Promotive actions of lncRNA EBLN3P involved in cervical cancer progression via interacting with miR-29c-3p and TAF15 to modify RCC2.

BACKGROUND: Cervical cancer is a common cancer that seriously affects women's health globally. The key roles of long non-coding RNAs (lncRNAs) in the onset and development of cervical cancer have attracted much attention. Our study aims to uncover the roles of lncRNA EBLN3P and miR-29c-3p and the mechanisms by which EBLN3P and miR-29c-3p regulate malignancy in cervical cancer. METHODS: Tumor and adjacent normal tissues were collected from cervical cancer patients, and the expression of EBLN3P and miR-29c-3p were analyzed via RT-qPCR. The capacities of proliferation, migration, and invasion were assessed using CCK-8, wound healing and transwell assays. The interaction among EBLN3P, miR-29c-3p and TAF15 was determined by luciferase, RNA immunoprecipitation and RNA pull-down assays, respectively. A subcutaneous tumor xenograft mouse model was established to evaluate the functional role of EBLN3P in vivo. RESULTS: The interaction and reciprocal negative regulation between EBLN3P and miR-29c-3p were uncovered in cervical cancer cells. Likewise, EBLN3P and miR-29c-3p expression patterns in tumor tissues presented a negative association. EBLN3P knockdown weakened cell proliferation, migration and invasion, but these effects were abrogated by miR-29c-3p depletion. Mechanistically, ALKBH5 might impaired EBLN3P stability to reduce its expression. EBLN3P functioned as a competing endogenous RNA (ceRNA) for miR-29c-3p to relieve its suppression of RCC2. Besides, EBLN3P enhanced RCC2 mRNA stability via interacting with TAF15. Furthermore, silencing of EBLN3P repressed the tumor growth in mice. CONCLUSION: Altogether, lncRNA EBLN3P positively regulates RCC2 expression via competitively binding to miR-29c-3p and interacting with TAF15, thereby boosting proliferation, migration, and invasion of cervical cancer cells.

Successful pregnancy in a female with embryonal rhabdomyosarcoma of the cervix who received biopsy and chemotherapy alone without recurrence after 16 years: a case report and literature review.

BACKGROUND: Embryonal rhabdomyosarcoma (ERMS) of the uterine cervix is rare, but the population affected is mostly underage females. The scope of surgery has now evolved from extensive to limited, and organ-preserving surgery combined with chemotherapy is recommended to preserve the patient's fertility. However, reports of birth outcomes are rare. CASE: A minor woman with cervical ERMS who underwent only an outpatient biopsy of the lesion had no residual lesion on subsequent multipoint cervical biopsy and refused radical surgery or cervical conization, after which the patient received a nonclassical regimen of chemotherapy. The patient stopped the chemotherapy on her own, but the patient conceived spontaneously 16 years later with a good pregnancy outcome and no recurrence. CONCLUSIONS: This case suggests that preservation of reproductive function is often feasible in immature women with cervical ERMS, and the prognosis is usually good as long as the primary tumour can be surgically removed and the lesion is free of residual disease. We also look forward to reports of subsequent growth and pregnancy outcomes in other children with reproductive tract RMS. In cervical ERMS, accurate evaluation of the disease and development of an individualized treatment plan are crucial, and the protection of reproductive function and psychological well-being deserves special attention.

TRIM44 facilitates ovarian cancer proliferation, migration, and invasion by inhibiting FRK.

Ovarian cancer (OC) is the leading cause of gynecologic cancer-related death in the world. Accumulating evidence indicated the important role of TRIM44 in cancer development. However, how TRIM44 displays in OC and the underlying mechanism remained unclear. TRIM44 and FRK expression in OC tissues and cell lines were investigated by western blot and RT-qPCR. Histotype of tissue samples and patients' data were analyzed. Kaplan-Meier Curve was performed to validate the effect of TRIM44. Colony formation assay, MTT assay, Transwell assay, and wound-healing assay were applied to elucidate the function of TRIM44 in OC cells. CHIP assay was used to explore the association between TRIM44 and FRK. Finally, we performed SKOV3 xenografts in Balb/c nude mice to further confirm the involvement of TRIM44 in OC development. We found TRIM44 highly expressed while FRK displayed low expression in OC cell lines and tissues. Moreover, analysis of histotype of tissues and patients' data and Kaplan-Meier Curve implied the important role of TRIM44 and FRK in tumor progression. Further in vitro study suggested that knocking down TRIM44 inhibited OC cells proliferation, migration, and invasion. Besides, FRK was identified as the target gene of TRIM44 in OC, and TRIM44 promoted OC cells proliferation, migration, and invasion by inhibiting FRK. Finally, in vivo animal experiment further confirmed the promotive effect of TRIM44 on OC progression. Our findings demonstrated that TRIM44 facilitated OC proliferation, migration, and invasion by inhibiting FRK, providing new insights for theoretical research and therapy of OC.

