ABSTRACT
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. The outcome of current standard treatments, as well as targeted therapies in advanced stages, are still unsatisfactory. Attention has been drawn to novel strategies for better treatment efficacy. Hepatocyte growth factor/c-mesenchymal-epithelial transition factor (HGF/c-Met) axis has been known as an essential element in the regulation of liver diseases and as an oncogenic factor in HCC. In this review, we collected the evidence of HGF/c-Met as a tumor progression and prognostic marker, discussed the anti-c-Met therapy in vitro, summarized the outcome of c-Met inhibitors in clinical trials, and identified potential impetus for future anti-c-Met treatments. We also analyzed the inconsistency of HGF/c-Met from various publications and offered reasonable explanations based on the current understanding in this area. In conclusion, HGF/c-Met plays a crucial role in the progression and growth of HCC, and the strategies to inhibit this pathway may facilitate the development of new and effective treatments for HCC patients.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/drug therapy , Cell Proliferation , Epithelial-Mesenchymal Transition , Hepatocyte Growth Factor , Humans , Liver Neoplasms/drug therapy , Proto-Oncogene Proteins c-met/metabolism , Signal TransductionABSTRACT
Although the risk of post-hepatectomy liver failure is severe and it affects the prognosis of patients,hepatectomy is the first choice for hepatocellular carcinoma patients.At present,the mechanism of liver regeneration and post-hepatectomy liver failure is unclear.In this paper,we reviewed the liver regeneration for three stages:initiation,proliferation and termination,and also reviewed the mechanism of post-hepatectomy liver failure.
ABSTRACT
Statins, hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors , are widely used as a class of lipid-lowering drugs in clinic. Recent studies have shown that the use of statins can be anti-inflammatory, anti-fibrosis and reduce the incidence of hepatocellular carcinoma (HCC), which may provide a new method for the preventive treatment of HCC. This article will review the current research progress of statins, including the clinical evidence, the molecular mechanisms of anti-inflammatory, anti-fibrosis and anti-tumor in liver.
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Objective To investigate the relationship between the polymorphism of transforming growth factor-β1 (TGF-β1 ) gene and risk of chronic hepatitis B virus(HBV)infection progressing to hepatocellular carcinoma(HCC).Methods 120 patients with chronic HBV infection(case group)and 100 age-and sex-matched healthy individuals(healthy control group)were randomly enrolled to this study.The polymerase chain reaction-restriction fragment length polymorphism technique was adopted to detect the single nucleotide polymorphism of TGF-β1 gene(T29C),and made the comparative analysis combined with TGF-β1 mRNA level. Results The risk of HCC occurrence in the patients carrying genotype CC was decreased than that in the patients carrying geno-type TT (OR=0.317,95%CI =0.110-0.913,P =0.033;OR=284,95%CI =0.093 -0.866,P =0.027),the risk of HCC in pa-tients carrying allele C was significantly decreased compared with that in the patients carrying allele T(OR =0.570,95%CI =0.341 -0.953,P =0.032;OR=0.548,95%CI =0.320-0.936,P =0.028).In the HCC group,the patients carrying genotype CC had the lower lever of TGF-β1 mRNA.Conclusion TGF-β1 gene polymorphism(T29C)may be related to the risk of chronic HBV infection progressing to HCC.
ABSTRACT
Early detection and treatment of hepatocellular carcinoma (HCC) is one of the most direct and effective ways to improve the long-term outcome of patients with HCC. The comparative study on clinicopathological characteristics of surgically resected micro HCC (≤1 cm), small HCC(≤3 cm), middle HCC (3-5 cm), and large HCC (>5 cm) showed that ≤3 cm small HCC had the features of DNA diploidy, well differentiation, relatively slow growth, encapsulation, rare long-distance metastatic foci and thrombosis, easy to be radically resected and long-term postoperative survival. It is suggested that HCC growing to about ≤3 cm is an important growth phase when the change of pathobiological characteristics of HCC from a relatively benign to a more malignant behavior would occur. This is also the important time to carry out radical treatment to get better results. Therefore,further research on the early diagnosis and treatment as well as the pathobiological features of small HCC ≤3 cm should be undertaken as one of the key clinical and pathological studies in the future.
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Objective To study the effects of chloroquine on proliferation and cell cycle of hepatocellular carcinoma cell line HepG2 cultured in vitro and provide basis for research on chloroquine in therapy for liver cancer.Methods HepG2 cells were divided into six groups:control group and chloroquine (8.00,16.00,32.00,64.00 and 128.00 mmol?L-1 )groups.The cell viability was determined by MTT,the cell cycle and apoptosis were detected by flow cytometry.Results Compared with control group,the cell viabilities were inhibited significantly 24 h after treated with chloroquine (32.00-128.00 mmol?L-1) or 48-72 h after treated with chloroquine (8.00-128.00 mmol?L-1) ( P
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Objective To investigate the expressions and clinical significance of the tumor supressor gene phosphatase and tensin homlog deleted on chromosome ten protein(PTEN) and oncogene phosphoserine/threonine protein kinase B(phospho-serine/threonine protein kinase Akt/PKB,pAkt) in hepatocellular carcinoma(HCC).Method The expressions of PTEN and pAkt in 65 cases of HCC and their pericarcinomatous tissues were detected by immunohistochemical staining with S-P method.Results The positive expression rate of PTEN in HCC was significantly lower than that in pericarcinomatous liver tissues,and the positive rate of pAkt was significantly higher than that in pericarcinomatous liver tissues(all P
