Effect of intraperitoneal recombinant human tumour necrosis factor alpha on malignant ascites

Räth, U.; Kaufmann, M.; Schmid, H.; Hofmann, Jutta; Wiedenmann, Bertram; Kist, Andreas M.; Kempeni, Joachim; Schlick, E.; Bastert, G.; Kommerell, B; Männel, Daniela N.

doi:10.1016/0277-5379(91)90467-r

Cited by 71 publications

(21 citation statements)

References 12 publications

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“…22 High concentrations of soluble TNF receptors have been found in ascites 22 and may explain why, in recent studies, malignant ascites responded to bolus intraperitoneal injections of TNF. 23 Administration of interferon-alpha 2b also has been shown to reduce ascites. 24 A more recent investigation has examined the effects of intraperitoneal administration of other cytokines on ascites formation in a murine model of ovarian cancer.…”

Section: Figmentioning

confidence: 98%

Markedly Elevated Levels of Vascular Endothelial Growth Factor in Malignant Ascites

et al. 1999

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Section: Figmentioning

confidence: 98%

Markedly Elevated Levels of Vascular Endothelial Growth Factor in Malignant Ascites

et al. 1999

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“…• A phase I trial using intraperitoneal recombinant TNF-a in 29 patients with refractory malignant ascites from various tumor types documented complete or partial resolution in 76% of patients. Side effects were mild, and included fever, chills, nausea, vomiting, and fatigue [51].…”

Section: Treatment Of Malignant Ascites Chung and Kozuchmentioning

confidence: 99%

Treatment of Malignant Ascites

Chung

Kozuch

2008

Curr. Treat. Options in Oncol.

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The management of malignant ascites is a significant challenge in gastrointestinal medical oncology. Current treatment strategies include diuretic therapy, paracentesis, peritoneal drains, and venous shunts. However, there are no established evidence-based guidelines, and there is a lack of randomized controlled trials identifying optimal therapy. Newer therapies are emerging and will need further study. By summarizing published studies, this review is intended to add some clarity to currently available strategies for the management of malignant ascites associated with hepatobiliary cancers. Notably, however, much of the available data for the management of malignant ascites comes from the gynecologic oncology experience, specifically from studies in ovarian cancer. Therefore, successful approaches used in this malignancy may be lead candidates for development in hepatobiliary cancer-associated ascites and are reviewed in this paper.

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“…TNF-· has been described to act through several different mechanisms [7, 8, 17-19, 40, 43, 46]. One mechanism is through recruitment of T cells [17,44]. In this tumor model, we theorize that TNF-· stimulates T cells, macrophages and natural killer cells to secrete other cytokines (IL1, IL8, IL6 and IL12) and recruit CD4+ and CD8+ T cells.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Established Tumor Is Associated with ICAM-1 Upregulation and Reversed by CD8 Depletion in a Tumor Necrosis Factor-Alpha Gene Transfected Mouse Mammary Tumor

Matory

Dorfman²,

Wu³

et al. 1999

Pathobiology

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Introduction: We have performed TNF-α gene transfection in a mouse mammary cancer line and found significant antitumor effects. We hypothesize that the antitumor effects observed in this model are mediated by ICAM-1 and by the recruitment of CD4+ and CD8+ T cells. In vivo (Balb/c mice) tumor growth inhibition, treatment of established tumor and the effects of ICAM-1 and CD4+ and CD8+ T cells were evaluated. Methods and Results: Gene transfection with highly efficient vectors resulted in secretion of large amounts of TNF-α (ELISA). In vivo antitumor effects were tested. The number of cells required to generate palpable tumor 7–10 days after subcutaneous injection was determined (1 × 10⁶). The same number of transfected cells were injected subcutaneously and compared to nontransfected controls. Tumors were measured blindly and size was analyzed on day 30 by the Wilcoxon rank sum test. Mean tumor size after injection of transfected cells is compared to that of controls. Control tumors reached the maximum allowable size by day 30 (4 cm²). On day 30 EMT6-TNF-α tumors were 0.48 cm² (p < 0.05). The effect of repeat injection (challenge was also tested. Animals were injected with transfected cells or wild-type control on day –6 and challenged with the same number of wild-type tumor cells on day 0. Significant immune protection against subsequent challenge was seen after first time injection with EMT6-TNF-α but not after first time EMT6 wild-type injection (1.62 vs. 4 cm²). Treatment of 6-day-old tumor was also evaluated. On day 30, mean tumor size in animals treated with EMT6-TNF-α was 0.9 cm² compared to 4 cm² for controls. In all experiments, CD8+ T cell depletion and CD4+ T cell depletion caused a reversal of TNF-α-induced inhibitory effects. In addition, in vivo antibody blocking of ICAM-1 in tumor growth experiments reversed antitumor effects (control 4 cm², TNF-α 0.2 cm² and ICAM-1 blocking 3.14 cm²). Using flow cytometry, MHC class I and II and ICAM-1 adhesion molecule expression of transfected tumor was tested. ICAM-I expression was significantly upregulated. MHC class II antigen expression was also increased. TNF-α-transfected human breast cancer was also evaluated. Three cell lines and fresh tumor were transfected to express TNF-α. In vitro analysis revealed ICAM-1 upregulation following transfection. Histologic analysis and immunohistochemical staining revealed TNF-α and ICAM-1 in transfected tumors and not in wild-type tumors. Conclusion: Highly significant in vivo tumor growth inhibition and immune protection after injection with TNF-α-transfected tumors appears to be mediated predominantly by CD8+ T cells and ICAM-1 upregulation. These findings suggest that TNF-α increases recruitment and adhesion of effector T cells.

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Effect of intraperitoneal recombinant human tumour necrosis factor alpha on malignant ascites

Cited by 71 publications

References 12 publications

Markedly Elevated Levels of Vascular Endothelial Growth Factor in Malignant Ascites

Markedly Elevated Levels of Vascular Endothelial Growth Factor in Malignant Ascites

Treatment of Malignant Ascites

Treatment of Established Tumor Is Associated with ICAM-1 Upregulation and Reversed by CD8 Depletion in a Tumor Necrosis Factor-Alpha Gene Transfected Mouse Mammary Tumor

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