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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In work involving modeling of response surfaces to describe the effects of cancer chemotherapy treatments, it is important to define activity and therapeutic synergism in a statistically defensible manner. This requires the construction of confidence intervals around the estimated optimal treatment which has been achieved by use of an indirect method first proposed by Box and Hunter. Activity for a drug or a combination can be claimed at 100(1 - alpha)% level of confidence when the 100(1 - alpha)% confidence interval about the optimal treatment excludes a zero dose. Results of treatment of B16 melanoma and Lewis lung carcinoma with 3,4-dihydroxybenzohydroxamic acid are used to demonstrate this definition. Extensions of this concept lead to a statistically valid definition of therapeutic synergism. If the confidence region about the optimum combination of k drugs does not contact any of the k - 1 dimensional subspaces, then a k drug therapeutic synergism can be claimed. In the event that a k drug therapeutic synergism cannot be claimed, there may be subsets of the drugs which do combine with therapeutic synergy. These concepts are demonstrated by two- and three-drug combination experiments in L1210-bearing C57BL/6 x DBA/2 F1 (B6D2F1) mice. Razoxane and dacarbazine show therapeutic synergism at a 95% confidence level. A three-drug combination of 5-fluorouracil, Teniposide, and mitomycin C is considered. In this case, although the estimated optimum treatment includes 48.1 mg of 5-fluorouracil per kg, 15.9 mg of Teniposide per kg, and 3.9 mg of mitomycin C per kg, the confidence region generated failed to confirm at an 80% level of confidence that 5-fluorouracil was a necessary component of the best treatment.
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PMID:Drug activity and therapeutic synergism in cancer treatment. 680 34

We report here the single and combined antitumor activity on B16 melanoma in female C57BL/6 X DBA/2F1 mice bearing s.c. tumors of sodium ascorbate, carbidopa-levodopa methyl ester, and dietary phenylalanine and tyrosine deficiency. Groups of 15 mice were fed continuously one of three test diets both with and without sodium ascorbate (30 mg/ml) in the drinking water beginning 2 weeks before inoculation of 10(6) melanoma cells. The test diets included the following amounts of tyrosine-phenylalanine: commercial, 1.09 and 0.64%; purified, 0.6 and 0.3%; and deficient, 0.08 and 0.04%. Drug-treated groups received daily injections of carbidopa (100 mg/kg) and levodopa methyl ester (1000 mg/kg) i.p. for 15 days beginning 1 day after tumor transplant. Tumor growth curves and median survival time were determined. Ascorbate stimulated tumor growth in the commercial diet group. In mice fed the purified diet, ascorbate inhibited growth in some tumors, while it had no effect on others. Ascorbate inhibited tumor growth in mice fed the deficient diet, which itself severely inhibited tumor growth, and in this group increased survival by 82%. Drug treatment had little effect on tumor growth and survival of mice fed the commercial diet, but it significantly decreased growth and moderately increased survival of mice fed the purified diet. The deficient diet enhanced drug activity and increased survival of tumor-bearing mice by 73%. Combined therapy had little effect in mice fed the commercial diet;l however, mice fed the purified diet and receiving drug and ascorbate had smaller tumors and lived 55% longer. In mice fed the deficient diet, the combination retarded tumor growth and increased survival dramatically by 123%. These data indicate that adding ascorbate and restricting tyrosine and phenylalanine in combination with levodopa methyl ester therapy may become an important strategy for treating malignant melanoma.
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PMID:Sodium ascorbate enhancement of carbidopa-levodopa methyl ester antitumor activity against pigmented B16 melanoma. 683 35

Hemicalcium ascorbate (Ca-Asc, 51 mM, 1% wt/vol), added to the drinking water, had the following effects in DBA/2 mice inoculated with 10(5) S91 (Cloudman) melanoma cells: 1) it delayed the appearance of visible tumors by 2-4 weeks; 2) it increased the survival rate at three months after tumor challenge by 12-50%; 3) it had no significant effect on the rate of tumor growth once the size of the tumors had reached 10 mm3; 4) the inhibition was maximal when the treatment with Ca-Asc was started at least one week prior to the inoculation of cells 5) when free ascorbic acid was used instead of Ca-Asc, the animals consumed 50% less water, they became dehydrated and the treatment was less effective; 6) Ca++ (51 mM) alone had no significant inhibitory effect.--Since Ca Asc (1 mM) was not toxic to S91 melanoma cells in vitro, we suggest that prophylactic treatment of the animals with Ca-Asc inhibited tumor development by increasing the resistance of the host.
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PMID:Inhibition of transplantable melanoma tumor development in mice by prophylactic administration of Ca-ascorbate. 683 4