[Relationship of Toll Like Receptors Expression and HPV16 Infection in Cervical Squamous Cell Cancer].

OBJECTIVE: To analyze the relationship between Toll like receptors (TLRs) mRNA expression levels and HPV16 infection in cervical squamous cell cancer (SCC). METHODS: Expression levels of TLRs mRNA and HPV16 in tissue samples collected from cervical squamous carcinoma and cervicitis were detected, and the relationship of TLRs mRNA expression and HPV infection was analyzed in two different disease groups. RESULTS: Expressions of TLRs mRNA were not related to HPV16 infection in cervical squamous cell cancer. Expression of TLR3 mRNA in cervical SCC was significantly lower than those of cervicitis. Expression of TLR5 mRNA was shown significant difference between moderately differentiated and poorly differentiated cervical SCC (P<0.05). CONCLUSION: Expressions of TLRs mRNA were not related to HPV16 infection in cervical SCC. TLR3 may play a role in the pathogenesis in cervical SCC.

[Studies on the lymphatic tropism and lymph cells apoptosis of cisplatin-nano carbon suspension in the rats].

OBJECTIVE: To research the lymphatic tropism and lymph cell apoptosis of cisplatin-nano carbon suspension in rats with the aim of proposing a new way for chemotherapy. METHODS: A total of 72 Wistar rats were randomly divided into two groups. For the experimental group, cisplatin-nano carbon suspension 0.3 ml (4 mg/ml) was injected subcutaneously into Wistar rats' plantar. For the control group, cisplatin 0.3 ml (4 mg/ml) was injected intravenously. Cisplatin concentration in the inguinal lymphatic tissue and plasma was determined by high performance liquid chromatography (HPLC) at 1, 2, 3, 4, 5 and 6 hours after drug administration. The apoptosis of lymph cell was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay (TUNEL). Targeting ability were evaluated and compared by targeting index (TI), selecting index (SI) and relative extraction efficiency (RE). SPSS 17.0 statistical software was used to analyze the differentiation of the cisplatin concentration and apoptosis index (AI) among various groups. DAS software was used to evaluate the lymphatic tropism. RESULTS: The cisplatin concentration of lymphatic tissue in experimental group were respectively (1.03± 0.32), (3.00±0.91), (2.20±0.73), (1.56±0.38), (1.30±0.74) and (0.78±0.34)µg/g after administration 1, 2, 3, 4, 5 and 6 hours, while in control group were (0.49±0.21), (1.02±0.70), (0.59±0.50), (0.56±0.21), (0.47±0.18) and (0.36±0.13)µg/g, in which there were significant difference at every times (all P < 0.05)except at 1 hour(P = 0.173). The cisplatin concentration in plasma were significant higher in the experimental group than those in the control group at various times(all P < 0.05), the former were respectively (0.57±0.28), (1.22 ± 0.45), (0.61 ± 0.18), (0.51 ± 0.13), (0.45 ± 0.13) and (0.40 ± 0.07) µg/ml, while the latter were respectively (3.12±0.33), (4.09±0.48), (2.56±0.38), (2.05±0.13), (1.81±0.28) and (1.44±0.40) µg/ml. Values of TI were respectively 2.12, 2.93, 3.73, 2.78, 2.76 and 2.19 and SI were 1.80, 2.45, 3.63, 3.07, 2.86 and 1.93. Value of RE was 2.86. The AI in experimental group were respectively (16.5±5.2)%, (30.2±2.8)%, (51.7 ± 4.3)%, (69.8 ± 3.2)%, (80.1 ± 4.3)% and (89.7 ± 8.5)% , while in control group were respectively(1.3±0.8)%, (2.4±1.7)%, (3.2±1.1)%, (3.9±2.6)%, (5.1±2.1)% and (6.3±2.3)%, in which there were significant difference at every points(all P < 0.05). CONCLUSIONS: The nano carbon has the character of lymphatic tropism, and could send cisplatin to lymphatic tissue to achieve a higher concentration. The trait may break a new way for chemotherapy targeting lymph metastasis.

Limitations of homologous recombination status testing and poly (ADP-ribose) polymerase inhibitor treatment in the current management of ovarian cancer.

