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

The therapeutic usefulness of chlorpromazine (CPZ) and caffeine (CAF) in combination with selected nitrosoureas was investigated in mice bearing L1210 leukemia, Lewis lung carcinoma, and B16 melanoma. We found that using BCNU with either CAF or CPZ was therapeutically superior to using either agent alone to treat mice bearing L1210 leukemia. Administering all three drugs in combination did not improve upon the therapeutic responses obtained with the two-drug combinations. In mice implanted with Lewis lung carcinoma or B16 melanoma, responses to treatment with the triple combination of methyl-CCNU, CAF, and CPZ suggested, but did not clearly establish, superiority over each two-drug combination or methyl-CCNU alone.
 ...
PMID:Therapeutic potentiation of nitrosoureas using chlorpromazine and caffeine in the treatment of murine tumors. 75 16

Frequency and distribution of 5-fluorodeoxyuridine (5-FdU) plus caffeine-induced fragile sites on chromosomes of peripheral blood lymphocytes (PBL) from 10 patients with cutaneous melanoma were studied in comparison with 10 PBL samples from normal donors of corresponding sex and age. The total number of breaks showed a significant difference among individuals in both groups, however, the average frequencies of 5-FdU plus caffeine-induced, as well as spontaneous damages in PBL from melanoma patients, were higher than those from healthy volunteers. The analysis of the breakpoint distribution showed a statistically significant increase in the expression of several fragile sites. The highest enhancement was observed at 1p32 and 1p22 sites (p less than 0.001). Earlier, the increase in the expression of 1p32 fragile sites was reported for neuroblastoma patients. We believe that enhanced expression of fragile sites in 1p may play a yet-unknown pathogenetic role in the development of some neuroectodermal tumors.
 ...
PMID:Enhanced expression of 1p32 and 1p22 fragile sites in lymphocytes in cutaneous malignant melanomas. 153 Aug 33

We have examined the effect of caffeine on the concomitant processes of the repair of potentially lethal damage (PLD) and the synthesis of X-ray-induced proteins in the human malignant melanoma cell line, Ul-Mel. Caffeine administered at a dose of 5mM after X radiation not only inhibited PLD repair but also markedly reduced the level of XIP269, a major X-ray-induced protein whose expression has been shown to correlate with the capacity to repair PLD. The expression of the vast majority of other cellular proteins, including seven other X-ray-induced proteins, remained unchanged following caffeine treatment. A possible role for XIP269 in cell cycle delay following DNA damage by X irradiation is discussed.
 ...
PMID:Effect of caffeine on the expression of a major X-ray induced protein in human tumor cells. 200 Apr 55

Human malignant melanoma cells (G-361) were irradiated with X-ray for different irradiation times. The amount of DNA damage was much increased by the treatment of the cells with HpO before X-ray irradiation. Furthermore, it was found that the caffeine inhibited effectively the repair of the damaged DNA. Furthermore, HpO was administered before X-ray irradiation of transplantable skin tumor in C3H mice and/or caffeine+ was to be given the mouse after X-ray irradiation. The growth of the tumor irradiated with HpO and/or caffeine was more inhibited and the necrotic area was more expanded than that of the tumor irradiated X-ray only. Labeling Index utilizing bromodeoxyuridine (BrdU) in the viable area of the treated tumor decreased when HpO and/or caffeine were administered. The amount of DNA damage more increased in the tumor cells irradiated with HpO than that irradiated only. And, the repair of the damaged DNA was more delayed in the tumor cells irradiated with HpO and caffeine than that irradiated with the other treatments. In conclusion, it was considered that HpO might be a radioactive sensitizer and caffeine enhanced the inhibition of the repair of DNA damaged. We hope that the treatment of X-ray radiation with HpO and caffeine is useful for clinical treatment of human malignant tumor.
 ...
PMID:[A sensitization effect of hematoporphyrin oligomer (HpO) and caffeine for X-ray radiation of skin cancer]. 221 35

