Biomedical subjects
H Y Ngan
Publications and source records attributed to H Y Ngan.
Carcinoma of the cervix uteri.
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Carcinoma of the corpus uteri.
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Carcinoma of the Fallopian tube.
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Gestational trophoblastic diseases.
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Gestational trophoblastic neoplasia, FIGO 2000 staging and classification.
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High incidence of somatic mitochondrial DNA mutations in human ovarian carcinomas.
To investigate the potential role of somatic mitochondrial DNA (mtDNA) mutations in tumorigenesis, the occurrence of mutations in mtDNA of ovarian carcinomas was studied. We sequenced the D-loop region of mtDNA of 15 primary ovarian carcinomas and their matched normal controls. Somatic mtDNA mutations were detected in 20% (3 of 15) tumor samples carrying single or multiple changes. Complete sequence analysis of the mtDNA genomes of another 10 pairs of primary ovarian carcinomas and control tissues revealed somatic mtDNA mutations in 60% (6 of 10) of tumor samples. Most of these mutations were homoplasmic, and most were T-->C or G-->A transitions, but one represented a differential length within a run of identical C residues. A region of mtDNA sequence including the 16S and 12S rRNA genes, the D-loop and the cytochrome b gene, may represent the zone of preferred mtDNA mutation in ovarian cancer. The high incidence of mtDNA mutations found in ovarian carcinomas and other human cancers suggests that genetic instability of mtDNA might play a significant role in tumorigenesis.
Primary peritoneal malignant mixed Müllerian tumors. A clinicopathologic, immunohistochemical, and genetic study.
BACKGROUND: Primary peritoneal malignant mixed Müllerian tumors (MMMTs) are rarely reported in the literature. METHODS: The clinical, pathologic, and immunohistochemical features of five cases of MMMT of female peritoneum were analyzed. The tumors were also investigated for expression of hormone receptors, specific BRCA-1 mutations, and clonality. RESULTS: The patients' ages ranged from 33 to 67 years. They presented with abdominal pain or mass. One case of peritoneal MMMT was associated with a synchronous endometrial carcinoma whereas another case was detected 2 years after the diagnosis of a primary adenocarcinoma of the fallopian tube. One patient died 1 month after diagnosis whereas 2 patients died with disease within 1 year. Both carcinomatous and sarcomatous elements are present in all the tumors. Squamous differentiation was noted in two cases. Heterologous elements, including chondroid, rhabodomyoblastic, and osteoid differentiation were detected in all tumors. Immunohistochemical studies confirm the biphasic differentiation with variable demonstration of neural and smooth muscle differentiation. All five MMMTs were negative for estrogen and progestogen receptors although the related endometrial and tubal carcinomas were positive. Heteroduplex analysis used to screen for specific BRCA-1 mutations were negative in all five MMMTs. Clonality study of the two MMMTs found in association with endometrial carcinoma and tubal carcinoma was inconclusive. CONCLUSIONS: Our study confirmed that primary peritoneal MMMTs were aggressive tumors with poor prognosis. The presence of synchronous or metachronous genital carcinomas suggests multifocal tumorigenesis from tissue of same embryologic origin. The lack of hormone receptor in these tumors indicates deviation from hormonal control. Specific BRCA-1 mutations found in ovarian carcinoma in Chinese patients could not be detected in our series.
Psychosocial adjustment in gynecologic cancer survivors: a longitudinal study on risk factors for maladjustment.
OBJECTIVE: The objective was to describe the change in psychosocial state over time and to identify risk factors for maladjustment in gynecologic cancer survivors. Awareness of these issues is important for planning supportive care services for cancer patients. METHODS: A longitudinal prospective study of patients with newly diagnosed gynecologic cancer using individual patients as their own control was performed. Patients were interviewed after confirmation of the diagnosis and were reassessed at 6 and 18 months after completion of treatment and with no evidence of recurrent disease. Psychological adjustment was measured by self-rating on self-esteem, outlook on life, self-role, and femininity. Neuroticism and anxiety were assessed using a neuroticism score and the Hamilton Anxiety Scale. Depressive symptoms were questioned directly. Social adjustment was assessed by changes in working capacity or work status, leisure activity, marital relationship, and sexual activity. RESULTS: Seventy-four women participated. Adjustment problems did not occur in the majority of patients. Psychosocial adjustment was different for patients receiving different types of treatments. Improvement in feminism (P = 0.050) and neuroticism (P = 0.010) was observed for patients receiving chemotherapy and deterioration was observed in patients treated with surgery. Deterioration in neuroticism was associated with lower education level (P = 0.032). With religious belief, there was better family support and more significant improvement in social activity (P = 0.038). CONCLUSION: Most patients adapted well. Patients at risk for psychosocial maladjustment include those who are treated surgically, less educated, and without religious belief.
Low incidence of HPV DNA in sera of pretreatment cervical cancer patients.
OBJECTIVE: The aim of this study was to investigate the feasibility of using DNA in the circulation as a diagnostic tool for cervical cancer. METHODS: We used PCR followed by Southern hybridization to detect human papillomavirus (HPV) DNA in serum samples taken from patients of cervical cancer before treatment. RESULTS: A total of 60 samples were analyzed. In a set of 40 samples, without knowledge of the HPV DNA status in the corresponding cervical carcinomas, we could detect 8 (20%) positive samples, of which 7 (17.5%) were HPV 16 and 1 (2.5%) was HPV 18. In another set of 20 samples, known to be HPV 16 infected in the corresponding cervical carcinomas, we detected only 4 (20%) HPV-16-positive samples. The occurrence of HPV DNA in sera of cervical cancer patients seems sporadic. CONCLUSION: The low incidence indicates that serum HPV DNA has limited application in the diagnosis of cervical cancer.