Homologous recombination (HR) is a highly conserved DNA repair system, in which aberrations can lead to the accumulation of DNA damage and genomic scars known as homologous recombination deficiency (HRD). The identification of mutations in key genes (i.e., BRCA1, and BRCA2 (BRCA)) and the quantification of large-scale structural variants (e.g., loss of heterozygosity) are indicators of the HRD phenotype. HRD is a stable biomarker and remains unchanged during recurrence, but fails to reveal the molecular profile of tumor progression. Moreover, interpretation of the current HRD score lacks comprehensiveness, especially for the HR-proficient group. Poly (ADP-ribose) polymerase (PARP) enzymes play an important role in the repair of DNA single-strand breaks, the blockage of which using PARP inhibitors (PARPi) can generate synthetic lethality in cancer cells with HRD. Although numerous studies have demonstrated that the benefit of PARPi is substantial in ovarian cancer (OC) patients, the efficacy is limited by the development of resistance, and seems to be irrespective of HR and/or BRCA mutation status. Moreover, in addition to improving progression-free survival, long-term benefit as overall survival brought by PARPi for advanced, recurrent and refractory OC patients remains unclear. Therefore, further investigations are needed to uncover the role of HR genes beyond BRCA and their interactions with other oncogenic pathways, to determine the value of HRD in the recurrent setting, and to identify alternative strategies for the precise management of advanced, refractory OC patients.

Prognostic value of fluorine-18-fluorodeoxyglucose positron emission tomography or PET-computed tomography in cervical cancer: a meta-analysis.

OBJECTIVE: We pooled the data from published studies to estimate the prognostic value of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) or PET/computed tomography (CT) in cervical cancer patients. METHODS: We searched MEDLINE, EMBASE, and PUBMED to identify studies investigating the association of 18F-FDG PET or PET/CT with clinical survival outcomes of patients with cervical cancer. The summarized hazard ratio (HR) was estimated by using fixed- or random-effect model according to heterogeneity between trails. RESULTS: We analyzed a total number of 1854 patients from 16 studies and found that positive pretreatment FDG-PET images were significantly associated with poorer event-free survival (hazard ratio [HR], 2.681; 95% confidence interval [CI], 2.059-3.490) and overall survival (HR, 2.063; 95% CI, 1.023-4.158). Furthermore, metabolic response of therapy as shown on posttreatment PET images was also capable of predicting event-free survival and overall survival with statistical significance, and the HR was 2.030 (95% CI, 1.537-2.681) and 2.322 (95% CI, 1.485-3.630), respectively. CONCLUSIONS: Uptake of 18F-FDG on PET or PET/CT either before or after treatment has a promising value of both predicting survival outcomes for patients with cervical cancer and identifying patients for more aggressive treatment.

Clinicopathologic characteristics, treatment, prognosis and pregnancy outcomes in rhabdomyosarcoma of the uterine cervix: a case series.

OBJECTIVES: In this retrospective observational study, cases from our institution were included and the published literature reviewed to investigate the diagnosis and prognosis of cervical rhabdomyosarcoma, a rare group of tumours. MATERIAL AND METHODS: The clinicopathological data of 12 patients with cervical rhabdomyosarcoma (RMS) treated at the West China Second University Hospital of Sichuan University from January 2006 to May 2023 were collected, and their clinicopathological characteristics, diagnoses, treatments, prognoses and pregnancy outcomes were retrospectively analysed. RESULTS: (1) Clinical characteristics: The ages of the 12 RMS patients ranged from 15 to 50 years, with a median age of 17 years. Five of the patients were adults, and seven were adolescents. The initial symptoms were vaginal bleeding in 5 patients, vaginal tissue prolapse in 6 patients, and abdominal pain and urinary frequency in 1 patient. Two patients were considered to have "cervical polyps" and underwent polypectomy at the other hospitals, but the cervical mass recurred soon thereafter. (2) Pathological features: The maximum tumour diameter ranged from 3 to 25 cm. The twelve cases of cervical RMS consisted of embryonal rhabdomyosarcoma (ERMS) in 7 adolescents, ERMS in 3 adults, and pleomorphic rhabdomyosarcoma (PRMS) in 2 adults. Immunohistochemical results showed the expression of one or more characteristic markers of RMS. We reclassified tumour stage according to the Intergroup Rhabdomyosarcoma Study (IRS) clinical group and tumour node metastasis (TNM) classification. (3) Treatment: Eight patients underwent radical surgery (66.7%, 8/12), including all 5 of the included adults and 3 of the adolescents, 2 of whom were treated 10 years ago. Conservative surgical resection was performed on four patients (33.3%, 4/12), all of whom were adolescents. Postoperative chemotherapy was given to all patients except one, but one patient who underwent radical surgery discontinued chemotherapy on her own without receiving a full course. Two of the ERMS patients underwent preoperative chemotherapy, and the lesions were significantly reduced. (4) Prognosis: One of the 12 patients with cervical RMS was lost to follow-up. Of the remaining 11 patients, 10 (including seven adolescents and three adults) survived tumour free (90.9%, 10/11), and 1 adult patient with existing pulmonary multiple metastases (IRS stage IV, T2N0M1) at the initial diagnosis survived 9 months with progression-free disease (9.1%, 1/11). The median survival time was 91 months (5 to 213 months). Among 4 patients receiving fertility-sparing management, 1 conceived and delivered successfully (25%). CONCLUSIONS: The treatment of cervical RMS must take the patient's age and reproductive intent into account. The overall prognosis for cervical RMS in children and adolescents is good, and conservative surgical resection combined with chemotherapy is recommended to preserve fertility. The pregnancy outcome is also worth anticipating. For patients who have completed childbirth, radical surgery is preferred. Approaches to accurately assessing the patient's condition, grasping the indications and scope of surgery, and developing chemoradiotherapy regimens deserve further exploration.

