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Lin Y, Ma Y, Chen Y, Huang Y, Lin J, Xiao Z, Cui Z. Diagnostic and prognostic performance of serum GPC3 and PIVKA-II in AFP-negative hepatocellular carcinoma and establishment of nomogram prediction models. BMC Cancer 2025; 25:721. [PMID: 40247208 PMCID: PMC12007284 DOI: 10.1186/s12885-025-14025-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 03/26/2025] [Indexed: 04/19/2025] Open
Abstract
OBJECTIVE A significant proportion, ranging from 20 to 40%, of individuals with hepatocellular carcinoma (HCC) do not exhibit elevated Alpha-fetoprotein (AFP) levels. This study aimed to evaluate the utility of serum glypican-3 (GPC3) and protein induced by vitamin K absence or antagonist II (PIVKA-II) in an AFP-negative HCC (N-HCC) population, and to develop nomogram diagnostic and prognostic prediction models utilizing GPC3 and PIVKA-II. METHODS Serum GPC3 and PIVKA-II levels were measured in this case-control study, followed by the establishment of a receiver operating characteristic (ROC) curve, restricted cubic spline (RCS), and Kaplan-Meier survival curve. Additionally, a diagnostic prediction nomogram was constructed using univariate and multivariate logistic regression. Furthermore, we utilized least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression to develop a prognostic prediction nomogram. The performance of these models was evaluated using ROC curve analysis and decision curve analysis (DCA). RESULTS Serum GPC3 and PIVKA-II expression levels were significantly elevated in untreated patients with N-HCC (especially stageI and tumor size < 3 cm) compared to those with AFP-negative benign liver disease (N-BLD). Derived from ROC analysis, the diagnostic cutoff points for GPC3 and PIVKA-II were set at 0.100 ng/mL and 40.00 mAU/mL, respectively. PIVKA-II demonstrated sensitivity and specificity of 84.62% and 90.38%, surpassing GPC3's 76.92% and 73.08%. The area under the ROC curve (AUC) for a diagnostic prediction nomogram incorporating GPC3, PIVKA-II, and gamma-glutamyltransferase (GGT) was 0.943 (95% CI: 0.912-0.974), superior to models using GPC3 or PIVKA-II alone. This model showed 95.20% sensitivity and 81.70% specificity in differentiating N-HCC from N-BLD. Stratifying patients into high-risk and low-risk groups using cutoff values established by RCS for GPC3 (0.124 ng/mL) and PIVKA-II (274 mAU/mL) revealed significant associations between these risk stratifications and patient survival. Finally, the use of GPC3-highrisk, cirrhosis, albumin (ALB), portal venous thrombosis (PVT), and surgical treatment as five parameters in the nomogram prognostic prediction model effectively differentiated between high- and low-risk prognostic patients with N-HCC with relatively high accuracy. CONCLUSIONS Serum GPC3 and PIVKA-II demonstrate clinical significance in the timely detection and prognosis assessment of N-HCC. The application of nomogram prediction models based on GPC3 and PIVKA-II stands as an important adjunctive tool for diagnosing and prognosticating N-HCC.
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Affiliation(s)
- Yingying Lin
- Laboratory of Biochemistry and Molecular Biology Research, Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, Fujian, China
| | - Yuefei Ma
- Department of Laboratory Medicine, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China
| | - Yan Chen
- Laboratory of Biochemistry and Molecular Biology Research, Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, Fujian, China
| | - Yepei Huang
- Laboratory of Biochemistry and Molecular Biology Research, Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, Fujian, China
| | - Jinchuan Lin
- Department of Laboratory Medicine, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China
| | - Zhenzhou Xiao
- Laboratory of Biochemistry and Molecular Biology Research, Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, Fujian, China.
| | - Zhaolei Cui
- Laboratory of Biochemistry and Molecular Biology Research, Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, Fujian, China.
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Matboli M, Diab GI, Saad M, Khaled A, Roushdy M, Ali M, ELsawi HA, Aboughaleb IH. Machine-Learning-Based Identification of Key Feature RNA-Signature Linked to Diagnosis of Hepatocellular Carcinoma. J Clin Exp Hepatol 2024; 14:101456. [PMID: 39055616 PMCID: PMC11268357 DOI: 10.1016/j.jceh.2024.101456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 06/09/2024] [Indexed: 07/27/2024] Open
Abstract
Background Hepatocellular carcinoma (HCC) is the third prime cause of malignancy-related mortality worldwide. Early and accurate identification of HCC is crucial for good prognosis, efficacy of therapy, and survival rates of the patients. We aimed to develop a machine-learning model incorporating differentially expressed RNA signatures with laboratory parameters to construct an RNA signature-based diagnostic model for HCC. Methods We have used five classifiers (KNN, RF, SVM, LGBM, and DNNs) to predict the liver disease (HCC). The classifiers were trained on 187 samples and then tested on 80 samples. The model included 22 features (age, sex, smoking, cirrhosis, non-cirrhosis, albumin, ALT, AST bilirubin (total and direct), INR, AFP, HBV Ag, HCV Abs, RQmiR-1298, RQmiR-1262, RQmiR-106b-3p, RQmRNARAB11A, and RQSTAT1, RQmRNAATG12, RQLnc-WRAP53, RQLncRNA- RP11-513I15.6). Results LGBM achieved the highest accuracy of 98.75% in predicting HCC among all models surpassing Random Forest (96.25%), DNN (91.25%), SVC (88.75%), and KNN (87.50%). Conclusion Our machine-learning model incorporating the expression data of RAB11A/STAT1/ATG12/miR-1262/miR-1298/miR-106b-3p/lncRNA-RP11-513I15.6/lncRNA-WRAP53 signature and clinical data represents a potential novel diagnostic model for HCC.
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Affiliation(s)
- Marwa Matboli
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine Ain Shams University, Cairo 11566, Egypt
| | - Gouda I. Diab
- Biomedical Engineering Department, Egyptian Armed Forces, Cairo, Egypt
| | - Maha Saad
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Modern University for Technology and Information, Cairo, Egypt
| | - Abdelrahman Khaled
- Bioinformatics Group, Center of Informatics Sciences (CIS), School of Information Technology and Computer Sciences, Nile University, Giza, Egypt
| | - Marian Roushdy
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine Ain Shams University, Cairo 11566, Egypt
| | - Marwa Ali
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine Ain Shams University, Cairo 11566, Egypt
| | - Hind A. ELsawi
- Department of Internal Medicine, Badr University in Cairo, Badr City, Egypt
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Syaiful RA, Mazni Y, Siagian NKP, Putranto AS, Jeo WS, Rahadiani N, Ibrahim F, Sihardo L, Marbun VMG, Lalisang ANL, Lalisang TJM. Surgical resection for hepatocellular carcinoma: a single-centre's one decade of experience. Ann Med Surg (Lond) 2024; 86:1289-1296. [PMID: 38463050 PMCID: PMC10923277 DOI: 10.1097/ms9.0000000000001746] [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: 09/07/2023] [Accepted: 01/10/2024] [Indexed: 03/12/2024] Open
Abstract
Background and aims Liver cancer is the third leading cause of global cancer deaths, and hepatocellular carcinoma is its most common type. Liver resection is one of the treatment options for hepatocellular carcinoma (HCC). This study aims to explore our hospital's more than a decade of experience in liver resection for HCC patients. Methods This is a retrospective cohort study on HCC patients undergoing resection from 2010 to 2021 in a tertiary-level hospital in Jakarta, Indonesia. Mortality rates were explored as the primary outcome of this study. Statistical analysis was done on possible predictive factors using Pearson's χ2. Survival analysis was done using the Log-Rank test and Cox Regression. Results Ninety-one patients were included in this study. The authors found that the postoperative mortality rates were 8.8% (in hospital), 11.5% (30 days), and 24.1% (90 days). Excluding postoperative mortalities, the long-term mortality rates were 44.4% (first year), 58.7% (3 years), and 69.7% (5 years). Cumulatively, the mortality rates were 46.4% (1 year), 68.9% (3 years), 77.8% (5 years), and 67.0% (all time). Significant predictive factors for cumulative 1-year mortality include large tumour diameter [odds ratio (OR) 14.06; 95% CI: 2.59-76.35; comparing <3 cm and >10 cm tumours; P<0.01], positive resection margin (OR 2.86; 1.17-77.0; P=0.02), and tumour differentiation (P=0.01). Multivariate analysis found hazard ratios of 6.35 (2.13-18.93; P<0.01) and 1.81 (1.04-3.14; P=0.04) for tumour diameter and resection margin, respectively. Conclusion The mortality rate of HCC patients undergoing resection is still very high. Significant predictive factors for mortality found in this study benefit from earlier diagnosis and treatment; thus, highlighting the importance of HCC surveillance programs.
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Affiliation(s)
| | - Yarman Mazni
- Digestive Surgery Division, Department of Surgery
| | | | | | | | - Nur Rahadiani
- Department of Anatomical Pathology, Cipto Mangunkusumo Hospital
| | | | - Lam Sihardo
- Digestive Surgery Division, Department of Surgery
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Lampimukhi M, Qassim T, Venu R, Pakhala N, Mylavarapu S, Perera T, Sathar BS, Nair A. A Review of Incidence and Related Risk Factors in the Development of Hepatocellular Carcinoma. Cureus 2023; 15:e49429. [PMID: 38149129 PMCID: PMC10750138 DOI: 10.7759/cureus.49429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/26/2023] [Indexed: 12/28/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a primary liver malignancy, ranking as the seventh most common cancer globally and the second leading cause of deaths due to cancer. This review examines the incidence of HCC, its associated risk factors, and constantly changing global trends. Incidence has been noted to be varying worldwide, particularly due to environmental and infectious risk factors. Chronic hepatitis B (HBV) and C (HCV) virus infections, alcohol abuse, aflatoxin exposure, diabetes, obesity, and tobacco consumption are some of the leading risk factors noted. Eastern Asia and sub-Saharan Africa were noted to have the highest disease burden for HCC, with China representing a considerably large majority. On the contrary, the United States reports a lower HCC incidence overall due to improved vaccination programs against HBV; however, with a rising incidence of prominent risk factor in non-alcoholic fatty liver disease (NAFLD), the trend may very well change. Gender disparities were noted to be evident with men experiencing higher rates of HCC compared to women, which may be due to various environmental and biological factors, including alcohol intake, smoking, and androgen hormone levels. Currently, efforts to reduce the overall incidence of HCC include universal HBV vaccinations, antiviral therapies, aflatoxin prevention measures, genetic screening for hereditary hemochromatosis, and early ultrasound evaluation in patients with liver cirrhosis. Understanding these evolving trends and risk factors is essential in combating the rising HCC incidence, especially in Western countries, where risk factors, such as obesity, diabetes, and metabolic disorders, are on the rise.
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Affiliation(s)
| | - Tabarak Qassim
- School of Medicine, Royal College of Surgeons in Ireland - Medical University of Bahrain, Busaiteen, BHR
| | - Rakshaya Venu
- College of Medicine, Saveetha Medical College, Chennai, IND
| | - Nivedita Pakhala
- College of Medicine, Sri Padmavathi Medical College for Women, Tirupati, IND
| | - Suchita Mylavarapu
- College of Medicine, Malla Reddy Medical College for Women, Hyderabad, IND
| | - Tharindu Perera
- General Medicine, Grodno State Medical University, Grodno, BLR
| | - Beeran S Sathar
- College of Medicine, Jagadguru Jayadeva Murugarajendra Medical College, Davanagere, IND
| | - Arun Nair
- Pediatrics, Saint Peter's University Hospital, Somerset, USA
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Li S, Yin S, Ding H, Shao Y, Zhou S, Pu W, Han L, Wang T, Yu H. Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention. Cell Prolif 2023; 56:e13346. [PMID: 36229407 DOI: 10.1111/cpr.13346] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 09/19/2022] [Accepted: 09/29/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Liver cancer is one of the common malignancies. The dysregulation of metabolism is a driver of accelerated tumourigenesis. Metabolic changes are well documented to maintain tumour growth, proliferation and survival. Recently, a variety of polyphenols have been shown to have a crucial role both in liver disease prevention and metabolism regulation. METHODS We conducted a literature search and combined recent data with systematic analysis to comprehensively describe the molecular mechanisms that link polyphenols to metabolic regulation and their contribution in liver protection and liver cancer prevention. RESULTS Targeting metabolic dysregulation in organisms prevents and resists the development of liver cancer, which has important implications for identifying new therapeutic strategies for the management and treatment of cancer. Polyphenols are a class of complex compounds composed of multiple phenolic hydroxyl groups and are the main active ingredients of many natural plants. They mediate a broad spectrum of biological and pharmacological functions containing complex lipid metabolism, glucose metabolism, iron metabolism, intestinal flora imbalance, as well as the direct interaction of their metabolites with key cell-signalling proteins. A large number of studies have found that polyphenols affect the metabolism of organisms by interfering with a variety of intracellular signals, thereby protecting the liver and reducing the risk of liver cancer. CONCLUSION This review systematically illustrates that various polyphenols, including resveratrol, chlorogenic acid, caffeic acid, dihydromyricetin, quercetin, catechins, curcumin, etc., improve metabolic disorders through direct or indirect pathways to protect the liver and fight liver cancer.
