Increased concentration of sialidases by HeLa cells might influence the cytotoxic ability of NK cells.

OBJECTIVE: Cancer cells reportedly have the ability to escape from the immune system, mainly from natural killer (NK) cells. Although the real mechanisms are complicated, some inhibitors that are secreted from the cancer cells might play an important role. This study's aim was to investigate the potential mediator released by cancer cells (HeLa) that contributes to the decreased cytotoxicity of NK cells. METHODS AND MATERIALS: An NK-HeLa coculture system was used to test the hypothesis that the presence of the potential mediator from cancer cells contributes to the decreased cytotoxicity of NK cells. RESULTS: After coculturing with HeLa cancer cells, the cytotoxicity of NK cells was decreased. When the coculture medium and culture medium containing commercialized sialidase were used to culture NK cells, the cytotoxicity of the NK cells was also inhibited. However, cytotoxicity was partially restored by a sialidase inhibitor (DANA). Western blot analysis of the HeLa cells after coculturing with NK cells demonstrated increased Neu2 and Neu3 expression in HeLa cells. CONCLUSIONS: The finding that Neu2 and Neu3 expression in cancer cells might be involved in the impaired function of NK cells, which could be restored by a sialidase inhibitor, provides a new concept that could be applied to the management of cancer.

Altered ganglioside GD3 in HeLa cells might influence the cytotoxic abilities of NK cells.

OBJECTIVE: Previously, we found that altered sialidases in HeLa cells in a natural killer-HeLa (NK-HeLa) coculture system contributed to the decreased cytotoxic ability of NK cells. However, changes that occur in the glycosylation of the HeLa cells in the NK-HeLa coculture system remain unknown. MATERIALS AND METHODS: An NK-HeLa coculture system was used to examine the changes that occur in the gangliosides of HeLa cells. RESULTS: GD3 expression in HeLa cells was significantly increased in the NK-HeLa coculture system. Exogenous ganglioside GD3 decreased the cytotoxic ability of the NK cells, which could be restored by the addition of the anti-GD3 antibody. Coadministration of GD3 and sialidase further decreased the cytotoxic ability of the NK cells, which could be partially restored by the addition of a sialidase inhibitor (DANA). GD3 expression in HeLa cells also decreased following DANA treatment. CONCLUSIONS: This study suggests that interactions between ganglioside GD3 and sialidases in HeLa cells influence the cytotoxic ability of NK cells.

Anti-Mullerian hormone serum level as a predictive marker of ovarian function in Taiwanese women.

BACKGROUND: Anti-Mullerian hormone (AMH), which is secreted by preantral and small antral follicles, has been found to be a valuable marker of ovarian reserve. The purpose of this study was to determine age-related changes in AMH levels that occur in Taiwanese women and to determine whether measuring AMH is a highly sensitive and specific tool for diagnosing polycystic ovarian syndrome (PCOS) in Taiwanese women. METHODS: A group of 59 healthy, fertile, regularly cycling women, a second group of seven patients with premature ovarian failure or menopause, and a third group of 45 PCOS patients were enrolled. Serum AMH concentrations were measured using an enzyme-linked immunosorbent assay. RESULTS: AMH levels in healthy fertile women with regular menstrual cycles demonstrated an age-related decline, with a rapid drop between 30-40 years of age that was followed by a slow decrease after 40 years old. All patients with premature ovarian failure and menopause had undetectable AMH levels. AMH levels in PCOS patients were found to be significantly higher than those measured in healthy fertile controls. The sensitivity and specificity of AMH for detecting PCOS in patients aged 29-38 years were calculated to be 74% and 79%, respectively, using an AMH cut-off value of 3.5 ng/mL. CONCLUSION: Here, we provide data on Taiwanese women that demonstrate age-related decline in AMH levels and establish an AMH-based method for detecting PCOS, which may be used as reference data for future AMH studies on Taiwanese women.

Detecting cytokeratin 19 mRNA in the peripheral blood cells of cervical cancer patients and its clinical-pathological correlation.

OBJECTIVE: The aim of this study was to study the presence of cytokeratin 19 (CK19)-expressing cancer cells in the blood of preoperative patients with FIGO stage Ib and IIb cervical cancers who received radical hysterectomy and to investigate the cells' clinical significance. METHODS: CK19 mRNA in the blood cells of the patients was detected preoperatively by a newly designed nested reverse transcriptase-polymerase chain reaction, which excluded pseudogenes a and b, performed on 84 patients with stage Ib and IIb cervical carcinoma. Possible correlations between clinicopathological factors were then analyzed. RESULTS: The sensitivity of this assay was 1 CK19-mRNA-positive cell per 10(6) peripheral blood mononuclear cells. Results showed that 21.4% of the 84 patients with cervical carcinoma had CK19-mRNA-positive cells in the blood, in comparison with 5.7% of the 35 patients with benign gynecological tumors and 0% of the 28 healthy controls (P = 0.037 and 0.006, respectively). The positive tests in the cervical cancer patients were not associated with prognostic factors including stage, pelvic lymph node metastasis, pathological types, bulky tumor size (> or =4 cm), differentiation, parametrial extension, lymphovascular space involvement, deep stromal invasion, or age. CONCLUSIONS: This study revealed the presence of circulating CK19-expressing cancer cells in the blood of patients with untreated early-stage cervical carcinomas, indicating that cervical cancer disseminated early. The survival effect of this phenomenon must be clarified. This detection assay provides an early checkpoint in the multistep process for developing metastasis in cervical cancer patients.

Analysis of genetic aberrations in uterine adenomyosis using comparative genomic hybridization.

OBJECTIVE: To use comparative genomic hybridization (CGH) to analyzefrozen tissuesfrom adenomyosis cases to discover and map genomic regions for chromosomal gains and losses. STUDY DESIGN: In a retrospective study, upper and lower threshold values of 1.20 and 0.80, respectively, were used to define positive findings. RESULTS: No positive recurrent gene copy number alterations were detected in the 25 cases of pathologically proven adenomyosis. CONCLUSION: Although CGH is extremely useful in investigating candidate genes in the development of adenomyosis, CGH was not useful in this study. Genetic changes might be indeed extremely rare in adenomyosis, or CGH was not sensitive enough to detect candidate genes.