Heterogeneity in Chemosensitivity and Acquisition of Drug Resistance in a Murine Model of Glioma

Bradford, Robert; Jl, Darling; Thomas, D. G. T.

doi:10.1007/978-94-009-3347-7_65

Cited by 3 publications

(5 citation statements)

References 8 publications

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“…It is unlikely that the failure of response to PCB is due to inadequate dosage levels since some systemic toxicity did occur at the highest dose. It is more likely that there is inherent resistance of 497-P(1) cells to PCB, as has been seen in in vitro studies (Bradford et al, 1987(Bradford et al, , 1988a.…”

Section: Chemotherapy Of Subcutaneous Tumoursmentioning

confidence: 97%

“…Variations in the proportions of VCR sensitive and resistant subpopulations may also influence the rapidity with which resistance to VCR can develop. It has been shown that this occurred rapidly when P497 intracerebral tumours were treated with VCR (Bradford et al, 1987). PCB was ineffective at any dosage level.…”

Section: Chemotherapy Of Subcutaneous Tumoursmentioning

confidence: 99%

“…The variable response to VCR observed with this model is of interest. The greatest variability in in vitro chemosensitivity of the cloned cell lines derived from VMDk P497 (Koppel et al, 1987) was to the vinca alkaloids VCR and vindesine (Bradford et al, 1987). The variability in response to VCR may reflect the different proportions of sensitive and resistant clonal subpopulations in 497-P(1) tumours.…”

Section: Chemotherapy Of Subcutaneous Tumoursmentioning

confidence: 99%

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The chemotherapeutic response of a murine (VM) model of human glioma

Bradford¹,

Darling²,

Thomas³

1990

Br J Cancer

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Summary Using a cell line derived from the VM spontaneous murine astrocytoma, a reliable in vitro-in vivo model of human malignant glioma has been developed. In this paper we examine the effects of cytotoxic drugs with known activity against other animal brain tumour models and human disease on the in vivo VM model. The drugs BCNU, CCNU and vincristine produced significant volume reduction in tumours growing at a subcutaneous location in syngeneic animals. Procarbazine was ineffective. Similarly, BCNU, CCNU and vincristine produced small but statistically significant increases in survival of VM mice bearing the intracerebral tumour, but procarbazine was again ineffective. The modest, but significant, response of the VM model to the nitrosoureas mimics the human situation more closely than previously described animal models.A cell line VMDk 497-P(1), derived from the VM spontaneous murine astrocytoma (Fraser, 1980), has been used to develop an in vitro-in vivo model of human glioma. The cell line can be grown as monolayer cultures and as multicellular tumour spheroids (Bradford et al., 1989a). It also produces tumours at subcutaneous and intracranial sites when inoculated into syngeneic VM mice. In a previous report (Bradford et al., 1989b) we described the development of the in vivo model and showed that cell line 497-P(1) provides the basis for a reliable and reproducible model of glioma, which fulfils many of the criteria required for experimental therapy.

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Section: Chemotherapy Of Subcutaneous Tumoursmentioning

confidence: 97%

Section: Chemotherapy Of Subcutaneous Tumoursmentioning

confidence: 99%

Section: Chemotherapy Of Subcutaneous Tumoursmentioning

confidence: 99%

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The chemotherapeutic response of a murine (VM) model of human glioma

Bradford¹,

Darling²,

Thomas³

1990

Br J Cancer

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“…The P497(pl) cell line of this tumour was used between passage levels 10 and 16 (Bradford et al, 1987).…”

Section: Tumour Modelmentioning

confidence: 99%

“…Cerebral oedema resulting from PDT has been reported in man (Muller & Wilson, 1987;McCulloch et al, 1984). It has been successfully controlled with intra/post-operative steroids (Kaye & Morstyn, 1987) have therefore used the meta-isomer m-THPP in the treatment of subcutaneously and intracranially transplanted VMDk mouse gliomas (Bradford et al, 1987;Bradford et al, 1989). Further, in view of the evidence for oxygen dependency of PDT in vitro Moan & Sommer, 1985) and in vivo (Henderson & Fingar, 1987;Gomer & Razum, 1984) we have studied the effect of PDT on tumours in animals breathing either air or 100% oxygen.…”

mentioning

confidence: 99%

Photodynamic therapy of a mouse glioma: intracranial tumours are resistant while subcutaneous tumours are sensitive