LncRNA MIR99AHG enhances adipocyte differentiation by targeting miR-29b-3p to upregulate PPARγ.

AIM: The aim is to identify new long noncoding RNAs (lncRNAs) involved in adipocyte differentiation. METHODS: High-throughput RNA sequencing of 3T3-L1 preadipocytes was carried out before and after differentiation to identify the target lncRNAs and miRNAs. The effects of lncRNA, miRNA and the network mechanism on adipocyte differentiation were evaluated in vitro and in vivo. Visceral adipose tissue (VAT) was collected from Chinese subjects with obesity or a normal body mass index (BMI), and the levels of lncRNAs, adipogenic genes and miRNAs were measured. RESULTS: MIR99AHG, miR-29b-3p were selected as the target lncRNA and miRNA. Short hairpin RNA against MIR99AHG inhibited the differentiation of 3T3-L1 preadipocytes, reduced the expression of the peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT enhancer-binding protein alpha (C/EBPα) and fatty acid binding protein 4 (FABP4) genes, upregulated the expression of miR-29b-3p. Overexpression of MIR99AHG showed the opposite effects. Overexpression of miR-29b-3p inhibited the differentiation of 3T3-L1 preadipocytes and decreased the PPARγ level, while inhibition of miR-29b-3p showed the opposite effects. MIR99AHG and PPARγ competed for binding to miR-29b-3p. In mice with high-fat diet-induced obesity, MIR99AHG and miR-29b-3p mRNA level were increased and decreased, respectively. Tail vein injection of adeno-associated virus 9-MIR99AHG-RNA interference (AAV9-MIR99AHG-RNAi) reduced the body weight, epididymal fat mass, MIR99AHG level and increased the expression of miR-29b-3p. The expression levels of MIR99AHG, PPARγ, C/EBPα and FABP4 in human visceral adipose tissue were higher in the obese group than in the normal weight group. CONCLUSIONS: MIR99AHG enhances adipogenesis by regulating miR-29b-3p and PPARγ, providing a new target for therapeutic intervention in obesity.

Chinese expert consensus on the clinical applications of aminolevulinic acid-based photodynamic therapy in female lower genital tract diseases (2022).

INTRODUCTION: With the younger onset age of female lower genital tract diseases, there are increasing demands for protecting organ and tissue structures to preserve fertility and, therefore, effective fertility-sparing treatments that cause minimal normal tissue damage and less adverse reactions are urgently needed. OBJECTIVE: This study is aimed at reviewing information and achieving consensus on recommendations on the clinical applications of aminolevulinic acid-based photodynamic therapy (ALA-PDT) in female lower genital tract diseases. METHODS: Members of the expert panel held online and in-person meetings to discuss and revise drafts created by the steering committee based on the literature review and the clinical experiences of the expert panel. Opinions of the experts were transcribed and discussed in detail to ensure that the consensus statement best reflects the current advances in the field and the experts' view. RESULTS: After numerous rounds of meetings, experts unanimously agreed on the importance of ALA-PDT in the treatment of cervical squamous intraepithelial lesions (SIL), vaginal SIL, vulvar SIL, vulvar lichen sclerosus (VLS), and condyloma acuminatumon (CA). Experts also reached consensus on the recommended treatment regimen and treatment methods. CONCLUSION: This consensus aimed to provide practical basis and guidance for the clinical applications of ALA-PDT in female lower genital tract diseases in China. Of note, this is the only expert consensus prepared by board-certified specialists in gynecology and obstetrics in China. More evidence-based clinical studies should be made to update and expand the current recommendations.

