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)

We report a case of adenocarcinoma of the prostate in a 41-year-old man with 47XXY karyotype (Klinefelter's syndrome) and chronic lymphocytic leukemia. The increased incidence of malignancy in individuals with Klinefelter's syndrome has been well documented for certain neoplasms. Adenocarcinoma of the prostate has not been reported previously in a patient with Klinefelter's syndrome and a 47XXY karyotype. Absence of mosaicism was confirmed by peripheral lymphocyte, skin fibroblast, bone marrow cell and spleen stroma fibroblast cultures. Chronic lymphocyte leukemia, especially the T-cell cytotoxic/suppressive variant, may additionally add to an immunological deficit. Since carcinoma of the prostate, Klinefelter's syndrome and chronic lymphocytic leukemia are common, the lack of a previous report is interesting. Etiological aspects are discussed.
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PMID:Adenocarcinoma of the prostate in a 41-year-old man with XXY karyotype and chronic lymphocytic leukemia: report of a case. 198 78

Through the extensive investigation of new mitomycin C (MMC) derivatives, several compounds with disulfide at N-7 were found to show activities superior to MMC against murine Sarcoma 180 solid tumor. Among them, 7-N-[[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl]]- mitomycin C (KW-2149) was selected for further evaluation of antitumor activity and toxicity in mice. KW-2149 exhibited activity superior to MMC in increasing survival of i.p. inoculated P388 leukemia-, M5076 sarcoma-, and B16 melanoma-bearing mice. KW-2149 administered i.v. also exhibited superior activity in inhibiting the growth of s.c. inoculated P388 leukemia, M5076 sarcoma, and colon 26 adenocarcinoma and in increasing survival of i.v. inoculated P388 leukemia- and M5076 sarcoma-bearing mice. Furthermore, KW-2149 remarkably increased the life span of MMC-resistant P388 leukemia- and L1210 leukemia-bearing mice. KW-2149 and MMC inhibited the growth of human tumors inoculated into nude mice. The activity of KW-2149 was prominent in human lung carcinoma Lu-65 and Lu-99, bladder carcinoma T24, and epidermoid carcinoma A431. KW-2149 was comparable to MMC in decreasing the number of WBC in the peripheral blood, and the thrombopenia induced by KW-2149 was mild and recovery was rapid. The in vitro anticellular spectrum of KW-2149 against 23 human tumor cell lines was similar to that of MMC. However, KW-2149 inhibited the growth of the cell lines at concentrations of 10- to 100-fold lower than MMC and showed efficient cytotoxicity against MMC-insensitive tumor cell lines. These included lung epidermoid carcinoma Calu-1, stomach carcinoma MKN-28, colon adenocarcinoma DLD-1, colon adenocarcinoma LoVo, bladder carcinoma HT-1197, sarcoma G-292, and melanoma SK-MEL-28 cells. These results indicate that KW-2149 bears interesting characteristics as a new anticancer drug and warrants further development.
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PMID:Antitumor activity of 7-N-[[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl]]-mitomycin C. 198 76

S 12363 is a new Vinca alkaloid derivative obtained by appending an optically active alpha-aminophosphonate at the C23 position of O4-deacetyl vinblastine. S 12363 was evaluated for cytotoxic and antitumor activity against a spectrum of murine and human tumors. This compound was, respectively, on average, 72- and 36-fold more cytotoxic than were vincristine and vinblastine, when tested on a panel of 2 murine and 37 human tumor cell lines using the microculture tetrazolium assay. S 12363 exhibited significant antitumor activity against murine transplantable tumors (i.p. and s.c. P388 leukemia, i.p. L1210 leukemia, i.p. and i.v. B16 melanoma, i.p. M5076 sarcoma, and s.c. colon adenocarcinoma 38), while no activity was observed on s.c. Lewis lung carcinoma. S 12363, when administered i.p., showed moderate activity on human NCI-H460 lung and PANC-1 pancreas tumor xenografts in nude mice. However, when it was administered i.v., it exerted a significant activity against human HT-29 colon, NCI-H460 lung, NCI-H125 lung, PANC-1 pancreas, and A-431 vulvar tumor xenografts. S 12363 was also active in vivo against a P388 leukemia subline resistant to vincristine. On the in vivo panel of tumors used in this study, S 12363 was at least as active as reference compounds, while its optimal dosage was 10- to 40-fold lower than that of vinblastine, depending on the models studied. The effects of schedule and route of administration on the antitumor activity of S 12363 were studied in both i.p. inoculated P388 leukemia and B16 melanoma, in which the activity was improved by single and intermittent treatment (Days 1, 8, and 15) and i.p. route. S 12363, which differs only by the configuration of the asymmetric carbon atom of the side chain, was 300-fold less cytotoxic and 1000-fold less potent in vivo than was S 12363. These results suggest that S 12363 could present a therapeutic advantage over its congeners and deserves further pharmacological evaluations.
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PMID:Preclinical antitumor activity of a new Vinca alkaloid derivative, S 12363. 201 95

