Treatment of Hepatocellular Carcinoma

Díaz-González, Álvaro; Reig, María; Bruix, Jordi

doi:10.1159/000445275

Cited by 75 publications

(42 citation statements)

References 39 publications

(43 reference statements)

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“…The clinical and diagnostic characteristics of the study group have been described previously 25 . LC and HCC patients were further classified according to Child-Pugh scores A, B, and C 26 and HCC patients were categorized according to the Barcelona Clinic Liver Cancer (BCLC) staging system 27 . The control group (healthy controls; HC) consisted of 297 healthy blood donors.…”

Section: Methodsmentioning

confidence: 99%

Upregulation of SMYD3 and SMYD3 VNTR 3/3 polymorphism increase the risk of hepatocellular carcinoma

Binh

Hoàn

Giang

et al. 2020

Sci Rep

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SMYD3 (SET and MYND domain-containing protein 3) is involved in histone modification, which initiates oncogenesis by activating transcription of multiple downstream genes. To investigate associations of variable numbers of tandem repeats (VNTR) variants in the SMYD3 gene promoter, SMYD3 serum levels and SMYD3 mRNA expression in hepatitis B virus (HBV) infection and clinical progression of related liver disease. SMYD3VNTRs were genotyped in 756 HBV patients and 297 healthy controls. SMYD3 serum levels were measured in 293 patients and SMYD3 mRNA expression was quantified in 48 pairs of hepatocellular tumor and adjacent non-tumor liver tissues. Genotype SYMD3 VNTR 3/3 was more frequent among HCC patients than in controls (P adjusted = 0.037). SMYD3 serum levels increased according to clinical progression of liver diseases (P = 0.01); HCC patients had higher levels than non-HCC patients (P = 0.04). Among patients with SMYD3 VNTR 3/3, HCC patients had higher SMYD3 levels than others (P < 0.05). SMYD3 mRNA expression was up-regulated in HCC tumor tissues compared to other tissues (P = 0.008). In conclusion, upregulation of SMYD3 correlates with the occurrence of HCC and SMYD3 VNTR 3/3 appears to increase the risk of HCC through increasing SMYD3 levels. SMYD3 may be an indicator for HCC development in HBV patients.Although effective hepatitis B virus (HBV) vaccines are in use worldwide, HBV-related liver diseases are still a major health concern with approximately 257 million chronic infections and 887,000 deaths in 2015 1 . HBV is the main cause of primary hepatocellular carcinoma (HCC) 2 . The risk of HCC development is approximately 40 times higher in chronic HBV carriers (CHB) than in non-carriers 3 . Vietnam has a high prevalence of HBV infections, ranging from 10-20% in the general population and 20-40% among high-risk groups 2,4 . As a result, Vietnam is one of the countries with a high incidence of HCC with >25,000 new cases reported in 2018 5,6 .Further to viral factors contributing to cancer development, methylation of histone proteins is an important mechanism involved in multiple types of cancers including HCC 7,8 . Methylation of histone proteins at lysine residues can lead to chromatin remodelling, transcription, and signal transduction 9 . The SET and MYND domain containing proteins (SMYDs) belong to a family of the multi-domain SET-containing histone lysine methyltransferases and play a crucial role in histone methylation. To date, five SMYD family members have been recognized (SMYD1-SMYD5). SMYD3 is the most important member, as several findings have demonstrated its role in tumor cell growth and its increased expression in various cancers.SYMD3 promotes dimethylation and trimethylation of histone H3 lysine 4 (H3K4), which initiates oncogenesis by activating transcription of multiple downstream target genes 10,11 . SYMD3 overexpression causes cell proliferation, migration and adhesion, whereas suppression by RNAi inhibits cell proliferation and migration, indicating that SMYD3 plays an important role i...

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Section: Methodsmentioning

confidence: 99%

Upregulation of SMYD3 and SMYD3 VNTR 3/3 polymorphism increase the risk of hepatocellular carcinoma

Binh

Hoàn

Giang

et al. 2020

Sci Rep

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“…1 The most prevalent etiological factor of HCC is HBV-HCV infection. [3][4][5] Surgery is only suitable for the treatment of early stage liver cancer patients. [3][4][5] Surgery is only suitable for the treatment of early stage liver cancer patients.…”

Section: Introductionmentioning

confidence: 99%

“…2 Although several therapeutic strategies are available for liver cancer, such as surgical resection, orthotopic liver transplantation, local ablation treatments, chemotherapy, and systemic therapy, they have not significantly reduced the mortality rates. [3][4][5] Surgery is only suitable for the treatment of early stage liver cancer patients. 4 Due to aggressive metastasis and high recurrence rate, the prognosis of patients with intermediate-stage or advanced-stage HCC is poor.…”

Section: Introductionmentioning

confidence: 99%

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Autophagy induction by xanthoangelol exhibits anti‐metastatic activities in hepatocellular carcinoma

