In Vivo Antiproliferative Effects of Gamma-Interferon and Tumor Necrosis Factor Alpha in a Rat Renal Cell Carcinoma Model System

Moorselaar, R. Jeroen A. van; Beniers, Anton J.M.C.; Hendriks, Ben Th.; Meide, P. H. Van Der; Schellekens, Huub; Debruyne, F.M.J.; Schalken, Jack A.

doi:10.1016/s0022-5347(17)40247-3

Cited by 13 publications

(3 citation statements)

References 18 publications

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“…Mean results from triplicate experiments plotted. 9 day experimental period, their growth remained depressed. In contrast, IFN-7 reduced the proliferation of EFO-27 cells only during the first 3 days of exposure, and thereafter their rate of growth recovered completely even during continuous exposure (Fig.…”

Section: Resultsmentioning

confidence: 94%

“…"'2' IFN-7 led to cytostatic inhibition of the growth of most human and murine cells, '3-5' which in many cultures was completely reversible.<6) Cytotoxic effects have been less common/7' but were noted in cultures originating from human renal'8' and ovarian'" carcinomas: their occurrence seems to depend on such factors as the tumor cell type, exposure to IFN-7 of only a small number of cells in vitro, or a low tumor burden in vivo. (9) Few studies have looked at the recovery of cells from the antiproliferative effects of IFN-7 after short-term exposure, followed by cultivation in the absence of the lymphokine; MCF-7 breast carcinoma cells recovered completely, but there was no recovery of ME-180 cervix carcinoma cells. '8' The effect of long-term treatment has been studied in some human and murine tumor cell cultures, and in the continued presence of IFN-7, resistance to its antiproliferative effects was induced in human breast'10' and in colon carcinoma cells."…”

Section: Introductionmentioning

confidence: 99%

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Antiproliferative and Recovery Effects During Treatment of Breast and Ovarian Carcinoma Cell Cultures with Interferon-γ

Klouche¹,

Kirchner²,

Hölzel³

1995

Journal of Interferon & Cytokine Research

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We studied the antiproliferative effects of human interferon-gamma (IFN-gamma) on cell lines derived from human carcinomas (three breast, two ovarian, and one renal) and recovery from these effects when IFN-gamma was removed after 6 or 72 h. IFN-gamma led to a dose-dependent and time-dependent cytostatic inhibition of all six tumor cell lines; the renal carcinoma cells were by far the most sensitive, and with these, cytotoxic effects were also seen. The 50% inhibitory dose (ID50) for each cell line was different and remarkably constant over many months. When cells were exposed to IFN-gamma for only 9 or 72 h, those from three lines recovered completely from the growth inhibitory effects, but from three only partially. When cultured for several weeks in the presence of 1600 U/ml of IFN-gamma, two lines developed increased resistance to IFN-gamma, one became much less sensitive, and two showed no changes in sensitivity. We saw no correlations between these changes during continuous exposure to IFN-gamma and the antiproliferative ID50 for each cell or whether the cells recovered completely from the inhibitory effects of IFN-gamma after short-term exposure. Nevertheless, cells with a population doubling time of less than 48 h had low to moderate sensitivity to IFN-gamma and seemed to recover more completely than those doubling in more than 61 h. Our results indicate great individual variation in the in vitro sensitivity of carcinoma cells to the antiproliferative effects of IFN-gamma.

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Section: Resultsmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Antiproliferative and Recovery Effects During Treatment of Breast and Ovarian Carcinoma Cell Cultures with Interferon-γ

Klouche¹,

Kirchner²,

Hölzel³

1995

Journal of Interferon & Cytokine Research

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“…28 The antitumor effect of TNFa has now been established in various animal model systems. 29,30 Bacillus CalmetteGuerin (BCG), an intravesical agent, appears to decrease the recurrence rate of superficial bladder cancer. BCG has been shown to induce TNFa, which may be a mechanism of action of BCG antitumor activity in superficial bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

Cloning and analysis of human UroplakinII promoter and its application for gene therapy in bladder cancer

