Long-term outcomes of vulvar or vaginal cancer patients undergoing laparoendoscopic single-site inguinal lymphadenectomy.

INTRODUCTION: Laparoendoscopic single-site inguinal lymphadenectomy (LESS-IL), a minimally invasive technique, has been reported in patients with vulvar or vaginal cancer regarding its safety and feasibility. However, the long-term outcomes, especially oncologic outcomes, are still lacking. We aimed to evaluate the long-term outcomes of LESS-IL to confirm its safety further. PATIENTS AND METHODS: Data were prospectively collected from patients with vulvar or vaginal cancer who underwent LESS-IL at our institution between July 2018 and June 2021. The patients were followed up for at least 12 months. All procedures were performed according to treatment standards. Short- and long-term complications and oncologic outcomes were analysed. RESULTS: A total of 16 patients undergoing 28 LESS-IL procedures were identified, amongst whom 4 underwent unilateral LESS-IL. The median numbers of excised groin lymph nodes were 9.0 (6.5-11.8) and 10.5 (8.3-12.0) in each left and right groin, respectively. Short-term complications occurred in 4 (25%) patients, including 18.7% lymphocele and 6.3% wound infection. Long-term complications regarding lower-limb lymphoedema appeared in 6 (37.5%) patients. Most short- and long-term complications were Clavien-Dindo 1 or 2, accounting for 90% of all post-operative issues. After a median follow-up of 27 (21.3-35.8) months, only 1 (6.3%) patient had isolated inguinal recurrence at 13 months postoperatively. No local or distant recurrence occurred. CONCLUSION: Our results suggest that LESS-IL is associated with little incidence of complications and promising oncologic outcomes, further demonstrating the safety and feasibility of the LESS-IL technique in patients requiring IL.

Evaluating the cost utility of estradiol plus dydrogesterone for the treatment of menopausal women in China.

AIM: Evaluate the cost utility of menopausal hormone therapy for women in China. MATERIALS AND METHODS: A bespoke Markov cost utility model was developed to evaluate a cohort of symptomatic perimenopausal women (>45 years) with intact uterus in China in accordance with China's Pharmacoeconomic guideline. Short (5-year) and long (10-year) treatment durations were evaluated over a lifetime model time horizon with 12-month cycle duration. Societal and healthcare payer perspectives were evaluated in the context of a primary care provider/prescriber, outpatient setting with inpatient care for patients with chronic conditions. Disease risk and mortality parameters were derived from focused literature searches, and China Diagnosis-related Group cost data was included. Comprehensive scenario, univariate and probabilistic sensitivity analysis were undertaken along with independent validation. This is the first model to include MHT-related disease risks. RESULTS: According to base case results, the total cost for MHT was 22,516$ (150,106¥) and total quality adjusted life years 12.32 versus total cost of no MHT 30,824$ (205,495¥) and total quality adjusted life years 11.16 resulting in a dominant incremental cost effectiveness ratio of -7,184$ (-47,898¥) per QALY. Results hold true over a range of univariate deterministic sensitivity and scenario analyses. Probabilistic analysis showed a 91% probability of being cost effective at a willingness to pay threshold of three times Gross Domestic Product per capita in China. CONCLUSION: Contingent on the structure and assumptions of the model, combination of estradiol plus dydrogesterone MHT is potentially cost saving in symptomatic women over the age of 45 years in China.

Menopausal hormone therapy is publicly funded in many countries to alleviate symptoms of menopause; however, uptake has been comparatively slow in China. This has implications for the estimated 168 million menopausal-aged women. This analysis is the first to evaluate the cost effectiveness of menopausal hormone therapy in China using best practice principles and incorporating longer term disease risks. Menopausal hormone therapy is potentially cost saving in the context of China.

Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases.

