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Biomedical subjects

H Y S Ngan

Publications and source records attributed to H Y S Ngan.

At least 19 recordsLinked to original sources
PubMed2006

Methylation profile in benign, borderline and malignant ovarian tumors.

PURPOSE: Promoter hypermethylation is a common phenomenon in neoplasm. The aims of this study were (a) to compare the methylation profiles in different types of ovarian tumors and (b) to determine the possible relationship between the methylation status and different clinicopathologic characteristics. METHODS: We examined the promoter methylation status of 9 tumor suppressor genes (RARbeta2, TMS1, RIZ1, P15, P16, PTEN, MINT31, APC and HIC1) in 89 ovarian cancers, 16 borderline ovarian tumors, 19 benign ovarian tumors, 16 normal ovarian tissue and 5 ovarian cancer cell lines. The methylation status was examined with respect to clinicopathologic characteristics of the ovarian cancer patients. RESULTS: Methylation indices for ovarian cancer, borderline ovarian tumor, benign ovarian tumor, normal ovarian tissue and ovarian cancer cell lines were 28.8, 20.1, 10.5, 11.8 and 42.2%, respectively. It was significantly higher in ovarian cancer, borderline ovarian tumor and ovarian cancer cell lines (X (2) test, P < 0.001, P = 0.01 and P < 0.001, respectively) than benign or normal ovarian tissues. In ovarian cancer, concurrent methylation of at least two genes (CM2) was associated with early stage disease (X (2) test, P = 0.035) and less recurrence (X (2) test, P = 0.020). When the methylation statuses of the nine genes as well as CM2 were included in multivariate Cox Regression analysis, CM2 was the only independent predictor for survival (P = 0.013). CONCLUSION: CM2 was an independent predictor for survival in ovarian cancer.

Cell Line, Tumor↗
PubMed2006

Association of decreased mitochondrial DNA content with ovarian cancer progression.

Mitochondrial DNA (mtDNA) content in ovarian carcinomas was assessed by quantitative PCR. Results show that mtDNA content in tumour cell was significantly higher than that in normal ovary. Change in mtDNA content was not related with patients' age or tumour stages. However, the average mtDNA copy number in pathological low-grade tumours was over two-fold higher than that in high-grade carcinomas (P=0.012). Moreover, type I carcinomas also had a significantly higher mtDNA copy number than in type II carcinomas (P=0.019). Change in mtDNA content might be an important genetic event in the progression of ovarian carcinomas.

Adenocarcinoma, Clear Cell↗
PubMed2006

Single nucleotide polymorphisms of follicle-stimulating hormone receptor are associated with ovarian cancer susceptibility.

Epidemiological studies suggested that ovulation was associated with ovarian carcinogenesis. Follicle-stimulating hormone (FSH) played an important role in follicular development and was recently found to affect growth of ovarian epithelial cells. Single nucleotide polymorphisms (SNPs) Thr307Ala and Asn680Ser were two non-synonymous variations in the coding region of the FSH receptor (FSHR) gene. This hitherto first case-control study investigating the association between these two FSHR SNPs and the risk of ovarian cancer involved 202 histopathologically confirmed ovarian cancer patients and 266 age-matched cancer-free control subjects using restriction fragment length polymorphism assay and direct sequencing. Our results demonstrated that the 307Ala and 680Ser carriers were associated with significantly increased risk of developing serous and mucinous types of ovarian cancers (P < 0.0005, OR = 2.60, 95% CI = 1.56-4.34; and P < 0.0005, OR = 2.89, 95% CI = 1.73-4.84, adjusted for age, respectively) but not endometrioid and clear cell types. The two SNPs were found to be in modest linkage disequilibrium, D' = 0.804 and 0.701, r2 = 0.581 and 0.406 for the cancer and control groups, respectively. The major haplotype of 307Ala-680Ser was also associated with higher cancer risk (P = 0.033, OR = 1.39, 95% CI = 1.03-1.88), especially for the serous and mucinous carcinomas (P = 0.001, OR = 1.82, 95% CI = 1.27-2.60). Our results suggested that the two FSHR SNPs might affect the susceptibility of women to specific subtypes of ovarian cancer. Different types of ovarian cancer might adopt distinct carcinogenetic pathways. Such understanding may be important in selecting patients for ovulation induction therapy.

Base Sequence↗
PubMed2006

Effect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model.