We preliminarily investigated the combined effects of cisplatin and caffeine on murine melanoma B16-BL6 cells in vitro. When caffeine was added before or simultaneously with cisplatin, there was little growth inhibition. The addition of 2.0 mM caffeine after 1 h of exposure to cisplatin inhibited growth and induced cell differentiation. This treatment resulted in fewer cells, and the numbers of melanosomes and mitochondria and the amount of Golgi's complex and endoplasmic reticulum were increased. DNA histograms obtained by flow cytometry showed that cells treated with cisplatin alone accumulated in the G2/M phase, with a partial G2 block. The addition of 2.0 mM caffeine after 1 h of treatment with cisplatin reduced this block. Caffeine caused murine melanoma B16-BL6 cells treated with cisplatin to differentiate, and this inhibited growth.
 ...
PMID:Growth inhibition and differentiation of murine melanoma B16-BL6 cells caused by the combination of cisplatin and caffeine. 251 52

Combined effect of cisplatin and caffeine on murine B16-BL6 melanoma cells was studied. Synergistic inhibition of the cell growth was observed when caffeine (2 mM) was added continuously after one hour exposure of cisplatin. On the other hand, when caffeine was added before one hour exposure of cisplatin or one hour simultaneous exposure with cisplatin, synergistic effect was not shown. In the analysis of DNA histogram obtained from flow cytometry, S and G2/M accumulation was observed by the treatment of cisplatin and that accumulation was reduced by the combination of cisplatin and caffeine. From this findings, it was suggested that caffeine would inhibit DNA repair process. Furthermore, according to morphological studies with hematoxylin-eosin stain and Fontana-Masson stain, the addition of caffeine alone resulted in mild swelling of melanoma cells and the decrease of nuclear-cytoplasmic ratio. The combination of cisplatin and caffeine caused marked swelling of melanoma cells and remarkable increase of dendrite-like processes. Melanogenesis was also enhanced by the addition of these two drugs. Many matured melanosomes, increases of mitochondria, Golgi's apparatus and endoplasmic reticula were observed by the use of electron microscope. These findings implied that the combination of cisplatin and caffeine induced a differentiation of murine melanoma cells.
 ...
PMID:[Combined effect of cisplatin and caffeine on murine B16-BL6 melanoma cells]. 273 93

Tonicity shock or caffeine postirradiation treatment makes evident fast-type potentially lethal damage (PLD). Caffeine expresses fast-type PLD more efficiently than tonicity shock in X-irradiated B-16 mouse melanoma cells, compared with V79 Chinese hamster cells. The survival curves of thermal neutrons for either V79 or B-16 cells exhibit no shoulder. Neither V79 nor B-16 cells show the sublethal damage (SLD) repair of thermal neutrons. Caffeine-sensitive fast-type PLD repairs exist in X-irradiated B-16 cells, as well as V79 cells. The fast-type PLD repair of B-16 cells exposed to thermal neutrons alone is rather less than that of X-irradiated cells. Furthermore, an extremely low level of fast-type PLD repair of B-16 cells with 10B1-paraboronophenylalanine (BPA) preincubation (20 hours) followed by thermal neutron irradiation indicated that 10B(n,alpha)7Li reaction effectively eradicates actively growing melanoma cells. The plateau-phase B-16 cells are well able to repair the slow-type PLD of X-rays. However, cells can not repair the slow-type PLD induced by thermal neutron irradiation with or without 10B1-BPA preincubation. These results suggest that thermal neutron capture therapy can effectively kill radioresistant melanoma cells in both proliferating and quiescent phases.
 ...
PMID:Sublethal and potentially lethal damage repair on thermal neutron capture therapy. 279 26