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Affiliation(s)
- Shuangfeng Li
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
| | - Shuangshuang Yin
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
| | - Hui Ding
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yingying Shao
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
| | - Shiyue Zhou
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
| | - Weiling Pu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
| | - Lifeng Han
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
| | - Tao Wang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
| | - Haiyang Yu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
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Liu DM, Leung TW, Chow PK, Ng DC, Lee RC, Kim YH, Mao Y, Cheng YF, Teng GJ, Lau WY. Clinical consensus statement: Selective internal radiation therapy with yttrium 90 resin microspheres for hepatocellular carcinoma in Asia. Int J Surg 2022; 102:106094. [PMID: 35662438 DOI: 10.1016/j.ijsu.2021.106094] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is subject to different management approaches and guidelines according to Eastern and Western therapeutic algorithms. Use of selective internal radiation therapy (SIRT) with resin yttrium 90 microspheres for HCC has increased in Asia in recent years, without clearly defined indications for its optimal application. The objective of this systematic review and expert consensus statement is to provide guidance and perspectives on the use of SIRT among patients with HCC in Asia. MATERIALS AND METHODS A systematic literature review identified current publications on HCC management and SIRT recommendations. A group of 10 experts, representing stakeholder specialties and countries, convened between August 2020 and March 2021 and implemented a modified Delphi consensus approach to develop guidelines and indications for use of SIRT for HCC in Asia. Final recommendations were organized and adjudicated based on the level of evidence and strength of recommendation, per approaches outlined by the American College of Cardiology/American Heart Association and Oxford Centre for Evidence-Based Medicine. RESULTS The experts acknowledged a general lack of evidence relating to use of SIRT in Asia and identified as an unmet need the lack of phase 3 randomized trials comparing clinical outcomes and survival following SIRT versus other therapies for HCC. Through an iterative process, the expert group explored areas of clinical relevance and generated 31 guidance statements and a patient management algorithm that achieved consensus. CONCLUSION These recommendations aim to support clinicians in their decision-making and to help them identify and treat patients with HCC using SIRT in Asia. The recommendations also highlight areas in which further clinical trials are needed to define the role of SIRT in management of HCC among Asian populations.
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Affiliation(s)
- David M Liu
- Department of Radiology, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Thomas Wt Leung
- Comprehensive Oncology Centre, Hong Kong Sanatorium & Hospital, Hong Kong
| | - Pierce Kh Chow
- National Cancer Centre Singapore, Singapore General Hospital, Duke-NUS Medical School, Singapore
| | - David Ce Ng
- Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, Singapore, Duke-NUS Medical School, Singapore
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yun Hwan Kim
- Department of Radiology, Presbyterian Medical Center, Jeonju, South Korea
| | - Yilei Mao
- Department of Liver Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Beijing, China
| | - Yu-Fan Cheng
- Department of Diagnostic Radiology, Liver Transplantation Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Gao-Jun Teng
- Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China
| | - Wan Yee Lau
- Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong.
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7
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Nguyen ALT, Blizzard CL, Yee KC, Campbell JA, Palmer AJ, de Graaff B. Hospitalisation costs of primary liver cancer in Australia: evidence from a data-linkage study. AUST HEALTH REV 2022; 46:463-470. [PMID: 35584964 DOI: 10.1071/ah21395] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 04/15/2022] [Indexed: 11/23/2022]
Abstract
ObjectiveThis study aimed to estimate the public hospital costs associated with primary liver cancer (PLC) in the first and second years following the cancer diagnosis.MethodsThis study linked administrative datasets of patients diagnosed with PLC in Victoria, Australia, from January 2008 to December 2015. The health system perspective was adopted to estimate the direct healthcare costs associated with PLC, based on inpatient and emergency costs. Costs were estimated for the first 12 months and 12-24 months after the PLC diagnosis and expressed in 2017 Australian dollars (A$). The cost estimated was then extrapolated nationally. The linear mixed model with a Box-Cox transformation of the costs was used to explore the relationship between costs and patients' sociodemographic and clinical characteristics.ResultsFor the first 12 months, the total and annual per-patient cost was A$211.4 million and A$63 664, respectively. Costs for the subsequent year were A$49.7 million and A$46 751, respectively. Regarding the cost extrapolation to Australia, the total cost was A$137 million for the first 12 months after notification and A$42.6 million for the period from 12 to 24 months. Higher costs per episode of care were mostly associated with older age, hepatocellular carcinoma type of PLC, metropolitan hospitals, and Asian birth region.ConclusionThis study showed the public hospital admission and emergency costs associated with PLC and the substantial economic burden this cancer has placed on the Australian health system.
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Affiliation(s)
- Anh Le Tuan Nguyen
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tas., Australia
| | | | - Kwang Chien Yee
- School of Medicine, University of Tasmania, Hobart, Tas., Australia
| | - Julie A Campbell
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tas., Australia
| | - Andrew J Palmer
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tas., Australia
| | - Barbara de Graaff
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tas., Australia
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Shukla PK, Zakariah M, Hatamleh WA, Tarazi H, Tiwari B. AI-DRIVEN Novel Approach for Liver Cancer Screening and Prediction Using Cascaded Fully Convolutional Neural Network. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:4277436. [PMID: 35154620 PMCID: PMC8825667 DOI: 10.1155/2022/4277436] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 12/18/2021] [Accepted: 01/05/2022] [Indexed: 01/01/2023]
Abstract
In experimental analysis and computer-aided design sustain scheme, segmentation of cell liver and hepatic lesions by an automated method is a significant step for studying the biomarkers characteristics in experimental analysis and computer-aided design sustain scheme. Patient to patient, the change in lesion type is dependent on the size, imaging equipment (such as the setting dissimilarity approach), and timing of the lesion, all of which are different. With practical approaches, it is difficult to determine the stages of liver cancer based on the segmentation of lesion patterns. Based on the training accuracy rate, the present algorithm confronts a number of obstacles in some domains. The suggested work proposes a system for automatically detecting liver tumours and lesions in magnetic resonance imaging of the abdomen pictures by using 3D affine invariant and shape parameterization approaches, as well as the results of this study. This point-to-point parameterization addresses the frequent issues associated with concave surfaces by establishing a standard model level for the organ's surface throughout the modelling process. Initially, the geodesic active contour analysis approach is used to separate the liver area from the rest of the body. The proposal is as follows: It is possible to minimise the error rate during the training operations, which are carried out using Cascaded Fully Convolutional Neural Networks (CFCNs) using the input of the segmented tumour area. Liver segmentation may help to reduce the error rate during the training procedures. The stage analysis of the data sets, which are comprised of training and testing pictures, is used to get the findings and validate their validity. The accuracy attained by the Cascaded Fully Convolutional Neural Network (CFCN) for the liver tumour analysis is 94.21 percent, with a calculation time of less than 90 seconds per volume for the liver tumour analysis. The results of the trials show that the total accuracy rate of the training and testing procedure is 93.85 percent in the various volumes of 3DIRCAD datasets tested.
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Affiliation(s)
- Piyush Kumar Shukla
- Computer Science & Engineering Department, University Institute of Technology, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal 462033, India
| | - Mohammed Zakariah
- College of Computer and Information Sciences, King Saud University, P.O. Box 51178, Riyadh 11543, Saudi Arabia
| | - Wesam Atef Hatamleh
- Department of Computer Science, College of Computer and Information Sciences, King Saud University, P.O. Box 51178, Riyadh 11543, Saudi Arabia
| | - Hussam Tarazi
- Department of Computer Science and Informatics, School of Engineering and Computer Science, Oakland University, Rochester Hills MI USA 318 Meadow Brook rd, Rochester, MI 48309, USA
| | - Basant Tiwari
- Department of Information Technology, Hawassa University, Institute of Technology, Hawassa, Ethiopia
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Sueshige Y, Shiraiwa K, Honda K, Tanaka R, Saito T, Tokoro M, Iwao M, Endo M, Arakawa M, Tatsuta R, Seike M, Murakami K, Itoh H. A Broad Range High-Throughput Assay for Lenvatinib Using Ultra-High Performance Liquid Chromatography Coupled to Tandem Mass Spectrometry With Clinical Application in Patients With Hepatocellular Carcinoma. Ther Drug Monit 2021; 43:664-671. [PMID: 34521802 DOI: 10.1097/ftd.0000000000000872] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 01/16/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Lenvatinib is increasingly being selected as the first-line treatment for unresectable hepatocellular carcinoma (HCC) based on the results of the REFLECT trial. However, early discontinuation of lenvatinib because of adverse effects is a frequent occurrence. Hence, lenvatinib is a difficult drug for use in the clinical setting. One of the causes is that the dose of lenvatinib is mainly determined by body weight alone, despite high interindividual variability. To overcome this problem, a dosing regimen of lenvatinib based on a population pharmacokinetic (PPK) model for HCC patients is proposed. The aim of this study was to develop a high-throughput quantification method for lenvatinib using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) that can be applied to a PPK analysis of HCC patients in the future. METHODS After a simple solid-phase extraction step using a 96-well plate, lenvatinib was analyzed by UHPLC-MS/MS in a positive electrospray ionization mode. RESULTS The novel method fulfilled the requirements of the US Food and Drug Administration guidance on bioanalytical method validation. The calibration curve was linear over the 0.2-1000 ng/mL concentration range. The average recovery rate was 98.63 ± 4.55% (mean ± SD). The precision was below 6.05%, and the accuracy was within 12.96% for all quality control levels. The matrix effect varied between 103.33% and 134.61%. This assay was successfully applied to the measurement of plasma concentrations in 6 HCC patients receiving lenvatinib. CONCLUSIONS A novel high-throughput UHPLC-MS/MS assay for quantification of lenvatinib in human plasma was successfully developed. This method can be applied to PPK analysis for patients receiving lenvatinib in the clinical setting.
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Affiliation(s)
- Yoshio Sueshige
- Department of Clinical Pharmacy, Oita University Hospital; and
| | - Ken Shiraiwa
- Department of Clinical Pharmacy, Oita University Hospital; and
| | - Koichi Honda
- Department of Gastroenterology, Oita University Faculty of Medicine, Yufu-shi, Oita, Japan
| | - Ryota Tanaka
- Department of Clinical Pharmacy, Oita University Hospital; and
| | - Tomoko Saito
- Department of Gastroenterology, Oita University Faculty of Medicine, Yufu-shi, Oita, Japan
| | - Masanori Tokoro
- Department of Gastroenterology, Oita University Faculty of Medicine, Yufu-shi, Oita, Japan
| | - Masao Iwao
- Department of Gastroenterology, Oita University Faculty of Medicine, Yufu-shi, Oita, Japan
| | - Mizuki Endo
- Department of Gastroenterology, Oita University Faculty of Medicine, Yufu-shi, Oita, Japan
| | - Mie Arakawa
- Department of Gastroenterology, Oita University Faculty of Medicine, Yufu-shi, Oita, Japan
| | - Ryosuke Tatsuta
- Department of Clinical Pharmacy, Oita University Hospital; and
| | - Masataka Seike
- Department of Gastroenterology, Oita University Faculty of Medicine, Yufu-shi, Oita, Japan
| | - Kazunari Murakami
- Department of Gastroenterology, Oita University Faculty of Medicine, Yufu-shi, Oita, Japan
| | - Hiroki Itoh
- Department of Clinical Pharmacy, Oita University Hospital; and
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10
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Teufel A, Quante M, Kandulski A, Hirth M, Zhan T, Eckardt M, Thieme R, Kusnik A, Yesmembetov K, Wiest I, Riemann JF, Schlitt HJ, Gockel I, Malfertheiner P, Ebert MP. [Prevention of gastrointestinal cancer]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:964-982. [PMID: 34507375 DOI: 10.1055/a-1540-7539] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Throughout the past decades, considerable progress has been made in the (early) diagnosis and treatment of gastrointestinal cancers. However, the prognosis for advanced stages of gastrointestinal tumors remains limited for many patients and approximately one third of all tumor patients die as a result of gastrointestinal tumors. The prevention and early detection of gastrointestinal tumors is therefore of great importance.For this reason, we summarize the current state of knowledge and recommendations for the primary, secondary and tertiary prevention of esophageal, stomach, pancreas, liver and colorectal cancer in the following.
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Affiliation(s)
- Andreas Teufel
- II. Medizinische Klinik, Sektion Hepatologie, Medizinische Fakultät Mannheim, Universität Heidelberg, Universitätsklinikum Mannheim, Mannheim.,Klinische Kooperationseinheit Healthy Metabolism, Zentrum für Präventivmedizin und Digitale Gesundheit Baden-Württemberg, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim
| | - Michael Quante
- Klinik für Innere Medizin II, Medizinische Universitätsklinik, Universitätsklinikum Freiburg, Freiburg im Breisgau
| | - Arne Kandulski
- Klinik und Poliklinik für Innere Medizin I, Universitätsklinikum Regensburg, Regensburg
| | - Michael Hirth
- II. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Universitätsklinikum Mannheim, Mannheim
| | - Tianzuo Zhan
- II. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Universitätsklinikum Mannheim, Mannheim
| | - Maximilian Eckardt
- II. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Universitätsklinikum Mannheim, Mannheim
| | - René Thieme
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Department für Operative Medizin (DOPM), Universitatsklinikum Leipzig, Leipzig
| | - Alexander Kusnik
- II. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Universitätsklinikum Mannheim, Mannheim
| | - Kakharman Yesmembetov
- Klinik für Gastroenterologie, Stoffwechselerkrankungen und Internistische Intensivmedizin (Med. III), RWTH Universitätsklinikum Aachen, Aachen
| | - Isabella Wiest
- II. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Universitätsklinikum Mannheim, Mannheim
| | | | - Hans Jürgen Schlitt
- Klinik und Poliklinik für Chirurgie, Universitatsklinikum Regensburg, Regensburg
| | - Ines Gockel
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Department für Operative Medizin (DOPM), Universitatsklinikum Leipzig, Leipzig
| | - Peter Malfertheiner
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Medizinische Fakultät Magdeburg, Magdeburg
| | - Matthias Philip Ebert
- II. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Universitätsklinikum Mannheim, Mannheim.,Klinische Kooperationseinheit Healthy Metabolism, Zentrum für Präventivmedizin und Digitale Gesundheit Baden-Württemberg, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim
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11
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Liu C, Wang YL, Yang YY, Zhang NP, Niu C, Shen XZ, Wu J. Novel approaches to intervene gut microbiota in the treatment of chronic liver diseases. FASEB J 2021; 35:e21871. [PMID: 34473374 DOI: 10.1096/fj.202100939r] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 08/05/2021] [Accepted: 08/09/2021] [Indexed: 02/07/2023]
Abstract
Recent investigations of gut microbiota have contributed to understanding of the critical role of microbial community in pathophysiology. Dysbiosis not only causes disturbance directly to the gastrointestinal tract but also affects the liver through gut-liver axis. Various types of dysbiosis have been documented in alcoholic liver disease (ALD), nonalcoholic fatty liver disease, autoimmune hepatitis (AIH), primary sclerosing cholangitis, and may be crucial for the initiation, progression, or deterioration to end-stage liver disease. A few microbial species have been identified as the causal factors leading to these chronic illnesses that either do not have clear etiologies or lack effective treatment. Notably, cytolysin-producing Enterococcus faecalis, Klebsiella pneumoniae and Enterococcus gallinarum were defined for ALD, NASH, and AIH, respectively. These groundbreaking discoveries drive a rapid development in innovative therapeutics, such as fecal microbial transplantation and implementation of specific bacteriophages in addition to prebiotics, probiotics, or synbiotics for intervention of dysbiosis. Although most emerging interventions are in preclinical development or early clinical trials, a better delineation of specific dysbiosis in these disorders at metabolic, immunogenic, or molecular levels in establishing particular causal effects aids in modulating or correcting the microbial community which is the part of daily life for human being.
