Prevalence of levator ani muscle avulsion and effect on quality of life in women with pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Levator ani muscle (LAM) avulsion is associated with pelvic organ prolapse (POP). There is limited information on the prevalence of LAM avulsion in Chinese women with POP. This study evaluated the prevalence of LAM avulsion in women presenting with POP and the effects on their quality of life (QoL). METHODS: This prospective study was conducted in a tertiary urogynecology center. Chinese women presenting with POP were recruited and completed standardized questionnaires exploring their symptoms and QoL and underwent gynecological examination to assess the stage of POP and involved compartments. Four-dimensional translabial ultrasound (US) was performed on all women, and evaluation of LAM avulsion was done offline. RESULTS: Three hundred and ninety-eight women completed the study. The prevalence of LAM avulsion was 38.9% [95% confidence interval (CI) 34.1-43.7%]; 31 (7.8%), 26 (6.5%), and 98 (24.6%) had left, right, and bilateral LAM avulsion, respectively. LAM avulsion was associated with a more advanced stage of prolapse (P < 0.005) and prolapse of stage ≥II of all three compartments. Bilateral LAM avulsion was associated with a more severe stage of prolapse. More women with LAM avulsion reported bothersome symptoms of prolapse and had higher Pelvic Organ Prolapse Distress Inventory (POPDI) and Urinary Incontinence Questionnaire (UIQ) scores, implying more impairment in QoL. However, after multivariate linear regression analysis, POP stage remained a significant predictor of POPDI and UDI scores (P ≤ 0.006); LAM avulsion was not a predictor (P = 0.2 and 0.27, respectively). CONCLUSIONS: LAM avulsion was detected in 39% of Chinese women with POP. It was associated with a more advanced POP stage, and these women had more impairment of QoL. However, LAM avulsion was not an independent factor influencing the QoL of these women.

An observational follow-up study on pelvic floor disorders to 3-5 years after delivery.

INTRODUCTION AND HYPOTHESIS: This study aimed to determine the prevalence of urinary incontinence (UI), fecal incontinence (FI), and pelvic organ prolapse (POP) 3-5 years after the first pregnancy and their associated risk factors. METHODS: We assessed 506 women using the Pelvic Floor Distress Inventory (PFDI) and the Pelvic Floor Impact Questionnaire (PFIQ). Maternal characteristics and obstetric data were analyzed using descriptive analysis, independent sample t test, chi-squared test, and logistic regression. RESULTS: The prevalence of UI, FI, and POP, respectively, at a mean of 43 months after first delivery was 40.8, 6.6, and 10.2% following vaginal delivery (VD) and 22.7, 4.5, and 4.5% following cesarean section (CS). Stress urinary incontinence (SUI) was reported by more women following VD than CS (38.7 vs 22.4%, P = 0.010). Compared with 8 weeks' postpartum, more women reported SUI at this later follow-up visit (40.1 vs 19.5%, P < 0.001), but fewer reported FI. More women who had an instrumental delivery reported symptoms of POP compared with those who had a normal VD. Higher body weight and weight gain from first trimester were risk factors of SUI [odds ratio (OR) 1.03] and urge urinary incontinence (UUI) (OR 1.18), respectively. Women who delivered vaginally had higher PFDI subscales scores. CONCLUSIONS: VD increased UI risk. Higher body weight and weight gain from first trimester were risk factors for SUI and UUI, respectively. More women reported symptoms of POP following an instrumental delivery than those who had a normal VD.

Chinese herbal medicines for unexplained recurrent miscarriage.

