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Shih HW, Lai Y, Hung HC, Lee JC, Wang YC, Wu TH, Lee CF, Wu TJ, Chou HS, Chan KM, Lee WC, Cheng CH. Liver Resection Criteria for Patients with Hepatocellular Carcinoma and Multiple Tumors Based on Total Tumor Volume. Dig Dis Sci 2024; 69:3069-3078. [PMID: 38824258 PMCID: PMC11341635 DOI: 10.1007/s10620-024-08500-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 05/11/2024] [Indexed: 06/03/2024]
Abstract
BACKGROUND In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits. METHODS We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method. RESULTS In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria. CONCLUSION Patients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.
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Affiliation(s)
- Hao-Wen Shih
- Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Yin Lai
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Hao-Chien Hung
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Jin-Chiao Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Yu-Chao Wang
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsung-Han Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Chen-Fang Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Ting-Jung Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Hong-Shiue Chou
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Kun-Ming Chan
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Chih-Hsien Cheng
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan.
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2
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Tseng TC, Yin WY. Minor hepatectomy for hepatocellular carcinoma in a patient with portal hypertension: A case report and review of the literature. Medicine (Baltimore) 2022; 101:e32176. [PMID: 36482633 PMCID: PMC9726341 DOI: 10.1097/md.0000000000032176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Curative modalities for early hepatocellular carcinoma (HCC) include liver resection (LR) and transplantation. For patients with portal hypertension (PH), liver transplantation (LT) is the preferred treatment but is oftentimes limited by organ shortage and can lead candidates to drop off due to disease progression, while hepatectomy has a higher risk of complications. This would pose a dilemma as to whether wait for donor organs or prioritize hepatectomy. PATIENT CONCERNS The patient was a 56-year-old male, a case of liver cirrhosis due to hepatitis C with sustained virological response following direct-acting antiviral agents. He was a liver transplant candidate, presented to the gastroenterology outpatient department for a recently-diagnosed liver tumor during a regular follow-up session. Pre-operative survey revealed PH manifested by thrombocytopenia, splenomegaly, huge splenorenal shunt and varices. The patient's Child-Pugh score was 7. INTERVENTIONS AND DIAGNOSIS Considering the patient's overall condition, tumor size and location, and a shortage of grafts, he underwent segment 5 and 6 partial hepatectomy. The pathological diagnosis was moderately differentiated HCC. OUTCOMES His postoperative course was complicated by refractory intraabdominal infection (IAI) and recovered under aggressive antibiotics treatment. He remained recurrence-free for over a year. CONCLUSION For patients with early resectable HCC, the approach of having a minor hepatectomy followed by salvage transplantation should serve as a compromising strategy. Tumor resection retards the progression of the disease. Comprehensive healthcare can expectantly improve clinical outcomes.
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Affiliation(s)
| | - Wen-Yao Yin
- School of Medicine, Tzu Chi University, Hualien, Taiwan
- Department of Surgery, Dalin Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- * Correspondence: Wen-Yao Yin, Division of Transplant Surgery, Department of Surgery, Dalin Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Road, Dalin Town, Chiayi County 622401, Taiwan (e-mail: )
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3
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Lee WC. Value of alpha-fetoprotein in hepatocellular carcinoma. Transl Gastroenterol Hepatol 2021; 6:52. [PMID: 34805574 DOI: 10.21037/tgh.2019.12.19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Accepted: 12/23/2019] [Indexed: 12/21/2022] Open
Affiliation(s)
- Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan
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4
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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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5
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Yuan Y, Cao W, Zhou H, Qian H, Wang H. CLTRN, Regulated by NRF1/RAN/DLD Protein Complex, Enhances Radiation Sensitivity of Hepatocellular Carcinoma Cells Through Ferroptosis Pathway. Int J Radiat Oncol Biol Phys 2021; 110:859-871. [PMID: 33508374 DOI: 10.1016/j.ijrobp.2020.12.062] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 12/10/2020] [Accepted: 12/17/2020] [Indexed: 12/24/2022]
