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1
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Wang M, Wang X, Wang Y, Gai Y, Ye J, Xu X, You X. Advances in the study of the mechanism of action of miR‑22 in liver lesions (Review). Oncol Lett 2024; 28:541. [PMID: 39310022 PMCID: PMC11413475 DOI: 10.3892/ol.2024.14674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 08/15/2024] [Indexed: 09/25/2024] Open
Abstract
Globally, nearly 2 million deaths annually are attributed to the development of liver diseases, with liver cancer and cirrhosis being particularly prominent, which makes liver disease a significant global health concern. Cirrhosis is closely linked to the evolution of hepatitis, hepatic fibrosis and fatty liver. However, most liver diseases have an insidious onset, are challenging to treat and the prognosis and efficacy of current therapies are unsatisfactory, which can result in irreversible functional damage to the liver. Therefore, there is an urgent need to explore the molecular mechanisms underlying liver disease and identify new biomarkers and therapeutic targets. In previous years, microRNAs (miRs), a class of short non-coding RNAs comprising 17-25 nucleotides, have attracted attention for their roles in various types of liver diseases. Among them, miR-22 serves a unique role in mediating multiple pathway mechanisms and epigenetic modifications and can act both as an inhibitor of liver cancer and a metabolic blocker. Given its close association with the liver, several studies have reported that the differential expression of miR-22 regulates the metabolic process of liver cancer and is involved in the evolution of hepatic fibrosis and steatohepatitis, making it a potential target for early diagnosis and treatment. The present manuscript aimed to comprehensively review the key role of miR-22 in the evolution of liver diseases and offer valuable references and guidance for subsequent studies by identifying its specific mechanism of action and future development prospects.
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Affiliation(s)
- Minghe Wang
- College of Second Clinical Medical, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Xuejing Wang
- College of Second Clinical Medical, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Yanqi Wang
- College of Clinical Medical, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Yikuo Gai
- College of Second Clinical Medical, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Jingran Ye
- College of Second Clinical Medical, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Xinyan Xu
- College of Second Clinical Medical, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Xue You
- Lin He's Academician Workstation of New Medicine and Clinical Translation, Jining Medical University, Jining, Shandong 272067, P.R. China
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2
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Şener N, Yakupoğlu A. Yttrium-90 transarterial radioembolization and capecitabine in hepatocellular carcinoma with portal vein involvement. Medicine (Baltimore) 2023; 102:e34674. [PMID: 37657033 PMCID: PMC10476730 DOI: 10.1097/md.0000000000034674] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Accepted: 07/19/2023] [Indexed: 09/03/2023] Open
Abstract
Hepatocellular carcinoma (HCC) with portal vein tumor thrombus is considered an advanced stage disease. Non-surgical local and systemic therapies are the only treatment options available. To analyze the survival and toxicity outcomes of systemic treatment concurrent with yttrium-90 transarterial radioembolization in HCC with liver-limited disease and portal vein involvement with Child-Pugh B liver reserve. The medical records of 22 patients who underwent yttrium-90 transarterial radioembolization concomitant with capecitabine chemotherapy as first-line treatment between 2014 and 2019 were retrospectively reviewed. Twenty-two patients were included in the study. Grade 3 to 4 side effects were evaluated, and hepatic encephalopathy developed in 1 patient after yttrium-90 transarterial radioembolization. In the fourth month of radiological evaluation, 11 patients had a partial response (50%), 5 patients had stable disease (22.7%), and 6 patients (27.3%) developed progressive disease. The median survival time was 21 months. Combined treatment with yttrium-90 transarterial radioembolization and capecitabine may be an effective and safe treatment option. Treatment was associated with a median overall survival of 21 months and a disease control rate of 72.7% at 4 months in patients with inoperable HCC.
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Affiliation(s)
- Nur Şener
- Department of Medical Oncology, Memorial Ataşehir Hospital, İstanbul, Turkey
| | - Abdullah Yakupoğlu
- Department of Interventional Radiology, Memorial Şişli Hospital, İstanbul, Turkey
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3
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Jiang B, Zhou Y, Liu Y, He S, Liao B, Peng T, Yao L, Qi L. Research Progress on the Role and Mechanism of IL-37 in Liver Diseases. Semin Liver Dis 2023; 43:336-350. [PMID: 37582401 PMCID: PMC10620037 DOI: 10.1055/a-2153-8836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/17/2023]
Abstract
Cytokines are important components of the immune system that can predict or influence the development of liver diseases. IL-37, a new member of the IL-1 cytokine family, exerts potent anti-inflammatory and immunosuppressive effects inside and outside cells. IL-37 expression differs before and after liver lesions, suggesting that it is associated with liver disease; however, its mechanism of action remains unclear. This article mainly reviews the biological characteristics of IL-37, which inhibits hepatitis, liver injury, and liver fibrosis by inhibiting inflammation, and inhibits the development of hepatocellular carcinoma (HCC) by regulating the immune microenvironment. Based on additional evidence, combining IL-37 with liver disease markers for diagnosis and treatment can achieve more significant effects, suggesting that IL-37 can be developed into a powerful tool for the clinical adjuvant treatment of liver diseases, especially HCC.
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Affiliation(s)
- Baoyi Jiang
- Institute of Digestive Disease, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China
| | - Yulin Zhou
- Department of Clinical Laboratory, Shunde New Rongqi Hospital, Foshan, China
| | - Yanting Liu
- Institute of Digestive Disease, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China
| | - Siqi He
- Institute of Digestive Disease, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China
| | - Baojian Liao
- Institute of Digestive Disease, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China
| | - Tieli Peng
- Institute of Digestive Disease, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China
| | - Leyi Yao
- Institute of Digestive Disease, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China
| | - Ling Qi
- Institute of Digestive Disease, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China
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Evirgen S, Cavus B, Gokturk S, Iliaz R, Ozkan ZG, Baran B, Ormeci AC, Soyer OM, Karaca C, Demir K, Besisik SF, Poyanli A, Akyuz F, Kaymakoglu S. Is the Y90-radioembolization treatment effective on the intermediate-advanced stage of hepatocellular carcinoma and what is the albumin-bilirubin score's prediction factor for survival? HEPATOLOGY FORUM 2023; 4:103-107. [PMID: 37822305 PMCID: PMC10564249 DOI: 10.14744/hf.2022.2022.0036] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 03/13/2023] [Indexed: 10/13/2023]
Abstract
Background and Aim Radioembolization (RE) is a one of the palliative treatments that have been used to down stage and/or increase the survival time in intermediate-advanced stages of HCC. We aimed to evaluate the clinical impact of RE and the clinical use of the albumin-bilirubin (ALBI) score as a predictor for survival in HCC patients. Materials and Methods Fifty-nine unresectable hepatocellular carcinoma (HCC) patients were enrolled. RE was performed in 28 of them (group 1) and 31 patients were followed up in the natural course (NC) (group 2). Patients were classified according to the Child-Pugh score (only cirrhotic patients), Barcelona clinic liver cancer (BCLC) staging, and ALBI scores were also calculated. Results All patients in Group 1 were cirrhotic and their BCLC stages were as follows: 60.7% stage B and 39.3% stage C. In Group 2, 83.9% of patients were cirrhotic and their BCLC stages were as follows: 9.7% stage B, 51.6% stage C, and 38.7% stage D. Mortality rates were 82% and 100% in Groups 1 and 2, respectively. The median overall survival (OS) was 13.5 months (95% CI: 10.4-16.6 months) and 4.5 months (95% CI: 3.5-5.5 months) in Groups 1 and 2, respectively (p=0.000). When RE was applied to patients with ALBI Grade 1 and 2, the median OS was statistically higher than in the NC group, respectively (p<0.001, p<0.001). Conclusion RE is an effective treatment method at the advanced stages of HCC. The ALBI score is a more useful and practical than the other prognostic tools.
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Affiliation(s)
- Sami Evirgen
- Department of Gastroenterology, Istanbul University School of Medicine, Istanbul, Turkiye
| | - Bilger Cavus
- Department of Gastroenterology, Istanbul University School of Medicine, Istanbul, Turkiye
| | - Suut Gokturk
- Department of Gastroenterology, Istanbul University School of Medicine, Istanbul, Turkiye
| | - Raim Iliaz
- Department of Gastroenterology, Istanbul University School of Medicine, Istanbul, Turkiye
| | - Zeynep Gozde Ozkan
- Department of Nuclear Medicine, Istanbul University School of Medicine, Istanbul, Turkiye
| | - Bulent Baran
- Department of Gastroenterology, Istanbul University School of Medicine, Istanbul, Turkiye
| | - Asli Ciftcibası Ormeci
- Department of Gastroenterology, Istanbul University School of Medicine, Istanbul, Turkiye
| | - Ozlem Mutluay Soyer
- Department of Gastroenterology, Istanbul University School of Medicine, Istanbul, Turkiye
| | - Cetin Karaca
- Department of Gastroenterology, Istanbul University School of Medicine, Istanbul, Turkiye
| | - Kadir Demir
- Department of Gastroenterology, Istanbul University School of Medicine, Istanbul, Turkiye
| | - Selman Fatih Besisik
- Department of Gastroenterology, Istanbul University School of Medicine, Istanbul, Turkiye
| | - Arzu Poyanli
- Department of Radiology, Istanbul University School of Medicine, Istanbul, Turkiye
| | - Filiz Akyuz
- Department of Gastroenterology, Istanbul University School of Medicine, Istanbul, Turkiye
| | - Sabahattin Kaymakoglu
- Department of Gastroenterology, Istanbul University School of Medicine, Istanbul, Turkiye
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5
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Lorente L, Rodriguez ST, Sanz P, González-Rivero AF, Pérez-Cejas A, Padilla J, Díaz D, González A, Martín MM, Jiménez A, Cerro P, Portero J, Barrera MA. Patients with hepatocellular carcinoma that die during the first year of liver transplantation have high blood sFasL concentrations. World J Clin Cases 2023; 11:1753-1760. [PMID: 36970008 PMCID: PMC10037289 DOI: 10.12998/wjcc.v11.i8.1753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/20/2023] [Accepted: 02/21/2023] [Indexed: 03/07/2023] Open
Abstract
BACKGROUND Fas ligand (FasL) is one ligand that activates extrinsic apoptosis pathway. High expression in lymphocytes of FasL have been found in patients with acute rejection of liver transplantation (LT). No high blood concentrations of soluble FasL (sFasL) have been found in patients with acute LT rejection; however, the samples size of those studies was small.
AIM To determine whether patients with hepatocellular carcinoma (HCC) that dead during the first year of LT have higher blood sFasL concentrations previously to LT that those who that remain alive in a study of higher sample size.
METHODS Patients underwent LT due to HCC were included in this retrospective study. Serum sFasL levels prior to LT were measured and one-year LT mortality was registered.
RESULTS Non-surviving patients (n = 14) showed higher serum sFasL levels [477 (269-496) vs 85 (44-382) pg/mL; P < 0.001] than surviving patients (n = 113). Serum sFasL levels (pg/mL) were associated with mortality (OR = 1.006; 95%CI = 1.003-1.010; P = 0.001) independently of age of LT donor in the logistic regression analysis.
CONCLUSION We report for the first time that HCC patients who die within the first year of HT have higher blood sFasL concentrations prior to HT than those who remain alive.
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Affiliation(s)
- Leonardo Lorente
- Intensive Care Unit, Hospital Universitario de Canarias, La Laguna 38320, Spain
| | - Sergio T Rodriguez
- Intensive Care Unit, Hospital Universitario Nuestra Señora Candelaria, Santa Cruz Tenerife 38010, Spain
| | - Pablo Sanz
- Department of Surgery, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz Tenerife 38010, Spain
| | | | - Antonia Pérez-Cejas
- Department of Laboratory, Hospital Universitario de Canarias, La Laguna 38320, Spain
| | - Javier Padilla
- Department of Surgery, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz Tenerife 38010, Spain
| | - Dácil Díaz
- Department of Digestive, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz Tenerife 38010, Spain
| | - Antonio González
- Department of Digestive, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz Tenerife 38010, Spain
| | - María M Martín
- Intensive Care Unit, Hospital Universitario Nuestra Señora Candelaria, Santa Cruz Tenerife 38010, Spain
| | - Alejandro Jiménez
- Research Unit, Hospital Universitario de Canarias, La Laguna 38320, Spain
| | - Purificación Cerro
- Transplant Unit, Hospital Universitario Nuestra Señora Candelaria, Santa Cruz Tenerife 38010, Spain
| | - Julián Portero
- Department of Radiology, Hospital Universitario Nuestra Señora Candelaria, Santa Cruz Tenerife 38010, Spain
| | - Manuel A Barrera
- Department of Surgery, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz Tenerife 38010, Spain
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Arian A, Abdullah AD, Taher HJ, Suhail Alareer H, Fotouhi M. Diagnostic Values of the Liver Imaging Reporting and Data System in the Detection and Characterization of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Cureus 2023; 15:e36082. [PMID: 37065286 PMCID: PMC10097431 DOI: 10.7759/cureus.36082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 03/10/2023] [Indexed: 03/14/2023] Open
Abstract
This review was undertaken to assess the diagnostic value of the Liver Imaging Reporting and Data System (LI-RADS) in patients with a high risk of hepatocellular carcinoma (HCC). Google Scholar, PubMed, Web of Science, Embase, PROQUEST, and Cochrane Library, as the international databases, were searched with appropriate keywords. Using the binomial distribution formula, the variance of all studies was calculated, and using Stata version 16 (StataCorp LLC, College Station, TX, USA), the obtained data were analyzed. Using a random-effect meta-analysis approach, we determined the pooled sensitivity and specificity. Utilizing the funnel plot and Begg's and Egger's tests, we assessed publication bias. The results exhibited pooled sensitivity and pooled specificity of 0.80% and 0.89%, respectively, with a 95% confidence interval (CI) of 0.76-0.84 and 0.87-0.92, respectively. The 2018 version of LI-RADS showed the greatest sensitivity (0.83%; 95% CI 0.79-0.87; I 2 = 80.6%; P < 0.001 for heterogeneity; T 2 = 0.001). The maximum pooled specificity was detected in LI-RADS version 2014 (American College of Radiology, Reston, VA, USA; 93.0%; 95% CI 89.0-96.0; I 2 = 81.7%; P < 0.001 for heterogeneity; T 2 = 0.001). In this review, the results of estimated sensitivity and specificity were satisfactory. Therefore, this strategy can serve as an appropriate tool for identifying HCC.