BACKGROUND: All-trans retinoic acid (ATRA) is a natural vitamin A derivative that has a profound effect on the regulation of cell growth, differentiation and death. AIM: To investigate the tissue dynamic and cellular invasion effects of ATRA in choriocarcinoma (CCA), an aggressive trophoblastic tumour, by using a three-dimensional organotypic culture model system and cell invasion assay, respectively. METHODS: An organotypic culture model of two CCA cell lines, JAR and JEG, was established. The effects of 1 microM ATRA on proliferation, differentiation and apoptosis on this CCA model were assessed by morphological assessment of the mitotic and apoptotic figures as well as by Ki-67 and caspase-related M30 cytoDeath antibody immunohistochemistry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay. The effect of ATRA on p53 and its regulated protein product, WAF1/Cip1, was also evaluated with DO7 and p21(WAF1) antibodies, respectively. Moreover, the effect of ATRA on cellular (CCA) invasion was also investigated with Cell Invasion Kit on the JEG cell line. RESULTS: ATRA was found to induce marked apoptosis in organotypic cultures of both cell lines, as evidenced by increased M30-positive cells (p<0.0001) and increased TUNEL-positive cells (p<0.0001) in treated cultures; to decrease proliferation, as evidenced by decreased Ki-67-positive cells (p<0.0001); and to decrease p53-DO7 immunoreactivity (p<0.0001) and increase p21(WAF1) (p<0.0001) immunoreactivity. 1.5 microM ATRA was found to effectively inhibit JEG cell invasion in the cell invasion assay. CONCLUSION: ATRA treatment was found to inhibit invasion and proliferation and enhance apoptosis, probably by the activation of caspases and induction of differentiation. ATRA and synthetic retinoids may be alternative agents for the treatment of CCA.

Antineoplastic Agents↗
PubMed2006

Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study.

BACKGROUND: Placental trophoblast can be considered to be pseudomalignant tissue and the pathogenesis of gestational trophoblastic diseases remains to be clarified. AIMS: To examine the role of caspases 8 and 10, identified by differential expression, on trophoblast tumorigenesis. METHODS: cDNA array hybridisation was used to compare gene expression profiles in choriocarcinoma cell lines (JAR, JEG, and BeWo) and normal first trimester human placentas, followed by confirmation with quantitative real time polymerase chain reaction and immunohistochemistry. Caspase 10 and its closely related family member caspase 8 were analysed. RESULTS: Downregulation of caspase 10 in choriocarcinoma was detected by both Atlastrade mark human cDNA expression array and Atlastrade mark human 1.2 array. Caspase 10 mRNA expression was significantly lower in hydatidiform mole (p = 0.035) and chorioarcinoma (p = 0.002) compared with normal placenta. The caspase 8 and 10 proteins were expressed predominantly in the cytotrophoblast and syncytiotrophoblast, respectively, with significantly lower expression in choriocarcinomas than other trophoblastic tissues (p < 0.05). Immunoreactivity for both caspase 8 and 10 correlated with the apoptotic index previously assessed by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (p = 0.02 and p = 0.04, respectively) and M30 (p < 0.001 and p = 0.003, respectively) approaches. CONCLUSIONS: These results suggest that the downregulation of capases 8 and 10 might contribute to the pathogenesis of choriocarcinoma.

Apoptosis↗
PubMed2005

The behaviors of seeking a second opinion from other health-care professionals and the utilization of complementary and alternative medicine in gynecologic cancer patients.

GOALS OF WORK: The aim of the study is to determine the predictors for seeking a second opinion and the utilization of complementary and alternative medicine (CAM) among gynecologic cancer patients. PATIENTS AND METHODS: Patients attending a gynecologic cancer clinic of a tertiary referral center were recruited over a period of 1 year. A survey was conducted for all the participants in a one-on-one basis. MAIN RESULTS: One hundred ninety-one patients were recruited. Eighty patients (41.9%) had consulted other health-care professionals (HCP) for a second opinion after they were diagnosed to have cancer and 89 (46.6%) had utilized CAM. In multivariate analysis, late-stage disease (OR=2.65, 95% CI 1.26-5.58), treatment with radiotherapy (OR=2.27, 95% CI 1.19-4.33) and tertiary education (OR=11.28, 95% CI 3.06-41.54) were independent predictors for seeking a second opinion from other HCP and utilization of CAM. Patients who sought a second opinion from other HCP were more likely to utilize CAM (OR=6.12, 95% CI 3.24-11.54). Eighty percent of the patients did not inform their usual caregiver their utilization of CAM. CONCLUSIONS: Seeking a second opinion from other HCP is common in gynecologic cancer patients. Patients who seek a second opinion are more likely to utilize CAM.

Adult↗
PubMed2005

Differential gene expression identified in complete hydatidiform mole by combining suppression subtractive hybridization and cDNA microarray.

Complete hydatidiform mole (CHM) is a type of gestational trophoblastic disease with pure paternal chromosome contribution and unpredictable malignant potential. As an attempt to assess the molecular pathogenesis of CHM, suppression subtractive hybridization (SSH) combined with cDNA microarray was used to compare the gene expression pattern of CHM compared with normal first-trimester placenta of similar gestational ages. cDNA microarray analysis using tissue-specific chips constructed with subtracted cDNA libraries identified 13 differentially expressed gene transcripts. Quantitative real-time polymerase chain reaction (PCR) confirmed up-regulation of human chorionic gonadotropin beta subunit (CGB) (P=0.0008) and KIAA1200 (P=0.0005), a G-protein regulator, as well as down-regulation of osteopontin (SPP1) (P<0.0001) in 14 genotyped CHM when compared with 15 normal placentas. These candidate genes may contribute toward understanding the mechanism involved with the development and progression of CHM.

Adult↗
PubMed2005

Potential application of the ATP cell viability assay in the measurement of intrinsic radiosensitivity in cervical cancer.