Abstract
PURPOSE Radiation therapy is a viable treatment option for patients with unresectable hepatocellular carcinoma (HCC). However, radiation resistance and adverse effects are issues that needs to be addressed. Herein, for the first time, we investigated the ability of collectrin (CLTRN) to enhance radiosensitivity in patients with HCC. METHODS AND MATERIALS Transcriptome sequencing technology (RNA-seq technology) was used to analyze the transcription-level changes in the genes in HepG2 cells before and after x-ray irradiation. Combining the results with the HCC tissue RNA-seq data, we determined the ultimate target gene through bioinformatics analysis and cellular verification. A series of cellular and molecular biology techniques were applied in vitro and in vivo to confirm whether CLTRN can enhance radiosensitivity in HCC cells. Subsequently, the downstream action mechanism, the upstream transcription factor, and the interaction proteins of CLTRN were determined. RESULTS First, we confirmed that CLTRN is the target gene for radiation therapy and verified the association between CLTRN and radiosensitivity. In vivo and in vitro experiments were performed. Investigation of the gene regulatory mechanism revealed that the genes analyzed at the transcriptome level after CLTRN overexpression were mostly enriched in the glutathione metabolic pathway. As glutathione metabolism forms a vital link in ferroptosis, we surmised that CLTRN is associated with ferroptosis. This was confirmed through detection of cellular iron, determination of reactive oxygen species levels, use of transmission electron microscopy, and monitoring of ferroptosis-related protein indicators. Lastly, we investigated whether nuclear respiratory factor 1 is the upstream transcription factor of CLTRN and whether dihydrolipoamide dehydrogenase and members of the RAS oncogene family are its interacting proteins. CONCLUSIONS CLTRN is a vital regulator of radiation sensitivity and could serve as a novel therapeutic target or prognostic marker in HCC treatment.
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Affiliation(s)
- Yin Yuan
- Department of General Surgery, First Affiliated Hospital of Suzhou University, Suzhou, China; Department of Hepatobiliary Surgery, Fifth Affiliated Hospital of Medical School of Nantong University, Taizhou, China
| | - Wen Cao
- Department of Liver Disease, Fifth Affiliated Hospital of Medical School of Nantong University, Taizhou, China
| | - Hongbing Zhou
- Department of Hepatobiliary Surgery, Fifth Affiliated Hospital of Medical School of Nantong University, Taizhou, China
| | - Haixin Qian
- Department of General Surgery, First Affiliated Hospital of Suzhou University, Suzhou, China.
| | - Honggang Wang
- Department of General Surgery, Fifth Affiliated Hospital of Medical School of Nantong University, Taizhou, China.
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6
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Qin L, Li C, Xie F, Wang Z, Wen T. Combination of albumin-bilirubin grade and clinically significant portal hypertension predicts the prognosis of patients with hepatocellular carcinoma after liver resection. Biosci Trends 2021; 15:41-49. [PMID: 33627573 DOI: 10.5582/bst.2021.01064] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
There is little information concerning whether incorporating clinically significant portal hypertension (CSPH) into albumin-bilirubin (ALBI) grading could improve its predictive capacity. In this study, we investigated the predictive ability of ALBI grade plus CSPH (ALBI-P score) for patients with hepatocellular carcinoma (HCC) after liver resection. Data from 1,679 patients were retrospectively reviewed. The ALBI-P score was calculated from the ALBI grade and a point for CSPH (0 for absence of CSPH and 1 for presence of CSPH). Independent risk factors for recurrence-free survival (RFS) and overall survival (OS) were analyzed. Multivariate analysis suggested that the ALBI-P score was an independent risk factor for both postoperative recurrence (HR = 1.441, 95% CI = 1.328-1.563, P < 0.001) and mortality (HR = 1.332, 95% CI = 1.156-1.535, P < 0.001). Both the RFS and OS of patients with an ALBI-P score of 1 were significantly better than those of patients with ALBI-P scores of 2 and 3 (5-year RFS of 38.9%, 26.1%, and 14.7%, respectively, P < 0.001; 5-year OS of 52.7%, 42.6%, and 29.3%, P < 0.001). When the ALBI-P score and BCLC stage were combined, the ALBI-P-BCLC score showed the highest area under the receiver operating characteristic curve to predict both postoperative recurrence and mortality compared with BCLC stage alone, BCLC stage combined with ALBI grade, or platelet-albumin-bilirubin grade. These results suggested incorporating CSPH into the ALBI grade could strengthen its prognostic power. The ALBI-P score may serve as a surrogate marker to predict HCC patient outcomes after liver resection.