The comparative carcinogenicities of N-hydroxy-N-acetyl-1-aminopyrene, N-acetyl-1-aminopyrene, and 1-, 2-, and 4-nitropyrene were determined following i.p. injection into weaning female CD rats (67 mumol/kg body weight in dimethyl sulfoxide; 3 times/week for 4 weeks). At sacrifice 61 weeks after the first injection the incidences of malignant mammary tumors were increased significantly to 45 and 24% in the 4-nitropyrene- and N-hydroxy-N-acetyl-2-aminofluorene-treated groups, respectively. Cellular altered foci in the liver were increased significantly in the N-acetyl-1-aminopyrene-, N-hydroxy-N-acetyl-1-aminopyrene-, and N-hydroxy-N-acetyl-2-aminofluorene- treated groups; the latter two compounds also led to significantly increased formation of hyperplastic nodules in this organ. Significant increases in leukemia induction were observed in animals treated with 2-nitropyrene or N-hydroxy-N-acetyl-2-aminofluorene. In an experiment designed to compare the influence of the route of administration on the carcinogenic potential of this agent, 1-nitropyrene was injected i.p. or s.c. into weanling female CD rats (100 mumol/kg body weight; once a week for 4 weeks). The animals were sacrificed at 87 to 90 weeks after the first treatment. The incidences of mammary gland tumors in animals receiving injections of 1-nitropyrene by either route (59%) were significantly higher than in solvent-injected controls (37%). The incidences of adenocarcinoma in the i.p. 1-nitropyrene group (28%) and fibroadenoma in the s.c. 1-nitropyrene group (52%) were significantly higher than in the control animals (7 and 27%, respectively). These data suggest that the demonstration of the weak carcinogenicity of 1-nitropyrene is probably more a function of the length of the observation period than of the routes of administration used here. A further exploration of the effect of the route of administration involved treatment of weanling female CD rats by direct injection of 1-, 2-, or 4-nitropyrene into the mammary fat pads. A total of 2.04 mumol of the nitrocompound in dimethyl sulfoxide was injected into the mammary glands under each of the 6 left nipples. The right mammary glands were treated with the solvent only. Injections of the thoracic nipple areas were carried out on day 1; inguinal areas were treated on day 2. The animals were sacrificed after 77 weeks. The number of mammary tumor-bearing animals (23 of 28), the number with fibroadenoma (15 of 28), and the number with adenocarcinoma (19 of 28) were significantly increased in the 4-nitropyrene-treated group as compared with animals treated with only dimethyl sulfoxide.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparative carcinogenicities of 1-, 2-, and 4-nitropyrene and structurally related compounds in the female CD rat. 203 29

The antitumor activity of a mitomycin derivative, 7-N-[2[[2-(gamma-glutamylamino)ethyl]dithio]ethyl]mitomycin C (KW-2149), was evaluated in murine and human tumor models, including a mitomycin C (MMC)-resistant tumor in vitro and in vivo. KW-2149 showed a profound effect against i.p. inoculated P388 leukemia on both a single and an intermittent administration schedule. Against s.c. implanted colon adenocarcinoma 38 (colon 38). KW-2149 was as effective as MMC in ILS% and in tumor growth inhibition on a single-administration schedule. Both compounds were similarly effective when an intermittent schedule was used. KW-2149 showed activity against human tumor xenografts and was effective in two of four non-small-cell lung carcinomas but was not effective against three gastric adenocarcinomas on the single-administration regimen. The activity of KW-2149 against gastric adenocarcinoma was inferior to that of MMC on a single-administration schedule. However, the antitumor activity of KW-2149 was higher on an intermittent schedule than on a single-administration regimen. The antitumor activity of KW-2149 against human tumor xenografts was similar to that of MMC on an intermittent schedule, and the former drug was effective against both gastric adenocarcinomas and both non-small-cell lung carcinomas. KW-2149 was more effective than MMC against a subline of P388 leukemia that is resistant to MMC in vitro as well as in vivo.
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PMID:Antitumor activity of a derivative of mitomycin, 7-N-[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl]mitomycin C (KW-2149), against murine and human tumors and a mitomycin C-resistant tumor in vitro and in vivo. 212 21

