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Kong Y, Huang X, Cao X, Tang F, Zhou X. Early Recurrence of Colorectal Liver Metastasis (Number ≤ 5 and Largest Diameter ≤ 3 cm) after Resection or Thermal Ablation: a Multi-center Study of Patterns, Safety, Survival and Risk Factors. J Gastrointest Cancer 2025; 56:77. [PMID: 40072796 DOI: 10.1007/s12029-025-01200-4] [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] [Accepted: 03/02/2025] [Indexed: 03/14/2025]
Abstract
OBJECTIVE To compare early recurrence patterns, safety, survival and investigate the clinical risk factors of early recurrence (ER) after liver resection or thermal ablation (TA) for patients with colorectal liver metastases (CRLM) with number ≤ 5 and largest diameter ≤ 3 cm. MATERIALS AND METHODS This retrospective study included patients with CRLM who underwent liver resection or TA between January 2016 and December 2021 at two hospitals in China. The Kaplan-Meier method and log-rank test were used to assess recurrence-free survival (RFS) and overall survival (OS). Risk factors for ER were analysed using univariate and multivariate Cox regression analyses. RESULTS 303 patients with 632 liver metastases were enrolled. The most common early recurrence pattern was intrahepatic recurrence (IHR) in resection group and TA group. There was no significant difference in 6-month RFS rate (65.81% vs 66.23%) and median OS (P = 0.10) between two groups. Patients without ER had better OS than those with ER (P < 0.05). The incidence of serious complications (P = 0.013), length of hospitalization (P < 0.01), and albumin-bilirubin (ALBI) score (P = 0.038) in TA group were significantly better than resection group. The diameter of liver metastases (HR: 4.89, 95% CI: 1.16-20.60; P = 0.031) and clinical risk score (CRS) (HR: 1.86, 95% CI: 1.06-3.25; P = 0.029) were independent risk factors for ER. CONCLUSION For CRLM with largest diameter ≤ 3 cm and number ≤ 5, the efficacy of receiving resection or TA is comparable, and the safety of TA is better. TA may be considered as the first-line local treatment option for patients with CRLM.
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Affiliation(s)
- Yaqing Kong
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xiaoyu Huang
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xiaojing Cao
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Fan Tang
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xiang Zhou
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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Ding W, Bi M, Gao Y, Zheng L, Chen J, Liu F, Yu J, Liang P. The influence of peritumoral parenchyma on local tumor progression of hepatocellular carcinoma after thermal ablation: a retrospective multicenter study. Abdom Radiol (NY) 2025; 50:710-719. [PMID: 39207515 DOI: 10.1007/s00261-024-04543-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2024] [Revised: 08/15/2024] [Accepted: 08/16/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND With the increasing importance of thermal ablation (TA) in hepatocellular carcinoma (HCC) treatment, local tumor progression (LTP) has become a nonignorable recurrence type after ablation. PURPOSES To analyze the influence of peritumoral liver parenchyma on LTP and to explore the possible reasons for this influence. METHODS Ablated HCCs with peritumoral parenchymal biopsy and ablation margins greater than 5 mm were included from two hospitals. The grade of necroinflammatory activity (G) and stage of fibrosis (S) of the parenchyma were evaluated by Scheuer staging system. Univariate/multivariate Cox model was used to analyze the possible factors influencing LTP. Peritumoral satellite focus rate, ablation energy, ablation volume after treatment, ablation volume after one-month, and volume reduction rate were collected and analyzed to explore the possible reasons for influence. Propensity score matching (PSM) was used to balance baselines across different groups. RESULTS 346 HCCs (64 with LTP, 282 without LTP) were enrolled from January 2013 to June 2022, with a median follow-up of 27 months. Univariate/multivariate analysis showed fibrosis was a protective factor in LTP (OR = 0.70, 95%CI: 0.55-0.89). The low-fibrosis group exhibited higher satellite focus rate (15.6% vs. 8.4%, p = 0.048), lower ablation energy (22637 ± 9424 J vs. 33352 ± 13779 J, p < 0.001) and higher volume reduction rate (0.33 ± 0.06 vs. 0.25 ± 0.06, p < 0.001) than the high-fibrosis group. Therefore, we speculated that the protective effect of fibrosis was due to its blocking of tumor invasion and reduction of sublethal zones. CONCLUSION Fibrosis of the peritumoral liver parenchyma is a stable protective factor in LTP occurrence.
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Affiliation(s)
- Wenzhen Ding
- Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Mingsen Bi
- Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yongyan Gao
- Third Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Lin Zheng
- Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - JiYe Chen
- Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Fangyi Liu
- Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jie Yu
- Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Ping Liang
- Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
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Wang W, Wu F, Wu Z, Zhang M, Lu Q. The XIAP inhibitor AZD5582 improves the treatment effect of microwave ablation on hepatocellular carcinoma. Front Immunol 2025; 16:1482954. [PMID: 39917292 PMCID: PMC11798986 DOI: 10.3389/fimmu.2025.1482954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 01/06/2025] [Indexed: 02/09/2025] Open
Abstract
Background and purpose Microwave ablation (MWA) is one of the first-line therapy recommended for early-stage hepatocellular carcinoma (HCC). However, the residual tumor, resulting from insufficient ablation, led to recurrence and metastasis of liver cancer. Novel combination strategies are urgently needed to enhance efficiency of MWA. Methods We detected the expression of XIAP protein after ablation in primary liver cancer patients using immunohistochemistry. Then, we established in vitro and in vivo IMWA models to further detect XIAP expression. We established an in vitro IMWA model by heating HCC cell lines and, at the same time, applied the XIAP inhibitor AZD5582 and verified the proliferation, migration, and pro-apoptotic ability of the XIAP inhibitor on tumor cells using CCK8, colony formation assay, cell scratch assay, and flow cytometry flow. The IMWA model of C57BL/6 and NTG mice were established, and AZD5582 was used in combination to evaluate the inhibitory and pro-apoptotic effects of different treatment regimens on tumor growth and to detect the local immune infiltration of C57BL/6 tumors. Finally, AZD5582 drug toxicity was detected to confirm its feasibility. Results XIAP protein expression is significantly increased in recurrent hepatocellular carcinoma tissues of patients who previously received microwave ablation therapy. In vitro experiments showed that the migration and proliferation ability of HCC cells was significantly reduced, and the level of apoptosis was increased after application of the XIAP inhibitor AZD5582. In vivo experiments further confirmed that ablation combined with the application of AZD5582 significantly reduced the proliferation ability of residual hepatocellular carcinoma. Concurrently, in C57 BL/6 mice with AZD5582 application, the level of local CD8+ T-cell infiltration in the tumor was increased, while the level of Foxp3+ regulatory T-cell infiltration was significantly reduced. The low toxicity of AZD5582 was further confirmed through hematological and pathological examinations of vital organs. These results provide new clues for hepatocellular carcinoma treatment, suggesting the potential role of XIAP inhibitors in hepatocellular carcinoma treatment and their impact in immunomodulation. Conclusions In this study, we found that the XIAP inhibitor AZD5582 modulates the immune microenvironment and inhibits the progression of post-ablation residual hepatocellular carcinoma.