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7
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Xiong D, Li J, He R, Li M, Pan Y, He X, Dang Y, Chen G. Highly expressed carbohydrate sulfotransferase 11 correlates with unfavorable prognosis and immune evasion of hepatocellular carcinoma. Cancer Med 2023; 12:4938-4950. [PMID: 36062845 PMCID: PMC9972111 DOI: 10.1002/cam4.5186] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 07/05/2022] [Accepted: 08/14/2022] [Indexed: 12/24/2022] Open
Abstract
Despite great advance has been made in multi-modality treatments for HCC patients, the effectiveness is far from satisfactory with worse survival outcome, which may be partly explainable by the anti-tumor deficiency of the immune system. It is necessary to clarify the molecular mechanism of HCC immunodeficiency. Here, we demonstrated that carbohydrate sulfotransferase 11 (CHST11) was upregulated in HCC and related to advanced TNM stage. HCC patients with TP53 mutation showed higher CHST11 expression. Survival analysis revealed that CHST11 was an independent prognostic biomarker in HCC. Cellular functional experiments indicated that knockdown of CHST11 in HCC inhibited cell proliferation and metastasis. Gene functional enrichment analyses indicated that CHST11 modulated pathways related to tumor growth, metastasis and immune regulation. Continuative immune-related analyses revealed that CHST11 expression facilitated Tregs infiltration in HCC and promoted the expression of checkpoints PD-L1/PD-1, resulting in the immunosuppression of HCC. Targeting CHST11 may inhibit Tregs infiltration and enhance the antineoplastic effect of immune checkpoint inhibitors, which provides a novel insight into the combination immunotherapy with Treg-modulating agents and PD-L1/PD-1 inhibitors.
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Affiliation(s)
- Dan‐dan Xiong
- Department of PathologyFirst Affiliated Hospital of Guangxi Medical UniversityNanningChina
| | - Jian‐di Li
- Department of PathologyFirst Affiliated Hospital of Guangxi Medical UniversityNanningChina
| | - Rong‐quan He
- Department of Medical OncologyFirst Affiliated Hospital of Guangxi Medical UniversityNanningChina
| | - Ming‐xuan Li
- Department of PathologyFirst Affiliated Hospital of Guangxi Medical UniversityNanningChina
| | - Yan‐qing Pan
- Department of PathologyFirst Affiliated Hospital of Guangxi Medical UniversityNanningChina
| | - Xiao‐lian He
- Department of PathologyFirst Affiliated Hospital of Guangxi Medical UniversityNanningChina
| | - Yi‐wu Dang
- Department of PathologyFirst Affiliated Hospital of Guangxi Medical UniversityNanningChina
| | - Gang Chen
- Department of PathologyFirst Affiliated Hospital of Guangxi Medical UniversityNanningChina
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Lorente L, Rodriguez ST, Sanz P, González-Rivero AF, Pérez-Cejas A, Padilla J, Díaz D, González A, Martín MM, Jiménez A, Cerro P, Portero J, Barrera MA. DNA and RNA oxidative damage in hepatocellular carcinoma patients and mortality during the first year of liver transplantation. World J Hepatol 2022; 14:1182-1189. [PMID: 35978670 PMCID: PMC9258248 DOI: 10.4254/wjh.v14.i6.1182] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 03/28/2022] [Accepted: 05/23/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Oxidative damage of DNA and RNA has been associated with mortality of patients with different diseases. However, there is no published data on the potential use of DNA and RNA oxidative damage to predict the prognosis of patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT).
AIM To determine whether patients with increased DNA and RNA oxidative damage prior to LT for HCC have a poor LT prognosis.
METHODS Patients with HCC who underwent LT were included in this observational and retrospective study. Serum levels of all three oxidized guanine species (OGS) were measured prior to LT since guanine is the nucleobase that forms DNA and RNA most prone to oxidation. LT mortality at 1 year was the end-point study.
RESULTS Surviving patients (n = 101) showed lower serum OGS levels (P = 0.01) and lower age of the liver donor (P = 0.03) than non-surviving patients (n = 13). An association between serum OGS levels prior to LT and 1-year LT (odds ratio = 2.079; 95% confidence interval = 1.356-3.189; P = 0.001) was found in the logistic regression analysis.
CONCLUSION The main new finding was that high serum OGS concentration prior to LT was associated with the mortality 1 year after LT in HCC patients.
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Affiliation(s)
- Leonardo Lorente
- Department ofIntensive Care, Hospital Universitario de Canarias, La Laguna 38320, Tenerife, Spain
| | - Sergio T Rodriguez
- Intensive Care Unit, Hospital Universitario Nuestra Señora Candelaria, Santa Cruz de Tenerife 38010, Spain
| | - Pablo Sanz
- Department of Surgery, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife 38010, Spain
| | | | - Antonia Pérez-Cejas
- Department of Laboratory, Hospital Universitario de Canarias, La Laguna 38320, Spain
| | - Javier Padilla
- Department of Surgery, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife 38010, Spain
| | - Dácil Díaz
- Department of Digestive, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife 38010, Spain
| | - Antonio González
- Department of Digestive, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife 38010, Spain
| | - María M Martín
- Intensive Care Unit, Hospital Universitario Nuestra Señora Candelaria, Santa Cruz de Tenerife 38010, Spain
| | - Alejandro Jiménez
- Research Unit, Hospital Universitario de Canarias, La Laguna 38320, Spain
| | - Purificación Cerro
- Transplant Unit, Hospital Universitario Nuestra Señora Candelaria, Santa Cruz de Tenerife 38010, Spain
| | - Julián Portero
- Department of Radiology, Hospital Universitario Nuestra Señora Candelaria, Santa Cruz de Tenerife 38010, Spain
| | - Manuel A Barrera
- Department of Surgery, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife 38010, Spain
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Li S, Li Y, Sun H, Jiang Y, Pan K, Su Y, Bu N. Mulberry fruit polysaccharides alleviate diethylnitrosamine/phenobarbital-induced hepatocarcinogenesis in vivo: the roles of cell apoptosis and inflammation. Bioengineered 2021; 12:11599-11611. [PMID: 34866538 PMCID: PMC8810071 DOI: 10.1080/21655979.2021.1993716] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Revised: 10/08/2021] [Accepted: 10/11/2021] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and chemoprevention represents a feasible treatment to reduce the mortality of this carcinoma. Mulberry fruit polysaccharides (MFP) possess immunoregulatory and anti-inflammatory effects, which have been reported to alleviate liver damage evoked by CCl4 or alcohol in previous reports. However, its chemopreventive effect against liver carcinogenesis is insufficient. The present study was aimed to investigate the possible role of MFP as a pro-apoptosis, and anti-inflammatory agent to possess its chemoprevention property. Hepatocarcinogenesis was induced by diethylnitrosamine/phenobarbital (DEN/PB) for 14 weeks. The DEN/PB-administered rats were co-treated with different doses of MFP (50 or 100 mg/kg body weight) by oral gavage for 14 weeks. Basic hepatic function indexes (AST, ALT, ALP, GGT, total bilirubin, and albumin), and hepatic tumor biomarkers (AFP, CEA, and CA19.9), together with histological assessment were performed. Besides, the hepatic apoptosis markers (Bcl-2, Bax, caspase3, and caspase9), inflammation markers (IL-1β, TNF-α, and NF-κB), and mutT homologue gene 1 (MTH1) were examined. Oral gavage of MFP inhibited the elevations of hepatic function indexes and hepatic tumor biomarkers and alleviated pathological changes in hepatic tissue. In addition, the hepatic apoptosis markers, inflammation markers, and the mRNA level of MTH1 were abnormal in DEN/PB group, which were reversed by MFP treatment. In conclusion, MFP is an effective agent that provides chemoprevention against DEN/PB-evoked hepatocarcinogenesis via inhibition of inflammation and induction of apoptosis.
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Affiliation(s)
- Shanshan Li
- Jia Musi Hospital of Traditional Chinese Medicine, Jia Musi, Hei Longjiang, China
| | - Yang Li
- Department of Gastroenterology, The First Affiliated Hospital of Harbin Medical University, Harbin, Hei Longjiang, China
| | - Hongjian Sun
- Department of Surgical Oncology, Jia Musi Central Hospital, Jia Musi, Hei Longjiang, China
| | - Yang Jiang
- Department of Surgical Oncology, Jia Musi Central Hospital, Jia Musi, Hei Longjiang, China
| | - Keming Pan
- Jia Musi Hospital of Traditional Chinese Medicine, Jia Musi, Hei Longjiang, China
| | - Yue Su
- Jia Musi Hospital of Traditional Chinese Medicine, Jia Musi, Hei Longjiang, China
| | - Nan Bu
- Jia Musi Hospital of Traditional Chinese Medicine, Jia Musi, Hei Longjiang, China
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Liu C, Zhu X, Jia Y, Chi F, Qin K, Pei J, Zhang C, Mu X, Zhang H, Dong X, Xu J, Yu B. Dasatinib inhibits proliferation of liver cancer cells, but activation of Akt/mTOR compromises dasatinib as a cancer drug. Acta Biochim Biophys Sin (Shanghai) 2021; 53:823-836. [PMID: 33961012 DOI: 10.1093/abbs/gmab061] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Indexed: 12/15/2022] Open
Abstract
Dasatinib is a multi-target protein tyrosine kinase inhibitor. Due to its potent inhibition of Src, Abl, the platelet-derived growth factor receptor (PDGFR) family kinases, and other oncogenic kinases, it has been investigated as a targeted therapy for a broad spectrum of cancer types. However, its efficacy has not been significantly extended beyond leukemia. The mechanism of resistance to dasatinib in a wide array of cancers is not clear. In the present study, we investigated the effect of dasatinib on hepatocellular carcinoma cell growth and explored the underlying mechanisms. Our results showed that dasatinib potently inhibited the proliferation of SNU-449 cells, but not that of other cell lines, such as SK-Hep-1, even though it inhibited the phosphorylation of Src on both negative and positive regulation sites in all these cells. Dasatinib activated the phosphoinositide-dependent protein kinase1 (PDK1)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in SK-Hep-1 cells, but not in SNU-449 cells. Blocking the Akt/mTOR signaling pathway strongly promoted the efficacy of dasatinib in SK-Hep-1 cells. In SNU-449 cells, dasatinib promoted apoptosis and the cleavage of caspase-3 and caspase-7, induced cell cycle arrest in the G1 phase, and inhibited the expression of Cyclin-dependent kinase (CDK4)/6/CyclinD1 complex. These findings demonstrate that dasatinib exerts its anti-proliferative effect on hepatocellular cell proliferation by blocking the Src family kinases; however, it causes Akt activation, which compromises dasatinib as an anti-cancer drug.
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Affiliation(s)
- Chang Liu
- Department of Biochemistry and Molecular Biology, Changzhi Medical College, Changzhi 046000, China
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Xiaoxia Zhu
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Yuqi Jia
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Fenqing Chi
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Keru Qin
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Jinhong Pei
- Department of Biochemistry and Molecular Biology, Changzhi Medical College, Changzhi 046000, China
| | - Chan Zhang
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Xiuli Mu
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Hongwei Zhang
- Department of Hematology, Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan 030013, China
| | - Xiushan Dong
- Department of General Surgery, Shanxi Bethune Hospital, Taiyuan 030032, China
| | - Jun Xu
- Department of General Surgery, The First Hospital of Shanxi Medical University, Taiyuan 030001, China
| | - Baofeng Yu
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
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11
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Zhang X, Zhang X, Li X, Bao H, Li G, Li N, Li H, Dou J. Connection Between CDC20 Expression and Hepatocellular Carcinoma Prognosis. Med Sci Monit 2021; 27:e926760. [PMID: 33788826 PMCID: PMC8020723 DOI: 10.12659/msm.926760] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) occurs frequently in China, with high morbidity and mortality. Cell division cycle 20 homolog (CDC20) is reportedly related to many cancers. In this study, we discuss a potential link of CDC20 expression to HCC patients’ prognoses. Material/Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess CDC20 expression in HCC and the paired noncancerous tissues. Chi-square analysis was used to assess potential association of CDC20 expression with clinicopathologic profiles among HCC patients. The overall survival for HCC patients with different CDC20 expressions was assessed using the Kaplan-Meier method. To evaluate the prognostic value for HCC patients, Cox regression analyses were performed. Results The expression of CDC20 was elevated among HCC specimens compared with adjacent noncancerous ones (P<0.05). The expression of CDC20 was significantly related to differentiation (P<0.001), tumor node metastasis stage (P<0.001), and lymphatic metastasis (P<0.001). Moreover, HCC patients with high CDC20 expression had dismal overall survival rates compared with low CDC20 expression (P<0.05). CDC20 alone could forecast HCC prognoses according to multivariable Cox regression analysis (hazard ratio=2.354, 95% confidence interval=1.177–4.709, P=0.016). Conclusions Overexpressed CDC20 may act as a reliable biomarker for dismal prognoses among HCC patients.
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Affiliation(s)
- Xianfeng Zhang
- Department of Hepatopancreatobiliary Surgery, Harrison International Peace Hospital, Hengshui, Hebei, China (mainland)
| | - Xianjun Zhang
- Department of Gynaecology, Harrison International Peace Hospital, Hengshui, Hebei, China (mainland)
| | - Xinguo Li
- Department of Hepatopancreatobiliary Surgery, Harrison International Peace Hospital, Hengshui, Hebei, China (mainland)
| | - Hongbing Bao
- Department of Hepatopancreatobiliary Surgery, Harrison International Peace Hospital, Hengshui, Hebei, China (mainland)
| | - Guang Li
- Department of Hepatopancreatobiliary Surgery, Harrison International Peace Hospital, Hengshui, Hebei, China (mainland)
| | - Ning Li
- Department of Hepatopancreatobiliary Surgery, Harrison International Peace Hospital, Hengshui, Hebei, China (mainland)
| | - Hengli Li
- Department of Hepatopancreatobiliary Surgery, Harrison International Peace Hospital, Hengshui, Hebei, China (mainland)
| | - Jian Dou
- Department of Hepatobiliary Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland)
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12
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Jin Q, Hu H, Yan S, Jin L, Pan Y, Li X, Peng Y, Cao P. lncRNA MIR22HG-Derived miR-22-5p Enhances the Radiosensitivity of Hepatocellular Carcinoma by Increasing Histone Acetylation Through the Inhibition of HDAC2 Activity. Front Oncol 2021; 11:572585. [PMID: 33718133 PMCID: PMC7943860 DOI: 10.3389/fonc.2021.572585] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 01/05/2021] [Indexed: 12/30/2022] Open
Abstract
Background With the development of radiotherapy technology, radiotherapy has been increasingly used to treat primary hepatocellular carcinoma (HCC). However, due to radioresistance and the intolerance of the adjacent organs to radiation, the effects of radiotherapy are often unsatisfactory. Therefore, it is necessary to study radiosensitization in HCC. Method A microarray was used to analyze the genes that were significantly associated with radiosensitivity. HCC cells, HepG2 and MHCC97H, were subjected to radiation in vitro. Real-time PCR was performed to determine MIR22HG (microRNA22 host gene) and miR-22-5p expression levels. Western blotting was performed to determine histone expression levels. A histone deacetylase (HDAC) whole cell assay was used to determine the activity of HDAC2. MTT, colony formation, 5-ethynyl-2′-deoxyuridine, and wound healing assays were performed to examine the function of MIR22HG and miR-22-5p in cellular radiosensitivity. Chromatin immunoprecipitation-PCR was used to confirm that HDAC2 affects the acetylation level of the MIR22HG promoter region. Finally, animal experiments were performed to demonstrate the in vivo effect of MIR22HG on the radiosensitivity of hepatoma. Results Irradiation can up-regulate MIR22HG expression and down-regulate HDAC2 expression. Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region and up-regulates MIR22HG expression. MIR22HG can increase radiosensitivity via miR-22-5p in HCC. Conclusion Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region, thereby up-regulating the expression of MIR22HG and promoting the production of miR-22-5p, and ultimately increasing the sensitivity of liver cancer radiotherapy.