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Affiliation(s)
- Li Qin
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.,West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Chuan Li
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Fei Xie
- Department of Hepato-pancreato-biliary Surgery, First People's Hospital of Neijiang, Neijiang, Sichuan, China
| | - Zhenxia Wang
- Department of Hepato-pancreato-biliary Surgery, Chengdu Second People's Hospital, Chengdu, Sichuan, China
| | - Tianfu Wen
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
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7
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Shen M, Shen Y, Fan X, Men R, Ye T, Yang L. Roles of Macrophages and Exosomes in Liver Diseases. Front Med (Lausanne) 2020; 7:583691. [PMID: 33072790 PMCID: PMC7542243 DOI: 10.3389/fmed.2020.583691] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 08/13/2020] [Indexed: 02/05/2023] Open
Abstract
Exosomes are small discoid extracellular vesicles (EVs) originating from endosomes that are 30-150 nm in diameter and have a double lipid layer. They participate in the immune response, cell migration, cell differentiation, and tumor invasion and mediate intercellular communication, regulating the biological activity of receptor cells through the proteins, nucleic acids, and lipids that they carry. Exosomes also play vital roles in the diagnosis and treatment of liver diseases. Macrophages, which show unique phenotypes and functions in complex microenvironments, can be divided into M1 and M2 subtypes. M1 macrophages function in immune surveillance, and M2 macrophages downregulate the immune response. Recent studies have shown that macrophages are involved in non-alcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Moreover, several studies have demonstrated that liver diseases are associated with exosomes derived from or transferred to macrophages. This review focuses on the participation of macrophages and exosomes in liver diseases.
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Affiliation(s)
- Mengyi Shen
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Shen
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoli Fan
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Ruoting Men
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Tinghong Ye
- Laboratory of Liver Surgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Li Yang
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
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8
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Fang P, Xiang L, Chen W, Li S, Huang S, Li J, Zhuge L, Jin L, Feng W, Chen Y, Pan C. LncRNA GAS5 enhanced the killing effect of NK cell on liver cancer through regulating miR-544/RUNX3. Innate Immun 2020; 25:99-109. [PMID: 30774011 PMCID: PMC6830859 DOI: 10.1177/1753425919827632] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
This study aimed to explore the role of lncRNA GAS5 in the regulation of the
killing effect of NK cells on liver cancer. Compared with a control group,
lncRNA GAS5, RUNX3, and NCR1 were down-regulated in NK cells of patients with
liver cancer, whereas miR-544 expression was up-regulated in NK cells of
patients with liver cancer. Activated NK cells had higher IFN-γ level. Knockdown
of GAS5 in activated NK cells decreased IFN-γ secretion, NK cell cytotoxicity,
the percentage of CD107a+ NK cells, and the apoptosis rate of HepG2 and Huh7
cells. We also proved the interaction of GAS5 and miR-544, and the negative
regulation role of GAS5 on miR-544. GAS5 overexpression in activated NK cells
increased RUNX3 expression, IFN-γ secretion, the NK cell cytotoxicity, the
percentage of CD107a+ NK cells, and the apoptosis rate of HepG2 cells, while
miR-544 mimic abolished the promotion effect of GAS5 overexpression. Finally,
in vivo experiments indicated an inhibition effect of GAS5
in tumor growth. LncRNA GAS5 overexpression enhances the killing effect of NK
cell on liver cancer through regulating miR-544/RUNX3.