BACKGROUND: Recurrent miscarriage affects 1% to 3% of women of reproductive age and mostly occurs before the 10th week of gestation (and around the same gestational week in subsequent miscarriages). Although most pregnant women may not recognise a miscarriage until uterine bleeding and cramping occur, a repeat miscarriage after one or more pregnancy loss and the chance of having a successful pregnancy varies. To date, there is no universally accepted treatment for unexplained recurrent miscarriage. Chinese herbal medicines have been widely used in Asian societies for millennia and have become a popular alternative to Western medicines in recent years. Many clinical studies have reported that Chinese herbal medicines can improve pregnancy outcomes for pregnant women who had previously suffered recurrent miscarriage. This systematic review evaluated the efficacy of Chinese herbal medicines for recurrent miscarriage. OBJECTIVES: To assess the effectiveness and safety of Chinese herbal medicines for the treatment of unexplained recurrent miscarriage. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (01 June 2015), Embase (1980 to 01 June 2015); Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 01 June 2015); Chinese Biomedical Database (CBM) (1978 to 01 June 2015); China Journal Net (CJN) (1915 to 01 June 2015); China Journals Full-text Database (1915 to 01 June 2015); and WanFang Database (Chinese Ministry of Science & Technology) (1980 to 01 June 2015). We also searched reference lists of relevant trials and reviews. We identified and contacted organisations, individual experts working in the field, and medicinal herb manufacturers. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials, including cluster-randomised trials, with or without full text, comparing Chinese herbal medicines (alone or combined with other intervention or other pharmaceuticals) with placebo, no treatment, other intervention (including bed rest and psychological support), or other pharmaceuticals as treatments for unexplained recurrent miscarriage. Cross-over studies were not eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all the studies for inclusion in the review, assessed risk of bias and extracted the data. Data were checked for accuracy. MAIN RESULTS: We included nine randomised clinical trials (involving 861 women). The trials compared Chinese herbal medicines (various formulations) either alone (one trial), or in combination with other pharmaceuticals (seven trials) versus other pharmaceuticals alone. One study compared Chinese herbal medicines and other pharmaceuticals versus psychotherapy. We did not identify any trials comparing Chinese herbal medicines with placebo or no treatment, including bed rest.Various Chinese herbal medicines were used in the different trials (and some of the classical the formulations were modified in the trials). The Western pharmaceutical medicines included tocolytic drugs such as salbutamol and magnesium sulphate; hormonal supplementation with human chorionic gonadotrophin (HCG), progesterone or dydrogesterone; and supportive supplements such as vitamin E, vitamin K and folic acid.Overall, the methodological quality of the included studies was poor with unclear risk of bias for nearly all the 'Risk of bias' domains assessed.Chinese herbal medicines alone versus other pharmaceuticals alone - the live birth rate was no different between the two groups (risk ratio (RR) 1.05; 95% confidence interval (CI) 0.67 to 1.65; one trial, 80 women). No data were available for the outcome of pregnancy rate (continuation of pregnancy after 20 weeks of gestation).In contrast, the continuing pregnancy rate (RR 1.27 95% CI 1.10 to 1.48, two trials, 189 women) and live birth rate (average RR 1.55; 95% CI 1.14 to 2.10; six trials, 601 women, Tau² = 0.10; I² = 73%) were higher among the group of women who received a combination of Chinese herbal medicines and other pharmaceuticals when compared with women who received other pharmaceuticals alone.For Chinese herbal medicines and psychotherapy versus psychotherapy alone (one study) - there was a higher live birth rate (RR 1.32; 95% CI 1.07 to 1.64; one trial, 90 women) in the group of women who received a combination of Chinese herbal medicines and psychotherapy compared to those women who received psychotherapy alone. No data were available on the continuing pregnancy rate for this comparison.Other primary outcomes (maternal adverse effect and toxicity rate and the perinatal adverse effect and toxicity rate) were not reported in most of the included studies. Two trials (341 women) reported that no maternal adverse effects were found (one trial compared (combined) medicines with other pharmaceuticals, and one trial compared combined Chinese herbal medicine alone versus other pharmaceuticals). One trial (Chinese herbal medicine alone versus other pharmaceuticals alone) reported that there were no abnormal fetuses (ultrasound) or after delivery.There were no data reported for any of this review's secondary outcomes. AUTHORS' CONCLUSIONS: We found limited evidence (from nine studies with small sample sizes and unclear risk of bias) to assess the effectiveness of Chinese herbal medicines for treating unexplained recurrent miscarriage; no data were available to assess the safety of the intervention for the mother or her baby. There were no data relating to any of this review's secondary outcomes. From the limited data we found, a combination of Chinese herbal medicines and other pharmaceuticals (mainly Western medicines) may be more effective than Western medicines alone in terms of the rate of continuing pregnancy and the rate of live births. However, the methodological quality of the included studies was generally poor.A comparison of Chinese herbal medicines alone versus placebo or no treatment (including bed rest) was not possible as no relevant trials were identified.More high-quality studies are needed to further evaluate the effectiveness and safety of Chinese herbal medicines for unexplained recurrent miscarriage. In addition to assessing the effect of Chinese herbal medicines on pregnancy rate and the rate of live births, future studies should also consider safety issues (adverse effects and toxicity for the mother and her baby) as well as the secondary outcomes listed in this review. This review would provide more valuable information if the included studies could overcome the problems in their designs, such as lacking of qualified placebo-controlled trials, applying adequate randomisation methods and avoiding potential bias.

