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)

Chemotherapy with 4'-O-tetrahydropyranyladriamycin (THP-ADM), a new derivative of Adriamycin, was equally or more effective against several experimental mouse tumors than it was with Adriamycin (ADM). When mice with P388 leukemia were given i.p. injections of THP-ADM or ADM daily for 9 consecutive days, the maximum increases in life span (ILSs) of the mice were 190 and 175%, respectively. Eight of 24 mice treated with THP-ADM were free of tumor, while one of 24 mice treated with ADM was free of tumor. A single i.p. injection of either drug was also effective; maximum ILS was 170% for mice treated with THP-ADM and 240% for those treated with ADM. Nine of 12 mice were found to be free of tumor. THP-ADM was equally or slightly more effective against P388 leukemia than was ADM when either drug was given i.v. The maximum ILS was 106% with THP-ADM and 77% with ADM when the drug was given for 9 consecutive days. Single i.v. injections of THP-ADM or ADM were almost equally (ILS, 100%) effective. Chemotherapy with THP-ADM was also very effective against L1210 leukemia. THP-ADM administered i.p. five times, every other day starting from Day 1, was more effective than ADM was against Lewis lung carcinoma, B16 melanoma, and colon adenocarcinoma 38 inoculated s.c. In the study with Lewis lung carcinoma, metastasis to the lungs was well suppressed by THP-ADM. ADM was more effective than was THP-ADM against colon adenocarcinoma 26. Because THP-ADM was more cytotoxic than or almost equally as cytotoxic as ADM against the established cell lines from the above mouse tumors, we suggest that THP-ADM is more efficiently transported into cultured cells.
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PMID:4'-O-tetrahydropyranyladriamycin as a potential new antitumor agent. 706 20

CC-1065 (NSC 298223) is the most cytotoxic agent tested against cells in culture in our laboratory. The 50% lethal doses for exponentially growing B16 melanoma and Chinese hamster ovary cells were 0.44 and 0.14 ng/ml, respectively, as compared to 35 and 500 ng/ml for Adriamycin. In the human tumor-cloning assay, 1-hr exposure to CC-1065 (0.1 ng/ml) caused greater than or equal to 50% lethality in a broad spectrum of tumors. The dose-survival curves for B16 and Chinese hamster ovary cells were characterized by an initial shoulder followed by an exponential decline with increasing dose. CC-1065 was more lethal to exponentially growing B16 cells (50% lethal dose = 0.44 ng/ml) than to plateau-phase cells (50% lethal dose = 1.2 ng/ml). CC-1065 inhibited DNA synthesis much more than did RNA or protein synthesis. After a 2-hr incubation with drug, inhibition of DNA synthesis was low immediately (0 hr) after drug exposure and reached maximum inhibition about 20 hr later. The doses for 50% inhibition of growth (0.18 ng/ml), survival (0.44 ng/ml), and DNA synthesis (0.15 ng/ml) were in the same range, whereas RNA synthesis was inhibited 50% at a much higher dose (5 ng/ml).
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PMID:CC-1065 (NSC 298223), a most potent antitumor agent: kinetics of inhibition of growth, DNA synthesis, and cell survival. 710 29

Human melanoma xenografts in immune-deprived mice have been used to assess the value of the agar diffusion chamber for chemosensitivity testing. Tumor cells were treated with melphalan, Adriamycin, or methyl trans-1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea either as solid tumors growing in mice or as suspensions in agar in i.p. diffusion chambers. Survival of clonogenic human tumor cells was measured by the agar diffusion chamber assay in both cases. Cell survival curves were log-linear for treatment of tumor cells in vivo or in the chambers. For melphalan the slopes of survival curves were significantly greater for treatment in the chambers than as solid tumors in vivo, but for methyl trans-1-(2-chloroethyl(-3-(4-methylcyclohexyl)-1-nitrosourea or Adriamycin, they were indistinguishable. Experiments with [14C]melphalan showed that the levels of drug achieved were less inside the diffusion chambers than in the tumors in vivo so that the sensitivity of tumor cells to melphalan was much greater when they were treated in chambers. The differences in drug exposure and in cellular chemosensitivity between chambers and tumors suggest caution in the interpretation of drug testing using this system, but the log-linear nature of the dose-response curves is an important feature which may be useful in the eventual development of optimal chemosensitivity testing systems.
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PMID:Use of the agar diffusion chamber for the exposure of human tumor cells to drugs. 712 12

