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The influence of ImuVert, a biological response modifier, on the growth and ganglioside composition of murine neural tumors

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Molecular and Chemical Neuropathology

Abstract

ImuVert is a biological response modifier (BRM) that has antitumor effects in humans and rats. The influence of ImuVert on the ganglioside composition of two experimental brain tumors, ependymoblastoma and CT-2A, was studied in C57BL/6J mice. Gangliosides are expressed on plasma membranes and can serve as markers to distinguish neural cells from nonneural cells in mouse brain tumors.N- acetylneuraminic (NeuAc) is the predominant sialic acid in mouse neural cells, whereasN-glycolylneuraminic (NeuGc) is a major sialic acid in nonneural cells, e.g., macrophages and lymphocytes. ImuVert treatment increased the NeuGc ganglioside concentration in the ependymoblastoma, but had no effect on the sialic acid concentration in the CT-2A brain tumor. ImuVert also had a slight inhibitory effect on the growth of both brain tumors.

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Abbreviations

BRM:

biological response modifier

HPTLC:

high-performance thin-layer chromatography

INF:

interferon

ip:

intraperitoneal

NeuAc:

N-acetylneuraminic acid

NeuGc:

N-glycolylneuraminic acid

20-MC:

20-methylcholanthrene

References

  • Ando S., Chang N.C., and Yu R. K. (1978) High performance thin layer chromatography and densitometric determination of brain ganglioside compositions of several species.Anal. Biochem. 89, 437–450.

    Article  PubMed  CAS  Google Scholar 

  • Bai H., Orlando J., and Seyfried T. N. (1992) Altered ganglioside composition in virally transformed rat embryo fibroblasts.Biochim. Biophys. Acta 1136, 23–27.

    Article  PubMed  CAS  Google Scholar 

  • Cunningham-Rundles S. and Pearson F. C. (1990) ImuVert activation of natural killer cytotoxicity and interferon gamma production via CD16 triggering.Int. J. Immunopharm. 12, 589–598.

    Article  CAS  Google Scholar 

  • Elmslie R. E., Ogilvie G. K., Dow S. W., Gasper P., Hoover E. A., Cooper M. F., and Pearson F. C. (1991) Evaluation of a biological response modifier derived fromSerratia marcescens: effects on feline macrophages and usefulness for the prevention and treatment of viremia in feline leukemia virus-infected cats.Mol. Biother. 3, 231–238.

    PubMed  CAS  Google Scholar 

  • Evans R. and Eidlen M. (1981) Macrophage accumulation in transplanted tumors is not dependent on host immune responsiveness or presence of tumorassociated rejection antigens.J. Reticuloend. Soc. 30, 425–437.

    CAS  Google Scholar 

  • Flavin H. J., Wieraszako A., and Seyfried T. N. (1991) Enhanced aspartate release from hippocampal slices of epileptic (El) mice.J. Neurochem. 56, 1007–1011.

    Article  PubMed  CAS  Google Scholar 

  • Hakamori S. I. and Kannagi R. (1983) Glycosphingolipids as tumor-associated and differentiation markers.J. Nat. Cancer Inst. 71, 231–251.

    Google Scholar 

  • Hoon D. S. B., Okun E., Banez M., Reiko F. I., and Morton D. L. (1991) Interleukin 4 alone and with gamma-interferon or alpha-tumor necrosis factor inhibits cell growth and modulates cell surface antigens on human renal cell carcinomas.Cancer Res. 51, 5687–5693.

    PubMed  CAS  Google Scholar 

  • Jaeckle K. A., Mittelman A., and Hill F. H. (1990) Phase II trial ofSerratia marcescens extract in recurrent malignant astrocytomas.J. Clin. Oncol. 8, 1408–1418.

    PubMed  CAS  Google Scholar 

  • Jimenez J. J., McCall C.A., Cirocco R. E., and Yunis A.A. (1990) Treatment with ImuVert aborts development of chloroleukemia in newborn rats.J. Biol. Resp. Mod. 9, 300–304.

