Serum gangliosides in cerebral astrocytoma

Lo, Hsiao S.; Hogan, Edward L.; Koontz, Daniel A.; Traylor, T. Dennis

doi:10.1002/ana.410080511

Cited by 26 publications

(5 citation statements)

References 24 publications

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“…For example, levels of G M3 and G D3 , prominent constituent gangliosides of normal human plasma, were slightly raised in the plasma of patients with melanoma, 5 as were those of G M3 in plasma of patients with cerebral astrocytoma. 6 In contrast, our study shows that a particular ganglioside, a major ganglioside of neuroblastoma tumour tissue not detectable in normal human plasma samples by standard thin-layer-chromatographic methods, is present in high concentrations in the plasma of patients with this malignant disorder. These findings support the hypothesis that changes in circulating gangliosides in patients with cancer are related to the tumour gangliosides themselves.…”

Section: Discussioncontrasting

confidence: 82%

“…An association between abnormalities in circulating gangliosides and the presence of tumour is suggested by the knowledge that membrane-bound gangliosides are, among other molecules on the cell surface, released by proliferating cells. 1,2 Findings of high concentrations of gangliosides in the circulation of tumour-bearing hosts, [3][4][5][6][7] which fall towards normal on removal of tumour, 4,5 support this association, as does the indirect evidence that binding between a monoclonal antibody and a colon-carcinoma-associated ganglioside is inhibited by the serum of patients with this tumour. 14 To date, however, direct thin-layer-chromatographic visualisation of gangliosides isolated and purified from the plasma of patients with cancer has not shown the presence of any ganglioside which was not also detected though perhaps in lower concentrations in the plasma of healthy normal donors.…”

Section: Discussionmentioning

confidence: 98%

“…These membrane-bound glycolipids are released or shed in vitro by many cells, especially proliferating cells such as tumour cells. 1,2 It has been suggested that high concentrations of gangliosides, present in the circulation of tumour-bearing hosts, [3][4][5][6][7] may be tumour-related. 4 To date, however, there has been no report of direct visualisation and identification of a ganglioside in the plasma of patients with cancer that has not also been detected in normal plasma.…”

Section: Introductionmentioning

confidence: 99%

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Detection of a Tumour-Associated Ganglioside in Plasma of Patients With Neuroblastoma

Ladisch¹,

Wu²

1985

The Lancet

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SummaryAn abnormal circulating ganglioside was found in patients with neuroblastoma. This ganglioside appeared as a single band by resorcinol-HCl staining of thin-layer chromatograms of purified total gangliosides isolated from as little as 1 ml of patient plasma. It is a major ganglioside of neuroblastoma tumour tissue and was present (250-1500 pmol lipid-bound sialic acid/ml) in the plasma of five patients with widespread neuroblastoma. In contrast, the ganglioside was not detected (<50 pmol/ml) in plasma samples of six patients in complete remission, nor in plasma samples of seventeen healthy children and adults. Measurement of this circulating tumourassociated ganglioside should be clinically useful in neuroblastoma, offering a new approach to the detection of tumour and the evaluation of therapy.

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Section: Discussioncontrasting

confidence: 82%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Detection of a Tumour-Associated Ganglioside in Plasma of Patients With Neuroblastoma

Ladisch¹,

Wu²

1985

The Lancet

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“…Others have reported that gangliosides (mostly GD3 and GM3) are shed into the serum of GBM patients (8,61). This shedding of gangliosides by GBMs may partly explain lymphopenia, apoptosis, and depressed T-cell function in the periphery of these patients (3,62,63).…”

Section: Discussionmentioning

confidence: 96%

Glioblastomas Induce T-Lymphocyte Death by Two Distinct Pathways Involving Gangliosides and CD70

