Gynecologic and Obstetric Investigation最新文献

Objective: Chemoresistance in ovarian cancer results in treatment failure, yet underlying mechanisms that regulate chemoresistance remain largely unclear. There is emerging evidence relating ovarian cancer drug resistance with bioactive sphingolipids and regulation of sphingolipid metabolism. This work investigated the expression and function of ceramide kinase (CerK), a lipid kinase that regulates central bioactive sphingolipids, in ovarian cancer, as well as the therapeutic potential of targeting CERK.

Design: The levels of ceramide, ceramide 1-phosphate (C1P), and Cerk in ovarian cancer and normal counterparts were measured. Functions of Cerk in ovarian cancer were examined.

Materials, setting, methods: Immunohistochemistry, ELISA, and mass spectrometry methods were used to measure the level of ceramides, C1P, and CerK in primary tissues. Proliferation and apoptosis assays were performed in ovarian cancer cells after CERK depletion, CERK overexpression, and NVP-231 treatment in the absence or presence of cisplatin.

Results: Compared to normal ovarian cells, CerK and its mediating bioactive sphingolipids ceramide and C1P were decreased in ovarian cancer tissues. Interestingly, cisplatin-resistant ovarian cancer cells displayed increased CerK, decreased ceramide, and increased C1P, and furthermore, that CerK level was closely associated with ceramide and C1P levels in ovarian cancer cells. Functional analysis demonstrated that CerK overexpression was sufficient to promote growth and confer chemoresistance in ovarian cancer cells. CerK inhibition via both genetic and pharmacological approaches suppressed growth and induced apoptosis in cisplatin-resistant cells, and furthermore, this significantly augmented cisplatin's efficacy.

Limitations: The functional analysis of C1P was performed on in vitro ovarian cancer cells. In vivo studies were needed to further confirm the effects of CERK inhibition.

Conclusions: Our work is the first to show the critical role of CerK as the underlying mechanism of ovarian cancer chemoresistance, through regulating ceramide and C1P.

Objectives: Midurethral slings are considered the gold standard for the surgical treatment of stress urinary incontinence (SUI), with an efficacy up to 80%. Another therapeutic option is the use of bulking agents, which create an artificial mass in the urethral submucosa, with an efficacy varying from 64% to 74%. Although bulking agents have a lower risk of complications than midurethral sling surgery, they are mainly used in case a midurethral sling is not an option or if midurethral sling surgery failed to cure stress urinary incontinence. In this study, we offer all patients with SUI in secondary care a choice between a single-incision midurethral sling procedure and treatment with a bulking agent. We want to examine patient preference and patient satisfaction for both procedures. We expect that offering both interventions in combination with standardized counselling will result in high patient satisfaction.

Design: In this non-randomized controlled trial, 266 patients will be objectively counselled for both interventions, after which all patients will choose between single-incision midurethral slings and polyacrylamide hydrogel (PAHG), followed by the standard care procedure for women with SUI.

Participants/materials, setting, methods: From January 1, 2021, onward, all consecutive adult patients (between 18 and 80 years of age) attending the outpatient gynaecology department with objectively confirmed, moderate to severe SUI will be eligible for enrolment in this non-randomized study. The primary outcome is patient satisfaction at 1 year, measured by the Patient Global Impression of Improvement; secondary outcomes are patient satisfaction at 3 months, objective and subjective cure at 3 months and 1 year, adverse events, post-operative pain, and cost-effectiveness. Differences in outcome measures will be assessed through logistic and linear regression analyses, both unadjusted and adjusted with covariate adjustment using the propensity score.

Results: No results are available yet.

Limitations: The major disadvantage of this study design is the potential confounding bias. We intend to eliminate this bias by applying propensity scoring.

Conclusion: By designing a non-randomized patient preference trial, we not only expect to demonstrate high patient satisfaction with both interventions but also provide insight into the possible role of PAHG-injections in the treatment of female SUI as a first-choice non-conservative treatment.

Objectives: The effect of telomerase inhibitor BIBR1532 on endometriotic cells was investigated to explore the inhibitory effect of targeting telomerase on endometriosis.

Design: In vitro primary cell culture study. Participants/Materials: Primary endometrial cells derived from eutopic and ectopic endometrium in patients with endometriosis.

Setting: The study was conducted in the university hospital.

Methods: Paired eutopic and ectopic endometrial cells were collected from 6 patients from January 2018 to July 2021. A TRAP assay was performed to detect the telomerase activity of the cells. MTT, cell cycle, apoptosis, migration, and invasion assays were performed to study the inhibitory effect of BIBR1532. Enrichment analysis was performed to identify the key pathways involved in endometriosis progression and telomerase action. Then, Western blotting was used to investigate the expression of related proteins.

