The effect of interferon on experimental metastases in immunocompetent and immunodeficient mice

Ramani, P.; Hart, Ian R.; Balkwill, Frances R.

doi:10.1002/ijc.2910370415

Cited by 27 publications

(22 citation statements)

References 16 publications

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“…The inhibition of experimental metastases has been suggested to be due to stimulation of NK cells (Hanna & Burton, 1981;Brunda et al, 1984;Nishimura et al, 1985). We have shown (Ramani et al, 1986) that rHuIFN-oa A/D (an IFN that has activity on murine cells) given after tumour challenge inhibited the experimental metastases of COLON 26 in BALB/c mice and Beige nude (T and NK cell deficient) mice. In addition, in the COLON 26 model, an increased clearance of radiolabelled tumour cells from the lungs was seen in IFN treated mice.…”

Section: Effect Of the Clearance Of Radiolabelled Cellsmentioning

confidence: 50%

“…Cells DX3-azac LT5.1, derived from DX3, a human melanoma cell line treated with azacytidine, was obtained from J. Ormerod, ICRF (Ormerod et al, 1986 (1988), 58, 350-354 904-511 (National Institute of Allergy and Infectious Disease, NIH, Bethesda, MD) as described by Ramani et al (1986).…”

Section: Micementioning

confidence: 99%

“…After 5 to 6 weeks, the mice were killed, the lungs were removed, and macroscopic lung metastases enumerated (Ramani et al, 1986). …”

Section: Micementioning

confidence: 99%

“…As shown, the doses of HuIFNs used in this study had no effect on the nude mouse lung NK cell activity (% lung cytotoxicity at effector target ratio of 100:1, mean+s.d., control=28+1, HuIFN-a (Nl)=27+0.8, rHuIFN-y=28+0.9). Stimulation of NK cell activity was seen when mice were treated with rHuIFNaA/D a hybrid IFN with equal activity on human and mouse cells (Rehberg et al, 1982). Effect of the lung macrophage activity of nude mice The effect of HuIFNs on the lung macrophage cytotoxicity was also measured after 4 days.…”

Section: Effect Of the Clearance Of Radiolabelled Cellsmentioning

confidence: 99%

“…inoculation inhibited the pulmonary metastases of murine osteogenic sarcoma. Recently, Ramani et al (1986) demonstrated the pure recombinant hybrid human IFN alpha, rHuIFN-x A/D, an IFN that has cross reactivity on mouse cells, significantly inhibited the establishment and development of pulmonary metastases of a mouse colon carcinoma.…”

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Human interferons inhibit experimental metastases of a human melanoma cell line in nude mice

Ramani¹,

Balkwill²

1988

Br J Cancer

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Summary Therapy with human lymphoblastoid interferon HuIFN-a(NI), or recombinant human interferon gamma, rHuIFN-y, inhibited experimental pulmonary metastases of the human melanoma cell line, DX3-azac, in BALB/c nude mice and significantly prolonged survival. The human IFNs had no effect on nude mouse lung and spleen NK cell activity, lung macrophage activity, haemoglobin or white cell counts. HuIFN-a(NI) had no effect on the levels of the IFN induced enzyme 2-5A synthetase in nude mouse lungs although the rHuIFN-y caused some elevation. In addition, clearance of radiolabelled Taylor-Papadimitriou, 1980), they can alter the state of tumour cell differentiation (Rossi, 1985), modulate surface antigen expression (Rosa et al., 1986), inhibit oncogene/expression and levels of oncogene product (Jonak & Knight, 1986), and induce reversion of the transformed phenotype to a normal phenotype (Brouty-Boye & Gresser, 1981). All these direct actions may play a role in limiting tumour spread.Interferons can also act on the tumour via their action on host defence cells (Gresser & Bourali-Maury, 1972;Gresser & Tovey, 1978;Gresser, 1985 Human tumour xenografts growing in nude mice serve as good models to dissociate the direct effects on human tumour from indirect effects on the murine host because of species specificity of the IFNs. Balkwill et al. (1982, 1985) have shown that HuIFNs directly inhibit the growth of subcutaneous human bowel, breast, lung and ovarian cancers in nude mice.As part of our studies into the antimetastatic actions of IFNs we decided to extend the nude mouse human tumour xenograft studies to an experimental metastases model. Transplanted human tumours do not metastasize easily in the nude mouse in spite of their aggressiveness in man. In our studies, we therefore used a variant of a human melanoma cell line, DX3, which had been selected from the parent line by treatment with the nucleoside analogue 5 azacytidine (5-azac) and serial passage in BALB/c nude mice. The selected variant DX3-azac LT5.1 showed a 40-fold increase in metastatic capacity (Ormerod et al., 1986