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Affiliation(s)
- Qiao Jin
- Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, China
| | - Hao Hu
- Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, China
| | - Siqi Yan
- Department of Oncological Radiotherapy, Hunan Academy of Traditional Chinese Medicine Affiliated Hospital, Changsha, China
| | - Long Jin
- Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, China
| | - Yuliang Pan
- Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, China
| | - Xiangjun Li
- Department of Oncology, The Second People's Hospital of Hunan Province, Changsha, China
| | - Yayi Peng
- Department of Oncology, The Second People's Hospital of Hunan Province, Changsha, China
| | - Peiguo Cao
- Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, China
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Mohamed DA, Fouda KA, Mohamed RS. <i>In vitro</i> Anticancer Activity of Quinoa and Safflower Seeds and Their Preventive Effects on Non-alcoholic Fatty Liver. Pak J Biol Sci 2020; 22:383-392. [PMID: 31930826 DOI: 10.3923/pjbs.2019.383.392] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND OBJECTIVE Non-alcoholic fatty liver disease (NAFLD) is not only the most common cause of liver diseases in humans but also it may complicate and become a risk factor for liver cancer. The present work aimed to evaluate the anticancer activity (in vitro) of quinoa and safflower seeds powder and their beneficial effects against NAFLD (in vivo). MATERIALS AND METHODS Proximate analysis, fatty acids profile, total phenolic and phytic acid of quinoa and safflower seeds were assessed. Also their anticancer activities (in vitro) against liver cancer were evaluated. The preventive effect of both seeds on NAFLD was evaluated using twenty four male rats. NAFLD was induced in rats by high fructose diet (HFD) for 4 weeks. The effects of HFD and HFD supplemented with 20% quinoa or safflower powder on plasma and liver lipids, lipid peroxidation, total protein, albumin as well as liver and kidney functions were determined. RESULTS Quinoa seeds powder was promising in cytotoxicity against hepatocarcinoma cell line HEPG2 (IC50 was 14.6 μg). Feeding rats on HFD produced dyslipidemia and significant increase in liver functions and lipid peroxidation with significant elevation in liver triglycerides and total cholesterol. Quinoa and safflower seeds powder produced improvement in the biochemical parameters with different degrees. CONCLUSION Quinoa and safflower seeds powder possessed cytotoxicity against hepatocarcinoma cell line HEPG2 and afford hepato-protection against NAFLD.
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Asemota J, Saleh M, Igbinovia O, Burns D. A Concise Review on Current Trends in Imaging and Surgical Management of Hepatocellular Carcinoma. Cureus 2020; 12:e9191. [PMID: 32818122 PMCID: PMC7426666 DOI: 10.7759/cureus.9191] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Accepted: 07/14/2020] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a primary cancer of the liver whose incidence has seen an upsurge in the United States within the last 2 decades. Despite improvements in detection and management techniques, the prognosis for patients with HCC generally remains poor. There are multiple factors that have been implicated in the etiology of HCC with cirrhosis occurring as a common final pathway. This review presents a concise summary of current trends in imaging and surgical management of HCC. An internet-based (PubMed) search using the search terms "hepatocellular carcinoma" and "imaging" and "surgical management" was performed. Our search was limited to articles related to human studies published in English during the period of 07/01/2011 to 06/30/2016. A review of all relevant articles was conducted, and findings were summarized. Modern imaging modalities employed in the diagnosis of HCC include ultrasound scan (USS), computed tomography (CT), and magnetic resonance imaging (MRI) scan. The utility of diagnostic imaging is enhanced when interpreted in conjunction with appropriate laboratory tests such as alpha-fetoprotein. The definitive treatment for HCC remains challenging; hepatic resection (HR) and liver transplantation (LT) are two approaches offering potentially curative options. For patients undergoing HR, important considerations include achieving maximum resection while maintaining optimal post-resection liver remnant volume (LRV) and functional capacity (FC), which can be assessed using 3-dimensional CT and indocyanine green clearance. Generally, an LRV of 40-50% is considered an acceptable lower limit for individuals with HCC compared to 20-30% among individuals with normal livers. With increasing knowledge of disease pathology, appropriate patient selection, coupled with advances in anesthesia and surgical technique, overall 5-year survival rates have significantly improved. Challenges associated with LT on the other hand include donor-liver shortages with resultant long wait times and continued disease progression. The scarcity of cadaveric-donor livers has led to employing living-donor livers. Ethical considerations with respect to subjecting potentially healthy donors to undue morbidity and mortality risk however remain. Additional donor-shortage circumventing strategies include employing marginal, domino, and split-organ liver transplants. For patients awaiting transplant, employing bridging therapy such as radiofrequency ablation and transhepatic artery chemoembolization might occasionally help slow disease progression and maintain transplant eligibility. Appropriate patient selection achieved through the Milan and UCSF criteria designed to guide allotment of donor livers to patients with the best chances of survival could help improve outcomes and 5-year survival rates. The main radiological options for diagnosis include USS, CT, and MRI. HR and LT are two distinct surgical options, which in practice can be used to complement one another. Appropriate patient selection is necessary to achieve maximum benefits from HCC therapies.
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Affiliation(s)
- Joseph Asemota
- Clinical Anatomy, St. George's University School of Medicine, True Blue, GRD
- Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, USA
- Internal Medicine, Howard University Hospital, Washington, USA
| | - Mohammed Saleh
- Internal Medicine, Howard University Hospital, Washington, USA
| | | | - Danny Burns
- Clinical Anatomy, St. George's University School of Medicine, St. George's, GRD
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Zhang G, Chen X, Ma L, Ding R, Zhao L, Ma F, Deng X. LINC01419 facilitates hepatocellular carcinoma growth and metastasis through targeting EZH2-regulated RECK. Aging (Albany NY) 2020; 12:11071-11084. [PMID: 32522890 PMCID: PMC7346057 DOI: 10.18632/aging.103321] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 04/28/2020] [Indexed: 12/24/2022]
Abstract
Long non-coding RNAs (lncRNAs) have been reported to play significant roles in human tumorigenesis, for example, in hepatocellular carcinoma (HCC). This study explored the role of LINC01419, a new lncRNA, in HCC. In vitro study revealed that LINC01419 promotes growth and migration of HCC cells. Genes that affected cell proliferation and cell migration were identified using RNA-sequence. Subsequently, it was confirmed that LINC01419 binds to EZH2, leading to histone methylation of the RECK promoter. Interaction between LINC01419 and FUS stabilized EZH2 mRNA thereby enhancing EZH2 expression. Conclusively, the results of this study confirm that LINC01419 may serve as a potential target for HCC diagnosis and treatment.
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Affiliation(s)
- Gong Zhang
- Department of Radiotherapy, People's Hospital of Shanxi Province, Taiyuan, China
| | - Ximin Chen
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Lei Ma
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Rui Ding
- Department of Radiotherapy, People's Hospital of Shanxi Province, Taiyuan, China
| | - Lihong Zhao
- Department of Radiotherapy, People's Hospital of Shanxi Province, Taiyuan, China
| | - Feng Ma
- Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Xubin Deng
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
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He JQ, Zheng MX, Ying HZ, Zhong YS, Zhang HH, Xu M, Yu CH. PRP1, a heteropolysaccharide from Platycodonis Radix, induced apoptosis of HepG2 cells via regulating miR-21-mediated PI3K/AKT pathway. Int J Biol Macromol 2020; 158:542-551. [PMID: 32380108 DOI: 10.1016/j.ijbiomac.2020.04.193] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 04/03/2020] [Accepted: 04/22/2020] [Indexed: 02/07/2023]
Abstract
Two polysaccharides (PRP1 and PRP2) were isolated from Platycodonis Radix. Preliminary structural analysis indicated that PRP1 was composed of glucose, fructose, and arabinose in a molar ratio of 1:1.91:1.59 with a molecular weight of 440 kDa, whereas PRP2 was composed of arabinose, fructose, and galactose in a molar ratio of 1:1.39:1.18 with a molecular weight of 2.85 kDa. Compared with PRP2, PRP1 exerted stronger anticancer activity in vitro. Treatment with 5-30 μg/ml of PRP1 significantly inhibited the proliferation of HepG2 cells in vitro, and oral administration at the doses of 75-300 mg/kg also reduced the tumor growth in vivo. The miRNA expression patterns of human liver cancer cells HepG2 in vivo under PRP1 treatment were established, and microRNA-21 (miR-21) as the onco-miRNA was appreciably downregulated. PRP1 repressed the expression of miR-21, which directly targeted and suppressed PTEN (a negative regulator of the PI3K/Akt signaling cascade), and subsequently upregulated the expression of PTEN but downregulated the PI3K/AKT pathway, thereby promoting liver cancer cell apoptosis. These findings indicated that PRP1 inhibited the proliferation and induced the apoptosis of HepG2 mainly via inactivating the miR-21/PI3K/AKT pathway. Therefore, PRP1 could be used as a food supplement and candidate for the treatment of liver cancer.
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Affiliation(s)
- Jia-Qi He
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China.
| | - Min-Xia Zheng
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China
| | - Hua-Zhong Ying
- Zhejiang Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou 310013, China
| | - Yu-Sen Zhong
- Zhejiang Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou 310013, China
| | - Huan-Huan Zhang
- Zhejiang Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou 310013, China
| | - Min Xu
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China.
| | - Chen-Huan Yu
- Zhejiang Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou 310013, China; Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Hangzhou 310018, China.
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Tang Y, Zeng Z, Wang J, Li G, Huang C, Dong X, Feng Z. Combined signature of nine immune-related genes: a novel risk score for predicting prognosis in hepatocellular carcinoma. Am J Transl Res 2020; 12:1184-1202. [PMID: 32355535 PMCID: PMC7191166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Accepted: 03/24/2020] [Indexed: 06/11/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common internal malignancies worldwide and is associated with a poor prognosis. There is an urgent need to identify diagnostic and prognostic biomarkers of HCC pathogenesis and progression. Accordingly, in this study, we analyzed differentially expressed immune-related genes (IRGs) from 329 patients with HCC from The Cancer Genome Atlas datasets. Functional analysis revealed that the IRGs had potential effects on tumor immune processes, such as inflammatory responses and growth factor activity. In the training group, we constructed a nine-IRG formula to predict prognosis in patients with HCC. To validate the protein and mRNA levels of these IRGs, we used the Human Protein Atlas database and quantitative PCR analysis and found that most protein expression levels matched the corresponding mRNA expression levels. Furthermore, we also validated the prognostic value of the new risk model in another independent cohort (n = 277) from a Gene Expression Omnibus dataset (GSE14520). Our data suggested that there was a significant association between our risk model and patient prognosis. Stratification analysis showed that the nine-IRG signature was significantly associated with overall survival in men. Finally, the signature was found to be correlated with various clinicopathological features. Intriguingly, the prognostic index based on the IRGs reflected infiltration by several types of immune cells. In summary, our data provided evidence that the nine-IRG signature could serve as an independent biomarker to predict prognosis in patients with HCC.
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Affiliation(s)
- Yunliang Tang
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang UniversityNanchang, Jiangxi, People’s Republic of China
| | - Zhenguo Zeng
- Department of Critical Care Medicine, The First Affiliated Hospital of Nanchang UniversityNanchang, Jiangxi, People’s Republic of China
| | - Jiao Wang
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanchang UniversityNanchang, Jiangxi, People’s Republic of China
| | - Guoyong Li
- Department of General Surgery, The First Affiliated Hospital of Nanchang UniversityNanchang, Jiangxi, People’s Republic of China
| | - Chao Huang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang UniversityNanchang, Jiangxi, People’s Republic of China
| | - Xiaoyang Dong
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang UniversityNanchang, Jiangxi, People’s Republic of China
| | - Zhen Feng
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang UniversityNanchang, Jiangxi, People’s Republic of China
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Guo H, Li P, Su L, Wu K, Huang K, Lai R, Xu J, Sun D, Li S, Deng Z, Wang Y, Guo H, Chen Z, Wang S. Low expression of IL-37 protein is correlated with high Oct4 protein expression in hepatocellular carcinoma. Gene 2020; 737:144445. [PMID: 32035244 DOI: 10.1016/j.gene.2020.144445] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Revised: 01/31/2020] [Accepted: 02/03/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The function of IL-37 in cancer remains largely unclear. The present research was to probe the protein expression of IL-37 and Oct4 in hepatocellular carcinoma (HCC), para-cancerous tissues (PT) and cancer cell lines, and discuss their relationship. METHODS Forty-nine HCC specimens and forty-nine PT samples were collected for immunohistochemical staining of IL-37 and Oct4 protein. Then, the correlations among IL-37, Oct4 and the clinical indicators were analyzed. In further in vitro studies, IL-37 was over expressed in HepG2 and MHCC97H cancer cell lines by gene transfection using a lipo3000 kit. Finally, the protein expression of IL-37 and Oct4 was detected by immunofluorescence and western blot to verify the in vivo correlation between IL and 37 and Oct4. RESULTS In HCC, IL-37 protein expression was weakly positive with a positive rate of 12.2% while Oct4 expression was strongly positive with a positive rate of 91.8%. In PT, strong positive IL-37 (83.7%) and weakly positive Oct4 (91.8%) were shown. The increased IL-37 and decreased Oct4 induced by IL-37 gene transfection were observed through IF in cells. In terms of clinical significance, the difference of IL-37 expression between HCC and PT was statistically significant (χ2 = 51.815, P = 3.2796 × 10-11). IL-37 in tumor tissues was associated with serum AFP (χ2 = 5.515, P = 0.048) and cirrhosis (χ2 = 7.451, P = 0.014). IL-37 expression of PT was link to gender (χ2 = 10.376, P = 0.013) and tumor size (χ2 = 8.118, P = 0.04). The expression of Oct4 in HCC was related to the patient's gender and cirrhosis. Importantly, there was a negative correlation between IL and 37 and Oct4 in tumor tissues (r = -0.299, P = 0.047) but not in PT (P > 0.05). Oct4 protein expression was down-regulated by IL-37 by 63.35% in HepG2 cells (P < 0.05) and 95.20% in MHCC97H cells (P < 0.05). CONCLUSION IL-37 expression in tumor tissues and PT was related to serum AFP and liver cirrhosis, tumor size, respectively. IL-37 protein expression was correlated with Oct4 in cancer cell lines and tumor tissues but not PT. The present study indicated that IL-37 might play a role in the development of HCC.
