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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. The risk factors for HCC include chronic hepatitis B and C virus infections, excessive alcohol consumption, obesity, metabolic disease, and aflatoxin exposure. In addition to these viral and environmental risk factors, individual genetic predisposition is a major determinant of HCC risk. Familial clustering of HCC has been observed, and a hereditary factor likely contributes to the risk of HCC development. The familial aggregation may depend on a shared environment and genetic background as well as the interactions of environmental and genetic factors. Genome-wide association studies (GWASs) are one of the most practical tools for mapping the patterns of inheritance for the most common form of genomic variation, single nucleotide polymorphisms. This approach is practical for investigating genetic variants across the human genome, which is affected by thousands of common genetic variants that do not follow Mendelian inheritance. This review article summarizes the academic knowledge of GWAS-identified genetic loci and their association with HCC. We summarize the GWASs in accordance with various chronic hepatitis virus infection statuses. This genetic profiling could be used to identify candidate biomarkers to refine HCC screening and management by enabling individual risk-based personalization and stratification. A more comprehensive understanding of the genetic mechanisms underlying individual predisposition to HCC may lead to improvements in the prevention and early diagnosis of HCC and the development of effective treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous microwave ablation (MWA) in the treatment of advanced hepatocellular carcinoma (HCC).Materials and Methods: Three thousand cases of advanced HCC patients were randomly divided into two groups: 1500 cases in the treatment group were treated with TACE combined with MWA and 1500 cases in the control group were treated with TACE.Results: The effective rate of the treatment group and control group was 71.4% and 42.8%, respectively, and the difference between the two groups was statistically significant (P < 0.05). During the follow-up period at 6, 12, 18, and 24 months postoperatively, the survival rates of the treatment group were 88.1%, 73.8%, 52.3%, and 33.3%, and the survival rates of the control group were 76.2%, 57.1%, 30.9%, and 9.5%, respectively. There was no significant difference in postoperative complications between the two groups.Conclusion: It is safe and effective to use TACE combined with MWA in the treatment of advanced HCC, and the effect of combined treatment is better than that of TACE alone. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Altered actin isoform expression occurs in some pathological conditions including muscular malignancies. This study was to investigate whether a similar event occurs in hepatocellular carcinoma. Methods: Cellular RNA was extracted from cancerous and non-cancerous hepatoma tissues. Reverse transcription (RT)-PCR followed by cloning and sequencing was performed to obtain populations of actin sequences. Phylogenetic analysis was carried out to identify novel actin isoforms. Interaction between the novel actin isoform and other cellular proteins was examined by the yeast two-hybrid system. The relative amounts of the novel actin isoform in the cancerous and non-cancerous tissues were further assayed using real-time PCR with specific primers. Results: When compared between the cancerous and non-cancerous tissues, the proportion of non-β-actins in the cancerous parts increased significantly in three of four cases included. Among the non-β-actins, a novel group of isoforms was identified, temporarily named κ-actins. Two genetically closely related sequences, FKSG30 and an actin-like sequence in the Cat Eye syndrome region, were found to cluster with the κ-actins. Protein interaction assay indicated that the interaction between κ-actin and prefoldin 2 was greatly diminished. The relative amounts of κ-actin increased in 12 of 20 cancerous tissues assayed. Conclusions: A novel class of actin isoforms was expressed in some hepatocellular carcinoma tissues, replacing β-actins to become the major constituents of actin cytoskeleton. [Copyright &y& Elsevier]