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Affiliation(s)
- Peipei Fang
- 1 Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, People's Republic of China.,2 Pediatric Hepatitis and Liver disease Clinical Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, People's Republic of China
| | - Luxia Xiang
- 1 Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, People's Republic of China.,2 Pediatric Hepatitis and Liver disease Clinical Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, People's Republic of China.,3 The Second School of Medicine, Wenzhou Medical University, People's Republic of China
| | - Weilai Chen
- 4 Department of Neurology, Wenzhou People's Hospital, People's Republic of China
| | - Shaoxun Li
- 1 Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, People's Republic of China.,2 Pediatric Hepatitis and Liver disease Clinical Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, People's Republic of China.,3 The Second School of Medicine, Wenzhou Medical University, People's Republic of China
| | - Shanshan Huang
- 1 Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, People's Republic of China
| | - Jie Li
- 1 Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, People's Republic of China
| | - Lu Zhuge
- 1 Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, People's Republic of China
| | - Lingxiang Jin
- 1 Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, People's Republic of China
| | - Wenke Feng
- 2 Pediatric Hepatitis and Liver disease Clinical Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, People's Republic of China
| | - Yiping Chen
- 2 Pediatric Hepatitis and Liver disease Clinical Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, People's Republic of China
| | - Chenwei Pan
- 1 Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, People's Republic of China.,2 Pediatric Hepatitis and Liver disease Clinical Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, People's Republic of China
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9
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Chan KM, Wu TH, Cheng CH, Lee CF, Wu TJ, Chou HS, Lee WC. Advantage of early liver transplantation whenever indicated for hepatocellular carcinoma recurrence after primary liver resection. Biomed J 2019; 42:335-342. [PMID: 31783994 PMCID: PMC6888715 DOI: 10.1016/j.bj.2019.04.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 10/26/2018] [Accepted: 04/09/2019] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Liver transplantation (LT) for recurrent hepatocellular carcinoma (HCC) following liver resection (LR) has been considered a promising strategy for improving patient's outcome. The study aimed to analyse patients from primary LR to LT for HCC and to provide additional information for decision-making in therapeutic strategies for patients with HCC. METHODS Among 776 LTs, a retrospective analysis of patients who had undergone LT for recurrent HCC after primary LR between May 2005 and 2017 February was performed. RESULTS During the follow-up period, the overall recurrence-free survival rates at 1, 3 and 5 years were 84.8%, 68.2% and 68.2%, and disease-specific overall-survival rates were 95.7%, 74.4% and 66.7% at 1, 3 and 5 years after LT, respectively. Beyond University of California at San Francisco (UCSF) transplantation criteria (p = 0.018, hazard ratio (HR) = 12.70), maximum tumor size ≥ 5 cm at LR (p = 0.012, HR = 7.90) and period between post-LR HCC recurrence and LT ≥ 1 year (p = 0.030, HR = 7.57) were prognostic factors of HCC recurrence after LT. Moreover, HCC recurrence after LT was the solely independent risk factor affecting overall survival of patients. CONCLUSION Large tumor size at LR should be taken into cautious tending to HCC recurrence even after salvage LT. Importantly, LT should be considered as soon as possible preferably within 1 year whenever post-LR recurrent HCC meets transplantation criteria.
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Affiliation(s)
- Kun-Ming Chan
- Department of General Surgery & Department of Organs Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
| | - Tsung-Han Wu
- Department of General Surgery & Department of Organs Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chih-Hsien Cheng
- Department of General Surgery & Department of Organs Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chen-Fang Lee
- Department of General Surgery & Department of Organs Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ting-Jung Wu
- Department of General Surgery & Department of Organs Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hong-Shiue Chou
- Department of General Surgery & Department of Organs Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wei-Chen Lee
- Department of General Surgery & Department of Organs Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
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10
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Chen HW, Shen AL, Liu LY, Peng J, Chu JF. Bear Bile Powder Inhibits Growth of Hepatocellular Carcinoma via Suppressing STAT3 Signaling Pathway in Mice. Chin J Integr Med 2019; 26:370-374. [DOI: 10.1007/s11655-019-3010-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/20/2017] [Indexed: 12/01/2022]
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11
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Lee WC, Wang YC, Cheng CH, Wu TH, Lee CF, Wu TJ, Chou HS, Chan KM. Myeloid-derived suppressor cells in the patients with liver resection for hepatitis B virus-related hepatocellular carcinoma. Sci Rep 2019; 9:2269. [PMID: 30783140 PMCID: PMC6381172 DOI: 10.1038/s41598-019-38785-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Accepted: 12/13/2018] [Indexed: 12/19/2022] Open
Abstract
Liver resection remains the popular treatment for hepatocellular carcinoma (HCC). The aim of this study was to explore the alteration of immune cells in HCC patients with liver resections. Nineteen patients were included and their peripheral blood samples were taken before and after liver resections for immune-cell analysis. The clinical characteristics showed that the median diameter of the resected tumors was 7.5 cm with a range from 1.4 to 16.5 cm. The analysis of immune cells showed that the percentage of CD4+ T-cells were not altered by liver resection, but the percentage of CD8+ T-cell was decreased from 31.7 ± 12.4% to 20.2 ± 10.4% at one week after liver resection (p = 0.006). For immunosuppressor cells, regulatory T-cells were not altered, but myeloid-derived suppressor cells (MDSC) were decreased from 7.75 ± 8.16% to 1.51 ± 1.32% at one month after liver resection (p = 0.022) in 10 of 19 patients with high frequency of MDSC. Furthermore, it was also found that MDSC population was linearly correlated to tumor volume. In conclusion, CD8+ T-cells and MDSC were altered by liver resection. The percentage of CD8+ T-cells was decreased by surgery, but the accumulation of MDSC was abrogated.
