Tony K.H. Chung

Antepartum depressive symptomatology is associated with adverse obstetric and neonatal outcomes.

Objective The purpose of this study was to examine if depressive symptomatology in pregnancy is associated with adverse obstetric and neonatal outcomes. Method In a prospective observational study, 959 women were followed up longitudinally from early pregnancy to postpartum. The level of depression was measured at baseline (first antepartum visit) and in late pregnancy using the Beck Depression Inventory (BDI). Adverse obstetric and neonatal outcomes were recorded at delivery. Results Depression in late pregnancy was associated with increased risk of epidural analgesia (33% vs. 19%, p = .01, adjusted RR = 2.56, 95% CI 1.24–5.30), operative deliveries (caesarean sections and instrumental vaginal deliveries) (39% vs. 27%, p = .02, adjusted RR = 2.28, 95% CI 1.15–4.53), and admission to neonatal care unit (24% vs. 19%, p = .03, adjusted RR = 2.18, 95% CI 1.02–4.66). These effects remained significant even when controlled for potential confounders, such as antepartum complications. Conclusion Previous studies have shown that antepartum anxiety or stress was associated with growth retardation, premature delivery, and epidural analgesia. Our findings add to this body of evidence, which together suggest an adverse impact of antepartum psychological morbidity on maternal and neonatal well-being.

Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers.

Chronic infections with the hepatitis B virus (HBV) and high-risk human papillomaviruses (HPVs) are important risk factors for hepatocellular carcinoma (HCC) and cervical cancer (CC), respectively. HBV and HPV are DNA viruses that almost invariably integrate into the host genome in invasive tumors. The viral integration sites occur throughout the genome, leading to the presumption that there are no preferred sites of integration. A number of viral integrations have been shown to occur within the vicinity of important cancer-related genes. In studies of HBV-induced HCC and HPV-induced CC, we have identified two HBV and three HPV integrations into the human telomerase reverse transcriptase (hTERT) gene. Detailed characterization of the integrations revealed that four integrations occurred within the hTERT promoter and upstream region and the fifth integration occurred in intron 3 of the hTERT gene. None of the integrations altered the hTERT coding sequence and all resulted in juxtaposition of viral enhancers near hTERT, with potential activation of hTERT expression. Our work supports the hypothesis that the sites of oncogenic viral integration are nonrandom and that genes at the sites of viral integration may play important roles in carcinogenesis.

Therapeutic potentials of gene silencing by RNA interference: principles, challenges, and new strategies.

During recent decades there have been remarkable advances in biology, in which one of the most important discoveries is RNA interference (RNAi). RNAi is a specific post-transcriptional regulatory pathway that can result in silencing gene functions. Efforts have been done to translate this new discovery into clinical applications for disease treatment. However, technical difficulties restrict the development of RNAi, including stability, off-target effects, immunostimulation and delivery problems. Researchers have attempted to surmount these barriers and improve the bioavailability and safety of RNAi-based therapeutics by optimizing the chemistry and structure of these molecules. This paper aimed to describe the principles of RNA interference, review the therapeutic potential in various diseases and discuss the new strategies for in vivo delivery of RNAi to overcome the challenges.

Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1

MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real‐time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti‐/pre‐miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR‐7, miR‐194 and miR‐449b, or overexpressing miR‐204, repressed migration, invasion and extracellular matrix‐adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR‐204, and two binding sites in the 3′‐untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR‐204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR‐204‐FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression‐ and metastasis‐related miRNAs offers a novel potential therapeutic strategy for the disease.

Dysregulated microRNAs and their predicted targets associated with endometrioid endometrial adenocarcinoma in Hong Kong women

The objective of this study, a parallel study to global gene expression profiling, was to identify dysregulated microRNAs (miRNAs) associated with endometrioid endometrial adenocarcinoma (EEC), examine their correlation with clinico‐pathological characteristics and identify predicted target genes of the dysregulated miRNAs. Using real‐time quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR), profiling of miRNA expression was performed in 30 EECs and 22 normal counterparts in which genome‐wide gene expression had been previously profiled and reported. Clustering analysis identified 30 miRNAs which were significantly dysregulated in EEC. The expression of a sub‐group of miRNAs was significantly correlated with clinico‐pathological characteristics including stage, myometrial invasion, recurrence and lymph node involvement. By searching for predicted miRNA targets that were linked to the dysregulated genes previously identified, 68 genes were predicted as candidate targets of these 30 dysregulated miRNAs. miR‐205 was significantly overexpressed in EECs compared with normal controls. After transfection of a miR‐205 inhibitor, the expression of miR‐205 in endometrial cancer cell line RL95‐2 cells decreased whereas its predicted target gene, JPH4, showed increased protein expression. JPH4 seems to be a real miR‐205 target in vitro and in vivo, and a candidate tumor suppressor gene in EEC. Based on this study in EEC, miRNAs predicted to be involved in tumorigenesis and tumor progression have been identified and placed in the context of the transcriptome of EEC. This work provides a framework on which further research into novel diagnosis and treatment of EEC can be focused.

Spontaneous abortion: a randomized, controlled trial comparing surgical evacuation with conservative management using misoprostol

OBJECTIVE To compare the efficacy of surgical evacuation of the uterus with medical evacuation using misoprostol in cases of spontaneous abortion. DESIGN A prospective, randomized, controlled trial. SETTING A university teaching hospital. PATIENT(S) Six hundred thirty-five women who aborted spontaneously and who consented to pretreatment randomization. INTERVENTION(S) Routine surgical evacuation or medical evacuation of the uterus using misoprostol. MAIN OUTCOME MEASURE(S) Immediate, short-term (2-3 weeks), and medium-term (6 months) medical complications. RESULT(S) There was a significantly lower incidence of immediate and short-term complications in the group treated with misoprostol compared with the surgically treated group. There were also fewer major complications in the 6 months after treatment in the medically treated group. Approximately 50% of the medically treated group subsequently required surgical evacuation, and these subjects required significantly more analgesia. CONCLUSION(S) Treatment with misoprostol can reduce the demand for surgical evacuation in cases of spontaneous abortion, and its use is associated with fewer medical complications.