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Affiliation(s)
- Wenhui Wang
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, China
| | - Fuyuan Wu
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, China
| | - Zhe Wu
- Tianfu Jincheng Laboratory, City of Future Medicine, Chengdu, China
| | - Mengfan Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China
| | - Qiang Lu
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, China
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Wu J, Zhou Z, Huang Y, Deng X, Zheng S, He S, Huang G, Hu B, Shi M, Liao W, Huang N. Radiofrequency ablation: mechanisms and clinical applications. MedComm (Beijing) 2024; 5:e746. [PMID: 39359691 PMCID: PMC11445673 DOI: 10.1002/mco2.746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 08/31/2024] [Accepted: 09/02/2024] [Indexed: 10/04/2024] Open
Abstract
Radiofrequency ablation (RFA), a form of thermal ablation, employs localized heat to induce protein denaturation in tissue cells, resulting in cell death. It has emerged as a viable treatment option for patients who are ineligible for surgery in various diseases, particularly liver cancer and other tumor-related conditions. In addition to directly eliminating tumor cells, RFA also induces alterations in the infiltrating cells within the tumor microenvironment (TME), which can significantly impact treatment outcomes. Moreover, incomplete RFA (iRFA) may lead to tumor recurrence and metastasis. The current challenge is to enhance the efficacy of RFA by elucidating its underlying mechanisms. This review discusses the clinical applications of RFA in treating various diseases and the mechanisms that contribute to the survival and invasion of tumor cells following iRFA, including the roles of heat shock proteins, hypoxia, and autophagy. Additionally, we analyze the changes occurring in infiltrating cells within the TME after iRFA. Finally, we provide a comprehensive summary of clinical trials involving RFA in conjunction with other treatment modalities in the field of cancer therapy, aiming to offer novel insights and references for improving the effectiveness of RFA.
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Affiliation(s)
- Jianhua Wu
- Department of Oncology, Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina
| | - Zhiyuan Zhou
- Department of Oncology, Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina
| | - Yuanwen Huang
- Department of Oncology, Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina
| | - Xinyue Deng
- Department of Oncology, Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina
| | - Siting Zheng
- Department of Oncology, Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina
| | - Shangwen He
- Department of Respiratory and Critical Care MedicineChronic Airways Diseases Laboratory, Nanfang Hospital, Southern Medical UniversityGuangzhouGuangdongChina
| | - Genjie Huang
- Department of Oncology, Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina
| | - Binghui Hu
- Department of Oncology, Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina
| | - Min Shi
- Department of Oncology, Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina
| | - Wangjun Liao
- Department of Oncology, Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina
| | - Na Huang
- Department of Oncology, Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina
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Baj J, Kołodziej M, Kobak J, Januszewski J, Syty K, Portincasa P, Forma A. Significance of Immune and Non-Immune Cell Stroma as a Microenvironment of Hepatocellular Carcinoma-From Inflammation to Hepatocellular Carcinoma Progression. Int J Mol Sci 2024; 25:10233. [PMID: 39408564 PMCID: PMC11475949 DOI: 10.3390/ijms251910233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 09/19/2024] [Accepted: 09/20/2024] [Indexed: 10/20/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common liver cancer as well as the most prevalent cause of death in the adult patient population with cirrhosis. The occurrence of HCC is primarily caused by chronic liver inflammation that might occur because of a viral infection, non-alcoholic fatty liver disease (NAFLD), or various lifestyle-associated factors. The objective of this review was to summarize the current knowledge regarding the microenvironment of HCC, indicating how immune- and non-immune-cell stroma might affect the onset and progression of HCC. Therefore, in the following narrative review, we described the role of tumor-infiltrating neutrophils, bone-marrow-derived cells, tumor-associated mast cells, cancer-associated fibroblasts, tumor-associated macrophages, liver-sinusoidal endothelial cells, lymphocytes, and certain cytokines in liver inflammation and the further progression to HCC. A better understanding of the HCC microenvironment might be crucial to introducing novel treatment strategies or combined therapies that could lead to more effective clinical outcomes.
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Affiliation(s)
- Jacek Baj
- Department of Correct, Clinical and Imaging Anatomy, Chair of Fundamental Sciences, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (J.B.); (J.J.)
| | - Magdalena Kołodziej
- Chair and Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland; (M.K.); (J.K.)
| | - Joanna Kobak
- Chair and Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland; (M.K.); (J.K.)
| | - Jacek Januszewski
- Department of Correct, Clinical and Imaging Anatomy, Chair of Fundamental Sciences, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (J.B.); (J.J.)
| | - Kinga Syty
- Institute of Health Sciences, John Paul the II Catholic University of Lublin, Konstantynów 1G, 20-708 Lublin, Poland;
| | - Piero Portincasa
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy;
| | - Alicja Forma
- Chair and Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland; (M.K.); (J.K.)
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Tang L, Hou Y, Huang Z, Huang J. Transarterial Chemoembolization Combined with Lenvatinib Plus Sequential Microwave Ablation for Large Hepatocellular Carcinoma Beyond Up-to-Seven Criteria: A Retrospective Cohort Study. Acad Radiol 2024; 31:2795-2806. [PMID: 38290885 DOI: 10.1016/j.acra.2024.01.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 01/07/2024] [Accepted: 01/08/2024] [Indexed: 02/01/2024]
Abstract
RATIONALE AND OBJECTIVES The aim of this study was to investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with Lenvatinib plus sequential microwave ablation (MWA) for the treatment of patients with large hepatocellular carcinoma (HCC) beyond up-to-seven criteria. MATERIALS AND METHODS This retrospective cohort study assessed the medical records of patients with large HCC who underwent TACE combined with Lenvatinib plus sequential MWA (TLM) or TACE plus sequential MWA (TM). Lenvatinib was administered to patients within 3-5 days after TACE and sequential MWA was performed once they met the criteria for curative ablation after TACE or the combination therapy. The progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared between two groups. RESULTS Of the 81 patients who underwent TLM or TM, 64 who met the eligibility criteria were included in this study. Among them, 28 patients underwent TLM and 36 underwent TM. The inverse probability weighting method (IPTW) was used to balance differences between two groups. The TLM group had longer PFS than the TM group (median, before IPTW: 18.53 vs. 5.62 months, p < 0.001; median, after IPTW: 28.27 vs. 5.30 months, p < 0.001). Univariate and multivariate analyses revealed that TLM and the maximum tumor diameter were independent prognostic factors for PFS. The overall incidence rate of minor complications related to TACE or MWA was lower in the TLM group (32.1% vs. 66.7%, p = 0.006). CONCLUSION TACE combined with Lenvatinib plus sequential MWA can prolong the progression-free survival of patients with large HCC beyond up-to-seven criteria.