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Affiliation(s)
- Hongsheng Guo
- Department of Histology and Embryology of the Basic Medical College, Guangdong Medical University, Dongguan, Guangdong Province 523808, China
| | - Peng Li
- Department of Histology and Embryology of the Basic Medical College, Guangdong Medical University, Dongguan, Guangdong Province 523808, China
| | - Liudan Su
- Institute of Laboratory Medicine, Guangdong Medical University, Dongguan, Guangdong Province 523808, China
| | - Kun Wu
- Institute of Laboratory Medicine, Guangdong Medical University, Dongguan, Guangdong Province 523808, China
| | - Kai Huang
- Second Clinical Medical College, Guangdong Medical University, Dongguan, Guangdong Province 523808, China
| | - Ruizhi Lai
- Second Clinical Medical College, Guangdong Medical University, Dongguan, Guangdong Province 523808, China
| | - Jing Xu
- Second Clinical Medical College, Guangdong Medical University, Dongguan, Guangdong Province 523808, China
| | - Dingbao Sun
- Second Clinical Medical College, Guangdong Medical University, Dongguan, Guangdong Province 523808, China
| | - Shuxian Li
- Department of Histology and Embryology of the Basic Medical College, Guangdong Medical University, Dongguan, Guangdong Province 523808, China
| | - Ziliang Deng
- Department of Histology and Embryology of the Basic Medical College, Guangdong Medical University, Dongguan, Guangdong Province 523808, China
| | - Yan Wang
- Department of Histology and Embryology of the Basic Medical College, Guangdong Medical University, Dongguan, Guangdong Province 523808, China
| | - Haina Guo
- Dongguan Maternal and Child Healthcare Hospital, Dongguan, Guangdong Province 520300, China
| | - Zhangquan Chen
- Institute of Laboratory Medicine, Guangdong Medical University, Dongguan, Guangdong Province 523808, China
| | - Sen Wang
- Department of Histology and Embryology of the Basic Medical College, Guangdong Medical University, Dongguan, Guangdong Province 523808, China.
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de Oliveira ARCP, Castanhole-Nunes MMU, Biselli-Chicote PM, Pavarino ÉC, da Silva RDCMA, da Silva RF, Goloni-Bertollo EM. Differential expression of angiogenesis-related miRNAs and VEGFA in cirrhosis and hepatocellular carcinoma. Arch Med Sci 2020; 16:1150-1157. [PMID: 32864004 PMCID: PMC7444729 DOI: 10.5114/aoms.2020.97967] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 01/24/2018] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTION Liver cirrhosis (LC) is a heterogeneous liver disease, the last stage of liver fibrosis, and the major risk factor for hepatocellular carcinoma (HCC). Our study aimed to evaluate the expression of microRNAs and the endothelial vascular growth factor (VEGFA) gene in LC and HCC. MATERIAL AND METHODS The sample group consisted of 46 tissue samples: 21 of LC, 15 of HCC, and 10 of non-tumoural and non-cirrhotic liver tissue (control group). MiRNAs were chosen based on a mirDIP prediction database as regulators of the VEGFA gene. Gene expression of VEGF and miRNAs was quantified by real-time quantitative polymerase chain reaction. VEGFA protein expression was evaluated by ELISA. RESULTS VEGFA gene expression was significantly overexpressed in LC compared to the control group (p < 0.0001). Hsa-miR-206 (p = 0.0313) and hsa-miR-637 (p = 0.0156) were down-expressed in LC. In HCC, hsa-miR-15b (p = 0.0010), hsa-miR-125b (p = 0.0010), hsa-miR-423-3p (p = 0.0010), hsa-miR-424 (p = 0.0313), hsa-miR-494 (p < 0.0001), hsa-miR-497 (p < 0.0001), hsa-miR-612 (p = 0.0078), hsa-miR-637 (p < 0.0001), and hsa-miR-1255b (p = 0.0156) presented down-expression. CONCLUSIONS Overexpression of VEGFA in LC suggests impairment of angiogenesis in this tissue. The differential expression of microRNAs in LC and HCC observed in our study can lead to the evaluation of possible biomarkers for these diseases.
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Affiliation(s)
- André R C P de Oliveira
- Departament of Molecular Biology, UPGEM - Genetics and Molecular Biology Research Unit, São José do Rio Preto Medical School - FAMERP, São José do Rio Preto, Brazil
- Study Group of Liver Tumors - GETF, Hospital de Base - São José do Rio Preto (SP) and Medical School Foundation - FUNFARME - São José do Rio Preto, Brazil
| | - Márcia M U Castanhole-Nunes
- Departament of Molecular Biology, UPGEM - Genetics and Molecular Biology Research Unit, São José do Rio Preto Medical School - FAMERP, São José do Rio Preto, Brazil
- Study Group of Liver Tumors - GETF, Hospital de Base - São José do Rio Preto (SP) and Medical School Foundation - FUNFARME - São José do Rio Preto, Brazil
| | - Patrícia M Biselli-Chicote
- Departament of Molecular Biology, UPGEM - Genetics and Molecular Biology Research Unit, São José do Rio Preto Medical School - FAMERP, São José do Rio Preto, Brazil
| | - Érika C Pavarino
- Departament of Molecular Biology, UPGEM - Genetics and Molecular Biology Research Unit, São José do Rio Preto Medical School - FAMERP, São José do Rio Preto, Brazil
| | - Rita de C M A da Silva
- Study Group of Liver Tumors - GETF, Hospital de Base - São José do Rio Preto (SP) and Medical School Foundation - FUNFARME - São José do Rio Preto, Brazil
| | - Renato F da Silva
- Study Group of Liver Tumors - GETF, Hospital de Base - São José do Rio Preto (SP) and Medical School Foundation - FUNFARME - São José do Rio Preto, Brazil
| | - Eny M Goloni-Bertollo
- Departament of Molecular Biology, UPGEM - Genetics and Molecular Biology Research Unit, São José do Rio Preto Medical School - FAMERP, São José do Rio Preto, Brazil
- Study Group of Liver Tumors - GETF, Hospital de Base - São José do Rio Preto (SP) and Medical School Foundation - FUNFARME - São José do Rio Preto, Brazil
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Zheng Y, Yu K, Huang C, Liu L, Zhao H, Huo M, Zhang J. Integrated bioinformatics analysis reveals role of the LINC01093/miR-96-5p/ZFAND5/NF-κB signaling axis in hepatocellular carcinoma. Exp Ther Med 2019; 18:3853-3860. [PMID: 31641376 PMCID: PMC6796351 DOI: 10.3892/etm.2019.8046] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2019] [Accepted: 08/19/2019] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a significant health burden worldwide and its pathogenesis remains to be fully elucidated. One of the means by which long non-coding (lnc)RNAs regulate gene expression is by interacting with micro (mi)RNAs and acting as competing endogenous (ce)RNAs. lncRNAs have important roles in various diseases. The aim of the present study was to examine the potential roles of lncRNAs in HCC. The RNA expression profiles of 21 paired tissues of HCC and adjacent non-tumor tissues were obtained from the Gene Expression Omnibus database. The differentially expressed RNAs were analyzed using the DESeq package in R. Expression validation and survival analysis of selected RNAs were performed using Gene Expression Profile Interactive Analysis and/or Kaplan-Meier Plotter. The target genes of the miRNAs were predicted using lncBase or TargetScan. Functional analyses were performed using the Database for Annotation, Visualization and Integrated Discovery, and regulatory networks were determined using Cytoscape. Long intergenic non-protein coding RNA 1093 (LINC01093) was identified as one of the most significantly downregulated lncRNAs in HCC tissues. Downregulated expression of LINC01093 was associated with poor prognosis. A ceRNA network involving LINC01093, miR-96-5p and zinc finger AN1-type containing 5 (ZFAND5) was established. According to functional analyses, NF-κB signaling was implicated in the regulatory network for HCC. The present study revealed that a LINC01093/miR-96-5p/ZFAND5/NF-κB signaling axis may have an important role in the pathogenesis of HCC, and further investigation of this axis may provide novel insight into the development and progression of HCC.
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Affiliation(s)
- Yahui Zheng
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Kangkang Yu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Chong Huang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Lu Liu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Hao Zhao
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Meisi Huo
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Jubo Zhang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
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21
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Xiao L, Zhou Z, Li W, Peng J, Sun Q, Zhu H, Song Y, Hou JL, Sun J, Cao HC, Zhongyi D, Wu D, Liu L. Chromobox homolog 8 (CBX8) Interacts with Y-Box binding protein 1 (YBX1) to promote cellular proliferation in hepatocellular carcinoma cells. Aging (Albany NY) 2019; 11:7123-7149. [PMID: 31495785 PMCID: PMC6756871 DOI: 10.18632/aging.102241] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2019] [Accepted: 08/22/2019] [Indexed: 12/24/2022]
Abstract
Polycomb group (PcG) proteins have recently been identified as critical regulators in tumor initiation and development. However, the function of CBX8 in human hepatocellular carcinoma (HCC) remains largely unknown. Our study was designed to explore the biological function and clinical implication of CBX8 in HCC. We investigated the interplay between CBX8 and cell cycle through Gene Set Enrichment Analysis and western blotting. Bioinformatics tools and co-immunoprecipitation were used to explore cell cycle regulation. Finally, we studied the expression and clinical significance of CBX8 in HCC through 3 independent datasets. CBX8 was upregulated in HCC and its expression correlated with cell cycle progression. CyclinD1 was downregulated by CBX8 knockdown but upregulated by CBX8 overexpression. YBX1 interacted with CBX8 and regulated the cell cycle. Moreover, targeting YBX1 with specific siRNA impaired CBX8-mediated regulation of CyclinD1. CBX8 overexpression boosted HCC cell growth, while CBX8 knockdown suppressed cell proliferation. Further, YBX1 interacted with CBX8. YBX1 knockdown compromised the proliferation of CBX8 overexpressing cells. CBX8 promotes HCC cell proliferation through YBX1 mediated cell cycle progression and is related to poor HCC prognoses. Therefore, CBX8 may serve as a potential target for the diagnosis and treatment of HCC.
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Affiliation(s)
- Lushan Xiao
- State Key Laboratory of Organ Failure Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Department of Infectious Diseases, Nan fang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Zixiao Zhou
- State Key Laboratory of Organ Failure Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Department of Infectious Diseases, Nan fang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Wenwen Li
- State Key Laboratory of Organ Failure Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Department of Infectious Diseases, Nan fang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Jie Peng
- Department of Oncology, The Second Affiliated Hospital, Guizhou Medical University, Kaili, P.R. China
| | - Qingcan Sun
- State Key Laboratory of Organ Failure Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Department of Infectious Diseases, Nan fang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Hongbo Zhu
- Department of Infectious Diseases, Nan fang Hospital, Southern Medical University, Guangzhou 510515, China.,Department of Medical Oncology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China
| | - Yang Song
- State Key Laboratory of Organ Failure Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Department of Infectious Diseases, Nan fang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Jin-Lin Hou
- State Key Laboratory of Organ Failure Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Department of Infectious Diseases, Nan fang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Jingyuan Sun
- State Key Laboratory of Organ Failure Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Department of Radiation Oncology, Nan fang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Hui-Chuan Cao
- State Key Laboratory of Organ Failure Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Department of Radiation Oncology, Nan fang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Dong Zhongyi
- State Key Laboratory of Organ Failure Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Department of Radiation Oncology, Nan fang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Dehua Wu
- State Key Laboratory of Organ Failure Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Department of Radiation Oncology, Nan fang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Li Liu
- State Key Laboratory of Organ Failure Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.,Department of Infectious Diseases, Nan fang Hospital, Southern Medical University, Guangzhou 510515, China
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22
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Lorente L, Rodriguez ST, Sanz P, González-Rivero AF, Pérez-Cejas A, Padilla J, Díaz D, González A, Martín MM, Jiménez A, Cerro P, Portero J, Barrera MA. High serum caspase-3 levels in hepatocellular carcinoma prior to liver transplantation and high mortality risk during the first year after liver transplantation. Expert Rev Mol Diagn 2019; 19:635-640. [PMID: 31084510 DOI: 10.1080/14737159.2019.1619549] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background: Higher liver caspase-3 activity has been found in patients with different liver diseases. However, there is no published data about circulating caspase-3 levels in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). Therefore, our objective in this study was to determine whether an association between circulating caspase-3 levels in HCC patients prior to LT and one-year mortality after LT exists. Methods: In this observational and retrospective study, we included HCC patients who underwent LT. We measured serum levels of caspase-3 (as the main executor of apoptosis) and caspase-cleaved cytokeratin (CCCK)-18 (to estimate apoptosis degree) before LT. Results: One-year surviving LT patients (n = 129) showed lower serum levels of caspase-3 (p = 0.004) and CCCK-18 (p = 0.001) than non-surviving LT patients (n = 16). Logistic regression analysis showed that serum caspase-3 levels prior to LT were associated with one-year after LT mortality (Odds Ratio = 2.612; 95% CI = 1.519-4.493; p = 0.001). We found a positive association between serum levels of caspase-3 and CCCK-18 (rho = 0.26; p = 0.002). Conclusions: Our study is the first one reporting data of circulating caspase-3 levels prior to LT for HCC, and an association between high serum caspase-3 levels previously to LT and survival at first year after LT.
