Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HO-221, N-[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea is a novel benzoylphenylurea derivative. We had interested in various pharmacological actions of benzoylphenylurea compounds. Therefore, many compounds were synthetized and tested in various screening systems. In the process with these tests, we found HO-221 which showed an excellent antitumor activity. The antitumor activity of HO-221 was judged from the survival time and the tumor weight of experimented tumor-bearing animals. HO-221 preparation was orally administered. The compound exhibited significant effects against various animal tumors (P388, L1210, M5076, LLC, C38, S180, W256), and especially effective against the solid tumors. HO-221 was also markedly effective to MX-1 and LX-1 implanted into nude mice. However, the effect against mouse B16 melanoma was moderate. In addition, HO-221 showed a schedule dependency and once every 4 or 7 days treatments were most effective. The antitumor activities of the compound against advanced L1210 and Lewis lung tumors were examined. Tegafur and ara-C were used as reference drug for the study. Three agents showed the antitumor activities against L1210. Against Lewis lung carcinoma, HO-221 showed both the increase of life span and the tumor growth inhibition. On the other hand, tegafur and ara-C were ineffective for the increase of life span.
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PMID:[Antitumor effect of a benzoylphenylurea derivative HO-221]. 226 Aug 71

In previous studies we showed that human sarcoma and melanoma cell lines synthesize and secrete into culture medium a glycoprotein, migrating in urea sodium dodecyl sulfate-polyacrylamide gel electrophoresis at Mr 140,000. It is not detected in cultures of the corresponding normal cells. Conditioned medium of the melanoma cell line HMB-2, producing among the cell lines tested the largest amounts of this glycoprotein, has now been used as a source for purification of the protein. NH2-terminal amino-acid sequence determination of the purified glycoprotein showed that it is identical to human alpha 2-macroglobulin (alpha 2M). Rabbit antibodies raised against the glycoprotein specifically reacted in immunoblotting and immunodiffusion tests with alpha 2M present in human plasma. Likewise, these antibodies immunoprecipitated from the conditioned media of 35S-methionine-labelled melanoma and osteosarcoma cell lines the protein which had a molecular weight corresponding to alpha 2M. alpha 2M was also synthesized and secreted by 2 strains of fetal lung fibroblasts but not by fetal skin fibroblasts or adult skin fibroblasts autologous to the osteosarcoma cell line.
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PMID:Human tumor cells synthesize and secrete alpha-2-macroglobulin in vitro. 241

A new series of highly lipid-soluble cis-bis-carboxylato(trans-R,R-1,2-diaminocyclohexane)platinum(II) complexes were synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), 195pt nuclear magnetic resonance (NMR)]. cis-bis-Neopentanoato(trans-R,R-1,2-diaminocyclohexane)platinum(II ) (NPDP), cis-bis-neodecanoato(trans-R,R-1,2-diaminocyclohexane)-platinum(II ) (NDDP), and cis-bis-n-decanoato(trans-R,R-1,2-diaminocyclohexane)-platinum(II) (DEDP) complexes were entrapped in multilamellar vesicles composed of dimyristoyl phosphatidylcholine (DMPC) and dimyristoyl phosphatidylglycerol (DMPG) at a 7:3 molar ratio and tested for toxicity and antitumor activity. The entrapment efficiency of the liposomal platinum (L-Pt) complexes (L-NPDP, L-NDDP, L-DEDP) was greater than 95%, and the stability in 0.9% NaCl solution at 4 degrees C was greater than 95% at day 14 in each case. The LD50 values of L-NPDP, L-NDDP, and L-DEDP when injected i.v. were 30, 54, and 150 mg/kg, respectively. L-NPDP, L-NDDP, and L-DEDP had no significant nephrotoxicity [as evidenced by a lack of elevated blood urea nitrogen (BUN) levels]. The percentages of T/C obtained after a single i.p. injection of the optimal dose of L-NPDP, L-NDDP, and L-DEDP tested against L1210 leukemia were 175%, 187%, and 212%, respectively [160% for cisplatin (CDDP)]. When a multiple i.p. injection schedule was used (on days 1, 5, and 9), L-NPDP, L-NDDP, and L-DEDP were more active than CDDP (percentage of T/C: 312%, 312%, 277%, and 220%, respectively). When injected i.v., only L-NDDP showed significant activity against L1210 leukemia i.v. (percentage of T/C: 186%). L-NDDP and L-DEDP were markedly active against L1210 leukemia resistant to CDDP (percentage of T/C: 200% and 145% vs 112% for CDDP). L-NPDP, L-NDDP, and L-DEDP also had good activity against i.p. B16 melanoma when they were injected i.p. on days 1, 5, and 9 (percentage of T/C: 206%, 225%, and 306%, respectively). L-NDDP and L-DEDP were more effective than CDDP in inhibiting the growth of liver metastases of murine M5076 reticulosarcoma, whereas L-NPDP was not active. The results obtained to date suggest that L-NDDP is the best L-Pt-complex candidate for further developmental studies.
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PMID:Toxicity and antitumor activity of cis-bis-carboxylato(trans-R,R-1,2-diaminocyclohexane) platinum(II) complexes entrapped in liposomes. 264 11