The effect of cisplatin (CDDP) in combination with etoposide (VP16) was examined on four human cell lines (one colon adenocarcinoma, LoVo; one ovarian carcinoma, IGROV-1; two small cell lung cancers, NCI-H146 and NCI-N592; and two murine leukemias, P388 and L1210). Simultaneous exposure to CDDP and subtoxic concentrations of VP16 for 1 h produced a cell killing in all cell lines comparable to that achieved by CDDP alone. Sequential exposure of NCI-H146 and NCI-N592 to CDDP for 1 h followed by VP16 for 96 h again produced an additive effect. When two of these cell lines were treated in in vivo models (i.p. P388 leukemia, s.c. NCI-N592) with suboptimal doses of the two drugs, a potentiation of the antitumor effects of the two drugs in simultaneous combination was evidenced by the increase in survival time and in the number of 'cures' in P388 leukemia bearing mice and by the inhibition of tumor size in NCI-N592. This comparative study, using the same cell lines in vitro and in vivo, indicates that the CDDP-VP16 potentiation observed in vivo does not reflect a specific interaction at the cellular-biochemical level. The results support the therapeutic interest of this combination (presumably as a result from favorable pharmacological interactions) even despite the lack of potentiation at cellular level, under comparable conditions of treatment.
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PMID:Different interaction of cisplatin and etoposide on in vivo and in vitro tumor systems. 213 Oct 31

We estimated antitumor activity of TUT-7 following p.o. administration using animal tumor models and human tumor xenografts. In mouse L 1210 leukemia system, antitumor activity of TUT-7 administered orally was as good as that by i.v. administration. Treatment involving schedules of every 4-days or daily administration was much more effective than single treatment. Therapiotic indices of this compound administered both p.o. or i.v. routes, were better than that of adriamycin administered i.v.. TUT-7 showed antitumor activities against various mouse tumors (L 1210 leukemia, P 388 leukemia, colon 38 adenocarcinoma, B 16 melanoma), LX-1 human tumor xenografts, and Yoshida sarcoma in rat. Base on above results, we concluded that oral administration is one of the useful route of TUT-7 administration.
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PMID:[Antitumor activities of orally administered 7-con-0-methylnogarol (TUT-7)]. 213 3

PD115934 (NSC 366140) is a soluble pyrazoloacridine derivative presently undergoing preclinical toxicology evaluation with the anticipation of Phase I human investigation. The agent displayed both human and murine solid tumor selectivity in vitro in a soft agar disk diffusion assay, relative to its activity against murine L1210 leukemia. In vivo it was highly active against solid tumors colon adenocarcinoma 38 and pancreas ductal carcinoma 03, which was consistent with the cellular cytotoxicity seen in the disk diffusion assay. A log cell kill of greater than 4.0 was demonstrated in vivo against both models. PD115934 was administered by both bolus and infusional therapy. After completion of these trials, it was determined that this compound was a schedule category III agent, i.e., a schedule-independent agent with peak plasma level toxicity. The main toxicity encountered with infusional therapy was myelosuppression. With bolus therapy, central nervous system toxicities were dose limiting. On the basis of our preclinical infusion studies, we recommend a 2-h infusion twice weekly in humans in order to obtain a total dose of 360 mg/m2 over 8 weeks.
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PMID:Antitumor efficacy of PD115934 (NSC 366140) against solid tumors of mice. 216 50

Datelliptium acetate (NSC 311152) is a water soluble analogue of ellipticine. It is a solid tumor selective compound. In vitro, in a disk diffusion, soft agar colony formation assay (25 micrograms/disk), the compound demonstrated solid tumor selectivity (compared to leukemia L1210) against colon adenocarcinoma 38 and pancreas ductal carcinoma 03. Upon intravenous administration, NSC 311152 was effective in vivo against a variety of murine solid tumors. Responses at maximum tolerated doses were: colon #07/A (T/C = 33%); 0.60 log cell kill), #38 [T/C = 0%; 4.2 log cell kill), colon #51/A (T/C = 2%; 1.2 log cell kill), undifferentiated colon #26/A (T/C = 38%; 0.4 log kill), mammary #16/C (T/C = 10%; 1.7 log cell kill), and pancreatic ductal carcinoma #03 (T/C = 0%; 80% cures through day 38). It was ineffective against pancreas #02 (T/C = 45%), mammary 17/A (T/C = 53%), and 17/A/ADR (T/C = 52%). At efficacious doses acute neurotoxicity (i.e. stupor and lethargy) and weight loss were noted (with rapid recovery from both toxicities). There were no delayed toxicities. The agent was slightly necrotizing and produced pain on SC injections. In lieu of its preclinical efficacy and toxicity profiles, we recommend further clinical investigation of this agent.
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PMID:Activity of datelliptium acetate (NSC 311152; SR 95156A) against solid tumors of mice. 217 44

Six out of 204 patients with Hodgkin's disease developed second malignant tumours 25, 30, 61, 65, 68 and 130 months following their treatment. The length of follow-up ranged between 24-233 months with a mean value of 95.8 months. Half of the tumours appeared within the volume irradiated. Five patients received radio- and polychemotherapy, only but one radiotherapy alone. The location of tumours found was as follows: 1 melanoma of the skin, 1 adenocarcinoma of the nasopharynx, 1 cancer of the rectum, 1 renal cell cancer as well as two cancers of the lung. Four patients are living following treatment of their secondary tumour. Until now no case of acute leukaemia could be observed.
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PMID:[Development of a secondary malignant tumor in patients with Hodgkin's disease]. 218 43


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