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Affiliation(s)
- Leonardo Lorente
- a Intensive Care Unit , Hospital Universitario de Canarias , Santa Cruz de Tenerife , Spain
| | - Sergio T Rodriguez
- b Intensive Care Unit , Hospital Universitario Nuestra Señora Candelaria , Santa Cruz Tenerife , Spain
| | - Pablo Sanz
- c Deparment of Surgery , Hospital Universitario Nuestra Señora de Candelaria , Santa Cruz Tenerife , Spain
| | | | - Antonia Pérez-Cejas
- d Laboratory Deparment , Hospital Universitario de Canarias , Santa Cruz de Tenerife , Spain
| | - Javier Padilla
- c Deparment of Surgery , Hospital Universitario Nuestra Señora de Candelaria , Santa Cruz Tenerife , Spain
| | - Dácil Díaz
- e Deparment of Digestive , Hospital Universitario Nuestra Señora de Candelaria , Santa Cruz Tenerife , Spain
| | - Antonio González
- e Deparment of Digestive , Hospital Universitario Nuestra Señora de Candelaria , Santa Cruz Tenerife , Spain
| | - María M Martín
- b Intensive Care Unit , Hospital Universitario Nuestra Señora Candelaria , Santa Cruz Tenerife , Spain
| | - Alejandro Jiménez
- f Research Unit , Hospital Universitario de Canarias , Santa Cruz de Tenerife , Spain
| | - Purificación Cerro
- g Transplant Unit , Hospital Universitario Nuestra Señora Candelaria , Santa Cruz Tenerife , Spain
| | - Julián Portero
- h Department of Radiology , Hospital Universitario Nuestra Señora Candelaria , Santa Cruz Tenerife , Spain
| | - Manuel A Barrera
- c Deparment of Surgery , Hospital Universitario Nuestra Señora de Candelaria , Santa Cruz Tenerife , Spain
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23
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Zhang W, Cai J, Wu B, Shen Z. pH-responsive hyaluronic acid nanoparticles coloaded with sorafenib and cisplatin for treatment of hepatocellular carcinoma. J Biomater Appl 2019; 34:219-228. [PMID: 31084233 DOI: 10.1177/0885328219849711] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Wei Zhang
- Tianjin First Center Hospital, Tianjin, China
| | - Jinzhen Cai
- Tianjin First Center Hospital, Tianjin, China
| | - Bin Wu
- Tianjin First Center Hospital, Tianjin, China
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24
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Liu C, Mu X, Wang X, Zhang C, Zhang L, Yu B, Sun G. Ponatinib Inhibits Proliferation and Induces Apoptosis of Liver Cancer Cells, but Its Efficacy Is Compromised by Its Activation on PDK1/Akt/mTOR Signaling. Molecules 2019; 24:molecules24071363. [PMID: 30959969 PMCID: PMC6480565 DOI: 10.3390/molecules24071363] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 03/30/2019] [Accepted: 04/04/2019] [Indexed: 12/14/2022] Open
Abstract
Ponatinib is a multi-target protein tyrosine kinase inhibitor, and its effects on hepatocellular carcinoma cells have not been previously explored. In the present study, we investigated its effects on hepatocellular carcinoma cell growth and the underlying mechanisms. Toward SK-Hep-1 and SNU-423 cells, ponatinib induces apoptosis by upregulation of cleaved caspase-3 and -7 and promotes cell cycle arrest in the G1 phase by inhibiting CDK4/6/CyclinD1 complex and phosphorylation of retinoblastoma protein. It inhibits the growth-stimulating mitogen-activated protein (MAP) kinase pathway, the phosphorylation of Src on both negative and positive regulation sites, and Jak2 and Stat3 phosphorylation. Surprisingly, it also activates the PDK1, the protein kinase B (Akt), and the mechanistic target of rapamycin (mTOR) signaling pathway. Blocking mTOR signaling strongly sensitizes cells to inhibition by ponatinib and makes ponatinib a much more potent inhibitor of hepatocellular carcinoma cell proliferation. These findings demonstrate that ponatinib exerts both positive and negative effects on hepatocellular cell proliferation, and eliminating its growth-stimulating effects by drug combination or potentially by chemical medication can significantly improve its efficacy as an anti-cancer drug.
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Affiliation(s)
- Chang Liu
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
| | - Xiuli Mu
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
| | - Xuan Wang
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
| | - Chan Zhang
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
| | - Lina Zhang
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
| | - Baofeng Yu
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
| | - Gongqin Sun
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
- Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI 02881, USA.
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25
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Low Serum Melatonin Levels Prior to Liver Transplantation in Patients with Hepatocellular Carcinoma are Associated with Lower Survival after Liver Transplantation. Int J Mol Sci 2019; 20:ijms20071696. [PMID: 30959735 PMCID: PMC6480689 DOI: 10.3390/ijms20071696] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Revised: 04/02/2019] [Accepted: 04/03/2019] [Indexed: 02/07/2023] Open
Abstract
Melatonin administration has been associated with different benefits in animals and patients suffering from liver diseases. However, there is no published data about circulating melatonin levels in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). Thus, the objective of this observational and retrospective study was to determine whether patients with HCC with lower serum melatonin levels prior to LT have a higher risk of one-year mortality after LT. We measured serum levels of melatonin, malondialdehyde (to assess lipid peroxidation), and total antioxidant capacity (to assess antioxidant state) before LT. One-year surviving LT patients (n = 129) showed higher serum levels of melatonin (p = 0.001) and total antioxidant capacity (p = 0.001) and lower serum levels of malondialheyde (p = 0.01) than non-surviving LT patients (n = 16). Logistic regression analysis showed that high serum melatonin levels prior to LT were associated with lower one-year LT mortality (odds ratio = 0.525; 95% confidence interval (CI) = 0.331–0.834; p = 0.006). We found an association between serum levels of melatonin with serum levels of malondialheyde (rho = −0.22; p = 0.01) and total antioxidant capacity (rho = 0.21; p = 0.01). Thus, the novel findings of our study were the association between high serum melatonin levels prior to LT and survival at first year after LT and the association between serum levels of melatonin with malondialheyde and total antioxidant capacity.
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26
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Madduru D, Ijaq J, Dhar S, Sarkar S, Poondla N, Das PS, Vasquez S, Suravajhala P. Systems Challenges of Hepatic Carcinomas: A Review. J Clin Exp Hepatol 2019; 9:233-244. [PMID: 31024206 PMCID: PMC6477144 DOI: 10.1016/j.jceh.2018.05.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Accepted: 05/10/2018] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular Carcinoma (HCC) is ubiquitous in its prevalence in most of the developing countries. In the era of systems biology, multi-omics has evinced an extensive approach to define the underlying mechanism of disease progression. HCC is a multifactorial disease and the investigation of progression of liver cirrhosis becomes much extensive with cultivating omics approaches. We have performed a comprehensive review about such challenges in multi-omics approaches that are concerned to identify the immunological, genetics and epidemiological factors associated with HCC.
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Affiliation(s)
- Dhatri Madduru
- Department of Biochemistry, Osmania University, Hyderabad 500007, TG, India
- Bioclues.org
| | - Johny Ijaq
- Department of Genetics and Biotechnology, Osmania University, Hyderabad 500007, TG, India
- Bioclues.org
| | | | | | | | - Partha S. Das
- Bioclues.org
- Patient MD, Chicago, IL 60640-5710, United States
| | - Silvia Vasquez
- Bioclues.org
- Instituto Peruano de Energía Nuclear, Avenida Canadá 1470, Lima, Peru
| | - Prashanth Suravajhala
- Bioclues.org
- Department of Biotechnology and Bioinformatics, Birla Institute of Scientific Research, Statue Circle 302001, RJ, India
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27
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Ding Y, Rao SX, Wang WT, Chen CZ, Li RC, Zeng M. Comparison of gadoxetic acid versus gadopentetate dimeglumine for the detection of hepatocellular carcinoma at 1.5 T using the liver imaging reporting and data system (LI-RADS v.2017). Cancer Imaging 2018; 18:48. [PMID: 30526674 PMCID: PMC6286579 DOI: 10.1186/s40644-018-0183-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Accepted: 11/29/2018] [Indexed: 12/15/2022] Open
Abstract
PURPOSE The goal of this study was to investigate the Liver Imaging Reporting and Data System (LI-RADS) v.2017 for the categorization of hepatocellular carcinomas (HCCs) with gadoxetic acid compared with gadopentetate dimeglumine-enhanced 1.5-T magnetic resonance imaging (MRI). MATERIAL AND METHODS We included 141 high-risk patients with 145 pathologically-confirmed HCCs who first underwent gadopentetate dimeglumine-enhanced 1.5-T followed by gadoxetic acid-enhanced 1.5-T MRI. Two independent radiologists evaluated the presence or absence of major HCC features and assigned LI-RADS categories after considering ancillary features on both MRIs. Finally, the sensitivity of LI-RADS category 5 (LR-5) and the frequencies of major HCC features were compared between gadoxetic acid- and gadopentetate dimeglumine-enhanced 1.5-T MRI using the Wilcoxon test. RESULTS The sensitivity of LR-5 for diagnosing HCCs was significantly different between gadoxetic acid- and gadopentetate dimeglumine-enhanced MRI (73.8% [107/145] vs 26.2% [38/145], P < 0.001; 71% [103/145] vs 29% [42/145], P < 0.001 for reviewers 1 and 2, respectively). Among the major HCC LI-RADS features, capsule appearance was less frequently demonstrated on gadoxetic acid-enhanced MRI than on gadopentetate dimeglumine-enhanced MRI (3.4% [5/145] vs 5.5% [8/145], P = 0.793; 4.1% [6/145] vs 5.5% [8/145], P = 0.87 for reviewers 1 and 2, respectively), and the frequency of arterial hyperenhancement was not significantly different between gadoxetic acid and gadopentetate dimeglumine (89% [129/145] vs 89% [129/145], P = 1.000). In addition, the frequency of a washout appearance was less in the transitional phase (TP) than in the portal venous phase (PVP) on gadoxetic acid-enhanced MRI (43% [46/107] vs 57% [61/107], P = 0.367). CONCLUSION Gadoxetic acid-enhanced MRI showed a comparable sensitivity to gadopentetate dimeglumine-enhanced MRI for the diagnosis of HCCs, and LI-RADS category 4 (LR-4) hepatic nodules were upgraded to LR-5 when taking into account the major features according to LI-RADS v.2017.
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Affiliation(s)
- Ying Ding
- Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai Institute of Medical Imaging, No138, Fenglin Road, Xuhui District, Shanghai, 200032 China
| | - Sheng-xiang Rao
- Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai Institute of Medical Imaging, No138, Fenglin Road, Xuhui District, Shanghai, 200032 China
- Department of Medical Imaging, Shanghai Medical College, Fudan University, No138, Fenglin Road, Xuhui District, Shanghai, 200032 China
| | - Wen-tao Wang
- Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai Institute of Medical Imaging, No138, Fenglin Road, Xuhui District, Shanghai, 200032 China
| | - Cai-zhong Chen
- Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai Institute of Medical Imaging, No138, Fenglin Road, Xuhui District, Shanghai, 200032 China
| | - Ren-chen Li
- Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai Institute of Medical Imaging, No138, Fenglin Road, Xuhui District, Shanghai, 200032 China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai Institute of Medical Imaging, No138, Fenglin Road, Xuhui District, Shanghai, 200032 China
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28
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Lorente L. New prognostic biomarkers of mortality in patients undergoing liver transplantation for hepatocellular carcinoma. World J Gastroenterol 2018; 24:4230-4242. [PMID: 30310256 PMCID: PMC6175764 DOI: 10.3748/wjg.v24.i37.4230] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 08/18/2018] [Accepted: 08/24/2018] [Indexed: 02/06/2023] Open
Abstract
The outcome prediction of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) was classically established using various macromorphological factors and serum alpha-fetoprotein levels prior to LT. However, other biomarkers have recently been reported to be associated with the prognosis of HCC patients undergoing to LT. This review summarizes clinical data on these new biomarkers. High blood levels of malondialdehyde, total antioxidant capacity, caspase-cleaved cytokeratin-18, soluble CD40 ligand, substance P, C-reactive protein, and vascular endothelial growth factor, increased neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in blood, high peripheral blood expression of human telomerase reverse transcriptase messenger ribonucleic acid, and high HCC expression of dickkopf-1 have recently been associated with decreased survival rates. In addition, high blood levels of des-gamma-carboxy prothrombin, and high HCC expression of glypican-3, E-cadherin and beta-catenin have been associated with increased HCC recurrence. Additional research is necessary to establish the prognostic role of these biomarkers in HCC prior to LT. Furthermore, some of these biomarkers are also interesting because their potential modulation could help to create new research lines for improving the outcomes of those patients.
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Affiliation(s)
- Leonardo Lorente
- Intensive Care Unit, Hospital Universitario de Canarias, Santa Cruz de Tenerife 38320, Spain
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29
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Wu J, Wang ST, Zhang ZJ, Zhou Q, Peng BG. CREB5 promotes cell proliferation and correlates with poor prognosis in hepatocellular carcinoma. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2018; 11:4908-4916. [PMID: 31949566 PMCID: PMC6962929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Accepted: 09/07/2018] [Indexed: 06/10/2023]
Abstract
CAMP responsive element binding protein 5 (CREB5) has been reported to be overexpressed in several types of human cancers and has crucial roles in regulating cell growth, proliferation, differentiation, and the cell cycle. However, the expression and function of CREB5 in hepatocellular carcinoma (HCC) remains unclear. The purpose of this study was to investigate the role of CREB5 in HCC, and its prognostic significance. We measured the expression of CREB5 in 91 specimens of paraffin-embedded HCC tissue by immunohistochemistry and performed a clinicopathological analysis. Gain of function and loss of function assays were used to evaluate the effect of CREB5 on cell proliferation in vitro. We found that up-regulation of CREB5 was associated with a poor prognosis, and CREB5 status was an independent prognostic factor. The overexpression of CREB5 increased the proliferation of SMMC-7721 cells, but the knockdown of CREB5 had the opposite effect. The results indicate that CREB5 may be useful when determining a treatment strategy for patients with HCC.
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Affiliation(s)
- Jian Wu
- Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou, Guangdong Province, PR China
| | - Shu-Tong Wang
- Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou, Guangdong Province, PR China
| | - Zi-Jian Zhang
- Department of General Surgery, The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen, Guangdong Province, PR China
| | - Qi Zhou
- Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou, Guangdong Province, PR China
| | - Bao-Gang Peng
- Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou, Guangdong Province, PR China
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30
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Kumar Y, Phaniendra A, Periyasamy L. Bixin Triggers Apoptosis of Human Hep3B Hepatocellular Carcinoma Cells: An Insight to Molecular and IN SILICO Approach. Nutr Cancer 2018; 70:971-983. [PMID: 30204479 DOI: 10.1080/01635581.2018.1490445] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most common liver cancer and is known to be resistant to conventional chemotherapy. The use of herbal medicine and supplements has increased over recent decades following side effects and resistant to conventional chemotherapy. The seeds of Bixa orellana L. commonly known as annatto have recently gained scientific attention due to presence of a carotenoid bixin for its substantial anticancer properties. However, molecular mechanisms underlying bixin-induced apoptosis are still unclear. Treatment of bixin significantly decreased the number of Hep3B cells and morphological study revealed the change in cellular and nuclear morphology that trigger the events of apoptosis confirmed by annexin V/PI staining. Further DCFDA and rhodamine 123 spectrofluorimetry study showed elevation in reactive oxygen species (ROS) production and loss of mitochondrial membrane potential (MMP), respectively. ROS production caused DNA damage and apoptosis was marked by cell cycle arrest, up-regulation of Bax and FasL protein as well as cleavage of caspase-9, caspase-8 and caspase-3 protein. Docking study with pro-apoptotic molecule Bax and surface Fas ligand exhibited energetically favourable binding interaction. Collectively, these results suggest that bixin capable of modulating the extrinsic and intrinsic molecules of apoptosis indicating its potential for development of promising candidate for hepatocellular carcinoma.
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Affiliation(s)
- Yogesh Kumar
- a Department of Biochemistry and Molecular Biology, School of Life Sciences , Pondicherry University , Kalapet , India
| | - Alugoju Phaniendra
- a Department of Biochemistry and Molecular Biology, School of Life Sciences , Pondicherry University , Kalapet , India
| | - Latha Periyasamy
- a Department of Biochemistry and Molecular Biology, School of Life Sciences , Pondicherry University , Kalapet , India
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Li Y, Zeng X, He J, Gui Y, Zhao S, Chen H, Sun Q, Jia N, Yuan H. Circular RNA as a biomarker for cancer: A systematic meta-analysis. Oncol Lett 2018; 16:4078-4084. [PMID: 30128031 DOI: 10.3892/ol.2018.9125] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Accepted: 06/19/2018] [Indexed: 01/01/2023] Open
Abstract
Circular RNAs (circRNAs) may serve as biomarkers for a potentially non-invasive diagnosis of cancer. To understand their diagnostic performance, a systematic meta-analysis of the published literature was conducted to review the diagnostic efficiency of circRNAs in patients with cancer. Eligible studies published up to November 30, 2017, on PubMed and EMBASE, were selected for the meta-analysis. All studies were carefully and independently reviewed by two researchers based on their titles and abstracts, following which full texts were perused for potential eligibility. All statistical analyses were performed by STATA 13.0 statistical software and Meta-DiSc 1.4. A total of 10 eligible studies were included. The pooled diagnostic odds ratio was 7.265. The pooled sensitivity was 0.708 and the pooled specificity was 0.722. The positive likelihood and negative likelihood ratios were 2.483 and 0.372, respectively. The area under the curve was 0.793. circRNA was determined to be a notably effective assistant diagnostic biomarker for cancer.