AbstractBackground: The purpose of this study was to determine the potential role of three-dimensional (3-D) conformal radiotherapy (RT) in treatment of unresectable hepatocellular carcinoma (HCC). Methods: Thirteen patients were included in this study, which was conducted between 1993 and 1996. Nine patients (group A) were treated with 3-D conformal RT alone because of main portal vein thrombosis, inferior vena cava thrombosis, obstructive jaundice and failure of previous transcatheter arterial chemoembolization (TACE) to control the disease. The remaining four patients (group B) were treated with a combination of TACE and 3-D conformal RT. Results: The greatest dimension of the main tumour in the whole group of patients ranged from 6 to 25 cm (median 15 cm). The radiation dose ranged from 40 to 60 Gy. The tumour response was evaluated by computed tomography scans of the liver 6–8 weeks after completion of radiotherapy. Partial response was observed in 58% of the patients (seven of 12) and minimal response in another 25% of patients (three of 12). One patient could not be evaluated because of the development of hepatic failure 1 month after completion of RT. All patients in group B lived for more than 1 year (range 16–40 months). In group A, one patient who had a large tumour (11 × 10 × 21 cm) with portal vein thrombosis was converted to become resectable after 45 Gy of radiation. The resection specimen revealed no residual cancer cells. This patient is alive longer than 15 months after treatment without the evidence of disease. Conclusions: Our experience indicates that HCC is more radiosensitive than it was traditionally expected. Three-dimensional reconstruction of tumour and surrounding organs helps to avoid excessive exposure of the liver and adjacent organs to RT and makes it a safer treatment modality for unresectable HCC. Our preliminary data show promise and are worthy of further study to explore the potential role of radiotherapy in the treatment strategy for HCC at various stages of involvement. © 1999 Blackwell Science Asia Pty Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Hepatocellular carcinoma (HCC) often develops on a background of chronic inflammation and a complex immunosuppressive network with increased regulatory T cells, impaired CD8+ T cells and the secretion of immunosuppressive cytokines. Previous clinical studies have reported a superior disease-free survival (DFS) following a radiofrequency-based ablation or resection in HCC tumours compared to conventional liver resection techniques. The aim of this study was to investigate whether there is any correlation with the use of a radiofrequency-assisted liver resection and clinical outcome. Material and Methods: Patients' peripheral blood was collected prior and 7 days following surgery from patients undergoing a liver resection for HCC. There were 5 liver resections performed using CUSA and 6 liver resections with the RF-based device, HabibTM 4X. The primary endpoint of the study was to assess the immunological parameters of circulating immune cell populations as well as serum cytokines. The Student's t-test, chi-square or Fisher's Exact test were applied for statistical comparisons, as appropriate. Results: Patients undergoing an RF-assisted liver resection with HabibTM 4X had a significant decrease in the inhibitory Treg cells (p = 0.002) and a significant increase in CD8+ T lymphocytes (p = 0.050) and CD4+CD45RO+/CD4+ memory T cells (p = 0.002) compared to those patients undergoing a liver resection with CUSA. It was also noted that the RF-assisted liver resection group had a significant decrease in circulating TGF-ß (p = 0.000), IL10 (p = 0.000) and a significant increase in IFN-gamma (p = 0. 027) and IL-17 compared to the CUSA group. Conclusion: A liver resection with RF-based device HabibTM 4X was associated with positive immunomodulatory changes in circulating immune cells and circulating cytokines which could explain the significant improvement in DFS. [ABSTRACT FROM AUTHOR]

Predicting a patient's risk of recurrence after the resection of liver metastases from colorectal cancer is critical for evaluating and selecting therapeutic approaches. Clinical and pathologic parameters have shown limited accuracy thus far. Therefore, we combined the clinical status with a genomic approach to stratify relapse-free survival in colorectal cancer liver metastases patients. To identify new molecular and genetic signatures specific to colorectal cancer with liver metastasis (CRCLM) patients, we conducted DNA copy number profiling on a cohort of 21 Taiwanese CRCLM patients using a comparative genomic hybridization (CGH) array. We identified a three-gene signature based on differential copy number alteration between patients with different statuses of (1) recurrence and (2) synchronous metastasis. In relapse hotspot regions, only three genes (S100PBP, CSMD2, and TGFBI) were significantly associated with the synchronous liver metastasis factor. A final set of three genes—S100PBP, CSMD2, TGFBI—significantly predicted relapse-free survival in our cohort (p = 0.04) and another CRCLM cohort (p = 0.02). This three-gene signature is the first genomic signature validated for relapse-free survival in post-hepatectomy CRCLM patients. Our three-gene signature was developed using a whole-genome CGH array and has a good prognostic position for the relapse-free survival of CRCLM patients after hepatectomy. [ABSTRACT FROM AUTHOR]

Abstract Hepatocellular carcinoma (HCC), as the commonest type in liver cancer, is in urgent need for better treatment target due to its high mortality and poor prognosis. The involvement of angiogenesis in HCC has been identified by multiple studies, but the underlying mechanism remains unclear. Long non-coding RNAs (LncRNAs) have been reported to regulate numerous cancers, including HCC. LncRNA-OR3A4 has been reported to exert oncogenic and angiogenetic functions in gastric cancer, but its role in HCC hasn't been elucidated. Present study aimed to uncover the biological role of OR3A4 in tumor progression and angiogenesis in HCC. The upregulation of OR3A4 in HCC tissues and cell lines and its prognostic significance were first identified. Loss-of-function assays, including CCK-8, transwell and tube formation assay, validated OR3A4 as a promoter for HCC progression and angiogenesis. The association of OR3A4 and AGGF1 with HCC and poor prognosis was identified by qRT-PCR and Kaplan-Meier analysis. Western blotting and spearman's correlation curve verified the effect of OR3A4 on AGGF1 level and their positive association. Rescue assays revealed that OR3A4 promoted cancer progression and angiogenesis in HCC via AGGF1/akt/mTOR. Together, present study revealed OR3A4 as a novel prognostic target for HCC, which regulated tumor progression and angiogenesis through AGGF1/akt/mTOR pathway. [ABSTRACT FROM AUTHOR]

Twelve patients with hepatocellular carcinoma and chronic hepatitis developed radiation-induced liver disease (RILD) after three-dimensional conformal radiotherapy. Six patients died of RILD and six recovered. Mean prescribed dose was 50.6±4.3 Gy, in a daily fraction of 1.8–2.0 Gy. Commonly used dosimetric parameters, such as fraction volume of normal liver with radiation dose >30 Gy, prediction score, and normal tissue complication probability, failed to differentiate the fatality and clinical types of this complication. Elevated transaminases are more frequently seen than ascites and elevated alkaline phosphamide are seen in patients with RILD. [Copyright &y& Elsevier]