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Affiliation(s)
- Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan.
- Chang-Gung University College of Medicine, Taoyuan, Taiwan.
| | - Yu-Chao Wang
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Chih-Hsien Cheng
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsung-Han Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Chen-Fang Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Ting-Jung Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Hong-Shiue Chou
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Kun-Ming Chan
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
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12
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Chan KM, Wu TH, Cheng CH, Lee CF, Wu TJ, Chou HS, Lee WC. Implementation of sorafenib treatment for advanced hepatocellular carcinoma: an illustration of current practice in Taiwan. Cancer Manag Res 2019; 11:1013-1021. [PMID: 30774429 PMCID: PMC6349081 DOI: 10.2147/cmar.s186678] [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] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Sorafenib is the first regimen listed in the treatment algorithm for hepatocellular carcinoma (HCC) worldwide. This study aimed to assess the efficacy of sorafenib treatment for advanced HCC in a clinical practice using a nationwide population study. METHODS All patients registered with a diagnosis of primary HCC and identified as having been prescribed sorafenib between August 2012 and December 2015 were selected from a national database and retrospectively reviewed. Outcomes related to prescription of sorafenib for these patients were further assessed. RESULTS A total of 9,738 patients were enrolled and analyzed. As a result, 32.33% of patients had an initial treatment response and were eligible for the prescribed second term (240 tablets/ term) of sorafenib and 8.91% of patients received more than three terms of sorafenib. Meanwhile, the duration of sorafenib usage beyond 6 months was noted in 15.49% of patients, including 10.59% of patients with a period of usage between 6 and 12 months and 4.9% of patients with more than 12 months usage. Survival analysis showed that patients who received locoregional therapy plus sorafenib had significantly better survival rates than those who underwent only sorafenib treatment. Certain patients who underwent hepatectomy (n=12) or liver transplantation (n=13) were subsequently free of HCC. CONCLUSION The disease control rate of sorafenib in advanced HCC patients in this study seemed similarly poorer as what has been previously reported by clinical trials. The combination of sorafenib and additional treatments could perhaps provide survival benefits and possibly cure disease in combination with surgical management.
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Affiliation(s)
- Kun-Ming Chan
- Department of General Surgery and Department of Organs Transplantation Institute, Chang G Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan,
| | - Tsung-Han Wu
- Department of General Surgery and Department of Organs Transplantation Institute, Chang G Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan,
| | - Chih-Hsien Cheng
- Department of General Surgery and Department of Organs Transplantation Institute, Chang G Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan,
| | - Chen-Fang Lee
- Department of General Surgery and Department of Organs Transplantation Institute, Chang G Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan,
| | - Ting-Jung Wu
- Department of General Surgery and Department of Organs Transplantation Institute, Chang G Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan,
| | - Hong-Shiue Chou
- Department of General Surgery and Department of Organs Transplantation Institute, Chang G Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan,
| | - Wei-Chen Lee
- Department of General Surgery and Department of Organs Transplantation Institute, Chang G Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan,
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13
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Dimitroulis D, Damaskos C, Valsami S, Davakis S, Garmpis N, Spartalis E, Athanasiou A, Moris D, Sakellariou S, Kykalos S, Tsourouflis G, Garmpi A, Delladetsima I, Kontzoglou K, Kouraklis G. From diagnosis to treatment of hepatocellular carcinoma: An epidemic problem for both developed and developing world. World J Gastroenterol 2017; 23:5282-5294. [PMID: 28839428 PMCID: PMC5550777 DOI: 10.3748/wjg.v23.i29.5282] [Citation(s) in RCA: 224] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Revised: 05/03/2017] [Accepted: 06/09/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy and the third cause of cancer-related death in the Western Countries. The well-established causes of HCC are chronic liver infections such as hepatitis B virus or chronic hepatitis C virus, nonalcoholic fatty liver disease, consumption of aflatoxins and tobacco smocking. Clinical presentation varies widely; patients can be asymptomatic while symptomatology extends from right upper abdominal quadrant paint and weight loss to obstructive jaundice and lethargy. Imaging is the first key and one of the most important aspects at all stages of diagnosis, therapy and follow-up of patients with HCC. The Barcelona Clinic Liver Cancer Staging System remains the most widely classification system used for HCC management guidelines. Up until now, HCC remains a challenge to early diagnose, and treat effectively; treating management is focused on hepatic resection, orthotopic liver transplantation, ablative therapies, chemoembolization and systemic therapies with cytotocix drugs, and targeted agents. This review article describes the current evidence on epidemiology, symptomatology, diagnosis and treatment of hepatocellular carcinoma.