Diethyldithiocarbamate (DDTC) has been shown to inhibit nephrotoxicity induced by cis-platinum (DDP) without inhibition of tumor response in the rat. We report here that DDTC at doses of 25-300 mg/kg inhibits DDP-induced nephrotoxicity and bone marrow toxicity in C57BL/6 X DBA/2F1 (hereafter called B6D2F1) mice, F344 rats, and beagle dogs and is also antiemetic in the dog. DDTC doses which afford excellent protection do not decrease median survival time following DDP treatment in L1210 and P388 leukemias, B16 melanoma, and Lewis lung and colon 26 carcinomas in B6D2F1 mice when DDTC is given 2 h after DDP. Preliminary experiments indicate that DDTC does not alter median survival time after treatment of P388 leukemia with the platinum analogues diammine(1,1-cyclobutanedicarboxylato)platinum(II) and cis-diisopropylamine-cis-dichloro-trans-dihydroxyplatinum(IV ). Maximum blood urea nitrogen levels after DDP treatment are reduced significantly by DDTC in all species; blood urea nitrogen elevation, total kidney platinum, weight loss, and leukopenia correlate with DDP-DDTC interval in the rat and indicate optimum protection at 2 h, the shortest interval examined. Bone marrow toxicity was assessed by peripheral white blood cell counts in all species and by marrow cellularity in the mouse. White blood cell nadirs were higher and bone marrow recovered more rapidly after DDTC compared with DDP given alone. DDP reduced marrow cellularity 50-60% in the mouse; administration of DDTC 2 h after DDP afforded no protection to the lymphocytes in the marrow but maintained the granulocyte + precursor population near control levels. DDTC plasma pharmacokinetic values have been determined after s.c., i.p., and i.v. administration in the mouse, rat, and dog. Peak plasma levels of 0.3-1.2 mM are observed after a 250-mg/kg dose, with a plasma half-life of 10-20 min. Our data indicate that DDTC may provide protection against most clinically significant toxicities arising from cis-platinum at doses which do not inhibit tumor response.
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PMID:Selective protection against cis-diamminedichloroplatinum(II)-induced toxicity in kidney, gut, and bone marrow by diethyldithiocarbamate. 300

A series of water-soluble N-substituted iminodiacetato(1,2-diaminocyclohexane)-platinum(II) complexes (IDP) were synthesized and tested for chemical stability, antitumor activity, and toxicity. The results obtained suggest that these complexes are relatively stable for more than 48 h when dissolved in water or phosphate buffer. All complexes had good in vitro cytotoxicity and were not cross-resistant with cis-dichloro-diammineplatinum(II) (DDP) in a DDP-resistant cell line in vitro. When the complexes were administered as a single i.p. injection to C57BL/6 X DBA/2F1 (hereafter called B6D2F1) mice inoculated with L1210 leukemia cells, a significant increase in mean survival time was observed, but there were few long-term survivors. When the complexes were administered on Days 1, 5, and 9 after tumor inoculation, however, cure rates of 50 to 85% were obtained. The oncolytic activity of the IDP complexes against L1210 ascites appeared much greater than that of DDP. The IDP complexes also had good antitumor activity when administered i.p. on Days 1, 5, and 9 following i.p. inoculation of B16 melanoma to B6D2F1 mice. Five of the six IDP complexes had no significant nephrotoxicity (as evidenced by lack of elevated blood urea nitrogen levels). N-Benzyl-iminodiacetato(1,2-diaminocyclohexane)-platinum(II) resolved into three distinct peaks of UV-absorbing material that corresponded with three distinct peaks of platinum-containing material. The exact chemical identity of the active component of this mixture is currently under investigation. The results obtained to date, however, suggest that the N-substituted iminodiacetato(1,2-diaminocyclohexane)-platinum(II) complexes are good candidates for further developmental studies.
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PMID:Water-soluble N-substituted iminodiacetato(1,2-diaminocyclohexane)-platinum(II) complexes as potential antitumor agents. 377 45