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Affiliation(s)
- Yulong Li
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China
| | - Xiaoli Zeng
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China
| | - Jianxun He
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China
| | - Yuan Gui
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China
| | - Song Zhao
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China
| | - Hua Chen
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China
| | - Qi Sun
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China
| | - Nan Jia
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China
| | - Hui Yuan
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China
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Chen J, Montagner A, Tan NS, Wahli W. Insights into the Role of PPARβ/δ in NAFLD. Int J Mol Sci 2018; 19:ijms19071893. [PMID: 29954129 PMCID: PMC6073272 DOI: 10.3390/ijms19071893] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Revised: 06/13/2018] [Accepted: 06/23/2018] [Indexed: 12/14/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a major health issue in developed countries. Although usually associated with obesity, NAFLD is also diagnosed in individuals with low body mass index (BMI) values, especially in Asia. NAFLD can progress from steatosis to non-alcoholic steatohepatitis (NASH), which is characterized by liver damage and inflammation, leading to cirrhosis and hepatocellular carcinoma (HCC). NAFLD development can be induced by lipid metabolism alterations; imbalances of pro- and anti-inflammatory molecules; and changes in various other factors, such as gut nutrient-derived signals and adipokines. Obesity-related metabolic disorders may be improved by activation of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)β/δ, which is involved in metabolic processes and other functions. This review is focused on research findings related to PPARβ/δ-mediated regulation of hepatic lipid and glucose metabolism and NAFLD development. It also discusses the potential use of pharmacological PPARβ/δ activation for NAFLD treatment.
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Affiliation(s)
- Jiapeng Chen
- Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore 308232, Singapore.
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
| | - Alexandra Montagner
- ToxAlim, Research Center in Food Toxicology, National Institute for Agricultural Research (INRA), 180 Chemin de Tournefeuille, 31300 Toulouse, France.
- Institut National de La Santé et de La Recherche Médicale (INSERM), UMR1048, Institute of Metabolic and Cardiovascular Diseases, 31027 Toulouse, France.
| | - Nguan Soon Tan
- Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore 308232, Singapore.
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
- KK Research Centre, KK Women's and Children Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore.
- Institute of Molecular and Cell Biology, Agency for Science Technology & Research, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
| | - Walter Wahli
- Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore 308232, Singapore.
- ToxAlim, Research Center in Food Toxicology, National Institute for Agricultural Research (INRA), 180 Chemin de Tournefeuille, 31300 Toulouse, France.
- Center for Integrative Genomics, University of Lausanne, Génopode, CH-1015 Lausanne, Switzerland.
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Lorente L, Rodriguez ST, Sanz P, Pérez-Cejas A, Abreu-González P, Padilla J, Díaz D, González A, Martín MM, Jiménez A, Cerro P, Barrera MA. Serum total antioxidant capacity prior to liver transplantation for hepatocellular carcinoma is associated with 1-year liver transplantation survival. J Int Med Res 2018; 46:2641-2649. [PMID: 29911482 PMCID: PMC6124293 DOI: 10.1177/0300060518768150] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Objective To determine whether there was an association between serum total antioxidant capacity (TAC) levels prior to in liver transplantation (LT) for hepatocellular carcinoma (HCC) and 1-year LT mortality. Methods This observational retrospective single-centre study of patients with LT for HCC measured serum levels of TAC and malondialdehyde (as a biomarker of lipid peroxidation) before LT. The study endpoint was 1-year LT mortality. Results This study included 142 patients who underwent LT for HCC. Patients who survived the first year (n = 127) had significantly lower aged liver donors, significantly higher serum TAC levels, and significantly lower serum malondialdehyde levels compared with the non-survivors (n = 15). Logistic regression analysis found that serum TAC levels (odds ratio [OR] 0.275; 95% confidence interval [CI] 0.135, 0.562) and the age of the LT donor (OR 1.050; 95% CI 1.009, 1.094) were associated with 1-year LT mortality. There was an inverse association between serum levels of TAC and malondialdehyde levels (rho = –0.22). Conclusions There was an association between low serum TAC levels prior to LT for HCC and mortality during the first year after LT. There was an inverse association between serum TAC levels and lipid peroxidation as measured by malondialdehyde levels.
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Affiliation(s)
- Leonardo Lorente
- 1 Intensive Care Unit, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
| | - Sergio T Rodriguez
- 2 Intensive Care Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz Tenerife, Spain
| | - Pablo Sanz
- 3 Deparment of Surgery, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz Tenerife, Spain
| | - Antonia Pérez-Cejas
- 4 Laboratory Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
| | - Pedro Abreu-González
- 5 Deparment of Physiology, Faculty of Medicine, University of the La Laguna, Santa Cruz de Tenerife, Spain
| | - Javier Padilla
- 3 Deparment of Surgery, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz Tenerife, Spain
| | - Dácil Díaz
- 6 Department of Digestive Medicine, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz Tenerife, Spain
| | - Antonio González
- 6 Department of Digestive Medicine, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz Tenerife, Spain
| | - María M Martín
- 2 Intensive Care Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz Tenerife, Spain
| | - Alejandro Jiménez
- 7 Research Unit, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
| | - Purificación Cerro
- 8 Transplant Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz Tenerife, Spain
| | - Manuel A Barrera
- 3 Deparment of Surgery, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz Tenerife, Spain
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Zhang DY, Zou XJ, Cao CH, Zhang T, Lei L, Qi XL, Liu L, Wu DH. Identification and Functional Characterization of Long Non-coding RNA MIR22HG as a Tumor Suppressor for Hepatocellular Carcinoma. Am J Cancer Res 2018; 8:3751-3765. [PMID: 30083257 PMCID: PMC6071531 DOI: 10.7150/thno.22493] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Accepted: 01/16/2018] [Indexed: 02/07/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) have recently been identified as critical regulators in tumor initiation and development. However, the function of lncRNAs in human hepatocellular carcinoma (HCC) remains largely unknown. Our study was designed to explore the biological function and clinical implication of lncRNA MIR22HG in HCC. Methods: We evaluated MIR22HG expression in 52-patient, 145-patient, TCGA, and GSE14520 HCC cohorts. The effects of MIR22HG on HCC were analyzed in terms of proliferation, invasion, and metastasis, both in vitro and in vivo. The mechanism of MIR22HG action was explored through bioinformatics, luciferase reporter, and RNA immunoprecipitation analyses. Results:MIR22HG expression was significantly down-regulated in 4 independent HCC cohorts compared to that in controls. Its low expression was associated with tumor progression and poor prognosis of patients with HCC. Forced expression of MIR22HG in HCC cells significantly suppressed proliferation, invasion, and metastasis in vitro and in vivo. Mechanistically, MIR22HG derived miR-22-3p to target high mobility group box 1 (HMGB1), thereby inactivating HMGB1 downstream pathways. Additionally, MIR22HG directly interacted with HuR and regulated its subcellular localization. MIR22HG competitively bound to human antigen R (HuR), resulting in weakened expression of HuR-stabilized oncogenes, such as β-catenin. Furthermore, miR-22-3p suppression, HuR or HMGB1 overexpression rescued the inhibitory effects caused by MIR22HG overexpression. Conclusion: Our findings revealed that MIR22HG plays a key role in tumor progression by suppressing the proliferation, invasion, and metastasis of tumor cells, suggesting its potential role as a tumor suppressor and prognostic biomarker in HCC.
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Lorente L, Rodriguez ST, Sanz P, Pérez-Cejas A, Padilla J, Díaz D, González A, Martín MM, Jiménez A, Cerro P, Barrera MA. Patients with high serum substance P levels previously to liver transplantation for hepatocellular carcinoma have higher risk of one-year liver transplantation mortality. Oncotarget 2018; 9:21552-21559. [PMID: 29765559 PMCID: PMC5940410 DOI: 10.18632/oncotarget.25097] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Accepted: 03/23/2018] [Indexed: 12/18/2022] Open
Abstract
Purpose Substance P is a tachykinins family member with inflammatory effects. Higher circulating levels of substance P have been found in patients with liver diseases and in patients with higher severity of liver diseases. The objective of this study was to determine whether serum levels of substance P levels, prior to liver transplantation (LT) for hepatocellular carcinoma (HCC) are associated with one-year LT mortality. Material and Methods In this observational retrospective unicenter study were included patients with LT for HCC. Serum levels of substance P were measured before LT. The end-point of the study was one-year mortality after LT. Results We found that one-year survivor patients (n = 127) showed a lower age in liver donors (p = 0.03) and lower levels of serum substance P levels (p = 0.003) than non-survivor patients (n = 15). Logistic regression analysis showed that serum levels of substance P (levels) were associated with one-year mortality (Odds Ratio = 1.011; 95% CI = 1.004–1.018; p = 0.002) controlling for the age of the LT donor. Conclusions We believe that our study is the first study reporting data on circulating levels of substance P previously to LT for HCC, and an association between elevated levels of serum substance P before LT and mortality during the first year of LT.
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Affiliation(s)
- Leonardo Lorente
- Intensive Care Unit, Hospital Universitario de Canarias, Santa Cruz de Tenerife, 38320, Spain
| | - Sergio T Rodriguez
- Intensive Care Unit, Hospital Universitario Nuestra Señora Candelaria, Santa Cruz de Tenerife, 38010, Spain
| | - Pablo Sanz
- Department of Surgery, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, 38010, Spain
| | - Antonia Pérez-Cejas
- Laboratory Department, Hospital Universitario de Canarias, San Cristóbal de La Laguna, 38320, Spain
| | - Javier Padilla
- Department of Surgery, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, 38010, Spain
| | - Dácil Díaz
- Department of Digestive, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, 38010, Spain
| | - Antonio González
- Department of Digestive, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, 38010, Spain
| | - María M Martín
- Intensive Care Unit, Hospital Universitario Nuestra Señora Candelaria, Santa Cruz de Tenerife, 38010, Spain
| | - Alejandro Jiménez
- Research Unit, Hospital Universitario de Canarias, San Cristóbal de La Laguna, 38320, Spain
| | - Purificación Cerro
- Transplant Unit, Hospital Universitario Nuestra Señora Candelaria, Santa Cruz de Tenerife, 38010, Spain
| | - Manuel A Barrera
- Department of Surgery, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, 38010, Spain
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Feng IC, Hsieh MJ, Chen PN, Hsieh YH, Ho HY, Yang SF, Yeh CB. Cantharidic acid induces apoptosis through the p38 MAPK signaling pathway in human hepatocellular carcinoma. ENVIRONMENTAL TOXICOLOGY 2018; 33:261-268. [PMID: 29159945 DOI: 10.1002/tox.22513] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Revised: 11/03/2017] [Accepted: 11/07/2017] [Indexed: 06/07/2023]
Abstract
Cantharidin analogs exhibit anticancer activities, including apoptosis. However, the molecular mechanisms underlying the effects of cantharidic acid (CA), a cantharidin analog, on apoptosis in hepatocellular carcinoma (HCC) cells are unclear. Thus, in this study, we evaluated the anticancer activities of CA by investigating its ability to trigger apoptosis in SK-Hep-1 cells. Our data demonstrated that CA effectively inhibited the proliferation of SK-Hep-1 cells in a dose-dependent manner. Furthermore, CA effectively triggered cell cycle arrest and induced apoptosis, as determined by flow cytometric analysis. Western blotting revealed that CA significantly activated proapoptotic signaling including caspase-3, -8, and -9 in SK-Hep-1 cells. Moreover, treatment of SK-Hep-1 cells with CA induced the activation of ERK, p38, and c-Jun N-terminal kinase. Moreover, the inhibition of p38 by specific inhibitors abolished CA-induced cell apoptosis. In conclusion, our results indicated that CA induces apoptosis in SK-Hep-1 cells through a p38-mediated apoptotic pathway and could be a new HCC therapeutic agent.
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Affiliation(s)
- I-Che Feng
- Division of Gastroenterology and Hepatology, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
- Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Ming-Ju Hsieh
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
| | - Pei-Ni Chen
- Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yi-Hsien Hsieh
- Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Hsin-Yu Ho
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Chao-Bin Yeh
- Department of Emergency Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
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Zhang S, Wang J, Wang H, Fan L, Fan B, Zeng B, Tao J, Li X, Che L, Cigliano A, Ribback S, Dombrowski F, Chen B, Cong W, Wei L, Calvisi DF, Chen X. Hippo Cascade Controls Lineage Commitment of Liver Tumors in Mice and Humans. THE AMERICAN JOURNAL OF PATHOLOGY 2018; 188:995-1006. [PMID: 29378174 DOI: 10.1016/j.ajpath.2017.12.017] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Revised: 12/11/2017] [Accepted: 12/28/2017] [Indexed: 02/05/2023]
Abstract
Primary liver cancer consists mainly of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). A subset of human HCCs expresses a ICC-like gene signature and is classified as ICC-like HCC. The Hippo pathway is a critical regulator of normal and malignant liver development. However, the precise function(s) of the Hippo cascade along liver carcinogenesis remain to be fully delineated. The role of the Hippo pathway in a murine mixed HCC/ICC model induced by activated forms of AKT and Ras oncogenes (AKT/Ras) was investigated. The authors demonstrated the inactivation of Hippo in AKT/Ras liver tumors leading to nuclear localization of Yap and TAZ. Coexpression of AKT/Ras with Lats2, which activates Hippo, or the dominant negative form of TEAD2 (dnTEAD2), which blocks Yap/TAZ activity, resulted in delayed hepatocarcinogenesis and elimination of ICC-like lesions in the liver. Mechanistically, Notch2 expression was found to be down-regulated by the Hippo pathway in liver tumors. Overexpression of Lats2 or dnTEAD2 in human HCC cell lines inhibited their growth and led to the decreased expression of ICC-like markers, as well as Notch2 expression. Altogether, this study supports the key role of the Hippo cascade in regulating the differentiation status of liver tumors.