Yang

Xie

Liu

et al. 2019

Cell Biochemistry & Function

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Xanthoangelol (XAG), a prenylated chalcone isolated from the Japanese herb Angelica keiskei Koidzumi, has been reported to exhibit antineoplastic properties. However, the specific anti-tumor activity of XAG in human hepatocellular carcinoma (HCC), and the relevant mechanisms are not known. Herein, we evaluated the effect of XAG against HCC in vitro and in vivo. Although XAG treatment did not significantly reduce the viability of the Hep3B and Huh7 cell lines, it suppressed cell migration, invasion, and EMT. This anti-metastatic effect of XAG was due to induction of autophagy, because treatment with the autophagy inhibitor 3-methyadenine (3-MA) or knockdown of the pro-autophagy Beclin-1 effectively abrogated the XAG-induced suppression of metastasis. Mechanistically, XAG induced autophagy via activation of the AMPK/mTOR signaling pathway, and XAG treatment dramatically increased the expression of p-AMPK while decreasing p-mTOR expression. In addition, blocking AMPK/mTOR axis with compound C abrogated the autophagy-mediated inhibition of metastasis. The murine model of HCC metastasis also showed that XAG effectively reduced the number of metastatic pulmonary nodules. Taken together, our results revealed that autophagy via the activation of AMPK/mTOR pathway is essential for the anti-metastatic effect of XAG against HCC. These findings not only contribute to our understanding of the anti-tumor activity of XAG but also provide a basis for its clinical application in HCC. Before this study, evidence of XAG on HCC was purely anecdotal; present study provides the first comprehensive assessments of XAG on HCC metastasis and investigates its underlying mechanism. Results suggest that XAG exerts anti-metastatic properties against HCC through inducing autophagy which is mediated by the activation of AMPK/mTOR signaling pathway. This research extends our knowledge about the antineoplastic properties of XAG and suggests that induction autophagy may represent future treatment strategies for metastatic HCC. KEYWORDSAMPK/mTOR, autophagy, HCC, metastasis, xanthoangelol Xiuwei Yang and Jing Xie are co-first authors and contributed equally to this work.

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“…The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used and accepted staging system for HCC, and has been endorsed by the European Association for the Study of Liver and the American Association for the Study of Liver Diseases. The BCLC staging system classifies HCC patients into 5 stages (0, A, B, C, and D), and allocates treatment strategy accordingly [6][7][8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

Impact of Tumor Factors on Survival in Patients with Hepatocellular Carcinoma Classified Based on Kinki Criteria Stage B2

Arizumi

Minami²,

Chishina³

et al. 2017

Dig Dis

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Background: Tumors classified based on the Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) are heterogeneous in nature. Previously, the Kinki criterion was proposed for a more precise subclassification of tumors in BCLC-stage B. However, tumors in sub-stage B2 include various size and number of HCCs even with the Kinki criteria, which could lead to heterogeneity for overall survival (OS). In this study, we assessed how the size and number of tumors affect the OS and time to progression (TTP) in patients with Kinki criteria stage B2 tumors and treated with transarterial chemoembolization (TACE). Methods: Of 906 HCC patients treated with TACE at Kindai University Hospital, 236 patients with HCC considered as Kinki criteria stage B2 were examined. They were classified into the following 4 groups according to the maximum tumor diameter and number of tumors: B2a group, tumor size ≤6 cm and total number of tumors ≤6; B2b group, size ≤6 cm and number >6; B2c group, size >6 cm and number ≤6; and B2d group, size >6 cm and number >6. The OS and TTP of patients in each group were compared. Results: There were 131 patients (55.5%) in the B2a group, 58 (24.6%) in the B2b group, 41 (17.4%) in the B2c group, and 6 (0.03%) in the B2d group. Comparison of the survivals revealed that the median OS was 2.8 years (95% CI 2.0-3.5) in the B2a group, 2.8 years (95% CI 2.0-3.3) in the B2b group, 1.9 years (95% CI 0.8-4.0) in the B2c group, and 2.3 years (95% CI 1.2-ND [no data]) in the B2d group, respectively (p = 0.896). The median TTP in B2a, B2b, B2c, and B2d sub-substage HCC were13.2, 12.1, 13.8, and 11.5 months, respectively (p = 0.047). The median TTP in B2a + B2c sub-substage patients was longer than that in B2b + B2d sub-substage HCC patients (14.0 months and 10.4 months; p = 0.002). Conclusion: No significant differences were observed in the OS among HCC patients subclassified based on the maximum tumor diameter and tumor number in Kinki criteria stage B2. Consequently, Kinki criteria stage B2 HCC is a homogeneous subgroup in terms of OS prediction. However, shorter TTP in B2b+B2c sub-substage HCC patients than that in B2a + B2c sub-substage HCC patients suggests that different treatment strategy, such as systemic therapy with targeted agents instead of TACE, may be suitable to preserve the liver function.

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Treatment of Hepatocellular Carcinoma

Cited by 75 publications

References 39 publications

Upregulation of SMYD3 and SMYD3 VNTR 3/3 polymorphism increase the risk of hepatocellular carcinoma

Upregulation of SMYD3 and SMYD3 VNTR 3/3 polymorphism increase the risk of hepatocellular carcinoma

Autophagy induction by xanthoangelol exhibits anti‐metastatic activities in hepatocellular carcinoma

Impact of Tumor Factors on Survival in Patients with Hepatocellular Carcinoma Classified Based on Kinki Criteria Stage B2

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