MiR-29c-3p inhibits epithelial-mesenchymal transition to inhibit the proliferation, invasion and metastasis of cervical cancer cells by targeting SPARC.

BACKGROUND: Cervical cancer is one of the most common gynecological malignancies. Cancer recurrence and the poor efficacy of cervical cancer treatments are mainly caused by invasion and metastasis of cervical cancer cells. This study is to investigate whether miR-29c-3p can inhibit epithelial-mesenchymal transition (EMT) by targeting secreted protein acidic and rich in cysteine (SPARC), thus inhibiting the invasion and metastasis of human cervical cancer cells. METHODS: The expression levels of miR-29c-3p and SPARC in cervical cancer tissues and non-tumor adjacent tissues, human normal cervical epithelial cell line Ect1/E6E7 and human cervical cancer cell lines HeLa, CaSki, C-33A, HT-3 and SiHa were detected. After the expression of miR-29c-3p and SPARC was intervened in C-33A and SiHa cells, RT-qPCR was used to detect the expression levels of miR-29c-3p and SPARC. Western blot was performed to observe the expression levels of SPARC and EMT-related proteins. The proliferation rate of C-33A and SiHa cells was measured using an MTT assay. The viability of the cells was determined using a cell colony formation assay. Apoptosis and cell cycle was measured using flow cytometry, and migration ability was observed using a wound healing assay. A transwell invasion assay was used to determine the invasion ability of the cells, whilst a dual-luciferase reporter assay verified that SPARC was a target gene of miR-29c-3p. RESULTS: miR-29c-3p was expressed at low levels in cervical cancer tissues and cells, while SPARC expression was upregulated. The luciferase reporter assay confirmed that miR-29c-3p targeted and bound to SPARC. MiR-29c-3p overexpression significantly inhibited the proliferation, invasion, migration, and cell cycle of cervical cancer cells, but promoted apoptosis. In the miR-29c-3p group (miR-29c-3p overexpression), EMT progression was inhibited by upregulating E-cadherin expression and downregulating N-cadherin, vimentin, and Snail expression, which was contrary to the results of the in-miR-29c-3p group (inhibition of miR-29c-3p expression). In the miR-29c-3p + SPARC group (miR-29c-3p overexpression + SPARC overexpression), the effect of miR-29c-3p overexpression on cervical cancer cell functions was reversed. CONCLUSIONS: miR-29c-3p can inhibit EMT by targeting SPARC, so as to inhibit the invasion and metastasis of cervical cancer cells.

Long non-coding RNA HAND2-AS1 delays cervical cancer progression via its regulation on the microRNA-21-5p/TIMP3/VEGFA axis.

Cervical cancer is a common cause of cancer-related mortality in women. Mounting evidence suggests that long non-coding RNAs (lncRNAs) function vitally in many cancers. In this study, we discovered that the regulation of the heart and neural crest derivatives expressed 2-antisense RNA 1 (HAND2-AS1) in cervical cancer. RT-qPCR was conducted to detect the expression of HAND2-AS1 and microRNA-21-5p (miR-21-5p). The relationship of HAND2-AS1 and miR-21-5p was identified by dual-luciferase reporter gene assay. The roles of HAND2-AS1, miR-21-5p and tissue inhibitor of metalloproteinases-3 (TIMP3) in cervical cancer were accessed via gain- and loss-of-function approaches. The expression of related proteins in the vascular endothelial growth factor A (VEGFA) signaling pathway was detected through Western blot analysis. Finally, xenografts of cervical cancer in nude mice were established to assess the effect of HAND2-AS1 on tumorigenesis in vivo. HAND2-AS1 and TIMP3 were downregulated in cervical cancer, which were identified to be associated with a poor prognosis of patients with cervical cancer. Moreover, HAND2-AS1 was upregulated the expression of TIMP3 through competitively binding to miR-21-5p. Overexpressed HAND2-AS1 or downregulated miR-21-5p inhibited cell proliferation, migration, and invasion while promoting cell apoptosis, in association with increased expression of proteins in VEGFA signaling pathway. These changes were reversed by silencing of TIMP3. Overexpressed HAND2-AS1 reduced the tumor formation ability in nude mice. In summary, HAND2-AS1 may exert inhibitory effects on cervical cancer cell growth and cervical cancer development through its regulation on the miR-21-5p/TIMP3/VEGFA axis. This highlights that HAND2-AS1 may serve as a potential target for cervical cancer diagnosis and treatment.