Urinary retention in the post-partum period: The relationship between obstetric factors and the post-partum post-void residual bladder volume

Objective. The three objectives of this study are: to investigate the incidence of post‐partum urinary retention after vaginal delivery, to investigate the relationship between various obstetric parameters and the post‐partum post‐void residual bladder volume and to study the natural progression of the post‐void residual bladder volume in patients with covert post‐partum urinary retention.

Identification of molecular markers and signaling pathway in endometrial cancer in Hong Kong Chinese women by genome-wide gene expression profiling

Endometrial cancer is the third most common gynecologic malignancy and the ninth most common malignancy for females overall in Hong Kong. Approximately 80% or more of these cancers are endometrioid endometrial adenocarcinomas. The aim of this study was to reveal genes contributing to the development of endometrioid endometrial cancer, which may impact diagnosis, prognosis and treatment of the disease. Whole-genome gene expression analysis was completed for a set of 55 microdissected sporadic endometrioid endometrial adenocarcinomas and 29 microdissected normal endometrium specimens using the Affymetrix Human U133 Plus 2.0 oligonucleotide microarray. Selected genes of interest were validated by quantitative real-time-polymerase chain reaction (qRT-PCR). Pathway analysis was performed to reveal gene interactions involved in endometrial tumorigenesis. Unsupervised hierarchical clustering displayed a distinct separation between the endometrioid adenocarcinomas and normal endometrium samples. Supervised analysis identified 117 highly differentially regulated genes (⩾4.0-fold change), which distinguished the endometrial cancer specimens from normal endometrium. Twelve novel genes including DKK4, ZIC1, KIF1A, SAA2, LOC16378, ALPP2, CCL20, CXCL5, BST2, OLFM1, KLRC1 and MBC45780 were deregulated in the endometrial cancer, and further validated in an independent set of 56 cancer and 29 normal samples using qRT-PCR. In addition, 10 genes were differentially regulated in late-stage cancer, as compared to early-stage disease, and may be involved in tumor progression. Pathway analysis of the expression data from this tumor revealed an interconnected network consisting of 21 aberrantly regulated genes involved in angiogenesis, cell proliferation and chromosomal instability. The results of this study highlight the molecular features of endometrioid endometrial cancer and provide insight into the events underlying the development and progression of endometrioid endometrial cancer.

Genome-wide gene expression profiling of cervical cancer in Hong Kong women by oligonucleotide microarray.

An analysis of gene expression profiles obtained from cervical cancers was performed to find those genes most aberrantly expressed. Total RNA was prepared from 29 samples of cervical squamous cell carcinoma and 18 control samples, and hybridized to Affymetrix oligonucleotide microarrays with probe sets complementary to over 20,000 transcripts. Unsupervised hierarchical clustering of the expression data readily distinguished normal cervix from cancer. Supervised analysis of gene expression data identified 98 and 139 genes that exhibited >2‐fold upregulation and >2‐fold downregulation, respectively, in cervical cancer compared to normal cervix. Several of the genes that were differentially regulated included SPP1 (Osteopontin), CDKN2A (p16), RPL39L, Clorf1, MAL, p11, ARS and NICE‐1. These were validated by quantitative RT‐PCR on an independent set of cancer and control specimens. Gene Ontology analysis showed that the list of differentially expressed genes included ones that were involved in multiple biological processes, including cell proliferation, cell cycle and protein catabolism. Immunohistochemical staining of cancer specimens further confirmed differential expression of SPP1 in cervical cancer cells vs. nontumor cells. In addition, 2 genes, CTGF and RGS1 were found to be upregulated in late stage cancer compared to early stage cancer, suggesting that they might be involved in cancer progression. The pathway analysis of expression data showed that the SPP1, VEGF, CDC2 and CKS2 genes were coordinately differentially regulated between cancer and normal. The present study is promising and provides potential new insights into the extent of expression differences underlying the development and progression of cervical squamous cell cancer. This study has also revealed several genes that may be highly attractive candidate molecular markers/targets for cervical cancer diagnosis, prognosis and therapy.

Screening for postnatal depression: are specific instruments mandatory?

BACKGROUND Few studies have examined the utility of rating scales developed in non-puerperal context in detecting postnatal depression. This study evaluated the utility of the General Health Questionnaire (GHQ) and the Beck Depression Inventory (BDI) in screening for depression among recently delivered women in Hong Kong. METHODS A prospective cohort of 145 Chinese women completed the GHQ, BDI and Edinburgh Postnatal Depression Scale (EPDS) 6 weeks after delivery. They were then assessed using the non-patient version of the Structured Clinical Interview for DSM-III-R (SCID-NP) to establish psychiatric diagnosis, against which the criterion validity of the GHQ and BDI was evaluated against this clinical diagnosis. The psychometric performance of the GHQ, BDI and EPDS in detecting postnatal depression was assessed using the receiver operating characteristic (ROC) curves. RESULTS Both Chinese GHQ and BDI had satisfactory sensitivity and positive predictive value in detecting postnatal depression. Their receiver operating characteristic (ROC) curves were comparable to that of the EPDS. LIMITATION The study was conducted in Chinese women using translated version of the rating scales. CONCLUSIONS The GHQ and BDI are useful for detecting postnatal depression among recently delivered Chinese women. The results of this study suggest that rating scales developed in non-puerperal context may also be applicable for postnatal depression.