Effect of human leukocyte interferon on malignant brain tumors

Hirakawa, Kimiyoshi; Ueda, Satoshi; Nakagawa, Yoshio; Suzuki, Kenzo; Fukuma, Seishi; Kita, Masakazu; Imanishi, Jirô; Kíshida, Tsunataro

doi:10.1002/1097-0142(19830601)51:11<1976::aid-cncr2820511103>3.0.co;2-d

Cited by 56 publications

(11 citation statements)

References 13 publications

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“…We therefore evaluated the gene expression profiles employing GeneChip in seven malignant human glioma-derived cell lines in an attempt to identify new marker(s) that could be applied clinically to predict the response to therapy and new target gene(s) for the therapy related to malignant glioma pathogenesis. One purpose of the present study was to identify molecular marker(s) that reflected therapeutic responses to the direct antitumor effect of IFN-β in malignant glioma cells, since IFN-β is known to be partially effective for treating malignant glioma patients; clinical trials of IFN-β have resulted in partial remission in 50% or more of patients tested (25,26), and the pharmaco-dynamics at the genomic level in humans remain poorly understood. To our knowledge, this is the first report on gene expression profiles to identify marker(s) that could be used clinically to predict malignant gliomas responses to IFN-β.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiles predicting the response to IFN-β and a combination of temozolomide and IFN-β in malignant gliomas

Yoshino

Tashiro²,

Ogino³

et al. 2011

Int J Oncol

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Abstract. Temozolomide (TMZ) is an alkylating agent that has yielded significant benefits and is a current standard agent in the treatment of malignant gliomas. However, its survival benefit remains unsatisfactory. Recently, a synergistic antitumor effect between TMZ and interferon-β (IFN-β) was reported in malignant glioma cells. The Japan Clinical Oncology Group (JCOG) brain tumor study group has recently began a randomized phase II study to evaluate the clinical effectiveness of combination therapy with TMZ and IFN-β in glioblastomas. However, it is not sufficient just to evaluate the mechanisms and establish an experimental basis for rational clinical therapy with IFN-β and TMZ. The precise mechanisms governing the direct effects of IFN-β and a combination of IFN-β and TMZ in gliomas are not yet fully understood. To gain insight into the mechanisms of sensitivity/resistance involving IFN-β and combination therapy with IFN-β and TMZ, and further to identify new marker(s) that could be used clinically to predict the response to such therapy and new target gene(s) for therapies related to malignant glioma patho genesis, we evaluated the gene expression profiles of human malignant glioma cell lines employing a high-density oligo nucleotide DNA array, GeneChip. We present a list of the most highly upregulated and downregulated genes which may be involved in conferring a response to IFN-β and synergistic effect between IFN-β and TMZ in malignant gliomas. Although the present study has several limitations, our reported candidate genes could represent not only potential molecular markers but also chemotherapy targets for improving the treatment outcome by devising strategies that are able to circumvent primary drug resistance in malignant gliomas.

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Section: Discussionmentioning

confidence: 99%

Gene expression profiles predicting the response to IFN-β and a combination of temozolomide and IFN-β in malignant gliomas

Yoshino

Tashiro²,

Ogino³

et al. 2011

Int J Oncol

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“…While it has been studied in the literature that IFN is effective on certain glioblastomas, medulloblastomas and metastatic tumors, it has also been reported that according to clinical results the treatment of brain tumors with IFN has been effective in only 18% of the cases. Regarding IFN-a, 13 and 7, there have been in vivo studies, in vitro studies, and reported clinical applications [11][12][13][14][15]. Recently, a therapy which combined an IFN with other IFNs, other chemotherapeutic agents, Or radiation therapy was reported [11,13,16,17].…”

Section: Discussionmentioning

confidence: 99%

Flow cytometric analysis of antineoplastic effects of interferon-?, ? and ? labelled with fluorescein isothiocyanate on cultured brain tumors

