Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melanoma and lung adenocarcinoma may be amenable for radiotherapy if it were possible to increase the presently used total dose. In order to investigate this, spheroids from two cell lines of human origin, one obtained from a BRO melanoma and one from an NCI-H125 lung adenocarcinoma were exposed to graded doses (3-9 Gy) of radiation with 18-MV photons. Radiation was applied either as a single dose or as split doses with an interval of 6 h to determine the extent of sublethal damage repair. Radiation response was quantified in terms of spheroid cure and specific growth delay. Both cells lines have previously been shown to be less sensitive than a neuroblastoma and a squamous cell carcinoma cell line grown as spheroids. Data obtained from the growth delay analysis were used to calculate the extent of split-dose recovery. Repaired dose for BRO spheroids did not increase after 7 Gy, whereas in NCI-H125, the repaired dose showed a steady increase. Recovery ratios did not differ between the two cell lines, but were lower than reported for normal tissues. Both cell lines revealed a low repair capacity was expressed by the beta-value of the linear-quadratic (LQ) equation. However, repair capacity for sublethal damage as expressed by the dose repaired and the beta-value of the LQ equation was not different from values reported earlier by us for neuroblastoma and squamous cell carcinoma when grown as spheroids. This indicates that the low radiosensitivity for the cell lines used in this study is determined by the alpha-value of the LQ equation. Our results support the clinical finding that the application of increased total radiation doses in the treatment of melanoma and lung adenocarcinoma may be feasible if radiation is applied in multiple small fractions to ensure normal tissue sparing.
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PMID:Sublethal damage repair in two radioresistant human tumor cell lines irradiated as multicellular spheroids. 187 10

We previously reported the binding specificities of two anti-ganglioside GD2 murine monoclonal antibodies (MAbs), A1-425 and A1-267, both of which are of IgG3 isotype. A1-425 reacts specifically with ganglioside GD2, whereas A1-267 binds preferentially to GD2 but also reacts with GD3 [Tai, T., Kawashima, I., Tada, N., & Dairiki, K. (1988) J. Biochem. 103, 682-687]. In this paper, they were used for comparative analyses of antibody-mediated cytotoxicity, i.e., antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human melanoma and neuroblastoma cell lines. Melanoma cells were found to contain GD2 and/or GD3, whereas neuroblastoma cells expressed only GD2. Both antibodies induced high levels of ADCC and CDC to GD2/GD3-positive cells with human peripheral large granular lymphocytes (LGL) as effector cells and in the presence of human serum, respectively. A good correlation was obtained between the contents of disialogangliosides and the binding level of the antibodies; both melanoma and neuroblastoma cells with larger amounts of GD2/GD3 showed a higher level of antibody binding than did the cells with a smaller amount of GD2/GD3. Surprisingly, ADCC did not correlate well with the binding level of the antibodies. Thus, A1-425 showed stronger lytic activity than A1-267 in spite of the binding level of A1-425 being similar to or lower than that of A1-267 on the cell surfaces. Antigen-antibody complexes composed of GD2 and A1-425 showed higher binding levels to LGL than complexes of GD2 and A1-267. In contrast, free MAb molecules gave minimum binding to LGL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monoclonal antibodies to disialogangliosides: characterization of antibody-mediated cytotoxicity against human melanoma and neuroblastoma cells in vitro. 212 21

The successful use of iodine-131-meta-iodobenzylguanidine (I-131-MIBG) scintigraphy for diagnosis of phaeochromocytoma and neuroblastoma stimulated investigation into its diagnostic and therapeutic usefulness in other neural crest tumours. It appears that there is a difference in capacity to absorb I-131-MIBG between the different tumour types. In I-131-MIBG scintigraphy of carcinoids there are more false negative results in comparison with phaeochromocytomas and neuroblastomas. Melanoma, also a neural crest tumor, turned out to be false negative in 100% of the cases reported until 1989. The authors present a case of a malignant melanoma with metastases in liver and stomach, concentrating I-131-MIBG. Biochemical examination demonstrated that this particular tumour was metabolically very active. It is suggested that the I-131-MIBG-positive scintigram of the melanoma may be related to the level of metabolic activity. By biochemical screening in proven cases of malignant melanoma it may be possible to select cases in which I-131-MIBG scintigraphy is worthwhile with a view to therapeutic application of I-131-MIBG.
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PMID:[Scintigraphy using I 131 iodobenzylguanidine and malignant melanomas]. 223 80

