Synchronous profiling of mRNA N6-methyladenosine modifications and mRNA expression in high-grade serous ovarian cancer: a pilot study.

This study aimed to synchronously determine epitranscriptome-wide RNA N6-methyladenosine (m6A) modifications and mRNA expression profile in high grade serous ovarian cancer (HGSOC). The methylated RNA immunoprecipitation sequencing (MeRIP-seq) was used to comprehensively examine the m6A modification profile and the RNA-sequencing (RNA-seq) was performed to analyze the mRNA expression profile in HGSOC and normal fallopian tube (FT) tissues. Go and KEGG analyses were carried out in the enrichment of those differentially methylated and expressed genes. MeRIP-seq data showed 53,794 m6A methylated peaks related to 19,938 genes in the HGSOC group and 51,818 m6A peaks representing 19,681 genes in the FT group. RNA-seq results revealed 2321 upregulated and 2486 downregulated genes in HGSOC. Conjoint analysis of MeRIP-seq and RNA-seq data identified differentially expressed genes in which 659 were hypermethylated (330 up- and 329 down-regulated) and 897 were hypomethylated (475 up- and 422 down-regulated). Functional enrichment analysis indicated that these differentially modulated genes are involved in pathways related to cancer development. Among methylation regulators, the m6A eraser (FTO) expression was significantly lower, but the m6A readers (IGF2BP2 and IGF2BP3) were higher in HGSOC, which was validated by the subsequent real-time PCR assay. Exploration through public databases further corroborated their possible clinical application of certain methylation regulators and differentially expressed genes. For the first time, our study screens the epitranscriptome-wide m6A modification and expression profiles of their modulated genes and signaling pathways in HGSOC. Our findings provide an alternative direction in exploring the molecular mechanisms of ovarian pathogenesis and potential biomarkers in the diagnosis and predicting the prognosis of the disease.

Sulforaphene suppressed cell proliferation and promoted apoptosis of COV362 cells in endometrioid ovarian cancer.

Aim: N6-methyladenosine (m6A) RNA methylation exerts a regulatory effect on endometrioid ovarian cancer (EOC), but the specific m6A regulator genes in EOC remain to be explored. This study investigated that sulforaphene (Sul) is implicated in EOC development by regulating methyltransferase-like 3 (METTL3). Methods: The dysregulated m6A RNA methylation genes in EOC were determined by methylated RNA immunoprecipitation (MeRIP-seq) and RNA sequencing. The roles of METTL3 and/or Sul on viability, proliferative ability, cell cycle, and apoptosis of EOC cells were determined by MTT, colony formation, flow cytometry, and TUNEL staining assay, respectively. The expression of METTL3 and apoptosis-related proteins in EOC cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays. Results: Five m6A RNA methylation regulators (METTL3, ELF3, IGF2BP2, FTO, and METTL14) were differentially expressed in EOC, among which METTL3 had the highest expression level. Silencing METTL3 reduced the clonal expansion and viability of EOC cells, and caused the cells to arrest in the G0/G1 phase. This also promoted apoptosis in the EOC cells and activated the FAS/FADD and mitochondrial apoptosis pathways. In contrast, overexpressing METTL3 had the opposite effect. Sul, in a dose-dependent manner, reduced the viability of EOC cells but promoted their apoptosis. Sul also increased the levels of IGF2BP2 and FAS, while decreasing the levels of KRT8 and METTL3. Furthermore, Sul was able to reverse the effects of METTL3 overexpression on EOC cells. Conclusions: Sul could suppress cell proliferation and promote apoptosis of EOC cells by inhibiting the METTL3 to activate the FAS/FADD and apoptosis-associated pathways.

Bioinformatic analysis the expression and clinical significance of CDRT15 in cholangiocarcinoma using TCGA database.