Clinicopathologic features and clinical outcomes of intravenous leiomyomatosis of the uterus: A case series.

RATIONALE: Intravenous leiomyomatosis (IVL) is a rare and special type of smooth muscle tumor originating in the uterus. It is classified as a benign disease according to its histological features but shows the behavioral characteristics of a malignant tumor. It is easily misdiagnosed and recurrent. The purpose of this study was to retrospectively analyze clinicopathological data of 25 cases of IVL in order to enhance clinicians' understanding of this rare disease. PATIENT CONCERNS: We screened and identified 25 cases of IVL at our hospital from October 2013 to January 2020. Five patients had tumors. DIAGNOSES: The diagnosis in each case was pathologically confirmed after surgical treatment. INTERVENTIONS: All patients were managed surgically. Although the surgical procedures were different, the surgical approach was geared towards achieving complete excision. Three patients received hormonal therapy with gonadotropinreleasing hormone agonists after surgery. OUTCOMES: We retrospectively reviewed all medical records and analyzed the clinicopathologic features and clinical outcomes of this disease as well as the correlations between the clinical features and risk of recurrence. Neither the symptoms nor the preoperative imaging results were suggestive of IVL in any of the cases. Except for two patients who were lost to follow-up, twenty-three patients who were followed up are still alive. Three patients experienced a recurrence. LESSONS: The clinical manifestations and ultrasound images of IVL in the early stages are not typical; thus, IVL is easily misdiagnosed as uterine leiomyoma. Radiologists, pathologists, and surgeons should have a thorough understanding of IVL and a high index of vigilance for IVL in clinical practice. Surgery should always be aimed at achieving complete tumor excision. Patients with large lesions (≥7 cm) and lesions extending to the broad ligament may have an increased risk of recurrence. Early detection, diagnosis, and treatment are very important; once the diagnosis is confirmed, regular follow-ups are crucial.

miR-326 inhibits the cell proliferation and cancer stem cell-like property of cervical cancer in vitro and oncogenesis in vivo via targeting TCF4.

BACKGROUND: Cervical cancer ranks as one of the most prevalent female malignancies globally, and its treatment with new targets has been the focus of current research. The present study set out to investigate the function of microRNA-326 (miR-326) in vitro and in vivo and to verify the direct targeting of transcription factor 4 (TCF4) by miR-326. METHODS: The detection of messenger RNA (mRNA) expressing miR-326 and TCF4 in cervical cancer cell lines and tumor samples was conducted using quantitative real-time polymerase chain (qRT-PCR). A dual-luciferase reporter assay was carried out to detect the target relationship of miR-326 with TCF4. A Cell Counting Kit-8 (CCK-8) assay was employed to detect the effect of miR-326 on CasKi cell viability. Flow cytometry and western blotting were employed to examine the effects of miR-326 on cancer stem cell (CSC)-like property. Tumor weight was measured in orthotopic xenograft mouse models. Immunohistochemistry was employed to analyze the protein expression levels of Ki-67, proliferating cell nuclear antigen (PCNA), CD44, and SRY-box 4 (SOX4). RESULT: Downregulation of the mRNA expression levels of miR-326 was observed in cervical cancer cell lines and tumor tissue, while the levels of TCF4 were upregulated. The dual-luciferase reporter assay revealed binding of miR-326 to the three prime untranslated region (3'-UTR) of TCF4. In vitro assays demonstrated that miR-326 inhibited CasKi cell proliferation through regulating TCF4. miR-326 also suppressed the CSC-like property of CasKi cells by targeting TCF4. Furthermore, the protein expression levels of cyclin D1, ß-catenin, and c-Myc were decreased when miR-326 was added to TCF4-transfected cells. In vivo assays demonstrated that miR-326 inhibited tumor weight, growth, and the protein expression levels of Ki-67, PCNA, CD44, SOX4, and ß-catenin. CONCLUSIONS: miR-326 acted in a tumor-suppressive manner through its regulation of TCF4, and has potential as a biomarker or therapeutic target for cervical cancer.

Management of Cervical Cancer in Pregnant Women: A Multi-Center Retrospective Study in China.

