Uterine torsion with degeneration and infarction of giant leiomyoma in a postmenopausal woman: A case report.

RATIONALE: Uterine torsion and giant leiomyoma are both rare diseases. Uterine torsion combined with giant leiomyoma with degeneration or infarction is easy to be misdiagnosed. We wrote this case to increase the accuracy and timeliness of medical staff's diagnosis and treatment of uterine fibroids combined with uterine torsion. PATIENT CONCERNS: We present a case of uterine torsion with degeneration and infarction of giant leiomyoma in a 66-year-old postmenopausal woman, who had a lump in her pelvis 10 years ago and suffered from acute abdominal pain half a day before hospitalization. DIAGNOSIS: The patient was considered as uterine torsion with huge abdominal mass by computed tomography and enhanced magnetic resonance imaging, and finally diagnosed as uterine torsion with giant leiomyoma through surgery and pathological examination. INTERVENTIONS AND OUTCOMES: The patient underwent exploratory laparotomy. In addition to the removal of huge uterine fibroids, the hysterectomy with double appendages was conducted. The histopathologic analysis showed "(Uterine tumor) leiomyoma with extensive edema, degeneration, infarction and calcification." The patient recovered well after operation and kept healthy in the follow-up to date. LESSONS: Although uterine torsion is extremely rare, early diagnosis and treatment are essential to prevent serious complications.

A novel necroptosis-associated miRNA signature predicting prognosis of endometrial cancer and correlated with immune infiltration.

OBJECTIVE: Necroptosis is a form of programmed cell death identified irrelevant to caspases, which plays an important role in the tumorigenesis and development of cancer. MicroRNAs (miRNAs) are important regulators of both necroptosis and cancer. MATERIALS AND METHODS: Expression of sixteen necroptosis-associated miRNAs were analyzed in 546 endometrial cancer (EC) tissues and 33 paracancerous samples from the Cancer Genome Atlas (TCGA). Cox regression analysis was used to evaluate the correlations between miRNAs and overall survival. MiRNAs risk score (Mrs) and nomogram were established to assess the potential value of necroptosis-related miRNAs on prognosis. Expression of miRNA-148a-3p in endometrial cancer cells and endometrial epithelial cells was detected by quantitative real-time PCR (qRT-PCR). The targets genes of miR-148a-3p were predicted using miRDB, miRTarBase and TargetScan and the prognostic-related genes were screened. Immune infiltration analysis was conducted to explore the potential mechanism of these target genes. RESULTS: We identified fourteen differentially expressed miRNAs and selected seven miRNAs (miR-15a-5p, miR148a-3p, miR-7-5p, miR-141-3p, miR-200a-5p, miR-223-3p, miR-16-5p) for prognostic-model construction. The area under the curve (AUC) of receiver operating characteristic (ROC) curve for 1-, 2- and 5-year survival were 0.678, 0.652 and 0.656 respectively. Multivariate analysis revealed that the Mrs was an independent prognostic factor considering other risk factors (HR = 1.928, 95% CI = 1.072-3.467, P = 0.028). Among these miRNAs, miRNA-148a-3p was up-regulated in cancer tissues and cells, and Kaplan-Meier analysis showed its significance in overall survival (OS). The target genes, DNAJB4 and PRNP, were associated with poor prognosis and correlated with tumor immune infiltration. CONCLUSIONS: Our study constructed a novel necroptosis-associated miRNAs model for prognosis prediction, and DNAJB4 and PRNP may be therapeutic targets for EC.

DNMT3B attenuated the inhibition of TET3 on epithelial-mesenchymal transition in TGF-ß1-induced ovarian cancer by methylating the TET3 promoter.

