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)

The half-lives of tyrosinase isozymes, a key enzyme in melanogenesis, have been determined using two different approaches: (a) cycloheximide treatment of mice bearing growing tumors and measurement of the residual enzymatic activity. This approach detected two soluble forms of cytosolic tyrosinase with half-lives of 1/2 and 8 h, respectively. The melanosomal isozyme showed a t1/2 of 3 1/2 h. (b) Metabolic labelling of tyrosinase with [35S]Met and immunoprecipitation analysis using a monoclonal antityrosinase. This method gave values slightly longer, 5 h and 9 1/2 h for the melanosomal and cytosolic tyrosinase, respectively. The origin of soluble tyrosinase and its utility to employ that enzymatic activity in melanoma chemotherapy using catechols as tyrosinase-dependent precursors of cytotoxic quinones is discussed.
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PMID:Half-lives of tyrosinase isozymes from Harding-Passey mouse melanoma. 312 37

A novel melanoma-associated differentiation Ag whose surface expression can be enhanced or induced by IFN-gamma was identified by mAb Me14/D12. Testing of numerous tumor cell lines and tumor tissue sections showed that Me14/D12-defined Ag was present not only on melanoma but also on other tumor lines of neuroectodermal origin such as gliomas and neuroblastomas and on some lymphoblastic B cell lines, on monocytes and macrophages. Immunoprecipitation by mAb Me14/D12 of lysates from [35S]methionine-labeled melanoma cells analyzed by SDS-PAGE revealed two polypeptide chains of 33 and 38 KDa, both under reducing and nonreducing conditions. Cross-linking experiments indicated that the two chains were present at the cell surface as a dimeric structure. Two-dimensional gel electrophoresis showed that the two chains of 33 and 38 KDa had isoelectric points of 6.2 and 5.7, respectively. Treatment of the melanoma cells with tunicamycin, an inhibitor of N-linked glycosylation, resulted in a reduction of the Mr from 33 to 24 KDa and from 38 to 26 KDa. Peptide maps obtained after Staphylococcus aureus V8 protease digestion showed no shared peptides between the two chains. Although biochemical data indicate that Me14/D12 molecules do not correspond to any known MHC class II Ag, their dimeric structure, tissue distribution, and regulation of IFN-gamma suggest that they could represent a new member of the MHC class II family.
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PMID:A novel IFN-gamma regulated human melanoma associated antigen gp33-38 defined by monoclonal antibody Me14/D12. I. Identification and immunochemical characterization. 313 51

Seventy Syrian golden hamsters bearing SC transplants of Greene melanoma were used to evaluate the degree of tumour uptake of several 11C-radiopharmaceuticals selected for their potential specificity for melanoma. Tissue distribution studies were performed at 30 and 60 min after IV injection of 11C-compounds and compared with the 24-h uptake of 67Ga-citrate. Gamma camera images were also compared. The highest tumour uptake at 1 h was observed with 11C-methionine (2.42% +/- 0.72%) and although activity in liver, spleen and kidney exceeded that in melanoma the tumour was demonstrated on gamma camera imaging. Melanoma localisation of 11C-chlorpromazine, 11C-flunitrazepam and 11C-ketanserine was comparable at 1% of the dose injected per gram of tumour. High activity in other organs, particularly liver, exceeded uptake in melanoma and attempts at tumour imaging were unsuccessful. Tumour accumulation of 11C-methiodide quinuclidinyl benzylate (MQNB), an 11C-imidazobenzodiazepine (Ro-15-1788) and 14C-pimozide was low and imaging studies were not attempted. None of the 11C-radiopharmaceuticals evaluated for melanoma affinity matched that of 67Ga-citrate. The 24-h tumour uptake of 67Ga-citrate was 4.07% +/- 1.37% dose injected per gram which allowed delineation of the melanoma by gamma camera imaging.
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PMID:Localization of 11C-radiopharmaceuticals in the Greene melanoma of hamsters. 315 76