Zhu

Zhang²,

Zeng

et al. 2004

Cancer Gene Ther

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The differential expression of the desired gene product in the target tissue is central for gene therapy. One approach is to use a tissue-specific promoter to drive therapeutic gene expression. UroplakinII (UPII) is a urothelium-specific membrane protein. To investigate the feasibility of targeting gene therapy for bladder cancer, a DNA fragment of 2542-bp upstream of the UPII gene was amplified by PCR and linked to a promoterless firefly luciferase reporter gene. The transient transfection showed that the DNA fragment resulted in preferential expression in bladder carcinoma cells, with negligible expression in nonurothelium cells. Furthermore, the DNA segment located between À2545 and À1608 decided the tissue-specificity of the UPII promoter, the segment located between À328 and À4 being the core promoter of UPII. We generated two recombinant adenoviruses under the control of the UPII promoter: Ad-hUPII-GFP, carrying green fluorescence protein (GFP), and Ad-hUPII-TNF, carrying the tumor necrosis factor alpha (TNFa). ELISA revealed that the secretion of TNFa by Ad-hUPII-TNF-infected bladder cancer cells was significantly higher than Ad-hUPII-TNF-infected nonurothelium cells. The conditioned medium from Ad-hUPII-TNF-infected bladder cancer cells apparently inhibited the proliferation of L929 cells, a TNFa-sensitive cell line, comparing to Ad-hUPII-TNF-infected nonurothelium cells. Intravesical inoculation with Ad-hUPII-TNF inhibited tumor growth in the orthotopic human bladder cancer model. The sustained high level of TNFa in urine was identified with ELISA. Taken together, these data suggest that most of the cis elements that confer the bladder-specificity and differentiationdependent expression of the human UPII gene reside in the 2542-bp sequence, and TNFa driven by the human UPII (hUPII) promoter is effective in the specific inhibition of bladder cancer growth both in vivo and in vitro. These results may yield a new therapeutic approach for bladder cancer and provide information on the molecular regulation of urothelial growth, differentiation, and disease.

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Differential antiproliferative activities of alpha‐ and gamma‐interferon and tumor necrosis factor alone or in combinations against two prostate cancer xenografts transplanted in nude mice

et al. 1991

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We have investigated the antiproliferative effects of recombinant human alpha- and gamma-Interferon (IFN) and recombinant human Tumor Necrosis Factor alpha (TNF) against the hormone-independently growing PC3 and DU145 prostatic tumor lines. Subcutaneous, peritumoral administration of the drugs was started 24 hours after subcutaneous implantation of 1-2 mm3 tumor pieces. IFN was given three times per week and TNF five times per week. IFN-alpha (dose-range 0.5-5 ng/gram bodyweight) had significant growth-inhibiting effects against the PC3 tumor, but showed no significant antitumor effects against the DU145 tumor. IFN-gamma monotherapy (dose-range 8-80 ng/gram bodyweight) was less effective than IFN-alpha. 500 ng/gram TNF produced growth inhibition of both tumors, whereas the lower dose (50 ng/g) was only effective against the PC3 tumor. IFN-alpha and -gamma combination treatment had significant antiproliferative effects against the PC3 tumor, but not against the DU145 tumor. Combinations of IFN-alpha and TNF were very effective against both xenografts; some combinations resulted in complete growth inhibition. IFN-gamma and TNF combinations also showed significant antitumor effects against both tumor lines. We therefore conclude that cytokine combination treatment may provide a new approach in the treatment of hormone-escaped prostatic tumors.

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In Vivo Antiproliferative Effects of Gamma-Interferon and Tumor Necrosis Factor Alpha in a Rat Renal Cell Carcinoma Model System

Cited by 13 publications

References 18 publications

Antiproliferative and Recovery Effects During Treatment of Breast and Ovarian Carcinoma Cell Cultures with Interferon-γ

Antiproliferative and Recovery Effects During Treatment of Breast and Ovarian Carcinoma Cell Cultures with Interferon-γ

Cloning and analysis of human UroplakinII promoter and its application for gene therapy in bladder cancer

Differential antiproliferative activities of alpha‐ and gamma‐interferon and tumor necrosis factor alone or in combinations against two prostate cancer xenografts transplanted in nude mice

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