Cholangiocarcinoma (CCA) is a common and lethal malignant tumor originating from bile duct epithelial cells. Various tumor biomarkers have been used for its clinical screening, such as carbohydrate antigen 19-9 and carcinoembryonic antigen. This study aimed to demonstrate the value of associated genes-CMT1A duplicated region transcript 15 (CDRT15) for prognosis of CCA by integrated bioinformatics analysis. We obtained CDRT15 expression data and clinical information on patients with CCA from The Cancer Genome Atlas database. Then, we processed the data by differentially expressed gene analysis, gene set enrichment analysis, statistical analysis, etc. Gene Ontology enrichment analysis was aimed to explore the function of gene-related proteins. Single-sample gene set enrichment analysis was used to analyze the correlation between CDRT15 and immune cells. Finally, we constructed the nomogram to predict the prognosis of patients with CCA. The analysis of data in The Cancer Genome Atlas database revealed that CDRT15 was overexpressed in CCA tissues. We performed the interrelation analysis of immune infiltration, showing that CDRT15 are mainly associated with the immune/inflammatory response. ROC curve showed that CDRT15 can be a diagnostic marker of CCA. Subsequently, the prognostic analysis showed that the high expression of CDRT15 was correlated with the poor OS, and patients with high CDRT15 expression may have a poor prognosis. CDRT15 is more highly expressed in CCA, thus we identified that CDRT15 could be an efficient biomarker for patients. CDRT15 expression was negatively correlated with prognosis of CCA. CDRT15 may be involved in the immune infiltration process of CCA.

The enhanced recovery after surgery (ERAS) protocol in elderly patients with acute cholecystitis: A retrospective study.

Enhanced recovery after surgery (ERAS) protocol is a perioperative management theory aimed at reducing the injury of surgical patients and accelerating postoperative recovery. It has been widely recognized and applied in elective surgery. This study aimed to evaluate the clinical value of the ERAS protocol during the perioperative period of laparoscopic cholecystectomy in elderly patients with acute cholecystitis. This study aimed to evaluate the clinical value of the ERAS protocol during the perioperative period of laparoscopic cholecystectomy in elderly patients with acute cholecystitis. We collected medical data from 126 elderly patients with acute cholecystitis from October 2018 to August 2021. Among the 126 patients, 70 were included in the ERAS group and 56 in the traditional group. We analyzed the clinical data and postoperative indicators of the 2 groups. No significant differences were observed regarding the general characteristics of the 2 groups (P > .05). The ERAS group had significantly earlier time to first flatus, time to first ambulation, and time to solid intake, compared with the traditional group (P < .001); additionally, the ERAS group had significantly shorter stay and gentler feeling of postoperative pain (P < .001). Furthermore, the ERAS group had significant incidences of lower postoperative lung (P = .029) and abdominal cavity infection (P = .025) compared to the traditional group. No significant difference was observed regarding the incidences of other postoperative complications between the 2 groups (P > .05). The ERAS protocol helps reduce elderly patients' stress reactions and accelerate postoperative recovery. Thus, it is effective and beneficial to implement the ERAS protocol during the perioperative period of elderly patients with acute cholecystitis.

Association between Prestored Smartphone Monitored Physical Activity and the Risk of HPV Infection and Cervical Cancer.