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Affiliation(s)
- Shanshan Zhang
- Tumor Immunology and Gene Therapy Center, Second Military Medical University, Shanghai, China; Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California; Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jingxiao Wang
- Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California; Second Clinical Medical School, Beijing University of Chinese Medicine, Beijing, China
| | - Haichuan Wang
- Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California; Liver Transplantation Division, Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Lingling Fan
- Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California
| | - Biao Fan
- Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California; Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute, Beijing, China
| | - Billy Zeng
- Department of Pediatrics, University of California, San Francisco, California; Institute for Computational Health Sciences, University of California, San Francisco, California
| | - Junyan Tao
- Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California
| | - Xiaolei Li
- Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California
| | - Li Che
- Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California
| | - Antonio Cigliano
- National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
| | - Silvia Ribback
- Institute of Pathology, University of Greifswald, Greifswald, Germany
| | - Frank Dombrowski
- Institute of Pathology, University of Greifswald, Greifswald, Germany
| | - Bin Chen
- Department of Pediatrics, University of California, San Francisco, California; Institute for Computational Health Sciences, University of California, San Francisco, California
| | - Wenming Cong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Lixin Wei
- Tumor Immunology and Gene Therapy Center, Second Military Medical University, Shanghai, China
| | - Diego F Calvisi
- Institute of Pathology, University of Greifswald, Greifswald, Germany.
| | - Xin Chen
- Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California.
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Ali MM, H Borai I, Ghanem HM, H Abdel-Halim A, Mousa FM. The prophylactic and therapeutic effects of Momordica charantia methanol extract through controlling different hallmarks of the hepatocarcinogenesis. Biomed Pharmacother 2017; 98:491-498. [PMID: 29287196 DOI: 10.1016/j.biopha.2017.12.096] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Revised: 12/17/2017] [Accepted: 12/19/2017] [Indexed: 02/08/2023] Open
Abstract
Inspite of the wide facilities for controlling cancer growth, there are little drugs to inhibit its metastasis or prevent its angiogenesis. Discovering such natural or synthetic multi-targeted agent that might strike different targets is considered as a vital goal for tumor controlling. In a previous study, the chemoprotective effect of methanol extract of Momordicacharantia (MEMC) on albino western rats bearing hepatocarcinogenesis was evaluated. The mechanism by which MEMC exert its anticancer properties was unknown. Therefore, we aimed in this study to investigate the possible role of MEMC as anti-proliferative, anti-angiogenic and anti-metastatic agent to exert its chemoprotective effect. The study was conducted on sixty albino western rats divided into six groups, 10 rats each. Diethylnitrosamine (DENA) was injected intraperitoneally (i.p.) at a dose of 200 mg/kg body weight once, 2 weeks later rats were received carbon tetrachloride (CCl4) subcutaneously (3 ml/kg/week) continued for 10 weeks. MEMC was orally produced to rats (40 mg/kg) alone, as well as before, at the same time and after DENA injection. Cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), caspase-3,-8 (Casp-3,-8), histone deacetylase (HDAC) and matrixmetalloproteinases-2,-9 (MMP-2,-9) were evaluated. MEMC treatment significantly decreased Cox-2, VEGF, HDAC and MMP-2,-9 and increased Casp-3,-8 as compared to DENAgroup,which demonstrated that the anticancer effect of MEMC may be through the inhibition of angiogenesis, proliferation and metastasis and the activation of apoptosis. The improvement in before-treated group was more pronounced than that in after- and simultaneous-treated groups, indicating thatMEMC may act as a prophylactic agent more than being a therapeutic agent.
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Affiliation(s)
- Mamdouh M Ali
- Biochemistry Department, Division of Genetic Engineering and Biotechnology, National Research Centre, Dokki, 12622, Giza, Egypt.
| | - Ibrahim H Borai
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Hala M Ghanem
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Abeer H Abdel-Halim
- Biochemistry Department, Division of Genetic Engineering and Biotechnology, National Research Centre, Dokki, 12622, Giza, Egypt
| | - Fatma M Mousa
- Biochemistry Department, Division of Genetic Engineering and Biotechnology, National Research Centre, Dokki, 12622, Giza, Egypt
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Du B, Zhang P, Tan Z, Xu J. MiR-1202 suppresses hepatocellular carcinoma cells migration and invasion by targeting cyclin dependent kinase 14. Biomed Pharmacother 2017; 96:1246-1252. [PMID: 29217161 DOI: 10.1016/j.biopha.2017.11.090] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 11/13/2017] [Accepted: 11/17/2017] [Indexed: 12/30/2022] Open
Abstract
Currently, hepatocellular carcinoma (HCC) patients still have poor survival outcomes mainly due to the powerful mobility of HCC cells. Increasing evidences hint that abnormally expressed miRNAs are capable to modulate HCC cells invasion and migration. MiR-1202 has been proposed as a ponderable molecular tumor marker in a variety of tumors. Here, results from real-time PCR indicated the decreased expression of miR-1202 in HCC. Clinically, statistical analysis showed that miR-1202 under-expression was closely associated with metastasis-related clinicopathologic characteristics. In addition, 5-year overall survival (OS) and disease-free survival (DFS) rates of HCC patients with high miR-1202 expression were much better than that in low miR-1202 group. Functionally, gain- and loss-of -function studies were performed to investigate the roles of miR-1202. Intriguingly, Would healing assay and Transwell assays indicated that elevated miR-1202 weakened HCC cells migration and invasion abilities, while miR-1202 knockdown presented the contrary effects. Furthermore, cyclin dependent kinase 14 (CDK14) was identified as a downstream target of miR-1202 by bioinformatics analysis, Dual luciferase reporter assay, detection of CDK14 expression and Pearson correlation analysis. More importantly, rescue experiments demonstrated that CDK14 mediated miR-1202 to exert its anti-tumor effects, which further confirmed the above finding. Taken together, miR-1202 may act as a new biomarker and potential therapeutic target for HCC.
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Affiliation(s)
- Bo Du
- Department of Hepatobiliary Surgery, The People's Hospital of Kaizhou District, Chongqing, 405400, PR China
| | - Peng Zhang
- Department of Hepatobiliary Surgery, The People's Hospital of Kaizhou District, Chongqing, 405400, PR China.
| | - Zhiming Tan
- Department of Hepatobiliary Surgery, The People's Hospital of Kaizhou District, Chongqing, 405400, PR China
| | - Jifan Xu
- Department of Hepatobiliary Surgery, The People's Hospital of Kaizhou District, Chongqing, 405400, PR China
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40
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Xie H, Yu H, Tian S, Yang X, Wang X, Yang Z, Wang H, Guo Z. What is the best combination treatment with transarterial chemoembolization of unresectable hepatocellular carcinoma? a systematic review and network meta-analysis. Oncotarget 2017; 8:100508-100523. [PMID: 29245997 PMCID: PMC5725039 DOI: 10.18632/oncotarget.20119] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 07/30/2017] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE To assess the comparative efficacy and safety of combination treatment with transarterial chemoembolization (TACE) for patients with unresectable hepatocellular carcinoma (HCC) through a systematic review and network meta-analysis and to identify what is the best combination treatment with TACE. MATERIALS AND METHODS A network meta-analysis was used to identify evidence from relevant randomized controlled trials. We searched databases for publications up to June 2017. The prespecified primary efficacy outcomes were treatment response and 6-month to 3-year overall survival (OS), while the secondary efficacy outcomes were 1- and 2-year disease-free survival (DFS); safety outcomes were advance effects of combination treatment. We conducted pairwise meta-analyses using a random-effects model and then performed random-effects network meta-analyses. RESULTS A total of 48 trials were eligible (50 analyses), involving 5627 patients and 19 treatment arms. In comparison with other types of combination therapy arms, network meta-analysis disclosed that TACE + three-dimensional conformal radiotherapy, TACE + percutaneous ethanol injection, TACE + percutaneous microwave coagulation therapy, TACE + percutaneous acetic acid injection, and TACE + sorafenib were the more effective methods in treatment response, 6-month to 3-year OS, and 1-2 year DFS; the adverse effects of TACE + sorafenib were serious. The study was registered with PROSPERO, number CRD42017071102. CONCLUSIONS When considering the efficacy, combination therapy with TACE seemed to offer clear advantages for patients with unresectable HCC. TACE + Three-dimensional conformal radiotherapy, TACE + Percutaneous ethanol injection, TACE + Percutaneous microwave coagulation therapy, and TACE + Percutaneous acetic acid injection are likely the best options to consider in the application of combination treatment.
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Affiliation(s)
- Hui Xie
- Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300070, China
- Department of Interventional Therapy, 302 Hospital of People's Liberation Army, Beijing 100039, China
| | - Haipeng Yu
- Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300070, China
| | - Shengtao Tian
- Department of Interventional Therapy, 302 Hospital of People's Liberation Army, Beijing 100039, China
| | - Xueling Yang
- Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300070, China
| | - Ximing Wang
- Department of Interventional Therapy, 302 Hospital of People's Liberation Army, Beijing 100039, China
| | - Zhao Yang
- Department of Interventional Therapy, 302 Hospital of People's Liberation Army, Beijing 100039, China
| | - Huaming Wang
- Department of Interventional Therapy, 302 Hospital of People's Liberation Army, Beijing 100039, China
| | - Zhi Guo
- Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300070, China
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High serum soluble CD40L levels previously to liver transplantation in patients with hepatocellular carcinoma are associated with mortality at one year. J Crit Care 2017; 43:316-320. [PMID: 29020665 DOI: 10.1016/j.jcrc.2017.09.032] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Revised: 08/29/2017] [Accepted: 09/15/2017] [Indexed: 12/17/2022]
Abstract
PURPOSE CD40L and its soluble form (sCD40L) are proteins of the tumor necrosis factor superfamily (TNFSF) that exhibit prothrombotic and proinflammatory properties when binding to CD40, which is a cell surface receptor of the tumor necrosis factor receptor superfamily (TNFRSF). High circulating levels of sCD40L have been associated with poor prognosis in patients with hepatocellular carcinoma (HCC). However, it is unknown whether there is an association between circulating sCD40L levels and survival in patients with HCC underwent to liver transplantation (LT), and this was the objective of that study. METHODS Serum sCD40L levels were measured in a total of 139 patients before LT (124 survivors at 1year of LT and 15 non-survivors). The end-point study was 1year survival after liver LT. RESULTS We found that 1-year non-surviving patients showed higher serum sCD40L levels than survivor patients (p=0.02). We found in logistic regression analysis that serum sCD40L levels higher than 321pg/mL (Odds Ratio=6.86; 95% confidence interval=2.06-22.76; p=0.002) and age of LT deceased donor were associated with death at 1year. CONCLUSIONS The new finding of our study was that high serum sCD40L levels previously to LT in patients with HCC are associated with higher mortality at one year.
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Gong J, Qi X, Zhang Y, Yu Y, Lin X, Li H, Hu Y. Long noncoding RNA linc00462 promotes hepatocellular carcinoma progression. Biomed Pharmacother 2017. [DOI: 10.1016/j.biopha.2017.06.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
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TURRI JAO, DECIMONI TC, FERREIRA LA, DINIZ MA, HADDAD LBDP, CAMPOLINA AG. Higher MELD score increases the overall cost on the waiting list for liver transplantation: a micro-costing analysis based study. ARQUIVOS DE GASTROENTEROLOGIA 2017; 54:238-245. [DOI: 10.1590/s0004-2803.201700000-35] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Accepted: 04/10/2017] [Indexed: 12/18/2022]
Abstract
ABSTRACT BACKGROUND: The pre-transplant period is complex and includes lots of procedures. The severity of liver disease predisposes to a high number of hospitalizations and high costs procedures. Economic evaluation studies are important tools to handle costs on the waiting list for liver transplantation. OBJECTIVE: The objective of the present study was to evaluate the total cost of the patient on the waiting list for liver transplantation and the main resources related to higher costs. METHODS: A cost study in a cohort of 482 patients registered on waiting list for liver transplantation was carried out. In 24 months follow-up, we evaluated all costs of materials, medicines, consultations, procedures, hospital admissions, laboratorial tests and image exams, hemocomponents replacements, and nutrition. The total amount of each resource or component used was aggregated and multiplied by the unitary cost, and thus individual cost for each patient was obtained. RESULTS: The total expenditure of the 482 patients was US$ 6,064,986.51. Outpatient and impatient costs correspond to 32.4% of total cost (US$ 1,965,045.52) and 67.6% (US$ 4,099,940.99) respectively. Main cost drivers in outpatient were: medicines (44.31%), laboratorial tests and image exams (31.68%). Main cost drivers regarding hospitalizations were: medicines (35.20%), bed use in ward and ICU (26.38%) and laboratorial tests (13.72%). Patients with MELD score between 25-30 were the most expensive on the waiting list (US$ 16,686.74 ± 16,105.02) and the less expensive were those with MELD below 17 (US$ 5,703.22 ± 9,318.68). CONCLUSION: Total costs on the waiting list for liver transplantation increased according to the patient’s severity. Individually, hospitalizations, hemocomponents reposition and hepatocellular carcinoma treatment were the main cost drivers to the patient on the waiting list. The longer the waiting time, the higher the total cost on list, causing greater impact on health systems.
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Sun X, Zhang Y, Xie M. Review. The role of peroxisome proliferator-activated receptor in the treatment of non-alcoholic fatty liver disease. ACTA PHARMACEUTICA 2017; 67:1-13. [PMID: 28231052 DOI: 10.1515/acph-2017-0007] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 10/06/2016] [Indexed: 12/24/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) has been defined as a spectrum of histological abnormalities and is characterized by significant and excessive accumulation of triglycerides in the hepatocytes in patients without alcohol consumption or other diseases. Current studies are targeting new molecular mechanisms that underlie NAFLD and associated metabolic disorders. Many therapeutic targets have been found and used in clinical studies. Peroxisome proliferator-activated receptors (PPARs) are among the potential targets and have been demonstrated to exert a pivotal role in modulation of NAFLD. Many drugs developed so far are targeted at PPARs. Thus, the aim of this paper is to summarize the roles of PPARs in the treatment of NAFLD.