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Section: Effect Of the Clearance Of Radiolabelled Cellsmentioning

confidence: 50%

Section: Micementioning

confidence: 99%

“…After 5 to 6 weeks, the mice were killed, the lungs were removed, and macroscopic lung metastases enumerated (Ramani et al, 1986). …”

Section: Micementioning

confidence: 99%

Section: Effect Of the Clearance Of Radiolabelled Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

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Human interferons inhibit experimental metastases of a human melanoma cell line in nude mice

Ramani¹,

Balkwill²

1988

Br J Cancer

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Tumor cell kinetics using two labels and flow cytometry

et al. 1994

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A flow cytometry based, single sampling method employing sequential bromodeoxyuridine (BrdUrd) and iododeoxyuridine (IdUrd) labeling with an intervening interval is examined. BrdUrd-specific and nonspecific monoclonal antibodies and flow cytometry are used to estimate the duration of DNA synthesis and the potential doubling time in tumor cell populations using a single sampling or biopsy. A correction for labeled, divided cells allows postlabel incubation intervals to exceed the length of the G2/M phase of the cell cycle. The method yields reliable results when tested in experimental tumor systems in vitro and in situ, as well as in nine human tumors labeled in situ. It uses a somewhat simpler analysis than the alternative relative movement method, requiring only labeling indices, rather than both a labeling index and relative movement, but does require the administration of two, rather than one, label. It provides an independent verification of and a useful single sampling alternative to the relative movement method for the estimation of the length of S phase and, from this, the potential doubling time in experimental or clinical human tumors. 0 1994 Wiley-Liss, Inc.Key terms: Cell kinetics, bromodeoxyuridine, iododeoxyuridine, human tumors Analyses of both experimental and clinical data indicate decreased local tumor control with prolongation of overall radiation therapy treatment times (4,13, 18,31,39). Such an effect is likely to be due, at least in part, to tumor clonogenic proliferation during treatment. Thus, a shortening of overall treatment times might increase the chance of local control in properly selected patients. Recent studies (4-6,37,38) indicate a striking similarity between these effective tumor doubling times during treatment (14,18,19,21,39) and a quantity called the tumor potential doubling time, Tpot, measured prior to treatment. Tpot is the minimum time for tumor volume doubling, taking growth fraction into account but ignoring cell loss. These data indicate that many human tumors-about one-half of all head and neck tumors, for example (371-have the potential to double their cell number in as short a time as five or fewer days. Such considerations have stimulated much interest in the in situ measurement of rates of tumor cell proliferation.The delayed biopsy, relative movement technique (7) permits the estimation of Tpot from a single biopsy without the use of radioisotopes required by previous cell cycle analysis methods (31). It employs bromodeoxyuridine (BrdUrd) or iododeoxyuridine (IdUrd) pulse labeling of the DNA of established tumor cell lines in vitro or of tumors in situ, followed, after a delay of several hours, by a single biopsy. Halogenated pyrimidine-specific monoclonal antibodies and propidium iodide staining of DNA are then employed with flow cytometry to determine the labeling index (LI) and a parameter called the relative movement that monitors the progression of labeled cells through the cell cycle. The length of S phase (T,) and the potential doubling time can then be ...

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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

Maury

Belardelli

1987

Intl Journal of Cancer

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Adult DBA/2 mice were injected s.c. with the highly malignant, interferon-resistant 3C18 line of Friend erythroleukemia cells (FLC). Eight or 9 days after established s.c. tumors had developed, the primary tumor was excised and mice were treated i.p. with either mouse interferon alpha/beta or a control preparation. At the time of surgery, mice already had tumor cells in the liver. All control-treated mice died in the ensuing 2 weeks with extensive tumor metastases in the liver and spleen. Interferon treatment resulted in an inhibition of the development of liver and spleen metastases and a markedly increased survival time. We conclude that interferon alpha/beta is effective as adjuvant therapy after surgery for metastatic disease in mice.

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The effect of interferon on experimental metastases in immunocompetent and immunodeficient mice

Cited by 27 publications

References 16 publications

Human interferons inhibit experimental metastases of a human melanoma cell line in nude mice

Human interferons inhibit experimental metastases of a human melanoma cell line in nude mice

Tumor cell kinetics using two labels and flow cytometry

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

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