Effects of interferons in neoplastic diseases of man

Borden, Ernest C.

doi:10.1016/0163-7258(88)90026-5

Cited by 18 publications

(4 citation statements)

References 77 publications

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“…The action of IFNs is initiated by their binding to a target cell membrane receptor: studies have shown that IFNs-or and -/I (type I TFNs) share a common receptor while IPN-7 (type I1 IFN) interacts with a different binding site (Branca & Baglioni,198 1: Orchansky et al 19 84). Kecently, progress has been made in the molecular characterization of these receptors, and a cDNA coding for the human lFN-a/p receptor and for The wide range of biological activities of IFNs account for their use in the treatment of a number of viral and malignant diseases (Borden. 1988).…”

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confidence: 99%

Characterization of specific functional receptors for HuIFN‐α on a human megakaryocytic cell line (Dami): expression related to differentiation

Martyré¹

1994

Br J Haematol

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Interferon-alpha (IFN-alpha) treatment has been shown to be highly effective in inhibiting human megakaryocytopoiesis and controlling thrombocytosis in patients with myeloproliferative disorders. These observations suggest that IFN-alpha might play some role in the biological feature of the megakaryocytic lineage and led us to investigate the presence of specific receptors for IFN-alpha on human megakaryocytic cells, i.e. the Dami cell line, and to study the regulation of their expression. Our study demonstrates that [125I]-recombinant human IFN-alpha ([125I]rHu-IFN-alpha) binds to high-affinity specific receptor on these cells. Scatchard analysis of binding data indicates the presence of homogeneous binding sites estimated in the range of 3000-5000, with an apparent equilibrium dissociation constant, Kd, of 1-2 x 10(-9) M. Also, [125I]rHuIFN-alpha binding capacity decreased in Dami cells incubated with unlabelled rHuIFN-alpha. This down-regulation which was dose-dependent appeared to result from a reduction of IFN-alpha cell surface receptors and was observed at doses that elicited antiproliferative effects in Dami cells. Cross-linking of [125I]rHuIFN-alpha to Dami membrane proteins using a bifunctional reagent yielded to a radioactive complex of approximately 150,000 kD on SDS-PAGE. Furthermore, in response to PMA, which induces the differentiation/maturation of the Dami cells as evaluated by surface marker and ploidy analysis, a 3-fold increase of the number of specific membrane receptors for IFN-alpha was observed, without any modification of either the affinity or the M(r) value of the cross-linked complex. Such an increase appeared to be restricted to IFN-alpha receptors; actually it was not observed in [125I]IFN-gamma binding experiments. Transcript analysis indicated that down-regulation and increased expression of the IFN-alpha receptor after PMA treatment are post-transcriptional events.

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confidence: 99%

Characterization of specific functional receptors for HuIFN‐α on a human megakaryocytic cell line (Dami): expression related to differentiation

Martyré¹

1994

Br J Haematol

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“…More encouraging results have been observed in experimental models utilizing IFN- [3 combined with other agents such as IFN-~, [2][3][4][5][6][7][8][9], mismatched double-stranded RNA [10,11], and cytostatic drugs [1]. In patients, however, combination therapy using rlFN-~ and rlFN-~/has met with little success.…”

Section: Introductionmentioning

confidence: 93%

“…In recent years several reports have dealt with the antiproliferative actions of fibroblast interferon on a variety of human neoplastic diseases including carcinomas of different sites, melanomas, sarcomas, and hematopoietic malignancies [1]. Thus far, the results obtained with IFN-fl delivered alone have been variable, but have indicated that IFN-[5 can be of some clinical efficacy in selected tumors.…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative effects of natural interferon beta alone and in combination with natural interferon gamma on human breast carcinomas in nude mice

Ozzello

1990

Breast Cancer Res Tr

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Nude mice bearing bilateral xenografts of human breast carcinoma cells (MCF-7 and BT20) were treated with 2 or 45-day cycles of intralesional (i.l.) injections of human natural interferon beta (nIFN-beta) alone or in combination with human natural interferon gamma (nIFN-gamma). The injections were administered to only 1 of the 2 tumors in each animal, thus making it possible to assess at the same time local therapeutic effects in the injected tumors and systemic effects in the contralateral ones. When n-IFN-beta was used as a single agent only mild local antitumor effects and virtually no systemic effects were observed. In contrast, the combined administration of nIFN-beta/nIFN-gamma produced marked antiproliferative effects, presumably as a result of the synergistic action of type I and type II IFNs. These effects ranged from complete regression documented histologically in 2 MCF-7 tumors to varying degrees of growth inhibition with persistence of residual microscopic or grossly detectable tumor. Local effects were more pronounced than systemic effects. The therapeutic efficacy of nIFN-beta proved to be greater than that of recombinant interferon beta (rIFN-beta). In MCF-7 tumors nIFN-beta appeared to be less effective than nIFN-alpha, whereas the opposite was true for BT20 tumors.

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“…Rekombinantes Interferon-a-2A wurde 1982 in die Klinik eingeführt. Von anfänglich hochgesteckten Erwartungen, wie der Behandlung von verschiedenen soliden Karzinomen, verbleiben zur Zeit als wichtigste Indikationen das Kaposi-Sarkom beim AIDS-Syndrom, die Non-Hodgkin-Lymphome, die chronischmyeloische Leukämie und die Haarzellenleukämie (6,9,17,25,29,30). Bei der letzteren kann es zu Therapieresistenz kommen infolge Bildung von neutralisierenden Antikörpern (29).…”

Section: Gewebefaktorenunclassified

Rekombinante Proteinwirkstoffe in der Humanmedizin

2008

Dtsch med Wochenschr

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Effects of interferons in neoplastic diseases of man

Cited by 18 publications

References 77 publications

Characterization of specific functional receptors for HuIFN‐α on a human megakaryocytic cell line (Dami): expression related to differentiation

Characterization of specific functional receptors for HuIFN‐α on a human megakaryocytic cell line (Dami): expression related to differentiation

Antiproliferative effects of natural interferon beta alone and in combination with natural interferon gamma on human breast carcinomas in nude mice

Rekombinante Proteinwirkstoffe in der Humanmedizin

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