Cancer cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts.

We have investigated the role of cytokine lymphotoxin in tumour-stromal interactions in human ovarian cancer. We found that lymphotoxin overexpression is commonly shared by the cancer cells of various ovarian cancer subtypes, and lymphotoxin-beta receptor (LTBR) is expressed ubiquitously in both the cancer cells and cancer-associated fibroblasts (CAFs). In monoculture, we showed that ovarian cancer cells are not the major lymphotoxin-responsive cells. On the other hand, our co-culture studies demonstrated that the cancer cell-derived lymphotoxin induces chemokine expression in stromal fibroblasts through LTBR-NF-κB signalling. Amongst the chemokines being produced, we found that fibroblast-secreted CXCL11 promotes proliferation and migration of ovarian cancer cells via the chemokine receptor CXCR3. CXCL11 is highly expressed in CAFs in ovarian cancer biopsies, while CXCR3 is found in malignant cells in primary ovarian tumours. Additionally, the overexpression of CXCR3 is significantly associated with the tumour grade and lymph node metastasis of ovarian cancer, further supporting the role of CXCR3, which interacts with CXCL11, in promoting growth and metastasis of human ovarian cancer. Taken together, these results demonstrated that cancer-cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts. Our findings suggest that lymphotoxin-LTBR and CXCL11-CXCR3 signalling represent therapeutic targets in ovarian cancer.

Inside-out versus outside-in transobturator tension-free vaginal tape: a 5-year prospective comparative study.

OBJECTIVE: To compare the 1-year and 5-year outcomes of transobturator tension-free vaginal tape with outside-in and inside-out approaches in women with urinary stress incontinence, and to identify risk factors for treatment failure at 5 years. METHOD: A prospective observational study was carried out for women with urinary stress incontinence who underwent transobturator tension-free vaginal tape from September 2004 to March 2008 in a tertiary urogynecology center. Women (n = 213) had either an outside-in (n = 124) or inside-out (n = 89) procedure. They were followed up annually until 5 years after the operation. Subjective cure was defined as women not experiencing any urine loss on physical activity. Objective cure was defined as no urine leak at cough during a standard urodynamic study. RESULTS: At a mean follow up of 59.2 months, the subjective cure rates were 81.7% and 84.1%; the objective cure rate were 82.6% and 82.5% for the outside-in and inside-out approach, respectively. There was no statistically significant difference between the procedures. De novo overactive bladder syndrome (10.6% in outside-in and 14.6% in inside-out approach; P = 0.40) and de novo detrusor overactivity (5.8% in outside-in and 15% in inside-out approach; P = 0.11) was also comparable between the two groups. Complications at the fifth year were low and not significantly different among both methods. CONCLUSION: The outside-in approach and inside-out approach are both safe and effective in treating women with urinary stress incontinence up to 5 years.

MicroRNA-182 plays an onco-miRNA role in cervical cancer.