Laparoendoscopic single-site surgery (LESS) has become a novel minimally invasive approach applied as an option to perform hysterectomy. The aim of the study was to evaluate the influence of LESS hysterectomy on the sexual function in women with benign gynecologic indications. From October 2016 to May 2021, a total of 486 premenopausal, sexually active women were eligible. Female sexual function index (FSFI) was used to assess sexual function preoperatively and 6, 12 months postoperatively. Total FSFI score ≤26.55 indicated female sexual dysfunction (FSD). Compared with pre-operation, each subdomain and total FSFI scores increased at 6 (all p < 0.05) and 12 months (all p < 0.001). Prevalence of FSD decreased at 6 (30 vs 39.9%, p = 0.002) and 12 months (27 vs 39.9%, p < 0.001). In patients with preoperative FSD, each subdomain and total FSFI scores improved at 6 and 12 months (all p < 0.001), while decreased at 6 months (p < 0.001) and had no significant difference at 12 months (p = 0.54) in patients without preoperative FSD. These results suggest that LESS hysterectomy has a significant positive effect on the sexual function in women with benign gynecologic diseases, especially those with preoperative FSD.

Effects of bisphenol A on uterine leiomyoma: In vitro and in vivo evaluation with mechanistic insights related to XBP1.

The incidence rate of human uterine leiomyomas is over 70% in the women of childbearing age, which has caused serious health and financial burden. Our previous study confirmed that Bisphenol A (BPA)，representative environmental estrogen, promoted the proliferation of human uterine leiomyomas and up-regulated the expression of cell proliferation-related genes. In this study, by combining ChIP-seq and RNA-seq, it was shown that after BPA intervention, H3K27ac modification levels and gene expression levels were altered in uterine leiomyomas cells. Moreover experimental verification found that BPA can regulate ITGA2 through the transcription factor XBP1, activate the downstream PI3K/AKT signaling pathway, eventually promote the proliferation of uterine leiomyomas. The present study provides new insights into the pathogenesis associated with exposure to BPA and other endocrine disruptors with similar effects by defining XBP1 as an important regulator, and which may act as an intervention and treatment target for uterine leiomyomas.

How to minimize the impact of COVID-19 on laparoendoscopic single-site surgery training?

BACKGROUND: Because of special technical challenges, laparoendoscopic single-site surgery (LESS) has been introduced into surgical practice, with surgeons required to have adequate training. The COVID-19 pandemic has significantly affected every aspect of healthcare systems, including LESS training, which must be modified to minimize the impact of the COVID-19 pandemic. METHODS: A 3-session training programme was designed in 2020 during the epidemic, which was modified in 2019 before the pandemic. Session 1 was an online study on LESS knowledge. Session 2 involved the trainees' self-directed simulator-training. Task performance was evaluated using the fundamentals of laparoscopic surgery (FLS) scoring. Session 3 was practical training, including trainers' live surgical video demonstrations and trainees' surgical video feedback after training. Video feedback performance was evaluated using the modified global rating scale (GRS). Furthermore, trainees completed a general self-efficacy (GSE) instrument. Forty-two gynaecology trainees were allocated into two groups: novices (n = 32) and experts (n = 10). RESULTS: Compared with pre-training, FLS scores improved in peg transfer (P < 0.001 and P = 0.01) and pattern cutting (P = 0.02 and P < 0.001) for novices and experts, respectively. Participants (81% versus 67%) provided first and second video feedback, respectively. Compared to the first feedback, the GRS scores of both groups improved significantly in the second feedback. All trainees showed an increase in GSE after training (P < 0.001). CONCLUSION: The modified LESS training programme is a practical and effective option that allows trainees to continue training during the epidemic.

Effectiveness of self-myofascial release combined with biofeedback and electrical stimulation for the management of myofascial pelvic pain: A randomized controlled trial.

