Hepatocellular carcinoma (HCC) is one of the most deadly types of cancer. Sorafenib is currently the only available first-line molecular targeted drug approved by the FDA for HCC. However, primary and secondary resistance is often encountered with treatment with sorafenib. Genomic alterations found in HCC represent potential targets to develop new drugs or new combinational strategies against this type of cancer. Here we analyzed genomic alterations from the TCGA database of HCC samples and the corresponding targeted drugs available to the clinic to identify candidate drugs that might hold promise when used in combination with sorafenib. Our results revealed that IL6, JAK1, LEPR and RAF1 related pathways were commonly altered in HCC, which have targeted drugs available in medical practice. Fourteen genes with available targeting drugs were frequently altered in HCC. The pathways and gene targets with the respective targeted drugs warrant further evaluation in clinical trials to determine their therapeutic value in the treatment of HCC, alone or in combination with sorafenib. In summary, the analysis of TCGA, identified a series of pathways with targeted drugs available that were altered in HCC. Combination treatment with specific targeted drugs, depending on the altered pathways found in individuals may provide a better treatment strategy that will ultimately improve individual patient survival.

Purpose: Circulating microRNA (miRNA) has been reported to have diagnostic value in multiple tumors. To identify serum miRNAs for early diagnosis of hepatocellular carcinoma (HCC), we analyzed the differential miRNA expression between HCC patients and controls.Methods: Real-time reverse transcription polymerase chain reaction (RT-PCR) was carried out to detect serum miR-16, miR-22, and miR-122 expression in 100 HCC patients and 100 controls (including hepatitis B, liver cirrhosis, liver metastases, hepatic hemangioma, health group, and each of them had 20 subjects). The miRNA expression results were combined with alpha-fetoprotein (AFP) to evaluate the diagnostic efficacy in HCC through receiver operating characteristic (ROC) curve. And the target genes were predicted through bioinformatics methods.Results: Compared with controls, the expression of miR-16 and miR-122 significantly increased in early-stage HCC patients, while no significant changes were detected in miR-22. The ROC curve analysis demonstrated that miR-16 and miR-122 had a high diagnostic efficacy (AUC 0.798 and 0.759), and it was improved when combined with AFP (AUC 0.862). When compared with each of the five groups in the controls, the results showed that miR-16 of HCC was significantly higher than liver cirrhosis (AUC 0.936), liver metastases, and health; miR-122 was significantly higher than liver metastases, hepatitis B, and health. Moreover, 175 and 101 potential target genes were regulated by miR-16 and miR-122, respectively. And most of the target genes were enriched in the PI3K, MAPK, FoxO signaling pathways, and pathways in cancer. Conclusion:Our findings illustrate that both circulating miR-16 and miR-122 can provide value for early diagnosis of HCC and they are potential biomarkers for the earlystage HCC.

Background Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has an extremely poor prognosis. We aimed to determine the latent relationships between TRIM36 regulation of apoptosis and the Wnt/β-catenin pathway in HCC. Methods Immunohistochemistry and western blotting were used to characterize the aberrant expression of TRIM36 in HCC and adjacent tissues. Clinical information was analyzed using Kaplan–Meier and Cox methods. RNA-seq of potential targets was conducted to detect the regulation of TRIM36. Apoptosis assays and cellular proliferation, invasion and migration were conducted in a loss- and gain-of-function manner in cultured cells to determine the biological functions of TRIM36. A rescue experiment was conducted to confirm the role of Wnt/β-catenin signaling in TRIM36 regulation. Finally, in vivo experiments were conducted using cell line-derived xenografts in nude mice to validate the central role of TRIM36 in HCC. Results TRIM36 expression was significantly downregulated in HCC tissues compared to adjacent non-tumor tissues. TRIM36 repressed the proliferation, migration, and invasion of Huh7 and HCCLM3 cells, whereas it stimulated apoptosis. Wnt/β-catenin signaling was inhibited by TRIM36, and rescue experiments highlighted its importance in HCC proliferation, migration, and invasion. In vivo experiments further confirmed the effects of sh-TRIM36 on HCC tumorigenesis, inhibition of apoptosis, and promotion of Wnt/β-catenin signaling. Conclusion Our study is the first to indicate that TRIM36 acts as a tumor suppressor in HCC. TRIM36 activates apoptosis and inhibits cellular proliferation, invasion, and migration via the Wnt/β-catenin pathway, which may serve as an important biomarker and promising therapeutic target for HCC.

In this paper, the analytical relationship among supply voltage, current, and structure parameters of the permanent magnet (PM) motor is cleverly deduced by using an intermediate-flux linkage. After further consideration of boundary conditions, the direct field-circuit coupled analytical model in integrated matrix form is subsequently constructed. Using this model, the vector potentials and currents of the motor can be calculated simultaneously, and the electromagnetic performance, such as the output torque, winding flux linkage, and so on can be further calculated by the vector potentials. Because the control parameters and motor structure parameters are both considered in the derivation process, the proposed analytical model can be used to analyse the motor operation performance under different control strategies. Its validity is finally verified on a 10-pole/12-slot PM motor. The results of the proposed direct field-circuit coupled analytical model are compared with those of field-circuit coupled time-stepping finite element model and experiment under speed-current double closed-loop and current closed-loop control strategies, respectively. The results of the proposed model are proved well with finite element simulation and experimental results.

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