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Affiliation(s)
- Chang Liu
- MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Department of Medical Microbiology & Parasitology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China
| | - Yu-Li Wang
- MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Department of Medical Microbiology & Parasitology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China
| | - Yong-Yu Yang
- MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Department of Medical Microbiology & Parasitology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China
| | - Ning-Ping Zhang
- Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, China.,Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai, China
| | - Chen Niu
- MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Department of Medical Microbiology & Parasitology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China
| | - Xi-Zhong Shen
- Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, China.,Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai, China
| | - Jian Wu
- MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Department of Medical Microbiology & Parasitology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China.,Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, China.,Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai, China
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12
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Huang S, Li D, Zhuang L, Sun L, Wu J. Identification of Arp2/3 Complex Subunits as Prognostic Biomarkers for Hepatocellular Carcinoma. Front Mol Biosci 2021; 8:690151. [PMID: 34307456 PMCID: PMC8299467 DOI: 10.3389/fmolb.2021.690151] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 06/14/2021] [Indexed: 01/15/2023] Open
Abstract
The actin-related protein 2/3 complex (Arp2/3) is a major actin nucleator that has been widely reported and plays an important role in promoting the migration and invasion of various cancers. However, the expression patterns and prognostic values of Arp2/3 subunits in hepatocellular carcinoma (HCC) remain unclear. In this study, The Cancer Genome Atlas (TCGA) and UCSC Xena databases were used to obtain mRNA expression and the corresponding clinical information, respectively. The differential expression and Arp2/3 subunits in HCC were analyzed using the “limma” package of R 4.0.4 software. The prognostic value of each subunit was evaluated using Kaplan–Meier survival analysis and Cox proportional hazards regression analyses. The results revealed that mRNA expression of Arp2/3 members (ACTR2, ACTR3, ARPC1A, APRC1B, ARPC2, ARPC3, ARPC4, ARPC5, and ARPC5L) was upregulated in HCC. Higher expression of Arp2/3 members was significantly correlated with worse overall survival (OS) and shorter progression-free survival (PFS) in HCC patients. Cox proportional hazards regression analyses demonstrated that ACTR3, ARPC2, and ARPC5 were independent prognostic biomarkers of survival in patients with HCC. The relation between tumor immunocyte infiltration and the prognostic subunits was determined using the TIMER 2.0 platform and the GEPIA database. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms of prognostic subunits in the carcinogenesis of HCC. The results revealed that ACTR3, ARPC2, and ARPC5 were significantly positively correlated with the infiltration of immune cells in HCC. The GSEA results indicated that ACTR3, ARPC2, and ARPC5 are involved in multiple cancer-related pathways that promote the development of HCC. In brief, various analyses indicated that Arp2/3 complex subunits were significantly upregulated and predicted worse survival in HCC, and they found that ACTR3, ARPC2, and ARPC5 could be used as independent predictors of survival and might be applied as promising molecular targets for diagnosis and therapy of HCC in the future.
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Affiliation(s)
- Shenglan Huang
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.,Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, China
| | - Dan Li
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.,Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, China
| | - LingLing Zhuang
- Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, China.,Department of Gynaecology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Liying Sun
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.,Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, China
| | - Jianbing Wu
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.,Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, China
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13
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A meta-analysis of the efficacy and safety of adjuvant sorafenib for hepatocellular carcinoma after resection. World J Surg Oncol 2021; 19:168. [PMID: 34112190 PMCID: PMC8194151 DOI: 10.1186/s12957-021-02280-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 05/28/2021] [Indexed: 02/08/2023] Open
Abstract
Background Sorafenib was reported as a useful adjuvant treatment in patients with hepatocellular carcinoma who underwent surgical resection. However, its therapeutic value remains controversial. This meta-analysis examined the available data regarding the efficacy and safety of sorafenib in patients with hepatocellular carcinoma after radical surgery. Methods The meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered in advance with PROSPERO (CRD42021233868). We searched PubMed, Embase, Cochrane Library, and Web of Science to identify eligible studies. Overall survival, recurrence-free survival, and recurrence rates were analyzed, and adverse events were reviewed. Hazard ratios or pooled risk ratios with 95% CIs were collected and analyzed using STATA version 12.0 in a fixed-effects or random-effects meta-analysis model. Results In total, 2655 patients from 13 studies were ultimately included in this meta-analysis. The combined results illustrated that sorafenib was associated with better overall survival than the control (hazard ratio = 0.71, 95% CI = 0.59–0.86; P < 0.001). Similarly, the drug also improved recurrence-free survival (hazard ratio = 0.68, 95% CI = 0.54–0.86, P = 0.001). Combined data revealed that patients treated with sorafenib after resection had a lower recurrence rate (pooled risk ratio = 0.78, 95% CI = 0.68–0.90, P < 0.001). The primary adverse events were hand-foot skin reaction, fatigue, and diarrhea of mild-to-moderate severity, whereas grade 4 adverse events were rare (< 1%). Conclusions This meta-analysis demonstrated that adjuvant sorafenib therapy after resection in patients with hepatocellular carcinoma could prolong overall survival and recurrence-free survival and reduce recurrence rates without intolerable side effects. However, more evidence is needed before reaching a definitive conclusion.
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14
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Nguyen ALT, Nguyen HTT, Yee KC, Palmer AJ, Blizzard CL, de Graaff B. A Systematic Review and Narrative Synthesis of Health Economic Evaluations of Hepatocellular Carcinoma Screening Strategies. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2021; 24:733-743. [PMID: 33933243 DOI: 10.1016/j.jval.2020.11.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 09/24/2020] [Accepted: 11/17/2020] [Indexed: 05/02/2023]
Abstract
OBJECTIVES Many economic evaluations of hepatocellular carcinoma (HCC) screenings have been conducted; however, these vary substantially with regards to screening strategies, patient group, and setting. This review aims to report the current knowledge of the cost-effectiveness of screening and describe the published data. METHODS We conducted a search of biomedical and health economic databases up to July 2020. We included full and partial health economic studies if they evaluated the costs or outcomes of HCC screening strategies. RESULTS The review included 43 studies. Due to significant heterogeneity in key aspects across the studies, a narrative synthesis was conducted. Most studies reported using ultrasound or alpha fetoprotein as screening strategies. Screening intervals were mostly annual or biannual. Incidence, diagnostic performance, and health state utility values were the most critical parameters affecting the cost-effectiveness of screening. The majority of studies reported HCC screening to be cost-effective, with the biannual ultrasound + alpha fetoprotein standing out as the most cost-effective strategy. However, few studies considered the utilization rate, and none considered the diagnostic performance of ultrasound in the context of central adiposity. Computed tomography and magnetic resonance imaging were also evaluated, but its cost-effectiveness was still controversial. CONCLUSIONS Although many studies suggested HCC screening was cost-effective, substantial limitations of the quality of these studies means the results should be interpreted with caution. Future modeling studies should consider the impact of central adiposity on the precision of ultrasound, real-world utilization rates and projections of increased HCC incidence.
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Affiliation(s)
- Anh Le Tuan Nguyen
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
| | - Hoa Thi Thu Nguyen
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
| | - Kwang Chien Yee
- School of Medicine, University of Tasmania, Hobart, Tasmania, Australia
| | - Andrew J Palmer
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia; Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia
| | | | - Barbara de Graaff
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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15
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Xu L, Yang W, Shu YF, Xu XF. Hepatocellular carcinoma and multiple myeloma with elevated globulin: a case report and literature review. J Int Med Res 2021; 48:300060520920395. [PMID: 32363985 PMCID: PMC7218943 DOI: 10.1177/0300060520920395] [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] [Indexed: 11/17/2022] Open
Abstract
A 60-year-old male patient presented with a serum α-fetoprotein (AFP) level of 2940.5 ng/mL accompanied by a significant increase in serum globulin. Hepatitis B virus (HBV) DNA was 2.85 × 103 (normal value <1.0 × 103). B-mode ultrasound and magnetic resonance imaging showed characteristic manifestations and he was clinically diagnosed with hepatocellular carcinoma in January 2015. He received radiofrequency ablation and tenofovir disoproxil anti-HBV therapy and his serum AFP and globulin levels were significantly reduced. In March 2018, he presented at our Hematology Department with fatigue and a pale complexion. At that time, his serum AFP level was normal, with hemoglobin 61 g/L and globulin 64.7 g/L. He was diagnosed with multiple myeloma (MM) by bone marrow examination, and immunofixation electrophoresis. The patient received PCD chemotherapy (bortezomib 2.0 g/dL on days 1, 4, 8, and 11 plus cyclophosphamide 0.3 g/dL on days 1-4 plus dexamethasone 20 mg/dL on days 1-2, 4-5, 8-9, and 11-12). The patient finally died of MM complicated by disseminated intravascular coagulation.
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Affiliation(s)
- Ling Xu
- Department of Hematology, HangZhou Red Cross Hospital, Hangzhou, Zhejiang, China
| | - Wei Yang
- Department of Hematology, HangZhou Red Cross Hospital, Hangzhou, Zhejiang, China
| | - Ye-Fei Shu
- Department of Hematology, HangZhou Red Cross Hospital, Hangzhou, Zhejiang, China
| | - Xiao-Feng Xu
- Department of Hematology, HangZhou Red Cross Hospital, Hangzhou, Zhejiang, China
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16
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Wu Q, Zhang Z, Dong H, Mei B. Combined resection for hepatocellular carcinoma with diaphragmatic invasion: a systematic review and meta-analysis. Minerva Med 2020; 111:354-361. [PMID: 33032395 DOI: 10.23736/s0026-4806.20.06407-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
INTRODUCTION According to the Staging System of Barcelona Clinic Liver Cancer (BCLC), diaphragmatic invasion (DI) is generally considered to be a manifestation of advanced hepatocellular carcinoma (HCC) with nearly no cure. However, some studies have indicated that combined liver and diaphragmatic resection may be a reasonably safe treatment option for HCC patients with diaphragmatic invasion. In this article, we conduct a systematic review to compare the short- and long-term surgical outcomes between HCC patients without diaphragmatic involvement who underwent hepatectomy alone and HCC patients with diaphragmatic involvement who underwent combined liver and diaphragmatic resection. EVIDENCE ACQUISITION PubMed, Web of Science, Embase and Cochrane library databases were searched. All related studies were checked. Hazard ratios (HR) with 95% confidence intervals were calculated for the comparison of cumulative overall survival (OS) and recurrence free survival (RFS). Odds ratios (OR) with 95% CI were calculated for the comparison of overall postoperative morbidity and mortality. EVIDENCE SYNTHESIS Seven studies met the inclusion criteria were included. There was no significant difference between the single hepatectomy group and combined liver and diaphragmatic resection group in the overall survival and recurrence free survival. Subgroup analysis showed a statistically significantly higher overall survival in HCC patients with diaphragmatic fibrous adhesion (DFA) compared with the DI group. However, there was no statistically significant difference in OS between the DI group and the single hepatectomy group. CONCLUSIONS For HCC patients with diaphragmatic involvement, combined liver and diaphragmatic resection might be considered no matter whether its diaphragmatic invasion or not.
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Affiliation(s)
- Qiqi Wu
- Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhiwei Zhang
- Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hanhua Dong
- Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bin Mei
- Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China -
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17
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Xie Y, Tian H, Xiang H. Is transcatheter arterial chemoembolization plus sorafenib better than chemoembolization plus placebo in the treatment of hepatocellular carcinoma? TUMORI JOURNAL 2020; 107:292-303. [PMID: 32729385 DOI: 10.1177/0300891620945029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVE To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus sorafenib compared with TACE plus placebo for hepatocellular carcinoma (HCC) using meta-analytical techniques. METHODS A search of PubMed, EMBASE, and Cochrane Library databases were done from inception to December 27, 2019. Published trials including a treatment group receiving TACE + sorafenib and a control group receiving TACE + placebo with data for at least 1-year survival or tumor response or time to progression were included. RESULTS Our study suggested that there was no evidence that TACE plus sorafenib was associated with a lower risk of disease progression compared with TACE plus placebo for treatment of HCC (hazard ratio 0.94 [95% confidence interval (CI), 0.84-1.05]), and no significant difference for treatment of HCC compared with TACE plus placebo in terms of 0.5-, 1-, 1.5-, and 2-year survival rates (risk ratio [RR] 1.01 [95% CI, 0.97-1.05]; RR 1.00 [95% CI, 0.92-1.08], RR 1.04 [95% CI, 0.89-1.23], RR 0.98 [95% CI, 0.72-1.34], respectively). The meta-analysis also showed that TACE + sorafenib seemed to have no significant difference for treatment of HCC compared with TACE + placebo in terms of complete response, partial response, stable disease, progressive disease, overall response rate, and disease control rate. There was an increased incidence of fatigue of grade 3/4 and elevation of aspartate aminotransferase and alanine aminotransferase of grade 3/4 in patients receiving TACE plus sorafenib compared with those receiving TACE plus placebo. CONCLUSIONS There is no additive benefit of TACE plus sorafenib compared to TACE plus placebo for HCC.