BACKGROUND: Myofascial pelvic pain (MFPP) caused by myofascial trigger points (MTrPs) is a major contributor to chronic pelvic pain in women. However, the effect of the patient's self-myofascial release (SMFR) is unclear. This study aimed to investigate the effect of SMFR combined with biofeedback and electrical stimulation (BES) therapy in comparison with BES alone in patients with MFPP. METHODS: A prospective randomized controlled study was conducted. Sixty-eight patients were randomly allocated into BES-SMFR group (n = 34) and BES group (n = 34). Every patient received 4 weeks of treatment, evaluated at baseline (T0), 4 weeks post-intervention (T4) and 12-week follow-up (T12). The primary outcome was pain intensity. The secondary outcomes were degree of activation of MTrPs, surface electromyography (sEMG) levels and Patient Global Impression of Improvement (PGI-I). RESULTS: Compared with the effect of BES, BES-SMFR treatment significantly decreased pain intensity and the degree of activation of MTrPs in the levator ani (p = 0.02) and obturator internus (p = 0.03), as well as the sEMG levels of the pre-test resting baseline and post-test resting baseline (all p < 0.01). The degree of activation of MTrPs in the piriformis and coccygeus (all p > 0.05) and the sEMG levels of the quick flicks and endurance contraction were not significantly different. The BES-SMFR treatment improved the PGI-I scale at T4 (p = 0.02) but not at T12 (p = 0.40). CONCLUSIONS: This study confirmed that the addition of SMFR to BES treatment resulted in superior outcomes compared with those with BES alone in patients with MFPP. SIGNIFICANCE STATEMENT: Myofascial pelvic pain (MFPP) is a major contributor of female chronic pelvic pain. Myofascial release has been used commonly for better pain release; however, poor therapeutic effect due to poor patient compliance is common in clinical practice. Therefore, in future research, there is a need to investigate the effect of patient's self-myofascial release (SMFR) technique, which can eliminate the need for frequent office visits and improve patient compliance to some extent, in patients with MFPP.

The influence of phenolic environmental estrogen on the transcriptome of uterine leiomyoma cells: A whole transcriptome profiling-based analysis.

OBJECTIVE: The study aimed to recognize potential molecular targets and signal pathways whereby phenolic environmental estrogen promotes the proliferation of uterine leiomyoma cells. METHODS: Primary cultured cell lines of uterine leiomyoma were treated with 0.1% DMSO, 10.0µmol/L Bisphenol A (BPA), and 32.0µmol/L Nonylphenol (NP) for 48 h before RNA-seq was performed. Those genes affected by BPA and NP were identified. Then, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and Protein-protein Interaction (PPI) analysis were performed. Quantitative real-time polymerase chain reaction (q-PCR) and western blot were used to verify the differentially expressed gene and protein. RESULTS: Compared to with the control group, 739 differentially expressed genes were identified in both the BPA group and the NP group. GO enrichment analysis showed that the most enriched GO terms were connective tissue development and G1/S transition of mitotic cell cycle, and extracellular matrix. The results of KEGG enrichment analysis showed that differentially expressed mRNA were enriched mainly in three primary pathways, including environmental information processing, human diseases, and cellular processes. The cell cycle, PI3K-Akt signaling pathway are significantly enriched. The q-PCR and western blot verified the cell cycle associated genes and proteins were upregulated in both BPA group and NP group. Both BPA and NP activated the PI3K-AKT signaling pathway. CONCLUSION: Phenolic environmental estrogens may promote the proliferation and cell cycle progression of uterine leiomyoma cells through rapid non-genomic ER signaling, which leads to disordered cell cycle regulation and accelerates the transition of the cell cycle from G0/G1 phase to S phase. In addition, as an external stimulant, phenolic estrogen promotes the upregulation of inflammatory factors in uterine leiomyomas.

Prognostic Significance of CA125 Dynamic Change for Progression Free Survival in Patients with Epithelial Ovarian Carcinoma.

