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)

A study was carried out to determine the interrelationship between the inhalation of nitrogen dioxide (0.4 +/- 0.50 ppm), lung metastases development from circulating cancer cells, and death rate from such metastases. C57 BL/6J mice were used in these experiments. Animals were divided into control and NO2-exposed groups, and were exposed to filtered air and 0.4 ppm of NO2, respectively. Following 12 weeks of exposure, all animals were infused intravenously with syngeneic, viable B16 melanoma cells. The results indicate that a subpopulation of NO2-exposed animals showed a significant increase in mortality rate during the early part of the experiment. The interpretation is that animals especially sensitive to the NO2 insult developed extensive metastases at an early stage. The question raised is whether or not the progression of human cancer is influenced by the inhalation of noxious pollutants in the ambient atmosphere.
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PMID:The mortality rate from lung metastases in animals inhaling nitrogen dioxide (NO2). 396 90

X-ray and heat survival curves were established for melanoma cells derived directly from surgical specimens of tumours in man by using the Courtenay soft agar colony assay. The plating efficiency for 11 of the 14 melanomas studied was sufficiently high (PE = 0.3-58%) to measure cell survival over at least two decades. Experiments repeated with cells stored in liquid nitrogen showed that the survival assay gave highly reproducible results. The melanomas exhibited individual and characteristic survival curves whether exposed to radiation or heat (43.5 degrees C). The Do-values were in the ranges 0.63-1.66 Gy (X-rays) and 33-58 min (heat). The survival curves were similar to those reported previously for human melanoma xenografts. The radiation sensitivity of the cells was not correlated to the heat sensitivity. Since the melanomas appeared to be very heterogeneous in radiation response in vitro as melanomas are known to be clinically, it is suggested that melanomas may be suitable for prospective studies aimed at establishing whether clinical radioresponsiveness somehow is related to in vitro survival curve parameters.
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PMID:Survival curves after X-ray and heat treatments for melanoma cells derived directly from surgical specimens of tumours in man. 403 1

Melphalan resistance developed previously in a human melanoma cell line (MM253) could not be further increased. Cross-resistance was found to nitrogen mustard but not to ultraviolet light radiation. A clone of MM253 had the same drug sensitivity and heterogeneous chromosome complements as did the parent culture. The melphalan-resistant cells (MM253-12M) had 2.6-fold the D0, 1.5-fold the size, 1.3-fold the RNA content, 1.4-fold the protein content, and 2.6-fold the DNA content of the sensitive parent line. There was no evidence for activation or detoxification of melphalan by intact melanoma cells or by mouse liver microsomes competent for the activation of other drugs. Melphalan transport was similar in both cell lines, reaching a steady-state level 3 times the concentration in the medium after 2.5 min. Both lines covalently bound the same total amount of [3H]melphalan per cell, but in MM253-12M a 50% decrease in binding to DNA was almost sufficient to account for the increase in resistance. The level of melphalan-induced DNA interstrand cross-links, which were heat labile but not alkali labile, reached a maximum during the 4-hr treatment period and then declined slowly. The degree of cross-linking in MM253-12M was 50% less than that in MM253. Unlike ultraviolet light, methyl methanesulfonate, and nitrogen mustard, melphalan at equitoxic doses did not damage the DNA sufficiently to immediately inhibit DNA synthesis. Although both lines were proficient for repair of ultraviolet light and methyl methane sulfonate damage, melphalan did not induce significant levels of DNA repair synthesis and had little effect on the rate of DNA chain elongation. In MM253 cells, strand breaks were detected only at high melphalan doses; MM253-12M formed breaks more readily. This evidence suggests that the cross-linking events and that developed resistance arises from decreased susceptibility to DNA to this damage.
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PMID:Mechanism of melphalan resistance developed in vitro in human melanoma cells. 616 26

Pulmonary fibrosis is a serious side effect that limits the therapeutic utility of bleomycin (BLM). Recently, it has been demonstrated that L-3, 4-dehydroproline (DHP), a proline analog, significantly reduced the extent of pulmonary fibrosis in rats administered BLM intratracheally. The present studies were performed to determine the effect of DHP on the oncolytic and toxicologic effects of BLM. DHP (25 mg/kg/day) administered sc concomitantly with BLM (4 mg/kg/day) for 9 consecutive days following a sc inoculation of B16 melanoma cells in BDF1 had no effect on tumor growth inhibition by BLM when tumor growth rate was assessed by tumor volume and by tumor weight. To determine the effect of DHP on the toxicity of BLM, DHP (25 mg/kg/day) and BLM (10 mg/kg/day) were administered to Sprague-Dawley rats for 5 consecutive days followed by 2 days of rest and 5 additional days of drug administration. BLM administration produced decreased body weight gain, acute leukocytopenia, delayed elevation in blood nitrogen levels, chronic lung and kidney disease, and alopecia. Animals administered BLM plus DHP had a similar toxicologic profile. One striking difference was that no animal administered BLM plus DHP developed alopecia, whereas five of eight rats administered BLM alone displayed this untoward effect. These results suggest that DHP neither diminishes the oncolytic activity nor exacerbates the nonpulmonary toxicity of BLM, DHP would appear, therefore, to be a potential candidate as an antifibrotic adjunct to BLM therapy.
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PMID:The effect of L-3, 4-dehydroproline on the antitumor activity and toxicity of bleomycin. 619 Feb 66