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Affiliation(s)
- Yong Xie
- Department of Interventional Radiology and Vascular Surgery, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Huan Tian
- Department of Radiology, The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Hua Xiang
- Department of Interventional Radiology and Vascular Surgery, The First Affiliated Hospital of Hunan Normal University, Changsha, China
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18
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Mai RY, Zeng J, Mo YS, Liang R, Lin Y, Wu SS, Piao XM, Gao X, Wu GB, Li LQ, Ye JZ. Artificial Neural Network Model for Liver Cirrhosis Diagnosis in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma. Ther Clin Risk Manag 2020; 16:639-649. [PMID: 32764948 PMCID: PMC7381792 DOI: 10.2147/tcrm.s257218] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 05/22/2020] [Indexed: 01/27/2023] Open
Abstract
Background Testing for the presence of liver cirrhosis (LC) is one of the most critical diagnostic and prognostic assessments for patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). More non-invasive tools are needed to diagnose LC but the predictive abilities of current models are still inconclusive. This study aimed to develop and validate a novel and non-invasive artificial neural network (ANN) model for diagnosing LC in patients with HBV-related HCC using routine laboratory serological indicators. Methods A total of 1152 HBV-related HCC patients who underwent hepatectomy were included and randomly divided into the training set (n = 864, 75%) and validation set (n = 288, 25%). The ANN model was constructed from the training set using multivariate Logistic regression analysis and then verified in the validation set. Results The morbidity of LC in the training and validation sets was 41.2% and 46.8%, respectively. Multivariate analysis showed that age, platelet count, prothrombin time and total bilirubin were independent risk factors for LC (P < 0.05). The area under the ROC curve (AUC) analyses revealed that the ANN model had higher predictive accuracy than the Logistic model (ANN: 0.757 vs Logistic: 0.721; P < 0.001), and other scoring systems (ANN: 0.757 vs CP: 0.532, MELD: 0.594, ALBI: 0.575, APRI: 0.621, FIB-4: 0.644, AAR: 0.491, and GPR: 0.604; P < 0.05 for all) in diagnosing LC. Similar results were obtained in the validation set. Conclusion The ANN model has better diagnostic capabilities than other commonly used models and scoring systems in assessing LC risk in patients with HBV-related HCC.
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Affiliation(s)
- Rong-Yun Mai
- Department of Hepatobilliary & Pancreatic Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, People's Republic of China.,Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning 530021, People's Republic of China.,Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, People's Republic of China
| | - Jie Zeng
- Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning 530021, People's Republic of China.,Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, People's Republic of China
| | - Yi-Shuai Mo
- Department of Hepatobilliary & Pancreatic Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, People's Republic of China.,Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, People's Republic of China
| | - Rong Liang
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, People's Republic of China.,Department of First Chemotherapy, Guangxi Medical University Cancer Hospital, Nanning 530021, People's Republic of China
| | - Yan Lin
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, People's Republic of China.,Department of First Chemotherapy, Guangxi Medical University Cancer Hospital, Nanning 530021, People's Republic of China
| | - Su-Su Wu
- Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning 530021, People's Republic of China.,Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, People's Republic of China
| | - Xue-Min Piao
- Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning 530021, People's Republic of China.,Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, People's Republic of China.,Department of First Chemotherapy, Guangxi Medical University Cancer Hospital, Nanning 530021, People's Republic of China
| | - Xing Gao
- Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning 530021, People's Republic of China.,Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, People's Republic of China.,Department of First Chemotherapy, Guangxi Medical University Cancer Hospital, Nanning 530021, People's Republic of China
| | - Guo-Bin Wu
- Department of Hepatobilliary & Pancreatic Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, People's Republic of China.,Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, People's Republic of China
| | - Le-Qun Li
- Department of Hepatobilliary & Pancreatic Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, People's Republic of China.,Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, People's Republic of China
| | - Jia-Zhou Ye
- Department of Hepatobilliary & Pancreatic Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, People's Republic of China.,Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, People's Republic of China
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19
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Li H, Li S, Geng J, Zhao S, Tan K, Yang Z, Feng D, Liu L. Efficacy evaluation of the combination therapy of sorafenib and transarterial chemoembolization for unresectable HCC: a systematic review and meta-analysis of comparative studies. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:540. [PMID: 32411763 PMCID: PMC7214895 DOI: 10.21037/atm.2020.02.115] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Background Sorafenib and transarterial chemoembolization (TACE) are the standard treatments recommended by guidelines for unresectable hepatocellular carcinoma (HCC). Although previous studies have shown the combination therapy of sorafenib and TACE to be safe, there is no consensus regarding its efficacy. This systematic review and meta-analysis, which was based on the findings of comparative clinical trials, was conducted to provide up-to-date and comprehensive information about the efficacy of combination therapy versus TACE monotherapy in unresectable HCC. Methods Multiple databases were systematically reviewed to screen studies through particular inclusion criteria. Hazard ratio (HR) with 95% confidence intervals (95% CIs) was collected and analyzed by Revman 5.3 in a fixed or random effects meta-analysis model. Adverse events (AEs) were also evaluated. Results This review ultimately included 14 comparative studies focused on combination therapy versus TACE monotherapy. Of these: 5 studies conducted TACE plus sorafenib versus TACE with placebo; 9 studies provided overall survival (OS) in combination groups which ranged from 10.3 to 29.7 months; and 10 studies provided time to progression (TTP) in combination groups which ranged from 2.6 to 10.8 months. The disease control rate (DCR) in combination groups ranged from 9.7% to 89.2% in 7 of the studies. After performing a random effects meta-analysis model, our study showed that OS (HR =0.65, 95% CI: 0.54-0.79, P<0.0001) and TTP (HR =0.72, 95% CI: 0.59-0.88, P=0.001) have been significantly improved in the combination therapy group when compared with the TACE monotherapy group. AEs mainly included hand-foot skin reaction (HFSR), fatigue and diarrhea and the majority of these were in grade 1 or grade 2. Conclusions Combination therapy has significant advantages over TACE monotherapy in terms of improving TTP and OS.
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Affiliation(s)
- Huichen Li
- The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, School of Basic Medicine, Fourth Military Medical University, Xi'an 710032, China
| | - Songlun Li
- Department of Blood Transfusion, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China
| | - Jie Geng
- Teaching and Research Section of Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Shoujie Zhao
- Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Kai Tan
- Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Zhenyu Yang
- Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Dayun Feng
- Department of Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Lei Liu
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
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Zhang ZM, Tan JX, Wang F, Dao FY, Zhang ZY, Lin H. Early Diagnosis of Hepatocellular Carcinoma Using Machine Learning Method. Front Bioeng Biotechnol 2020; 8:254. [PMID: 32292778 PMCID: PMC7122481 DOI: 10.3389/fbioe.2020.00254] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 03/12/2020] [Indexed: 12/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a serious cancer which ranked the fourth in cancer-related death worldwide. Hence, more accurate diagnostic models are urgently needed to aid the early HCC diagnosis under clinical scenarios and thus improve HCC treatment and survival. Several conventional methods have been used for discriminating HCC from cirrhosis tissues in patients without HCC (CwoHCC). However, the recognition successful rates are still far from satisfactory. In this study, we applied a computational approach that based on machine learning method to a set of microarray data generated from 1091 HCC samples and 242 CwoHCC samples. The within-sample relative expression orderings (REOs) method was used to extract numerical descriptors from gene expression profiles datasets. After removing the unrelated features by using maximum redundancy minimum relevance (mRMR) with incremental feature selection, we achieved “11-gene-pair” which could produce outstanding results. We further investigated the discriminate capability of the “11-gene-pair” for HCC recognition on several independent datasets. The wonderful results were obtained, demonstrating that the selected gene pairs can be signature for HCC. The proposed computational model can discriminate HCC and adjacent non-cancerous tissues from CwoHCC even for minimum biopsy specimens and inaccurately sampled specimens, which can be practical and effective for aiding the early HCC diagnosis at individual level.
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Affiliation(s)
- Zi-Mei Zhang
- Key Laboratory for Neuro-Information of Ministry of Education, School of Life Sciences and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, China
| | - Jiu-Xin Tan
- Key Laboratory for Neuro-Information of Ministry of Education, School of Life Sciences and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, China
| | - Fang Wang
- Key Laboratory for Neuro-Information of Ministry of Education, School of Life Sciences and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, China
| | - Fu-Ying Dao
- Key Laboratory for Neuro-Information of Ministry of Education, School of Life Sciences and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, China
| | - Zhao-Yue Zhang
- Key Laboratory for Neuro-Information of Ministry of Education, School of Life Sciences and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, China
| | - Hao Lin
- Key Laboratory for Neuro-Information of Ministry of Education, School of Life Sciences and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, China
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21
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Luo CL, Rong Y, Chen H, Zhang WW, Wu L, Wei D, Wei XQ, Mei LJ, Wang FB. A Logistic Regression Model for Noninvasive Prediction of AFP-Negative Hepatocellular Carcinoma. Technol Cancer Res Treat 2019; 18:1533033819846632. [PMID: 31106685 PMCID: PMC6535757 DOI: 10.1177/1533033819846632] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
α-Fetoprotein is commonly used in the diagnosis of hepatocellular carcinoma. However, the diagnostic significance of α-fetoprotein has been questioned because a number of patients with hepatocellular carcinoma are α-fetoprotein negative. It is therefore necessary to develop novel noninvasive techniques for the early diagnosis of hepatocellular carcinoma, particularly when α-fetoprotein level is low or negative. The current study aimed to evaluate the diagnostic efficiency of hematological parameters to determine which can act as surrogate markers in α-fetoprotein-negative hepatocellular carcinoma. Therefore, a retrospective study was conducted on a training set recruited from Zhongnan Hospital of Wuhan University-including 171 α-fetoprotein-negative patients with hepatocellular carcinoma and 102 healthy individuals. The results show that mean values of mean platelet volume, red blood cell distribution width, mean platelet volume-PC ratio, neutrophils-lymphocytes ratio, and platelet count-lymphocytes ratio were significantly higher in patients with hepatocellular carcinoma in comparison to the healthy individuals. Most of these parameters showed moderate area under the curve in α-fetoprotein-negative patients with hepatocellular carcinoma, but their sensitivities or specificities were not satisfactory enough. So, we built a logistic regression model combining multiple hematological parameters. This model presented better diagnostic efficiency with area under the curve of 0.922, sensitivity of 83.0%, and specificity of 93.1%. In addition, the 4 validation sets from different hospitals were used to validate the model. They all showed good area under the curve with satisfactory sensitivities or specificities. These data indicate that the logistic regression model combining multiple hematological parameters has better diagnostic efficiency, and they might be helpful for the early diagnosis for α-fetoprotein-negative hepatocellular carcinoma.
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Affiliation(s)
- Chang-Liang Luo
- 1 Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Yuan Rong
- 1 Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Hao Chen
- 2 Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Wu-Wen Zhang
- 1 Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Long Wu
- 3 Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Diao Wei
- 4 Department of Blood Transfusion, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Xiu-Qi Wei
- 5 Department of Laboratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Lie-Jun Mei
- 6 Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Fu-Bing Wang
- 1 Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China
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The Antitumor Potential of Extract of the Oak Bracket Medicinal Mushroom Inonotus baumii in SMMC-7721 Tumor Cells. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:1242784. [PMID: 31662769 PMCID: PMC6778873 DOI: 10.1155/2019/1242784] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Revised: 08/06/2019] [Accepted: 08/30/2019] [Indexed: 02/06/2023]
Abstract
Inonotus baumii, a traditional medicinal mushroom, has been historically used in China and other countries of East Asia for the treatment of various diseases. The aim of this study is to investigate the antitumor activity of the extract of I. baumii (EIB) against hepatocellular carcinoma and the possible mechanism involved. The MTT assay was used to evaluate the proliferative activity of SMMC-7721 cells treated with EIB. Hoechst 33258 and JC-1 staining were used to determine nuclear morphological changes and mitochondrial membrane potential, respectively. Flow cytometry analysis indicated that EIB blocked the cell cycle at the S phase and induced significant apoptosis. EIB increased the protein expression of Bax, cytochrome c, cleaved caspase-3, and decreased Bcl-2 in SMMC-7721. Moreover, EIB induced autophagy, indicated by the increase of autophagy-related protein expression of LC3-II and decrease of p62, and the AMPK/mTOR/ULK1 pathway was involved in the autophagic cell death. In vivo, EIB was found to strongly inhibit the growth of tumors in BALB/c nude mice. Our results indicated that I. baumii might be a potential natural therapeutic agent for liver cancer, as it could induce apoptosis and autophagy in HCC cells.