BACKGROUND This study aimed to investigate the value of CA125 dynamic change in PFS prediction for patients with epithelial ovarian carcinoma (EOC). MATERIAL AND METHODS Data analysis was performed using SPSS 24.0 statistical software with progression-free survival (PFS) as an outcome measure. Kaplan-Meier method was used to analyze the relationship between PFS and preoperative and postoperative NLR, PLR and CA125 levels, CA125 half-life, CA125-negative time, age, FIGO stage, histopathology, differentiation, vessel carcinoma embolus, and ascites. The survival curves were compared by the log-rank test. Based on the results of single-factor analysis, the Cox model was used for multifactor analysis to analyze independent risk factors affecting the PFS of epithelial ovarian carcinoma. RESULTS A total of 117 patients with EOC were selected from January 2012 to January 2019 to carry out a retrospective study. Univariate analyses showed that PFS of the patients with EOC was associated with differentiation, vessel carcinoma embolus, FIGO stage, CA125 half-life, CA12- negative time, and preoperative NLR (P<0.05). Multivariate analysis by the Cox model showed that vessel carcinoma embolus, CA125 half-life, differentiation, and preoperative NLR are the independent risk factors for PFS in patients with EOC. CONCLUSIONS The serum CA125 dynamic as reflected by CA125 half-life is the most important independent prognostic factor in patients with EOC. The simplicity of CA125 monitoring and its correlation with EOC patient survival can identify patients with poor prognosis through monitoring CA125 half-life, which can provide a reference value for use in clinical practice.

Laparoendoscopic single-site inguinal lymphadenectomy in gynecology: preliminary experience at a single institution.

PURPOSE: Laparoendoscopic single-site surgery (LESS), a promising innovation in minimally invasive surgery, has been used in treating gynecologic oncology diseases. There have been no reports in the literature regarding LESS for inguinal lymphadenectomy (LESS-IL) in gynecologic conditions. We aimed to evaluate the feasibility, safety, and outcomes of LESS-IL. METHODS: Six patients with vulvar or vaginal cancer underwent LESS-IL from July 2018 to March 2019. Data regarding the intraoperative and postoperative outcomes were analyzed. RESULTS: All patients successfully underwent a bilateral LESS-IL without conversion. LESS pelvic lymphadenectomy via an umbilical incision was also performed in a patient with vaginal cancer. The median operation time for the single-port laparoendoscopic inguinal lymphadenectomies was 105 min (range 70-134), with a median estimated blood loss of 108 ml (range 40-170). Median time of hospitalization was 7.5 days (range 5-10). A median of 11 (6-15) lymph nodes were dissected in a unilateral groin. The suction drains were removed after a median duration of 5 days (range 3-7). There were no skin-related or lymph-related postoperative complications. At a median follow-up period of 9 months, all the patients were alive and no recurrence was found. CONCLUSION: LESS-IL is a feasible and safe technique for the surgical management of gynecologic cancers.

Ovarian Cancer Stem Cells with High ROR1 Expression Serve as a New Prophylactic Vaccine for Ovarian Cancer.

Tumor vaccines offer a number of advantages for cancer treatment. In the study, the vaccination with cancer stem cells (CSCs) with high expression of the type I receptor tyrosine kinase-like orphan receptor (ROR1) was evaluated in a murine model for the vaccine's immunogenicity and protective efficacy against epithelial ovarian carcinoma (EOC). CD117+CD44+ CSCs were isolated from human EOC HO8910 cell line using a magnetic-activated cell sorting system; murine ID8 EOC suspension sphere cells, which are collectively known as cancer stem-like cells, were acquired from serum-free suspension sphere-forming culture. Mice were subcutaneously immunized with the repeat cycles of freezing and thawing whole HO8910 CD117+CD44+ CSCs and ID8 cancer stem-like cells, respectively, followed by a challenge with HO8910 or ID8 cells at one week after final vaccination. The results showed that the CSC vaccination significantly induced immunity against EOC growth and markedly prolonged the survival of EOC-bearing mice in the prophylactic setting compared with non-CSC vaccination. Flow cytometry showed significantly increased immunocyte cytotoxicities and remarkably reduced CSC counts in the CSC-vaccinated mice. Moreover, the protective efficacy against EOC was decreased when the ROR1 expression was downregulated by shRNA in CSC vaccines. The findings from the study suggest that CSC vaccines with high ROR1 expression were highly effective in triggering immunity against EOC in vaccinated mice and may serve as an effective vaccine for EOC immunoprophylaxis.

