Association between serum levels of soluble tumor necrosis factor receptors/CA 125 and disease progression in patients with epithelial ovarian malignancy: a gynecologic oncology group study.

Background: A prospective study was undertaken within the Gynecologic Oncology Group to determine whether serum levels of soluble tumor necrosis factor receptors I (sTNFR-I) and II (sTNFR-II), alone or in combination with CA 125, were associated with clinicopathologic characteristics or outcome in patients with epithelial ovarian malignancies.

Methods: Quantitative immunoassays were performed on valid pretreatment serum specimens obtained from patients with epithelial ovarian malignancies to assess levels of sTNFR-I, sTNFR-II, and CA 125. The authors then analyzed the results of these immunoassays for potential correlations with clinicopathologic characteristics and outcome.

Lymphocyte and monocyte-induced motility of MCF-7 cells by tumor necrosis factor-alpha.

A potentially important tumor-host interaction is increased tumor-cell invasiveness in response to motility factors derived from stromal and lymphoid cells. Conditioned medium of IL-2-stimulated lymphocytes and fractions enriched in either T cells, natural killer (NK) cells, or monocytes induced motility in MCF-7 breast carcinoma cells. ELISA and antibody neutralization studies demonstrated that this effect was due to tumor necrosis factor-alpha (TNF-alpha) secretion by the lymphoid cells or the enriched fractions.

Prostaglandin-E2 regulation of tumor necrosis factor receptor release in human monocytic THP-1 cells.

Recent in vitro studies indicate that tumor necrosis factor (TNF) production in human monocytic THP-1 cells is suppressed by action of arachidonic acid metabolite prostaglandin-E2 (PGE2). PGE2 stimulation of human monocytic cell line THP-1 demonstrates that PGE2 not only regulates TNF activity at production levels, but does so through the release of two soluble TNF receptors (BP-55, BP-75) as well. PGE2 can thus exert a regulatory effect on TNF biologic activity by interfering with its ability to reach cell membrane receptors.

Identification of the proteolytic enzyme which cleaves human p75 TNF receptor in vitro.

The extracellular domains of the human 55 and 75 kD TNF receptors (p55 and p75 TNF-R) are proteolytically cleaved to produce 30 and 40 kD soluble fragments, respectively. In this study, the enzymatic activity involved in the cleavage of human p75 TNF-R, named TNF-R releasing enzyme (TRRE), was identified in the culture supernatant of PMA-stimulated THP-1 cells using an activity assay system established by our group. When THP-1 cells were stimulated with PMA, TRRE was released rapidly into the supernatant, reaching maximal activity within 3 hours.

Involvement of two types of TNF receptor in TNF-alpha induced neutrophil apoptosis.

We previously demonstrated that tumor necrosis factor-alpha (TNF-alpha) induces rapid human neutrophil apoptosis. In this paper, we examined which of the TNF receptors, p55 kDa TNF receptor (55-R) or p75 kDa TNF receptor (75-R), or both are involved in this process using specific rabbit antisera. Antibodies to 55-R (anti55-R) or 75-R (anti75-R) alone did not induce neutrophil apoptosis.