Drug Resistance in Hepatocellular Carcinoma: Theoretical Basis and Therapeutic Aspects.

Primary liver cancer is one of the most common malignant tumors with high mortality and increasing incidence worldwide. Currently, chemotherapy is an important comprehensive treatment for moderate or advanced liver cancer. Despite the effective therapeutic effects initially achieved by chemotherapy, the high phenotypic and molecular heterogeneity of liver cancer cells facilitates resistance to conventional chemotherapy or targeted therapy and even leads to multidrug resistance (MDR), which is one of the major obstacles for clinical chemotherapy. Drug resistance exhibits multiple and complex molecular mechanisms to antagonize therapy under pharmacological pressure, including overexpression of drug efflux transporters, downstream adaptive response (such as apoptosis, autophagy, and endoplasmic reticulum stress), dysfunction of DNA damage repair (DDR), epigenetic modification, tumor microenvironment (TME) as well as extracellular matrix (ECM). In this paper, we summarize the recent research progress and intervention strategies for drug resistance in hepatocellular carcinoma (HCC), which will provide a promising therapeutic strategy for overcoming MDR in liver cancer.

NAMPT promotes the malignant progression of HBV-associated hepatocellular carcinoma through activation of SREBP1-mediated lipogenesis.

Metabolic reprogramming is a hallmark of cancer. The nicotinamide phosphoribosyltransferase (NAMPT)-mediated salvage pathway maintains sufficient cellular NAD levels and is required for tumorigenesis and development. However, the molecular mechanism by which NAMPT contributes to HBV-associated hepatocellular carcinoma (HCC) remains not fully understood. In the present study, our results showed that NAMPT protein was obviously upregulated in HBV-positive HCC tissues compared with HBV-negative HCC tissues. NAMPT was positively associated with aggressive HCC phenotypes and poor prognosis in HBV-positive HCC patients. NAMPT overexpression strengthened the proliferative, migratory, and invasive capacities of HBV-associated HCC cells, while NAMPT-insufficient HCC cells exhibited decreased growth and mobility. Mechanistically, we demonstrated that NAMPT activated SREBP1 (sterol regulatory element-binding protein 1) by increasing the expression and nuclear translocation of SREBP1, leading to the transcription of SREBP1 downstream lipogenesis-related genes and the production of intracellular lipids and cholesterol. Altogether, our data uncovered an important molecular mechanism by which NAMPT promoted HBV-induced HCC progression through the activation of SREBP1-triggered lipid metabolism reprogramming and suggested NAMPT as a promising prognostic biomarker and therapeutic target for HBV-associated HCC patients.

Application of contrast-enhanced intraoperative ultrasonography in the decision-making about hepatocellular carcinoma operation.

AIM: To evaluate the detection and differentiation ability of contrast-enhanced intraoperative ultrasonography (CE-IOUS) in hepatocellular carcinoma (HCC) operations. METHODS: Clinical data of 50 HCC patients were retrospective analyzed. The sensitivity, specificity, false negative and false positive rates of contrast enhanced magnetic resonance imaging (CE-MRI), IOUS and CE-IOUS were calculated and compared. Surgical strategy changes due to CE-IOUS were analyzed. RESULTS: Lesions detected by CE-MRI, IOUS and CE-IOUS were 60, 97 and 85 respectively. The sensitivity, specificity, false negative rate, false positive rate of CE-MRI were 98.2%, 98.6%, 98.6%, 60.0%, respectively; for IOUS were 50.0%, 90.9%, 1.8%, 1.4%, respectively; and for CE-IOUS were 1.4%, 40.0%, 50.0%, 9.1%, respectively. The operation strategy of 9 (9/50, 18.0%) cases was changed according to the results of CE-IOUS. CONCLUSION: Compared with CE-MRI, CE-IOUS performs better in detection and differentiation of small metastasis and regenerative nodules. It plays an important role in the decision-making of HCC operation.