    CAS  Google Scholar 

  • Looney W. B., Mayo A. A., Allen P. M., Morrow J. Y., and Morris H. P. (1973) A mathematical evaluation of tumour growth curves in rapid, intermediate and slow growing rat hepatoma.Br. J. Cancer 27, 341–344.

    PubMed  CAS  Google Scholar 

  • McCall C., Weimer L., Campbell P., Riches D., and Urban R. (1988) Macrophage activation induced by a biological response modifier derived fromSerratia marcescens.J. Cell Biochem. 12E (suppl.), 175.

    Google Scholar 

  • McCall C. A., Weimer L., Baldwin S., and Pearson F. C. (1989) Biotherapy: a new dimension in cancer treatment.Bio/Technology 7, 231–240.

    Article  CAS  Google Scholar 

  • Mercurio A. M., Schwarting G. A., and Robbins P. W. (1984) Glycolipids of the mouse peritoneal macrophage. Alterations in amount and surface exposure of specific glycolipid species in response to inflammation and tumoricidal activation.J. Exp. Med. 160, 1114–1125.

    Article  PubMed  CAS  Google Scholar 

  • Morantz R. A., Wood G. W., Foster M., Clark M., and Gollahon M. S. (1979a) Macrophages in experimental and human brain tumors. Part 1.J. Neurosurg. 50, 298–304.

    PubMed  CAS  Google Scholar 

  • Morantz R. A., Wood G. W., Foster M., Clark M., and Gollahon M. S. (1979b) Macrophages in experimental and human brain tumors. Part 2.J. Neurosurg. 50, 305–311.

    PubMed  CAS  Google Scholar 

  • Ridley A. and Cavanagh J. B. (1971) Lymphocytic infiltration in gliomass: evidence of possible host resistance.Brain 94, 117–124.

    Article  PubMed  CAS  Google Scholar 

  • Rossi M. L., Esiri M. M., Jones N. R., Coakham H. B., Moss T. H., Cruz-Sanchez F. F., and Carey M. P. (1991) Characterization of the mononuclear cell infiltrate and HLA-Dr expression in 19 oligodendrogliomas.Surg. Neurol. 3, 119–125.

    Article  Google Scholar 

  • Rubin R., Sutton C. H., and Zimmerman H. M. (1968) Experimental ependymoblastoma (fine structure).J. Neuropathol. Exp. Neurol. 42, 1–15.

    Google Scholar 

  • Schauer R. (1985) Sialic acids and their roles as biological masks.Trends Biochem. Sci. 10, 357–360.

    Article  CAS  Google Scholar 

  • Schiffer D., Chio A., Giordana M. T., Mauro A., Migheli A., and Vigliani M. C. (1989) The vascular response to tumor infiltration in malignant gliomas.Acta Neuropath. (Berl.) 77, 369–378.

    Article  CAS  Google Scholar 

  • Schwarting G. A. and Gajewski A. (1983) Glycolipids of murine lymphocyte subpopulations.J. Biol. Chem. 258, 5693–5698.

    Google Scholar 

  • Seyfried T. N., Glaser G. H., and Yu R. K. (1978) Cerebral, cerebellar, and brain stem gangliosides in mice susceptible to audiogenic seizures.J. Neurochem. 31, 21–27.

    Article  PubMed  CAS  Google Scholar 

  • Seyfried T. N., Itoh T., Glaser G. H., Miyazawa N., and Yu R. K. (1981) Cerebellar gangliosides and phospholipids in mutant mice with ataxia and epilepsy: the tottering/leaner syndrome.Brain Res. 216, 429–436.

    Article  PubMed  CAS  Google Scholar 

  • Seyfried T. N., Yu R. K., Saito M., and Albert M. (1987) Ganglioside composition of an experimental mouse brain tumor.Cancer Res. 47, 3538–3542.