OBJECTIVE: This study was to determine the prevalence of HPV in non-vaccinated women from East China, and the association between prestored smartphone monitored physical activity and the risk of human papillomaviruses (HPV) infection and cervical cancer. METHODS: We retrospectively reviewed medical records of unvaccinated women received first-time cervical HPV screening in the Affiliated Cancer Hospital of University of Chinese Academy of Sciences between March 2018 and December 2019. HPV genotyping was examined by the GenoArray. Physical activity defined by any movements at speeds of 0.5-2 m/s was obtained from smartphones. We collected prestored physical activity data for 6 months prior to the HPV screening. Logistic regression models were applied to determine the association between physical activity and the risk of HPV infection and cervical cancer. RESULTS: A total of 11,730 women were initially included. Women with cervical cancer had significantly higher prevalence of infection with any high-risk (HR) HPV, or with individual HPV16, 18, 31, 33, 45, 52 and 58. Among them, 896 controls and 289 cervical cancer women had information of smartphone monitored physical activity. Multivariate logistic regression analysis showed that more daily physical activity time (or distance) was a protective factor for infection with any HR HPV, or infection with HPV16, but not other individual HPVs. Increased age, less physical activity time (or distance), and infection with any HR HPV (16, 18, 31, 52 and 58) were associated with a significantly increased risk of cervical cancer. In contrast, obesity was not associated with risk of HPV infection and cervical cancer. CONCLUSION: The high prevalence of HPV infection in unvaccinated women highlights the importance of prevention. More daily physical activity time (or distance) may help to reduce the risk of HPV infection and cervical cancer. Smartphone monitoring is an effective tool for recording physical activity.
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Prognostic and Clinicopathological Significance of C-Reactive Protein to Albumin Ratio in Patients with Bile Duct Cancer: A Meta-Analysis.

Recent studies have explored the prognostic role of the C-reactive protein to albumin ratio (CAR) in patients with bile duct cancer (BTC), but the results have been inconsistent. This study aimed to provide insight into the prognostic significance of the CAR in BTC prior to treatment using a meta-analysis. Summarized hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for prognosis and clinicopathological features using fixed or random effects models. Fourteen studies with a total of 1,543 subjects were included in this meta-analysis. Elevated CAR was significantly associated with poor overall survival (HR = 2.17, 95% CI = 1.81-2.60, P < 0.001) and decreased disease-free survival or recurrence-free survival (HR = 2.53, 95% CI = 1.98-3.25, P < 0.001) in BTC. In addition, high CAR was significantly associated with the presence of lymph node metastasis (OR = 1.54, 95% CI = 1.12- 2.13, P = 0.008), bile duct invasion (OR = 2.64, 95% CI = 1.54-4.54, P < 0.001), and tumor stages III-IV (OR = 3.11, 95% CI = 1.05-9.20, P = 0.040). However, there was no significant association between CAR and sex, microvascular invasion, or resection. An elevated CAR was significantly related to worse long-term and short-term survival and advanced clinicopathological features of BTC. CAR could serve as a valuable, noninvasive prognostic marker in patients with BTC.

Comprehensive Analysis of the Transcriptome-Wide m6A Methylome in Endometrioid Ovarian Cancer.

Emerging studies have revealed that N6-methyladenosine modification is involved in the development of various cancers. However, the m6A modification pattern of endometrioid ovarian cancer (EOC) has not been demonstrated. In the present study, high-throughput sequencing combined with methylated RNA immunoprecipitation (MeRIP-seq) and RNA sequencing were used to obtain the transcriptome-wide m6A modifications of endometrioid ovarian cancer for the first time. The roles of methyltransferase-like 3 (METTL3) in EOC cell line COV362 were explored. In total, 39,237 m6A-modified peaks related to 17,082 genes were identified in the EOC group, and 52,848 m6A peaks representing 19,349 genes were detected in endometriosis group. Functional enrichment analysis revealed that m6A enriched genes were associated with tight junctions, cell adhesion molecules, platinum drug resistance, adherens junction, and more. METTL3 knockdown in the COV362 cells significantly decreased cell proliferation, promoted cell apoptosis, and induced cell cycle arrest at the G0/G1 phase. Our study presented the transcriptome-wide m6A modifications of endometrioid ovarian cancer for the first time and revealed various differentially expressed genes with methylated m6A modifications. This study may provide new directions for in-depth research of the underlying molecular mechanisms and signaling pathways of EOC development and progression.

Case report: Giant cystic ileal gastrointestinal stromal tumor with an atypical intratumoral abscess.