OBJECTIVES: The purposes of this study were to identify aberrantly expressed miRNAs and investigate their pathogenic roles in cervical cancer. METHODS: miRNA expression was assessed in cervical cancer cell lines, micro-dissected normal cervical epithelium cells and primary cervical carcinoma by TaqMan RT-PCR. Spatial expression of miR-182 in cervical carcinoma and normal cervix was explored by in situ hybridization. HeLa xenograft mice model was used for evaluation of the effect on tumor growth of miR-182 inhibitor. Western blot, flow cytometry and gene expression analysis were used for identification of the functional role of miR-182 in HeLa cells. RESULTS: Two up-regulated (miR-182 and -183) and nine down-regulated (miR-211, 145, 223, 150, 142-5p, 328, 195, 199b, 142-3p) microRNAs were consistently identified in cervical cancer cell lines. Further investigation confirmed the most up-regulated miRNA (miR-182) was significantly elevated in primary cervical carcinoma and discovered a significant correlation between the increased expression of miR-182 and advanced stages of cervical cancer. In HeLa xenograft mouse model, we demonstrated that inhibition of the miR-182 could exert the effect of tumor growth regression. Western blot, flow cytometry and pathway analysis for the HeLa cells with miR-182 over/down-expression in vitro showed that miR-182 was involved in apoptosis and cell cycle pathways, it also associated with the regulation of FOXO1. CONCLUSIONS: Our findings indicated that miR-182 plays an onco-miRNA role in cervical cancer and its alteration is associated with cervical cancer pathogenesis by disrupting cell proliferation.

Responsiveness of the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire in women undergoing treatment for pelvic floor disorders.

INTRODUCTION AND HYPOTHESIS: This study evaluated the responsiveness and minimal important differences (MID) of the Chinese Pelvic Floor Distress Inventory (PFDI) and Pelvic Floor Impact Questionnaire (PFIQ) in women undergoing urodynamic stress incontinence (USI) and/or pelvic organ prolapse (POP) treatment. METHODS: One hundred and fifty-six women were assessed using the PFDI and PFIQ before and after they received continence surgery and or pelvic floor repair (PFR) surgery, or vaginal pessary. Symptom severity was recorded using a visual analog scale (VAS) before and after treatment as was rating of their satisfaction with the treatment they received. Responsiveness of the PFDI and PFIQ were evaluated by effect sizes, standardized response mean, paired samples t test or Wilcoxon Signed Rank Test. MID in the PFDI and PFIQ for different treatments were determined by satisfaction rating, change in VAS scoring, and distribution-based methods. RESULTS: There were significant improvements in the respective subscales of PFDI and PFIQ, demonstrating moderate to great responsiveness after different treatments. The estimation of MID for the Urinary Distress Inventory (UDI) was -30 to -14 and the Urinary Impact Questionnaire (UIQ) was -28 to -14 for women who underwent continence surgery. The MID for the Pelvic Organ Prolapse Distress Inventory (POPDI) was -44 to -21, the Pelvic Organ Prolapse Impact Questionnaire (POPIQ) -40 to -27, the UDI -22 to -16, the UIQ -37 to -31, the Colo-Rectal-Anal Distress Inventory (CRADI) -37 to -14, and the Colo-Rectal-Anal Impact Questionnaire (CRAIQ) -34 to -6 for women who underwent PFR surgery; and estimation of MID for the POPDI was -16, the POPIQ -29, the UDI -28, the UIQ -17, the CRADI -25, and the CRAIQ -31 for women who received a vaginal pessary. The MID of the respective subscales were supported by the distribution-based methods. CONCLUSIONS: The Chinese PFDI and PFIQ instruments are responsive to change in women undergoing continence surgery, PFR surgery or vaginal pessary for USI or POP.

Clinical and psychological impact after surgical, medical or expectant management of first-trimester miscarriage--a randomised controlled trial.

BACKGROUND: The management of first-trimester miscarriage has been studied extensively in recent years. However, relatively little attention has been focussed on woman's satisfaction and psychological impact from different treatment modalities. AIM: To investigate the clinical and psychological outcomes of surgical, medical and expectant management of first-trimester miscarriage. MATERIALS AND METHODS: A prospective randomised controlled trial of 180 women suffering miscarriage managed by either surgical evacuation, medical evacuation or expectant management was conducted in a university-affiliated, tertiary referral hospital. The complete miscarriage rate, clinical symptomatology, complications, women's satisfaction and the psychological impact were evaluated. RESULTS: Women in surgical evacuation (98.1%) had a significantly higher complete miscarriage rate when compared with medical evacuation (70%) and expectant management (79.3%). Women who had surgical evacuation had significantly shorter duration of vaginal bleeding, but higher rate of infection. Women who had medical evacuation had significantly more gastrointestinal symptoms. Despite differences in efficacy and complication profile, there was no significant difference in satisfaction among groups. There were no significant differences in terms of psychological well-being, depression scores, anxiety level, fatigue symptoms as measured in General Health Questionnaire-12, Beck Depression Inventory, Spielberger's State Anxiety Inventory and fatigue scale at treatment and four weeks after treatment. However, women with active intervention had greater post-traumatic stress symptoms as measured in Chinese version of Impact of Event Scale-Revised at the time of treatment when compared with women in expectant management. CONCLUSION: Without substantial differences in the clinical and psychological impact between different treatment modalities, a more conservative approach with expectant management for miscarriage may be an option for women.

