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

Supernatants of established cultures of human neoplastic and normal cells have been shown to contain a number of different biological activities, including inhibition of DNA synthesis as measured by thymidine uptake. We have found that supernatants of melanoma cell lines contain an inhibitor of thymidine uptake which is heat labile, ultraviolet sensitive, non-filtrable (0.22 mu) and partially sedimentable at 20,000 x g. The mechanism of action of the inhibitor involves the degradation of 3H-thymidine to a non-utilisable form, which we detect by failure of uptake of 3H-thymidine by cultures of mitogen stimulated lymphocytes to which the inhibitor is added. While microbiological tests have failed to reveal mycoplasma contamination of inhibitor producing cultures, treatment of these cultures with kanamycin suppresses inhibitor production. Qualitative evaluation of DNA synthesis by the inhibitor producing cultures using autoradiography and fluorescent DNA staining has confirmed the presence of mycoplasma. With the widespread use of established cell lines in cancer research, it is imperative that screening for mycoplasma contamination go beyond routine microbiological assays. Detection of 3H-thymidine degradation by cell culture supernatants is an additional simple and sensitive indirect test which could be used for this purpose.
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PMID:Characterisation of an inhibitor of thymidine uptake produced by cultured human melanoma cells. 74 9

Sociopolitical and economic climates between 1950 and 1975 favored the funding of cancer research, attracted imaginative policy makers, encouraged investigators, and generated new knowledge for clinical application. Important advances during this period include the discovery that DNA alteration is requisite for carcinogenesis and that DNA repair processes are important deterrents in the development of cancer. The better understanding of the histogenesis of epidermal cancer and melanoma has potential clinical value. More easily grasped is the progress made in the therapeutic control of mycosis fungoides and epidermal cancer. Complete control of epidermal cancer is now a foreseeable reality.
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PMID:Cutaneous oncology 1950-1975. 77 91

The history and origin of the science of photobiology are reviewed. Interest in the biologic effects of light gradually increased, beginning with the discovery of ultraviolet and infrared radiation early in the 19th century. The basis of experimental photobiology was laid by the studies of Raab and Tappeiner on photodynamic action and the early uses of phototherapy by Finsen and Dorno. The discovery of the association of porphyrins with some light-related skin diseases and of the capability of chemical agents such as coal tar and bergamot to induce phototoxic contact dermatitis resulted in a flurry of clinical investigations leading to better understanding of the processes of phototoxicity and photoallergy. The early epidemiologic studies of Unna and Dubreuilh relating solar radiation exposure to the formation of actinic keratoses and non-melanoma skin cancer were experimentally confirmed in animals by Findlay, Roffo, and Blum. In the most recent quarter century (1950-1975), cellular and molecular photobiology has been refined. The studies on photochemistry of nucleic acid and of damage and repair mechanisms in DNA have set the stage for understanding the basic processes of biologic effects of light and promise the development of useful applications of specifically directed phototherapy and prevention of such light-induced diseases as skin cancer.
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PMID:Cutaneous photobiology: past, present and future. 77 94

The therapeutic activity of ftorafur was compared to that of 5-fluorouracil (5-FU) in a number of tumor systems. The drugs were active against ip L1210 leukemia when administered ip, sc, or orally. Administration every fourth day x 3 proved to be the most effective treatment schedule for both drugs, although significant activity was seen on all treatment schedules tested. Both congeners had activity against sc implanted L1210 leukemia as well as a limited effect on the ic implanted tumor. 5-FU produced greater increases in lifespan of mice bearing L1210 leukemia than did ftorafur. 5-FU was also more effective against ip B16 melanoma and ip Gardner 6C3HED lymphosarcoma. Ftorafur was ineffective in the treatment of mice bearing ip P388 leukemia, a tumor which is quite sensitive to 5-FU. At approximately equimolar doses both drugs produced a persistent inhibition of 2'-deoxyuridine incorporation into DNA of L1210 cells in vivo. Ftorafur produced a greater inhibition of uridine incorporation into RNA than did 5-FU, which may account for the lower therapeutic activity of ftorafur. In combination chemotherapy of L1210 leukemia 5-FU plus ftorafur was no more effective than 5-FU alone, neither of the congeners was synergistic with either adriamycin or actinomycin D, and in combination with methotrexate therapeutic synergism was observed with 5-FU but not with ftorafur. After eight transplant generations of exposure to ftorafur, a subline of L1210 leukemia became totally resistant to ftorafur and simultaneously cross-resistant to 5-FU. Doses of ftorafur and 5-FU which were optimally effective in mice bearing the parental L1210 line were lethal to mice implanted with the ftorafur-resistant subline. When treatment of the resistant subline was discontinued after nine transplant generations of exposure to ftorafur, sensitivity to 5-FU returned after three transplant generations without ftorafur. The subline retained its resistance to ftorafur until eight transplant generations after cessation of ftorafur treatment. Another subline of L1210 leukemia exposed to 5-fU for 20 transplant generations proved to be completely resistant to 5-fu and cross-resistant to ftorafur. The mutual cross-resistance between ftorafur and 5-FU supports the contention that ftorafur acts primarily as a depot form of 5-FU.
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PMID:Comparison of 5-fluorouracil and ftorafur. II. Therapeutic response and development of resistance in murine tumors. 79 50