This study intends to investigate the effects of DNA methyltransferase 3B (DNMT3B) and ten-eleven translocation 3 (TET3) on transforming growth factor-ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) in ovarian cancer (OV) cells. According to the specific experiments, the cells were treated with TGF-ß1 for 48 h, and then the expressions of EMT-related proteins (E-cadherin, Vimentin and Snail), TET3 and DNMT3B were quantified by Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Methprimer, methylation-specific PCR (MSP), bisulfite sequencing PCR (BSP) and chromatin immunoprecipitation (ChIP) were used to determine the regulation of DNMT3B on TET3 promoter. The impacts of DNMT3B and TET3 upon the EMT-related proteins and OV cell migration and invasion abilities were evaluated through the rescue experiments and the loss- and gain-of-function experiments. In line with the results, TGF-ß1 down-regulated TET3 and E-cadherin levels, up-regulated Vimentin and Snail levels, promoted migratory and invasive abilities, and increased methylation level of TET3 promoter in OV cells, which however were reversed by shDNMT3B. The binding of DNMT3B to TET3 promoter facilitated the methylation of TET3 promoter. Overexpressed TET3 inhibited the migratory and invasive abilities and EMT of OV cells, whereas shTET3 did the opposite. ShTET3 also offset the regulatory effects of shDNMT3B on EMT, migration and invasion of OV cells. To conclude, DNMT3B mitigates the suppression of TET3 on TGF-ß1-induced EMT in OV cells by methylating the promoter region of TET3.

Leiomyomatosis peritonealis disseminata with low-grade malignant change: A case report.

BACKGROUND: Leiomyomatosis peritonealis disseminata (LPD) is a rare disease characterized by multiple leiomyomas spread all over the peritoneal cavity. It is commonly described as benign in women of reproductive age. Malignant LPD is much rarer. METHODS: We present a case of LPD with low potential malignant change in a 43-year-old female, who felt a lump in her abdomen after laparoscopic myomectomy 10 years ago and laparoscopic hysterectomy 8 years ago. The patient underwent exploratory laparotomy and salpingectomy, greater omentectomy, and pelvic and abdominal mass resection were performed during the surgery. The pathological findings revealed LPD with low potential malignant change, with strong expression of estrogen receptor and progesterone receptor. The patient refused oophorectomy and chose gonadotropin-releasing hormone agonists injection postoperatively. RESULTS: No recurrence was found during the follow-up to date. CONCLUSION: Surgery is the main treatment for LPD, and endocrine therapy is another choice. Although it is reported mostly benign, we need to be alert to the possibility of malignancy.

Granulocytic sarcoma of cervix: A rare case report.

RATIONALE: Granulocytic sarcoma (GS) is an uncommon extramedullary tumor, and involvement of the female reproductive system is very rare. PATIENT CONCERNS: We present a case of cervical GS in a 45-year-old woman who presented with repeated vaginal bleeding after sex for 1 month. DIAGNOSIS: The patient was diagnosed with cervical GS mainly based on pathological immunohistochemical examination and further progressed to acute myeloid leukemia (AML) based on bone marrow puncture and cytogenetic analysis. INTERVENTIONS AND OUTCOMES: The patient underwent hysterectomy and bilateral adnexectomy, and subsequently received AML-type chemotherapy. She relapsed 3 months after therapy and progressed to AML. The patient was then treated with chemotherapy with cytosine arabinoside and idarubicin again and achieved complete remission after 1 cycle. Currently, she is still receiving therapy combined with cytosine arabinoside and idarubicin, and has been alive for 13 months. LESSONS: Although GS of the reproductive system is rare, it should be included in the differential diagnosis of gynecological neoplasms and should be treated with AML-type chemotherapy protocols.

Chemotherapy for ovarian cancer during pregnancy: A systematic review and meta-analysis of case reports and series.