Uterine tumors resembling ovarian sex-cord tumor: A case report and literature review.

Uterine tumors resembling ovarian sex-cord tumor (UTROSCT) are a rare, multi-phenotype sex-cord tumors, containing a structure which is characteristic with the trabecular, cord, nests, and false adenoid arrangement. In addition, CD99-positive was a basis for diagnosis of the disease. With uncertain malignant potential and relapse, these patients should be closely followed up. This article is to summarize clinical and pathological features, diagnosis and differential diagnosis, treatment, and prognosis of UTROSCT.

Meta-analysis on the performance of p16/Ki-67 dual immunostaining in detecting high-grade cervical intraepithelial neoplasm.

AIM: Although routine screening contributes to substantial reductions in cervical cancer morbidity and mortality, the low specificity of HPV detection and limited sensitivity of cervical cytology necessitates the application of more optimized markers, such as the newly-introduced p16/Ki-67 dual-staining method. Here we reviewed several studies to evaluate the performance of this method in cervical cancer screening. METHODS: An electronic database search was performed on PubMed, Web of Science, CNKI and Wanfang Database for studies assessing p16/Ki-67 dual immunostaining in the diagnosis of high-grade cervical intraepithelial neoplasm (HGCIN) with abnormal cytological morphologies. Two reviewers screened literatures, extracted data and assessed the quality of the included studies independently. Meta-analysis was performed using ReV. Man 5.2 and Meta-DiSc 1.2 software packages. RESULTS: The absolute sensitivity of p16/Ki-67 dual staining for diagnosing HGCIN ranged from 80% to 94%, while the sensitivity of triage method with hrHPV testing ranged from 78% to 96%. The specificity of p16/Ki-67 testing and hrHPV detection for predicting absence of CIN2+ ranged from 39% to 79% and 15% to 44%, respectively. Quantitative meta-analysis showed that the pooled sensitivity of p16/ki-67 dual staining is 0.88 [95'CI (0.86-0.90)], the pooled specificity is 0.58 [95'CI (0.56-0.60)]. For hrHPV testing, the pooled sensitivity and pooled specificity is 0.94 [95'CI (0.93-0.96)] and 0.32 [95'CI (0.29-0.34)], respectively. CONCLUSIONS: p16/Ki-67 dual immunostaining had comparable sensitivity and improved specificity in screening HGCIN or CC when compared with hrHPV detection. Further studies may be beneficial to assess the efficacy of this novel biomarker, which can be potentially used as one of the initial screening assays.

The effect of TGF-ß signaling on regulating proliferation of uterine leiomyoma cell via ERα signaling activated by bisphenol A, octylphenol and nonylphenol in vitro.

OBJECTIVES: To study the transforming growth factor beta (TGF-ß) signaling pathway in interactions with estrogen receptor alpha (ERα) signaling pathway mediating the growth of human uterine leiomyoma (UL) activated by phenolic environmental estrogens (EEs). METHODS: The subcultured UL cells were used to determine the validation of TGF-ß3 for the viability of human UL cells using CCK-8 assay, mRNA expressions of ERα, and c-fos by quantitative reverse transcription polymerase chain reaction method, and expressions of p-Smad3, SnoN, and c-fos proteins by Western blot assay in each treatment group. RESULTS: Compared with each of EEs or TGF-ß3 treatment, slightly decrease in the proliferation rate of UL was detected in the coexistence of each EE with TGF-ß3. Interestingly, mRNA expressions of ERα and c-fos reduced in the setting of coexistence of TGF-ß3 and EEs. Somehow, the expression of p-Smad3 and c-fos proteins significantly decreased in each of E2, bisphenol A (BPA), nonylphenol (NP), and octylphenol (OP) group, as well as the expression of SnoN protein significantly reduced only in BPA and NP groups, followed by TGF-ß3 treatment. With the overlaid action of ICI 182,780, the expression of p-Smad3 protein significantly increased in OP group, but slightly increased in E2, BPA, NP, and OP groups. However, compared with the control group, the expression of SnoN and c-fos proteins significantly decreased in the same setting. CONCLUSION: Both ERα signaling pathway and TGF-ß signaling pathway have different roles in governing UL cell proliferation. The phenolic EEs can be a promoter to the proliferation of UL cells, which is mediated by ERα signaling pathway and cross-talked with TGF-ß signaling pathway.

