CKAP2 promotes cervical cancer progression by modulating the tumor microenvironment via NF-κB signaling.

This study aimed to investigate whether CKAP2 could promote cervical cancer (CC) progression by modulating the tumor microenvironment (TME) via NF-κB signaling. The communication between cervical cancer cells and the TME, including THP-1 and HUVECs, was tested. Gain- and loss-of-function assays were performed to elucidate the role of CKAP2 in cervical cancer progression. Western blot analysis was exploited to investigate the potential involved mechanism involved. Here, we reported that cervical cancer tissues were enriched with macrophages and microvessels. CKAP2 increased the tumor-promoting macrophage population. The overexpression of CKAP2 not only promoted endothelial cell viability and tube formation but also increased vascular permeability, and vice versa. Moreover, CKAP2 promoted cervical cancer progression via NF-κB signaling. This effect could be blocked by the NF-κB signaling inhibitor JSH-23. Our findings indicated that CKAP2 could promote cervical cancer progression by modulating the TME via NF-κB signaling.

Single-cell transcriptomics reveals cellular heterogeneity and molecular stratification of cervical cancer.

Cervical cancer (CC) is the most common gynecological malignancy, whose cellular heterogeneity has not been fully understood. Here, we performed single-cell RNA sequencing (scRNA-seq) to survey the transcriptomes of 57,669 cells derived from three CC tumors with paired normal adjacent non-tumor (NAT) samples. Single-cell transcriptomics analysis revealed extensive heterogeneity in malignant cells of human CCs, wherein epithelial subpopulation exhibited different genomic and transcriptomic signatures. We also identified cancer-associated fibroblasts (CAFs) that may promote tumor progression of CC, and further distinguished inflammatory CAF (iCAF) and myofibroblastic CAF (myCAF). CD8+ T cell diversity revealed both proliferative (MKI67+) and non-cycling exhausted (PDCD1+) subpopulations at the end of the trajectory path. We used the epithelial signature genes derived from scRNA-seq to deconvolute bulk RNA-seq data of CC, identifying four different CC subtypes, namely hypoxia (S-H subtype), proliferation (S-P subtype), differentiation (S-D subtype), and immunoactive (S-I subtype) subtype. The S-H subtype showed the worst prognosis, while CC patients of the S-I subtype had the longest overall survival time. Our results lay the foundation for precision prognostic and therapeutic stratification of CC.

Partial Reconstruction of Uterus Cervix in Rat by Decellularized Human Uterine Cervical Scaffold Combined with Adipose-Derived Stem Cells (ADSCs).

Surgical management for cervical malformation remains as the main therapeutic challenge for gynecologists. A theoretical alternative is to generate a bioengineered uterus cervix, which requires scaffold structure and appropriate cellular constituents. Here, human uterine cervical tissue was decellularized with detergents to produce an acellular scaffold that retained extracellular matrix (ECM), characterized through histochemical studies and DNA assessments. Recellularized scaffold was then established by decellularized scaffold reseeding with adipose-derived stem cells (ADSCs) isolated from rats. We tested these bioengineering samples in a rat model of partial cervical defect and found that recellularized scaffold improved regeneration abilities of the uterine cervix, promoted better vascularization, and achieved positive pregnancy outcomes. These results suggest that decellularized human uterine cervical scaffold combined with ADSCs could be used for uterine cervical regeneration and provide insights into treatments for cervical malformation.

Diagnostic Dilemma of Retroperitoneal Schwannomas Encountered in a Specialized Gynecology Hospital.

BACKGROUND: This study analyzed the potential diagnosis and therapeutic challenges of retroperitoneal schwannoma (RSs) in a specialized gynecology hospital. METHODS AND MATERIALS: A retrospective review was performed in our hospital from 2000 to 2018. A literature search of RSs was conducted using PubMed database. RESULTS: 45 patients were identified (22 from our hospital and 23 from the literature review). The majority of patients presented asymptomatic (22/45). Among them, 25 cases were misdiagnosed as adnexal cysts, 13 uterine fibroids, 1 ovarian malignancy and 6 pelvic masses. Intraoperative exploration revealed that the masses were located in the retroperitoneal space. The median diameter was 6.2 cm (range 3.0-9.8 cm) in our hospital compared with 9.3 cm (6-15 cm) in literature review. Complete resection was performed in 37 patients and subtotal resection in 8 patients. The pathological results confirmed the diagnosis of benign schwannoma and no recurrence was found in the follow-up data. CONCLUSION: The preoperative diagnosis of RSs is difficult to make because of its nonspecific characteristics. In a specialized gynecology hospital, it is more important to differentiate the benign and malignant of mass before surgery. Surgical complete resection of tumor is recommended and recurrence is unusual after complete resection.

Single-cell transcriptomics reveals the landscape of intra-tumoral heterogeneity and transcriptional activities of ECs in CC.