Background: This retrospective multi-center study aimed to describe the epidemiological characteristics, clinical features, and management of patients with cervical cancer in pregnancy (CCIP) and evaluate maternal and infant outcomes. Methods: The data of patients with CCIP were retrospectively collected from those diagnosed and treated in 17 hospitals in 12 provinces in China between January 2009 and November 2017. The information retrieved included patients' age, clinical features of the tumor, medical management (during pregnancy or postpartum), obstetrical indicators (i.e., gestational age at diagnosis, delivery mode, and birth weight), and maternal and neonatal outcomes. Survival analyses were performed using Kaplan-Meier survival curves and log-rank tests that estimated the overall survival of patients. Results: One-hundred and five women diagnosed with CCIP (median age = 35 years) were identified from ~45,600 cervical cancer patients (0.23%) and 525,000 pregnant women (0.020%). The median gestational age at cancer diagnosis was 20.0 weeks. The clinical-stage of 93.3% of the patients with CCIP was IB1, 81.9% visited the clinic because of vaginal bleeding during pregnancy, and 72.4% had not been screened for cervical cancer in more than 5 years. To analyze cancer treatments during pregnancy, patients were grouped into two groups, termination of pregnancy (TOP, n = 67) and continuation of pregnancy (COP, n = 38). Analyses suggested that the TOP group was more likely to be diagnosed at an earlier gestational stage than the COP group (14.8 vs. 30.8 weeks, p < 0.001). The unadjusted hazard ratio for the COP group's overall survival was 1.063 times that of the TOP group (95% confidence interval = 0.24, 4.71). There were no significant differences between the TOP and COP groups in maternal survival (p = 0.964). Thirty-three of the infants of patients with CCIP were healthy at the end of the follow-up period, with a median age of 18 ± 2.8 months. Conclusions: Most patients with CCIP had not been screened for cervical cancer in over 5 years. The oncologic outcomes of the TOP and COP groups were similar. A platinum-based neoadjuvant chemotherapy regimen could be a favorable choice for the management of CCIP during the second and third trimesters of pregnancy.

[Clinicopathologic features of 234 cases with borderline ovarian tumors].

OBJECTIVE: To determine the clinicopathologic characteristics and prognostic factors that may be used to predict the poor outcome of patients with borderline ovarian tumors. METHODS: All cases with borderline ovarian tumors treated in the West China Second University Hospital from January 2001 to June 2007 were analyzed retrospectively for clinicopathologic features, treatment parameters and outcome of treatment. Univariate and multivariate analyses were used to assess independent prognostic factors using the logistic regression model. RESULTS: The median age of 234 patients was 40.1 years with a range of 14 to 80 years. There were 101 (43.2%), 94 (40.2%), 19 (8.1%), 12 (5.1%), 8 (3.4%) cases of serous, mucinous, mixed, endometrioid and clear cell tumors, respectively. Out of 234 cases, 182 (77.8%) underwent laparotomy and 45 (19.2%) underwent laparoscopy. Seven women underwent laparoconversion. Fertility sparing surgery was performed on 119 cases (50.9%) and radical surgery was performed on 115 cases (49.1%). Totally 161 (68.8%) patients had stage I, 19 (8.1%) had stage II, 54 (23.1%) had stage III, and none had stage IV disease. Sixty-four women received postoperative chemotherapy. The median follow-up was 40 months with a range of 8 to 78 months. Recurrence was found in 26 cases (11.1%) during follow-up, and no tumor-related death was reported. The logistic regression model showed that surgery procedure (OR = 2.304, P = 0.024), cyst rupture (OR = 2.213, P = 0.038), stage (OR = 4.114, P < 0.01), microinvasion (OR = 2.291, P = 0.046) and peritoneal implants (OR = 2.101, P = 0.016) were the five independent prognostic factors affecting recurrence. CONCLUSIONS: Although patients with borderline ovarian tumors have an excellent prognosis, the risk of recurrence remains in some patients. Emphasis should be put on these patients with high risk factors and preventive strategies should be taken to prevent their progression.

[Inhibition effect and mechanisms of quercetin on surgically induced endometriosis].

OBJECTIVE: To evaluate the therapeutic effect of quercetin on the rat endometriosis models and the relationship between the inhibition effect and the expression of HSP70 and VEGF. METHODS: A surgical model to simulate endometriosis was established and the rats were divided into four groups. After 3 weeks of daily administration of quercetin, dazazol, combined quercetin+dazazol, and placebo, the potential rule of quercetin to inhibit endometriosis in rats were evaluated by measuring the implants, examining the histology and detecting the expression of heat shock protein 70 (HSP70) and vascular endothelial growth factor (VEGF) in ectopic endometrium with immunohistochemistry. RESULTS: Compared to placebo, quercetin [100 mg/(kg x d)], dazazol [36 mg/(kg x d)], and combined quercetin + dazazol decreased the size of implants significantly respectively, and there was no significant difference among the three groups. HSP70 and VEGF were both significantly reduced by quercetin or combination treatment, but no significant difference was seen between quercetin and combination treatment groups. CONCLUSION: Quercetin inhibits surgically induced endometriosis in rats, and the possible mechanism is to inhibit the expression of HSP70 and VEGF.