Pelvic floor muscle training improves quality of life of women with urinary incontinence: a prospective study.

BACKGROUND: Women suffering from urinary incontinence have impaired quality of life (QoL). Pelvic floor muscle training (PFMT) has been recommended to be the first-line treatment for them. AIMS: This study evaluated the role of (PFMT) in women with urinary incontinence. MATERIALS AND METHODS: All women suffering from urinary incontinence without pelvic organ prolapse who attended the urogynaecology unit of a university hospital from January 2009 to June 2010 were recruited. Urinary symptoms and impact on QoL were assessed using the Chinese validated Urogenital Distress Inventory short form (UDI-6) and Incontinence Impact Questionnaire short form (IIQ-7) before and after PFMT. Urodynamic studies (UDS) were used to differentiate the diagnoses of urinary incontinence. RESULTS: Three hundred and seventy-two women, aged 52.3 ± 10.8 years and practised PFMT for 9.9 ± 7.3 months, completed the study. Over 65% recorded improvement in both UDI-6 and IIQ-7. Stratified for urodynamic diagnosis, stress incontinence group and those who had no UDS abnormality had significant improvement in their urinary symptoms and QoL after PFMT. UDI-6 and IIQ-7 also improved significantly after PFMT in groups where the clinical presentation was stress incontinence, overactive bladder symptoms or mixed urinary incontinence. Age was not associated with a significant difference in the response to PFMT. CONCLUSIONS: Pelvic floor muscle training appears to be an effective first-line intervention for improving urinary symptoms and QoL of women presenting with urinary incontinence. Future studies on long-term effectiveness and cost-effectiveness are also required.

Symptoms, quality of life, and factors affecting women's treatment decisions regarding pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: We performed an investigation of symptoms, quality of life (QOL), and factors affecting women's treatment choice of pelvic organ prolapse (POP). METHODS: Three hundred and eight women presenting with POP were assessed by Pelvic Floor Distress Inventory (PFDI), Pelvic Floor Impact Questionnaire (PFIQ), Short Form-36 (SF-36), Pelvic Organ Prolapse Quantification (POP-Q) system, and urodynamic studies. Treatment was arranged according to each woman's preference after counseling. Factors affecting treatment choice were evaluated. Descriptive statistics, chi-square or Fisher exact test, analysis of variance (ANOVA) test, and logistic regression analysis were used. RESULTS: Patients had high prevalence of urinary, prolapse, and bowel symptoms. Their QOL was impaired, with Urinary Impact Questionnaire (UIQ) higher than the Pelvic Organ Prolapse Impact Questionnaire (POPIQ) score and lower SF-36 score compared with the population norm. Logistic regression analysis indicated that complication from vaginal pessary, urodynamic stress incontinence (USI), stage of prolapse, and Pelvic Organ Prolapse Distress Inventory (POPDI) scoring were factors for choosing surgical treatment. CONCLUSIONS: Women with POP had great symptomatic distress and impaired QOL. Complication from vaginal pessary, USI, stage of prolapse, and POPDI scores were factors increasing the likelihood of the patient choosing surgical treatment.

Placental site in the second trimester of pregnancy and its association with subsequent obstetric outcome.