Cervical cancer (CC) is the fourth leading cause of deaths in gynecological malignancies. Although the etiology of CC has been extensively investigated, the exact pathogenesis of CC remains incomplete. Recently, single-cell technologies demonstrated advantages in exploring intra-tumoral diversification among various tumor cells. However, single-cell transcriptome analysis (single-cell RNA sequencing [scRNA-seq]) of CC cells and microenvironment has not been conducted. In this study, a total of 20,938 cells from CC and adjacent normal tissues were examined by scRNA-seq. We identified four tumor cell subpopulations in tumor cells, which had specific signature genes with different biological functions and presented different prognoses. Among them, we identified a subset of cancer stem cells (CSCs) that was related to the developmental hierarchy of tumor progression. Then, we compared the expressive differences between tumor-derived endothelial cells (TECs) and normal ECs (NECs) and revealed higher expression of several metabolism-related genes in TECs. Then, we explored the potential biological function of ECs in vascularization and found several marker genes, which played a prior role in connections between cancer cells and ECs. Our findings provide valuable resources for deciphering the intra-tumoral heterogeneity of CC and uncover the developmental procedure of ECs, which paves the way for CC therapy.

Occult vaginal cancer recurrence after hysterectomy: a case report and literature review.

Vaginal cancer is a rare disease of the lower genital tract. We present the case of a 54-year-old woman with occult vaginal cancer after hysterectomy for cervical intraepithelial neoplasia (CIN) III. Despite persistently negative cytology and colposcopy results, a lesion was finally detected by vagino-recto-abdominal examination and she underwent radical parametrectomy and lymph node dissection. We consider the possibility that transabdominal suturing of the vaginal cuff after hysterectomy may reduce the ability to detect subsequent vaginal lesions, and discuss the benefits of a vaginal suture approach. We recommend that suturing the vagina apex transvaginally instead of transabdominally would benefit patients during follow-up.

Transplantation of menstrual blood-derived mesenchymal stem cells (MbMSCs) promotes the regeneration of mechanical injuried endometrium.

PURPOSE: The ultimate cause of intrauterine adhesions (IUAs) is the substantial destruction of the endometrium, which makes the regeneration of endometrium difficult. The purpose of this study was to observe menstrual blood-derived mesenchymal stem cells (MbMSCs)'s effect on the endometrial regeneration with different methods of transplantation. We also studied whether MbMSCs transfected with the FGF2 gene can improve the regenerative effect. METHODS: 75 female SD rats with endometrium removed were used as IUA models. These IUA models were divided into 5 groups: group A was the IUA control, group B received a scaffold transplant, group C received a scaffold+MbMSC transplant, group D received a scaffold+FGF2-MbMSC transplant, and group E received FGF2-MbMSCs injected via the tail vein. After the intervention, 5 rats from each group were sacrificed on the 7th day and the 28th day respectively. The distribution of MbMSCs in endometrium was traced using enhanced green fluorescent protein. The endometrial morphology, number of endometrial glands, area of endometrial fibrosis and immunohistochemistry (IHC) of Ki67, VEGF, and CD31 were evaluated. In addition, the fertility of all groups was tested. RESULTS: On the 7th day after transplantation, enhanced green fluorescent protein showed that there were more MbMSCs in the uterine cavity of group D than that of group E. The endometrial morphology of groups A and B was atrophic and thinned with a high proportion of fibrosis in the endometrium. The endometrium of groups C, D and E was thickened, contained more glands, exhibited reduced fibrosis, and had increased expression of Ki67, VEGF and CD31. The endometrial regenerative effect from high to low was D > C > E with significant differences between each two groups. The fertility test verified the regenerative effect. CONCLUSIONS: These results suggest that the injection of MbMSCs into the tail vein was an effective way to stimulate endometrial regeneration, but the effect was not so well as the intrauterine transplant of MbMSCs with scaffold. The FGF2-transfected MbMSCs exhibited enhanced regenerative effect.

Cervical Cancer: Emerging Immune Landscape and Treatment.

Immune cells are essential for defending the body's balance and have increasingly been implicated in controlling tumor growth. In cervical cancer (CC), the immune landscape is extensively connected with human papillomavirus (HPV) status. Recent insights from studies have revealed that as a result of infection with HPV, immune cell populations such as lymphocytes or monocytes change during carcinogenesis. Immune therapy, in particular checkpoint inhibitors, those targeting PD-1 or PD-L1, has shown promising efficacy. This article reviews the immune landscape and immunotherapy of CC.

Evaluation of Uterine Artery Embolization on Myoma Shrinkage: Results from a Large Cohort Analysis.