Contraceptive efficacy and safety of estradiol valerate/dienogest in a healthy female population: a multicenter, open-label, uncontrolled Phase III study.

BACKGROUND: To investigate the efficacy and safety of a combined oral contraceptive containing estradiol valerate and dienogest (EV/DNG) in healthy Asian women. METHODS: In this multicenter Phase III study, women received oral EV/DNG in a 28-day regimen for 13 cycles. The primary efficacy endpoint was the number of unintended pregnancies, measured by the Pearl Index (PI); secondary efficacy endpoints included bleeding pattern and cycle control parameters. Adverse events were monitored during the study and overall satisfaction with treatment was determined on completion of the study. RESULTS: A total of 954 Asian women (97.7% of subjects assigned to study medication; mean age 33.4 years) were treated. Five pregnancies were reported during EV/DNG treatment over 796.34 relevant woman-years of exposure, giving an unadjusted PI of 0.63 and a cumulative failure rate of 0.0049; 3 pregnancies during EV/DNG treatment over 760.35 relevant woman-years of exposure gave an adjusted PI of 0.39. The bleeding pattern improved during the reporting periods within the study. The proportion of women who experienced withdrawal bleeding decreased with treatment (84.9% of women during Cycle 1 vs 79.3% in Cycle 13), and the mean length of withdrawal bleeding decreased with treatment (4.2 vs 3.4 days). The number and maximum length of intracyclic bleeding/spotting episodes also decreased with EV/DNG. EV/DNG was well tolerated, and 92% of women included in the study were very satisfied or somewhat satisfied with EV/DNG. CONCLUSION: EV/DNG showed high contraceptive efficacy, was well tolerated in Asian women, and may be effectively used in this population. CLINICAL TRIALS REGISTRY: ClinicalTrials.gov identifier: NCT01638910.

Performance of P16/Ki67 dual staining in triaging hr-HPV-positive population during cervical Cancer screening in the younger women.

BACKGROUND: Cervical cancer is the most common malignancy from the female reproductive tract, and usually develops from low-grade or high-grade squamous intraepithelial lesions (LSIL or HSIL). Detecting the precancerous lesion during the LSIL-HSIL-invasive cancer sequelae can effectively interrupt the oncogenesis and decrease the incidence of invasive carcinoma. The aim of this study is to evaluate the performance of P16/Ki67 dual staining in triaging hr-HPV-positive population. METHODS: Conventional gynecological examination, cervical cytology and hr-HPV testing were given to all patients. Specimens were collected for cytology examination and HPV genotyping. According to cytology results, patients were divided into cervical cancer group, HSIL group, LSIL group and benign lesion group. Sensitivity and specificity of the dual staining method in each histopathologic group was obtained and compared. RESULTS: Among the108 patients participated in the study, 65 were diagnosed as normal, 15 as LSIL, 20 as HSIL and 8 as CC, by histopathologic examination. Dual staining of p16/Ki67 on cytology specimen provided a positive predictive value of 86% and the negative predictive value of 96%. The sensitivity approached 96.43% when combining ThinPrep cytological test (TCT) with the dual staining, with a specificity of 60% in detecting HSIL. Joint detection of TCT and p16/Ki67 dual staining displayed the highest specificity among all the attempted combinations of detection methods. CONCLUSIONS: This study demonstrated that p16/Ki-67 dual staining represents an effective method for cervical cancer screening. Application of this method could lead to a reduction of unnecessary colposcopy referrals and misdiagnosis.