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MESH Headings
- Ablation Techniques/methods
- Alcohol Drinking/adverse effects
- Antineoplastic Agents/therapeutic use
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/epidemiology
- Carcinoma, Hepatocellular/etiology
- Carcinoma, Hepatocellular/therapy
- Diagnosis, Differential
- Early Detection of Cancer/methods
- Hepatectomy/methods
- Hepatitis B, Chronic/complications
- Hepatitis B, Chronic/epidemiology
- Hepatitis B, Chronic/virology
- Hepatitis C, Chronic/complications
- Hepatitis C, Chronic/epidemiology
- Hepatitis C, Chronic/virology
- Humans
- Incidence
- Liver/diagnostic imaging
- Liver/pathology
- Liver/surgery
- Liver Cirrhosis/complications
- Liver Neoplasms/diagnosis
- Liver Neoplasms/epidemiology
- Liver Neoplasms/etiology
- Liver Neoplasms/therapy
- Liver Transplantation/methods
- Neoplasm Staging
- Non-alcoholic Fatty Liver Disease/complications
- Practice Guidelines as Topic
- Prevalence
- Risk Factors
- Tobacco Smoking/adverse effects
- Tomography, X-Ray Computed
- Treatment Outcome
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14
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Lee WC, Chou HS, Wu TJ, Lee CF, Hsu PY, Hsu HY, Wu TH, Chan KM. Down-regulation of metabolic proteins in hepatocellular carcinoma with portal vein thrombosis. Clin Proteomics 2017; 14:29. [PMID: 28785178 PMCID: PMC5541415 DOI: 10.1186/s12014-017-9164-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 07/17/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma is an aggressive malignancy with poor prognosis and easy to recur even the tumor is totally removed by surgery. Portal vascular invasion is one of the major factors contributing to tumor recurrence and poor prognosis. However, why hepatocellular carcinoma is easy to grow into vessels is unclear. METHODS Surgical specimens from seven hepatocellular carcinoma patients with portal vein thrombosis and seven patients without vascular invasion were utilized to analyze protein expression by proteomic technique. The proteins in the tumors were separated by 2-dimensional electrophoresis. Protein patterns in the gels were recorded as digitalized images. The differences of expression in hepatocellular carcinoma with or without portal vein thrombosis were identified by mass spectrometry. RESULTS Clinically, the tumors with portal vein thrombosis were larger than those without portal vein thrombosis. The median survival time for the patients with portal vein thrombosis was much shorter [4 (ranged 2.5-47) vs. 53 (ranged 33-85) months, p = 0.002]. By analyzing the protein expression in cancer tissues with or without portal vein thrombosis, the differences of protein expression were mainly metabolic enzymes. Carbonic anhydrase I, betaine-homocysteine S-methyltransferase 1, fumarate hydratase, isovaleryl-CoA dehydrogenase, short-chain specific acyl-CoA dehydrogenase and arginase-1 were all down-regulated in the tumors with portal vein thrombosis. CONCLUSION Metabolic enzymes and cytosol carbonic anhydrases were downregulated in hepatocellular carcinoma with portal vein thrombus. The deficiency of metabolic enzymes and cytosol carbonic anhydrases may alter cellular metabolisms and acid-base balance in hepatocellular carcinoma, which may facilitate to invade portal vein.
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Affiliation(s)
- Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, 5, Fu-Hsing Street, Kwei-Shan Township, Taoyuan, Taiwan
| | - Hong-Shiue Chou
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, 5, Fu-Hsing Street, Kwei-Shan Township, Taoyuan, Taiwan
| | - Ting-Jung Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, 5, Fu-Hsing Street, Kwei-Shan Township, Taoyuan, Taiwan
| | - Chen-Fang Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, 5, Fu-Hsing Street, Kwei-Shan Township, Taoyuan, Taiwan
| | - Pao-Yueh Hsu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, 5, Fu-Hsing Street, Kwei-Shan Township, Taoyuan, Taiwan
| | - Hsiu-Ying Hsu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, 5, Fu-Hsing Street, Kwei-Shan Township, Taoyuan, Taiwan
| | - Tsung-Han Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, 5, Fu-Hsing Street, Kwei-Shan Township, Taoyuan, Taiwan
| | - Kun-Ming Chan
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, 5, Fu-Hsing Street, Kwei-Shan Township, Taoyuan, Taiwan
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15
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Wong LL, Hernandez BY, Shvetsov YB, Kawano Y, Tang ZY, Ji JF. Liver resection for early hepatocellular cancer: Comparison of centers in 3 different countries. World J Hepatol 2016; 8:1327-1335. [PMID: 27872684 PMCID: PMC5099585 DOI: 10.4254/wjh.v8.i31.1327] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 06/28/2016] [Accepted: 08/16/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To compare patients who underwent resection of early stage hepatocellular cancer (HCC) in three different countries.