We have studied the kinetics of suppression of tyrosinase activity and tumorigenicity in unsynchronized B16 mouse melanoma cells (clone B559) exposed to 5-bromodeoxyuridine (BrdU, 3 mug/ml) for one or two cell divisions, then cultured in BrdU-free medium (RM) for five or six days. Bromouracil replaced about 23% of thymine residues after 24 hours (1 cell division) and almost 40% after 48 hours (2 cell divisions) in the presence of BrdU. Upon subsequent growth in RM the extent of replacement declined in a manner consistent with dilution by new DNA synthesis, reaching 5-10% substitution by day 7 of these experiments. Tyrosinase activity was significantly reduced after treatment with BrdU for 24 or 48 hours but continued to decline after the cultures were changed to RM, approaching undetectable levels on day 7. The time course of reduction was similar to that previously determined in cells grown continuously for seven days in the presence of BrdU. Therefore, suppression of tyrosinase activity can result from incorporation of BrdU during a single cell cycle, but requires about seven days for full manifestation of the effect. Tumorigenicity decreased to 55% after 24 hours and to 15% after 48 hours with BrdU but rapidly reversed to approach that of untreated melanoma cells when subsequently grown in RM for 5-6 days. The effects of BrdU on total RNA or protein synthesis, or on plating efficiency appeared insufficient to account for the degree of suppression observed. Our results indicate that substitution by bromouracil into either strand of DNA loci controlling tyrosinase activity or tumorigenic potential may be sufficient for suppression. In addition, they demonstrate that such brief treatment with BrdU may be used to probe the regulation of differentiated function and tumorigenicity in these melanoma cells.
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PMID:Suppression of melanoma cell tyrosinase activity and tumorigenicity after incorporation of bromouracil for one or two cell divisions. 81 76

Theophylline, a phosphodiesterase inhibitor, was found to be a potent stimulator of melanogenesis in the RPMI 3460 hamster melanoma cell line. This stimulation was greater than that caused by either dibutyryl cyclic AMP (db-cAMP) or another phosphodiesterase inhibitor, papaverine. Theophylline and db-cAMP treatments also produced strikingly different morphologies in the monolayered cells. The theophylline effect on melanogenesis was diminished by db-cAMP, whereas simultaneous treatment of cells with db-cAMP and papaverine produced greater stimulation of melanotic activity than either agent acting alone. Theophylline, therefore, may have phenotypic effects that are at least partially independent of phosphodiesterase inhibition. Theophylline stimulated melanin biosynthesis, as measured by rates of 2-[2-14C] thiouracil incorporation, and also caused an increase in the level of tyrosinase (EC 1.10.3.1) activity. This melanotic stimulation was prevented by the presence of cordycepin or cycloheximide. Theophylline inhibited DNA synthesis and mitosis in the melanoma cell cultures but stimulated protein synthesis. However, inhibition of proliferation and the first appearance of induced melanotic activity did not bear an immediate direct relationship to one another.
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PMID:Stimulation of melanotic expression in a melanoma cell line by theophylline. 81 64