Chlorpromazine (CPZ) and caffeine (CFN) enhance the cytotoxicity of nitrosoureas in conventional murine tumor systems, but this effect was not confirmed in a randomized clinical trial which compared the action of semustine (MeCCNU) against the combination of MeCCNU, CPZ, and CFN. Since differences in repair systems are known to exist between cells of human or murine origin, we have employed a human melanoma xenograft system to quantify the drug interaction. The enhancement in human melanoma cells was similar to that observed with conventional murine tumor systems. Alkaline elution studies and determination of radioactivity from labeled MeCCNU pointed to increased drug retention and fixation of DNA damage as the mechanism of enhancement. Although toxicity studies were limited to murine tissues, there was evidence of increased toxicity, especially if MeCCNU was combined with both CPZ and CFN. Thus, a true therapeutic synergism may not be present for the combination. Some explanations for the failure to detect such drug interaction in clinical trials and the relevance of advanced preclinical tumor systems are discussed.
 ...
PMID:Enhancement of semustine-induced cytotoxicity by chlorpromazine and caffeine in a human melanoma xenograft. 375 39

The Mer- human melanoma cell line MM253c1 was treated four times with cyclophosphamide activated in situ with rat liver microsomes, the fourth cycle being preceded by treatment with the mutagenic methylating agent N-methyl-N1-nitro-N-nitrosoguanidine. The resulting subline (MM253c1-4CG) showed increased resistance to activated cyclophosphamide; the resistance of seven allogeneic human tumor lines and of a fibroblast strain spanned the two extremes represented by the autologous MM253c1 lines. MM253c1-4CG cells were highly resistant to killing by methylating agents, a property indicative of conversion to the Mer+ phenotype. Compared with the parent line, MM253c1-4CG cells were resistant to DNA cross-linking agents having different structures and transport mechanisms (melphalan, mechlorethamine, and mitomycin) and were slightly more resistant to doxorubicin, gamma rays, and hydroxyurea, but were not resistant to killing by acrolein, cytarabine, hydrogen peroxide, 254 nm UV, [3H]thymidine, or vincristine. No difference in the intracellular concentration of potential alkylation targets (RNA, protein, and SH groups) was found, and neither cell line appeared able to activate cyclophosphamide or detoxify its metabolites. Caffeine and 3-aminobenzamide had no synergistic effect upon cyclophosphamide toxicity in either cell line. 3-Aminobenzamide showed synergism with the methylating agent 5-(3-methyl-1-triazeno)imidazole-4-carboxamide, the effect being greater in MM253c1-4CG than in MM253c1 cells. These results suggest that in vitro activation of cyclophosphamide produces a metabolite similar in stability to phosphoramide mustard, resistance to such toxicity being associated not with conversion to the Mer+ phenotype but with some intracellular change with confers resistance to a variety of DNA cross-linking agents.
 ...
PMID:Cyclophosphamide resistance developed in a human melanoma cell line. 652 97

In the human melanoma cell line MM127 , the melphalan survival curve was linear and exhibited reciprocity with respect to concentration and treatment time. The survival curve of an allogeneic line, MM253c1 , exhibited a shoulder and, on a concentration X time basis, was resistant to 1-hr compared with 4-hr treatment. This type of resistance, which was not found using chlorambucil, nitrogen mustard, or methyl methanesulfonate, could be overcome by simultaneous hyperthermia (42 degrees) but not by treatment with thymidine or caffeine. Both lines had similar levels of DNA interstrand cross-linking (perchlorate renaturation method) after 1-hr treatment, but MM253c1 cells were able to repair most of this damage during the next 23 hr. The cross-links formed in MM253c1 cells after 1 hr were predominantly heat sensitive and photoresistant , whereas those formed in MM127 cells were heat resistant and photosensitive. These results suggest that melphalan formed repairable (possibly diadeninyl or adeninyl - guaninyl ) cross-links in MM253c1 cells during the first hr of treatment and nonrepairable , possibly diguaninyl cross-links in MM127 cells at all stages of treatment. It appears therefore that the mode of action of melphalan and the effect of synergistic agents may not be identical in all cells.
 ...
PMID:Dependence on treatment time of melphalan resistance and DNA cross-linking in human melanoma cell lines. 672 5


1 2 3 4 Next >>