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Affiliation(s)
- Lu Tang
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China (L.T., Y.H., Z.H., J.H.); State Key Laboratory of Oncology in South China, Guangzhou 510060, Guangdong, China (L.T., Y.H., Z.H., J.H.); Guangdong Provincial Clinical Research Center for Cancer, Guangzhou 510060, Guangdong, China (L.T., Y.H., Z.H., J.H.); Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong, China (L.T., Y.H., Z.H., J.H.)
| | - Yingwen Hou
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China (L.T., Y.H., Z.H., J.H.); State Key Laboratory of Oncology in South China, Guangzhou 510060, Guangdong, China (L.T., Y.H., Z.H., J.H.); Guangdong Provincial Clinical Research Center for Cancer, Guangzhou 510060, Guangdong, China (L.T., Y.H., Z.H., J.H.); Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong, China (L.T., Y.H., Z.H., J.H.)
| | - Zhimei Huang
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China (L.T., Y.H., Z.H., J.H.); State Key Laboratory of Oncology in South China, Guangzhou 510060, Guangdong, China (L.T., Y.H., Z.H., J.H.); Guangdong Provincial Clinical Research Center for Cancer, Guangzhou 510060, Guangdong, China (L.T., Y.H., Z.H., J.H.); Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong, China (L.T., Y.H., Z.H., J.H.)
| | - Jinhua Huang
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China (L.T., Y.H., Z.H., J.H.); State Key Laboratory of Oncology in South China, Guangzhou 510060, Guangdong, China (L.T., Y.H., Z.H., J.H.); Guangdong Provincial Clinical Research Center for Cancer, Guangzhou 510060, Guangdong, China (L.T., Y.H., Z.H., J.H.); Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong, China (L.T., Y.H., Z.H., J.H.).
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Santos GPDL, Kulcsar MAV, Capelli FDA, Steck JH, Fernandes KL, Mesa CO, da Motta-Leal-Filho JM, Scheffel RS, Vaisman F, Martins GLP, Szejnfeld D, Amoedo MK, de Menezes MR, Rahal A, Matos LL. Brazilian Consensus on the Application of Thermal Ablation for Treatment of Thyroid Nodules: A Task Force Statement by the Brazilian Society of Interventional Radiology and Endovascular Surgery (SOBRICE), Brazilian Society of Head and Neck Surgery (SBCCP), and Brazilian Society of Endocrinology and Metabolism (SBEM). ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2024; 68:e230263. [PMID: 39420896 PMCID: PMC11213574 DOI: 10.20945/2359-4292-2023-0263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 02/07/2024] [Indexed: 10/19/2024]
Abstract
There is increasing interest in ultrasound-guided ablation treatments for thyroid diseases, including benign and malignant ones. Surgeons, radiologists, and endocrinologists carry out these treatments, and various organizations within these specialties have recently released multiple international consensus statements and clinical practice standards. The aim of the present consensus statement is to provide guidance, cohesion, and standardization of best practices for thermal ablation procedures of thyroid nodules. The statement includes the indications for these procedures, preprocedural evaluations, technical aspects of the procedures, posttreatment care, follow-up, complications, and training recommendations. This document was written by a panel of specialists from the Brazilian Society of Interventional Radiology and Endovascular Surgery (SOBRICE), the Brazilian Society of Head and Neck Surgery (SBCCP), and the Brazilian Society of Endocrinology and Metabolism (SBEM). The statement does not aim to provide criteria for assessing the capability of specialists to perform the procedure. Instead, it aims to promote the standardization of best practices to reduce potential adverse outcomes. Additionally, it strives to enhance the delivery of high-quality care and the widespread adoption of these technologies on a national level. The recommendations collectively serve as a guidebook for applying best practices in thyroid ablation.
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Affiliation(s)
- Gustavo Philippi de Los Santos
- Hospital Universitário Universidade Federal de Santa Catarina FlorianópolisSC Brasil Hospital Universitário da Universidade Federal de Santa Catarina, Florianópolis, SC, Brasil
| | - Marco Aurélio Vamondes Kulcsar
- Sociedade Brasileira de Cirurgia de Cabeça e Pescoço São PauloSP Brasil Sociedade Brasileira de Cirurgia de Cabeça e Pescoço, São Paulo, SP, Brasil
- Faculdade Israelita de Ciências da Saúde Albert Einstein São PauloSP Brasil Faculdade Israelita de Ciências da Saúde Albert Einstein,São Paulo, SP, Brasil
| | - Fabio de Aquino Capelli
- Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo São PauloSP Brasil Serviço de Cirurgia de Cabeça e Pescoço, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
| | - Jose Higino Steck
- Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo São PauloSP Brasil Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
- Divisão de Otorrinolaringologia Universidade Estadual de Campinas CampinasSP Brasil Divisão de Otorrinolaringologia, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | | | - Cleo Otaviano Mesa
- Universidade Federal da Paraíba João PessoaPB Brasil Universidade Federal da Paraíba, João Pessoa, PB, Brasil
- Serviço de Endocrinologia e Metabologia Hospital de Clínicas Universidade Federal do Paraná CuritibaPR Brasil Serviço de Endocrinologia e Metabologia, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brasil
| | - Joaquim Mauricio da Motta-Leal-Filho
- Faculdade de Medicina Pontifícia Universidade Católica do Paraná CuritibaPR Brasil Faculdade de Medicina, Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brasil
- Departamento de Radiologia Instituto do Câncer do Estado de São Paulo São PauloSP Brasil Departamento de Radiologia, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | - Rafael Selbach Scheffel
- Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo São PauloSP Brasil Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
- Serviço de Tireoide Hospital de Clínicas de Porto Alegre Porto AlegreRS Brasil Serviço de Tireoide, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brasil
| | - Fernanda Vaisman
- Departamento de Farmacologia Universidade Federal do Rio Grande do Sul Porto AlegreRS Brasil Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
- Instituto Nacional do Câncer Rio de JaneiroRJ Brasil Instituto Nacional do Câncer (INCA), Rio de Janeiro, RJ, Brasil
| | - Guilherme Lopes Pinheiro Martins
- Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo São PauloSP Brasil Serviço de Cirurgia de Cabeça e Pescoço, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
- Universidade Federal do Rio de Janeiro Rio de JaneiroRJ Brasil Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
- Hospital Sírio-Libanês São PauloSP Brasil Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Denis Szejnfeld
- Hospital Samaritano São PauloSP Brasil Hospital Samaritano, São Paulo, SP, Brasil
| | - Mauricio Kauark Amoedo
- Departamento de Radiologia Intervencionista Universidade Federal de São Paulo São PauloSP Brasil Departamento de Radiologia Intervencionista, Universidade Federal de São Paulo, São Paulo, SP, Brasil
- Radioclínica SalvadorBA Brasil Radioclínica, Salvador, BA, Brasil
- Hospital Santa Izabel SalvadorBA Brasil Hospital Santa Izabel, Salvador, BA, Brasil
- Santa Casa da Bahia SalvadorBA Brasil Santa Casa da Bahia, Salvador, BA, Brasil
- Hospital da Bahia SalvadorBA Brasil Hospital da Bahia, Salvador, BA, Brasil
| | - Marcos Roberto de Menezes