AIM: This study aims to investigate the safety and efficacy of chemotherapy in ovarian cancer patients in pregnancy. METHODS: In this study, eligible studies were searched on PubMed, Embase, and Cochrane Library databases up to December 31, 2020. Data were calculated and presented by frequency and percentage, mean ± standard deviation (SD), and median (range), respectively. Kaplan-Meier survival analysis was performed to estimate overall survival (OS) and progression-free survival (PFS). RESULTS: Finally, 34 studies including 40 ovarian cancer cases receiving chemotherapy during pregnancy were included. All 40 patients received chemotherapy during pregnancy. During the follow-up, seven of 37 (18.9%) women had a relapse and four of them (4/7, 57.1%) died of recurrence. Survival analysis failed to reach median OS and PFS within the follow-up (range 3-72 months). Better OS and PFS after chemotherapy in pregnancy were obtained in women with early-stage ovarian cancer (I) compared with those with advanced stage (III-IV). Neither OS nor FS differed between women treated with multi-drugs and those with monotherapy. Forty-one newborns were delivered from 40 pregnant women. Thirty-four (34/41, 82.9%) were completely healthy at birth and the end of follow-up (range 0.18-160 months). However, one newborn died 5 days after birth due to multiple congenital malformations, and another one developed Tourette's syndrome, aphasia, Asperger's syndrome as well as speech delay. CONCLUSIONS: This meta-analysis first reveals the efficacy and safety of chemotherapy for ovarian cancer during pregnancy, especially for early-stage patients. Cisplatin or carboplatin is suggested to be used as monotherapy to reduce adverse effects.

LncRNA OIP5-AS1 upregulates snail expression by sponging miR-34a to promote ovarian carcinoma cell invasion and migration.

BACKGROUND: Although OIP5-AS1 has been characterized as an oncogenic lncRNA in many types of cancer, its role and underlying mechanism in ovarian carcinoma (OC) remains unknown. This study aimed to investigate the role of OIP5-AS1 in OC. METHODS: OC tissues and non-tumor tissues (ovary tissues within 3 cm around tumors) were collected from 58 OC patients (age range 36 to 67 years old, mean age 51.4 ± 5.9 years old). The expression of OIP5-AS1 and snail in paired tissues were determined by RT-qPCR. The interaction between OIP5-AS1 and miR-34a was predicted by IntaRNA2.0 and confirmed by dual luciferase reporter assay. The effects of overexpression of OIP5-AS1 and miR-34a on the expression of snail were analyzed by RT-qPCR and Western blotting. Cell invasion and migration were analyzed by Transwell assay. RESULTS: We observed that the expression of OIP5-AS1 and snail was upregulated and positively correlated with each other in OC. RNA-RNA interaction analysis showed that OIP5-AS1 might sponge miR-34a. In OC cells, overexpression of OIP5-AS1 resulted in the upregulated expression of snail, while overexpression of miR-34a downregulated the expression of snail. In addition, overexpression of miR-34a reduced the effects of overexpression of OIP5-AS1 on the expression of snail. In cell invasion and migration assay, overexpression of OIP5-AS1 and snail resulted in increased OC cell invasion and migration, while overexpression of miR-34a decreased OC cell invasion and migration. Moreover, overexpression of miR-34a attenuated the effects of OIP5-AS1 overexpression on OC cell invasion and migration. CONCLUSIONS: Therefore, OIP5-AS1 may upregulate snail expression in OC by sponging miR-34a to promote OC cell invasion and migration.

LncRNA OIP5-AS1 upregulates snail expression by sponging miR-34a to promote ovarian carcinoma cell invasion and migration

