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

Bradley, NJ; Darling, John L.; Oktar, Nezih; Bloom, H. J. G.; Thomas, D. G. T.; Davies, A. J. S.

doi:10.1038/bjc.1983.272

Cited by 28 publications

(8 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with previous studies [31][32][33] suggesting that gliomas are more sensitive to IFN-~ than IFN-o~. Although many cells exhibit an anti-proliferative response to IFN-7 [6,7,10,35], some, including a rat glioma cell line [36], astrocytes [37], T cells [38] and keratinocytes [39] have been shown to proliferate when treated with IFN-7.…”

Section: Discussionsupporting

confidence: 80%

Interferon-? inhibits proliferation and progression through S phase of the cell cycle in five glioma cell lines

et al. 1996

View full text Add to dashboard Cite

The growth inhibitory effect of IFN-beta was evaluated in 5 human glioma cell lines (AO2V4, GJC, GJR, NN and NNR) and in normal astrocyte cultures (SC and TM). All 5 glioma cell lines showed an anti-proliferative response to IFN-beta whereas normal glial cells were non-responsive. IFN-beta at 10, 100 and 500 U/ml lead to a 30%, 70% and 80% relative decrease in cell number after 12 days, respectively in AO2V4 cells. GJC and GJR cell lines also responded significantly to the lowest concentration of IFN-beta tested and at 500 U/ml the relative cell number decreased 55%. The NN and NNR cells were the least responsive to IFN-beta with maximum growth inhibition of 30% at 500 U IFN-beta/ml. Following treatment with IFN-beta, AO2V4, GJC, GJR and normal astrocytes all expressed mRNA encoding the anti-viral protein, 2-5A synthetase demonstrating that IFN-beta bound to receptors on all four cell lines and activated signal transduction pathways required for induction of an anti-viral protein. A determination of the relative number of viable cells showed that none of these cells exhibited a significant decrease in cell viability. Since the antiproliferative response to IFN-beta was not primarily due to cell death, the effect of IFN-beta on cell cycle progression was evaluated by flow cytometry. All treated glioma cell lines showed a relative increase in proportion of cells in S phase. AO2V4 cells had a 50%-80% increase in the percentage of cells in S phase, whereas GJC, GJR and NNR had percentage increases of 20%-40%. IFN-beta treatment of normal astrocytes did not significantly alter their cell cycle profile. These data suggest that IFN-beta exerts its antiproliferative effect on glioma cells by arresting the ordered progression through S phase or decreasing entry into G2/M phase of the cell cycle.

show abstract

Section: Discussionsupporting

confidence: 80%

Interferon-? inhibits proliferation and progression through S phase of the cell cycle in five glioma cell lines

et al. 1996

View full text Add to dashboard Cite

show abstract

“…Both ct and 131FN have been reported to inhibit in vitro, at certain concentrations the growth of the glioma cell line, and to induce differentiation of anaplastic cells [6,9,3]. The regression or inhibition of tumor growth is induced by higher IFN dosages, but to a lesser …”

Section: Discussionmentioning

confidence: 99%

Local immunotherapy (β-IFN) and systemic chemotherapy in primary glial tumors

et al. 1991

View full text Add to dashboard Cite

Dosage and schedules for the treatment of malignant glial tumors using IFN (interferon) are still uncertain and controversial. In this study we give the preliminary results of treatment in 28patients with glioblastoma multtforme (GBM). 6 patients were treated with local injection offldFN through an Ommaya reservoir; 4 patients with fl-IFN followed by systemic chemotherapy (Cisplatin + Etoposide), and 18 patients with chemotherapy only. Two end points were evaluated: 1) Whether or not the patients responded to treatment. 2) Length of Time to Tumor Progression (TTP) after surgery. We found that IFN alone was ineffective. Results were improved when local immunotherapy was associated with systemic chemotherapy. New drugs and investigation of possible pharmacological synergism are needed.

show abstract

“…These results are summarized in Figure 2. In this connection, a recent study by others [7] suggests that alpha interferons are relatively inert in relation to antimitotic behavior against human brain tumors, thus suggesting the increased importance of further laboratory and clinical studies with beta interferon or agents such as double-stranded RNAs which cause the local production of interferons beta and gamma.…”

Section: Discussionmentioning

confidence: 99%

Human non-malignant and malignant brain tumor derived cell cultures: proliferation and sensitivity to natural human fibroblast (beta) interferon

Cook¹,

Nidzgorski²,

Roane

et al. 1987

J Neuro-Oncol

View full text Add to dashboard Cite

Twenty-one human brain tumor biopsies were processed by mechanical and enzymatic methods to produce mixed cell suspensions. Cultures were prepared in small plastic flasks, and primary outgrowth occurred in 16/21 cultures. The period required for primary outgrowth ranged from 3 days to 14 days. We established serial propagation with 15/16 of the primary cultures. Sensitivity to HuIFN-beta was determined between passages 3 to 12, using a microassay based on cell viability (uptake of a supravital stain, neutral red). Extracted dye was quantified in acidic-methanol using the MR580 Microelisa Autoreader (Dynatech). We observed a broad range of responsiveness to the drug among the 12 cell-strains tested. Thus, 4 cell strains were relatively sensitive; 4 were resistant to 10(4) IRU/ml of purified HuIFN-beta. Four cell strains exhibited a level of responsiveness that was intermediate to that of these two groups. During propagation of these biopsies, cytopathology suggestive of paramyxovirus-infection appeared in 4 of the cell-strains. This characteristic was not uniformly associated with high sensitivity to human beta interferon which is a very potent, naturally occurring antiviral substance. Our results support the concept that information concerning sensitivity to HuIFN-beta and other cytostatic agents may be rapidly obtained using microcultures of brain tumor cultures in conjunction with supravital stain uptake studies. Additionally, these results suggest that further clinical studies with beta interferon should be undertaken to define the parameters which determine successful in vivo application.

show abstract

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

Cited by 28 publications

References 20 publications

Interferon-? inhibits proliferation and progression through S phase of the cell cycle in five glioma cell lines

Interferon-? inhibits proliferation and progression through S phase of the cell cycle in five glioma cell lines

Local immunotherapy (β-IFN) and systemic chemotherapy in primary glial tumors

Human non-malignant and malignant brain tumor derived cell cultures: proliferation and sensitivity to natural human fibroblast (beta) interferon

Contact Info

Product

Resources

About