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Shi J, Shi L, Geng J, Liu R, Gong X, Bo X, Chen N, Liu Q, Yang Y, Wang Z. Status of evidence-based chronic diseases prevention implementation in Shanghai, China: A qualitative study. Int J Health Plann Manage 2019; 34:912-925. [PMID: 31368209 DOI: 10.1002/hpm.2863] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Given the rapid increase in chronic disease epidemics in developing countries and the lagging research and practice in evidence-based chronic diseases prevention (EBCDP), we evaluated the status of public health practitioners' implementation of EBCDP and its impeding factors in China, as well as made a comparison between China and the developed countries to encourage better utilisation of this new field of science in China. METHODS We interviewed health practitioners and patients from various health institutions in China and conducted a literature review to assess the current status of EBCDP practice in developed countries and identify the contextual driving factors. RESULTS China is in its initial stage of EBCDP practice, as it lacks evidence-based interventions. Moreover, health practitioners' awareness of EBCDP is inadequate. The lack of policy support, especially funding, has restricted the efficiency and quality of EBCDP in terms of its adoption, implementation, and maintenance. Currently, EBCDP practice is limited to the practitioners' spontaneous behaviours. The literature review showed that developed countries practising EBCDP did well in evidence development and awareness; however, much has yet to be explored regarding practitioners' adoption and implementation and the maintenance of evidence-based practice. The impeding factors in developed countries were related to individual (patients and physicians) and organisational factors (such as resources, leaders, and climate). CONCLUSION To promote EBCDP practice in China, more evidence for effective chronic disease prevention programmes is needed, and multiple and flexible measures should be implemented for a successful transition to evidence-based practice.
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Affiliation(s)
- Jianwei Shi
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, China.,Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
| | - Leiyu Shi
- Department of Health Policy and Management, Primary Care Policy Center, Johns Hopkins University, Baltimore, Maryland, USA
| | - Jinsong Geng
- Department of Medical Informatics, Evidence-based Medical Center, Medical School of Nantong University, Nantong, China
| | - Rui Liu
- Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xin Gong
- School of Medicine, Tongji University, Shanghai, China
| | - Xiaojie Bo
- School of Medicine, Tongji University, Shanghai, China
| | - Ning Chen
- School of Medicine, Tongji University, Shanghai, China
| | - Qian Liu
- School of Economics and Management, Tongji University, Shanghai, China
| | - Yan Yang
- School of Economics and Management, Tongji University, Shanghai, China
| | - Zhaoxin Wang
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, China.,General Practice Center, Nanhai Hospital, Southern Medical University, Guangzhou, China
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Zhou J, Yang W, Zhang S, He X, Lin J, Zhou T, Li Y, Wang G, Chen J. Diagnostic value of angiopoietin-like protein 2 for CHB-related hepatocellular carcinoma. Cancer Manag Res 2019; 11:7159-7169. [PMID: 31534368 PMCID: PMC6681069 DOI: 10.2147/cmar.s217170] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Accepted: 07/15/2019] [Indexed: 12/25/2022] Open
Abstract
Purpose Angiopoietin-like protein 2 (ANGPTL2) is a secretory glycoprotein with various functions in vascular biology, inflammation and tumor development. As shown in our previous studies, ANGPTL2 expression positively correlates with liver fibrosis stages in chronic hepatitis B (CHB) patients. The aim of this study was further to assess whether ANGPTL2 represents a potential biomarker for detecting hepatocellular carcinoma (HCC). Patients and methods This study enrolled 361 participants including healthy controls (HCs) and patients with CHB, liver cirrhosis (LC) and HCC. A discovery cohort consisted of 35 HCs and 55 patients with HCC. A total of 271 participants, including 45 HCs, 125 patients with CHB, 38 patients with LC, and 63 patients with HCC were enrolled in a validation cohort. Serum ANGPTL2 levels were detected using a human ANGPTL2 assay kit, and hepatic expression of ANGPTL2 was analyzed using immunohistochemistry. Results In the discovery cohort, a significantly higher serum ANGPTL2 level was detected in HCC than in HCs (73.49±33.87 vs 30.54±9.86; p<0.001). The results of the receiver operating characteristic curve indicated a significantly higher area under the curve for the ability of the ANGPTL2 to predict HCC than alpha fetoprotein (AFP). In the validation cohort, serum ANGPTL2 level gradually increased with the progression of chronic hepatitis B virus infection and reached the highest level in HCC. Immunohistochemical staining also confirmed these findings. The serum ANGPTL2 displayed better diagnostic efficiency not only for differentiating HCC from HC but also for differentiating HCC from high-risk controls (CHB+LC). Furthermore, the combination of ANGPTL2 and AFP may increase the diagnostic accuracy for HCC compared to ANGPTL2 or AFP alone. Importantly, ANGPTL2 levels also correlated with the detection of AFP-negative HCC. Conclusions ANGPTL2 may be used as a promising biomarker for the diagnosis of CHB-related HCC.
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Affiliation(s)
- Jiyuan Zhou
- Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology Medical Center, Shenzhen 518035, Guangdong, People's Republic of China
| | - Wanna Yang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing 100034, People's Republic of China
| | - Shu Zhang
- Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology Medical Center, Shenzhen 518035, Guangdong, People's Republic of China
| | - Xuanqiu He
- Department of Infectious Disease, Peking University Shenzhen Hospital, Shenzhen 518035, Guangdong, People's Republic of China
| | - Jiatian Lin
- Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology Medical Center, Shenzhen 518035, Guangdong, People's Republic of China
| | - Tao Zhou
- Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology Medical Center, Shenzhen 518035, Guangdong, People's Republic of China
| | - Yaqin Li
- Department of Infectious Disease, Peking University Shenzhen Hospital, Shenzhen 518035, Guangdong, People's Republic of China
| | - Guiqiang Wang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing 100034, People's Republic of China.,The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310013, Zhejiang, People's Republic of China
| | - Junhui Chen
- Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology Medical Center, Shenzhen 518035, Guangdong, People's Republic of China
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Liu Y, Chen X, Gao X, Chen JX, Chen J. Apatinib-induced hyperammonemic encephalopathy. J Oncol Pharm Pract 2019; 26:465-470. [PMID: 31068089 DOI: 10.1177/1078155219846253] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Apatinib is an orally administered small-molecule vascular endothelial growth factor receptor-2 inhibitor that has demonstrated encouraging anticancer activity across a broad range of malignancies, including gastric cancer, non-small-cell lung cancer, breast cancer, and hepatocellular carcinoma. We report a case of probable apatinib-induced hyperammonemic encephalopathy in a 69-year-old male. The patient received apatinib as targeted therapy for hepatocellular carcinoma and presented with acute confusion and hypersomnolence after four days of medication initiation. He showed improvement on drug withdrawal; then he resumed apatinib with a half dose and had a recurrence. Possible underlying mechanisms that include direct neuronal effect and antiangiogenic properties are discussed. We would like to draw attention to the potential risk of vascular endothelial growth factor receptor-tyrosine kinase inhibitors induced hyperammonemic encephalopathy even with a low dosage. Clinicians should be aware of any unexplained neurological syndrome after the initiation of apatinib in patients with hepatocellular carcinoma.
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Affiliation(s)
- Yan Liu
- Department of Pharmacy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiao Chen
- Department of Pharmacy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiang Gao
- Department of Pharmacy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jing-Xiu Chen
- Department of Pharmacy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jie Chen
- Department of Pharmacy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Abstract
Despite advancements in early diagnosis and medico-surgical treatment, hepatocellular carcinoma (HCC) is still a major cancer that causes substantial mortality in Asian countries. Liver transplantation (LT) has been accepted worldwide as the most effective treatment modality for patients with HCC; however, with the high incidence of HCC and low organ donation rate, Asia has developed distinctive features of indications and strategies for the application of LT. Unlike Western countries, living donor liver transplantation (LDLT) accounts for most LT cases for HCC in Asian countries, and most major transplantation centers perform LDLT for HCC patients with extended criteria. This article reviewed the current practice and outcome of LDLT for HCC from an Asian perspective and summarized the strategies that the high-volume LT centers in Asia use to obtain satisfactory oncologic results.
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张 磊, 范 志, 康 华, 王 宇, 刘 树, 单 忠. [High-performance liquid chromatography-mass spectrometry-based serum metabolic profiling in patients with HBV-related hepatocellular carcinoma]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2019; 39:49-56. [PMID: 30692066 PMCID: PMC6765583 DOI: 10.12122/j.issn.1673-4254.2019.01.08] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Indexed: 12/22/2022]
Abstract
OBJECTIVE To explore the diagnostic value of the serum metabolites identified by high-performance liquid chromatography-mass spectrometry (HPLC/MS) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS A total of 126 patients admitted to Tianjin Third Central Hospital were enrolled, including 27 patients with HBV-related hepatitis with negative viral DNA (DNA-N), 24 with HBV-related hepatitis with positive viral DNA, 24 with HBV-related liver cirrhosis, 27 with HBV-related HCC undergoing surgeries or radiofrequency ablation, and 24 with HBV-related HCC receiving interventional therapy, with 25 healthy volunteers as the normal control group. Serum samples were collected from all the subjects for HPLC/MS analysis, and the data were pretreated to establish an orthogonal partial least- squares discriminant analysis (OPLS-DA) model. The differential serum metabolites were preliminarily screened by comparisons between the HBV groups and the control group, and the characteristic metabolites were identified according to the results of non-parametric test. The potential clinical values of these characteristic metabolites were evaluated using receiver operator characteristic curve (ROC) analysis. RESULTS A total of 25 characteristic metabolites were identified in the HBV- infected patients, including 9 lysophosphatidylcholines, 2 fatty acids, 17α-estradiol, sphinganine, 5-methylcytidine, vitamin K2, lysophosphatidic acid, glycocholic acid and 8 metabolites with few reports. The patients with HBV- related HCC showed 22 differential serum metabolites compared with the control group, 4 differential metabolites compared with patients with HBV-related liver cirrhosis; 10 differential metabolites were identified in patients with HBV-related HCC receiving interventional therapy compared with those receiving surgical resection or radiofrequency ablation. From the normal control group to HBV-related HCC treated by interventional therapy, many metabolites underwent variations following a similar pattern. CONCLUSIONS We identified 25 characteristic metabolites in patients with HBV-related HCC, and these metabolites may have potential clinical values in the diagnosis of HBV-related HCC. The continuous change of some of these metabolites may indicate the possibility of tumorigenesis, and some may also have indications for the choice of surgical approach.
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Affiliation(s)
- 磊 张
- 天津大学化工学院，天津 300072Chemical Engineering Institute, Tianjin University, Tianjin 300072 China
- 天津市第三中心医院检验科//天津市人工细胞重点实验室//卫生部人工细胞工程技术研究中心，天津 300170Clinical Laboratory Department of Tianjin Third Central Hospital, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin 300170 China
| | - 志娟 范
- 天津市第三中心医院检验科//天津市人工细胞重点实验室//卫生部人工细胞工程技术研究中心，天津 300170Clinical Laboratory Department of Tianjin Third Central Hospital, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin 300170 China
| | - 华 康
- 天津市第三中心医院检验科//天津市人工细胞重点实验室//卫生部人工细胞工程技术研究中心，天津 300170Clinical Laboratory Department of Tianjin Third Central Hospital, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin 300170 China
| | - 宇凡 王
- 天津市第三中心医院检验科//天津市人工细胞重点实验室//卫生部人工细胞工程技术研究中心，天津 300170Clinical Laboratory Department of Tianjin Third Central Hospital, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin 300170 China
| | - 树业 刘
- 天津市第三中心医院检验科//天津市人工细胞重点实验室//卫生部人工细胞工程技术研究中心，天津 300170Clinical Laboratory Department of Tianjin Third Central Hospital, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin 300170 China
| | - 忠强 单
- 天津大学化工学院，天津 300072Chemical Engineering Institute, Tianjin University, Tianjin 300072 China
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Wei PL, Huang CY, Chang YJ. Propyl gallate inhibits hepatocellular carcinoma cell growth through the induction of ROS and the activation of autophagy. PLoS One 2019; 14:e0210513. [PMID: 30653551 PMCID: PMC6336332 DOI: 10.1371/journal.pone.0210513] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Accepted: 12/23/2018] [Indexed: 12/19/2022] Open
Abstract
The poor prognosis of hepatocellular carcinoma (HCC) has been attributed to a high frequency of tumor metastasis and recurrence even after successful surgical resection. With less than 30% of patients benefiting from curative treatment, alternative treatment regimens for patients with advanced HCC are needed. Propyl gallate (PG), a synthetic antioxidant used in preserving food and medicinal preparations, has been shown to induce cancer cell death, but the anticancer effects of PG in HCC are unclear. In the present study, we demonstrated that PG inhibited HCC cell proliferation in vitro and in zebrafish models in vivo in a dose- and time-dependent manner. PG also induced cell apoptosis and increased the number of necrotic cells in a time- and dose-dependent manner as determined using a high-content analysis system. We found that PG also increased the intracellular levels of superoxide and reactive oxidative stress as well as the formation of autophagosomes and lysosomes. Regarding the molecular mechanism, PG did not alter the levels of autophagy-related 5 (ATG5), ATG5/12 or Beclin-1 but increased the rate of the LC3-I to LC3-II conversion, suggesting autophagy induction. PG exposure increased the levels of the pro-apoptotic proteins cleaved caspase-3, cleaved PARP, Bax, and Bad and a decreased level of the anti-apoptotic protein Bcl-2. In conclusion, we demonstrate that PG inhibits HCC cell proliferation through enhanced ROS production and autophagy activation. Finally, PG-treated cells induced cell apoptosis and may be a new candidate for HCC therapy.