BACKGROUND: Although OIP5-AS1 has been characterized as an oncogenic lncRNA in many types of cancer, its role and underlying mechanism in ovarian carcinoma (OC) remains unknown. This study aimed to investigate the role of OIP5-AS1 in OC. METHODS: OC tissues and non-tumor tissues (ovary tissues within 3 cm around tumors) were collected from 58 OC patients (age range 36 to 67 years old, mean age 51.4 ± 5.9 years old). The expression of OIP5-AS1 and snail in paired tissues were determined by RT-qPCR. The interaction between OIP5-AS1 and miR-34a was predicted by IntaRNA2.0 and confirmed by dual luciferase reporter assay. The effects of overexpression of OIP5-AS1 and miR-34a on the expression of snail were analyzed by RT-qPCR and Western blotting. Cell invasion and migration were analyzed by Transwell assay. RESULTS: We observed that the expression of OIP5-AS1 and snail was upregulated and positively correlated with each other in OC. RNA-RNA interaction analysis showed that OIP5-AS1 might sponge miR-34a. In OC cells, overexpression of OIP5-AS1 resulted in the upregulated expression of snail, while overexpression of miR-34a downregulated the expression of snail. In addition, overexpression of miR-34a reduced the effects of overexpression of OIP5-AS1 on the expression of snail. In cell invasion and migration assay, overexpression of OIP5-AS1 and snail resulted in increased OC cell invasion and migration, while overexpression of miR-34a decreased OC cell invasion and migration. Moreover, overexpression of miR-34a attenuated the effects of OIP5-AS1 overexpression on OC cell invasion and migration. CONCLUSIONS: Therefore, OIP5-AS1 may upregulate snail expression in OC by sponging miR-34a to promote OC cell invasion and migration.

Preoperative albumin-to-fibrinogen ratio predicts chemotherapy resistance and prognosis in patients with advanced epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is the majority ovarian cancer (OC) type with a poor prognosis. This present study aimed to investigate potential prognostic factors including albumin-to-fibrinogen ratio (AFR) for advanced EOC patients with neoadjuvant chemotherapy (NAC) followed by debulking surgery. METHODS: A total of 313 advanced EOC patients with NAC followed by debulking surgery from 2010 to 2017 were enrolled. The predictive value of AFR for the overall survival (OS) was evaluated by receiver operating characteristic (ROC) curve analysis. The univariate and multivariate Cox proportional hazards regression analyses were applied to investigate prognostic factors for advanced EOC patients. The association between preoperative AFR and progression free survival (PFS) or OS was determined via the Kaplan-Meier method using log-rank test. RESULTS: The ROC curve analysis showed that the cutoff value of preoperative AFR in predicting OS was determined to be 7.78 with an area under the curve (AUC) of 0.773 (P < 0.001). Chemotherapy resistance, preoperative CA125 and AFR were independent risk factors for PFS in advanced EOC patients. Furthermore, chemotherapy resistance, residual tumor and AFR were significant risk factors for OS by multivariate Cox analysis. A low preoperative AFR (≤7.78) was significantly associated with a worse PFS and OS via the Kaplan-Meier method by log-rank test (P < 0.001). CONCLUSIONS: A low preoperative AFR was an independent risk factor for PFS and OS in advanced EOC patients with NAC followed by debulking surgery.

Spatiotemporal expression pattern of Sjfz7 and its expression comparison with other frizzled family genes in developmental stages of Schistosoma japonicum.

Wnts are secreted signaling molecules that are implicated in a variety of growth-related processes. Frizzled proteins have been identified as receptors for Wnt ligands in vertebrates and invertebrates, but a functional role for dioecious flatworm Frizzleds has not been determined. To evaluate the endogenous role of Frizzled proteins during development, we have identified and characterized a Schistosoma japonicum frizzled gene (Sjfz7). We found that Sjfz7 encodes a 698 amino acid protein with typical characteristics of Frizzled proteins. The immunohistochemical localization pattern showed that Sjfz7 protein was extensively distributed in almost all tissues of S. japonicum, including subtegumental muscle cells, parenchymal cells, intestinal epithelial cells and male and female germ cells. This indicated that Sjfz7-mediated Wnt signaling might be associated with the development of musculature, intestinal tract and reproductive organs in schistosome. Comparing mRNA levels between frizzled family members showed that Sjfz7 mRNA was consistently higher in the developmental stages analyzed, suggesting that Sjfz7 may be responsible for more functional tasks than other frizzled family members. Comparing frizzled mRNA levels between not fully developed and normal worms suggested that Wnt signaling might be abnormal in not fully developed worms.

20(S)-Rg3 blocked epithelial-mesenchymal transition through DNMT3A/miR-145/FSCN1 in ovarian cancer.