Lindsay

Berenbaum²,

Bonnett³

et al. 1991

Br J Cancer

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Summary Subcutaneous and intracranial VMDk tumours were treated with photodynamic therapy (PDT) using a new sensitiser, m-THPP. Subcutaneous tumours were highly sensitive to PDT but intracranial tumours were much more resistant, requiring a 30-fold increase in sensitiser dose to produce equivalent levels of necrosis. Resistance of intracerebral tumours was not due to failure of the sensitiser to enter tumours. Necrosis of intracranial tumours was increased when mice breathed 100% oxygen during PDT while subcutaneous tumour necrosis was unaffected.Malignant astrocytic tumours, glioblastoma multiforme and malignant astrocytoma, run a particularly aggressive course; median survival after surgery being less than 1 year (Walker et al., 1980;Salcman, 1980). They do not metastasise and death is most commonly due to local recurrence of the tumour. Therefore, any improvement in local control would be expected to prolong survival. Photodynamic therapy (PDT) was proposed as an adjuvant therapy for the treatment of human brain tumours, after removal of the bulk of the tumour by radical surgery. PDT relies on the fact that certain systemically administered photosensitisers localise in and are retained by tumours (and also normal tissues). Exposure of the tumour to light which activates the photosensitiser leads to rapid necrosis, which is probably due to cell membrane damage by singlet oxygen (Moan et al., 1979). Brain tumours may be good candidates for PDT as photosensitisers so far investigated do not cross the blood brain barrier (BBB), but accumulate in brain tumours, which lack an effective barrier. Thus, administration of a photosensitiser before surgical debulking of the tumour, followed by illumination of the tumour bed to destroy remaining tumour cells, may conceivably eradicate the tumour.Initial applications of PDT to brain tumours in man produced equivocal results (Perria et al., 1980; Laws et al., 1981;McCulloch et al., 1984). Treatment protocols varied widely and, though there were some remissions, rapid tumour regrowth often occurred. Recent trials using more intensive PDT regimens have produced more promising results (Kaye & Morstyn, 1987;Muller & Wilson, 1987;Kaye, 1989), and have stimulated renewed interest in this treatment.Animal experiments have shown that, with the photosensitisers available for clinical use, haematoporphyrin derivative (HpD) and Photofrin II, PDT treatments which produce tumour kill also cause severe cerebral oedema and necrosis of normal brain (Rounds et al., 1982;Bonnett et al., 1984), which is probably due to damage to the endothelium of small blood vessels . Cerebral oedema resulting from PDT has been reported in man (Muller & Wilson, 1987;McCulloch et al., 1984). It has been successfully controlled with intra/post-operative steroids (Kaye & Morstyn, 1987) have therefore used the meta-isomer m-THPP in the treatment of subcutaneously and intracranially transplanted VMDk mouse gliomas (Bradford et al., 1987;Bradford et al., 1989). Further, in view of the evidence for oxygen dependenc...

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The Development of an Animal Model of Glioma for Use in Experimental Neuro-oncology

Bradford

Darling

Thomas

1989

British Journal of Neurosurgery

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A cell line, 497-P(1), derived from the VM spontaneous murine astrocytoma has been used to develop an in vitro in vivo model of human glioma. This paper describes the growth characteristics of tumours produced after intracerebral or subcutaneous inoculation of 497-P(1) cells into syngeneic VM mice. The results show that cell line 497-P(1) provides the basis for a reproducible animal model of glioma which fulfils many of the criteria required for experimental therapy studies.

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Heterogeneity in Chemosensitivity and Acquisition of Drug Resistance in a Murine Model of Glioma

Cited by 3 publications

References 8 publications

The chemotherapeutic response of a murine (VM) model of human glioma

The chemotherapeutic response of a murine (VM) model of human glioma

Photodynamic therapy of a mouse glioma: intracranial tumours are resistant while subcutaneous tumours are sensitive

The Development of an Animal Model of Glioma for Use in Experimental Neuro-oncology

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