Anti‐tumor effects of interferon in mice injected with interferonsensitive and interferon‐resistant friend leukemia cells. VI. Adjuvant therapy after surgery in the inhibition of liver and spleen metastases

Maury, Chantal; Belardelli, Filippo

doi:10.1002/ijc.2910390623

Cited by 17 publications

(11 citation statements)

References 19 publications

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“…Previous work showed that potent preparations of mouse interferon alp exerted an anti-metastatic effect when injected at the site of tumor implantation (Belardelli et al, 1983) or as adjuvant therapy after excision of established primary S.C. FLC tumors (Gresser et al, 1987). In the latter experiments, interferon therapy was effective even if initiated when tumor metastases were already present in the liver (Gresser er al., 1987).…”

Section: Mice After Intravenous Inoculation Of Friend Erythroleukemiamentioning

confidence: 96%

Interferon treatment markedly inhibits the development of tumor metastases in the liver and spleen and increases survival time of mice after intravenous inoculation of friend erythroleukemia cells

Gresser

Maury

Woodrow

et al. 1988

Intl Journal of Cancer

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To investigate the effect of interferon treatment on the development of tumor metastases, DBA/2 mice were injected i.v. with 2 X 10(6) Friend erythroleukemia cells (FLC) (equivalent to about 5 X 10(5) LD50). FLC multiplied rapidly in the liver and spleen and all untreated or control treated mice died between 7 and 12 days. Daily treatment of mice with potent preparations of mouse interferon alpha/beta was initiated 3 to 72 hr after i.v. inoculation of tumor cells, at times when FLC were already present in the liver and spleen. Interferon treatment resulted in a 100 to 1,000-fold inhibition of the multiplication of FLC in the liver and spleen and a marked increase in mean survival time. Small numbers of tumor cells persisted in the liver and spleen in some interferon-treated mice and could be recovered by bioassay several weeks after tumor inoculation. Most interferon-treated mice died with tumor in the ensuing months. Three of 34 interferon-treated mice were considered cured as they were alive at 386, 325 and 284 days after tumor inoculation. Daily treatment of tumor-inoculated mice with human recombinant interferons alpha D and alpha BDDD, which had antiviral activity on mouse cells in culture, also increased the survival time of mice injected i.v. with FLC. The use of the interferon-resistant 3C18 line of FLC suggests that the marked inhibition of development of established liver and spleen metastases was not due to a direct effect of interferon on the tumor cells, but was host-mediated.

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Section: Mice After Intravenous Inoculation Of Friend Erythroleukemiamentioning

confidence: 96%

Interferon treatment markedly inhibits the development of tumor metastases in the liver and spleen and increases survival time of mice after intravenous inoculation of friend erythroleukemia cells

Gresser

Maury

Woodrow

et al. 1988

Intl Journal of Cancer

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“…Cure of metastatic malignancies can result when micrometastases are eliminated in patients at highest risk for recurrence after surgical removal of a primary tumour. effectiveness as a surgical adjuvant for murine tumours provided the rationale leading to pioneering clinical studies that suggested benefit of impure IFNα when given after surgery for osteosarcoma 217,218 . This surgical adjuvant approach was the basis for evalua tion of IFNα2 in patients at high risk for recurrence of melanoma.…”

Section: Glucocorticoidsmentioning

confidence: 99%

Interferons at age 50: past, current and future impact on biomedicine

Borden

Sen

Uzé

et al. 2007

Nat Rev Drug Discov

1,021

1,058

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The family of interferon (IFN) proteins has now more than reached the potential envisioned by early discovering virologists: IFNs are not only antivirals with a spectrum of clinical effectiveness against both RNA and DNA viruses, but are also the prototypic biological response modifiers for oncology, and show effectiveness in suppressing manifestations of multiple sclerosis. Studies of IFNs have resulted in fundamental insights into cellular signalling mechanisms, gene transcription and innate and acquired immunity. Further elucidation of the multitude of IFN-induced genes, as well as drug development strategies targeting IFN production via the activation of the Toll-like receptors (TLRs), will almost certainly lead to newer and more efficacious therapeutics. Our goal is to offer a molecular and clinical perspective that will enable IFNs or their TLR agonist inducers to reach their full clinical potential.