Epithelial-mesenchymal transition (EMT) is one of the key mechanisms mediating cancer progression. MicroRNAs (miRs) are essential regulators of gene expression by suppressing translation or causing degradation of target mRNA. Growing evidence illustrates the crucial roles of miRs dysregulation in cancer development and progression. Here, we have found for the first time that the ginsenoside 20(S)-Rg3, a pharmacologically active component of Panax ginseng, potently increases miR-145 expression by downregulating methyltransferase DNMT3A to attenuate the hypermethylation of the promoter region in the miR-145 precursor gene. Restoration of DNMT3A reverses the inhibitory effect of 20(S)-Rg3 on EMT. FSCN1 is verified as the target of miR-145 to suppress EMT in human ovarian cancer cells. The results from nude mouse xenograft models further demonstrate the suppressive effect of miR-145 on malignant progression of ovarian cancer. Taken together, our results show that 20(S)-Rg3 blocks EMT by targeting DNMT3A/miR-145/FSCN1 pathway in ovarian cancer cells, highlighting the potentiality of 20(S)-Rg3 to be used as a therapeutic agent for ovarian cancer.

A Feedback Loop Between miR-30a/c-5p and DNMT1 Mediates Cisplatin Resistance in Ovarian Cancer Cells.

BACKGROUND: Many microRNAs (miRs) are dysregulated in cancers, and aberrant miR expression patterns have been suggested to correlate with chemo-resistance of cancer cells. We aim to study the role of miR-30 family members in cisplatin-resistance of ovarian cancer cells. METHODS: qRT-PCR was used to compare differential expression levels of miR-30 family members in ovarian cancer cell line A2780 and its cisplatin-resistant derivative CP70. Changes of cisplatin-sensitivity in miR-30a-5p- and miR-30c-5p-overexpressed-CP70 cells and miR-30a-5p- and miR-30c-5p-inhibited-A2780 cells were examined by CCK8 assay and apoptosis analysis using flow cytometry; targets of miR-30a/c-5p were analyzed by western blotting and luciferase reporter assay; methylation regulation of pre-miR-30a/c-5p was examined by methylation specific PCR. RESULTS: miR-30a-5p and miR-30c-5p, in contrast to other miR-30 family members, dramatically decreased in cisplatin-resistant CP70 cells due to overexpressed-DNMT1 induced aberrant methylation. miR-30a/c-5p in turn directly inhibited DNMT1 as well as Snail. Forced expression of miR-30a/c-5p or knocking down of DNMT1 and Snail promoted cisplatin susceptibility and partially reversed epithelial-mesenchymal transition (EMT) in CP70 cells, while inhibition of miR-30a/c-5p or ectopic expression of DNMT1 and Snail induced cisplatin resistance and partial EMT in cisplatin-sensitive A2780 cells. CONCLUSIONS: A feedback loop between miR-30a/c-5p and DNMT1 is a potent signature for cisplatin-resistance and EMT in ovarian cancer, promising a potential target for improved anti-cancer treatment.

TET3 inhibits TGF-ß1-induced epithelial-mesenchymal transition by demethylating miR-30d precursor gene in ovarian cancer cells.

BACKGROUND: Abnormal DNA methylation/demethylation is recognized as a hallmark of cancer. TET (ten-eleven translocation) family members are novel DNA demethylation related proteins that dysregulate in multiple malignances. However, their effects on ovarian cancer remain to be elucidated. METHODS: The changes of TET family members during TGF-ß1-induced epithelial-mesenchymal transition (EMT) in SKOV3 and 3AO ovarian cancer cells were detected. TET3 was ectopically expressed in TGF-ß1-treated ovarian cancer cells to examine its effect on TGF-ß1-induced EMT phenotype. The downstream target of TET3 was further identified. Finally, the relationships of TET3 expression to clinic-pathological parameters of ovarian cancer were investigated with a tissue microarray using immunohistochemistry. RESULTS: TET3 was downregulated during TGF-ß1-initiatd epithelial-mesenchymal transition (EMT) in SKOV3 and 3AO ovarian cancer cells. Overexpression of TET3 reversed TGF-ß1-induced EMT phenotypes including the expression pattern of molecular markers (E-cadherin, Vimentin, N-cadherin, Snail) and migratory and invasive capabilities of ovarian cancer cells. miR-30d was identified as a downstream target of TET3, and TET3 overexpression resumed the demethylation status in the promoter region of miR-30d precursor gene, resulting in restoration of miR-30d (an EMT suppressor of ovarian cancer cells proven in our previous study) level in TGF-ß1-induced EMT. We further found that TET3 expression was decreased in ovarian cancer tissues, especially in serous ovarian cancers. The overall positivity of TET3 was inversely correlated with the grade of differentiation status of ovarian cancer. CONCLUSION: Our results revealed that TET3 acted as a suppressor of ovarian cancer by demethylating miR-30d precursor gene promoter to block TGF-ß1-induced EMT.