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Affiliation(s)
- Po-Li Wei
- Department of Surgery, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
- Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan
- Cancer Research Center and Translational Laboratory, Department of Medical Research, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
| | - Chien-Yu Huang
- Department of Surgery, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
- * E-mail: (YJC); (CYH)
| | - Yu-Jia Chang
- Cancer Research Center and Translational Laboratory, Department of Medical Research, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- International PhD Program in Medicine, Taipei Medical University, Taipei, Taiwan
- * E-mail: (YJC); (CYH)
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Sun X, Zheng G, Li C, Liu C. Long non‑coding RNA Fer‑1‑like family member 4 suppresses hepatocellular carcinoma cell proliferation by regulating PTEN in vitro and in vivo. Mol Med Rep 2018; 19:685-692. [PMID: 30431133 DOI: 10.3892/mmr.2018.9629] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2016] [Accepted: 06/22/2018] [Indexed: 11/06/2022] Open
Abstract
The aim of the present study was to investigate the potential role of long non‑coding RNA Fer‑1‑like family member 4 (FER1L4) in the proliferation of hepatocellular carcinoma (HCC) through the regulation of phosphatase and tensin homolog (PTEN) expression. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to detect the expression levels of FER1L4 and PTEN mRNA in HCC tissues, and western blotting was performed to measure the protein expression level of PTEN; MTT and colony formation assays were performed to detect the cell proliferative ability. Furthermore, nude mice were injected with transfected HCC cells and the tumor volume and weight were measured. The results indicated that FER1L4 was expressed at a low level in human HCC tissues compared with adjacent normal tissues. Functional studies indicated that FER1L4 may inhibit the proliferative ability of HCC cells. In addition, PTEN was highly expressed in HCC tissues compared with normal adjacent tissues and was positively associated with FER1L4. In addition, it was demonstrated that FER1L4 inhibited the proliferative ability of HCC cells in vitro, and silencing FER1L4 expression by small interfering RNAs promoted the growth of HCC tumors in vivo. Therefore, FER1L4 may be a potent therapeutic target for HCC.
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Affiliation(s)
- Xinyi Sun
- Department of Gastroenterology, Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China
| | - Guoqi Zheng
- Department of Gastroenterology, Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China
| | - Chunying Li
- Department of Gastroenterology, Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China
| | - Chendi Liu
- Department of Gastroenterology, Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China
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30
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Changjun L, Feizhou H, Dezhen P, Zhao L, Xianhai M. MiR-545-3p/MT1M axis regulates cell proliferation, invasion and migration in hepatocellular carcinoma. Biomed Pharmacother 2018; 108:347-354. [PMID: 30227328 DOI: 10.1016/j.biopha.2018.09.009] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 09/02/2018] [Accepted: 09/03/2018] [Indexed: 12/16/2022] Open
Abstract
Studies have shown that metallothionein 1 M (MT1M) is a tumor suppressor gene which is frequently down-regulated in human hepatocellular carcinoma (HCC). The methylation of MT1M promoter region is one of the important transcriptional regulation mechanisms that contribute to the loss of its expression. In our study, we found that there are still half of the 55 HCC tumor tissues in our cohort do not share the promoter methylation of MT1M. So, we speculated there maybe another mechanism participating in the downregulation of MT1M in HCC. Then, we provided evidences that miR-545-3p, which served as a tumor promoter, post-transcriptionally regulate MT1M in HCC through binding to its untranslated region (3'UTR). Taking together, we investigated the role of miR-545-3p in the process of HCC through regulating MT1M.
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Affiliation(s)
- Liu Changjun
- Department of Hepatobiliary Surgery, Hunan People's Hospital, Changsha 410005, China; Department of General surgery, the Third Xiangya Hospital of Central South University, Changsha 410013, China
| | - Huang Feizhou
- Department of General surgery, the Third Xiangya Hospital of Central South University, Changsha 410013, China.
| | - Peng Dezhen
- Department of Medicine-Neurology, the Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Lei Zhao
- Department of Hepatobiliary Surgery, Hunan People's Hospital, Changsha 410005, China
| | - Mao Xianhai
- Department of Hepatobiliary Surgery, Hunan People's Hospital, Changsha 410005, China
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31
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Wang WD. Diagnosis and treatment of hepatocellular carcinoma with portal hypertension. Shijie Huaren Xiaohua Zazhi 2018; 26:1429-1433. [DOI: 10.11569/wcjd.v26.i24.1429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Wei-Dong Wang
- Department of Hepatobiliary Surgery, Shunde Hospital, Southern Medical University (Shunde First People's Hospital of Foshan), Foshan 528300, Guangdong Province, China
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32
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Yang C, Qin S. Apatinib targets both tumor and endothelial cells in hepatocellular carcinoma. Cancer Med 2018; 7:4570-4583. [PMID: 30109780 PMCID: PMC6144148 DOI: 10.1002/cam4.1664] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Revised: 06/11/2018] [Accepted: 06/16/2018] [Indexed: 12/14/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed malignancies worldwide with poor prognosis and tends to be hypervascular. Aberrant expression of the vascular endothelial growth factor 2 (VEGFR‐2) has been implicated in the progression of HCC and represents a valid target for anticancer therapy. Apatinib, a small molecule inhibitor of VEGFR‐2 tyrosine kinase, shows strong antitumor activity in various tumors. This study is designed to evaluate the activity of apatinib on both human umbilical vein vascular endothelial cells (HUVECs) and HCC cell lines (in vitro and in vivo), and also to investigate the characteristics and possible mechanisms underlying these effects by molecular biology methods. Following the results in our study, apatinib inhibited phosphorylation of VEGFR‐2 in HUVECs and blocked in vitro endothelial cell migration and tube formation. Concentration‐dependent antiproliferative effects of apatinib were also observed in all 6 HCC cell lines including SK‐Hep‐1, HepG2, Hep3B, Huh‐7, PLC/PRF/5, SMMC‐7721. Moreover, response to apatinib of HCC cell lines was significantly correlated with VEGFR‐2 expression level. Additionally, apatinib significantly inhibit VEGF‐triggered VEGFR‐2 phosphorylation and activation of downstream signaling molecules such as Akt and ERK1/2 in HCCs. Apatinib can also induce a cell cycle arrest at G2/M phase and promote HCC apoptosis tested in vitro. In vivo data showed that apatinib can effectively inhibit tumor growth, decreased angiogenesis, as well as induced HCC apoptosis (in some tumors), and thus prolonged animal survival in a mouse xenograft model of human HCC. Our findings suggested that apatinib is a highly potent, oral active anti‐angiogenic, and anti‐HCC agent. The results from current study provide a clear biological rationale to evaluate apatinib as a new agent in HCC in clinical setting, especially for the VEGFR‐2 overexpression ones.
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Affiliation(s)
- Chaoxu Yang
- Post-Doctoral Research Center in Nanjing General Hospital of Eastern Theater Command, Nanjing, China.,Cancer Center of BaYi Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, Nanjing, China
| | - Shukui Qin
- Cancer Center of BaYi Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, Nanjing, China
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33
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Kim S, Choi S, Yoon JH, Kim Y, Lee S, Park T. Drug response prediction model using a hierarchical structural component modeling method. BMC Bioinformatics 2018; 19:288. [PMID: 30367591 PMCID: PMC6101092 DOI: 10.1186/s12859-018-2270-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Component-based structural equation modeling methods are now widely used in science, business, education, and other fields. This method uses unobservable variables, i.e., "latent" variables, and structural equation model relationships between observable variables. Here, we applied this structural equation modeling method to biologically structured data. To identify candidate drug-response biomarkers, we first used proteomic peptide-level data, as measured by multiple reaction monitoring mass spectrometry (MRM-MS), for liver cancer patients. MRM-MS is a highly sensitive and selective method for proteomic targeted quantitation of peptide abundances in complex biological samples. RESULTS We developed a component-based drug response prediction model, having the advantage that it first combines collapsed peptide-level data into protein-level information, facilitating subsequent biological interpretation. Our model also uses an alternating least squares algorithm, to efficiently estimate both coefficients of peptides and proteins. This approach also considers correlations between variables, without constraint, by a multiple testing problem. Using estimated peptide and protein coefficients, we selected significant protein biomarkers by permutation testing, resulting in our model for predicting liver cancer response to the tyrosine kinase inhibitor sorafenib. CONCLUSIONS Using data from a cohort of liver cancer patients, we then "fine-tuned" our model to successfully predict drug responses, as demonstrated by a high area under the curve (AUC) score. Such drug response prediction models may eventually find clinical translation in identifying individual patients likely to respond to specific therapies.
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Affiliation(s)
- Sungtae Kim
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826 South Korea
| | - Sungkyoung Choi
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826 South Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, 03080 South Korea
| | - Youngsoo Kim
- Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, 03080 South Korea
| | - Seungyeoun Lee
- Department of Mathematics and Statistics, Sejong University, Seoul, 05006 South Korea
| | - Taesung Park
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826 South Korea
- Department of Statistics, Seoul National University, Seoul, 08826 South Korea
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34
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Duan XH, Li H, Han XW, Ren JZ, Li FY, Ju SG, Chen PF, Kuang DL. Upregulation of IL-6 is involved in moderate hyperthermia induced proliferation and invasion of hepatocellular carcinoma cells. Eur J Pharmacol 2018; 833:230-236. [DOI: 10.1016/j.ejphar.2018.06.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Revised: 06/08/2018] [Accepted: 06/08/2018] [Indexed: 02/07/2023]
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35
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Lin CL, Kao JH. Review article: the prevention of hepatitis B-related hepatocellular carcinoma. Aliment Pharmacol Ther 2018; 48:5-14. [PMID: 29722445 DOI: 10.1111/apt.14683] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 02/08/2018] [Accepted: 04/03/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Ample evidence indicates an aetiological association of persistent hepatitis B virus (HBV) infection with hepatocellular carcinoma (HCC). Several viral, host and external risk factors for the development of HBV-related HCC have been documented. AIMS To summarise and discuss the risk stratification and the preventive strategies of HBV-related HCC. METHODS Recent published studies identified from PubMed were comprehensively reviewed. The key words included chronic hepatitis B, HBV, hepatocellular carcinoma, prevention and antiviral therapy. RESULTS The incidence of HCC is extremely high in HBV hyperendemic areas. For HBV patients left untreated, significant risk factors for HCC include male gender, aging, advanced hepatic fibrosis, persistent serum transaminase elevation, specific HBV entry receptor (NTCP) genotype, PM2.5 exposure, HBeAg positivity, HBV genotype C/D/F, high proportion of core promoter mutation, pre-S deletion, high serum levels of HBV DNA and HBsAg as well as co-infection with HCV, HDV and HIV. Primary prevention of HBV-related HCC can be achieved through universal HBV vaccination and anti-viral prophylaxis for high viraemic mothers. The goal of secondary prevention has been reached by effective anti-viral therapy to reduce the risk of HCC development in chronic hepatitis B patients. However, whether HCC is prevented or delayed deserves further examination. Finally, several studies confirmed the tertiary preventive effect of anti-viral therapy in reducing risk of HCC recurrence after curative therapies. CONCLUSIONS Through the strategies of three-level prevention, the global burden of HBV-related HCC should decline over time and even be eliminated in conjunction with HBV cure.
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Affiliation(s)
- C-L Lin
- Department of Gastroenterology, Taipei City Hospital, Taipei, Taiwan.,Department of Psychology, National Chengchi University, Taipei, Taiwan
| | - J-H Kao
- Graduate Institute of Clinical Medicine, National Taiwan University, College of Medicine, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan.,Department of Medical Research, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan
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36
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Tang Z, Peng H, Chen J, Liu Y, Yan S, Yu G, Chen Q, Tang H, Liu S. Rap1b enhances the invasion and migration of hepatocellular carcinoma cells by up-regulating Twist 1. Exp Cell Res 2018; 367:56-64. [PMID: 29559227 DOI: 10.1016/j.yexcr.2018.03.019] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 03/15/2018] [Accepted: 03/16/2018] [Indexed: 02/04/2023]
Abstract
Rap1b was found be dysregulated in several types of cancers. Previously, we have demonstrated that Rap1b affects proliferation, migration and invasion of hepatocellular carcinoma (HCC) cells. However, the definite function of Rap1b in HCC remains unknown. Here, we reported that Rap1b was significantly up-regulated in HCC tissues compared with the non-tumoral liver tissues. Overexpression of Rap1b promoted tumor growth and migration in vitro and tumor formation in vivo. Oppositely, inhibition of Rap1b suppressed the proliferation and migration of HCC cells. Mechanism study revealed that Rap1b could up-regulate Twist 1 expression by enhancing its promoter activity. We concluded that Rap1b increased Twist 1 expression by targeting its promoter activity to induce proliferation and migration of HCC cells.
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Affiliation(s)
- Zhenrong Tang
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, China
| | - Hong Peng
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Chongqing Medical University, 1 Yi Xue Yuan Road, Chongqing, China
| | - Juan Chen
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Chongqing Medical University, 1 Yi Xue Yuan Road, Chongqing, China
| | - Yuyang Liu
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Chongqing Medical University, 1 Yi Xue Yuan Road, Chongqing, China
| | - Shaoying Yan
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Chongqing Medical University, 1 Yi Xue Yuan Road, Chongqing, China
| | - Gangfeng Yu
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Chongqing Medical University, 1 Yi Xue Yuan Road, Chongqing, China
| | - Qiuxu Chen
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Chongqing Medical University, 1 Yi Xue Yuan Road, Chongqing, China
| | - Hua Tang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Chongqing Medical University, 1 Yi Xue Yuan Road, Chongqing, China.
| | - Shengchun Liu
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, China.