Mice of four different inbred strains (CBA, Balb/c, C57Bl/6 and DBA/2), bearing different transplanted tumours (methylcholanthrene-induced sarcomas, B16 melanoma and P-815 mastocytoma), were tested for cellular immune reactivity to the synthetic encephalitogenic peptide of human myelin basic protein by the leucocyte adherence inhibition (LAI) assay. All exhibited reactivity at about the same optimal concentration of peptide. Normal mice of all strains and pregnant CBA mice were non-reactive. Blocking of LAI was detected with serum obtained 10 or more days after tumour transplantation. Sera from mice bearing different transplanted tumours abrogated the adherence-inhibitory effect of peptide on sensitized syngeneic peritoneal leucocytes. The blocking factors were cross-reactive between different tumours only within the same mouse strain, indicating a requirement for genetic compatibility between donors of the reactive cells and the serum blocking factors.
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PMID:Restricted activity of serum blocking factors related to a common tumour antigen in mice. 684 50

We examined the ability of uridine to increase the therapeutic index of 5-fluorouracil (FUra) against C57BL/6 X DBA/2 F1 mice bearing a Day 1 B16 melanoma or L1210 leukemia. FUra (400, 600, or 800 mg/kg, i.p.) followed in 24 hr by a 5-day s.c. infusion with uridine (5 g/kg/day, s.c.) was compared with the maximum tolerated dose of FUra (200 mg/kg, i.p.) plus a 5-day infusion with 0.9% NaCl solution. High-dose FUra plus delayed infusion with uridine was more effective than FUra (200 mg/kg) in inhibiting the growth of the B16 melanoma. High-dose FUra plus uridine rescue was, however, no more effective than FUra (200 mg/kg) in increasing the survival times of mice bearing the L1210 leukemia. To see if uridine rescue from FUra toxicity correlated with effects against a sensitive normal tissue, bone marrow nucleated cellularity of normal, non-tumor-bearing mice was monitored after drug treatment. In mice treated with FUra (200 mg/kg) followed in 24 hr by a 5-day infusion with either uridine (5 g/kg/day) or 0.9% NaCl solution, there was not as great a decrease in cellularity at the nadir with uridine, and, in addition, uridine accelerated recovery as compared to 0.9% NaCl solution. Furthermore, uridine (5 g/kg/day), but not thymidine (dThd) (5 g/kg/day) or 2'-deoxyuridine (dUrd) (5 g/kg/day), had a sparing effect on the depression in bone marrow nucleated cellularity seen at the nadir on Day 4 after Fura (200 mg/kg). The specificity of uridine to rescue mice from the lethal toxicity of the related fluorinated pyrimidines, 5-fluorouridine and 5-fluoro-2'-deoxyuridine, was also examined. Mice were treated with 5-fluorouridine (250 mg/kg, i.p.) followed in 24 hr by a 5-day infusion with uridine (1, 5, or 10 g/kg/day), dThd (1, 5, or 10 g/kg/day), or dUrd (1 or 5 g/kg/day). Uridine (1, 5, or 10 g/kg/day) rescued mice from the lethal toxicity of 5-fluorouridine, whereas dThd or dUrd was ineffective. Similarly, a 5-day infusion with uridine, but not dThd or dUrd, rescued mice from the lethal toxicity of 5-fluoro-2'-deoxyuridine (1800 mg/kg, i.p.).
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PMID:Use of uridine rescue to enhance the antitumor selectivity of 5-fluorouracil. 685 Jun 28

The growth rate of Cloudman S91 melanoma cells was compared in groups of normal and immunologically compromised DBA/2 mice that had undergone thymectomy and treatment with antilymphocyte serum. Tumor growth was markedly accelerated in the immunosuppressed animals. Other groups of normal and immunosuppressed animals were treated with daily injections of either histamine, the H-2 antihistamine cimetidine, the H-1 antihistamine pyrilamine; or the mast cell stabilizer proxicromil. Histamine treatment accelerated tumor growth, but only in normal animals and had little effect on tumor growth in immunocompromised hosts. Cimetidine treatment tended to increase tumor growth in normal hosts but this was statistically significant in only 1 of 3 experiments. In contrast, treatment with cimetidine, pyrilamine, or proxicromil always resulted in significant retardation of tumor growth in immunosuppressed animals. These data are consistent with the notion that thymectomy and treatment with antilymphocyte serum results in enhanced tumor growth that is in part due to activation of histamine-dependent suppressor cells. In this system, histamine activation of suppressor cells may be reversed by treatment with either antihistamines or proxicromil, a drug that prevents mast cell release of histamine. However, since the effects of these drugs seem to depend on the immune status of the host, thorough evaluation of immunoregulatory function and careful testing to determine whether histamine blockers reduce or promote tumor growth would seem indicated when immunomodulatory treatment with these drugs is contemplated.
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PMID:The effect of histamine, antihistamines, and a mast cell stabilizer on the growth of cloudman melanoma cells in DBA/2 mice. 686 77