Results: BIBR1532 treatment significantly inhibited the growth of eutopic and ectopic endometrial cells, with apoptosis and cell cycle signaling involved. Migration and invasion, important characteristics for the establishment of ectopic lesions, were also inhibited by BIBR1532. The MAPK signaling cascade, related to telomerase and endometriosis, was decreased in eutopic and ectopic endometrial stromal cells with the treatment of BIBR1532.

Limitations: The severe side effects of telomerase inhibitors might be the main obstacle to clinical application, so it is necessary to find better drug delivery methods in vivo.

Conclusions: The telomerase inhibitor BIBR1532 affects endometrial cell proliferation, migration, and invasion in endometriosis.

Introduction: Placental mesenchymal dysplasia (PMD) is a benign lesion that is often misdiagnosed as complete (CHM) or partial hydatidiform mole. PMD usually results in live birth but can be associated with several fetal defects. Herein, we report PMD with CHM in a singleton placenta with live birth.

Case presentation: A 34-year-old gravida 2, para 1, living 1 (G2P1L1) woman was referred on suspicion of a molar pregnancy in the first trimester. Maternal serum human chorionic gonadotrophin levels were increased during early pregnancy, with multicystic lesions and placentomegaly observed on ultrasonography. Levels decreased to normal with no fetal structural abnormalities observed. A healthy male infant was delivered at 34 gestational weeks. Placental p57KIP2 immunostaining and short tandem repeat analysis revealed three distinct histologies and genetic features: normal infant and placenta, PMD, and CHM. Gestational trophoblastic neoplasia was diagnosed and up to fourth-line chemotherapy administered.

Conclusion: Distinguishing PMD from hydatidiform moles is critical for avoiding unnecessary termination of pregnancy. CHM coexisting with a live fetus rarely occurs. This case is unique in that a healthy male infant was born from a singleton placenta with PMD and CHM.

Introduction: This study was performed to clarify the effects of angiotensin converting enzyme (ACE) I/D polymorphism on the risk of insulin resistance and polycystic ovary syndrome (PCOS).

Methods: Six genotype models and the mean difference (MD)/standardized mean difference (SMD) were applied to evaluate the effects of ACE I/D polymorphism on insulin resistance and PCOS risk.

Results: Thirteen studies with 3,212 PCOS patients and 2,314 controls were collected. In the pooled analysis and Caucasian subgroup, the ACE I/D polymorphism was significantly associated with PCOS risk, even after removing the non-Hardy-Weinberg equilibrium (HWE) studies. Moreover, the positive effect of ACE I/D polymorphism in PCOS was mainly presented in Caucasians (removing non-HWE, DD + DI vs. II: odds ratio [OR] = 2.15, p = 0.017; DD vs. DI + II: OR = 2.64, p = 0.007; DD vs. DI: OR = 2.48, p = 0.014; DD vs. II: OR = 3.31, p = 0.005; D vs. I: OR = 2.02, p = 0.005) compared to Asians. Interestingly, only in Asians was the ACE I/D polymorphism significantly correlated to insulin levels (DI vs. II: SMD = 0.19, 95% CI = (0.03, 0.35), p = 0.023) and HOMA-IR (DI vs. II: MD = 0.50, 95% CI = (0.05, 0.95), p = 0.031).

Conclusions: The D allele of the ACE I/D polymorphism promotes PCOS development. Moreover, the ACE I/D polymorphism was also associated with insulin-resistant PCOS, especially among Asians.

Objectives: The purpose of this study was to investigate the effect of aspirin on epithelial HPV16-transformed cells and its antitumor effects, in an experimental HPV16-positive tumor model.

Design: The design of the study is experimental (in vitro and in vivo).

Participants/materials, setting, and methods: SiHa and BMK-16/myc cells were treated with aspirin and cell proliferation was determined by MTT; Caspase-Glo 3/7 Assay was used to determine apoptosis. The tumor-bearing mice group was treated with 50 mg/gr/day of aspirin (orally) during 30 days and the antitumor effect was determined.

Results: Here, we provide evidence that aspirin has a negative effect on proliferation and induces apoptosis in the human (SiHa) and murine (BMK-16/myc) HPV16 cells. Furthermore, aspirin showed inhibition of tumor growth, and in mice treated with aspirin prior to implantation of tumor cells, the tumor growth was delayed. Also, the effect of aspirin increased survival in tumor-bearing mice and in mice pre-treated with aspirin.

Limitations: It is necessary to carry out in vitro and in vivo studies of the molecular mechanisms involved in the effects of aspirin on tumor cells.

Conclusion: Aspirin showed antiproliferative effects in tumor cells and inhibited tumor progression and could be effective as a chemopreventive agent. Thus, aspirin deserves further exploration for the treatment of cervical cancer and other neoplasms.