Human melanoma cells express high levels of GM3 and GD3 gangliosides whereas normal melanocytes have only low levels of GD3 but maintain their expression of GM3. In order to understand the basis for this difference, the levels of the sialyltransferase that converts GM3 to GD3 (CMP-N-acetylneuraminic acid:GM3 sialyltransferase or GD3 synthase, EC 2.4.99.8) were analyzed in melanoma and other cell lines. Enzyme levels were determined in vitro using membrane preparations and measuring the addition of [14C]-N-acetylneuraminic acid from CMP-[14C]-N-acetylneuraminic acid to GM3 in the presence of Triton CF-54. Sialyltransferase levels in 44 human cancer cell lines (including melanoma, neuroblastoma, astrocytoma, various carcinomas, and leukemias) and cultures of normal melanocytes and kidney epithelial cells were compared, and the products were identified by thin layer chromatography and fluorography. Melanoma cell lines exhibited the highest levels of incorporation and GD3 was found to be the major product. GM3 was also formed, apparently from endogenous lactosylceramide. Very low levels of GD3 synthase were found in normal melanocytes. Neuroblastoma and some astrocytoma cell lines also had significant levels of GD3 synthase. Some other cell lines incorporated high levels of radioactivity but the products did not correspond to GD3 and the major product was usually GM3. In general the levels of GD3 synthase correlated with the expression of GD3 in the various cell types. These results point to higher levels of GD3 synthase being directly responsible for the enhanced expression of GD3 in melanoma.
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PMID:Sialyltransferase levels and ganglioside expression in melanoma and other cultured human cancer cells. 280 71

The growth characteristics of 6 human cell line derived multicellular tumor spheroids (MTS) were studied. Melanoma MTS (C32, HML-A, HML-B) were slow growing with baseline growth rates of 13.9 to 27.3 microns diameter/day. Neuroblastoma MTS (Lan-1, NB-100, NB-134) grew rapidly, with baseline growth rates of 32.1 to 40.3 microns diameter/day, that is, 1.2 to 2.9 times as fast as the melanomas. Delay constants were calculated for all six lines. The neuroblastomas were more sensitive to radiation than melanomas, as reflected in a greater value for the radiation-induced growth delay constant. One neuroblastoma line, Lan-1, was highly radioresponsive; that is, after a subcurative dose of radiation, the MTS diameter decreased beyond the original diameter, which was followed by recovery and regrowth. Irrespective of these initial changes in diameter, growth delay sensitivity (value of delay constant) was the same for Lan-1 and NB-100, an MTS line that did not show the responsive pattern.
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PMID:Response of human neuroblastoma and melanoma multicellular tumor spheroids (MTS) to single dose irradiation. 372 38

Melanoma and neuroblastoma are diagnosed by their clinical and histological features, including evidence of melanogenesis and neural differentiation respectively, by tumour cells. These criteria are occasionally inadequate. Melanoma and neuroblastoma are derived from a system of cells characterized by the content, precursor uptake and decarboxylation of particular amines (APUD cells). Neurone specific enolase (NSE) has been proposed as a specific marker for neural elements and APUD cells. Immunohistochemical cytoplasmic and fibrillary localization of this enzyme was demonstrated in formalin-fixed, paraffin-processed sections of melanoma and neuroblastoma, constituting and additional aid to the identification of these tumours. The demonstration of an enzyme of the glycolytic pathway within tumour cells has implications following the effects of anti-tumour agents and these are discussed.
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PMID:Neurone specific enolase: an aid to the diagnosis of melanoma and neuroblastoma. 612 Jan 37

A human melanoma cell line, M14 , adapted to grow in serum free synthetic media was examined for its expression and secretion of several serologically defined melanoma associated antigens (MAA) previously described in this laboratory. Melanoma associated antigen expression and secretion was identical to that of M14 cells grown in parallel in serum supplemented medium. Spent synthetic media was found to be an enriched serum free source for the initial isolation of 100 kilodalton secreted glycoprotein MAA. M14 melanoma cells grown in synthetic media were also shown to be adaptable to the double agar clonogenic assay facilitating the examination of clonal heterogeneity in functional studies of MAA in melanoma tumor biology. Recent investigations from this laboratory have focused on characterizing human melanoma associated antigens (MAA) found either as secreted or cell surface associated glycoproteins in human melanoma cell lines. In these studies, monoclonal and polyclonal antiserums to melanoma cell components have been developed to specifically identify these MAAs immunochemically and provide a means to study the structural biochemistry of these determinants. At this time we have identified two antigens on which our research efforts are targeted: 1) a 100,000 dalton secreted glycoprotein (100K) common to melanoma, sarcoma and neuroblastoma tumor cell lines, and 2) a 250,000 dalton-high molecular weight component glycoprotein-proteoglycan complex which is thus far restricted to melanoma cells. The ultimate goal of our efforts is two-fold. Initially, we hope to develop schemes to isolate these melanoma associated antigens in sufficient quantities to obtain detailed structural information on these molecules, and secondly, we wish to implicate these glycoproteins in functional aspects of the biology of metastatic human melanoma in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antigenic expression of human melanoma cells in serum-free medium. 673 Nov 48