Background: Gastrointestinal stromal tumors (GISTs) are typically solid, sometimes with small cystic areas, but rarely manifest as predominantly cystic neoplasms. In addition, cystic intestinal GISTs with intratumoral abscess formation are rare. Case presentation: We present the case of a 49-year-old male patient with a history of frequent and urgent urination for 2 weeks. Radiologic studies revealed a large cystic mass in the lower abdomen. The patient underwent abdominal laparotomy, which revealed a large cystic mass arising from the distal ileum invading the sigmoid mesocolon and apex vesicae. Partial resection of the ileum along with the tumor and the adjacent bladder was performed. Macroscopic examination revealed that the cystic mass contained a large amount of foul-smelling pus and a tumor-bowel fistula. The final pathology revealed an abdominal stromal tumor. Postoperative recovery was uneventful, and adjuvant imatinib mesylate 400 mg was administered daily. No tumor recurrence or metastasis was observed during the 9-month follow-up period. Conclusion: Fingings of a cystic tumor in the abdomen should raise concern for cystic GISTs. This case report reviews a rare presentation of an ileal giant cystic GIST with atypical intratumoral abscess formation. Complete surgical resection and adjuvant imatinib is still the mainstay treatment for GISTs.

Different prognosis of stage IIIB cervical cancer patients with lower third of vaginal invasion and those without.

OBJECTIVE: Previous studies have evaluated the prognostic factors of patients with stage IIIB cervical cancer. However, there was only one study evaluating the relationship between LTI (lower third of vaginal invasion) and the prognosis of the patients with stage IIIB cervical cancer. Our research aimed to assess different therapeutic outcomes of the stage IIIB CCP (cervical cancer patients) with or without LTI. METHODS: From December 2007 to December 2014, patients with FIGO (International Federation of Gynecology and Obstetrics, 2009) stage IIIB cervical cancer admitted and treated in Zhejiang Cancer Hospital were enrolled and evaluated in this retrospective research. Different clinicopathological variables and treatment outcomes were analyzed by using multivariate and univariate Cox regression models and chi-square or Fisher's exact test. RESULTS: The number of enrolled patients was 622, among which 74 cases were with LTI and 548 without. The two- and five-year OS (overall survival) rates in non-LTI group were 79.9% and 58.9%, and the OS rates in LTI group were 68.9% and 38.8%, respectively (P = 0.001). The two- and five-year PFS (progression-free survival) rates in non-LTI group were 63.3% and 53.1%, and the PFS rates in LTI group were 45.9% and 37.0% respectively (P = 0.002). Multivariate Cox regression analysis indicated that histological type, total treatment time, hydronephrosis, and treatment protocol were factors significantly affecting the PFS rates in stage IIIB CCP, and OS rates were associated with histological type, hydronephrosis, treatment protocol, and LTI. CONCLUSIONS: Our study showed that stage IIIB CCP with LTI had worse prognosis than those without LTI.

Heat maps present the spatial distribution of human papillomavirus infection in Zhejiang Province, China.

Determining the spatial distribution of human papillomavirus (HPV) and performing accurate public health analyses helps to distinguish areas of healthcare that require further research, and enables therapeutic techniques and approaches in healthcare to be focused more accurately. A total of 4,560 women were enrolled in the present study. Flow-through hybridization and gene chip assays were used to detect the genotypes of HPV infection. Heat maps were then generated to present the spatial distribution of HPV infections in Zhejiang Province according to genotype. Of the exfoliated cervical cell samples from the 4,560 women, HPV was detected in 1,886 samples. HPV-16, -58, -52 and -18 were the most prevalently identified genotypes in the population included in the present study. HPV-16 and -58 infections were mainly distributed in the northern and central regions of Zhejiang Province, such as in Hangzhou and Shaoxing, where the prevalence was higher than that in the southern regions (P<0.05). HPV-18 infection was widespread throughout Zhejiang Province, but had a much lower infection rate in Ningbo and Huzhou (P<0.05). High infection rates of HPV-52 were mainly detected in Hangzhou and the eastern coastal areas of Wenzhou, with a relatively low rate of infection in the center of the province (P<0.05). In conclusion, HPV-16, -58, -52 and -18 were the four most prevalent HPV genotypes observed in Zhejiang Province. Heat maps were created to display the spatial distribution of HPV infection according to genotype, which varied by geographical regions. The results indicate that for individuals in Ningbo or Wenzhou, bivalent or quadrivalent vaccines may be suitable, but for those in Hangzhou and Shaoxing, nonavalent vaccines are strongly recommended.