- Departamento de Oncologia Sociedade Brasileira de Radiologia Intervencionista e Cirurgia Endovascular São PauloSP Brasil Departamento de Oncologia, Sociedade Brasileira de Radiologia Intervencionista e Cirurgia Endovascular, São Paulo, SP, Brasil
- Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo São PauloSP Brasil Centro de Intervenção Guiada por Imagem, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
| | - Antonio Rahal
- Centro de Intervenção Guiada por Imagem Hospital Sírio-Libanês São PauloSP Brasil Centro de Intervenção Guiada por Imagem, Hospital Sírio-Libanês, São Paulo, SP, Brasil
- Área do Núcleo de Imagem e de Intervenção em Tireoide Hospital Israelita Albert Einstein São PauloSP Brasil Área do Núcleo de Imagem e de Intervenção em Tireoide, Hospital Israelita Albert Einstein, São Paulo, SP, Brasil
| | - Leandro Luongo Matos
- Faculdade Israelita de Ciências da Saúde Albert Einstein São PauloSP Brasil Faculdade Israelita de Ciências da Saúde Albert Einstein,São Paulo, SP, Brasil
- Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo São PauloSP Brasil Serviço de Cirurgia de Cabeça e Pescoço, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
- Sociedade Paulista de Radiologia São PauloSP Brasil Radiologia Intervencionista, Sociedade Paulista de Radiologia, São Paulo, SP, Brasil
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Frenkel N, Poghosyan S, van Wijnbergen JW, Rinkes IB, Kranenburg O, Hagendoorn J. Differential cytokine and chemokine expression after ablation vs. resection in colorectal cancer liver metastasis. Surg Open Sci 2024; 18:29-34. [PMID: 38318321 PMCID: PMC10838949 DOI: 10.1016/j.sopen.2024.01.005] [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: 08/01/2023] [Revised: 11/23/2023] [Accepted: 01/10/2024] [Indexed: 02/07/2024] Open
Abstract
Background Surgical resection remains the main curative treatment for colorectal liver metastases (CRLM). Radiofrequency ablation (RFA) is increasingly employed for small, deep lying or otherwise inoperable lesions. However, RFA can induce pro-tumorigenic effects on residual tumor cells, hereby possibly promoting tumor recurrence. Contrastingly, post-RFA tumor debris as an antigen source can also generate anti-cancer immune responses. Utilizing this, current studies on combining RFA with immune therapy appear promising. Here, in an attempt to shed light on this controversy, cytokines involved in inflammation, (lymph)angiogenesis, immune cell recruitment and tumor cell invasion were investigated post-RFA versus post-resection in CRLM patients. Methods Cytokine and chemokine serum levels pre-operation, 4 h and 24 h post-operation were analyzed in CRLM patients undergoing RFA (n = 8) or partial hepatectomy (n = 9) using Multiplex immunoassays. Statistical analyses were performed between as well as within individual intervention groups. Results Post-RFA, significantly increased levels of acute phase proteins SAA1 and S100A8, IL-6, IL-1Ra, MIP3b (CCL19) and MMP9 were observed along with decreases in Fibronectin, MCP-1 (CCL2), and Tie-2. Post-resection, increased levels of PDGFbb, I309 (CCL1), Apelin, MIF, IL-1b and TNFα were seen. All p-values <0.05. Conclusion Pro-inflammatory responses mediated by different cytokines were seen after both RFA and resection, possibly influencing residual tumor cells and tumor recurrence. As both ablation and resection trigger inflammation and immune cell recruitment (albeit via distinct mechanisms), these data suggest that further research may explore combining immune therapy with not only RFA but also resection. Key message Analysis of patients' serum after radiofrequency ablation versus resection of colorectal liver metastases (CRLM) showed that these interventions trigger inflammation and immune cell recruitment, via different cyto- and chemokine pathways. This suggests a possible future strategy of combining immune therapy with not only ablative techniques but also with resection of CRLM.
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Affiliation(s)
| | | | - Jan Willem van Wijnbergen
- Laboratory for Translational Oncology, University Medical Center Utrecht and Utrecht University, Heidelberglaan 100, 3584CX Utrecht, the Netherlands
| | - Inne Borel Rinkes
- Laboratory for Translational Oncology, University Medical Center Utrecht and Utrecht University, Heidelberglaan 100, 3584CX Utrecht, the Netherlands
| | - Onno Kranenburg
- Laboratory for Translational Oncology, University Medical Center Utrecht and Utrecht University, Heidelberglaan 100, 3584CX Utrecht, the Netherlands
| | - Jeroen Hagendoorn
- Laboratory for Translational Oncology, University Medical Center Utrecht and Utrecht University, Heidelberglaan 100, 3584CX Utrecht, the Netherlands
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9
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Pastori C, Nafie EHO, Wagh MS, Mammarappallil JG, Neal RE. Pulsed Electric Field Ablation versus Radiofrequency Thermal Ablation in Murine Breast Cancer Models: Anticancer Immune Stimulation, Tumor Response, and Abscopal Effects. J Vasc Interv Radiol 2024; 35:442-451.e7. [PMID: 38042523 DOI: 10.1016/j.jvir.2023.11.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 11/14/2023] [Accepted: 11/22/2023] [Indexed: 12/04/2023] Open
Abstract
PURPOSE To compare the immune response and survival after size-matched radiofrequency (RF) ablation and a proprietary form of pulsed electric field (PEF) ablation in murine tumors. MATERIAL AND METHODS Orthotopically inoculated EMT6 or 4T1 murine tumors received sham, RF ablation, or PEF ablation. 4T1 tumor ablations included subgroups with intraperitoneal checkpoint inhibition immunotherapy (αPD-1). Blood was collected for cytokine profiling and flow cytometry. Tumor size was measured and survival was monitored. Tumor samples were processed for histology, immunohistochemistry, flow cytometry, and cytokine profiling. Lungs were collected from 4T1-bearing mice for hematoxylin and eosin histology to assess metastatic spread and abscopal effect induced by ablation. RESULTS PEF elicited distinct immunomodulatory effects, with clear differences in serum and tumor cytokine profiles compared with RF ablation, including intratumoral downregulation of vascular endothelial growth factor, hypoxia-inducible factor 1α, c-MET, interleukin-10, Ki67, and tumor necrosis factor-α (all P < .05). PEF increased innate immune activation, with enhanced recruitment of dendritic cells, M1 macrophages, and natural killer cells coupled with a reduction in M2 macrophages and myeloid-derived suppressor cells (all P < .05). Concurrently, PEF strengthened adaptive immunity compared with RF ablation, characterized by increased antigen-specific T cells and decreased regulatory T cells (all P < .05). PEF stalled tumor growth and increased survival at the end of the study (≥4× versus RFA). Finally, PEF promoted an abscopal effect of clearing metastases in the lungs, which was stronger in combination with αPD-1 than with PEF alone. CONCLUSIONS The proprietary form of PEF used in this study evoked a preferential immunostimulatory profile versus RF ablation thermal ablation in mice, with implications for enhancing the therapeutic effectiveness of checkpoint inhibition immunotherapy for immunotherapy-unresponsive tumors.
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Affiliation(s)
- Chiara Pastori
- Department of Research, Galvanize Therapeutics, Redwood City, California
| | - Ebtesam H O Nafie
- Department of Research, Galvanize Therapeutics, Redwood City, California
| | - Mukta S Wagh
- Department of Research, Galvanize Therapeutics, Redwood City, California
| | | | - Robert E Neal
- Department of Research, Galvanize Therapeutics, Redwood City, California.