IL-21-secreting hUCMSCs combined with miR-200c inhibit tumor growth and metastasis via repression of Wnt/ß-catenin signaling and epithelial-mesenchymal transition in epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) with insidious characteristic manifests no symptoms in its early onset but most patients have advanced and distant cancer metastasis at diagnosis. Innovative early diagnosis and effective treatment of EOC are urgently needed. METHODS: In the study, we developed a novel agent of IL-21-secreting human umbilical cord mesenchymal stem cells (hUCMSCs) combined with miR-200c to evaluate its effects on SKOV3 EOC in vitro and in vivo. RESULTS: hUCMSCs-LV-IL-21 combined with miR-200c significantly inhibited the SKOV3 cell mobility and tumorigenesis compared with hUCMSCs-LV-IL-21, hUCMSCs-LV-vector, and hUCMSCs, respectively. These were reflected in decreasing the tumor sizes and elongating the tumor bearing nude mouse survival, accompanied with increasing the serum cytokine levels of IFN-γ, IL-21 and TNF-α as well as the splenocyte cytotoxicity. In addition, the expression of ß-catenin, cyclin-D1, Gli1, Gli2, and ZEB1 was decreased but the E-cadherin expression was increased in tumor tissues of mice treated with hUCMSCs-LV-IL-21 plus miR-200c. CONCLUSION: We demonstrated that the synergistic effect of fighting SKOV3 EOC is attributable to repression of Wnt/ß-catenin signaling and epithelial-mesenchymal transition in SKOV3 EOC. The findings may provide a new strategy for therapy of EOC.

Cytochrome P450 1A1 gene polymorphisms and cervical cancer risk: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aims to examine whether the MspI and Ile462Val polymorphisms of cytochrome P450 1A1 (CYP1A1) are associated with cervical cancer risk. METHODS: Eligible case-control studies were identified dated until July 2017. Pooled odds ratios (ORs) were used to assess the strength of the association between the two variants and cervical cancer risk. RESULTS: Thirteen studies were eligible (2148 cases and 2252 controls) concerning MspI polymorphism and 8 studies were eligible (1466 cases and 1690 controls) for Ile462Val polymorphism. MspI polymorphism seemed to result in cervical cancer risk in any genetic model (C allele vs T allele: OR = 1.44, 95% confidence interval [CI] = 1.16-1.79; heterozygous model: OR = 1.40, 95% CI = 1.08-1.82; homozygous model: OR = 2.22, 95% CI = 1.48-3.33, dominant model: OR = 1.50, 95% CI = 1.14-1.98 and recessive model: OR = 1.80, 95% CI = 1.35-2.41); similar significantly increased risk was found among Caucasians and Asians. Ile462Val polymorphism was associated with elevated cervical cancer risk (Val allele vs Ile allele: OR = 1.85, 95% CI = 1.27-2.67; heterozygous model: OR = 1.42, 95% CI = 1.28-1.61; homozygous model: OR = 2.94, 95% CI = 1.15-7.54; dominant model: OR = 2.00, 95% CI = 1.33-3.00); this finding was replicated upon Caucasian population. CONCLUSION: This meta-analysis demonstrated that polymorphisms in MspI and Ile462Val of CYP1A1 were risk factors for developing cervical cancer.

Targeted Therapy of Ovarian Cancer with Angiogenesis Inhibitors.

Specific blocking of interactions between ligands and receptors along the angiogenic pathways represents an effective approach for enhancing the efficacy as well as reducing adverse effects of chemotherapy. Over the past decade, there was a rapid progression in the application of this therapeutic strategy in cancer treatment. Anti-angiogenic therapy is the most promising targeted therapy for ovarian cancer. The addition of bevacizumab to conventional chemotherapy, either in the first-line setting or at disease relapse, may improve overall survival (OS) of ovarian cancer patients, at least in a subset of patients with poor prognosis. In this article, we summarize published data on the major agents used for anti-angiogenic therapy in ovarian cancers. We will review the molecular mechanisms, results of clinical trial of existing agents and describe the development of new agents. The limitations and side effects of angiogenesis inhibitor are also discussed.