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“…In the model in which FLC are injected s.c., for example, mice died in the weeks following tumor injection, not of the large S.C. tumors but of overwhelming liver and spleen metastases (62). Eight days after S.C. inoculation of FLC tumor cells had already implanted and multiplied in the liver and spleen (65). Nevertheless, if interferon treatment is initiated at this time (8 days after tumor inoculation), a marked increase in survival time was observed and some of the mice were considered cured (65).…”

Section: -898103mentioning

confidence: 99%

“…Eight days after S.C. inoculation of FLC tumor cells had already implanted and multiplied in the liver and spleen (65). Nevertheless, if interferon treatment is initiated at this time (8 days after tumor inoculation), a marked increase in survival time was observed and some of the mice were considered cured (65). We extended these experiments and injected several million FLC i.v.…”

Section: -898103mentioning

confidence: 99%

Antitumor Effects of Interferon

Gresser

1989

Acta Oncologica

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Both natural and recombinant interferons have shown definite antitumor activity in some patients with some malignancies. The history of the development of interferon as an antitumor agent is reviewed, with special attention to its use in mice bearing 'spontaneously' appearing tumors and in mice injected with tumorigenic viruses or transplantable tumor cells. Interferon can inhibit the growth of primary tumors as well as the development of metastases. These experimental results have provided some indications as to the probable optimal regimens of interferon administration in man. Although the mechanisms of interferon's antitumor activity are unknown, it seems likely that interferon can act directly on the tumor cells as well as on the tumor bearing host. Key words:Interferons, antitumor effects, animal studies, review.It is now generally accepted that interferons can exert some antitumor activity in some patients with some tumors (1). The extent of the antitumor effects of interferon has been variable: some patients have had a complete or partial remission, whereas therapy was apparently ineffective in other patients. We do not know whether this difference in response of patients with a given histologic type of tumor reflects differences in the biology of these tumors or differences in the responses of different individuals to interferon. Several common cancers do not yet appear to be amenable to interferon therapy alone; pulmonary, gastric, colonic, prostatic and breast cancer. We do not know why this is so.How does interferon exert an antitumor effect? Most of our information comes from cell culture experiments or experiments in mice, and these may or may not be relevant to patients bearing autochthonous tumors. I will assume that these experimental results have some relevance and try to present the state of our current understanding of the various possible mechanisms responsible for the antitumor actions of interferon. I shall try first to trace the origin of the observation that interferon inhibits tumor growth, and then touch on the evolution of our understanding of interferon's biologic role. Lastly, I shall try to give some answers-all incomplete-to the question posed: How does interferon inhibit tumor growth?In 1965 we began a series of experiments to determine whether interferon could inhibit viral-induced leukemias in mice (2-5). It was thought at the time that the increase in the number of leukemic cells in mice was related to the continued multiplication of the leukemia-inducing viruses (Friend and Rauscher viruses). Our reasoning was simple.These leukemias resembled subacute or chronic viral infections. Interferon was an antiviral substance. If we injected enough interferon repeatedly throughout the course of the disease we might diminish viral multiplication and thus diminish the evolution of the leukemic process. There were, however, two seemingly good reasons not to do the experiment. First, it was believed that interferon would only act prophylactically, i.e. before the virus was injected...

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Anti‐tumor effects of interferon in mice injected with interferonsensitive and interferon‐resistant friend leukemia cells. VI. Adjuvant therapy after surgery in the inhibition of liver and spleen metastases

Cited by 17 publications

References 19 publications

Interferon treatment markedly inhibits the development of tumor metastases in the liver and spleen and increases survival time of mice after intravenous inoculation of friend erythroleukemia cells

Interferon treatment markedly inhibits the development of tumor metastases in the liver and spleen and increases survival time of mice after intravenous inoculation of friend erythroleukemia cells

Interferons at age 50: past, current and future impact on biomedicine

Antitumor Effects of Interferon

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