OBJECTIVE: To determine if placental location in the second trimester of pregnancy is associated with adverse pregnancy outcomes. METHODS: We performed a retrospective study on 16 236 patients having ultrasound examination at 14 to 23 weeks of gestation between 2000 and 2007. The placental location was classified into one of four groups: 'central', 'fundal', 'lateral' and 'covering Os'. Obstetric outcomes of non-central placenta were compared to those with 'central' placenta. RESULTS: Women with a 'fundal' placenta were at increased risk of developing pre-eclampsia (PET) (odds ratios (OR) = 2.27; 95% confidence intervals (CI), 1.31-3.93), a preterm delivery before 34 weeks (OR = 2.23; 95% CI, 1.18-4.22), a non-vertex presentation (OR = 3.48; 95% CI, 2.49-4.86), undergoing a manual removal of placenta (MROP) following a vaginal delivery (OR = 7.1; 95% CI, 4.24-11.85) and small for gestational age (SGA) (OR = 1.35; 95% CI, 1.03-1.79). Women with a 'lateral' placenta were at increased risk of developing PET (OR = 2.04; 95% CI, 1.28-3.25), spontaneous preterm delivery before 34 weeks (OR = 2.04; 95% CI, 1.04-3.98), MROP (OR = 6.75; 95% CI, 4.4-10.33) and SGA (OR = 1.82; 95% CI, 1.48-2.23). Five women with a 'cover Os' placenta had an increased risk of postpartum haemorrhage (>1000 mL) (OR = 6.18; 95% CI 2.29-16.65) if they had a vaginal delivery. CONCLUSION: Non-central placental location in the second trimester is associated with an increase risk of adverse obstetric outcome.

Chinese validation of Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire.

INTRODUCTION AND HYPOTHESIS: The purpose of this study was to investigate the reliability and validity of the Chinese version of Pelvic Floor Distress Inventory (PFDI) and Pelvic Floor Impact Questionnaire (PFIQ). METHODS: Women who presented for pelvic floor disorders completed the Chinese version of PFDI and PFIQ, SF-36, a 3-day urinary and fecal diary. POP-Q assessment, urodynamic study, anal manometry, and ultrasound were performed where appropriate. RESULTS: Five hundred and ninety-seven women completed the study. The Cronbach's alpha and test-retest reliability of PFDI and PFIQ was 0.92 and 0.98, and 0.77 and 0.79, respectively. Convergent validity was demonstrated with negative correlation of PFDI and PFIQ with SF-36; positive correlation of staging of prolapse, urinary or fecal incontinent episodes with the respective subscales of PFDI and PFIQ. CONCLUSIONS: The Chinese version of PFDI and PFIQ are reliable and valid condition-specific health-related quality of life questionnaires for women with pelvic floor disorders.

Cryotherapy as the treatment modality of postcoital bleeding: a randomised clinical trial of efficacy and safety.

BACKGROUND: Postcoital bleeding is a common gynaecological problem that impacts on a woman's quality of life and sexual function. There is little systematic research into its management. AIMS: To assess the efficacy and side-effects of cryotherapy as treatment for postcoital bleeding. METHODS: A prospective randomised controlled trial was conducted in a tertiary referral hospital in Hong Kong. A total of 85 women who presented with postcoital bleeding were recruited, and randomised to cryotherapy or no treatment. The treatment group received cryotherapy with compressed carbon dioxide through a cryoprobe placed on the cervix, and controls had cryoprobe on the cervix without compressed carbon dioxide flow. All recruited women were followed up two weeks, three months and six months to review their symptoms and response to the treatment. RESULTS: The treatment group had a significantly better long-term cure rate and improvement rate. At six months, the cryotherapy group reported a cure rate of 72.1% while that in the control group the cure rate was 50.0% (P = 0.04). The number needed to treat was 5. The mean improvement rate of the cryotherapy group was 82.88% +/- 35.87 but was only 61.62% +/- 55.30 in the control group (P = 0.04). The results were more significant in women with the defined pathological cervix. Apart from the vaginal discharge at second week follow up in the treatment group, there was no statistical significant difference in side-effects and complications among two groups. CONCLUSION: Our study demonstrated that cryotherapy is a safe and an effective treatment for postcoital bleeding.

Long non-coding RNA HAND2-AS1 inhibits invasion and metastasis in endometrioid endometrial carcinoma through inactivating neuromedin U.