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37
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Wei Y, Ye W, Zhao W. Serum Iron Levels Decreased in Patients with HBV-Related Hepatocellular Carcinoma, as a Risk Factor for the Prognosis of HBV-Related HCC. Front Physiol 2018; 9:66. [PMID: 29467672 PMCID: PMC5808349 DOI: 10.3389/fphys.2018.00066] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Accepted: 01/18/2018] [Indexed: 12/15/2022] Open
Abstract
Background: Hepatocellular carcinoma (HCC) is common and the second leading causes of cancer-related deaths. HCC usually occurs on the basis of chronic liver diseases. At present, the study of iron metabolism in chronic liver diseases was limited to chronic HCV infection, nonalcoholic fatty liver disease, and alcoholic liver disease. This study aimed to investigate the effect of serum iron levels on the progression of chronic HBV infection and the relationship with the prognosis of HBV-related HCC. Methods: A respective study involving 277 healthy individuals as controls (HC), 295 patients with chronic hepatitis B (CHB), 224 patients with HBV-related liver cirrhosis (HBV-related LC), and 586 patients with HBV- related HCC were enrolled in this study. Hematological parameters, HBVDNA and liver biochemistry were analyzed. Child-Pugh grade and BCLC stage of the HBV-related HCC patients were calculated. Results: The serum iron levels were lowest in the HBV- related HCC group as compared with HC, CHB, and HBV-related LC groups (35.07 ± 6.97, 27.37 ± 10.26, 24.53 ± 10.36 vs. 17.90 ± 0.14, P < 0.001). Strikingly, serum iron levels were lowest in HBV- related HCC patients with tumor size more than 10 cm as compared with HBV- related HCC patients with tumor size smaller than 3, 3-5, and 5-10 cm by subgroup analysis (22.12 ± 0.94, 21.44 ± 1.41, 15.65 ± 0.98 vs. 13.36 ± 1.15, P < 0.001). Serum iron levels significantly decreased with worsening Child-Pugh grades and BCLC stages in HBV-related HCC group. In addition, serum iron levels was positively correlated with Retinol-Binding Protein, total bile acid, hemoglobin, and lymphocyte and negatively correlated with white blood cell (WBC) and platelet in HBV- related HCC group. ROC curve analysis showed serum iron levels at 15.1 μmol/L as the optimal cut-off point for determining the survival of HBV-related HCC. By the Cox regression model analysis, serum iron levels <15.1 μmol/l together with higher AFP levels, worse BCLC stages, and larger tumor size showed higher mortality of HBV-related HCC patients (hazard ratio = 2.280, 95% confidence interval, 1.815-2.865; P < 0.001). Conclusions: Serum iron levels affected the progression of chronic HBV infection. The prognosis of HBV- related HCC patients with serum iron levels <15.1 μmol/l together with higher AFP levels, worse BCLC stages, and larger tumor lesion were poor.
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Affiliation(s)
- Yanyan Wei
- Medical School, Southeast University, Nanjing, China
| | - Wei Ye
- Medical School, Southeast University, Nanjing, China.,The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, China
| | - Wei Zhao
- Medical School, Southeast University, Nanjing, China.,The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, China
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38
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Ruan DY, Lin ZX, Wang TT, Zhao H, Wu DH, Chen J, Dong M, Lin Q, Wu XY, Li Y. Nomogram for preoperative estimation of long-term survival of patients who underwent curative resection with hepatocellular carcinoma beyond Barcelona clinic liver cancer stage A1. Oncotarget 2018; 7:61378-61389. [PMID: 27542216 PMCID: PMC5308658 DOI: 10.18632/oncotarget.11358] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2016] [Accepted: 08/10/2016] [Indexed: 02/07/2023] Open
Abstract
Background and Aims This retrospective cohort study developed a prognostic nomogram to predict the survival of hepatocellular carcinoma (HCC) patients diagnosed as beyond Barcelona clinic liver cancer stage A1 after resection and evaluated the possibility of using the nomogram as a treatment algorithm reference. Results The predictors included in the nomogram were total tumour volume, Child-Turcotte-Pugh class, plasma fibrinogen and portal vein tumour thrombus. Patients diagnosed as beyond A1 were stratified into low-, medium- and high-risk groups using nomogram scores of 0 and 51 with the total points of 225. Patients within A1 exhibited similar recurrence-free survival (RFS) and overall survival (OS) rates compared with the low-risk group. Patients in the medium-risk group exhibited a similar OS but a worse RFS rates compared with patients within A1. The high-risk group was associated with worse RFS and OS rates compared with the patients within A1 (3-year RFS rates, 27.0% vs. 60.3%, P < 0.001; 3-year OS rates, 49.2% vs. 83.1%, P < 0.001). Methods A total of 352 HCC patients undergoing curative resection from September 2003 to December 2012 were included to develop a nomogram to predict overall survival after resection. Univariate and multivariate survival analysis were used to identify prognostic factors. A visually orientated nomogram was constructed using a Cox proportional hazards model. Conclusions This user-friendly nomogram offers an individualized preoperative recurrence risk estimation and stratification for HCC patients beyond A1 undergoing resection. Resection should be considered the first-line treatment for low-risk patients.
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Affiliation(s)
- Dan-Yun Ruan
- Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangdong, China
| | - Ze-Xiao Lin
- Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangdong, China
| | - Tian-Tian Wang
- Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangdong, China
| | - Hui Zhao
- Department of Liver Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Dong-Hao Wu
- Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangdong, China
| | - Jie Chen
- Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangdong, China
| | - Min Dong
- Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangdong, China
| | - Qu Lin
- Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangdong, China
| | - Xiang-Yuan Wu
- Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangdong, China
| | - Yang Li
- Department of Liver Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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39
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Nielsen JA, Putcha RV, Roberts CA. The Increasing Incidence of Remote Metastasis: A Case Report of Metastatic Hepatocellular Carcinoma to the Rectosigmoid. TUMORI JOURNAL 2018; 100:e31-4. [DOI: 10.1177/030089161410000220] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
As the fifth most common malignancy worldwide, survival rates of hepatocellular carcinoma (HCC) have only slightly improved over the years due to early-stage detection. HCC is well known to metastasize to the lung, lymph nodes, and musculoskeletal regions; however, only 0.5% to 6% of HCCs metastasize to the gastrointestinal tract. In the case described here, a CT scan and subsequent colonoscopy of a 51-year-old Asian male with a history of hepatitis B and HCC revealed a mass lesion of metastatic HCC 12 cm from the anal verge. Because metastatic HCC to the lower gastrointestinal tract has only recently been reported, it is speculated that the prolonged survival of patients is also increasing the incidence of extrahepatic metastasis, giving the disease greater opportunity to spread to more distant regions of the body. This case may be the farthest metastasis within the gastrointestinal tract to date.
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Affiliation(s)
| | | | - Cory A Roberts
- Division of Gastrointestinal Pathology, ProPath Services, LLP, Dallas, Texas, USA
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40
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Zou WJ, Huang Z, Jiang TP, Shen YP, Zhao AS, Zhou S, Zhang S. Pirfenidone Inhibits Proliferation and Promotes Apoptosis of Hepatocellular Carcinoma Cells by Inhibiting the Wnt/β-Catenin Signaling Pathway. Med Sci Monit 2017; 23:6107-6113. [PMID: 29276937 PMCID: PMC5749136 DOI: 10.12659/msm.907891] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) is the most important cause of cancer-related deaths worldwide. Pirfenidone is an orally available small molecule with therapeutic potential for fibrotic diseases. Material/Methods In this study, we analyzed the effects of different pirfenidone concentrations on the proliferation of HepG2 HCC cells using Cell Counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was performed to measure the apoptotic effects of pirfenidone on HepG2 cells. Western blot analysis was performed to detect the expression of β-catenin and p-β-catenin. Results Pirfenidone inhibited proliferation and promoted HepG2 cell apoptosis. In addition, Western blot results indicated that pirfenidone suppressed β-catenin expression in HepG2 cells. To assess the mechanism, we treated HepG2 cells with pirfenidone, and pirfenidone plus the β-catenin activator, SB-216763. The results revealed that SB-216763 accelerated proliferation and inhibited apoptosis in HepG2 cells treated with pirfenidone. Western blot results showed that SB-216763 upregulated β-catenin expression in HepG2 cells treated with pirfenidone. Conclusions In conclusions, pirfenidone may be a potential drug for HCC treatment.
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Affiliation(s)
- Wei-Jie Zou
- Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China (mainland)
| | - Zhi Huang
- Department of Interventional Radiology, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang, Guizhou, China (mainland)
| | - Tian-Peng Jiang
- Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China (mainland)
| | - Ya-Ping Shen
- Department of Interventional Radiology, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang, Guizhou, China (mainland)
| | - An-Su Zhao
- Institute of Biology and Engineering, Guizhou Medical University, Guiyang, Guizhou, China (mainland)
| | - Shi Zhou
- Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China (mainland)
| | - Shuai Zhang
- Department of Interventional Radiology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, Guizhou, China (mainland)
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Cao Y, Cao J, Yu B, Wang S, Liu L, Tao L, Sun W. Berbamine induces SMMC-7721 cell apoptosis via upregulating p53, downregulating survivin expression and activating mitochondria signaling pathway. Exp Ther Med 2017; 15:1894-1901. [PMID: 29434780 PMCID: PMC5776608 DOI: 10.3892/etm.2017.5637] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Accepted: 11/22/2017] [Indexed: 12/20/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a primary malignancy in the liver, which is a global health problem. The present study aimed to observe the apoptotic effects of berbamine on SMMC-7721 cell lines and to investigate the effects of berbamine on induction of the intrinsic apoptotic pathway. The human HCC SMMC-7721 cells were cultured and cell morphology observed using a phase contrast microscope. SMMC-7721 cell apoptosis was examined by employing a flow cytometry assay. The nuclei of SMMC-7721 cells were stained with DAPI and observed by utilizing a laser fluorescence microscope. Cytochrome c (Cyto c) levels were evaluated by using immunofluorescence staining. The reverse transcription-semi-quantitative polymerase chain reaction (RT-sqPCR) and western blot analysis were used to examine the mRNA and protein levels of B-cell lymphoma 2, (Bcl-2), Bax, Bcl-2-associated X, apoptosis regulator, p53 and survivin, respectively. Berbamine inhibited SMMC-7721 cell growth at 20 and 0 µmol/l, compared with control group (0 µmol/l berbamine). DAPI results demonstrated that berbamine affected the nucleus morphology of SMMC-7721 cells. Berbamine at a concentration of 20 µmol/l (P<0.05) and 40 µmol/l (P<0.01) significantly enhanced apoptosis rate compared with control group. Berbamine triggered Cyto c release from SMMC-7721 cell nuclei to the cytoplasm. Berbamine (10, 20, 40 µmol/l) significantly enhanced Bax and p53 levels and decreased Bcl-2 and survivin levels compared with control group, according to RT-sqPCR and western blot assay findings. In conclusion, berbamine induced SMMC-7721 cell apoptosis, through upregulating p53 expression and downregulating survivin expression, which further triggered mitochondria signaling pathway-mediated apoptosis.
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Affiliation(s)
- Ying Cao
- Department of Pharmacy, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China
| | - Jianbo Cao
- Department of Pharmacy, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China
| | - Binbin Yu
- Department of Pharmacy, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China
| | - Shusheng Wang
- Department of Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China
| | - Lili Liu
- Department of Pharmacy, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China
| | - Li Tao
- Department of Pharmacy, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China
| | - Wanping Sun
- Laboratory of Molecular Diagnostics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, P.R. China
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Zhang K, Che S, Su Z, Zheng S, Zhang H, Yang S, Li W, Liu J. CD90 promotes cell migration, viability and sphere‑forming ability of hepatocellular carcinoma cells. Int J Mol Med 2017; 41:946-954. [PMID: 29251325 PMCID: PMC5752240 DOI: 10.3892/ijmm.2017.3314] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Accepted: 11/29/2017] [Indexed: 01/04/2023] Open
Abstract
Cluster of differentiation (CD)90 (Thy-1) was proposed as a marker for the liver cancer stem cells that are responsible for tumorigenic activity, however its involvement in the progression of hepatocellular carcinoma (HCC) remains unknown. The aim of the present study was to determine the effect of CD90 on the biological functions of HCC and to investigate the associated circular RNA (circRNA) involved in this process. The analysis of the in vitro data demonstrated that CD90+ cells isolated from SK-Hep-1 cells exhibited increased viability, migration and invasive abilities compared with CD90− cells. In addition, circRNA expression profiles in CD90+ and CD90− cells were screened using a microarray assay and hsa_circ_0067531 and hsa_circ_0057096 were identified to be expressed at significantly different levels. It was additionally demonstrated that the expression of hsa_circ_0067531 in HCC tissues was significantly decreased compared with normal adjacent tissues. Overall, the results of the present study suggested that CD90 may be used as a potential biomarker for HCC. Furthermore, it was demonstrated that hsa_circ_0067531 may affect the biological functions of CD90+ HCC cells and may be a promising candidate to aid in the diagnosis and therapy of HCC.