BACKGROUND: Intrinsic radiosensitivity using the clonogenic assay and the cell surviving fraction at 2 Gy (SF2) has been shown to be an independent prognostic factor for patient response to radiotherapy in carcinoma of the cervix. The clonogenic assay has significant shortcomings, making it unsuitable for routine clinical use. The ATP cell viability assay (ATP-CVA) has been shown to have a high tumor evaluability rate, technical simplicity, and reproducibility in chemosensitivity testing. AIMS: This study compares the ATP-CVA with the clonogenic assay in the in vitro radiosensitivity testing of cervical cancer cell lines. Correlation of in vitro radiosensitivity and in vivo patient response was also determined. METHODS: Five cervical carcinoma cell lines (SiHa, HeLa, Caski, C-33A, and C4-1) were tested using the ATP-CVA and the clonogenic assay. Survival curves were plotted and the mean SF2 values obtained by the two different assay methods were compared using ANOVA to see if there were significant differences. Mean SF2 values obtained from 27 cervical cancers were compared with clinical outcomes. RESULTS: The SF2 values for the cell lines ranged from 0.28 to 0.67 when tested using the ATP-CVA. Using the clonogenic assay, the SF2 values ranged from 0.27 to 0.70. ANOVA with Bonferroni pairwise multiple comparison showed no significant difference between the mean SF2 values for the individual cell lines between the two assay methods. Twenty-three cervical cancer samples (85%) were evaluable for SF2 using ATP-CVA. The mean SF2 values of patients who had locoregional failure were significantly higher than those who achieved local control (P <0.01). CONCLUSIONS: Testing intrinsic radiosensitivity using the surviving fraction at 2 Gy (SF2) is comparable using the two assay methods of ATP-CVA and clonogenic assay. The ATP-CVA should be further investigated in the testing of intrinsic radiosensitivity in patients with cervical cancer.

Adenosine Triphosphate↗
PubMed2005

Replicative MCM7 protein as a proliferation marker in endometrial carcinoma: a tissue microarray and clinicopathological analysis.

AIMS: To assess, in tissue microarray (TMA), the proliferative activity of endometrial carcinoma using one of the minichromosome maintenance (MCM) proteins (MCM7), and to explore its potential value for prognosis. MCM proteins are essential for eukaryotic DNA replication and have recently been used to define the proliferative compartments in human tissues. METHODS AND RESULTS: Immunohistochemistry for MCM7 and Ki67 was performed on TMAs constructed from 212 cases of endometrial carcinoma. MCM7 and Ki67 expression was quantified according to the extent of nuclear staining. An analysis was carried out of the association between MCM7 expression and that of Ki67 and the clinicopathological characteristics of endometrial carcinoma. MCM7 and Ki67 immunoreactivity was clearly evident in the nuclei of tumour cells. MCM7 and Ki67 labelling indices in endometrial carcinomas correlated with each other (P < 0.001). A significant correlation existed between the MCM7 labelling index and histological grade (P = 0.008) and patients' age at diagnosis (P < 0.001). Well-differentiated carcinomas and younger patients had a lower MCM7 index. Poor survival was observed in patients with endometrial carcinoma with a high MCM7 index (P = 0.03) and MCM7 was found to be an independent prognostic factor by multivariate analysis (P = 0.04). The Ki67 labelling index correlated with histological grade (P = 0.01) but had no significant prognostic impact (P = 0.50). CONCLUSIONS: In this TMA study on endometrial carcinoma, MCM7 was found to be a more reliable and useful marker than Ki67 in assessing tumour proliferation and in the prognosis of patients.

Adolescent↗
PubMed2005

Id helix-loop-helix proteins are differentially expressed in gestational trophoblastic disease.

AIMS: To assess the expression of Id proteins in trophoblastic tissues and to correlate this with clinical parameters, proliferative and apoptotic indices as well as to related oncogene expression. METHODS AND RESULTS: Immunohistochemistry for Id1, Id2, Id3 and Id4 was performed on 83 trophoblastic tissues including 17 normal first-trimester placentas, seven term placentas, 47 hydatidiform moles (HM), and 12 spontaneous miscarriages. The four Id proteins were predominantly expressed in the villous and implantation site intermediate trophoblast. Expression of Id1 in HM was significantly higher than that in normal placenta (P = 0.0006) and spontaneous miscarriage (P = 0.0001) but did not correlate with subsequent development of gestational trophoblastic neoplasia (GTN). Id1 expression correlated with the proliferation index as assessed by MCM7 (P = 0.003) and Ki67 (P = 0.017) and with the apoptotic activity assessed by TUNEL (P = 0.001) and M30 CytoDeath antibody (P = 0.013). Moreover, the expression of Id1 correlated with the expression of p53 (P = 0.004), p21(WAF1) (/CIP1) (P = 0.003) but not with p16 (P = 0.107). CONCLUSIONS: Id proteins may play a role in the regulation of proliferative and apoptotic activity in trophoblastic tissue and are potentially useful in differentiating molar and non-molar gestation, but are not helpful in predicting GTN.

Cell Cycle Proteins↗