Mucinous cystic neoplasm of the liver: A case report.

BACKGROUND: Mucinous cystic neoplasm of the liver (MCN-L) is a cyst-forming epithelial neoplasm. The most distinguishing feature is the ovarian-type subepithelial stroma on pathological examination. CASE SUMMARY: An abdominal ultrasound incidentally revealed a liver tumor in a 32-year-old woman. Physical and laboratory examination results did not reveal any abnormalities. Enhanced abdominal computed tomography (CT) revealed a cystic space measuring 7.2 cm × 5.4 cm in the liver. Subsequent CT showed an increase in tumor size. Thus, we performed surgical resection of the tumor and gallbladder. Postoperative histopathological examination confirmed the diagnosis of MCN-L. At the 6-mo of follow-up, no recurrence was observed on ultrasound or CT. CONCLUSION: Since preoperative diagnosis of MCN-L is difficult, active surgery is recommended and helpful for the diagnosis and treatment of MCN-L.

Using BI-RADS Stratifications as Auxiliary Information for Breast Masses Classification in Ultrasound Images.

Breast Ultrasound (BUS) imaging has been recognized as an essential imaging modality for breast masses classification in China. Current deep learning (DL) based solutions for BUS classification seek to feed ultrasound (US) images into deep convolutional neural networks (CNNs), to learn a hierarchical combination of features for discriminating malignant and benign masses. One existing problem in current DL-based BUS classification was the lack of spatial and channel-wise features weighting, which inevitably allow interference from redundant features and low sensitivity. In this study, we aim to incorporate the instructive information provided by breast imaging reporting and data system (BI-RADS) within DL-based classification. A novel DL-based BI-RADS Vector-Attention Network (BVA Net) that trains with both texture information and decoded information from BI-RADS stratifications was proposed for the task. Three baseline models, pre-trained DenseNet-121, ResNet-50 and Residual-Attention Network (RA Net) were included for comparison. Experiments were conducted on a large scale private main dataset and two public datasets, UDIAT and BUSI. On the main dataset, BVA Net outperformed other models, in terms of AUC (area under the receiver operating curve, 0.908), ACC (accuracy, 0.865), sensitivity (0.812) and precision (0.795). BVA Net also achieved the high AUC (0.87 and 0.882) and ACC (0.859 and 0.843), on UDIAT and BUSI. Moreover, we proposed a method that integrates both BVA Net binary classification and BI-RADS stratification estimation, called integrated classification. The introduction of integrated classification helped improving the overall sensitivity while maintaining a high specificity.

lncRNA DLGAP1-AS2 Knockdown Inhibits Hepatocellular Carcinoma Cell Migration and Invasion by Regulating miR-154-5p Methylation.

OBJECTIVE: DLGAP1-AS2 has been characterized as an oncogenic lncRNA in glioma. Our preliminary microarray analysis revealed the altered expression of DLGAP1-AS2 in hepatocellular carcinoma (HCC), but the role of DLGAP1-AS2 in HCC remains unknown. METHOD: Expression of DLGAP1-AS2 and miR-154-5p in paired HCC and nontumor tissues from 62 HCC patients was determined by RT-qPCR. The 62 HCC patients were followed up for 5 years to analyze the prognostic value of DLGAP1-AS2 for HCC. DLGAP1-AS2 knockdown and miR-154-5p overexpression was achieved in HCC cells to study the relationship between them. Methylation of miR-154-5p was analyzed by methylation-specific PCR. Cell proliferation was analyzed by CCK-8 assay. RESULTS: DLGAP1-AS2 was upregulated in HCC and predicted poor survival. miR-154-5p was downregulated in HCC and inversely correlated with DLGAP1-AS2. In HCC cells, DLGAP1-AS2 knockdown resulted in the upregulation of miR-154-5p expression and decreased methylation of miR-154-5p gene. Transwell assay showed that DLGAP1-AS2 knockdown and miR-154-5p overexpression inhibited cell invasion and migration, and the combination of LGAP1-AS2 knockdown and miR-154-5p overexpression showed stronger effects. CONCLUSION: DLGAP1-AS2 knockdown may inhibit HCC cell migration and invasion by regulating miR-154-5p methylation.

