Growth of human gliomas in immune-deficient mice: a possible model for pre-clinical therapy studies

Bradley, NJ; Bloom, H. J. G.; Davies, A. J. S.; Swift, S. M.

doi:10.1038/bjc.1978.197

Cited by 37 publications

(7 citation statements)

References 12 publications

(14 reference statements)

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“…In general, xenografts derived directly from patient biopsies retain more morphologic and molecular marker properties of the source tumors than those derived from cell lines (10,27). Thus, we established allografts by directly transplanting medulloblastoma tumor tissue isolated from Ptc1…”

Section: Resultsmentioning

confidence: 99%

Shh Pathway Activity Is Down-Regulated in Cultured Medulloblastoma Cells: Implications for Preclinical Studies

Sasai

Romer

Lee³

et al. 2006

Cancer Research

139

126

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Gene expression profiling indicates that the Sonic Hedgehog (Shh) pathway is active in f30% of human medulloblastomas, suggesting that it could provide a useful therapeutic target. Previously, we showed that spontaneous medulloblastomas in Ptc1 +/À p53 À/À mice could be eradicated by treatment with a small-molecule inhibitor (HhAntag) of Smoothened (Smo).Here, we compared the responses of mouse medulloblastoma cells propagated in flank allografts, either directly or after culture in vitro, to HhAntag. We found that Shh pathway activity was suppressed in medulloblastoma cells cultured in vitro and it was not restored when these cells were transplanted into the flank of nude mice. The growth of these transplanted tumor cells was not inhibited by treatment of mice with doses of HhAntag that completely suppressed Smo activity. Interestingly, tumor cells transplanted directly into the flank maintained Smo activity and were sensitive to treatment with HhAntag. These findings indicate that propagation of tumor cells in culture inhibits Smo activity in a way that cannot be reversed by transplantation in vivo, and they raise concerns about the use of cultured tumor cells to test the efficacy of Shh pathway inhibitors as anticancer therapies.

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Section: Resultsmentioning

confidence: 99%

Shh Pathway Activity Is Down-Regulated in Cultured Medulloblastoma Cells: Implications for Preclinical Studies

Sasai

Romer

Lee³

et al. 2006

Cancer Research

139

126

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“…Previous work has established the feasibility of both subcutaneous and intracranial sites of tumour transplantation in immune-deficient rodents (Rana et al, 1977;Bradley et al, 1978;Shapiro et al, 1979). The reason for using two different implantation sites was to evaluate the possibility that the intracranial microenvironment was unique with respect to oxygenation owing to differences in tumour interstitial pressure, tumour blood flow and/or vascular architecture.…”

Section: Discussionmentioning

confidence: 99%

Anomalous patterns of nitroimidazole binding adjacent to necrosis in human glioma xenografts: possible role of decreased oxygen consumption

Parliament¹,

Franko²,

Allalunis-Turner³

et al. 1997

Br J Cancer

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Summary In contrast to reports of extensive hypoxia in human gliomas in situ measured by P02 histography, non-invasive methods of assessing glioma oxygenation, including nitroimidazole binding, have yielded surprisingly contradictory results. In order to investigate the relationship of necrosis, hypoxia, nitroreductase activity and cellular respiration in human gliomas, subcutaneous models using the human glioma cell lines M059K, M006 and M01 Ob were developed in the murine SCID host. Intracranial growth of the M006 line was achieved in nude rats. The nitroreductive capacity of glioma cell lines was assessed and found to be similar to transplanted tumours previously reported in the literature. This suggests that if substantial numbers of viable hypoxic cells were present in situ in gliomas, then nitroimidazole-binding techniques should be capable of identifying them. Inter-tumour variability in the amount of necrosis was seen. M006 xenografts growing in subcutaneous and intracranial sites revealed extensive necrotic regions histologically, some of which were surrounded by cells labelled heavily for [3H]misonidazole, while other areas were lightly labelled. Similar binding patterns were seen for subcutaneous M059K tumours, while subcutaneous M01 Ob tumours display necroses of which almost all were surrounded by heavily labelled cells. The oxygen consumption rates of tumour cell lines grown in vivo, in which venous P02 concentrations are of the order of 2-5%, were two to sevenfold less than those of the same lines grown as monolayers in vitro under oxygen concentrations of 18%. We postulate that glioma cell lines behave as 'oxygen conformers', in that their rate of oxygen consumption appears to vary with the availability of oxygen. Together with the misonidazole-binding data, the results in this glioma tumour model are consistent with coordinate inhibition or down-regulation of respiration under moderate hypoxia.

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“…(Table I) (Darling et al, 1983) Animals The mice used in these experiments were from the inbred CBA/Ca strain, bred and maintained at the Chester BeattyResearch Laboratories. Theywere T-cell deprived and implanted with tumour as described previously (Bradley et al, 1978). The method used to estimate HLI sensitivity of monolayer cell cultures was that of Morgan et al (1983).…”

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confidence: 99%

The failure of human leukocyte interferon to influence the growth of human glioma cell populations: in vitro and in vivo studies

Bradley¹,

Darling²,

Oktar³

et al. 1983

Br J Cancer

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Five high-grade (3 grade III and 2 grade IV) astrocytoma tumour cell populations were treated with a preparation of Human Leukocyte Interferon either in monolayer cell culture or as multicellular spheroids in vitro or as xenografts growing in immune-deprived mice in vivo. A moderate and transient sensitivity was seen in one grade III tumour when tested in both of the in vitro assays, but no inhibition of growth was seen in vivo. Two tumours which were apparently resistant to Interferon treatment responded to orthodox chemotherapy. When used in conjunction with BCNU, Interferon was not effective in prolonging delay in tumour growth. It is concluded that Interferon is unlikely to be an effective agent in the treatment of malignant brain tumours.

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Growth of human gliomas in immune-deficient mice: a possible model for pre-clinical therapy studies

Cited by 37 publications

References 12 publications

Shh Pathway Activity Is Down-Regulated in Cultured Medulloblastoma Cells: Implications for Preclinical Studies

Shh Pathway Activity Is Down-Regulated in Cultured Medulloblastoma Cells: Implications for Preclinical Studies

Anomalous patterns of nitroimidazole binding adjacent to necrosis in human glioma xenografts: possible role of decreased oxygen consumption

The failure of human leukocyte interferon to influence the growth of human glioma cell populations: in vitro and in vivo studies

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