In vitro antiproliferative efficacy of Interferon-alpha,-gamma and Tumor Necrosis Factor on two human renal tumor xenografts

Beniers, A. J. M. C.; Peelen, W. P.; Hendriks, Ben Th.; Schalken, J. A.; Romijn, Johannes C.; Debruyne, F.M.J.

doi:10.1007/bf00263641

Cited by 9 publications

(4 citation statements)

References 42 publications

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“…Significant improvements in the efficacy of experimental cancer therapies have been made by utilization of biological response modifiers [1][2][3]. TNF is a wellcharacterized secretory product of macrophages, which has shown direct antitumor activity in vivo as well as in vitro [11,12].…”

mentioning

confidence: 99%

Differential sensitivity of hormone-responsive and unresponsive human prostate cancer cells (LNCaP) to tumor necrosis factor

1992

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Two sublines, the hormone-sensitive LNCaP-FGC and the insensitive LNCaP-r (resistant) carcinoma cell lines, originating from the parental human prostatic carcinoma cell line LNCaP were tested for sensitivity to human tumor necrosis factor-alpha (TNF) using the MTT assay. Irrespective of the culture conditions, i.e., whether FGC cell growth was hormone stimulated or hormone deprived, a clear dose-related response was observed between the concentration of TNF (range: 5-5000 U/ml) in the culture medium and the percentage of growth inhibition. In medium containing androgen-depleted serum, in which FGC cells showed reduced proliferative activity, the percentage of inhibition by a concentration of 100 U/ml TNF was substantially higher than that found in hormone-stimulated cells (90% and 60%, respectively). In contrast to the FGC cells, the hormone-insensitive LNCaP-r cells were almost completely resistant to the action of TNF. Growth of the FGC cells was almost completely inhibited, whereas growth of the LNCaP-r cells was retarded with only 20% at dosages up to 5000 U/ml. This substantial difference in TNF responsiveness could not be ascribed to differences in TNF-binding capacity, as both the FGC and LNCaP-r cells were found to contain identical numbers of TNF-receptors (approximately 1000 sites/cell). A possible association between hormone responsiveness and TNF sensitivity is suggested for these LNCaP sublines.

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confidence: 99%

Differential sensitivity of hormone-responsive and unresponsive human prostate cancer cells (LNCaP) to tumor necrosis factor

1992

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“…Few studies have been performed with rIFN 7 [8,18,20,22] and they resulted generally in a low (<10%) response rate. On the basis of in vitro observations indicating a synergism between rIFN 7 and rlFNcz [2,3,12], combined studies have been initiated resulting in response rates from 0-16% [7,21].…”

Section: Discussionmentioning

confidence: 99%

“…The most predominant presentation of neuropathy was tickling at the fingertips and in 3 patients subjective signs of muscle weakness. Side-effects related to the central nervous system included drowsiness (in 8 patients), confusion (1), disorientation (2), and mood disturbances (2).…”

Section: Toxicitymentioning

confidence: 99%

Phase I/II study of recombinant interferon α and γ in advanced progressive renal-cell carcinoma

Mulder¹,

Debruyne²,

Franssen³

et al. 1990

Cancer Immunol Immunother

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In vitro studies have documented the synergistic antiviral and antiproliferative activity of recombinant interferon alpha (rIFN alpha) and rIFN gamma. Furthermore, rIFN gamma is a strong immunomodulator with optimal effects at a relative low dose (0.1 mg/m2). On the basis of these observations, we began a phase I/II study with the combination of rIFN gamma at 100 micrograms/m2 (2 x 10(6) IU/m2) and rIFN alpha 2c 6 micrograms/m2 (2 x 10(6) IU/m2), injected twice a week subcutaneously. In cases of stable or progressive disease we increased the dose of rIFN alpha 2c every 2 weeks by 6 micrograms/m2 until the maximum tolerated dose was reached. A total of 32 patients with proven progressive renal-cell carcinoma were included. Of the 31 eligible patients, 21 were male and 10 female, their average age was 57.2 years (range 35-72), 28 had had nephrectomy, their median Karnofsky performance status was 90% (70%-100%), and their tumors were localized predominantly to visceral tissue. In 2, response was complete and in 6 it was partial, for a response rate of 25%. The disease had stabilized in 5 patients and progressed in 16. The median duration of partial response was 14 months (8-16 months); of 2 cases of complete response, 1 persists (23+ months), and the other suffered a relapse after 22 months. The median time to response was 24 weeks (18-24 weeks). The maximum tolerated dose of rIFN alpha was 30 micrograms/m2 (range of 6-36 micrograms/m2). Side-effects included those known to be associated with interferon treatment. One patient developed septicemia during a period with grade 4 leukopenia. Our study permits no conclusion regarding the additional value of rIFN gamma.

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“…Whereas some cell lines exhibited significant killing with TNF [38], other cell lines were less sensitive to the toxic effects of the cytokine [20,27]. TNF has also been shown to exert a dose-dependent inhibition of softagar colony formation of human renal cell lines [6,7,38].…”

Section: Tumor Necrosis Factor and Renal-cell Carcinomamentioning

confidence: 99%

Isolated perfusion of the kidney with tumor necrosis factor for localized renal-cell carcinoma

et al. 1996

World J Urol

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In vitro antiproliferative efficacy of Interferon-alpha,-gamma and Tumor Necrosis Factor on two human renal tumor xenografts

Cited by 9 publications

References 42 publications

Differential sensitivity of hormone-responsive and unresponsive human prostate cancer cells (LNCaP) to tumor necrosis factor

Differential sensitivity of hormone-responsive and unresponsive human prostate cancer cells (LNCaP) to tumor necrosis factor

Phase I/II study of recombinant interferon α and γ in advanced progressive renal-cell carcinoma

Isolated perfusion of the kidney with tumor necrosis factor for localized renal-cell carcinoma

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