Search

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., (Copyright © 2012. Published by Elsevier B.V.)

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., (Copyright © 2012. Published by Elsevier B.V.)

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., (Copyright © 2011. Published by Elsevier B.V.)

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.

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.

Purpose: To establish a radioimmunodetection (RAID) system for localization of cervical cancer by labeling 111-indium ((111)In) to a monoclonal antibody against cytokeratin 19 (MAb Cx-99), and detecting it with a hand-held gamma detector in an animal model., Methods: MAb Cx-99 was labeled with 111-Indium by the DTPA chelating method. From the second day to the seventh day after injection of this immunoconjugate into athymic nude mice bearing cervical cancer cell line CC7T xenografts, the biodistribution ratios of tumor and non-tumor radioactivity were detected by a hand-held gamma detector. Data were also correlated with the data detected by the conventional gamma counter., Results: The labeling efficiency of this (111)In-labeled MAb Cx-99 and (111)In-labeled MOPC was 91.6% and 95.5%, respectively. After injection, the liver, kidney and lung were initially noticed to have high radioactivity, but the localization of tumor/tissue ratios increased progressively as time passed, indicating the effect of delayed detection for distinguishing tumor from non-tumor tissues. Except for the spleen, the range of tumor/tissue ratios was 1.18-32.7 and 1.14-39.35 for the fourth day and the seventh day, respectively. The tumor/spleen ratio remained low until the seventh day after injection, thus indicating that the spleen might have a different excretion rate., Conclusion: This study indicated the feasibility of a hand-held detection system in the localization of cervical cancer after injection of (111)In-labeled MAb Cx-99. The effect of delayed detection was obvious by the decreasing high bindings in the liver, spleen and kidney, with the applicable detection time being four to seven days after injection.

We analyzed genomic aberrations in 20 cervical adenocarcinomas by comparative genomic hybridization (CGH). Most tissue samples (85%) showed DNA copy number changes; gains were more common than losses. The most consistent region of chromosomal gain was mapped to chromosome arm 3q, found in 70% of the cases, with a minimal common region of 3q28-ter. Other recurrent amplifications of genetic material were detected on 17q (45%), 1p (30%), 1q (25%), and 11q (20%). High-level copy number increases were found in chromosomal regions 3q27-ter and 9pter-13. DNA losses were seldom observed, occurring primarily in underrepresented regions of chromosome arms 4q, 13q, and 18q. The presence of high-risk human papilloma virus genomes in the cervical adenocarcinoma samples was detected in 90% of the cases. However, there was no correlation between human papilloma virus type and the pattern of genomic changes. This study is the first report of CGH analysis in human cervical adenocarcinoma. Among the major genomic alterations, our results demonstrate the importance of DNA copy increases of chromosome arm 3q in the development of cervical adenocarcinoma and identify other amplified chromosomal regions that are also associated with cervical carcinogenesis.

Background: Germline BRCA1 mutations of sporadic ovarian cancers are presumed to be rare events, except among specific populations. To date, the status of germline BRCA1 mutations in Taiwanese with primary epithelial ovarian carcinoma (PEOC) is still unknown. In this study, we tried to answer part of this question., Methods: Sixty-four patients documented with PEOC, four patients with family history of breast and/or ovary cancer syndrome and five patients with sporadic primary serous peritoneal carcinoma (PSPC) were enrolled in this retrospective study from January 1994 through June 1999. At the same time, 50 normal healthy Taiwanese without family history were enrolled in this study. Germline DNA from these patients was screened for mutations in the BRCA1 gene using polymerase chain reaction-based single-stranded conformation polymorphism analysis (PCR-SSCP). Shifting DNA bands were sequenced., Results: One of the 64 patients with PEOC (1.6%) exhibited germline BRCA1 heterozygous mutation which was exon11 single-base substitution at nucleotide1047 (CAG to TAG). One of the five patients with PSPC (20%) exhibited an exon11 single-base substitution at nucleotide 914 (TCT to TCC) with resultant silent mutation. One of the normal healthy Taiwanese (2%) was found to have an exon 2 single-base substitution at nucleotide 152 (A-->C) which was also a silent mutation. No mutations of BRCA1 were detected in four patients with a family history of breast and/or ovarian cancer., Conclusions: Based on this study, it was very difficult to obtain precise data to prove the value of applying genetic testing of BRCA1 mutations in Taiwanese patients with sporadic epithelial ovarian cancers or sporadic PSPC and even with a family history of breast and/or ovarian cancer because of its rare event and because of the too small number of cases available in this study.

Background: Ovarian cancer is a well-known disease with a poor prognosis. Due to the relatively small number of cases in Taiwan, the outcome and prognostic factors of patients with primary epithelial ovarian carcinoma are unknown., Methods: We retrospectively studied patients with proven surgical and pathologic (Federation Internationale de Gynecologie et d'Obstetrique) FIGO IIIC primary epithelial ovarian carcinoma. All patients underwent standard staging surgery, including washing cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy, retroperitoneal lymphadenectomy, infracolic omentectomy and excisional biopsy of all suspicious lesions followed by adjuvant chemotherapy with four to 12 courses of cyclophosphamide, epirubicin and cisplatin (CEP) or cyclophosphamide, adriamycin and cisplatin (CAP) intravenously, every three weeks. To avoid the coeffects of chemotherapy and surgical procedures upon the outcome, patients who received paclitaxel-based regimens or underwent incomplete surgery were excluded. Ninety-eight patients from 1990 to 1996 were identified., Results: The mean follow-up time was 28.7 months, ranging from 5.4 months to 105.9 months. The cumulative five-year disease-free survival rate for all patients was 31.6%. Optimal debulking surgery was completed in 41.8% of patients, which contributed to long-term patient survival (54% vs 16%, p < 0.0001), compared to patients without optimal debulking surgery. Optimal debulking surgery was the only statistically significant independent prognostic factor for five-year disease-free survival using multivariate analysis., Conclusions: To improve survival of patients with FIGO stage IIIC epithelial ovarian carcinoma, optimal debulking surgery should be performed as the initial form of surgical intervention.