SOX2 knockdown slows cholangiocarcinoma progression through inhibition of transcriptional activation of lncRNA PVT1.

Cholangiocarcinoma (CCA) has accounted for a high rate of mortality and morbidity in the recent years. Long non-coding RNAs (lncRNAs) play an important role in different cellular environments, including cancer. As such, they have been used as potential targets during CCA therapy. The objective of this study was to investigate the effects of lncRNA PVT1 on CCA and its mechanisms behind lncRNA PVT1 regulation. The interactions among SOX2, lncRNA PVT1, miR-186 and SEMA4D were verified by chromatin immunoprecipitation, RNA immunoprecipitation and dual luciferase reporter gene assay. Gain- and loss-of-function experiments were conducted to explore the modulatory effects of SOX2, lncRNA PVT1, miR-186 and SEMA4D on cell viability, migration and invasion of CCA by CCK-8 and Transwell assays. In vivo effects of lncRNA PVT1 or SEMA4D were studied in a nude mouse model. MiR-186 was poorly expressed while SOX2, lncRNA PVT1 and SEMA4D were highly expressed in CCA cells. SOX2 induced the transcriptional activation of lncRNA PVT1 expression to promote proliferation, migration and invasion of CCA cells. LncRNA PVT1 bound to miR-186 and miR-186 was found to target SEMA4D. The overexpression of lncRNA PVT1 and SEMA4D, as well as the inhibition of miR-186 led to elevated CCA cell proliferation, migration and invasion. In vivo experiments confirmed the inhibitory role of lncRNA PVT1 knockdown or SEMA4D knockdown in CCA. All in all, SOX2 down-regulated miR-186 through the transcriptional activation of lncRNA PVT1, whereas elevating SEMA4D expression, thus promoting the progression of CCA.

Study of upfront surgery versus neoadjuvant chemotherapy followed by interval debulking surgery for patients with stage IIIC and IV ovarian cancer, SGOG SUNNY (SOC-2) trial concept.

BACKGROUND: Two randomized phase III trials (EORTC55971 and CHORUS) showed similar progression-free and overall survival in primary or interval debulking surgery in ovarian cancer, however both studies had limitations with lower rate of complete resection and lack of surgical qualifications for participating centers. There is no consensus on whether neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) could be a preferred approach in the management of advanced epithelial ovarian cancer (EOC) in the clinical practice. METHODS: The Asian SUNNY study is an open-label, multicenter, randomized controlled, phase III trial to compare the effect of primary debulking surgery (PDS) to NACT-IDS in stages IIIC and IV EOC, fallopian tube cancer (FTC) or primary peritoneal carcinoma (PPC). The hypothesis is that PDS enhances the survivorship when compared with NACT-IDS in advanced ovarian cancer. The primary objective is to clarify the role of PDS and NACT-IDS in the treatment of advanced ovarian cancer. Surgical quality assures include at least 50% of no gross residual (NGR) in PDS group in all centers and participating centers should be national cancer centers or designed ovarian cancer section or those with the experience participating surgical trials of ovarian cancer. Any participating center should be monitored evaluating the proportions of NGR by a training set. The aim of the surgery in both arms is maximal cytoreduction. Tumor burden of the disease is evaluated by diagnostic laparoscopy or positron emission tomography/computed tomography scan. Patients assigned to PDS group will undergo upfront maximal cytoreductive surgery within 3 weeks after biopsy, followed by 6 cycles of standard adjuvant chemotherapy. Patients assigned to NACT group will undergo 3 cycles of NACT-IDS, and subsequently 3 cycles of adjuvant chemotherapy. The maximal time interval between IDS and the initiation of adjuvant chemotherapy is 8 weeks. Major inclusion criteria are pathologic confirmed stage IIIC and IV EOC, FTC or PPC; ECOG performance status of 0 to 2; ASA score of 1 to 2. Major exclusion criteria are non-epithelial tumors as well as borderline tumors; low-grade carcinoma; mucinous ovarian cancer. The sample size is 456 subjects. Primary endpoint is overall survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02859038.