Chahlavi¹,

et al. 2005

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Here we report that glioblastoma multiforme (GBM) mediates immunosuppression by promoting T-cell death via tumorassociated CD70 and gangliosides that act through receptordependent and receptor-independent pathways, respectively. GBM lines cocultured with T cells induced lymphocyte death. The GBM lines were characterized for their expression of CD70, Fas ligand (FasL), and tumor necrosis factor-A (TNF-A), and the possible participation of those molecules in T-cell killing was assessed by doing GBM/T cell cocultures in the presence of anti-CD70 antibodies, Fas fusion proteins, or anti-TNF-A antibodies. CD70 but not TNF-A or FasL is responsible for initiating T-cell death via the receptor-dependent pathway. Of the four GBM cell lines that induced T-cell death, three highly expressed CD70. Two nonapoptogenic GBM lines (CCF3 and U138), on the other hand, had only minimally detectable CD70 expression. Blocking experiments with the anti-CD70 antibody confirmed that elevated CD70 levels were involved in the apoptogenicity of the three GBM lines expressing that molecule. Gangliosides were found to participate in the induction of T-cell apoptosis, because the glucosylceramide synthase inhibitor (PPPP) significantly reduced the abilities of all four apoptogenic lines to kill the lymphocytes. Highperformance liquid chromatography (HPLC) and mass spectroscopy revealed that GM2, GM2-like gangliosides, and GD1a were synthesized in abundance by all four apoptogenic GBM lines but not by the two GBMs lacking activity. Furthermore, gangliosides isolated from GBM lines as well as HPLC fractions containing GM2 and GD1a were directly apoptogenic for T cells. Our results indicate that CD70 and gangliosides are both products synthesized by GBMs that may be key mediators of T-cell apoptosis and likely contribute to the T-cell dysfunction observed within the tumor microenvironment. (Cancer Res 2005; 65(12): 5428-38)

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“…Ando et al 30 showed that GM2 blocked NK effector-target binding in the singlecell assay. Increased concentrations of GM2 and/or GM3 was observed in the circulation of patients with tumors including neuroblastoma and glioma 31 . These gangliosides shedding from growing tumors may result in high concentration in the tumor microenvironment.…”

Section: Fig 1 Nk Cell Activity Against K562 Target Cells Percentagmentioning

confidence: 99%

Immunological alterations in patients with primary tumors in central nervous system

Peraçoli

Montelli

Soares

et al. 1999

Arq. Neuro-Psiquiatr.

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-Natural killer (NK) cells play an important role in immune surveillance against tumors. The present work aimed to study the cytotoxic activity of NK cells and T cell subsets in peripheral blood of 13 patients with primary tumors in central nervous system (CNS). As controls 29 healthy subjects with the age range equivalent to the patients were studied. The methods employed were: a) determination of cytotoxic activity of NK cells towards K562 target cells, evaluated by single cell-assay; b) enumeration of CD3+ lymphocytes and their CD4+ and CD8+ subsets defined by monoclonal antibodies; c) the identification of tumors were done by histologic and immunochemistry studies. The results indicated that adults and children with tumor in CNS display reduced percentage of total T cells, helper/inducer subset and low helper/suppressor ratio. The cytotoxic activity of NK cells was decreased in patients with CNS tumors due mainly to a decrease in the proportion of targetbinding lymphocytes. These results suggest that cytotoxic activity of NK cells may be affected by the immunoregulatory disturbances observed in patients with primary tumors in CNS. KEY WORDS: brain tumors, NK cells, T cell subsets.Alterações imunológicas em pacientes com tumores primários no sistema nervoso central RESUMO -As células natural killer (NK) desempenham importante papel na vigilância imunológica contra tumores. O objetivo do presente trabalho foi estudar a atividade citotóxica de células NK e as subpopulações de células T no sangue periférico de 13 pacientes com tumores primários no sistema nervoso central (SNC). Como controle foram estudados 29 indivíduos saudáveis com faixa etária equivalente aos pacientes. Os métodos empregados foram: a) determinação da atividade citotóxica de células NK contra células alvo K562; b) quantificação de linfócitos CD3+ e subpopulações CD4+ e CD8+ por meio de anticorpos monoclonais; c) identificação dos tumores por análise histológica e imuno-histoquímica. Os resultados indicaram que adultos e crianças com tumores no SNC apresentam diminuição na percentagem de linfócitos T, da subpopulação de células T auxiliares e da relação células auxiliares/supressoras. A atividade citotóxica de células NK esteve deprimida em pacientes com tumores devido principalmente à diminuição da capacidade de formar conjugados com a célula alvo K562. Os resultados sugerem que a atividade de células NK pode ser afetada por distúrbios imunorregulatórios observados em pacientes com tumores primários no SNC. PALAVRAS-CHAVE: tumores cerebrais, células NK, subpopulações de células T.Most cancers result from interaction of genetic and environment factors; however, genetic factors by themselves explains only about 5% of all cancer. The others have been atributed to environmental factors, that may interact with genetic cancer susceptibility and individual response 1 .

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Serum gangliosides in cerebral astrocytoma

Cited by 26 publications

References 24 publications

Detection of a Tumour-Associated Ganglioside in Plasma of Patients With Neuroblastoma

Detection of a Tumour-Associated Ganglioside in Plasma of Patients With Neuroblastoma

Glioblastomas Induce T-Lymphocyte Death by Two Distinct Pathways Involving Gangliosides and CD70

Immunological alterations in patients with primary tumors in central nervous system

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