Endometrioid endometrial carcinoma (EEC) is one of the common causes of cancer-related mortality in women. Mounting evidences suggest that long noncoding RNAs (lncRNAs) function in multiple cancers. In this study, we discovered that HAND2-AS1, a lncRNA transcribed antisense adjacent to Heart and Neural Crest Derivatives Expressed 2 (HAND2) in chromosome 4q33-34, is significantly down-regulated in EEC. HAND2-AS1 and HAND2 were frequently down-regulated in EEC tissues, especially in poor differentiated tumor tissues. Down-regulation of HAND2-AS1 and HAND2 was correlated with tumor grade, lymph node metastasis and recurrence of EEC patients. HAND2-AS1 and HAND2 were co-downregulated by promoter DNA hypermethylation in EEC. Overexpression of HAND2-AS1 in EEC cells demonstrated that HAND2-AS1 suppressed migration and invasion of EEC cells. Similarly, overexpression of HAND2 also inhibited migration and invasion EEC cells indicating that HAND2-AS1 and HAND2 had a concordant role in the progression of EEC. However, HAND2 was not regulated by HAND2-AS1 in EEC. Furthermore, the anti-tumorigenic effect of HAND2-AS1 was mediated by down-regulating NMU, which has an oncogenic role in EEC. Our findings therefore provide the first evidence that HAND2-AS1 is a critical tumor suppressor in EEC.

Transcriptional repression of WEE1 by Kruppel-like factor 2 is involved in DNA damage-induced apoptosis.

Human Kruppel-like factor 2 (KLF2) is a Cys(2)/His(2) zinc-finger-containing transcriptional factor, which is involved in multiple cellular pathways. Utilizing gene expression profiling to identify aberrantly expressed genes in ovarian cancer, we found that KLF2 was significantly and specifically downregulated in ovarian tumors. After reintroducing KLF2 into ovarian cancer cell lines, we observed decreased cell growth and increased sensitivity to DNA damage-induced apoptosis. Analysis of genes that could be potential targets of KLF2 revealed that KLF2 negatively regulated WEE1 expression. WEE1 encodes a tyrosine kinase that regulates the G2/M cell cycle transition. Expression of KLF2 markedly repressed the transcription of WEE1 by directly binding to an SP1/CPBP motif located between -252 bp and the start codon of the WEE1 promoter. Both activation and zinc-finger domains of KLF2 were required for this suppression of Wee1 expression. In addition, we demonstrated that Wee1 expression prevents cancer cells from undergoing apoptosis in response to DNA damage; however, this resistance was abolished by coexpression of KLF2, which inhibits WEE1 transcription. Thus, the level of WEE1 is regulated by KLF2 and enhanced KLF2 expression sensitizes cells to DNA damage-induced apoptosis.

Fetal anaemia as a cause of fetal injury: diagnosis and management.

PURPOSE OF REVIEW: This review provides up-to-date information on the diagnosis and management of fetal anaemia. RECENT FINDINGS: Exciting advances in the field of red blood cell isoimmunization are phasing out the need for invasive procedures. Rhesus blood group genotyping using fetal DNA in maternal plasma has been introduced into clinical practice with remarkable success. The role of middle cerebral artery peak systolic velocity in screening for fetal anaemia has been confirmed in various causes of fetal anaemia. A recent review of a successful Iran national screening programme for thalassaemia provided a timely and valuable educational opportunity. The value of intrauterine transfusion as a treatment for fetal anaemia was demonstrated by both high success rate and low procedure-related pregnancy loss rate. SUMMARY: Fetal anaemia is one of the severe fetal conditions that affect the worldwide population. Rhesus isoimmunization remains an important health issue despite the recommendation for anti-D immunoglobulin prophylaxis and injection after sensitizing events. Noninvasive ultrasound diagnostic methods have replaced traditional invasive procedures in the assessment of fetus at risk of anaemia due to various causes, including red blood cell isoimmunization, parvovirus B19 infection and thalassaemia. The increased availability of intrauterine transfusion will help to improve the prognosis of these anaemic fetuses.

When to induce labor for post-term? A study of induction at 41 weeks versus 42 weeks.