Primary yolk sac tumor originating from the endometrium: A case report and literature review.

RATIONALE: Yolk sac tumors (YSTs) are malignant germ cell tumors that secrete alpha-fetoprotein (AFP). These tumors commonly develop in infants, young children, and young women and often originate in the gonads. Primary endometrial YST is a very rare malignancy, and a primary endometrial YST in the absence of abnormal AFP levels is even rarer. PATIENT CONCERNS: A 38-year-old woman presented with the chief complaint of prolonged menstruation and increased menstrual bleeding with a duration of more than 2 months. DIAGNOSES: Postoperative pathology confirmed a diagnosis of endometrial YST with metastasis to the greater omentum (stage IVB). INTERVENTIONS: The patient underwent a laparoscopic extrafascial hysterectomy, bilateral adnexectomy, pelvic lymphadenectomy, abdominal para-aortic lymphadenectomy, omentectomy, and appendectomy. Additionally, she received 6 courses of multidrug chemotherapy (bleomycin, etoposide, and cisplatin; BEP). OUTCOMES: After completing chemotherapy, the patient underwent regular follow-up examinations. No recurrence was noted during a 24-month follow-up period. LESSONS: YST is mainly treated using surgery and chemotherapy, which may spare endocrine functions in young patients. The BEP regimen appears to be an effective postoperative chemotherapy regimen for patients with endometrial YST.

[Expression of AIB1 protein in epithelial ovarian cancer cells and its impact on apoptosis].

OBJECTIVE: To investigate the expression of AIB1 (amplified in breast cancer 1) protein in epithelial ovarian cancer cells and to analyze the relationship between AIB1 protein and the apoptosis modulated proteins: P53 and Bcl-2. METHODS: The expressions of AIB1, P53 and Bcl-2 proteins in 24 normal ovaries, 24 benign ovarian tumors, 18 borderline ovarian tumors and 69 epithelial ovarian cancers were examined with immunohistochemical method SP. The expressions of estrogen receptor (ER) and progesterone receptor (PR) were also examined to reveal their relation with AIB1 expression. RESULTS: 1) The AIB1 protein expressed in 65.22% ovarian cancers, greater than in normal ovaries (8.33%), benign ovarian tumors (25.00%) and borderline ovarian tumors (38.89%). The overexpression of AIB1 protein occurred in 36.23% ovarian cancers. Ovarian cancers poorly-differentiated, at a late clinical stage and with lymph node involvement had higher AIB1 overexpression than those well-differentiated and moderately-differentiated, and those at an early clinical stage and without lymph node involvement. 2) The expression of AIB1 was positively correlated with the expression of P53 (r = 0.342, P = 0.004) and Bcl-2 proteins (r = 0.311, P = 0.009) in the ovarian cancers. There was no correlations between the AIB1 expression and the ER and PR. CONCLUSION: AIB1 protein expression increases in ovarian cancers, which is associated with the higher malignant biological behavior. The overexpression of AIB1 may be involved in the carcinogenesis and the development of epithelial ovarian cancers through a hormone independent pathway. Our findings suggest a possible correlation between AIB1 and apoptosis modulated proteins P53 and Bcl-2.

[Temporospatial expression of cyclin G1 in normal human endometria].

OBJECTIVE: To study the temporospatial expression of cyclin G1 protein and mRNA in normal human endometrium and its physiological implications. METHODS: Human endometria samples were taken from 15 women in proliferative phase, 11 in early secretory phase, and 15 in mid-late secretary phase. Cyclin G1 protein and mRNA in the normal human endometria were measured by immunohistochemistry and in situ hybridization, respectively. RESULTS: The expression of cyclin G1 protein in the epithelium cells was low in proliferative phase. The expression increased at early secretary phase and reached the highest at mid-late secretary phase. The expression of cyclin G1 protein in stromal cells only appeared at mid-late secretary phase. The cyclin G1 protein was localized in nucleus. The expression of cyclin G1 mRNA was localized in cytoplasma, but had similar cycles as the expression of cyclin G1 protein. CONCLUSION: The expression of Cyclin G1 in normal human endometria is progesterone dependence.