Glioma Biology in vitro: Goals and Concepts

Westphal, Manfred; Hänsel, Marianne; Nausch, H.; Rohde, Eva; Köppen, Johannes; Fiola, Martin; Hölzel, F.; Herrmann, H. D.

doi:10.1007/978-3-7091-8978-8_23

Cited by 5 publications

(2 citation statements)

References 11 publications

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“…The results, however, often show little correlation with the patient's response to therapy [l. 10, 231. This discrepancy might be caused by lack of cellular heterogeneity in the culture models used [22].…”

Section: Introductionmentioning

confidence: 99%

Long‐term culture of organotypic multicellular glioma spheroids: a good culture model for studying gliomas

Kaaijk

Troost

Das

et al. 1995

Neuropathology Appl Neurobio

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Gliomas, as well as other solid tumours, contain tumour stroma composed of connective tissue, macrophages, capillaries and other non-cellular constituents. Therefore, a homogeneous culture of tumour cells alone, as is often used as a culture model for gliomas, is not ideal to study all aspects of gliomas. In the present study we describe an alternative culture model, i.e. organotypic multicellular spheroids (OMS), that histologically closely resembles the tumour in vivo. Glioma explants, obtained at surgery from five patients, were cultured on agarose to form OMS, which were cultured for up to 16 weeks. At regular intervals, OMS were fixed and histological and immunocytochemical analyses were carried out. The histology as well as the immunocytochemical characteristics of the OMS proved to be almost unchanged after a culture period of 16 weeks. In contrast to monolayer cultures, glial fibrillary acidic protein (GFAP) expression in the OMS is preserved after 16 weeks of culture. However, in OMS from three out of five patients, small GFAP-negative cells appeared in the outer cell layers between 1 and 2 weeks of culture. Furthermore, after about 6 weeks of culture, the capillaries disappeared from the OMS. After prolonged culture, tumour cell heterogeneity, the cellular composition, and the histology of the OMS still closely resembled the tumour in vivo. It is suggested that OMS provide a good long-term culture model for the study of gliomas.

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Section: Introductionmentioning

confidence: 99%

Long‐term culture of organotypic multicellular glioma spheroids: a good culture model for studying gliomas

Kaaijk

Troost

Das

et al. 1995

Neuropathology Appl Neurobio

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“…Using these culture models it appeared that several drugs that are able to cross the BBB show a high cytolytic activity in vitro, whereas glioma patients respond poorly to these drugs (Yung et al, 1982;Kimmel et al, 1987;Yung 1989). Lack of cellular heterogeneity in the cell lines used and selection of themosensitive subpopulations during culture are the most likely explanation for this discrepancy (Yung et al, 1982;Kimmel et al, 1987;Westphal et al, 1988;Yung, 1989).…”

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confidence: 99%

Daunorubicin and doxorubicin but not BCNU have deleterious effects on organotypic multicellular spheroids of gliomas

Kaaijk

Troost²,

Boer³

et al. 1996

Br J Cancer

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Summary In the present study organotypic multicellular spheroids (OMS) were used to study the effects of chemotherapeutic agents on malignant gliomas. Compared with the frequently used cell line models, OMS have several advantages with respect to the preservation of the cellular heterogeneity and the structure of the original tumour. OMS prepared from seven glioma specimens were treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), daunorubicin or doxorubicin. After exposure to these drugs, the histology and cell proliferation of the OMS were analysed by immunohistochemistry and image analysis. Furthermore, the expression of Pglycoprotein (P-gp) and multidrug resistance-related protein (MRP), which both can contribute to resistance to daunorubicin and doxorubicin, were immunohistochemically investigated. We found that OMS from gliomas are sensitive for daunorubicin and doxorubicin but not for BCNU in terms of tissue destruction and decrease in cell proliferation. In addition, all gliomas were P-gp and MRP negative, which is in accordance with the sensitivity for daunorubicin and doxorubicin. Considering the potential use of several new alternative drug delivery methods, such as intratumoural implantation of drug-impregnated polymers or liposomal encapsulation of cytostatic drugs, daunorubicin and doxorubicin might be effective in the treatment of malignant gliomas.

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Growth Factors in Gliomas Revisited

Hamel

Westphal

2000

Acta Neurochir (Wien)

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Overexpression or untimely expression of wild-type or mutated protein growth factors and their receptors is associated with the biology of malignant gliomas and other types of cancer. It may result in unchecked tumour cell proliferation, migration/invasion into normal tissue, tumour angiogenesis, escape from immune surveillance, and decreased apoptotic cell death, i.e. after treatment with cytotoxic agents. This often involves activation of growth factor receptors either by simultaneous production of growth factors and corresponding receptors on the same or adjacent tumour cells or by constitutive receptor activation due to mutations. In several instances, the cellular genes encoding these growth factors and receptors are homologous to transforming genes/oncogenes from tumourigenic retroviruses and have thus been regarded as cellular proto-oncogenes. In recent years much progress has been made towards a better understanding of the function of these molecules and how they lead to the aggressive phenotype of malignant gliomas and its inherent resistance to adjuvant therapies. This, still insufficient, knowledge is a prerequisite for the development of novel therapies for this non-curable disease. The aim of this review is to address relevant growth factor receptor systems with emphasis on their particular role in glioma biology.

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Glioma Biology in vitro: Goals and Concepts

Cited by 5 publications

References 11 publications

Long‐term culture of organotypic multicellular glioma spheroids: a good culture model for studying gliomas

Long‐term culture of organotypic multicellular glioma spheroids: a good culture model for studying gliomas

Daunorubicin and doxorubicin but not BCNU have deleterious effects on organotypic multicellular spheroids of gliomas

Growth Factors in Gliomas Revisited

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