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Affiliation(s)
- Xin Sun
- Department of Pharmacy Wuxi No. 2 People´s Hospital The Affiliated Hospital of Nanjing Medical University , Wuxi , Jiangsu 214002, China
| | - Yan Zhang
- Department of Gynecology and Obstetrics, Wuxi Maternal and Child Health Hospital, The Affiliated Hospital of Nanjing Medical University , Wuxi , Jiangsu, 214002, China
- Department of Pharmacology College of Pharmaceutical Sciences Soochow University , Suzhou , Jiangsu 215123, China
| | - Meilin Xie
- Department of Pharmacology College of Pharmaceutical Sciences Soochow University , Suzhou , Jiangsu 215123, China
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Than NN, Ghazanfar A, Hodson J, Tehami N, Coldham C, Mergental H, Manas D, Shah T, Newsome PN, Reeves H, Shetty S. Comparing clinical presentations, treatments and outcomes of hepatocellular carcinoma due to hepatitis C and non-alcoholic fatty liver disease. QJM 2017; 110:73-81. [PMID: 27634970 PMCID: PMC5444673 DOI: 10.1093/qjmed/hcw151] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Indexed: 01/06/2023] Open
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is increasing in incidence in the UK and globally. Liver cirrhosis is the common cause for developing HCC. The common reasons for liver cirrhosis are viral hepatitis C (HCV), viral hepatitis B and alcohol. However, HCC caused by non-alcoholic fatty liver disease (NAFLD)-cirrhosis is now increasingly as a result of rising worldwide obesity. AIM : To compare the clinical presentation, treatment options and outcomes of HCC due to HCV and NAFLD patients. METHODS Data were collected from two liver transplant centres in the UK (Birmingham and Newcastle upon Tyne) between 2000 and 2014. We compared 275 patients with HCV-related HCC against 212 patients with NAFLD- related HCC. RESULTS Patients in the NAFLD group were found to be significantly older ( P < 0.001) and more likely to be Caucasian ( P < 0.001). They had lower rates of cirrhosis ( P < 0.001) than those in HCV-HCC group. The NAFLD group presented with significantly larger tumours ( P = 0.009), whilst HCV patients had a higher alpha fetoprotein ( P = 0.018). NAFLD patients were more commonly treated with TACE ( P = 0.005) than the HCV patients, whilst the HCV group were significantly more likely to be transplanted ( P < 0.001). In patients selected for liver transplantation, 5-year survival rates in NAFLD were not significantly different from HCV-HCC (44 and 56% respectively, P = 0.102). CONCLUSION In this study, NAFLD patients presented with larger tumours that were less likely to be amenable to curative therapy, as compared with HCV patients. Despite this disadvantage, patients with NAFLD had similar overall survival compared to patients with HCV.
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Affiliation(s)
- Nwe Ni Than
- From the Liver Unit, University Hospitals Birmingham NHS Trust, Birmingham, Edgbaston, UK
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - Anwar Ghazanfar
- Liver Unit, Newcastle Upon Tyne NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - James Hodson
- From the Liver Unit, University Hospitals Birmingham NHS Trust, Birmingham, Edgbaston, UK
| | - Nadeem Tehami
- From the Liver Unit, University Hospitals Birmingham NHS Trust, Birmingham, Edgbaston, UK
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - Chris Coldham
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - Hynek Mergental
- From the Liver Unit, University Hospitals Birmingham NHS Trust, Birmingham, Edgbaston, UK
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - Derek Manas
- Liver Unit, Newcastle Upon Tyne NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Tahir Shah
- From the Liver Unit, University Hospitals Birmingham NHS Trust, Birmingham, Edgbaston, UK
| | - Philip N. Newsome
- From the Liver Unit, University Hospitals Birmingham NHS Trust, Birmingham, Edgbaston, UK
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - Helen Reeves
- Liver Unit, Newcastle Upon Tyne NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Shishir Shetty
- From the Liver Unit, University Hospitals Birmingham NHS Trust, Birmingham, Edgbaston, UK
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK
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Lai XB, Nie YQ, Huang HL, Li YF, Cao CY, Yang H, Shen B, Feng ZQ. NIMA-related kinase 2 regulates hepatocellular carcinoma cell growth and proliferation. Oncol Lett 2017; 13:1587-1594. [PMID: 28454295 PMCID: PMC5403431 DOI: 10.3892/ol.2017.5618] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Accepted: 10/27/2016] [Indexed: 12/29/2022] Open
Abstract
NIMA-related kinase 2 (Nek2) is often upregulated in human cancer and is important in regulating the cell cycle and gene expression, and maintaining centrosomal structure and function. The present study aimed to investigate the expression pattern, clinical significance, and biological function of Nek2 in hepatocellular carcinoma (HCC). mRNA and protein levels of Nek2 were examined in HCC and corresponding normal liver tissues. The MTT and soft agar colony formation assays, and flow cytometry were employed to assess the roles of Nek2 in cell proliferation and growth. In addition, western blot analysis was performed to assess the expression of cell cycle- and proliferation-related proteins. The results revealed that Nek2 was upregulated in HCC tissues and cell lines. The clinical significance of Nek2 expression was also analyzed. Inhibiting Nek2 expression by siRNA suppressed cell proliferation, growth, and colony formation in hepatocellular carcinoma cell line HepG2 cells, induced cell cycle arrest in the G2/M phase by retarding the S-phase, and promoted apoptosis. Furthermore, Nek2 depletion downregulated β-catenin expression in HepG2 cells and diminished expression of Myc proto-oncogene protein (c-Myc), cyclins D1, B1, and E and cyclin-dependent kinase 1, whilst increasing protein levels of p27. This demonstrates that overexpression of Nek2 is associated with the malignant evolution of HCC. Targeting Nek2 may inhibit HCC cell growth and proliferation through the regulation of β-catenin by the Wnt/β-catenin pathway and therefore may be developed as a novel therapeutic strategy to treat HCC.
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Affiliation(s)
- Xiao-Bo Lai
- Department of Gastroenterology and Hepatology, The First Municipal People's Hospital of Guangzhou, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.,Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, Guangdong 510180, P.R. China
| | - Yu-Qiang Nie
- Department of Gastroenterology and Hepatology, The First Municipal People's Hospital of Guangzhou, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.,Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, Guangdong 510180, P.R. China
| | - Hong-Li Huang
- Department of Gastroenterology and Hepatology, The First Municipal People's Hospital of Guangzhou, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.,Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, Guangdong 510180, P.R. China
| | - Ying-Fei Li
- Department of Gastroenterology and Hepatology, The First Municipal People's Hospital of Guangzhou, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.,Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, Guangdong 510180, P.R. China
| | - Chuang-Yu Cao
- Department of Gastroenterology and Hepatology, The First Municipal People's Hospital of Guangzhou, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.,Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, Guangdong 510180, P.R. China
| | - Hui Yang
- Department of Gastroenterology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510282, P.R. China
| | - Bo Shen
- Department of Gastroenterology and Hepatology, The First Municipal People's Hospital of Guangzhou, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.,Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, Guangdong 510180, P.R. China
| | - Zhi-Qiang Feng
- Department of Gastroenterology and Hepatology, The First Municipal People's Hospital of Guangzhou, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.,Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, Guangdong 510180, P.R. China
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Sun W, Wang Y, Cai M, Lin L, Chen X, Cao Z, Zhu K, Shuai X. Codelivery of sorafenib and GPC3 siRNA with PEI-modified liposomes for hepatoma therapy. Biomater Sci 2017; 5:2468-2479. [DOI: 10.1039/c7bm00866j] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
A novel liposomal system incorporating branched PEI was prepared to efficiently codeliver sorafenib and GPC3 siRNA for hepatocellular carcinoma therapy.
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Affiliation(s)
- Weitong Sun
- PCFM Lab of Ministry of Education
- School of Materials Science and Engineering
- Sun Yat-Sen University
- Guangzhou
- China
| | - Yong Wang
- PCFM Lab of Ministry of Education
- School of Materials Science and Engineering
- Sun Yat-Sen University
- Guangzhou
- China
| | - Mingyue Cai
- Department of Minimally Invasive Interventional Radiology and Department of Radiology
- The Second Affiliated Hospital of Guangzhou Medical University
- Guangzhou
- China
| | - Liteng Lin
- Department of Minimally Invasive Interventional Radiology and Department of Radiology
- The Second Affiliated Hospital of Guangzhou Medical University
- Guangzhou
- China
| | - Xiaoyan Chen
- PCFM Lab of Ministry of Education
- School of Materials Science and Engineering
- Sun Yat-Sen University
- Guangzhou
- China
| | - Zhong Cao
- Department of Biomedical Engineering
- School of Engineering
- Sun Yat-sen University
- Guangzhou
- China
| | - Kangshun Zhu
- Department of Minimally Invasive Interventional Radiology and Department of Radiology
- The Second Affiliated Hospital of Guangzhou Medical University
- Guangzhou
- China
| | - Xintao Shuai
- PCFM Lab of Ministry of Education
- School of Materials Science and Engineering
- Sun Yat-Sen University
- Guangzhou
- China
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Gao Y, Wang G, Zhang C, Lin M, Liu X, Zeng Y, Liu J. Long non-coding RNA linc-cdh4-2 inhibits the migration and invasion of HCC cells by targeting R-cadherin pathway. Biochem Biophys Res Commun 2016; 480:348-354. [PMID: 27765630 DOI: 10.1016/j.bbrc.2016.10.048] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Accepted: 10/16/2016] [Indexed: 12/18/2022]
Abstract
Long non-coding RNAs (LncRNAs) have played very important roles in the malignancy behaviors of hepatocellular carcinoma (HCC). Linc-cdh4-2 (TCONS_00027978) is a novel LncRNA that has been identified in HCC tissues from our previous study. Overexpression of linc-cdh4-2 in HCC cell lines (SK-Hep-1 and Huh7) significantly decreases the migration and invasion abilities of these cells, while knockdown the expression of linc-cdh4-2 significantly increases the migration and invasion abilities. Interestingly, neither the over expression nor the knock down of linc-cdh4-2 could affect the viability and proliferation of HCC cells. Mechanistically, the linc-cdh4-2 could up-regulate the protein level of R-cadherin through direct binding that might improve the protein stability. Over expression of linc-cdh4-2 could significantly increase the protein levels of R-cadherin and decrease the protein levels of small GTPase RAC1, and vice-versa. Further knockdown R-cadherin in linc-cdh4-2 stably overexpressed cells, could significantly upregulate the protein levels of RAC1 and improve the cell migration and invasion abilities. Taken together, the novel linc-cdh4-2 may negatively regulate the motility of the HCC cells through targeting R-cadherin-RAC1 signaling pathway.
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Affiliation(s)
- Yunzhen Gao
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, PR China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, PR China
| | - Gaoxiong Wang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, PR China
| | - Cuilin Zhang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, PR China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, PR China
| | - Minjie Lin
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, PR China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, PR China
| | - Xiaolong Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, PR China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, PR China
| | - Yongyi Zeng
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, PR China; Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, PR China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, PR China.
| | - Jingfeng Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, PR China; Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, PR China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, PR China.
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Hu XX, Yang ZX, Liang HY, Ding Y, Grimm R, Fu CX, Liu H, Yan X, Ji Y, Zeng MS, Rao SX. Whole-tumor MRI histogram analyses of hepatocellular carcinoma: Correlations with Ki-67 labeling index. J Magn Reson Imaging 2016; 46:383-392. [PMID: 27862582 DOI: 10.1002/jmri.25555] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Revised: 10/26/2016] [Accepted: 10/27/2016] [Indexed: 12/14/2022] Open
Abstract
PURPOSE To evaluate whether whole-tumor histogram-derived parameters for an apparent diffusion coefficient (ADC) map and contrast-enhanced magnetic resonance imaging (MRI) could aid in assessing Ki-67 labeling index (LI) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS In all, 57 patients with HCC who underwent pretreatment MRI with a 3T MR scanner were included retrospectively. Histogram parameters including mean, median, standard deviation, skewness, kurtosis, and percentiles (5th , 25th , 75th , 95th ) were derived from the ADC map and MR enhancement. Correlations between histogram parameters and Ki-67 LI were evaluated and differences between low Ki-67 (≤10%) and high Ki-67 (>10%) groups were assessed. RESULTS Mean, median, 5th , 25th , 75th percentiles of ADC, and mean, median, 25th , 75th , 95th percentiles of enhancement of arterial phase (AP) demonstrated significant inverse correlations with Ki-67 LI (rho up to -0.48 for ADC, -0.43 for AP) and showed significant differences between low and high Ki-67 groups (P < 0.001-0.04). Areas under the receiver operator characteristics (ROC) curve for identification of high Ki-67 were 0.78, 0.77, 0.79, 0.82, and 0.76 for mean, median, 5th , 25th , 75th percentiles of ADC, respectively, and 0.74, 0.81, 0.76, 0.82, 0.69 for mean, median, 25th , 75th , 95th percentiles of AP, respectively. CONCLUSION Histogram-derived parameters of ADC and AP were potentially helpful for predicting Ki-67 LI of HCC. LEVEL OF EVIDENCE 3 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;46:383-392.
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Affiliation(s)
- Xin-Xing Hu
- Department of Radiology, Zhongshan Hospital, Fudan University, and Shanghai Medical Imaging Institute, Shanghai, China
| | - Zhao-Xia Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, and Shanghai Medical Imaging Institute, Shanghai, China
| | - He-Yue Liang
- Department of Radiology, Zhongshan Hospital, Fudan University, and Shanghai Medical Imaging Institute, Shanghai, China
| | - Ying Ding
- Department of Radiology, Zhongshan Hospital, Fudan University, and Shanghai Medical Imaging Institute, Shanghai, China
| | - Robert Grimm
- MR Application Development, Siemens Healthcare, Erlangen, Germany
| | - Cai-Xia Fu
- Siemens Shenzhen Magnetic Resonance, Shenzhen, China
| | - Hui Liu
- MR Collaboration NE Asia, Siemens Healthcare, Shanghai, China
| | - Xu Yan
- MR Collaboration NE Asia, Siemens Healthcare, Shanghai, China
| | - Yuan Ji
- Department of Pathology, Zhongshan hospital, Fudan University, Shanghai, China
| | - Meng-Su Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, and Shanghai Medical Imaging Institute, Shanghai, China
| | - Sheng-Xiang Rao
- Department of Radiology, Zhongshan Hospital, Fudan University, and Shanghai Medical Imaging Institute, Shanghai, China
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50
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Liu DG, Chen J, Wang HX, Li BX. Increased expression of urotensin II is associated with poor prognosis in hepatocellular carcinoma. Oncol Lett 2016; 12:4961-4968. [PMID: 28105202 PMCID: PMC5228350 DOI: 10.3892/ol.2016.5344] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2015] [Accepted: 09/01/2016] [Indexed: 12/19/2022] Open
Abstract
Urotensin II (UII) and the urotensin II receptor (UT) exhibit mitogenic effects on tumor growth. Our previous study demonstrated that the UII/UT system is upregulated in hepatocellular carcinoma (HCC) and may enhance the proliferation of human hepatoma cells. However, the clinical significance of UII/UT expression in HCC remains unclear. The present study assessed UII messenger RNA (mRNA) expression in 129 surgical specimens obtained from HCC patients using reverse transcription quantitative-polymerase chain reaction. The association between UII mRNA expression and clinicopathological parameters and overall survival rates was also investigated. The results revealed that UII and UT mRNA expression was significantly increased in HCC tissue compared with adjacent non-cancerous liver tissue (P<0.001). Furthermore, a significant correlation was identified between UII expression and histological differentiation (P<0.01), tumor size (P<0.01) and tumor stage (P=0.026). Kaplan-Meier survival analysis indicated that overall survival time was significantly shorter in patients with high UII expression, compared with those with low UII expression (P<0.001). Multivariate analyses indicated that UII expression was an independent predictor of overall survival (odds ratio, 1.12; P<0.001). In addition, UII mRNA was correlated with vascular endothelial growth factor mRNA expression. Therefore, UII expression is an independent biomarker for the prognosis of patients with HCC and thus, the UII/UT system may present a novel therapeutic target for the treatment of HCC.
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Affiliation(s)
- Dian-Gang Liu
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China; Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Jing Chen
- Department of Gastroenterology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China
| | - Hong-Xia Wang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P.R. China
| | - Bao-Xin Li
- Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
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