To investigate the feasibility of using tissue obtained from human tumor xenografts for in vitro screening of antineoplastic agents, we grew human tumor colony-forming units (CFU) in semisold agar from xenografts serially passaged in nude mice. Growth of human tumor CFU was accomplished from nine xenografts representing five different histological tumor types (ovarian carcinoma, adenocarcinoma of the colon, malignant melanoma, epidermoid carcinoma of the lung, and malignant astrocytoma). Cloning efficiency ranged from 0.04 to 0.1% and showed significant variability both between tumor types and between individual animals bearing the same type of xenograft. A high percentage of tumor CFU was in S phase [47 +/- 20% (S.D.)] as determined by the thymidine "suicide" technique. The number of tumor CFU observed increased linearly with increasing numbers of cells plated. In vitro drug sensitivity of the tumor CFU was assessed to Adriamycin, cis-platinum, and melphalan. The patterns of drug sensitivity were found to be reproducible and stable over a period of 9 months. Drug sensitivity curves to Adriamycin for five xenografts representing four tumor types showed complex patterns with plateau portions similar to those described for tumor CFU from primary tumors. The rank order of sensitivity of the tumors was compared to that of normal granulocyte-macrophage progenitors and, with the exception of the melanomas, was found to correlate well with clinical experience (order of sensitivity = colon less than ovary less than bone marrow). Growth of human tumor CFU from xenografts represents a reproducible and stable means for the study of the biology of tumor CFU and has potential applications as a means for screening new anticancer agents.
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PMID:In vitro growth and drug sensitivity of tumor colony-forming units from human tumor xenografts. 721 53

Eradication of drug-resistant tumor foci is essential to the successful treatment of metastasis with chemotherapeutic agents. In this study, we examined the in vitro sensitivity to a variety of chemotherapeutic agents of tumor cells from parental tumors, from their in vitro-cloned populations, and from their spontaneous metastases. Three murine tumors were studied: the B16 melanoma; the K-1735 melanoma; and the UV-2237 fibrosarcoma. In addition, we also examined the in vitro drug sensitivity of cells from the A-375 human melanoma and its various subpopulations. The drugs used in these studies were Adriamycin, 4'-(9-acridinylamino)methanesulfon-m-anisidine, bleomycin, 5-)3,3-dimethyl-1-triazeno)imidazole-4-carboxamide, vincristine, and vindesine. The growth-inhibiting activity of the drugs was recorded in values which were derived from plotting the logarithm of the drug concentration versus the growth rate (percentage of control) of the treated cells and which determined the molar concentration of drugs necessary to reduce doubling by 50%. Our results demonstrate that differences in drug response exist among cells populating a parental tumor (in vitro cloned), between the parental line and its metastatic subpopulations (in vivo-selected lines), and among the various spontaneous metastases. These extensive differences in drug sensitivity could have profound implications for the treatment of metastases with cytotoxic drugs.
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PMID:Differences in drug sensitivity among tumor cells from parental tumors, selected variants, and spontaneous metastases. 724 62

We measured the effect of 6 standard (Adriamycin, BCNU, DTIC, melphalan, vinblastine, actinomycin D) and 3 Phase II agents (cis-platinum, vindesine, AMSA) on melanoma colony-forming units (CFU) in soft agar from biopsies of 50 patients with metastatic melanoma. Melanoma CFU demonstrated marked heterogeneity in chemosensitivity to these 9 drugs. Reduction in survival of CFU below 38% at one-tenth the pharmacologically achievable 1h concentration (our operational definition of chemosensitivity) was obtained in only 19% of 200 in vitro trials, and was usually the same whether or not patients had been exposed to prior chemotherapy, suggesting that melanoma CFU are inherently resistant to presently available chemotherapeutic drugs. The soft-agar assay was 86% accurate (25/29 cases) in identifying drugs to which the tumour was resistant in vivo, and 63% accurate (12/19 trials) in identifying drugs to which the tumour was clinically sensitive, counting mixed responses as responses. In contrast, if mixed responses were classified as progressive disease, the accuracy of identification of sensitivity fell to 42% (8/19 trials). These investigations furnish a quantitative description of the chemosensitivity of human metastatic melanoma CFU. Additionally, these studies serve as a useful step towards the development of an in vitro chemosensitivity test for human melanoma, and provide an operational quantitative basis for further exploration of in vitro-directed therapy in metastatic neoplasms.
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PMID:Quantitation of drug sensitivity by human metastatic melanoma colony-forming units. 732 91

