Evaluation of the circulating fraction of the HER-2/neu oncogene in patients with cervical cancer.

OBJECTIVE: To evaluate circulating HER-2/neu in cervical cancer patients prior to and following treatment. METHODS: Controls, and patients with either cervical dysplasia or cancer taken from an active gynecologic oncology service were evaluated for the expression of HER-2/neu in serum by ELISA before and following surgery, radiation, chemotherapy or combinations thereof. The resulant data was then evaluated for significance by either ANOVA or non-parametric testing. RESULTS: Mean differences were noted for patients with cervical cancer compared to controls. Patients with a good response to the chemotherapy indicated an increase in the serum oncogene, while those not responding either had no marked change or decreased the level of serum HER-2/neu. CONCLUSIONS: As serum HER-2/neu is a membrane bound portion of the intact molecule, these results suggest that due to the induction of cell death and breakdown, the liberation of this fraction (increased levels in the serum), is a viable indicator of response to treatment in some patients. A more detailed examination of this possibility along with expanded correlation with tissue expression is required.

Cervical cancer cells induce apoptosis of cytotoxic T lymphocytes.

The goal of immunotherapy is to eliminate tumors by generating tumor-specific cytotoxic T lymphocytes (CTLs) in patients or by adoptively transferring ex vivo-activated CTLs into patients. Clinical trials have shown that tumor-specific CTLs often disappear before tumors are completely eliminated. In this study, the authors show that CTLs specific for cervical tumor cells undergo apoptosis after they are co-cultured with cervical tumor cells. The established cervical tumor cell lines and cervical cancer tissues express CD95 (Fas/Apo-1) ligand. The tumor cell-induced T-cell apoptosis can be blocked by an inhibitory anti-CD95 (APO-1/Fas) antibody, indicating that tumor cells induce apoptosis of CTLs through CD95-CD95 ligand interaction. Addition of interleukin-2 (IL-2) and IL-7 into the culture rescues the CTL from tumor cell-induced apoptosis. The rescued T cells retain their full antitumor cytotoxicity. These data suggest that human cervical tumor cells might actively down-regulate a cellular immune response by inducing apoptosis of specific T cells during immunotherapy. Local use of IL-2 and IL-7 as adjuvants may promote survival of the CTL and, thus, enhance the efficacy of immunotherapy.

Transforming growth factor-alpha levels in the serum and ascites of patients with advanced epithelial ovarian cancer.

A variety of cytokines have been identified to play a role in ovarian cancer. In this pilot study, we sought to determine whether transforming growth factor-alpha (TGF-alpha) was detectable in the serum and ascites of women with advanced stage epithelial ovarian cancer. TGF-alpha was measured using an enzyme-linked immunosorbent assay and was present in 18 of 25 control sera. Prior to treatment for stage III or IV epithelial ovarian cancer, 18 patients had undetectable serum levels of TGF-alpha, while 18 had values ranging from 10.6 to 531.7 pg/ml. The group with undetectable levels had a 6-month greater median survival; detectable TGF-alpha might be a negative prognostic indicator. In a separate group undergoing second-look laparotomy, differences in median TGF-alpha values versus controls and the primary study group approached significance. TGF-alpha was detected in significantly more control peritoneal fluid samples than in patient ascites. A larger study is warranted.