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

Mononuclear blood cells from 40 healthy donors, 25 patients with melanoma and 35 patients with lung cancer were tested for suppressor cell activity and response to phytohemagglutinin (PHA). The suppressor cell activity was measured by determining the ability of Mitomycin C (MMC)-treated mononuclear cells from patients and controls to suppress the in vitro response of responder cells to PHA. Mononuclear cells from one healthy donor were stored in liquid nitrogen for use as responder cells. Indomethacin-sensitive suppression was also measured. In both groups of patients the mean values of suppressor cell activity in co-culture were higher than those in control group. When patients were subdivided in groups according to the clinical stage, the level of suppressor cell activity increased with the stage. Indomethacin-sensitive suppression was detected in some patients but the differences between patient and control groups were not statistically proved. An inverse relationship was observed between indomethacin-sensitive suppression and the PHA response.
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PMID:Suppressor cells in melanoma and lung cancer: correlation with the clinical stage. 622 Nov 96

The clinical effect of intralesional injection of interleukin-2 (IL-2)-cultured autologous lymphocytes was assessed in seven patients with cutaneous, recurrent tumor nodules (12 melanoma and 8 mammary cancer lesions). Each tumor nodule was injected 3-10 times, once weekly, with IL-2-cultured lymphoid cells (CLC), 40-400 million cells at each injection. Lymphoid cells obtained from buffy coats were separated on Ficoll-Paque, cryopreserved in liquid nitrogen, thawed, and cultured for 1-2 weeks in the presence of crude IL-2 (containing phytohemagglutinin) before injection. CLC were tested for sterility, percent E-rosette-forming cells, and cytotoxicity against K562, allogeneic melanoma, and breast cancer cell lines and autologous tumor cells. Enhanced cytotoxicity was expressed by IL-2 CLC, as compared with nonstimulated peripheral blood lymphocytes (PBL). Arrest of tumor growth (compared with untreated lesions) was observed in eight lesions and partial regression in three lesions. Moreover, complete regression was noted in one large melanoma lesion treated with low-dose irradiation prior to intralesional administration of CLC and in three small intracutaneous melanoma lesions treated with CLC only. Histopathological findings of responding lesions showed infiltration with lymphoid cells and macrophages, with the tumor cells sparsely dispersed. No untoward side effects of CLC injections were observed. The present study points to the feasibility of trials of adoptive immunotherapy in cancer patients as indicated by the following: (a) response of lymphoid cells to IL-2 adequate--although reduced--in patients with metastatic disease, including those after chemo- or radiotherapy; (b) possibility of cryopreservation of PBL and repeated culturing in IL-2 after thawing, with cytotoxic activity unimpaired; (c) demonstrably enhanced cytotoxicity in vitro of IL-2 CLC; (d) demonstrable--although limited--clinical response to in situ treatments with IL-2 CLC; (e) good tolerance of treatment with CLC.
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PMID:Intralesional injection of interleukin-2-expanded autologous lymphocytes in melanoma and breast cancer patients: a pilot study. 633 37

The works of Zimmermann, Fraunfelder et al. and Migdal offer reasons for postulating atraumatic procedures for the enucleation of malignant melanoma of the choroid. Cryosurgery represents an effective method of blocking the melanoma prior to enucleation in such a manner that an intraoperative dissemination of tumor cells is unlikely. The technology which is at present widely used for this purpose (Fraunfelder et al.) has considerable disadvantages. For examples cryoapplication is only possible with favorable, i.e., peripheral tumor localization, since the cryoapplicator cannot be introduced into the orbit. Therefore, a cup-shaped cryoapplicator chilled by liquid nitrogen has been developed which can be introduced into the orbit. The operating temperature of -196 degrees C causes the half of the eyeball in which the tumor is located to freeze within 100 seconds. Subsequently the applicator is removed and the enucleation is continued in the traditional manner. The technical suitability of this procedure has meanwhile been demonstrated in 12 enucleations.
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PMID:[Cryoenucleation in malignant melanoma of the choroid]. 649 78

Two batches of 110 females C57Bl mice were grafted with B 16 melanoma, the first batch at the age of 67 days, the second at 82 days. The animals were divided into groups of 10, and kept under a LD 12 : 12 regimen. The growth of the tumors was more rapid in the second batch. This was accompanied in this batch, by a decrease in body growth, a diminution of heart rate and an increase in QRSII amplitude. Significant decreases in carbon dioxide emission (VCO2) level, mostly during the dark period of time, when the mice had their greatest activity, and decrease in respiratory photic variations at light transitions were obtained when the tumors were well developed. Harmonic analysis of the continuous recording of carbon dioxide shows slight changes in VCO2 ultradian (40 minutes less than tau less than 12 hours) rhythms. The effects on respiration were confirmed by different survival rates and rectal temperatures between tumor grafted and controls submitted to an acute nitrogen normobaric hypoxia.
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PMID:Effects of B16 melanoma transplantation on the respiration of grouped C57Bl female mice. 652 37


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