A longitudinal study on quality of life after gynecologic cancer treatment.
OBJECTIVE: The objective was to describe the pattern of quality of life (QOL) over time and to assess the impact of age, symptoms, disease parameters, and treatment on the overall QOL. METHODS: A longitudinal study on patients with newly diagnosed gynecologic cancer using individual patients as their own control was performed. The 33-item EORTC QLQ-C30(+3) was used as the QOL measure. Patients were assessed before treatment, after completion of treatment, and at 6, 12, and 24 months. Spearman's correlation analyses were performed. A mixed effect model was fitted to the data. Bonferroni pairwise comparisons were used to analyze the different variables. RESULTS: One hundred forty-four women completed the study. Overall QOL improved after the completion of treatment but remained the same throughout the 2 years after treatment. The individual patient's QOL before treatment was insignificant while the impact of treatment on the individual patient was significant in determining QOL after treatment. There was a strong correlation for all time points in most factors, indicating that the global health status, functional scales, and symptom scales exhibit a dependent change over time. Relief in symptoms was associated with improvements in functional scales. The scores on overall QOL were lower for younger patients and for patients treated with chemotherapy than for patients treated with surgery. CONCLUSIONS: Strategies for supportive care need to focus on symptom management. Psychosocial interventions, to be effective, should include all patients and should aim to reduce the impact of treatment on the individual patient.
Anti-apoptotic proteins, apoptotic and proliferative parameters and their prognostic significance in cervical carcinoma.
The inhibitor of apoptosis proteins (IAP) suppress apoptosis induced by a variety of stimuli. The aims of this study were to: (a) compare the expression of X-linked IAP (Xiap) and Human IAP-2 (Hiap-2) in cervical carcinoma cells and normal cervix, (b) determine the correlation between IAP expression and tumour apoptosis or proliferation, and (c) assess their prognostic significance in cervical carcinomas. Paraffin-embedded tissue sections were retrieved from 77 patients with cervical squamous carcinomas prior to treatments and 47 normal subjects. Tumour apoptosis was determined by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuracil triphosphate (dUTP) nick-end labelling (TUNEL) and apoptotic index (AI), and the proliferative rate was measured by Ki-67 and mitotic (MI) indices. Immunoreactive Xiap and Hiap-2 were found in both cervical cancer cells and normal tissues. IAP expressions in cancers did not correlate with apoptotic and proliferative parameters, disease stage and patient survival. The lower AI and Ki-67 index were associated with a better survival. In conclusion, the basal expression levels of IAPs have no prognostic significance, but AI and Ki-67 expression are potential prognostic indicators in cervical carcinoma.
pRb-expressing adenovirus Ad5-Rb attenuates the p53-induced apoptosis in cervical cancer cell lines.
The retinoblastoma protein (pRb), the gene product of the first reported tumour suppressor gene, is functionally inactivated by the E7 protein of high-risk human papillomavirus (HPV) found in most human cervical cancers. We have, in this study, constructed an adenoviral vector expressing wild-type pRb (Ad5-Rb) and used the constructed Ad5-Rb to transfect the osteosarcoma cell line Saos-2, and three cervical cancer cell lines HeLa, SiHa and C-33A. Our results showed that pRb caused G1 arrest in Saos-2 cells after transfection with Ad5-Rb. The number of colonies formed by the Ad5-Rb-transfected Saos-2 cells in soft agar was also found to be significantly lower (P<0.05) than those transfected with the adenoviral control expressing Escherichia coli beta-galactosidase (Ad5-LacZ). The transfection of Ad5-Rb caused an increase in the population of SiHa and C-33A cells in the G1 phase from 53.0 and 52.9% to 72.4 and 64.3%, respectively, but not in the HeLa cells. However, Ad5-Rb did not show any inhibitory effect on the growth of SiHa, HeLa and C-33A cells, and inhibition of colony formation in soft agar was not observed either. In contrast, flow cytometric analysis showed that Ad5-p53, a p53-expressing adenovirus, induced apoptosis, i.e. the appearance of sub-G1 peak, in all three tested cervical cancer cell lines. Nevertheless, the Ad5-p53-induced apoptosis was partially inhibited when Ad5-Rb was added simultaneously. These findings suggested that pRb may not be a good candidate for cervical cancer gene therapy. Our data also showed that the use of full-length pRb in combination with TP53 might not be a suitable strategy for cancer gene therapy.
Mitomycin C and cisplatin enhanced the antitumor activity of p53-expressing adenovirus in cervical cancer cells.
This study investigated the enhanced antitumor activity of Ad5-p53 in combination with mitomycin C (MMC) or cisplatin (DDP) in cervical cancer cell lines SiHa and C-33A. MMC and DDP inhibited the growth of SiHa and C-33A cells in a dose-dependent manner, and the combination of MMC or DDP with Ad5-p53 showed a stronger growth inhibition than those treated with either Ad5-p53, MMC, or DDP alone. As evidenced by the formation of the approximately 200 bp DNA ladder and the appearance of sub-G1 peak, both MMC and DDP induced apoptosis in cervical cancer cells. Western blot analysis of p53 showed that MMC/DDP did not induce the increase of p53 protein in SiHa cells nor the increase of the cellular and nuclear p53 protein in Ad5-p53 transfected Saos-2 cells. Taken together, these results suggested that the combination of Ad5-p53 and MMC/DDP may serve as an effective therapeutic regime for human cervical cancer treatment.