miR-30d Blocked Transforming Growth Factor ß1-Induced Epithelial-Mesenchymal Transition by Targeting Snail in Ovarian Cancer Cells.

OBJECTIVE: MicroRNAs (miRs) are essential regulators of gene expression by suppressing translation or causing degradation of target mRNA. Growing evidence sheds light on the crucial roles of miR dysregulation in cancer development and progression. In this study, we focused on the role of miR-30d in transforming growth factor ß1 (TGF-ß1)-initiated epithelial-mesenchymal transition (EMT) in ovarian cancer cells. METHODS: Transforming growth factor ß1 (10 ng/mL) was used to initiate EMT in SKOV3 and 3AO cells. The expression of miR-30 family members was determined by quantitative real-time polymerase chain reaction. Messenger RNA and protein levels of E-cadherin, N-cadherin, vimentin, and Snail were detected by quantitative real-time polymerase chain reaction and Western blot, respectively. Cell migration and invasion capacities were evaluated by Transwell chamber assay. Luciferase activity assay was performed to verify the direct inhibition of Snail by miR-30d. RESULTS: MiR-30b, MiR-30c, and MiR-30d were down-regulated during TGF-ß1-induced EMT in SKOV3 and 3AO ovarian cancer cells. Restoration of miR-30d by miR-30d mimic reversed TGF-ß1-induced EMT phenotypes including the morphological changes, expression pattern of molecular markers (E-cadherin, N-cadherin), and migratory and invasive capabilities in ovarian cancer cells. Furthermore, Snail was identified as the direct target of miR-30d. CONCLUSIONS: Our results revealed that miR-30d functioned as a suppressor of ovarian cancer progression by decreasing Snail expression and thus blocking TGF-ß1-induced EMT process, suggesting the potentiality of miR-30d analogs to be used as therapeutics for ovarian cancer.

Ginsenoside 20(S)­Rg3 inhibits the Warburg effect through STAT3 pathways in ovarian cancer cells.

Cancer cells prefer to metabolize glucose through aerobic glycolysis, known as the Warburg effect. It plays a crucial role in proliferation and progression of cancer cells. However, the complete mechanism remains elusive. In recent studies, the signal transducer and activator of transcription 3 (STAT3) signaling has been discovered to have roles in cancer­associated changes in metabolism. In this study, we find that the ginsenoside 20(S)­Rg3, a pharmacologically active component of the traditional Chinese herb Panax ginseng, inhibits glycolysis in ovarian cancer cells by regulating hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2). We also show that 20(S)­Rg3 regulates HK2 through downregulation of p­STAT3 (Tyr705). Furthermore, overexpression of STAT3 in ovarian cancer cells weakened the suppression of Warburg effect induced by 20(S)­Rg3. Importantly, 20(S)­Rg3 treatment represses HK2 expression in nude mouse xenograft models of ovarian cancer. Taken together, our results show that 20(S)­Rg3 inhibits the Warburg effect by targeting STAT3/HK2 pathway in ovarian cancer cells, highlighting the potentiality of 20(S)­Rg3 to be used as a therapeutic agent for ovarian cancer.