OBJECTIVE: There are still contradictory opinions on the success rates of uterine artery embolization (UAE) for the treatment of myomas. In this scenario, our study aims to assess the effect of UAE on myoma shrinkage. MATERIALS AND METHODS: The study included 337 women in reproductive age affected by a single symptomatic intramural myoma and declined surgery, undergoing UAE. The uterus and myoma diameters and volumes were determined on ultrasonographic scans before and 3, 6, and 12 months after the procedure. RESULTS: The mean uterine volume before intervention was 226.46 ± 307.67 mm3, whereas myoma volume was 51.53 ± 65.53 mm3. Further myoma progression was registered in only four patients. In remaining women, uterus volume in average decreased for 149.99 ± 156.63 mm3, whereas myomas decreased for 36.57 ± 47.96 mm3. The mean volume reduction rate of the uterus was 49.54 ± 35.62 and for myoma was 57.58 ± 30.71. A significant decrease in both uterine and myoma volume was registered in every stage of the follow-up. The highest average decrease in uterine volume was in the first 3 months and myoma volume between 3 and 6 months following UAE. After 12 months follow-up, successful outcome (volume regression >50% respect to the baseline) was registered for uterus in 97.4% and for myoma in 67.9% of investigated patients. CONCLUSION: UAE was proven to allow a good success rate and can be considered as an effective alternative procedure for myoma treatment.

Smad signaling coincides with epithelial-mesenchymal transition in a rat model of intrauterine adhesion.

PURPOSE: Intrauterine adhesion (IUA) is a fibrotic disease mainly caused by tissue injury, yet the mechanism is poorly understood. The aim of this study was to investigate the roles of TGF-ß1/BMP7/Smad signaling coincident with epithelial-mesenchymal transition (EMT) in IUA. METHODS: Twenty-four female SD rats were divided into IUA and sham groups. For each animal, a mechanical injury or sham operation was performed on the left uterus (IUA-L, Sham-L), and the right uterus (IUA-R, Sham-R) was used as the control. Animals were sacrificed in batches on days 7 and 28. The endometrial morphology, number of endometrial glands, microvascular density (MVD), area of endometrial fibrosis and immunohistochemistry (IHC) analysis of biomarkers of EMT, as well as levels of TGF-ß1, phosphorylated Smad3 (pSmad3), BMP7, phosphorylated Smad1/5 (pSmad1/5) and estrogen receptor (ER) were evaluated. Besides, the correlation between these IHC markers was also analyzed. RT-PCR and western blot were used to test relevant genes. RESULTS: Compared with other groups, the IUA-L group showed a significant decrease in the number of glands and MVD. And it also showed a significant increase in the stromal fibrosis rate and a-SMA level. Moreover, in the IUA-L group, TGF-ß1 and pSmad3 levels were consistently high, and levels of BMP7, pSmad1/5 and ER were low. EMT markers E-cadherin was decreased, while N-cadherin was increased. Sham and control groups showed no significant difference in these markers. In addition, E-cadherin with a-SMA, fibrosis rate with BMP7, TGF-ß1 with pSmad3 and BMP7 with pSmad1/5 showed correlation in IUA-L group, which had statistical significance. The mRNA expression of TGF-ß1, a-SMA and ccn2 in 7 d IUA-L was higher than 7 d IUA-R while BMP7 was lower, which had significant difference. The protein expression of BMP7 in 7 d IUA-L was lower than 7 d IUA-R, which had significant difference. CONCLUSIONS: These results suggest a potential role of Smad signaling together with EMT in endometrial fibrosis development.

Risk Factor Analysis of Persistent High-Grade Squamous Intraepithelial Lesion After Loop Electrosurgical Excision Procedure Conization.

OBJECTIVE: The aim of the study was to analyze the clinical outcomes of high-grade squamous intraepithelial lesion (HSIL) 6 months after loop electrosurgical excision procedure (LEEP). We explored the risk factors of persistent cervical HSIL after LEEP and evaluated the methods of follow-up. PATIENTS AND METHODS: This retrospective study included women who underwent a LEEP and had a diagnosis of HSIL in their LEEP specimen during 2011 to 2015. The purpose was to determine the risk factors among these women for having persistent HSIL disease at their 6-month follow-up visit. At their follow-up visit, each woman underwent cervical cytology and high-risk human papilloma virus (hrHPV) testing, colposcopy-directed punch biopsy, and/or endocervical curettage. RESULTS: A total of 3582 women were enrolled. There were 9 cases invasive cervical cancer found and 101 women had persistent HSIL. The persistence rate was higher in women 50 years or older. The circumference, length, and width of LEEP specimens did not differ statistically between the persistent and nonpersistent group. The persistence rate among women with positive LEEP specimen margins was higher than among women with negative margins. Positive endocervical margins were associated with a higher rate of persistence than positive ectocervical margins. Multivariate logistic analysis showed that age, positive margins, abnormal cytology, and positive hrHPV during follow-up were all independent risk factors for persistent HSIL lesions. CONCLUSIONS: Being 50 years or older, positive margins, particularly endocervical margins, and having abnormal cytology and positive hrHPV testing during follow-up were risk factors for persistent HSIL lesions after LEEP conization. Colposcopy plays an indispensable role in the diagnosis of persistent HSIL and progression.