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

Immunofluorescence was used to examine antibodies to cellular antigens in the sera of patients with malignant melanoma. Sera from 60 melanoma patients and from 33 control individuals (13 normal subjects and 20 disease controls) were studied. Ninety % of the melanoma sera were found to have antinuclear antibodies when epithelial cell lines or melanoma lines were used as substrates for their detection, compared to 18% in the control group. Antinucleolar antibodies and anticytoplasmic antibodies were present in 32 and 17%, respectively, in malignant melanoma but none in the controls. Antinuclear and antinucleolar antibodies could be classified into different types according to different patterns of staining and susceptibility of antigens to digestion with DNase, RNase, and trypsin. Certain types of antibodies, such as those showing granular nuclear staining, appeared to be associated with less advanced stages of malignant melanoma, whereas those showing nucleolar and large speckled nuclear staining were associated with more advanced stages of the disease.
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PMID:Antinuclear, antinucleolar, and anticytoplasmic antibodies in patients with malignant melanoma. 633 6

Deoxyribonuclease activities were examined in isoelectric focusing fractions of non-histone, chromatin-associated and nucleoplasmic proteins of isolated normal human lymphoblastoid and mouse melanoma cell nuclei using parallel procedures. A very similar series of eight DNA endonucleases, each active on calf thymus DNA and containing no exonuclease activity, were found in the chromatin proteins of both cell lines. Several differences were observed: an activity in human cells at pI 6.6 was absent from murine cells, and there was an increased activity in mouse cells at pI 4.4 and a decreased activity at pI 7.3, as compared with corresponding human cell activities. Assay of these fractions against supercoiled, circular phage PM2 DNA showed greater activity among the fractions with acidic pI valves and slightly lower activities in the murine cells than in the human cells. Analysis of the nucleoplasmic fractions showed a series of DNA endonuclease and exonuclease activities which were again very similar between the two cell lines, although greater endonuclease activity at pI 4.4 occurred in mouse than in human nucleoplasm. These results demonstrate an entire series of deoxyribonuclease activities in both chromatin and nucleoplasm which are nearly identical in two very different mammalian cell lines, suggesting that many of these enzymes are ubiquitous in mammalian cell nuclei.
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PMID:Nuclear deoxyribonuclease activities in human lymphoblastoid and mouse melanoma cells. A comparative study. 715 90

As part of a programme to study the predictive clinical value of a soft agar assay for measuring chemosensitivity of human melanomas in vitro, we have observed the effect of three disaggregation methods on the yield of tumor cells, plating efficiency in soft agar and chemosensitivity. The yields and plating efficiencies obtained, as well as sensitivity to DTIC, CCNU, vinblastine and abrin, were about the same whether collagenase/pronase/DNase-treatment, trypsin/EDTA-treatment or mechanical treatment was used. When melanoma xenografts of different sizes were studied, an inverse relationship between tumor size and plating efficiency was found, whereas chemosensitivity was unaffected by tumor size. The highest plating efficiencies of melanoma cells, both from patient biopsies and from xenografts, were obtained when red blood cells were present and a low oxygen concentration (5%) was used. The results demonstrate that, in the case of melanomas, the fraction of tumor cells that are clonogenic in vitro depends on the size of the tumors, and even more so on the culture conditions used. An important finding was that chemosensitivity in vitro appears to be unaffected by the disaggregation method and by tumor size.
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PMID:Cultivation of human melanomas in soft agar. Factors influencing plating efficiency and chemosensitivity. 731 75

We analyzed the biochemical nature of beta m-actin protein found in mouse B16 melanoma. When we carried out immunostaining with the antibody specific to beta m-actin, filamentous immunofluorescence was observed in B16-F1, a low-metastatic cell line expressing beta m-actin, but not in highly metastatic B16-F10 that did not express beta m-actin. When a purified actin fraction containing beta m-actin was polymerized and immunoprecipitated with anti-beta m-actin antibody, the immunoprecipitate contained beta m-, beta- and gamma-actin. This indicated that the beta m-actin was incorporated into an actin filament together with beta- and gamma-actin in vitro, and this phenomenon was consistently suggested by cellular double immunostaining with anti-beta m-actin and common anti-actin antibody. When the actin fraction containing beta m-actin under a regular depolymerizing condition was subjected to immuno-adsorption assay using anti-beta m antibody and protein-A Sepharose, the immunoadsorbed aggregates contained beta m-, beta- and gamma-actin. This indicates that the actin fraction was not completely depolymerized and contained beta m-actin-containing oligomers, which were too small to be precipitated with anti-beta m-actin antibody alone. The incomplete depolymerization of the beta m-actin-containing fraction was also suggested by the much lower DNase 1 inhibition activity of the beta m-actin-containing fraction than that of beta- and gamma-actin fraction. Furthermore, a DNase 1 binding assay showed that cytoplasmic supernatant prepared from B16-F1 under a low-ionic condition contained less monomeric actin than the cytoplasmic preparation from B16-F10. These results suggested that beta m-actin protein in B16 melanoma probably inhibits the dynamic conversion between the monomeric and polymerized forms of actin, leading to a decrease in cell motility and consequently the suppression of invasiveness and metastasis.
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PMID:Intracellular localization and biochemical function of variant beta-actin, which inhibits metastasis of B16 melanoma. 807 Nov 15