Growth and metastasis of human tumor cells in immunodeficient nude mice were improved when tumor cells were inoculated within a vascularized artificial polyurethane sponge matrix. The sponges had been implanted 7-10 days earlier and were vascularized at the time of cell injection. All cell lines tested, including colon carcinoma-derived lines from primary tumors (HT29, PT3 and PT4) or from liver metastasis (LM3), and a metastatic variant from a melanoma (MeWo-Met) grew in a high percentage (78-94%) of the inoculated sponge grafts. When growth in sponge grafts is compared with growth at a subcutaneous site, the sponge matrix appears to increase tumorigenicity, at least for some cell lines. Regular formation of metastases was observed when cells had been injected into sponges. Most metastases were found in a second sponge graft implanted at a contralateral site, but some were also found at other s.c. sites. In vivo depletion of NK cells by pre-treatment with cyclophosphamide could not further enhance the formation of metastasis. Tumor cells from fresh surgical specimens could be propagated in sponge matrix grafts and subsequently established as cell lines in tissue culture.
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PMID:Growth and metastasis of human tumors in nude mice following tumor-cell inoculation into a vascularized polyurethane sponge matrix. 319 37

Studies were performed to investigate the effects of the endogenous opioid peptide methionine enkephalin on experimental metastasis of the murine B-16 melanoma and on murine splenic natural killer cell activity. Methionine enkephalin was shown to significantly inhibit tumor metastasis and significantly enhance splenic natural killer cell activity. These results indicate that the endogenous opioids can modulate the immune response and tumor defense and that methionine-enkephalin may prove to be a beneficial adjunct to the therapy of neoplastic disease.
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PMID:Inhibition of pulmonary metastases and enhancement of natural killer cell activity by methionine-enkephalin. 323 55

Intratumor macrophage numbers are enhanced by the administration of chemotactic f-MET-LEU-PHE - antitumor antibody - conjugates. The four f-MET-peptides f-MET-LEU-PHE, f-MET-LEU-PHE-o-methylester, formyl-norleucyl-phenylalanine and formyl-methionyl-phenylalanine, all chemotactic for human monocytes, where evaluated alone and conjugated to the melanoma directed monoclonal antibody ZME 018. f-MET-LEU-PHE-o-methyl-ester is the most active peptide, whereas f-MET-LEU-PHE - ZME 018 is the most active conjugate, not only inducing a response at the lowest concentration, but also the highest migrating cell numbers.
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PMID:Chemotactic monoclonal antibody conjugates: a comparison of four different f-Met-peptide-conjugates. 326 21

Homologous human macrophage hybridoma cell lines were obtained by somatic cell fusion between peripheral blood monocyte-derived macrophages and a subclone of the myelomonocytic cell line, U937-F9. The hybridoma cell lines grown in vitro for more than a year were confirmed by manifestations of phagocytosis, adherence, nonspecific esterase, acid phosphatase, chromosome numbers and other cell surface antigens. Cell surface antigens on hybridomas were detected by flow cytometry analysis with monoclonal antibodies. With interclonal differences, a typical phenotype of hybridoma cells was CDw14+, OKM5+, Mac-1+ (equivalent to OKM1 and Mol), OKT9+, HLA-DR- and CD20+. After stimulation with lipopolysaccharide and calcium ionophore A23187, culture supernatants of clones c18A and c29A showed cytotoxic activity against human melanoma A375 Met-Mix and other cell lines which were resistant to the tumor necrosis factor, lymphotoxin and interleukin 1. This cytotoxic factor was found to be distinct from the tumor necrosis factor, lymphotoxin and interleukin 1 using the anti-tumor necrosis factor, anti-lymphotoxin and anti-interleukin 1 antisera.
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PMID:Homologous human macrophage hybridomas that produce a novel cytotoxic factor in their culture supernatants. 328 4