When cultured in vitro, human malignant melanoma cells proliferated in two patterns: In one the cells were polygoneal or spheroidal unequal in form and size, whereas in the other, the cells were elongated, fusiform, poorly delimited, with various degrees of atypism. Antisera to each of these two types of malignant melanoma cell cultures were raised in rabbits. The antiserum cytotoxic activity was assessed against 10 cultures of malignant melanoma cells, 10 mammary carcinoma, 2 fibrosarcoma and 10 normal skin fibroblasts. Prior and at intervals post surgery, the cytotoxic activity of serum from 10 patients with malignant melanoma was assessed against the above cell cultures. Based on their cytotoxic activities, the sera drawn from patients with melanoma thirty days after surgery had the highest cytotoxicity and could be classified into two groups similar to the rabbit antisera. Glycoprotein fractions were isolated from 3 M KCl extracts of the two melanoma cell types, i.e. from patients ShA and ZBJ. These glycoproteins stimulated 14C-2-thymidine uptake and DNA-polymerase activity of peripheral blood lymphocytes from post surgery melanoma patient. The glycoproteins had no effect on peripheral blood lymphocytes from normal donors.
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PMID:Human malignant melanoma cells: morphological and immunological variations. 84 Mar 39

A radioimmune assay for the antitumor agent, macromomycin, using purified, radioiodine-labeled macromomycin and antisera raised in rabbits against a carbodiimide-catalyzed macromycin-Limulus polyphemus hemocyanin complex has been developed. Radiolabeled macromomycin was prepared by direct iodination of the polypeptide antibiotic with the use of iodine monochloride or solid-state lactoperoxidase. Antibody-bound drug was isolated from free macromomycin with dextran-coated, activated charcoal. The standard curve of the sequential saturation assay was linear on a logit-log plot and indicated a lower limit of sensitivity of approximately 100 pg macromomycin. The radioimmune assay was suitable for measuring macromomycin in the presence of other antitumor drugs, and detection of macromomycin was quantitative when it was added to normal human serum or urine. Drug binding to melanoma and mammary carcinoma cell surfaces could be inhibited by preincubating macromomycin with affinity-purified antimacromomycin antibodies. However, once the drug was bound to cell surfaces, addition of antimacromomycin antibodies did not result in removal of the drug from cell surfaces or in reversal of macromomycin-induced inhibition of thymidine incorporation into cellular DNA. Antimacromovide useful tools for developing pharmacokinetic and toxicity studies of macromomycin, as well as for analyzing the mechanism(s) of action of the drug.
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PMID:Radioimmune assay and characteristics of antibodies to macromomycin (NSC 170105). 84 45

RNA biosynthesis catalyzed with DNA-dependent RNA polymerase was demonstrated in the reconstructed system containing isolated lymphocyte nuclei, Mg2+ or Mn2+ salts, ammonium sulphate, in the presence of four nucleosidetriphosphates. Both the Mg2+ and Mn2+-dependent forms of this enzyme were revealed in the nuclei of normal lymphocytes and those of patients suffering from melanoma, carcinoma of the lung and sarcoma. The activities of both forms of RNA-polymerase were greater in the nuclei of the lymphocytes from sick individuals than in the normal analogues. DNA-dependent RNA-polymerase sensitivity to dexamethasone and PHA of the nuclei of lymphocytes obtained from patients with carcinoma of the lung, melanoma, and sarcoma was decreased in comparison with the normal.
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PMID:[Sensitivity of the lymphocyte RNA-synthesizing system of patients with different malignant neoplasms to phytohemagglutinin and dexamethasone]. 85 72

The kinetics of initial arrest in organs, distribution, survival, and fate of 125I-iododeoxyuridine-labeled B16 melanoma tumor cells injected intravenously into normal, tumor-sensitized and immune manipulated syngeneic and allogeneic mice were investigated. Groups of animals were killed at intervals ranging from two minutes to 14 days after intravenous tumor cell injection. Lungs, liver, spleen and blood were collected from each animal and processed so that radioactivity associated with DNA of tumor cells viable at the time of sacrifice could be monitored. The following conclusions can be made: initial tumor cell arrest in organs is influenced by the host immune status but it does not correlate with the survival kinetics or development into tumors. The same tumor, which was rejected in mice after a subcutaneous tumor challenge, grew in the lungs after intravenous injection. Therefore, rejection of a subcutaneous challenge as the sole criterion of host immunity to neoplasms should be questioned. Allogeneic animals are not appropriate for use as a model system for the study of experimental metastasis. Animals sensitized to a tumor exhibit kinetic patterns of tumor cell arrest and survival that differ from normal syngeneic hosts.
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PMID:Relationship of host immune status to tumor cell arrest, distribution, and survival in experimental metastasis. 88 May 70


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