Aberrant expression of Notch1/numb/snail signaling, an epithelial mesenchymal transition related pathway, in adenomyosis.

BACKGROUND: Epithelial mesenchymal transition (EMT) is involved in the pathogenesis of adenomyosis, and Notch signaling is crucial to EMT. The objective of this study was to explore Notch1/Numb/Snail signaling in adenomyosis. METHODS: The expression levels of the members of the Notch1/Numb/Snail signaling cascade in normal endometria (proliferative phase: n = 15; secretory phase: n = 15; postmenopausal phase: n = 15) and adenomyotic endometria (proliferative phase: n = 15; secretory phase: n = 15) were determined by immunohistochemistry analysis. RESULTS: We found that the expressions of Notch1 and the EMT-related proteins N-cadherin, Snail and Slug were upregulated in the ectopic endometrium of adenomyosis compared with normal endometrium. Numb, a negative regulator of Notch signaling, was significantly decreased in adenomyosis. In addition, reduced immunoexpression of E-cadherin was observed in adenomyosis. CONCLUSIONS: We conclude that Notch1/Numb/Snail signaling plays an important role in the pathogenesis and development of adenomyosis.

Can magnetic resonance spectroscopy differentiate endometrial cancer?

OBJECTIVES: To investigate whether the choline-containing compounds (Cho) obtained from three-dimensional (1)H magnetic resonance (MR) spectroscopy can differentiate endometrial cancer (ECa) from benign lesions in endometria or in submucosa (BLs-ESm) and is associated with the aggressiveness of ECa. METHODS: Fifty-seven patients (ECa, 38; BLs-ESm, 19) underwent preoperative multi-voxel MR spectroscopy at 3.0 T. The ratio of the sum of the Cho peak integral to the sum of the unsuppressed water peak integral (Cho/water) and the coefficient of variation (CV) used to describe the variability of Cho/water in one lesion were calculated. RESULTS: Mean Cho/water (±standard deviation [SD]) was (3.02 ± 1.43) × 10(-3) for ECa and (1.68 ± 0.33) × 10(-3) for BLs-ESm (p < 0.001). Mean Cho/water was (4.42 ± 1.53) × 10(-3) for type II ECa and (2.65 ± 1.17) × 10(-3) for type I ECa (p = 0.001). There were no significant differences among different stages of ECa (p = 0.107) or different grades of ECa (p = 0.142). The Cho/water was positively correlated with tumour stage (r = 0.386, p = 0.017) and size (r = 0.333, p = 0.041). The CV was also positively correlated with tumour stage (r = 0.537, p = 0.001) and size (r = 0.34, p = 0.037). CONCLUSION: The Cho/water can differentiate ECa from BLs-ESm and differentiate type II from type I ECa, but cannot differentiate different stages of ECa or different grades of ECa. Cho/water increased with the increase of tumour stage and size. KEY POINTS: • First report to attempt to assess ECa aggressiveness with magnetic resonance spectroscopy (MRS). • MRS can differentiate type I from type II ECa. • MRS can differentiate ECa from BLs-ESm. • MRS cannot differentiate different stages of ECa or different grades of ECa. • Cho/water increased with the increase of tumour stage and size.

[Impact on ovarian reserve function by different homostasis methods during laparoscopic cystectomy in treatment of ovarian endometrioma].