et al. 1991

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Antineoplastic effects of interferons (IFNs) on brain tumors have often been reported in the literature, however, so far as we know, there are no reports of the study on the antineoplastic effect of IFNs (alpha, beta, and gamma) labelled with fluorescein isothiocyanate (FITC) using flow cytometry (FCM). Three established glioma cell lines and 11 cultured cells of brain tumor from surgical specimens were exposed to IFN-alpha, beta, and gamma at the concentrations of 10(2)-10(5) IU/ml for 24 h, respectively. Using FCM, the viability of the cells was evaluated with fluorescein diacetate stain and the cell cycle was analyzed from the DNA-histogram with propidium iodide stain. Furthermore, FITC-labelled IFN-alpha, beta and gamma were also contacted with each cell to calculate respective positive cells. The viability decreased about 60% on day 1 and day 3, indicating the effect of IFN-alpha and beta on U373MG cells and on some cultured glioma cells from surgical materials, whereas, IFN-gamma had no effects. Antineoplastic effect of each IFN well correlated with FITC-positive rates, demonstrating S phase block in the cell cycle. IFN-gamma had no antineoplastic effects, whereas IFN-alpha and beta showed antineoplastic effects, which fact suggested that IFN-gamma receptor be different from those of IFN-alpha and beta. The method of FITC-labelling for IFNs with the aid of FCM has the advantages as follows: 1) Antineoplasticity of IFN can be simply evaluated with FCM; 2) It is easy to analyze the action mechanism of IFN; 3) Information on the receptor is obtainable; and 4) Sensitivity can be evaluated prior to administration of IFN, suggesting possibilities of clinical application of this method.

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“…In addition, local administration of IFN by Ommaya reservoir can yield CSF IFN levels up to 10 000 XRU/ml [30] and occasional clinical responses have been noted [30,33,35]. However, in the number of phase I and phase IX clinical studies using IFN-a, XFN-t3 or poly(XCLC) individually that have been reported [30][31][32][33][34][35][36], clinical improvement, as measured by CT scans or neurologic symptoms, appear to be sporadic and generally short-lived. Combination IFN/IFN or IFN/Ampligen treatment may increase the intensity of the clinical effect and widen the scrope of patients whose tumors will respond to treatment with these biological response modifiers.…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies in tissue culture [16,[24][25][26][27][28], nude mice [25,29] and in the clinic [30][31][32][33][34][35][36] have investigated the use of IFN-a, IFN-/3 or dsRNA in the treatment of various brain tumors. Evidence for the effectiveness of IFN or dsRNA therapy has been presented, however, the number of responding tumors is low and not consistent in respect to the type of IFN or dsRNA, dose of drug used or route of administration.…”

Section: Introductionmentioning

confidence: 99%

Sensitivities of human glioma cell lines to interferons and double-stranded RNAs individually and in synergistic combinations

Dick

Hubbell

1987

J Neuro-Oncol

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The antiproliferative effects of human interferons (IFNs) and double-stranded RNAs (dsRNAs) were studied in five human glioma cell lines. Dose response curves were generated over a 72 hour treatment period. The concentration of interferon or double-stranded RNA necessary to produce a 50% antiproliferative response (GI50) was calculated by linear regression analysis. Two cell lines were more sensitive to IFN-beta than to IFN-alpha, one cell line was more sensitive to IFN-alpha than to IFN-beta and two cell lines had approximately equal sensitivities to both interferons. All cell lines showed some sensitivity to either IFN-alpha or IFN-beta. IFN-gamma had no antiproliferative effect on any of the cell lines. In addition, only one of the cell lines displayed sensitivity to dsRNA, in which the response to poly(I).poly(C) was greater than that to a mismatched analogue of poly(I).poly(C), r(I)n.r(C12,U)n (Ampligen). There was no correlation between the sensitivities to type I IFNs (alpha and beta), type II IFN (gamma) or the dsRNAs. The antiproliferative effect of combinations of IFNs, or IFNs and Ampligen, was studied in one of the cell lines. A significant synergistic antitumor effect was seen with all of the IFN/Ampligen combinations (p less than 0.02), including IFN-gamma/Ampligen, even though these cells were resistant to IFN-gamma alone. Synergy was also seen in the IFN-alpha/IFN-gamma (p less than 0.02) and IFN-beta/IFN-gamma (p less than 0.05) combinations. The IFN-alpha/IFN-beta combination gave an additive antitumor effect. These results indicate that IFN-alpha and IFN-beta alone or combinations of type I IFNs, type II IFNs and Ampligen can be effective in inhibiting the growth of glioma cells.

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Effect of human leukocyte interferon on malignant brain tumors

Cited by 56 publications

References 13 publications

Gene expression profiles predicting the response to IFN-β and a combination of temozolomide and IFN-β in malignant gliomas

Gene expression profiles predicting the response to IFN-β and a combination of temozolomide and IFN-β in malignant gliomas

Flow cytometric analysis of antineoplastic effects of interferon-?, ? and ? labelled with fluorescein isothiocyanate on cultured brain tumors

Sensitivities of human glioma cell lines to interferons and double-stranded RNAs individually and in synergistic combinations

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