OBJECTIVE: To evaluate the pregnancy outcomes of two policies of timing of induction of labor for post-term pregnancies. STUDY DESIGN: It is a retrospective study in a University obstetric unit from 1997 to 2002. Five thousand eight hundred and ninety-two singleton, cephalic pregnancies with gestational age at delivery at or more than 41 completed weeks were studied. They were divided into two groups. Group A included women who delivered from January 1997 to February 1999 when the policy of the department was to induce labor for post-maturity at 42 weeks of gestation. Group B included those delivered between March 1999 and December 2002 when the timing of induction for post-term was advanced to 41 weeks. The intrapartum characteristics, delivery and perinatal outcomes were analyzed by Student's t-test and Chi-square test for continuous and categorical variables, respectively. RESULTS: Two thousand one hundred and seventy-six women were studied in Group A and 3716 in Group B. Twenty-nine percent of these pregnancies in Group A required induction of labor whereas 20.3% were for post-term. In Group B, 58% of pregnancies had labor induction and 55% for post-maturity. For the pregnancies undergoing induction of labor for post-term, both the duration of labor (P<0.001) and the need of intrapartum epidural analgesia were increased (OR 1.3, 95% CI: 1.0-1.6) in Group B. However, there was no significant difference in the mode of delivery, apgar scores and stillbirths between the two study periods. CONCLUSION: Compared to routine induction at 42 weeks, induction at 41 weeks is associated with a significantly higher risk of use of medical interventions and associated complications, with no observable benefits.

Local administration of siRNA through Microneedle: Optimization, Bio-distribution, Tumor Suppression and Toxicity.

Although RNA interference may become a novel therapeutic approach for cancer treatment, target-site accumulation of siRNA to achieve therapeutic dosage will be a major problem. Microneedle represents a better way to deliver siRNAs and we have evaluated for the first time the capability of a silicon microneedle array for delivery of Gapdh siRNA to the skin in vivo and the results showed that the microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively. For the further study in this field, we evaluated the efficacy of the injectable microneedle device for local delivery of siRNA to the mouse xenograft. The results presented here indicate that local administration of siRNA through injectable microneedle could effectively deliver siRNA into the tumor region, and inhibit tumor progression without major adverse effects.

Expression genomics of cervical cancer: molecular classification and prediction of radiotherapy response by DNA microarray.

PURPOSE: The incidence and mortality rates of cervical cancer are declining in the United States; however, worldwide, cervical cancer is still one of the leading causes of death in women, second only to breast cancer. This disparity is at least partially explained by the absence of or comparatively ineffective screening programs in the developing world. Recent advances in expression genomics have enabled the use of DNA microarray to profile gene expression of various cancers. These expression profiles may be suitable for molecular classification and prediction of disease outcome and treatment response. We envision that expression genomics applied in cervical cancer may provide a more rational approach to the classification and treatment of the disease. EXPERIMENTAL DESIGN: In this report, we examined the expression profiles of cervical cancer compared with normal cervical tissues in DNA microarrays that contained approximately 11,000 features that correspond to either human transcripts with known function or anonymous expressed sequence tags. RESULTS: Our results showed that normal cervical tissues were completely segregated from the cancer samples using about 40 genes whose expressions were significantly different between these specimens. In addition, clinical stage IB and stage IIB tumors could also be classified based on their signature expression patterns. Most importantly, some of the tumor samples were further stratified into two major groups based on their response to radiotherapy, and we were able to predict the response of these patients to radiotherapy from their expression profiles. CONCLUSIONS: Gene expression profiling by DNA microarray may be used for further molecular classification of disease stages and prediction of treatment response in cervical cancer.

Prediction of chemotherapeutic response in ovarian cancer with DNA microarray expression profiling.

Ovarian carcinoma is a leading cause of gynecologic cancer death in women. Despite treatment, a large number of women with ovarian cancer eventually relapse and die of the disease. Hence, recurrent ovarian cancer continues to be a therapeutic dilemma, possibly a result of the emergence of drug resistance during relapse. Recent advances in expression genomics enable global transcript analysis that leads to molecular classification of cancers and prediction of outcome and treatment response. We did a cDNA microarray examination of the expression profiles of eight primary ovarian cancers stratified into two groups based on their chemotherapeutic response. We applied a voice-speech-pattern recognition algorithm for microarray data analysis and were able to model and predict the response of these patients to chemotherapy from their expression profiles. Hence, gene expression profiling by means of DNA microarray may be applied diagnostically for predicting treatment response in ovarian cancer.