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

Bradford, Robert; Darling, John L.; Thomas, D. G. T.

doi:10.3109/02688698909002795

Cited by 9 publications

(9 citation statements)

References 28 publications

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“…The ratio of the mean treated tumour to the mean control tumour volume (T/C) on day 21 was determined. Mean growth delay (GD) was measured by the method described by Houghton and Houghton (1983) Chemotherapy of intracerebral tumours VM mice were inoculated intracerebrally with 497-P(1) cells in the manner previously described (Pilkington et al, 1985;Bradford et al, 1989b ILS=(T/C)x 100% ILS values from experiments which were performed on two separate occasions were averaged to yield the mean increased life-span. An ILS of 25% was considered as indicative of activity (Geran et al, 1974).…”

Section: Cell Linesmentioning

confidence: 99%

“…Control groups consisted of at least 10 tumours. The growth curve of untreated tumours is Gompertzian in form and the volume doubling time is approximately 1.4 days and 5.1 days at small and large volumes respectively (Bradford et al, 1989b). The complete results are shown in Table I. BCNU Eight tumours were treated with a single dose of 30 mg kg-' BCNU on day 10 following inoculation.…”

Section: Chemotherapy Of Subcutaneous Tumoursmentioning

confidence: 99%

“…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. …”

mentioning

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: Cell Linesmentioning

confidence: 99%

Section: Chemotherapy Of Subcutaneous Tumoursmentioning

confidence: 99%

mentioning

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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“…497-P(1) can be grown in the brain or flank of syngeneic VM mice or in vitro as a monolayer culture [9]. In this paper we describe the preparation of MTS from 497-P(1) cells and their response to cytotoxic agents with known efficacy against human malignant glioma.…”

Section: Introductionmentioning

confidence: 99%

The VM model of glioma: Preparation of multicellular tumour spheroids (MTS) and their response to chemotherapy

Bradford

Sier

et al. 1990

J Neuro-Oncol

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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 therapeutic model of human glioma. In this study we describe the preparation of MTS from this cell line. The in vitro chemosensitivity of 497-P(1) MTS has been examined and compared to the sensitivity of the monolayer culture. BCNU and CCNU both produced growth delay in MTS at doses below the ID50 of the monolayer culture. MTS, however, were considerably more resistant to vincristine and procarbazine when compared to the monolayer culture.

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“…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.…”

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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

Cited by 9 publications

References 28 publications

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

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

The VM model of glioma: Preparation of multicellular tumour spheroids (MTS) and their response to chemotherapy

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

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