Endo B (melanotic) and W (amelanotic) human malignant melanomas originated from the same tumor, both known to be heterogeneous in drug sensitivity to ACNU [( 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitroso- urea hydrochloride]), were treated experimentally with a combination therapy of ACNU and hyperthermia in mice. Whereas Endo W melanoma has no sensitivity, Endo B melanoma is sensitive to ACNU alone. However, in both types of melanomas, a marked synergistic effect of the combination therapy was noted. Histologically, marked degeneration of both tumor cells was detected. These results strongly suggest that thermochemotherapy may overcome the tumor heterogeneity in drug sensitivity.
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PMID:Thermochemotherapy for malignant melanoma: overcoming heterogeneity in drug sensitivity. 385 51

A melanoma-associated oncofetal antigen, gp87 (a p97-like molecule), defined by the monoclonal antibody (MoAb) 140.240 has been purified to homogeneity from the spent medium of cultured melanoma cells by a two-step immunoadsorbent procedure. The first immunoadsorbent step using glutaraldehyde-insolubilized MoAb 140.240 (ascites fluid) resulted in a 13-fold enrichment with 93% recovery in the bound material. In the second immunoadsorbent step constructed by the purified IgG2a of MoAb 140.240 (culture fluid) coupled to CNBr-activated Sepharose 4B the bound material from the first step was further purified resulting in a 330-fold purification with 90% recovery. SDS-polyacrylamide gel electrophoretic analysis of the final purified material revealed a single band migrating as a polypeptide with an approximate molecular weight of 87 Kd, consistent with the size of the molecule immunoprecipitated by MoAb 140.240 from lysates of radiolabelled melanoma cells. Preliminary amino acid analysis indicates a particularly high proportion of phenylalanine in gp87. We have also compared gp87 with two well defined antigens, HLA-A,B,C (integral membrane protein) and "94K" melanoma/carcinoma-associated antigen (peripheral membrane protein) with respect to antigen extractability from melanoma cells using phosphate-buffered saline, 0.1 M urea, 3 M NaCl, or nonionic detergent (NP-40). The results showed that whereas 94K antigen was extractable by each of the four different solutions, gp87, similar to HLA-A,B,C antigens, could only be extracted with NP-40, strongly suggesting that gp87 is an integral melanoma cell component.
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PMID:Immunopurification, characterization, and nature of membrane association of human melanoma-associated oncofetal antigen gp87 defined by monoclonal antibody 140.240. 388 78

The purification of two isoenzymes of tyrosinase has been carried out in Harding-Passey mouse melanoma. One is found in the cytosol and the other one bound to melanosomes. Both migrate as single bands on sodium dodecyl sulphate/polyacrylamide gels, having an apparent Mr of 58 000. Solubilized particulate tyrosinase showed an aggregation equilibrium involving a monomer, tetramer, octamer and a high-Mr micellar form with Brij 35, the solubilizing agent. H.p.l.c. studies indicated a interconversion between those species, the monomer contribution increasing with the sample dilution. The tetramer and the octamer probably represent the predominant forms in vivo. Soluble tyrosinase showed a simpler aggregation equilibrium, involving two forms, monomer and tetramer, with the same interconversion pattern. Fluorescence studies suggested that tryptophan residues were exposed to the aqueous environment when tyrosinase was dissociated by dilution. Tyrosinase shows a tendency to aggregate, at low protein concentration, and a resistance to dissociation by urea or SDS so remarkable that gel-permeation chromatography in 4M-urea does not affect the equilibrium, and the band obtained on SDS/polyacrylamide-gel electrophoresis is a dimer.
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PMID:Aggregation equilibria of tyrosinase of Harding-Passey mouse melanoma. 392 35

The novel antitumor antibiotic, trioxacarcin C, was studied for antitumor activities against murine tumor systems. When mice with i.p.-inoculated B16 melanoma were given intraperitoneal injections of trioxacarcin C, the maximal T/C% was 164 by successive administration of 0.125 mg/kg/day (day 1 approximately 10). It also gave the prolongation of life span of mice bearing i.p. P388 leukemia (T/C 141%) by i.p. injection for 10 days, and inhibited the growth of sarcoma 180 (T/C 42%) and Lewis lung carcinoma implanted s.c. (T/C 23%) by i.v. administration for 6 or 7 days. It inhibited the growth of P388 leukemia cells in vitro and showed significant inhibition on the colony formation of HeLa S3 cells. DNA and RNA synthesis were more strongly inhibited than protein synthesis by trioxacarcin C. Also, it induced strand scission of PM-2 DNA without reducing agents or metals. It did not effect the number of white blood cells and blood urea nitrogen value of the peripheral blood.
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PMID:Antitumor activity of trioxacarcin C. 619 42

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


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