The synchronization of the circadian rhythms of [3H]thymidine uptake (as gauge of DNA synthesis and presumably of cell proliferation) in colon, thymus, and Harding-Passey melanoma were studied in 456 male BALB/c X DBA/2F1 mice under a 12-hr-light, 12-hr-dark regimen. In two groups of animals, the feeding time was restricted to 4 hr/day (either at the beginning of the light span or at the beginning of the dark span). The circadian rhythms in body temperature and [3H]thymidine uptake in the colon were determined in their timing primarily by the time of food intake. In contrast, the circadian rhythm of [3H]thymidine uptake in the thymus and in the transplanted melanoma remained synchronized with the lighting regimen, and under the conditions of this study, was not altered in its timing by the change in feeding time. It thus appears feasible to alter the phase relations between certain circadian rhythms of host and tumor. If applicable to the human situation, this observation might be of interest for the scheduling of chemo- and radiotherapy, in an attempt to obtain maximal effects upon the tumor with minimal undesired side effects upon vital functions of the host.
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PMID:Change in phase relations of circadian rhythms in cell proliferation induced by time-limited feeding in BALB/c X DBA/2F1 mice bearing a transplantable Harding-Passey tumor. 687 48

A factor which is responsible for the growth inhibitory properties of certain mouse sera and related to NK-activity, has been studied. The factor was isolated from hybrid B6D2F1 (C57Bl/6 x DBA/2) serum, which is histo-compatible with the mouse tumour (B16 melanoma) used and has high NK-activity. Growth inhibitory activity was measured in an in vitro assay. It was independent of complement activation. The responsive factor was isolated and characterized by ion exchange chromatography. Concanavalin A affinity chromatography, gel filtration and iso-electric focusing. It appears to be a protein and had been labelled growth-inhibitory factor (GIF). It has a molecular weight of 230 000-260 000 daltons and an iso-electric point in the pH range 4.6-5.0. It was not retained on Concanavalin A columns.
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PMID:Purification and characterization of a mouse serum protein with growth inhibitory properties in vitro against tumor cell lines. 688 Jul 47

Normal resident peritoneal macrophages from C3D2 (C3H/Tif X DBA/2) F1 mice were activated in vitro by culturing with semisyngeneic tumour cells. The tumour cells originated from a methylcholanthrene-induced sarcoma (MC1M) growing in vivo in ascites form. Macrophage-mediated cytotoxicity was evaluated after 5 days of in vitro culture, using five different target cells. Semisyngeneic (L 929), allogeneic (B16 melanoma), and xenogeneic (HeLa) tumour cell lines and normal allogeneic fibroblast cell lines (3T3, 3T6) were tested. The morphology and kinetics of the cytotoxicity reaction were studied by scanning electron microscopy and compared with release of radioactivity from 14C-thymidine-labelled target cells. The activated macrophages were able to kill the semisyngeneic, allogeneic, and xenogeneic tumour cell lines tested under conditions that did not affect normal fibroblasts. The requirement for T cells during activation of the macrophages was also tested. The cytotoxicity decreased markedly when T cells were removed from the macrophage cultures before activation or when macrophages from nude mice were used in the experiments.
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PMID:In vitro cytotoxicity of mouse macrophages activated by coculture with syngeneic sarcoma cells. 698 15

An animal model which allows for the implantation and development of intracutaneous melanoma is described. Intradermal vesicles are created by a negative pressure apparatus in DBA/2J mice. S91 melanoma cells are injected into the blister cavities. Tumor growth occurs within 7 days and the yield approaches 100%. This model is a rapid, efficient, and applicable system for the study of melanoma growth dynamics and of the effects of systemic and topical anti-tumor agents on melanoma proliferation.
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PMID:Animal model of intracutaneous melanoma. 705 52


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