Mouse monoclonal antibodies against tumour-associated gangliosides GD2 (14.G2a) and GD3 (MB 3.6) were tested to mediate antibody-dependent cellular cytotoxicity (ADCC) with various effector cells or complement-dependent cytolysis (CDC). We also evaluated the immunomodulating potential of interferons in combination with cellular cytotoxicity. Using effector:target (E/T) ratios of 40:1, ADCC with effector cells such as granulocytes or mononuclear blood cells was not detectable against melanoma cell lines GR, SK-MEL-28 and G-361 which preferentially express GD3 and bind antibody MB 3.6. Neuroblastoma cell line SK-N-LO, which was used for comparative purposes, mainly expressed GD2 and the tumour cells were killed effectively after labelling with antibody 14.G2a. Granulocytes did not show significant killing of melanoma cells by ADCC, but neuroblastoma cells were killed very efficiently. Peripheral blood mononuclear cells (PBMC) also failed to kill melanoma cells. Interferon-beta slightly stimulated PBMC and increased killing of neuroblastoma cells, but no additive effects with ADCC were detectable. Incubation of target cells with interferons produced no significant differences in susceptibility of the target cells to interferon-activated PBMC cytotoxicity. Despite the lack of effectiveness in mediating cellular cytotoxicity, GD3 antibody MB 3.6 showed strong complement-dependent cytolysis in the presence of human plasma. There were remarkable differences in individual activity and different susceptibility of the melanoma cell lines. We assume that CDC may have more activity against melanoma cells than cytotoxicity associated with various effector cells.
Melanoma Res 1994 Apr
PMID:Activation of cellular cytotoxicity and complement-mediated lysis of melanoma and neuroblastoma cells in vitro by murine antiganglioside antibodies MB 3.6 and 14.G2a. 806 95

GD3 Synthase (alpha 2,8sialyltransferase) (EC 2.4.99.8) cDNA has been cloned by eukaryotic cell expression cloning. Using this cDNA as a probe, the expression level of the gene in human cancer cell lines was analysed by Northern blotting and RT-PCR, then correlated with the ganglioside expression and enzyme activity. Melanoma cell lines showed extremely strong bands in Northern blot and RT-PCR/Southern analysis. The enzyme activity was also very high in melanomas as expected. Neuroblastoma and astrocytoma lines showed relatively low levels of the gene expression, whereas they expressed high levels of GD2. Although the mRNA level of the GD3 synthase gene and enzyme activity in individual cell lines correlated positively, some cell lines showed much higher activity than expected from the mRNA level. Among leukaemia lines, adult T cell leukaemia-associated (HTLV-I+) lines showed fairly high levels of the mRNA. On the other hand, T-ALL lines showed very low levels. In addition, GD3 and GD2 expression and mRNA level of the gene during T lymphocyte activation were analysed. Only GD3 expression was induced by any of the stimulatory reagents used, and corresponding up-regulation of the GD3 synthase gene was shown in RT-PCR/Southern analysis.
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PMID:Expression of alpha 2,8-sialyltransferase (GD3 synthase) gene in human cancer cell lines: high level expression in melanomas and up-regulation in activated T lymphocytes. 874 67

Neuroblastoma has long been recognized to show spontaneous regression during fetal development and in the majority of stage 4s infants < 1 year of age with disseminated disease. Stage 4s disease regresses with no chemotherapy in 50% of the patients. The mechanism by which this occurs is not understood but may be programmed cell death or apoptosis. Betulinic acid (BA) has been reported to induce apoptosis in human melanoma with in vitro and in vivo model systems. Melanoma, like neuroblastoma, is derived from the neural crest cell. We hypothesised that neuroblastoma cells have the machinery for programmed cell death and that apoptosis could be induced by betulinic acid. Nine human neuroblastoma cell lines were treated in vitro with BA at concentrations of 0-20 micrograms/ml for 0-6 days. Profound morphological changes were noted within 3 days. Cells withdrew their axonic-like extensions, became non-adherent and condensed into irregular dense spheroids typical of apoptotic cell death (ED50 = 14-17 micrograms/ml). DNA fragmentation analysis showed ladder formation in the 100-1200 bp region in 3/3 neuroblastoma cell lines treated with BA for 24-72 h. Thus, apparently BA does induce AP in neuroblastoma in vitro. This model will be utilised to investigate the role of apoptosis-related genes in neuroblastoma proliferation and to determine the therapeutic efficacy of BA in neuroblastoma in vivo.
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PMID:Betulinic acid induces apoptosis in human neuroblastoma cell lines. 951 43


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