Transcription factor HIF1α promotes proliferation, migration, and invasion of cholangiocarcinoma via long noncoding RNA H19/microRNA-612/Bcl-2 axis.

Cholangiocarcinoma, which is the most common invasive malignant tumor of the biliary tract, has poor prognosis. There is evidence suggesting that hypoxia-inducible factor 1α (HIF1α) plays an important role in cholangiocarcinoma. Also, microRNA-612 (miR-612) is another key regulator of cholangiocarcinoma. In this study, we investigate the scantly documented interaction of HIF1α and miR-612 in cholangiocarcinoma. We first undertook microarray-based cholangiocarcinoma gene expression profiles to screen out the differentially expressed long noncoding RNAs (lncRNAs) and genes. We used reverse transcription quantitative polymerase chain reaction to detect the expression of HIF1α in normal bile duct and cholangiocarcinoma tissues, and in corresponding cells lines. Cell counting kit 8, scratch, and Transwell assays were used to detect the proliferation, migration and invasion of cholangiocarcinoma cells. Cell cycle distribution and apoptosis were detected by flow cytometry. ChIP, dual luciferase reporter gene assay, RNA pull-down, and RNA immunoprecipitation were used to verify relationship between HIF1α and lncRNA H19, and lncRNA H19 and miR-612. We also monitored tumor formation in nude mice to verify the effect of HIF1α on cholangiocarcinoma. HIF1α expression was elevated in cholangiocarcinoma tissues and cells. Silencing HIF1α reduced proliferation, migration, and invasion of cholangiocarcinoma cells. HIF1α transcriptionally activated the expression of lncRNA H19. Overexpression of miR-612 could rescue the proliferation, migration and invasion of cholangiocarcinoma cells caused by lncRNA H19 overexpression. Taken together, HIF1α activated lncRNA H19-mediated miR-612/Bcl-2 pathway to promote cholangiocarcinoma, suggesting a promising therapeutic target for cholangiocarcinoma.

Efficacy and safety of sofosbuvir-containing regimens in patients with chronic hepatitis C virus infection after liver transplantation: a meta-analysis.

BACKGROUND: This meta-analysis evaluated the efficacy and safety of a sofosbuvir (SOF)-containing regimen in patients with hepatitis C virus (HCV) infection after liver transplantation (LT). METHODS: We performed a systematic search for relevant published data on the PubMed, EMBASE, and Cochrane Library databases. Studies that evaluated any regimen in which SOF was used to treat patients with HCV infection after LT and reported the sustained virologic response 12 weeks (SVR12) after therapy were included. RESULTS: A total of 12 studies, involving 892 patients, were included in this analysis. The pooled estimate of SVR12 (sustained virologic response 12 weeks) was 88.1%. Subgroup analysis showed that patients who received SOF plus other DAAs had higher SVR12 than those treated with SOF plus ribavirin or peg-IFN. The pooled incidence of any adverse events (AEs) was 73.7%. CONCLUSIONS: The results of this study showed that the treatment response of SOF-containing regimens in patients with HCV infection after LT was satisfactory. However, more attention needs to be paid to the high rate of AEs associated with such regimens.

Correlation Between Single Nucleotide Polymorphisms of an miRNA Binding Site in the 3'UTR of PTEN and Risk of Cervical Cancer Among the Han Chinese.

