Potential ganglioside antigens associated with human gliomas

Fredman, Pam; Holst, Hans von; Collins, V. Peter; Ammar, Ahmed A.; Dellheden, Birgitta; Wahrén, Britta; Granholm, Lars; Svennerholm, Lars

doi:10.1080/01616412.1986.11739744

Cited by 50 publications

(24 citation statements)

References 17 publications

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“…The general reduction in total tumor ganglioside concentration appears to be associated with malignancy as each of these tumors were highly malignant. Reduced ganglioside concentration also occurs in experimental rat neural tumors (Chou et al, 1979), and in a variety of human neural tumors including neuroblastoma (Yates et al, 1979;Eto and Shinoda, 1982), primitive neuroectodermal tumor (Yates et al, 1979), meningioma (Eto and Shinoda, 1982;Berra et al, 1983), and malignant astrocytoma (Kostic and Buchheit, 1970;Aruna and Basu, 1975;Manuelidis et al, 1977;Yates et al, 1979;Traylor and Hogan, 1980;Eto and Shinoda, 1982;Berra et al, 1985;Fredman et al, 1986Fredman et al, , 1988Fredman, 1988). The reduced ganglioside concentration of malignant brain tumors may be partly a result of displacement or death of ganglioside-rich neurons coupled with a rapid proliferation of ganglioside-poor tumorigenic cells.…”

Section: Discussionmentioning

confidence: 99%

Ganglioside distribution in murine neural tumors

Seyfried

El-Abbadi

Roy

1992

Molecular and Chemical Neuropathology

106

111

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The ganglioside composition of seven experimental brain tumors was examined in C57BL/6J mice. The tumors were produced from 20-methylcholanthrene (20-MC) implantation into either the cerebrum or cerebellum and were maintained in serial transplants through many generations. The tumors studied were grown subcutaneously as solid tumors, and cells from two of the tumors were also studied in culture. Histologically, all of the tumors were similar and could be broadly classified as highly malignant, poorly differentiated anaplastic astrocytomas. The total ganglioside sialic acid content of the solid tumors was markedly lower than that in adult mouse brain. In addition to N-acetylneuraminic acid (NeuAc), the gangliosides in the solid tumors contained significant amounts of N-glycolylneuraminic acid (NeuGc). The seven solid tumors fell into two general groups with respect to ganglioside composition. Furthermore, the differences in ganglioside composition between the two tumor groups were strongly associated with differences in tumor cell cohesion. The tumors in one group had high levels of GM3 hematosides, low levels of oligosialogangliosides, and grew as firm cohesive tissues. The tumors in the other group, however, had lower levels of GM3 hematosides, noticeable amounts of oligosialogangliosides and grew as soft noncohesive tissues. In culture, clonal cells from one of the tumors in the first group grew as clumps or islands and contained GM3 as the only major ganglioside, whereas clonal cells from a tumor in the second group grew as sheets or monolayers and contained little GM3, but expressed several gangliosides with complex structures. In marked contrast to the gangliosides in the solid tumors, the gangliosides in the cultured tumor cells contained trace amounts of NeuGc. Since NeuGc containing gangliosides are abundant in mouse nonneural tissues, the high content of NeuGc gangliosides in the solid tumors may arise from infiltration of nonneural tissue elements, e.g., macrophages, lymphocytes, and endothelial cells.

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Section: Discussionmentioning

confidence: 99%

Ganglioside distribution in murine neural tumors

Seyfried

El-Abbadi

Roy

1992

Molecular and Chemical Neuropathology

106

111

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“…Therefore, chemotherapy has been widely combined with mAbs which suppress advantageous factors for tumor cell growth or survival, e.g. anti-glycoprotein P, 37) anti-interleukin 6,38) anti-EGF receptor, 39,40) or anti-VEGF. 41) Many of them enhanced the cytotoxicity of chemotherapeutic agents in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…2) In human malignant tumor cells, neuroectodermderived tumor cells such as melanomas, neuroblastomas, and gliomas frequently express characteristic gangliosides for individual tumor types. [3][4][5][6] Sarcomas, 7) gastric cancers, 8,9) T cell leukemias [10][11][12] and small cell lung cancer (SCLC) cells 13) also express specific gangliosides. Specific monoclonal antibodies (mAbs) to these tumor-associated ganglioside antigens have been utilized for diagnosis, 14,15) prediction of the prognosis, 16,17) and detection of residual tumors.…”

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confidence: 99%

An Anti‐GD2 Monoclonal Antibody Enhances Apoptotic Effects of Anti‐cancer Drugs against Small Cell Lung Cancer Cells via JNK (c‐Jun Terminal Kinase) Activation