To evaluate the specificity and applicability to the study of human tumor cells of the reverse transcription (RT) in situ PCR and RT polymerase chain reaction (PCR) in situ hybridization techniques, we examined five melanoma cell lines and five nonmelanoma lines for tyrosinase mRNA using primers specific for tyrosinase. Each procedural step was optimized and minutely controlled, and results from the in situ techniques and solution-phase RT-PCR were compared. All melanoma lines showed a specific pattern of perinuclear cytoplasmic reaction not seen in nonmelanoma lines. There was exact agreement between the results from the RT in situ PCR and RT-PCR in situ hybridization techniques and those from solution-phase RT-PCR. Ribonuclease digestion abolished cytoplasmic staining, as did omission of the reverse transcriptase step. Nuclear staining was seen in melanoma and nonmelanoma lines, apparently as a result of DNA synthesis from repair-replication and mispriming or nonspecific amplification. Neither high concentrations of deoxyribonuclease nor long incubation periods abolished this effect completely. Demonstration of cytoplasmic mRNA by RT in situ PCR and RT-PCR in situ hybridization specifically identifies cells of melanocytic lineage.
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PMID:Demonstration of cytoplasmic tyrosinase mRNA in tissue-cultured cells by reverse transcription (RT) in situ polymerase chain reaction (PCR) and RT PCR in situ hybridization. 902 34

Antinuclear autoantibodies (ANAs) of healthy aged mice were recently found to specifically interact with the surface of various tumor vs. normal cells. We characterize the specificity of three monoclonal ANAs from healthy aged Balb/c mice by indirect immunofluorescent staining of fixed Hep-2 cells, ELISA assays, and Western blotting analysis. Two of these monoclonal antibodies, 2C5 and 1G3, exhibited specificity for nucleosomes. Subsequent flow cytometry experiments demonstrated that the 2C5 antibody recognizes nucleosomes on the surface of mouse EL4 T-lymphoma cells because antibody binding could be eliminated by pretreatment of these cells with DNase or heparin and approximately 10-fold increased after preincubation of cells with nucleosomes. The injection of monoclonal antibody 2C5 into ANA-negative young mice 1 day before tumor cell inoculation and on days 1, 3, and 5 thereafter significantly suppressed tumor development and increased survival. The antitumor activity of the 2C5 antibody is demonstrated for two syngeneic mouse tumor models, EL4 T-lymphoma and B16 melanoma. In vitro analyses revealed antibody-dependent cellular cytotoxicity (ADCC) as one antitumor mechanism of the 2C5 antibody. Based on these results, we postulate a beneficial role of antinucleosome autoantibodies as tumor-protective agents for an aging host or for antibody-mediated cancer therapy, and further speculate that the presence of such antibodies represents a so far unrecognized mechanism of immune surveillance against tumors.
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PMID:A novel class of antitumor antibodies: nucleosome-restricted antinuclear autoantibodies (ANA) from healthy aged nonautoimmune mice. 943 97

Cryptolepine hydrochloride is an indoloquinoline alkaloid isolated from the roots of Cryptolepis sanguinolenta. It is characterized by a multiplicity of host-mediated biological activities, including antibacterial, antiviral, and antimalarial properties. To date, the molecular basis for its diverse biological effects remains largely uncertain. Several lines of evidence strongly suggest that DNA might correspond to its principal cellular target. Consequently, we studied the strength and mode of binding to DNA of cryptolepine by means of absorption, fluorescence, circular, and linear dichroism, as well as by a relaxation assay using DNA topoisomerases. The results of various optical and gel electrophoresis techniques converge to reveal that the alkaloid binds tightly to DNA and behaves as a typical intercalating agent. In DNAase I footprinting experiments it was found that the drug interacts preferentially with GC-rich sequences and discriminates against homo-oligomeric runs of A and T. This study has also led to the discovery that cryptolepine is a potent topoisomerase II inhibitor and a promising antitumor agent. It stabilizes topoisomerase II-DNA covalent complexes and stimulates the cutting of DNA at a subset of preexisting topoisomerase II cleavage sites. Taking advantage of the fluorescence of the indoloquinoline chromophore, fluorescence microscopy was used to map cellular uptake of the drug. Cryptolepine easily crosses the cell membranes and accumulates selectively into the nuclei rather than in the cytoplasm of B16 melanoma cells. Quantitative analyses of DNA in cells after Feulgen reaction and image cytometry reveal that the drug blocks the cell cycle in G2/M phases. It is also shown that the alkaloid is more potent at inhibiting DNA synthesis rather than RNA and protein synthesis. Altogether, the results provide direct evidence that DNA is the primary target of cryptolepine and suggest that this alkaloid is a valid candidate for the development of tumor active compounds.
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PMID:The DNA intercalating alkaloid cryptolepine interferes with topoisomerase II and inhibits primarily DNA synthesis in B16 melanoma cells. 954 44