Nogalamycin is an anthracycline antibiotic which was markedly cytotoxic in vitro and was active against several tumor systems in vivo. We compare here the lethality of several nogalamycin analogs against Chinese hamster ovary (CHO), mouse leukemia (L1210), and mouse melanoma (B16) cells in culture. 7-con-O-Methylnogarol (7-con-OMEN) was the most lethal of all the analogs tested. Thus, for CHO cells exposed for two hr to the drug, the 50% lethal doses of 7-con-OMEN, nogalamycin, and dis-nogamycin were 0.25, 2.7, and 5.8 micrograms/ml, respectively. In general, CHO cells were less sensitive than B16 or L1210 cells to most compounds. All compounds gave dose-survival curves which consisted of a shoulder region followed by a region of exponential decline in survival. The nogalamycin analogs nogalamycin, dis-nogamycin, 7-con-O-methylnogalarol, and 7-con-OMEN were selected for further study because of their greater lethality in vitro and antitumor activity in vivo. The lethality of these compounds was compared to that of Adriamycin. 7-con-OMEN was more toxic to CHO cells than was Adriamycin but was less toxic to B16 and L1210 cells. All of these compounds (except 7-con-O-methylnogalarol which was not tested) were more lethal to exponentially growing cells than to plateau-phase cells. The survival response after different periods of exposure to these drugs was compared. In order to make valid comparisons of the time-survival response to different drugs, the drug concentrations chosen were such that they were equitoxic after a two-hr exposure. Under these conditions, the order of lethality after long-term exposure (8 hr to 24 hr) was nogalamycin > dis-nogamycin > 7-con-OMEN, Adriamycin > 7-con-O-methylnogalarol. With all the drugs, the rate of cell death increased with increasing drug concentrations.
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PMID:Cell kill kinetics of several nogalamycin analogs and adriamycin for Chinese hamster ovary, L1210 leukemia, and B16 melanoma cells in culture. 744 58

In order to establish the usefulness of the human tumor-nude mouse system as a predictive screen for anticancer agents, 17 tumors (3 breast, 3 colon, 3 lung, 3 melanoma, 2 ovary, 1 prostate, 1 sarcoma, and 1 larynx), serially transplantable in athymic mice, were used to study antitumor activity of doxorubicin (Adriamycin). BALB/c nude mice were treated i.v. on a weekly basis for 3 to 4 weeks, starting when the tumor volume became relatively large (advanced stage of tumor treatment). All the tumors except lung tumor T 293 showed a 90 to 100% take rate and stable growth. Doxorubicin, at dose levels of 6 and 10 mg/kg/injection i.v. every week for 3 weeks, showed significant activity against all of the three breast tumors studied. As was expected on the basis of clinical data, doxorubicin showed no antitumor activity against the three different colon tumors. In the case of lung tumors, statistically significant activities against oat cell carcinoma T 293 and epidermoid carcinoma T 222 were observed. In contradiction to clinical data, doxorubicin was found to have significant activity against various melanomas studied and slight but not statistically significant activity against ovarian tumor T 17. Experimental results obtained using doxorubicin against prostate, sarcoma, and larynx tumors also parallel the reported clinical data.
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PMID:Therapeutic response of human tumor xenografts in athymic mice to doxorubicin. 744 72

Human malignant melanoma was transplanted to the cheek pouch of immunosuppressed (corticosteroid-treated) hamsters. Significant differences were observed in tumor growth constants for animals treated with methotrexate, DTIC, BCNU, and vincristine (P < 0.05) compared to controls. However, no appreciable effect was demonstrated for Adriamycin, 5-FU, and cytoxan. In addition, single doses as high as 400 mg/kg body weight of methotrexate were no more effective than other agents now used against this neoplasm.
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PMID:Chemotherapy against human melanoma in the hamster cheek pouch. 745 85

Cells from 3 human tumours have been grown in soft agar contained in Millipore diffusion chambers and implanted i.p. in mice. Clonal growth was obtained from fresh biopsy samples, from cryopreserved tissue, and from xenografts of the tissues in immune-suppressed mice. The radiosensitivities of a melanoma and an ovarian carcinoma were evaluated by in vitro irradiation before assay for colony formation. Xenografting did not modify the radiosensitivity of the melanoma. Cells from another tumour were exposed to Adriamycin or cyclophosphamide whilst contained within i.p. diffusion chambers; the sensitivity was similar for cryopreserved and xenografted cells. The results encourage further attempts to quantify the sensitivity of human tumour cells by these methods.
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PMID:Clonogenic cell survival in cryopreserved human tumour cells. 747 Mar 78


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