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10
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Kuo CY, Tsai CH, Wu JK, Cheng SP. Sublethal thermal stress promotes migration and invasion of thyroid cancer cells. PLoS One 2024; 19:e0298903. [PMID: 38394093 PMCID: PMC10889624 DOI: 10.1371/journal.pone.0298903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 01/31/2024] [Indexed: 02/25/2024] Open
Abstract
OBJECTIVE Radiofrequency ablation is a viable option in the treatment of benign thyroid nodules. Some reports suggest that thermal ablation may also be safe for the management of low-risk thyroid cancer. In this study, we applied transient heat treatment to thyroid cancer cells to mimic clinical scenarios in which insufficient ablation leads to incomplete eradication of thyroid cancer. METHODS Differentiated thyroid cancer cell lines B-CPAP, TPC-1, and FTC-133 were subjected to heat treatment at different temperatures for 10 min. Effects on cell growth, clonogenicity, wound healing assay, and Transwell invasion were determined. RESULTS Heat treatment at 45°C or higher reduced cell growth, whereas viability of thyroid cancer cells was not changed after heat treatment at 37, 40, or 42°C. Heat treatment at 40°C increased the number of colony formations by 16% to 39%. Additionally, transient heat treatment at 40°C resulted in a 1.75-fold to 2.56-fold higher migratory activity than treatment at 37°C. Invasive capacity was increased after heat treatment, ranging from 115% to 126%. Expression of several epithelial-mesenchymal transition markers, including ZEB1, N-cadherin, and MMP2, was upregulated following heat treatment at 40°C. CONCLUSION We for the first time demonstrate that sublethal thermal stress may increase clonogenicity, migration, and invasion of thyroid cancer cells.
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Affiliation(s)
- Chi-Yu Kuo
- Department of Surgery, MacKay Memorial Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, MacKay Medical College, New Taipei City, Taiwan
| | - Chung-Hsin Tsai
- Department of Surgery, MacKay Memorial Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, MacKay Medical College, New Taipei City, Taiwan
| | - Jun Kui Wu
- Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan
| | - Shih-Ping Cheng
- Department of Surgery, MacKay Memorial Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, MacKay Medical College, New Taipei City, Taiwan
- Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan
- Institute of Biomedical Sciences, MacKay Medical College, New Taipei City, Taiwan
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11
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Mandt T, Bangar A, Sauceda C, Das M, Moderbacher C, Ghani M, Webster N, Newton I. Stimulating Antitumoral Immunity by Percutaneous Cryoablation and Combination Immunoadjuvant Therapy in a Murine Model of Hepatocellular Carcinoma. J Vasc Interv Radiol 2023; 34:1516-1527.e6. [PMID: 37178816 PMCID: PMC10852103 DOI: 10.1016/j.jvir.2023.05.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 04/18/2023] [Accepted: 05/04/2023] [Indexed: 05/15/2023] Open
Abstract
PURPOSE To test the hypothesis that antitumoral immunity can be induced after cryoablation (cryo) of hepatocellular carcinoma (HCC) through coadministration of the immunostimulant CpG and an immune checkpoint (programmed cell death 1 [PD-1]) inhibitor. MATERIALS AND METHODS Sixty-three immunocompetent C57BL/6J mice were generated with 2 orthotopic HCC tumor foci: 1 for treatment and 1 to observe for antitumoral immunity. Tumors were treated with incomplete cryo alone or intratumoral CpG and/or a PD-1 inhibitor. The primary endpoint was death or when the following criteria for sacrifice were met: tumor > 1 cm (determined using ultrasound) or moribund state. Antitumoral immunity was assessed using flow cytometry and histology (tumor and liver) as well as enzyme-linked immunosorbent assay (serum). Analysis of variance was used for statistical comparisons. RESULTS At 1 week, the nonablated satellite tumor growth was reduced by 1.9-fold (P = .047) in the cryo + CpG group and by 2.8-fold (P = .007) in the cryo + CpG + PD-1 group compared with that in the cryo group. Compared with cryo alone, the time to tumor progression to endpoints was also prolonged for cryo + CpG + PD-1 and cryo + CpG mice, with log-rank hazard ratios of 0.42 (P = .031) and 0.27 (P < .001), respectively. Flow cytometry and histology showed increased cytotoxic T-cell infiltration (P = .002) and serum levels of the proinflammatory cytokine interferon-γ (P = .015) in tumors and serum of cryo + CpG mice compared with those in tumors and serum of mice treated with cryo alone. High serum levels of the anti-inflammatory cytokine tumor growth factor-β and the proangiogenesis chemokine C-X-C motif chemokine ligand 1 were correlated with a shorter time to endpoints and faster tumor growth. CONCLUSIONS Cryo combined with the immunostimulant CpG promoted cytotoxic T-cell infiltration into tumors, slowed tumor growth, and prolonged the time to progression to endpoints in an aggressive murine HCC model.
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Affiliation(s)
- Tyler Mandt
- Health Department of Radiology, University of California San Diego, San Diego
| | - Amandip Bangar
- Health Department of Radiology, University of California San Diego, San Diego
| | - Consuelo Sauceda
- Health Department of Radiology, University of California San Diego, San Diego
| | - Manasi Das
- Health Department of Radiology, University of California San Diego, San Diego
| | | | - Mansur Ghani
- Health Department of Radiology, University of California San Diego, San Diego
| | - Nicholas Webster
- San Diego Veteran's Affairs, University of California San Diego, San Diego
| | - Isabel Newton
- San Diego Veteran's Affairs, University of California San Diego, San Diego.
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12
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Brandi N, Renzulli M. The Synergistic Effect of Interventional Locoregional Treatments and Immunotherapy for the Treatment of Hepatocellular Carcinoma. Int J Mol Sci 2023; 24:ijms24108598. [PMID: 37239941 DOI: 10.3390/ijms24108598] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 05/05/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
Immunotherapy has remarkably revolutionized the management of advanced HCC and prompted clinical trials, with therapeutic agents being used to selectively target immune cells rather than cancer cells. Currently, there is great interest in the possibility of combining locoregional treatments with immunotherapy for HCC, as this combination is emerging as an effective and synergistic tool for enhancing immunity. On the one hand, immunotherapy could amplify and prolong the antitumoral immune response of locoregional treatments, improving patients' outcomes and reducing recurrence rates. On the other hand, locoregional therapies have been shown to positively alter the tumor immune microenvironment and could therefore enhance the efficacy of immunotherapy. Despite the encouraging results, many unanswered questions still remain, including which immunotherapy and locoregional treatment can guarantee the best survival and clinical outcomes; the most effective timing and sequence to obtain the most effective therapeutic response; and which biological and/or genetic biomarkers can be used to identify patients likely to benefit from this combined approach. Based on the current reported evidence and ongoing trials, the present review summarizes the current application of immunotherapy in combination with locoregional therapies for the treatment of HCC, and provides a critical evaluation of the current status and future directions.
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Affiliation(s)
- Nicolò Brandi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
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13
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How Biology Guides the Combination of Locoregional Interventional Therapies and Immunotherapy for Hepatocellular Carcinoma: Cytokines and Their Roles. Cancers (Basel) 2023; 15:cancers15041324. [PMID: 36831664 PMCID: PMC9954096 DOI: 10.3390/cancers15041324] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 02/13/2023] [Accepted: 02/14/2023] [Indexed: 02/22/2023] Open
Abstract
As most patients with hepatocellular carcinoma (HCC) are diagnosed at the intermediate or advanced stage and are no longer eligible for curative treatment, the overall survival rate of HCC remains unsatisfactory. Locoregional interventional therapies (LITs), and immune checkpoint inhibitor (ICI)-based immunotherapy, focus on treating HCC, but the efficacy of their individual application is limited. Therefore, the purpose of this review was to discuss the biological roles of cytokines and their therapeutic potential in the combination therapy of LITs and ICI-based immunotherapy. The two common techniques of LITs are ablative and transarterial therapies. Whether LITs are complete or incomplete can largely affect the antitumor immune response and tumor progression. Cytokines that induce both local and systemic responses to LITs, including interferons, interleukins, chemokines, TNF-α, TGF-β, VEGF, and HGF, and their roles are discussed in detail. In addition, specific cytokines that can be used as therapeutic targets to reduce immune-related adverse events (irAEs) are introduced. Overall, incomplete LITs in a tumor, combined with specific cytokines, are thought to be effective at improving the therapeutic efficacy and reducing treatment-induced irAEs, and represent a new hope for managing unresectable HCC.