OBJECTIVE: To investigate the impact on ovarian reserve function by different hemostasis methods during laparoscopic surgery in treatment of ovarian endometrioma. METHODS: From September 2008 to February 2010, 162 cases with ovarian endometrioma undergoing laparoscopic surgery in Shandong Provincial Hospital were enrolled in this study. At the 3rd day of the menstrual cycle before surgery and the 1st, 3rd, 6th and 12th cycle after surgery, serum FSH and anti-mullerian hormone (AMH) and ultrasound basal antral follicle count (AFC) and peak systolic velocity (PSV) were examined and compared. Based on hemostasis method, those patients were divided into 3 groups, including 54 cases in bipolar hemostasis, 54 cases in ultrasonic scalpel hemostasis and suture after excision of endometrioma. RESULTS: (1) Before surgery: no significant different factors among three groups before surgery were observed, including age, size of endometrioma, the level of FSH, AMH, AFC, PSV(P > 0.05). (2) Ovarian reserve function after surgery: 1) FSH: at the 1st, 3rd, 6th and 12th month follow-up, the FSH in the bipolar group was (11.7 ± 4.0), (9.9 ± 4.0), (9.5 ± 4.3), (9.5 ± 3.9) U/L, and the FSH in ultrasonic scalpel group was (11.4 ± 4.3), (9.7 ± 4.0), (9.2 ± 3.7), (9.9 ± 4.6) U/L, were significantly higher than (9.3 ± 3.8), (6.7 ± 3.0), (6.5 ± 3.2), (6.4 ± 2.2) U/L in suture group respectively (all P < 0.05). 2) AMH: at the 1st, 3rd, 6th and 12th month follow-up, the AMH in the bipolar group was (1.8 ± 0.9), (1.8 ± 1.0), (1.9 ± 1.0), (2.0 ± 1.0) µg/L, and the AMH in the ultrasonic scalpel group was (1.6 ± 0.8), (1.8 ± 1.0), (2.0 ± 1.1), (2.1 ± 1.0) µg/L, which were significantly lower than (2.8 ± 1.7), (2.9 ± 1.6), (3.0 ± 1.3), (3.2 ± 1.5) µg/L in suture group, respectively (all P < 0.05). 3) AFC: there was no significant difference of APC among the three groups in the 1st month after surgery. However, at the 3rd, 6th and 12th month follow-up, the AFC of 4.8 ± 1.4, 5.9 ± 1.5, 6.1 ± 1.5 in the suture group was significant higher than 3.7 ± 1.4, 4.1 ± 1.4, 4.0 ± 1.5 in bipolar group and 3.6 ± 1.3, 4.0 ± 1.1, 3.9 ± 1.5 in ultrasonic group, respectively (all P < 0.05). 4) PSV: at the 1st, 3rd, 6th and 12th month follow-up, the PSV of the bipolar group (7.9 ± 3.5), (8.1 ± 3.3), (8.4 ± 3.1), (8.6 ± 3.0) cm/s in bipolar group and (8.1 ± 3.5), (8.0 ± 3.0), (7.9 ± 3.2), (8.0 ± 2.9) cm/s in ultrasonic group were significant lower than (10.9 ± 3.3), (12.0 ± 3.2), (11.8 ± 3.0), (12.1 ± 4.1) cm/s in suture group, respectively. (all P < 0.05). CONCLUSIONS: Bipolar or ultrasonic scalpel hemostasis during laparoscopic excision of ovarian endometrioma is associated with a significant reduction in ovarian reserve. Electrocoagulation of the ovarian tissue should be avoided.

A case of endocervical adenocarcinoma of the gastric type that was repeatedly misdiagnosed: A case report and literature review.

RATIONALE: Gastric-type endocervical adenocarcinoma (GAS) is non-human papillomavirus-associated cervical cancer and the location of the lesions is in the cervical canal mostly. PATIENT CONCERNS: Vaginal discharge is mistakenly thought to be caused by uterine fibroids. Misdiagnosis leads to disease progression. DIAGNOSES: Magnetic resonance imaging is an auxiliary tool and pathology is the gold standard for the diagnosis. INTERVENTIONS: Surgery and supplementary radiotherapy and chemotherapy ± targeted therapy are the main treatment methods. OUTCOMES: GAS with high malignant degree poor prognosis and insidious development, tends to develop toward the cervical canal and is lack of specific tumor markers, so it is easy to misdiagnosis and missed diagnosis. LESSONS: This case highlights the importance of improving the understanding of GAS. And when patients perform vaginal discharge, cervical canal hypertrophy, and cervical cancer screening negative, clinicians ought to be highly alert to GAS.

Increased NKG2A+CD8+ T-cell exhaustion in patients with adenomyosis.

Immune dysregulation has long been proposed to be associated with adenomyosis, but the underlying mediators and mechanisms remain largely unexplored. Here, we used flow cytometry to investigate the alterations in immune cell subsets in adenomyotic uteri and analyze the phenotype and function of abnormal immune cells. We found that an increase in cluster of differentiation (CD)8+ T-cell number was the predominant alteration in ectopic lesions in patients with adenomyosis and was significantly associated with the severity of adenomyosis. Importantly, we identified an exhausted natural killer group protein 2A (NKG2A)+CD8+ T-cell subset that was associated with the severity of adenomyosis and found that the number of these cells was significantly increased in the eutopic endometrium and ectopic lesions. In addition, the increases in the expression of NKG2A ligand histocompatibility leucocyte antigen E and interleukin-15 in glandular epithelial cells in the adenomyotic microenvironment might contribute to CD8+ T-cell exhaustion by promoting NKG2A expression on CD8+ T cells or inhibiting the effector function of these cells. In conclusion, our data revealed a previously unrecognized role for NKG2A+CD8+ T-cell exhaustion in the pathogenesis of adenomyosis, indicating that therapeutic interventions designed to target and reinvigorate exhausted CD8+ T cells may be beneficial for patients with adenomyosis.

Current Status of Tissue Regenerative Engineering for the Treatment of Uterine Infertility.

With the recent developments in tissue engineering, scientists have attempted to establish seed cells from different sources, create cell sheets through various technologies, implant them on scaffolds with various spatial structures, or load scaffolds with cytokines. These research results are very optimistic, bringing hope to the treatment of patients with uterine infertility. In this article, we reviewed articles related to the treatment of uterine infertility from the aspects of experimental treatment strategy, seed cells, scaffold application, and repair criteria so as to provide a basis for future research.

MicroRNA-324-5p affects the radiotherapy response of cervical cancer via targeting ELAV-like RNA binding protein 1.