Previous studies have demonstrated the presence of two distinct antigens, B700 and B50, which are unique to murine melanoma. One of these, B700 has been studied in detail, and is present on 5 different murine melanomas; it can function as a transplantation antigen in at least 3 of them (B16, JB/RH and K1735). The synthesis and presentation of these antigens has been studied as a function of cell culture conditions. Direct immunofluorescence studies of cells in serial culture indicate that the expression of B700 and B50 antigens at the cell surface and in the cytoplasm increases as a function of time in culture, over 1-5 days. By day 5, when the cells are confluent, all cells show some degree of antibody binding. Parallel 35S-methionine pulse chase labeling experiments show that incorporation into Triton soluble proteins, and Triton insoluble SDS soluble proteins, increases to a peak at 3.5 days after subculturing, then decreases as the cells reach confluence. Incorporation into proteins shed into the culture supernatant continued throughout the time course of cell growth to confluence. However, as the cells become confluent, total protein synthesis shifts towards greater production of the antigens (both cellular and shed). The sum of the results suggest that tumor growth may succeed in vivo by the wholesale production of "decoy" antigens.
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PMID:Temporal synthesis and presentation of antigens by cultured B16 melanoma cells. 333 35

Tumor cell invasion of basement membranes is required at several steps in the process of metastasis. To study the genetic and biochemical events mediating invasion, a variant cell line (TK) was selected from the metastatic M2 K1735 murine melanoma cell line. A novel selection procedure was used, based on in vitro and in vivo invasion and growth upon basement membrane and stroma. Additionally, two extrapulmonary metastases of the TK cell line, TK-Eve and TK-Liver, were established as cell lines and characterized. The TK cell line demonstrates greater metastatic potential in vivo and invasive ability in vitro than the parent M2 cell line, confirming the validity of the selection procedure. In addition, the M2 and TK cell lines were examined for other cell functions involved in the metastatic process. Cellular growth rates and sensitivity to T lymphocyte and natural killer cell lysis were not determining factors in the metastatic potentials of the M2 and selected cell lines; possible macrophage contribution to metastatic behavior was noted. [35S]methionine pulse labeling of protein synthesis and karyotypic analysis confirm the close relationship of parental and selected cell lines.
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PMID:A novel method for selection of invasive tumor cells: derivation and characterization of highly metastatic K1735 melanoma cell lines based on in vitro and in vivo invasive capacity. 335 13

Metastatic variants of the B16 melanoma displaying high experimental metastatic potential have been shown to express high levels of a 72,000-dalton glycoprotein (Met-72) on their cell surface (Kimura AK, Xiang J: J Nat Can Inst 76:1247-1253, 1986). Monoclonal antibodies (MoAb) directed against the Met-72 determinant have been used in this study as immunohistochemical reagents on preparations of fresh B16 melanoma tumors and their metastases. These immunohistochemical analyses have utilized frozen sections, impression smears, and cytospin preparations of fresh tumors harvested at various time points during tumor growth, to view the presence and location of Met-72-positive metastatic variants within tumor masses. Biotinylated anti-Met-72 MoAbs were reacted with freshly dissociated tumor cells from a B16 melanoma ovarian metastasis. These cells were then reacted with fluorescein isothiocyanate (FITC)-streptavidin and analyzed by flow cytometry. A discrete population of positively staining cells was detected and isolated by cell sorting techniques. Met-72-positive cells were then cloned and reanalyzed after several weeks of in vitro expansion and found to have high experimental metastatic potential to ovaries. Frozen sections of subcutaneous tumors and their metastases were analyzed by immunoperoxidase techniques. A consistent finding in these studies has been that the few tumor cells which showed high intensity of Met-72 staining were positioned perivascularly and at the invading front of B16 melanoma tumors.
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PMID:Isolation and visualization of Met-72-positive, metastatic variants present in B16 melanoma tumor masses. 337 5


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