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14
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Zhou Y, Liu X, Zhang W, Xu Y, Zhang Q, Xiong S, Tang H, Luo B. HMGB1 released from dead tumor cells after insufficient radiofrequency ablation promotes progression of HCC residual tumor via ERK1/2 pathway. Int J Hyperthermia 2023; 40:2174709. [PMID: 36755436 DOI: 10.1080/02656736.2023.2174709] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2023] Open
Abstract
BACKGROUND Radiofrequency ablation (RFA) is a first-line treatment for early-stage hepatocellular carcinoma (HCC). However, the recurrence after RFA remains an urgent challenge. Current studies have shown that residual tumor after RFA is an important cause of recurrence. OBJECTIVE We hypothesized that the products of dead tumor cells after RFA have direct effects on the development of residual tumors. Further, we investigated the underlying mechanisms. METHODS The proliferation and invasion ability of HepG2 and Huh7 cells were assessed using CCK-8, colony formation, EdU, transwell invasion and migration assay. Immunofluorescence and western blotting were used to show HMGB1 released from dead tumor cells. The levels of MMP2, MMP9, CyclinE1 and pERK1/2 were determined using western blotting. Finally, in vivo validation was performed in BALB/c nude mice xenograft tumor models. RESULTS The products of dead tumor cells after thermal treatment can promote the proliferation and invasion of residual HCC cells. Dead tumor cells could release high-mobility group box 1 (HMGB1) after thermal treatment. Similar to the products of dead tumor cells, the recombinant protein of HMGB1 can promote the proliferation and invasion of residual HCC cells. Moreover, HMGB1 could bind to receptor of advanced glycation end-products. Then, it activated the ERK1/2 pathway and significantly upregulated the expressions of MMP2, MMP9, and CyclinE1. CONCLUSION Our study reveals that HMGB1 released by dead tumor cells after thermal treatment can promote the proliferation and invasion of residual HCC cells. Hence, the HMGB1/RAGE/ERK1/2 pathway is a potential target for improving the prognosis of HCC after radiofrequency ablation.
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Affiliation(s)
- Yingshi Zhou
- Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaodi Liu
- Laboratory of Ultrasound Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Wenyue Zhang
- Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yanni Xu
- Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qi Zhang
- Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shiyu Xiong
- Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Haifeng Tang
- Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Baoming Luo
- Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
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15
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Chen S, Zeng X, Su T, Xiao H, Lin M, Peng Z, Peng S, Kuang M. Combinatory local ablation and immunotherapies for hepatocellular carcinoma: Rationale, efficacy, and perspective. Front Immunol 2022; 13:1033000. [PMID: 36505437 PMCID: PMC9726793 DOI: 10.3389/fimmu.2022.1033000] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 10/25/2022] [Indexed: 11/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. Local ablation, such as radiofrequency ablation, microwave ablation, cryoablation and irreversible electroporation, etc., are well established in elimination and control of HCC. However, high recurrence rate after local ablation remains the biggest challenge for HCC management. Novel and effective therapeutic strategies to improve long-term survival are urgently needed. Accumulating studies have reported the role of ablation in modulating the tumor signaling pathway and the immune microenvironment to both eliminate residual/metastatic tumor and promote tumor progression. Ablation has been shown to elicit tumor-specific immune responses by inducing massive cell death and releasing tumor antigen. Immunotherapies that unleash the immune system have the potential to enhance the anti-tumor immunity induced by ablation. Multiple combinatory strategies have been explored in preclinical and clinical studies. In this review, we comprehensively summarize the latest progress on different mechanisms underlying the effects of ablation on tumor cells and tumor microenvironment. We further analyze the clinical trials testing the combination of ablation and immunotherapies, and discuss the possible role of immunomodulation to boost the anti-tumor effects of ablation and prevent HCC recurrence.
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Affiliation(s)
- Shuling Chen
- Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xuezhen Zeng
- Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China,Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Tianhong Su
- Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Han Xiao
- Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Manxia Lin
- Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhenwei Peng
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Sui Peng
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Ming Kuang
- Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China,Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China,*Correspondence: Ming Kuang,
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16
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Wu S, Li Z, Yao C, Dong S, Gao J, Ke S, Zhu R, Huang S, Wang S, Xu L, Ye C, Kong J, Sun W. Progression of hepatocellular carcinoma after radiofrequency ablation: Current status of research. Front Oncol 2022; 12:1032746. [PMID: 36483051 PMCID: PMC9723167 DOI: 10.3389/fonc.2022.1032746] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 11/04/2022] [Indexed: 05/27/2024] Open
Abstract
Hepatocellular carcinoma (HCC) remains an important disease for health care systems in view of its high morbidity, mortality, and increasing incidence worldwide. Radiofrequency ablation (RFA) is preferred to surgery as a local treatment for HCC because it is safer, less traumatic, less painful, better tolerated, causes fewer adverse reactions, and allows more rapid postoperative recovery. The biggest shortcoming of RFA when used to treat HCC is the high incidence of residual tumor, which is often attributed to the vascular thermal deposition effect, the wide infiltration zone of peripheral venules, and the distance between satellite foci and the main focus of the cancer. Recurrence and progression of the residual tumor is the most important determinant of the prognosis. Therefore, it is important to be aware of the risk of recurrence and to improve the efficacy of RFA. This review summarizes the relevant literature and the possible mechanisms involved in progression of HCC after RFA. Current studies have demonstrated that multimodal treatments which RFA combined with other anti-cancer approaches can prevent progression of HCC after RFA.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Jian Kong
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, China
| | - Wenbing Sun
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, China
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17
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Dong S, Li Z, Kong J, Wu S, Gao J, Sun W. Arsenic trioxide inhibits angiogenesis of hepatocellular carcinoma after insufficient radiofrequency ablation via blocking paracrine angiopoietin-1 and angiopoietin-2. Int J Hyperthermia 2022; 39:888-896. [PMID: 35848416 DOI: 10.1080/02656736.2022.2093995] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
Abstract
OBJECTIVES Angiogenesis occurs during tumor progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA). Arsenic trioxide (ATO) shows promising therapeutic potential in advanced HCC. Whether ATO regulates angiogenesis and can be used to prevent tumor progression in HCC after insufficient RFA is still unknown. METHODS Insufficient RFA was simulated using a water bath. MTT assay and tube formation assay were used to evaluate the effects of ATO on viability and proangiogenic abilities of SMMC7721 and HepG2 cells after insufficient RFA in vitro. The molecular changes with the treatment of ATO were evaluated through Western blot. An ectopic nude mice model was used to evaluate the effect of ATO on the tumor of SMMC7721 cells in vivo after insufficient RFA. RESULTS In this study, HepG2 and SMMC7721 cells after insufficient RFA (named HepG2-H and SMMC7721-H, respectively) showed higher proliferation than the untreated cells and promoted tube formation of endothelial cells in a paracrine manner. ATO eliminated the difference in proliferation between untreated and RFA-treated cells and suppressed angiogenesis induced by HCC cells after insufficient RFA through the Ang-1 (angiopoietin-1)/Ang-2 (angiopoietin-2)/Tie2 pathway. Hif-1α overexpression abolished the inhibitory effect of ATO on angiogenesis in HCC after insufficient RFA. ATO inhibited tumor growth and angiogenesis in HCC after insufficient RFA. CONCLUSIONS Our results demonstrate that ATO blocks the paracrine signaling of Ang-1 and Ang-2 by inhibiting p-Akt/Hif-1α and further suppresses the angiogenesis of HCC after insufficient RFA.