A single-arm phase III study exploring the efficacy and safety of LNG-IUS 8, a low-dose levonorgestrel intrauterine contraceptive system (total content 13.5 mg), in an Asia-Pacific population.

OBJECTIVE: The objective was to evaluate the efficacy and safety of a low-dose levonorgestrel intrauterine system with total content 13.5 mg (average approximately 8 µg/24 h over the first year; LNG-IUS 8; Jaydess®) in an Asia-Pacific population. STUDY DESIGN: An open-label, single-arm phase III study conducted at 25 centers in China, Australia and Korea assessed LNG-IUS 8 use over 3 years in nulliparous and parous women (N=1114) aged 18-40 years with regular menstrual cycles (21-35 days). Primary outcome was pregnancy rate, expressed as the Pearl Index. Secondary outcomes included 3-year cumulative failure rate, treatment-emergent adverse events (TEAEs), discontinuation rate, bleeding profile and placement pain. RESULTS: The full analysis set comprised 925 women (mean age 31.6 years, 6.4% nulliparous). Overall unadjusted Pearl Index was 0.35 (95% confidence interval 0.15-0.70); the 3-year cumulative failure rate was 0.9% (95% confidence interval 0.4-1.9). TEAEs and study drug-related TEAEs were reported in 70.1% and 31.2% of women, respectively. Overall, 27.9% of women discontinued the study, 16.9% due to adverse events. Frequent or prolonged bleeding (World Health Organization criteria) decreased from the first to the twelfth 90-day reference intervals (from 5.0% to 0.7% and from 44.1% to 3.0%, respectively), and the percentage of women with amenorrhea increased over time (from 0.4% to 10.8%). Pain on placement was reported as "none" or "mild" in 91.9% of women. CONCLUSIONS: LNG-IUS 8 was an effective and well-tolerated contraceptive method, providing another option for women in the Asia-Pacific region. IMPLICATIONS: In this phase III study, LNG-IUS 8 was shown to be highly effective and well tolerated in an Asia-Pacific population and was not associated with any new or unexpected safety events. LNG-IUS 8 provides another contraceptive option for women in the Asia-Pacific region.

Synthetic paclitaxel-octreotide conjugate reverses the resistance of paclitaxel in A2780/Taxol ovarian cancer cell line.

The high mortality of ovarian cancer is partly due to the frequent resistance of ovarian cancer to current chemotherapy agents such as paclitaxel and platinum. Somatostatin analogue (SSTA) has been shown to inhibit the proliferation of some tumors through binding to somatostatin receptor (SSTR) and activation of Ras-, Rapl- and B-Raf-dependent extracellular signal-regulated kinase 2 (Erk2). It was reported that paclitaxel-octreotide conjugate (POC) exhibited enhanced tumor growth inhibition with reduced toxicity. In the present study, we prepared the POC and investigated its effects and mechanism for the reversal of drug resistance in paclitaxel-resistant ovarian cancer cell line. We demonstrated that treatment with POC led to more cell apoptosis than either paclitaxel or octreotide (OCT) alone. Moreover, the expression of multidrug resistance 1 (MDR1) and vascular endothelial growth factor (VEGF) mRNA, and protein decreased in a dose-dependent manner while the expression of SSTR remained stable following treatment with POC. Although the exact action, in vivo effects and pharmacologic kinetics of POC remain to be investigated, we have demonstrated the feasibility for the synthesis of POC, and more significantly, provided a potential approach to overcome the resistance of ovarian cancer against taxol. The findings also shed some new light on the mechanisms underlying the development of resistance to taxol by ovarian cancer cells.