Discrepant effects of interferon on murine syngeneic ascites tumors and their solid metastastzing counterparts

Ryd, Walter; Hagmar, Björn; Lundgren, Erik; Strannegård, Örjan

doi:10.1002/ijc.2910230319

Cited by 12 publications

(6 citation statements)

References 25 publications

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“…It has been reported previously that the site of tumor growth influenced the anti-tumor efficacy of crude preparations of IFN-a/a (Marquet et al, 1984;Ryd et al, 1979). Our data with a pure recombinant IFN-a have confirmed this result and extended the observation to another model.…”

Section: Discussionsupporting

confidence: 94%

The anti‐tumor effect of recombinant interferon alpha or gamma is influenced by tumor location

Brunda

Sulich

Bellantoni

1987

Intl Journal of Cancer

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The in vivo anti-tumor effects of a recombinant human hybrid interferon alpha, rHuIFN-alpha A/D, and recombinant murine interferon gamma (rMuIFN-gamma) were evaluated against experimental hepatic metastases and s.c. tumor growth of the murine reticulum cell sarcoma M5076. The 2 interferons were equally active in preventing experimental hepatic metastases. However, the interferons differed in their relative ability to influence the growth of the same tumor when treatment was initiated following injection of tumor cells. Greater efficacy was obtained in the treatment of metastatic foci in the liver with rHuIFN-alpha A/D, while rMuIFN-gamma was more active in the therapy of an s.c. growing M5076 tumor. These results demonstrate that the same tumor growing at different sites can have different relative sensitivities to IFN-alpha and IFN-gamma.

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Section: Discussionsupporting

confidence: 94%

The anti‐tumor effect of recombinant interferon alpha or gamma is influenced by tumor location

Brunda

Sulich

Bellantoni

1987

Intl Journal of Cancer

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“…Numerous reports in the literature on a dual outcome of immunotherapy have been related to: (1) timing [23], (2) dose [8], (3) route of administration [14], (4) tumor site [17], and (5) manipulation of the tumor [2]. Host factors rather than direct effects of the agents are considered to determine the dual outcome.…”

Section: Discussionmentioning

confidence: 99%

Effects of the interferon-inducer ABPP on colon cancer in rats; importance of tumor load and tumor site

Eggermont

Marquet

Bruin

et al. 1986

Cancer Immunol Immunother

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ABPP (2-amino-5-bromo-6-phenyl-4-pyrimidinone) is a pyrimidinone with known interferon-inducing, natural killer (NK) cell activity enhancing, antiviral and antitumor properties in several animal species. Its effect on CC531, a dimethylhydrazine-induced, transplantable, weakly immunogenic adenocarcinoma of the colon in WAG rats, was studied. ABPP was found to have no direct cytotoxic effect on CC531 cells in vitro. When small cubes of tumor of equal weight were implanted under the renal capsule, administration of 250 mg/kg of ABPP i.p. on day 0 and +1 led repeatedly to significant (p less than 0.02 up to p less than 0.001) inhibition of tumor growth, when measured on day +7. Lower doses or a single dose of ABPP did not achieve this effect. Late administration (on day +6 and +7) of 250 mg/kg of ABPP in this model was found to have no effect on tumor growth when measured on day +13. When 5 X 10(5) tumor cells were injected in the portal vein, administration of 250 mg/kg of ABPP i.p. on day 0 and +1 reduced significantly (p = 0.002) the number of liver metastases, when counted on day +30. Survival in this group was significantly prolonged (p less than 0.01). However when ABPP was given on day +6 and +7, significantly more (p less than 0.02) metastases in the liver were counted on day +30. The results show a significant antitumor effect of ABPP against tumor CC531 in the subrenal capsule assay (SRCA) model as well as in the liver metastasis model when administered at the time of tumor inoculation. Late administration of ABPP did not inhibit tumor growth in the SRCA and significantly enhanced the development of liver metastases. The role of timing, tumor site, and the mechanisms by which this dual outcome of immunotherapy with ABPP is mediated are discussed. The results of these experiments may have important implications for the design of clinical studies with ABPP.

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“…would also have observed an anti-tumor effect had we increased the amount of interferon injected s.c.) Although exceptions to this generalization have been noted in our work and in that of others (Ryd et al, 1979), the intra-or peritumoral administration of interferon might be expected to prove worthwhile in patients (see Strander, 1985).…”

Section: Discussionmentioning

confidence: 55%

Anti‐tumor effects of interferon in mice injected with interferon‐sensitive and interferon‐resistant friend leukemia cells. IV. Definition of optimal treatment regimens

Belardelli

Maury

Tovey

et al. 1986

Intl Journal of Cancer

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Mouse interferon alpha/beta exerted a similar anti-tumor effect in DBA/2 mice injected i.p. with Friend erythroleukemia cells (FLC) either sensitive or resistant to interferon as determined by both in vitro and in vivo assays. Using this tumor system we attempted to define optimal treatment regimens for interferon administration. Interferon was most effective when injected at the site of tumor inoculation rather than at a distant site. Two factors seemed of especial importance: the amount of interferon injected and the frequency of interferon administration. Thus, for daily administration of interferon, the antitumor effect was directly related to the amount of interferon injected. For a given total dose of interferon, repeated administration of small doses of interferon was more effective than administration of a larger dose at more widely spaced intervals. The anti-tumor efficacy of interferon was independent of the number of FLC inoculated when 10(2) to 10(5) FLC were injected, but interferon treatment was less effective when 10(6) or 10(7) FLC were injected. The relevance of these results to the use of interferon in patients with cancer is discussed.

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Discrepant effects of interferon on murine syngeneic ascites tumors and their solid metastastzing counterparts

Cited by 12 publications

References 25 publications

The anti‐tumor effect of recombinant interferon alpha or gamma is influenced by tumor location

The anti‐tumor effect of recombinant interferon alpha or gamma is influenced by tumor location

Effects of the interferon-inducer ABPP on colon cancer in rats; importance of tumor load and tumor site

Anti‐tumor effects of interferon in mice injected with interferon‐sensitive and interferon‐resistant friend leukemia cells. IV. Definition of optimal treatment regimens

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