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Affiliation(s)
- Ketao Zhang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat‑Sen Memorial Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510120, P.R. China
| | - Siyao Che
- Department of Hepatobiliary Surgery, Gaozhou People's Hospital, Gaozhou, Guangdong 525200, P.R. China
| | - Zheng Su
- Department of Hepatobiliary Surgery, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550000, P.R. China
| | - Shangyou Zheng
- Department of Hepatopancreatobiliary Surgery, Sun Yat‑Sen Memorial Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510120, P.R. China
| | - Huayao Zhang
- Department of Mammary Gland and Thyroid Gland Surgery, The Third People's Hospital of Dongguan, Dongguan, Guangdong 523000, P.R. China
| | - Shanglin Yang
- Department of Hepatobiliary Surgery, Affiliated Foshan Hospital of Southern Medical University, Foshan, Guangdong 528000, P.R. China
| | - Wenda Li
- Department of Hepatobiliary Surgery, Sun Yat‑Sen Memorial Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510120, P.R. China
| | - Jianping Liu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat‑Sen Memorial Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510120, P.R. China
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Annual Change in FIB-4, but not in APRI, was a Strong Predictor for Liver Disease Progression in Chinese Patients with Chronic Hepatitis C. HEPATITIS MONTHLY 2017. [DOI: 10.5812/hepatmon.57250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Pu M, Wang J, Huang Q, Zhao G, Xia C, Shang R, Zhang Z, Bian Z, Yang X, Tao K. High MRPS23 expression contributes to hepatocellular carcinoma proliferation and indicates poor survival outcomes. Tumour Biol 2017; 39:1010428317709127. [PMID: 28714366 DOI: 10.1177/1010428317709127] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma is one of the most prevalent neoplasms and the leading cause of cancer-related mortality worldwide. Mitochondrial ribosomal protein S23 is encoded by a nuclear gene and participates in mitochondrial protein translation. Mitochondrial ribosomal protein S23 overexpression has been found in many types of cancer. In this study, we explored mitochondrial ribosomal protein S23 expression in primary hepatocellular carcinoma tissues compared with matched adjacent non-tumoral liver tissues using mitochondrial ribosomal protein S23 messenger RNA and protein levels collected from public databases and clinical samples. Immunohistochemistry was performed to analyze the relationship between mitochondrial ribosomal protein S23 and various clinicopathological features. The results indicated that mitochondrial ribosomal protein S23 was significantly overexpressed in hepatocellular carcinoma. High mitochondrial ribosomal protein S23 expression was correlated with the tumor size and tumor–metastasis–node stage. Moreover, patients with high mitochondrial ribosomal protein S23 expression levels presented poorer survival rates. Mitochondrial ribosomal protein S23 was an independent prognostic factor for survival, especially at the early stage of hepatocellular carcinoma. In addition, the downregulation of mitochondrial ribosomal protein S23 decreased the proliferation of hepatocellular carcinoma in vitro and in vivo. In conclusion, we verified for the first time that mitochondrial ribosomal protein S23 expression was upregulated in hepatocellular carcinoma. High mitochondrial ribosomal protein S23 levels can predict poor clinical outcomes in hepatocellular carcinoma, and this protein plays a key role in tumor proliferation. Therefore, mitochondrial ribosomal protein S23 may be a potential therapeutic target for hepatocellular carcinoma.
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Affiliation(s)
- Meng Pu
- Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
| | - Jianlin Wang
- Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
| | - Qike Huang
- Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
| | - Ge Zhao
- Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
| | - Congcong Xia
- Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
| | - Runze Shang
- Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
| | - Zhuochao Zhang
- Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
| | - Zhenyuan Bian
- Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
| | - Xishegn Yang
- Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
| | - Kaishan Tao
- Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
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45
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Yu Y, Song J, Zhang R, Liu Z, Li Q, Shi Y, Chen Y, Chen J. Preoperative neutrophil-to-lymphocyte ratio and tumor-related factors to predict microvascular invasion in patients with hepatocellular carcinoma. Oncotarget 2017; 8:79722-79730. [PMID: 29108352 PMCID: PMC5668085 DOI: 10.18632/oncotarget.19178] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 06/29/2017] [Indexed: 02/07/2023] Open
Abstract
Small hepatocellular carcinoma (HCC) is less invasive and has a better prognosis, but it still has a high recurrence rate. Microvascular invasion (MVI), as a poor prognostic indicator, is of great importance for treating of patients with HCC. The objective of the present study was to evaluate the predictive value of preoperative neutrophil-to-lymphocyte ratio and possible clinical parameters to MVI in patients with HCC. A total of 157 operable patients with HCC having a tumor diameter of less than or equal to 5 cm were enrolled in this study. The utility of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and other clinical parameters was evaluated using receiver operating characteristic curves. MVI was identified as an independent influencing factor for disease-free survival in patients with HCC who underwent curative resection, using the multivariate Cox proportional hazards regression model. The independent parameters associated with MVI were determined using logistic analysis. Multivariate analyses indicated that the neutrophil-to-lymphocyte ratio [hazard ratio, 1.705; 95% confidence interval, 0.467–6.232; P = 0.022)], platelet-to-lymphocyte ratio (hazard ratio, 1.048; 95% confidence interval, 1.006–1.092; P = 0.025), and a-fetoprotein (hazard ratio, 1.012; 95% confidence interval, 1.003–1.021; P = 0.007) were significantly associated with MVI independently. Therefore, this study concluded that the preoperative neutrophil-to-lymphocyte ratio and a-fetoprotein might serve as useful biomarkers for predicting MVI in patients with HCC.
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Affiliation(s)
- Yanlong Yu
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
| | - Jiuling Song
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
| | - Ran Zhang
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
| | - Zhonghua Liu
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
| | - Qiang Li
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
| | - Ying Shi
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
| | - Ying Chen
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
| | - Jinming Chen
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
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Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J, Tateishi R, Han KH, Chawla YK, Shiina S, Jafri W, Payawal DA, Ohki T, Ogasawara S, Chen PJ, Lesmana CRA, Lesmana LA, Gani RA, Obi S, Dokmeci AK, Sarin SK. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int 2017; 11:317-370. [PMID: 28620797 PMCID: PMC5491694 DOI: 10.1007/s12072-017-9799-9] [Citation(s) in RCA: 1612] [Impact Index Per Article: 201.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Accepted: 05/02/2017] [Indexed: 02/06/2023]
Abstract
There is great geographical variation in the distribution of hepatocellular carcinoma (HCC), with the majority of all cases worldwide found in the Asia-Pacific region, where HCC is one of the leading public health problems. Since the "Toward Revision of the Asian Pacific Association for the Study of the Liver (APASL) HCC Guidelines" meeting held at the 25th annual conference of the APASL in Tokyo, the newest guidelines for the treatment of HCC published by the APASL has been discussed. This latest guidelines recommend evidence-based management of HCC and are considered suitable for universal use in the Asia-Pacific region, which has a diversity of medical environments.
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Affiliation(s)
- Masao Omata
- Department of Gastroenterology, Yamanashi Prefectural Central Hospital, Kofu-city, Yamanashi, Japan.
- The University of Tokyo, Tokyo, Japan.
| | - Ann-Lii Cheng
- Department of Oncology and Internal Medicine, National Taiwan University Hospital, National Taiwan University Cancer Center and Graduate Institute of Oncology, National Taiwan University, Taipei, Taiwan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka-Sayama, Osaka, Japan
| | - Jeong Min Lee
- Department of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jidong Jia
- Beijing Key Laboratory of Translational Medicine on Cirrhosis, National Clinical Research Center for Digestive Diseases, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yoghesh K Chawla
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University, Tokyo, Japan
| | - Wasim Jafri
- Department of Medicine, Aga Khan University and Hospital, Karachi, Pakistan
| | | | - Takamasa Ohki
- Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Pei-Jer Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Cosmas Rinaldi A Lesmana
- Digestive Disease and GI Oncology Center, Medistra Hospital, University of Indonesia, Jakarta, Indonesia
- Department of Internal Medicine, Cipto Mangunkusumo Hospital, University of Indonesia, Jakarta, Indonesia
| | - Laurentius A Lesmana
- Digestive Disease and GI Oncology Center, Medistra Hospital, University of Indonesia, Jakarta, Indonesia
| | - Rino A Gani
- Department of Internal Medicine, Cipto Mangunkusumo Hospital, University of Indonesia, Jakarta, Indonesia
| | - Shuntaro Obi
- Third Department of Internal Medicine, Teikyo University School of Medicine, Chiba, Japan
| | - A Kadir Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Daucosterol Inhibits the Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells via Wnt/β-Catenin Signaling. Molecules 2017; 22:molecules22060862. [PMID: 28574485 PMCID: PMC6152702 DOI: 10.3390/molecules22060862] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Revised: 05/15/2017] [Accepted: 05/20/2017] [Indexed: 12/20/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The purpose of this study was to determine the effects of daucosterol on HCC by investigating Wnt/β-catenin signaling. In this study, HepG2 and SMMC-7721 cells were treated with varying concentrations of daucosterol, and the corresponding inhibitory effects on HCC cells were examined via CCK-8 assays. Cell migration and invasion abilities were detected via transwell assays. β-Catenin and phospho (p)-β-catenin levels were analyzed via western blotting. Our results showed that daucosterol reduced the proliferation, migration, and invasion capacities of HCC cells in a concentration-dependent manner. In addition, daucosterol reduced the levels of β-catenin and p-β-catenin in HepG2 and SMMC-7721 cells. Furthermore, the Wnt signaling pathway inhibitor SB-216763 was used to treat HepG2 and SMMC-7721 cells with daucosterol. Our results showed that co-treatment with daucosterol and SB-216763 abolished the effects of daucosterol on cell inhibition ratios, cell migration, and cell invasion. These findings indicated that daucosterol inhibited cell migration and invasion in HCC cells via the Wnt/β-catenin signaling pathway. Therefore, our study highlights the use of daucosterol as a promising therapeutic strategy for HCC treatment.
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Hu B, Sun M, Liu J, Hong G, Lin Q. MicroRNA-204 suppressed proliferation and motility capacity of human hepatocellular carcinoma via directly targeting zinc finger E-box binding homeobox 2. Oncol Lett 2017; 13:3823-3830. [PMID: 28521482 DOI: 10.3892/ol.2017.5907] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Accepted: 01/26/2017] [Indexed: 01/08/2023] Open
Abstract
Abnormal expression levels of microRNA-204 (miR-204) have been identified in various types of human cancer. However, the expression and functions of miR-204, and the underlying molecular mechanism involved in the initiation and progression of hepatocellular carcinoma (HCC), require further investigation. The results of the present study demonstrated that miR-204 is downregulated in HCC tissues and cell lines. Notably, zinc finger E-box binding homeobox 2 (ZEB2) was identified as a direct target of miR-204 in HCC. In addition, miR-204 negatively regulates ZEB2 expression level in HCC cells at the post-transcriptional level. In functional studies, the overexpression of miR-204 inhibited the proliferation, migration and invasion of HCC cells. Furthermore, the knockdown of ZEB2 may mimic the functions of miR-204 in HCC cells, suggesting that ZEB2 is a direct functional target of miR-204. In conclusion, the results of the present study indicated that miR-204 suppresses the tumor growth, migration and invasion of HCC cells by directly targeting ZEB2, and may serve as a novel therapeutic target for HCC.
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Affiliation(s)
- Bin Hu
- Department of Laboratory Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
| | - Ming Sun
- Department of Reproductive Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
| | - Jiajun Liu
- Department of Infectious Diseases, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
| | - Guolin Hong
- Department of Laboratory Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
| | - Qin Lin
- Department of Radiation Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
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Park SJ, Jang JY, Jeong SW, Cho YK, Lee SH, Kim SG, Cha SW, Kim YS, Cho YD, Kim HS, Kim BS, Park S, Bang HI. Usefulness of AFP, AFP-L3, and PIVKA-II, and their combinations in diagnosing hepatocellular carcinoma. Medicine (Baltimore) 2017; 96:e5811. [PMID: 28296720 PMCID: PMC5369875 DOI: 10.1097/md.0000000000005811] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Alpha-fetoprotein (AFP), Lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) are widely used as tumor markers for the diagnosis of hepatocellular carcinoma (HCC). This study compared the diagnostic values of AFP, AFP-L3, and PIVKA-II individually and in combination to find the best biomarker or biomarker panel.Seventy-nine patients with newly diagnosed HCC and 77 non-HCC control patients with liver cirrhosis were enrolled. AFP, AFP-L3, and PIVKA-II were measured in the same serum samples using microchip capillary electrophoresis and a liquid-phase binding assay on an automatic analyzer. Receiver-operating characteristic curve analyses were also applied to all combinations of the markers.When the 3 biomarkers were analyzed individually, AFP showed the largest area under the receiver-operating characteristic curve (AUC) (0.751). For combinations of the biomarkers, the AUC was highest (0.765) for "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL." The combination of "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL and AFP-L3 > 10%" had worse sensitivity and lower AUC (P = 0.001). The highest AUC of a single biomarker was highest for AFP and of a combination was "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL," with this also being the case when the cut-off value of AFP and AFP-L3 was changed.Alpha-fetoprotein showed the best diagnostic performance as a single biomarker for HCC. The diagnostic value of AFP was improved by combining it with PIVKA-II, but adding AFP-L3 did not contribute to the ability to distinguish between HCC and non-HCC liver cirrhosis. These findings were not altered when the cut-off value of AFP and AFP-L3 was changed.
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Affiliation(s)
- Sang Joon Park
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul
| | - Jae Young Jang
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul
| | - Soung Won Jeong
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul
| | - Young Kyu Cho
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul
| | - Sae Hwan Lee
- Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan
| | - Sang Gyune Kim
- Department of Internal Medicine, College of Medicine, Soonchunhyang University, Bucheon
| | - Sang-Woo Cha
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul
| | - Young Seok Kim
- Department of Internal Medicine, College of Medicine, Soonchunhyang University, Bucheon
| | - Young Deok Cho
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul
| | - Hong Soo Kim
- Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan
| | - Boo Sung Kim
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul
| | | | - Hae In Bang
- Department of Laboratory Medicine, Soonchunhyang University, Seoul, Republic of Korea
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50
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Abstract
Hepatocellular carcinoma (HCC) is a prominent malignancy in the Asia-Pacific region. Despite considerable knowledge about it's scope and nature this malignancy remains incurable. This manuscript reviews the epidemiology of this cancer, its pathogenesis, risk factors, potential prevention, surveillance, treatment, and the oncology nurses’ role relative to this malignancy. A literature search from the past decade was performed using the PubMed and CINAHL databases using the search terms “hepatocellular carcinoma,” “Asia,” and “nursing issues”. Themes such as etiology, prevention, treatment, and prognosis were included in this synthesis which has particular relevance to oncology nurses within the Asia-Pacific region.
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Affiliation(s)
- Deborah A Boyle
- Advanced Oncology Nursing Resources, Inc., Huntington Beach, CA, USA
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