Objective: To analyze the association between a single nucleotide polymorphism (SNP) in the 3' untranslated region (UTR) of the phosphatase and tensin homolog (PTEN) gene, that is within a microRNA (miRNA) binding site, and the risk of Chinese Han cervical cancer. Methods: A case-control study was carried out to analyze the genotype of the PTEN rs34140758 locus in 210 surgically treated, Han Chinese, cervical cancer patients and 210 healthy controls. The levels of the miRNAs hsa-miR-586 and hsa-miR-622 and the PTEN mRNA were analyzed by real-time reverse transcription-quantitative polymerase chain reaction in the cancerous and adjacent normal tissues from all cases. HeLa cells were transfected with the miRNAs, hsa-miR-586 and hsa-miR-622, to analyze their effects on PTEN gene expression. Results: After adjusting for age, body-mass index, alcohol consumption, smoking, and familial history of cancer, the PTEN rs34140758 A allele carriers were 1.47 times more likely to suffer from cervical cancer than the C allele carriers (odds ratio [OR] = 1.47, 95% confidence interval [CI]: 1.17-1.72, p = 0.001). Both hsa-miR-586 and hsa-miR-622 were highly expressed in the cancerous tissues of the cervical cancer patients, whereas PTEN expression was low. HeLa cell transfection experiments showed that hsa-miR-586 and hsa-miR-622 inhibited PTEN gene expression. The results of a dual-luciferase reporter assay showed that the PTEN gene is a target for both hsa-miR-586 and hsa-miR-622. Conclusion: The PTEN 3'UTR rs34140758 locus SNP is associated with the risk of cervical cancer in the Han Chinese population. The molecular mechanism may be that the rs34140758 SNP affects the regulation of PTEN gene expression through interaction with the hsa-miR-586 and hsa-miR-622 miRNAs.

A phase II trial of cytoreductive surgery combined with niraparib maintenance in platinum-sensitive, secondary recurrent ovarian cancer: SGOG SOC-3 study.

BACKGROUND: In China, secondary cytoreductive surgery (SCR) has been widely used in ovarian cancer (OC) over the past two decades. Although Gynecologic Oncology Group-0213 trial did not show its overall survival benefit in first relapsed patients, the questions on patient selection and effect of subsequent targeting therapy are still open. The preliminary data from our pre-SOC1 phase II study showed that selected patients with second relapse who never received SCR at recurrence may still benefit from surgery. Moreover, poly(ADP-ribose) polymerase inhibitors (PARPi) maintenance now has been a standard care for platinum sensitive relapsed OC. To our knowledge, no published or ongoing trial is trying to answer the question if patient can benefit from a potentially complete resection combined with PARPi maintenance in OC patients with secondary recurrence. METHODS: SOC-3 is a multi-center, open, randomized, controlled, phase II trial of SCR followed by chemotherapy and niraparib maintenance vs chemotherapy and niraparib maintenance in patients with platinum-sensitive second relapsed OC who never received SCR at recurrence. To guarantee surgical quality, if the sites had no experience of participating in any OC-related surgical trials, the number of recurrent lesions evaluated by central-reviewed positron emission tomography-computed tomography image shouldn't be more than 3. Eligible patients are randomly assigned in a 1:1 ratio to receive either SCR followed by 6 cycles of platinum-based chemotherapy and niraparib maintenance or 6 cycles of platinum-based chemotherapy and niraparib maintenance alone. Patients who undergo at least 4 cycles of chemotherapy and must be, in the opinion of the investigator, without disease progression, will be assigned niraparib maintenance. Major inclusion criteria are secondary relapsed OC with a platinum-free interval of no less than 6 months and a possibly complete resection. Major exclusion criteria are borderline tumors and non-epithelial ovarian malignancies, received debulking surgery at recurrence and impossible to complete resection. The sample size is 96 patients. Primary endpoint is 12-month non-progression rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03983226.