A multitherapy resistance (MTR) factor produced by Cloudman S91 mouse melanoma cells rescues a responsive cell line after gamma-irradiation, short wavelength ultraviolet light, mitomycin C, vinblastine and actinomycin D. A similar activity with respect to ionizing radiation is now shown to be produced by human melanoma cells and by both human and mouse breast cancer cells but not by five normal cell lines. In these studies, the factor produced in serum-free conditioned medium (SFCM) by Cloudman S91/I3 cells is further characterized. Its activity in a clonogenic assay using related Cloudman S91/amel cells is destroyed by trypsin but not by DNase and is stable for at least 8 days at a variety of temperatures including 37 degrees C. Molecules greater than 30 kDa from SFCM collected from S91/I3 cells were concentrated and separated by preparative zonal electrophoresis (PZE). Bioactivity was present in both the cathode- and the anode-running fractions. The active acidic (anode) fractions were analysed by preparative isoelectric focusing. Bioactivity was present between pI 3.5 and 4.2. These PZE fractions were also used to immunize two rabbits, both of which produced antiserum that abrogated the bioactivity of SFCM and of the PZE cathode fractions. Antiserum also decreased the survival of irradiated S91/I3 producer cells that do not respond to SFCM but nonetheless must require MTR proteins for the expression of radiation resistance. These studies present a model for the production of rescue factors by non-clonogenic tumour cells that may persist in some tumours for considerable periods of time.
Melanoma Res 1999 Feb
PMID:Therapeutic resistance: characterization and inactivation by specific antiserum of a putative protein family produced by tumour cells. 1033 33

The authors analyzed the effect of several 15-amino acid peptides with sequences related to tumor-rejection antigens, tyrosinase, and the MAGE family on peripheral blood mononuclear cells from healthy donors cultured for periods of 1 to 7 days. Some of these peptides promoted stimulation of monocytes, manifested by phenotypic changes, release of interleukin (IL)-1a, IL-6, and tumor necrosis factor-alpha, and induction of nitric oxide synthase on differentiated CD14++/+ CD16+ DR++ monocytes. An increase in the percentage of cytotoxic monocytes (CD14+/- CD16+) containing granule-associated DNase activity was also observed. Active peptides induced the release of IL-2 and interferon-gamma. Nonspecific natural killer and lymphokine-activated killer cell-mediated cytotoxicity was also observed against classical target cell lines (K-562 and Daudi) and allogenic melanoma cell lines AC and BB, together with an increase in granule-associated DNase in the natural killer cell-enriched population. Monocytes were needed to enhance this innate response, because peptides failed to induce the release of IL-2 on monocyte-depleted peripheral blood mononuclear cells. Data show an enhancement of the rapid innate immune response by peptides related to tumor rejection antigens and suggest that they could also determine the nature of a slow and more definitive specific immune response against tumor cells.
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PMID:Immunoregulating properties of peptides related to tumor rejection antigens: effect on human monocytes and natural killer cells. 1074 48

Immunostaining of the cell cycle-associated Ki-67 antigen was studied, using the Ki-67-specific MIB-1 monoclonal antibody on slides prepared by cytocentrifugation of cultured A375 melanoma cells. Immunomorphological analysis of the Ki-67 immunostaining pattern of both nuclear and nucleolar locations was carried out following pre-treatment of the slides including ribonuclease and deoxyribonuclease pre-digestion of the cells. Immunostaining of nucleolar Ki-67 was reduced by ribonuclease pre-digestion, but was not altered by deoxyribonuclease pre-treatment. Ribonuclease did not reduce the staining intensity of Ki-67 in the nuclear matrix, but the intensity decreased after deoxyribonuclease pre-digestion. We suggest that the Ki-67 molecule may play an important role in ensuring contact between nuclear DNA and nucleolar RNA during transcriptional processes in cell proliferation.
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PMID:Effect of Ribonuclease A and Deoxyribonuclease I on Immunostaining of Ki-67 in Cultured Melanoma Cells. 1117 87


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