Yoshida

Kawaguchi

Sato

et al. 2002

Japanese Journal of Cancer Research

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Small cell lung cancer (SCLC) cell lines specifically express ganglioside GD2, and anti-GD2 monoclonal antibodies (mAbs) caused suppression of cell growth and induced apoptosis of SCLC cells with single use. Here, enhancement of the cytotoxic effects of various anti-cancer drugs with an anti-GD2 mAb was demonstrated. The cytotoxicity of all six drugs examined was markedly enhanced, i.e. 2.4-7.8-fold increase of cell sensitivity in terms of IC 50 . In particular, the combination of cisplatin (CDDP) with an anti-GD2 mAb resulted in prominent enhancement of cytotoxicity even in low-moderate GD2-expressing lines. The anti-GD2 mAb induced weak activation of c-Jun terminal kinase (JNK) in SCLC cells, and all anti-cancer drugs also induced its activation to various degrees. When CDDP and an anti-GD2 mAb were used together, significantly stronger JNK activation was observed corresponding to the cytotoxic effects, suggesting that synergistic phosphorylation of JNK with two reagents induced prominent apoptosis. The essential role of JNK in the induction of SCLC apoptosis with CDDP and anti-GD2 mAb was confirmed by experiments with a JNK inhibitor, curcumin. These results suggest that anti-GD2 mAbs would be very efficient in combination with anti-cancer drugs, both to achieve SCLC-specific cytotoxicity and to enhance its magnitude. Key words: Apoptosis -Small cell lung cancer -Chemotherapy -JNK -GD2Gangliosides are enriched in nervous tissues of vertebrates 1) and their expression is spatio-temporally regulated.2) In human malignant tumor cells, neuroectodermderived tumor cells such as melanomas, neuroblastomas, and gliomas frequently express characteristic gangliosides for individual tumor types.3-6) Sarcomas, 7) gastric cancers, 8,9) T cell leukemias [10][11][12] and small cell lung cancer (SCLC) cells 13) also express specific gangliosides. Specific monoclonal antibodies (mAbs) to these tumor-associated ganglioside antigens have been utilized for diagnosis, 14,15) prediction of the prognosis, 16,17) and detection of residual tumors.18) In particular, anti-ganglioside mAbs have been tried for immunotherapy of melanomas 19,20) and neuroblastomas. 21)During the early stage of mAb application, anti-GD3 mAb R24 was used for the first time in the treatment of recurrent melanomas, and showed the ability to reduce the tumor size or halt the progression.19) Anti-GD2 mAb was also applied in the treatment of neuroblastomas to extend remission.22) Moreover, a human mAb reactive with GD2 was tried for cutaneous melanomas with some effects. 20)However, further development of antibody therapy has not been successful mainly due to xenogeneic immunogenicity of mouse antibodies and poor penetration of antibodies into tumor tissues.Recently, application of mAbs for the treatment of various cancers has been re-evaluated based on the progress in recombinant molecular technology and protein engineering with site-directed mutagenesis. Anti-c-erbB2/HER2/neu mAb was used in the therapy of advanced stages of breast cancers 23) and anti-CD20 mAb ...

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“…It has been reported that human glioma biopsies show elevation of monosialylated GM3 and GM2 and their disialylated derivatives GD3 and GD2 (12)(13)(14). The increase of GD3 was most significant, but the correlation between GD3 and malignancy remains obscure (15,16).…”

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confidence: 95%

Stage-specific embryonic antigen-4 as a potential therapeutic target in glioblastoma multiforme and other cancers

Lou

Wang²,

Yeh³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Glioblastoma multiforme (GBM) is a deadly brain tumor. More than 50% of patients who suffer from GBM die within 15 mo even received all possible medical treatment. In this study we report that the glycolipid stage-specific embryonic antigen-4 (SSEA-4) is highly expressed on the surface of both GBM cells and GBM specimens. We further demonstrate that the growth of GBM tumor is inhibited when anti–SSEA-4 antibody is administered to experimental mice, suggesting a research proof of concept for the treatment GBM and other SSEA-4 + cancers.

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Potential ganglioside antigens associated with human gliomas

Cited by 50 publications

References 17 publications

Ganglioside distribution in murine neural tumors

Ganglioside distribution in murine neural tumors

An Anti‐GD2 Monoclonal Antibody Enhances Apoptotic Effects of Anti‐cancer Drugs against Small Cell Lung Cancer Cells via JNK (c‐Jun Terminal Kinase) Activation

Stage-specific embryonic antigen-4 as a potential therapeutic target in glioblastoma multiforme and other cancers

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