ABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) is a type of primary liver cancer with high mortality. Circular RNAs (circRNAs) have been confirmed to be involved in the development of HCC, but the functions of circ_0011232 in HCC remain ill-defined. METHODS: Quantitative real-time polymerase chain reaction, western blot assay, or immunohistochemistry assay was performed to determine the levels of circ_0011232, miR-503-5p, and AKT3. RNase R assay and actinomycin D assay were conducted to analyze the feature of circ_0011232. Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, colony formation assay, flow cytometry analysis, wound-healing assay, and transwell assay were conducted to evaluate HCC cell proliferation, colony formation, apoptosis, migration, and invasion. Dual-luciferase reporter assay was carried out to confirm the relationships among circ_0011232, miR-503-5p, and AKT3. The murine xenograft assay was conducted to verify the function of circ_0011232 in tumor growth in vivo. RESULTS: Circ_0011232 and AKT3 were upregulated, while miR-503-5p was decreased in HCC tissues and cells. Circ_0011232 knockdown repressed HCC cell proliferation, colony formation, migration, and invasion, and promoted apoptosis in vitro and blocked tumor growth in vivo. MiR-503-5p was a target of circ_0011232. MiR-503-5p inhibition reversed the effects of circ_0011232 knockdown on HCC cell development. Moreover, AKT3 was confirmed to be a target of miR-503-5p, and AKT3 overexpression abolished the inhibitory effects on HCC cell progression caused by miR-503-5p. CONCLUSION: Circ_0011232 facilitated HCC progression via miR-503-5p/AKT3 axis, which might provide a novel treatment strategy for HCC.
ABSTRACT
BACKGROUND: This study aimed to investigate the work status of clinicians in China and their management strategy alteration for patients with hepatocellular carcinoma (HCC) during the COVID-19 pandemic. METHODS: A nationwide online questionnaire survey was conducted in 42 class-A tertiary hospitals across China. Experienced clinicians of HCC-related specialties responded with their work status and management suggestions for HCC patients during the pandemic. RESULTS: 716 doctors responded effectively with a response rate of 60.1%, and 664 were included in the final analysis. Overall, 51.4% (341/664) of clinicians reported more than a 60% reduction of the regular workload and surgeons declared the highest proportion of workload reduction. 92.5% (614/664) of the respondents have been using online medical consultation to substitute for the "face-to-face" visits. Adaptive adjustment for the treatment strategy for HCC was made, including the recommendations of noninvasive and minimally invasive treatments such as transcatheter arterial chemoembolization for early and intermediate stage. Targeted therapy has been the mainstay for advanced stage and also as a bridge therapy for resectable HCC. DISCUSSION: During the COVID-19 pandemic, online medical consultation is recommended to avoid social contact. Targeted therapy as a bridge therapy is recommended for resectable HCC considering the possibility of delayed surgery.
Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/therapy , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Liver Neoplasms/therapy , Pandemics , SARS-CoV-2 , Surveys and QuestionnairesABSTRACT
Associations between ABCB1 and XPC genetic polymorphisms and risk of developing colorectal cancer (CRC) as well as clinical outcomes in CRCs with chemotherapy were investigated. A case-control study was performed on the ABCB1 C3435T, G2677T/A and XPC Lys939Gln polymorphisms in 428 CRC cases and 450 hospital- based, age and sex frequency-matched controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. We observed that the ABCB1 3435CT or CC+CT variants were significantly linked with increasing risk of developing CRC (adjusted OR (95% CI): 1.814 (1.237-2.660), P=0.0022; adjusted OR (95% CI): 1.605 (1.117-2.306), P=0.0102, respectively). Moreover, the distribution frequency of XPC AC genotype or AC+CC genotypes also showed a tendency towards increasing the suscepbility for CRC (P=0.0759 and P=0.0903, respectively). Kaplan-Meier curves showed that the ABCB1 C3435T variant was associated with a tendency toward longer progression-free survival (PFS) (n=343, Log-rank test: P=0.063), and the G2677T/A variant genotypes (GT+TT+GA+AA) with a tendency for longer OS in postoperative oxaliplatin-based patients (n=343, Log-rank test: P=0.082). However, no correlation of the XPC Lys939Gln polymorphism was found with PFS and OS in patients with postoperative oxaliplatin-based chemotherapy (n=343). Our study indicated that ABCB1 polymorphisms might be candidate pharmacogenomic factors for the prediction of CRC susceptibility, but not for prognosis with oxaliplatin chemosensitivity in CRC patients.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , DNA-Binding Proteins/genetics , Genetic Predisposition to Disease , Neoplasm Recurrence, Local/genetics , Polymorphism, Genetic/genetics , ATP Binding Cassette Transporter, Subfamily B , Adult , Aged , Aged, 80 and over , Asian People/genetics , Case-Control Studies , Colorectal Neoplasms/mortality , Colorectal Neoplasms/therapy , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/therapy , Neoplasm Staging , Prognosis , Survival RateABSTRACT
XRCC1 genetic polymorphisms could be associated with increased risk of various cancer, including hepatocellular carcinoma (HCC), the fifth most common cancer. We here conducted a study to explore the role of selective SNPs of the XRCC1 and XPD genes in the prognosis of HCC. A total of 231 cases were collected, and genotyping of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XPD Lys751Gln and XPD Asp312Asn was performed by duplex polymerase-chain-reaction with the confronting-two-pair primer method. Our findings indicated XRCC1 399Gln/Gln genotype was associated with a significant difference in the median survival time compared with patients carrying Arg/Trp and Arg/Arg genotypes, and individuals with XPD 751 Gln/ Gln genotype had a significantly greater survival time than patients carrying Lys/Lys and Lys/Gln genotypes. The Cox's regression analysis showed individuals carrying XRCC1 399Trp/Trp genotype had 0.55 fold risk of death from HCC than Arg/Arg genotype. Similarly, XPD 751Gln/Gln had a strong decreasein comparison to XPD Lys/Lys carriers with an HR of 0.34. These results suggest that polymorphisms in XRCC1 and XPD may have functional significance in the prognosis of HCC.