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Affiliation(s)
- Shuying Dong
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China
| | - Zhuxin Li
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China
| | - Jian Kong
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China
| | - Shilun Wu
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China
| | - Jun Gao
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China
| | - Wenbing Sun
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China
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Ding WZ, Liu S, Liu F, Cheng Z, Yu X, Han ZY, Yu J, Liang P. Are all local tumour progressions of HCC related to thermal ablation? A study of the causes and classification of local tumour progression. Eur Radiol 2022; 32:8518-8526. [PMID: 35704110 DOI: 10.1007/s00330-022-08913-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 05/26/2022] [Accepted: 05/30/2022] [Indexed: 11/30/2022]
Abstract
OBJECTIVES Local tumour progression (LTP) is believed to be a negative consequence of imperfect thermal ablation, but we wondered if all LTP is truly due to imperfect ablation. METHODS This study included 185 LTPs occurring within 1 cm of the ablation zone (AZ) after clinical curative thermal ablation for ≤ 5 cm hepatocellular carcinoma between 2010 and 2019. The AZ was divided into 8 quadrants by coronal, sagittal, and horizontal planes. Two methods, visual assessment through pre- and post-MRI (VA) and tumour mapping for 3D visualisation pre- and post-MRI fusion (MF), were used to assess which AZ quadrant included the shortest ablation margin (AM) by three doctors. LTP subclassification was based on whether LTP contacted the AZ margin (contacted LTP and dissociated-type LTP) and occurrence at different time points (12, 18, and 24 months). RESULTS Fleiss's Kappa of VA and MF was 0.769 and 0.886, respectively. Cohen's Kappa coefficient between VA and MF was 0.830. For all LTPs, 98/185 (53.0%) occurred in the shortest AM quadrant, which showed a significant central tendency (p < 0.001). However, only 8/51 (15.7%) dissociated - type LTPs and 6/39 (15.4%) LTPs after 24 months occurred in the shortest AM quadrant, which showed no evenly distributed difference (p = 0.360 and 0.303). CONCLUSIONS MF is an accurate and convenient method to assess the shortest AM quadrant. LTP is a central tendency in the shortest AM quadrant, but dissociated-type and LTPs after 24 months are not, and these LTP types could be considered nonablation-related LTPs. KEY POINTS • LTPs are not evenly distributed around the AZ. More than half of LTPs occur in the shortest AM quadrant. • Subgroup analysis showed that the occurrence of contacted-type LTPs (tumour margin has direct contact with the AZ) within 24 months after ablation indeed had a high proportion in the shortest AM quadrant, and they could be called ablation-related LTPs. • However, the dissociated-type LTPs (tumour margin adjacent to but not in contact with the AZ) or LTPs occurring beyond 24 months after ablation were evenly distributed around the AZ, and they could be called nonablation-related LTPs.
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Affiliation(s)
- Wen-Zhen Ding
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
| | - Sisi Liu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
| | - Fangyi Liu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
| | - Zhigang Cheng
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
| | - Xiaoling Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
| | - Zhi-Yu Han
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
| | - Jie Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China.
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19
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Comparison of the Efficacy Among Transcatheter Arterial Chemoembolization (TACE)-Radiofrequency Ablation Plus Apatinib, TACE Plus Apatinib, and TACE Alone for Hepatocellular Carcinoma: A Retrospective Study. Cardiovasc Intervent Radiol 2022; 45:780-790. [PMID: 35410405 DOI: 10.1007/s00270-022-03141-y] [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: 09/09/2021] [Accepted: 03/28/2022] [Indexed: 11/02/2022]
Abstract
BACKGROUND This study aimed to investigate the efficacy and safety of apatinib plus transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) in the therapy of hepatocellular carcinoma (HCC) patients. METHODS From December 2015 to June 2018, 175 eligible participants were included in our research. Twenty-four patients who received apatinib plus TACE and RFA were categorized as the TACE + RFA-A group, 82 patients who received apatinib plus TACE were categorized as the TACE-A group, and 69 patients who received TACE alone were categorized as the TACE group. Treatment complications, treatment response, overall survival (OS), and time to progression (TTP) were recorded. Survival analyses were compared. Univariate and multivariate Cox analyses were conducted to investigate the predictive factors for OS and TTP. A subgroup analysis was carried out. RESULTS The median TTP was 8.0 months (95% CI 6.7-9.3) in the TACE + RFA-A, which was longer than the TACE-A group (6.0 months, 95% CI 4.8-7.2) and TACE group (3.0 months, 95% CI 2.3-3.7); the difference was statistically significant (P < 0.001). The median OS was 23.0 months (95% CI 12.6-33.4) in the TACE + RFA-A group, 18.0 months (95% CI 16.2-19.8) in the TACE-A group, and 8.0 months (95% CI 5.3-10.7) in the TACE group; the difference was statistically significant (P < 0.001). The objective response rate (ORR) was higher in TACE + RFA-A t group (M1, 70.8% vs 65.9% vs. 46.4%, P = 0.023; M3, 58.3% vs. 53.7% vs. 26.1%, P = 0.001). Multivariate Cox analysis demonstrated that treatment strategy and tumor size were independent prognostic factors for the OS and TTP, whereas the Child-Pugh stage was predictive factor of OS. No treatment-related death was observed. The toxicity was comparable between the two groups. CONCLUSION TACE combined with RFA plus apatinib is a safe three-modality treatment for the intermediate or advanced HCC, and it demonstrated better efficacy than TACE plus apatinib or TACE alone.
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20
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Guo Y, Ren Y, Dong X, Kan X, Zheng C. An Overview of Hepatocellular Carcinoma After Insufficient Radiofrequency Ablation. J Hepatocell Carcinoma 2022; 9:343-355. [PMID: 35502292 PMCID: PMC9056053 DOI: 10.2147/jhc.s358539] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 04/04/2022] [Indexed: 12/13/2022] Open
Abstract
Radiofrequency ablation (RFA) is a commonly used treatment for hepatocellular carcinoma (HCC), however, various complex conditions in clinical practice may lead to insufficient radiofrequency ablation (IRFA), allowing residual HCC to survive. In clinical practice and laboratory models, IRFA plays an important role in rapid tumor progression. Therefore, targeting the residual HCC and avoiding IRFA were worthwhile methods. A deeper understanding of IRFA is required; IRFA contributes to the improvement of proliferative activity, migration rates, and invasive capacity, and this may be due to the involvement of multiple complex processes or proteins, including epithelial mesenchymal transitions (EMTs), cancer stem cells (CSCs), autophagy, heat shock proteins (HSPs), changes of non-tumor cells and extracellular matrix, altered immune microenvironment, hypoxia-inducible factors (HIFs), growth factors, epigenetic alterations, and metabolic reprogramming. We focus on the processes of the above mechanisms and possible therapeutic approach, with a review of the literature. Additionally, we recapitulated the construction methods of various experimental models of IRFA (in vivo and in vitro).
