lived 50% longer than controls. This agent had previously been shown to be active in treatment of the Theagenion-Bahner angiosarcoma, the T8 Guerin tumor, L1210 leukemia and P388 leukemia.
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PMID:Activity of 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstane-17-oic-13,17-lactam(p-(bis(2-chloroethyl)amino)-phenyl) acetate(NSC 290205) in murine solid tumors. 706 63


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