Cervical cancer (CC) seriously threatens the health of women. Radiation therapy (RT) is the major treatment for CC. However, the recurrent CC can acquire resistance to RT. Thus, it is necessary to find a new method for reversing RT resistance in CC. It has been reported that miR-324-5p can suppress the progression of multiple cancers. However, whether it can reverse resistance to RT in CC remains unclear. qRT-PCR and Western blotting were used to detect gene and protein expression in CC cells, respectively. Cell proliferation was tested by CCK-8 assay and colony formation assay. In addition, cell apoptosis was detected by flow cytometry. Transwell assays were performed to detect cell migration. Dual luciferase reporter assay and TargetScan were used to explore the targets of microRNA-324-5p (miR-324-5p). MiR-324-5p was downregulated in CC cells. Overexpression of miR-324-5p sensitized CC cells to RT. In addition, miR-324-5p mimics significantly induced apoptosis and inhibits the migration of CC cells in the presence of 137 Cs ionizing radiation. Furthermore, miR-324-5p sensitized CC cells to ionizing radiation by targeting ELAV-like RNA binding protein 1 (ELAVL1). MiR-324-5p overexpression affects the radiotherapy response of CC by targeting ELAVL1, which may serve as a new target for the treatment of CC.

Expression profile of long non-coding RNAs is altered in endometrial cancer.

This study was to uncover the role of long non-coding RNA (lncRNA) in the process of endometrial cancer (EC) development using microarray technique to obtain the expression profiles of lncRNAs in EC and its adjacent normal tissues. A total of 45 pieces of pathologically-proven EC tissues were used in this study. All samples were frozen in liquid nitrogen immediately after resection and stored at -80°C for future use. The detection of lncRNA and transcripts was conducted using microarray analysis. To understand the biochemical function of lncRNA, bioinformatics analyses (gene ontology and pathway analyses) were performed. To further investigate the relationship between lncRNAs and EC, subgroup analysis was conducted. In order to validate the consistency of the lncRNAs with microarray data, qRT-PCR was performed. In this study, 30586 lncRNAs and 26109 transcripts (fold change ≥ 2.0) were found in the tested EC. In particular, compared with normal tissues, 4010 the lncRNA were up-regulated, and 3350 of them were down-regulated. Seven of the lncRNAs were in accordance with microarray data in qRT-PCR. Among these lncRNAs, 3 were up-regulated and 4 were down-regulated. Furthermore, pathway analysis revealed that 24 pathways were correlated to the up-regulated transcripts, while 27 pathways were associated with the down-regulated transcripts. Our study demonstrated that the expressions of a large amount of lncRNAs were altered in EC in comparison to normal tissues, suggesting that lncRNAs could potentially serve as a diagnostic biomarker that is beneficial for the diagnosis and therapy of EC.

Hyperreactio luteinalis after delivery: a case report and literature review.

Hyperreactio luteinalis (HL), characterized by bilateral functional multicystic ovarian enlargement during pregnancy and puerperium, mostly occurs in third trimester. As a rare benign disease, HL is usually self-limited. However, some cases are dignosed by unnecessary operation. This is a case report of HL appearing a week after delivery. The patient took a puncture biopsy of ovarian tumor guided by ultrasound to rule out of ovarian malignancy. Without any specific treatment, the disease regressed spontaneously.

Can the signal-to-noise ratio of choline in magnetic resonance spectroscopy reflect the aggressiveness of endometrial cancer?

RATIONALE AND OBJECTIVES: To differentiate endometrial cancer (ECa) from benign lesions in endometrial or in submucosa (BLs-ESm), and investigate whether the signal-to-noise ratio (SNR) of choline-containing compounds (Cho) obtained from three-dimensional (1)H magnetic resonance spectroscopy (MRS) is associated with the aggressiveness of ECa. MATERIALS AND METHODS: Thirty-three patients with ECa and 15 patients with BLs-ESm underwent preoperative multivoxel (1)H MRS at 3 T MR. The amplitude of Cho peak of each voxel was recorded, and the corresponding SNR of Cho peak (ChoSNR) was calculated. The maximum ChoSNR (max ChoSNR) for each lesion was identified. The max ChoSNR of ECa and BLs-ESm, as well as type I ECa and type II ECa, was compared. The relationship between max ChoSNR and pathologic characteristics of tumors, including tumor grade, stage, type, and tumor size, was analyzed. RESULTS: The mean max ChoSNR (±standard deviation [SD]) was 30.93 ± 16.89 for ECa and 10.40 ± 3.07 for BLs-ESm (P < .001). The mean max ChoSNR for type II ECa (48.54 ± 21.46) was higher than that for type I ECa (26.19 ± 12.02, P = .001). There were no significant differences among different grades (P = .449). The Spearman coefficient between max ChoSNR and stage was 0.423 (P = .014); the difference existed only between Ia and III ECa (P = .048). The Pearson coefficient between ChoSNR and tumor size was 0.515 (P = .002). CONCLUSIONS: The max ChoSNR obtained from MRS can differentiate ECa from BLs and type I ECa and type II ECa, but cannot differentiate between each grade ECa and each International Federation of Gynecology and Obstetrics stage ECa. However, max ChoSNR increased with the increase in International Federation of Gynecology and Obstetrics stage and size of ECa.