    PubMed  CAS  Google Scholar 

  • Seyfried T. N., El-Abbadi M., and Roy M. L. (1992) Ganglioside distribution in murine neural tumors.Mol. Chem. Neuropathol. 17, 147–167.

    Article  PubMed  CAS  Google Scholar 

  • Shinonaga M., Chang C. C., Suzuki N., Sato M., and Kuwabara T. (1988) Immunohistological evaluation of macrophage infiltrates in brain tumors.J. Neurosurg. 68, 259–265.

    PubMed  CAS  Google Scholar 

  • Siddiqui B. and Young K. S. (1984) Effects of sodium butyrate, dimethyl sulfoxide, and retinoic acid on glycolopids of human rectal adenocarcinoma cells.Cancer Res. 44, 1648–1652.

    PubMed  CAS  Google Scholar 

  • Svennerholm L. (1957) Quantitative estimation of sialic acids.Biochim. Biophys. Acta 24, 604–612.

    Article  PubMed  CAS  Google Scholar 

  • Warren R. P., McCall C. A., and Urban R. W. (1989) Augmentation of natural killer cell activity by ImuVert: a biological response modifier derived fromSerratia marcescens.Mol. Biother. 1, 145–151.

    PubMed  CAS  Google Scholar 

  • Weisenthal L. M., Dill P. L., and Pearson F. C. (1991) Effect of prior cancer chemotherapy on human tumor-specific cytoxicity in vitro in response to immunopotentiating biologic response modifiers.J. Nat. Cancer Inst. 83, 37–42.

    Article  PubMed  CAS  Google Scholar 

  • Yates A. J. (1988) Glycolipids and gliomas: A review.Neurochem. Pathol. 8, 157–179.

    PubMed  CAS  Google Scholar 

  • Yates A. J., Stephens R. E., Markowitz D. L., Elder P. J., Sirinek L. P., and Whisler M. D. (1985) Resistance to natural killer cytolysis and neutral glycolipid composition of cultured human glioma and fetal brain cells.J. Neuropathol. Exp. Neurol. 44, 371–383.

    Article  PubMed  CAS  Google Scholar 

  • Yates A. J., Markowitz D. L., Stephens R. E., Pear D. K., and Whisler R. L. (1988) Growth inhibition of cultured human glioma cells by beta-interferon is not dependent on changes in ganglioside composition.J. Neuropathol. Exp. Neurol. 47, 119–127.

    Article  PubMed  CAS  Google Scholar 

  • Yohe H. C. and Ryan J. L. (1986) Ganglioside expression in macrophages from endotoxin responder and nonresponder mice.J. Immunol. 137, 3921–3927.

    PubMed  CAS  Google Scholar 

  • Yohe H. C., Coleman D. L., and Ryan J. L. (1985) Ganglioside alterations in stimulated murine macrophages.Biochim. Biophys. Acta 818, 81–86.

    Article  PubMed  CAS  Google Scholar 

  • Yohe H. C., Cuny C. L., Macala L. J., Saito M., McMurray W. J., and Ryan, J. L. (1991) The presence of sialidase-sensitive sialosylgangliotetraosyl ceramide (GM1b) in stimulated murine macrophages.J. Immunol. 146, 1900–1908.

    PubMed  CAS  Google Scholar 

  • Yu R. K. and Ledeen R. W. (1970) Gas-liquid chromatographic assay of lipid-bound sialic acids: measurement of gangliosides in brains of several species.J. Lipid Res. 11, 506–516.

    PubMed  CAS  Google Scholar 

  • Zimmerman H. M. and Arnold H. (1941) Experimental brain tumors: 1. Tumors produced with methylcholanthrene.Cancer Res. 1, 919–938.

    CAS  Google Scholar 

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Cotterchio, M., Seyfried, T.N. The influence of ImuVert, a biological response modifier, on the growth and ganglioside composition of murine neural tumors. Molecular and Chemical Neuropathology 20, 163–172 (1993). https://doi.org/10.1007/BF02815369

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