METHODS This retrospective study characterizes 573 stage I/II HCC patients treated with liver resection in 3 tertiary-referral centers: Tokyo (n = 250), Honolulu (n = 146) and Shanghai (n = 177).
RESULTS Shanghai patients were younger, predominantly male, hepatitis-B seropositive (94%) and cirrhotic (93%). Tokyo patients were older and more likely to have hepatitis-C (67%), smaller tumors, low albumin, and normal alpha-fetoprotein. The Honolulu cohort had the largest tumors and 30% had no viral hepatitis. Age-adjusted mortality at 1 and 5-years were lower in the Tokyo cohort compared to Honolulu and there was no difference in mortality between Shanghai and Honolulu cohorts. Elevated alpha-fetoprotein, low albumin and tumor > 5 cm were associated with increased 1-year mortality. These factors and cirrhosis were independently associated with increased 5-year mortality. Independent risk factors of survival varied when examined separately by center.
CONCLUSION The profile of early-stage HCC patients is strikingly different across countries and likely contributes to survival differences. Underlying differences in patient populations including risk factors/comorbidities influencing disease progression may also account for variation in outcomes.
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A Hybrid Chalcone Combining the Trimethoxyphenyl and Isatinyl Groups Targets Multiple Oncogenic Proteins and Pathways in Hepatocellular Carcinoma Cells. PLoS One 2016; 11:e0161025. [PMID: 27525972 PMCID: PMC4985065 DOI: 10.1371/journal.pone.0161025] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Accepted: 07/28/2016] [Indexed: 12/20/2022] Open
Abstract
Small molecule inhibitors that can simultaneously inhibit multiple oncogenic proteins in essential pathways are promising therapeutic chemicals for hepatocellular carcinoma (HCC). To combine the anticancer effects of combretastatins, chalcones and isatins, we synthesized a novel hybrid molecule 3’,4’,5’-trimethoxy-5-chloro-isatinylchalcone (3MCIC). 3MCIC inhibited proliferation of cultured HepG2 cells, causing rounding-up of the cells and massive vacuole accumulation in the cytoplasm. Paxillin and focal adhesion plaques were downregulated by 3MCIC. Surprisingly, unlike the microtubule (MT)-targeting agent CA-4 that inhibits tubulin polymerization, 3MCIC stabilized tubulin polymers both in living cells and in cell lysates. 3MCIC treatment reduced cyclin B1, CDK1, p-CDK1/2, and Rb, but increased p53 and p21. Moreover, 3MCIC caused GSK3β degradation by promoting GSK3β-Ser9 phosphorylation. Nevertheless, 3MCIC inhibited the Wnt/β-catenin pathway by downregulating β-catenin, c-Myc, cyclin D1 and E2F1. 3MCIC treatment not only activated the caspase-3-dependent apoptotic pathway, but also caused massive autophagy evidenced by rapid and drastic changes of LC3 and p62. 3MCIC also promoted cleavage and maturation of the lysosomal protease cathepsin D. Using ligand-affinity chromatography (LAC), target proteins captured onto the Sephacryl S1000-C12-3MCIC resins were isolated and analyzed by mass spectrometry (MS). Some of the LAC-MS identified targets, i.e., septin-2, vimentin, pan-cytokeratin, nucleolin, EF1α1/2, EBP1 (PA2G4), cyclin B1 and GSK3β, were further detected by Western blotting. Moreover, both septin-2 and HIF-1α decreased drastically in 3MCIC-treated HepG2 cells. Our data suggest that 3MCIC is a promising anticancer lead compound with novel targeting mechanisms, and also demonstrate the efficiency of LAC-MS based target identification in anticancer drug development.
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