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Affiliation(s)
- Yusheng Guo
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China
| | - Yanqiao Ren
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China
| | - Xiangjun Dong
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China
| | - Xuefeng Kan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China
- Correspondence: Chuansheng Zheng, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Tel/Fax +86-27-85726290, Email
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21
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Liu N, Jiang F, Ye M, Wang B, Ge D, Chang S. HuR confers IL-17a-induced migration and invasion of gastric cancer cells via upregulation of Snail translation. Cytokine 2022; 153:155830. [PMID: 35247650 DOI: 10.1016/j.cyto.2022.155830] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 02/07/2022] [Accepted: 02/08/2022] [Indexed: 02/07/2023]
Abstract
Human gastric cancer is a leading cause of cancer mortality in the world wide. We found that the expression of IL-17a was significantly increased in gastric cancer cells. Treatment with recombinant IL-17a (rIL-17a) can increase migration, invasion and epithelial to mesenchymal transition (EMT) of gastric cancer cells. Further, Snail, a key factor to regulate EMT, was significantly increased in rIL-17a-treated gastric cancer cells. While knockdown of Snail can abolish IL-17a-induced EMT of gastric cancer cells. Mechanistically, IL-17a can promote the translation efficiency of Snail, while had no effect on its mRNA expression or protein stability. Further, we found that IL-17a can increase the expression of HuR, which markedly promoted translation of Snail mRNA. While knockdown of HuR can reverse rIL-17a-induced expression of Snail and EMT of gastric cancer cells. Collectively, our data suggested that HuR confers IL-17a induced migration and invasion of gastric cancer cells via upregulation of Snail translation.
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Affiliation(s)
- Ning Liu
- Department of Gastrointestinal Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, Hainan Province, China
| | - Fan Jiang
- Center of Gerontology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, Hainan Province, China
| | - Mulin Ye
- Department of Gastrointestinal Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, Hainan Province, China
| | - Bangjie Wang
- Department of Gastrointestinal Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, Hainan Province, China
| | - Dongsheng Ge
- Department of Gastrointestinal Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, Hainan Province, China
| | - Shunwu Chang
- Department of Gastrointestinal Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, Hainan Province, China.
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22
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Li R, Tian Y, Zhu B, Wang Y, Dang R, Zhao L, Yang S, Li Y, Wen N. Graphene-containing metal-organic framework nanocomposites for enhanced microwave ablation of salivary adenoid cystic carcinoma. NANOSCALE ADVANCES 2022; 4:1308-1317. [PMID: 36133686 PMCID: PMC9419482 DOI: 10.1039/d1na00729g] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 01/15/2022] [Indexed: 06/16/2023]
Abstract
Salivary adenoid cystic carcinoma (SACC), one of the most common malignant tumors in the head and neck region, is characterized by high postoperative recurrence rate and poor prognosis. Microwave (MW) ablation possesses advantages in preserving SACC patients' facial aesthetics and oral function, but unfortunately, it suffers from low therapeutic efficacy due to the limited MW-thermal efficiency. Moreover, the insufficient thermal ablation may aggravate hypoxic state in tumors, which is deleterious to the treatment of residual tumors and aggressive tumors. Hence, MW ablation has been rarely applied in treating head and neck tumors in recent years. To minimize the unfavorable outcomes and maximize the therapeutic effects of MW ablation, a MW sensitizer coupled with a self-sufficient oxygen nanoagent was employed for the first time in MW ablation to treat head and neck tumors. We prepared a graphene-containing metal-organic framework (ZIF67@Gr-PEG), which exhibited excellent MW thermal conversion ability endowed by the incorporated Gr and showed in situ oxygen generation capacity derived from the ZIF67 matrix. In an animal experiment, ZIF67@Gr-PEG-based MW ablation with a temperature up to 66.1 °C exhibited a high tumor ablation rate. More importantly, insufficient MW ablation-induced high expressions of HIF-1α and VEGF were observed in our experiment, whereas the levels of tumor hypoxia and angiogenesis were efficiently decreased in MW ablation with the assistance of ZIF67@Gr-PEG nanocomposites (NCs). Notably, our strategy for MW ablation not only evidences the great potential of ZIF67@Gr-PEG but also promotes the translation of thermotherapeutic graphene from basic research to clinical practice.
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Affiliation(s)
- Ruozhen Li
- Medical School of Chinese PLA Beijing 100853 China
- Department of Stomatology, The First Medical Center, Chinese PLA General Hospital No. 28 Fuxing Road Beijing 100853 China
| | - Yaping Tian
- Birth Defects Prevention and Control Technology Research Center, Translational Medicine Research Center, Chinese PLA General Hospital 28 FuXing Road Beijing 100853 China
| | - Biao Zhu
- Department of Stomatology, The First Medical Center, Chinese PLA General Hospital No. 28 Fuxing Road Beijing 100853 China
| | - Yu Wang
- Department of Oncology, Air Force Medical Center, PLA No. 30 FuCheng Road, Haidian District Beijing 100142 China
| | - Ruijie Dang
- Department of Stomatology, The First Medical Center, Chinese PLA General Hospital No. 28 Fuxing Road Beijing 100853 China
| | - Lisheng Zhao
- Department of Stomatology, The First Medical Center, Chinese PLA General Hospital No. 28 Fuxing Road Beijing 100853 China
| | - Shuo Yang
- Department of Stomatology, The First Medical Center, Chinese PLA General Hospital No. 28 Fuxing Road Beijing 100853 China
| | - Yunxia Li
- Department of Stomatology, The First Medical Center, Chinese PLA General Hospital No. 28 Fuxing Road Beijing 100853 China
| | - Ning Wen
- Department of Stomatology, The First Medical Center, Chinese PLA General Hospital No. 28 Fuxing Road Beijing 100853 China
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23
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Chen X, Huang Y, Chen H, Chen Z, Chen J, Wang H, Li D, Su Z. Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression. J Nanobiotechnology 2022; 20:34. [PMID: 35033089 PMCID: PMC8760822 DOI: 10.1186/s12951-021-01161-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Accepted: 11/24/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Insufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied. RESULTS Our data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial-mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo. CONCLUSIONS This work provides a new paradigm for the treatment of residual HCC after IRFA.
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Affiliation(s)
- Xuehua Chen
- Department of Ultrasound, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, Guangdong, China.,Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, Guangdong, China
| | - Yongquan Huang
- Department of Ultrasound, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, Guangdong, China.,Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, Guangdong, China
| | - Hui Chen
- Department of Ultrasound, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, Guangdong, China.,Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, Guangdong, China
| | - Ziman Chen
- Department of Ultrasound, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, Guangdong, China
| | - Jiaxin Chen
- Department of Ultrasound, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, Guangdong, China
| | - Hao Wang
- Fine Chemical Industry Research Institute, School of Chemistry, Sun Yat-sen University, Guangzhou, 510275, Guangdong, China.
| | - Dan Li
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, Guangdong, China.
| | - Zhongzhen Su
- Department of Ultrasound, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, Guangdong, China. .,Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, Guangdong, China.
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24
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Wang K, Wang C, Jiang H, Zhang Y, Lin W, Mo J, Jin C. Combination of Ablation and Immunotherapy for Hepatocellular Carcinoma: Where We Are and Where to Go. Front Immunol 2022; 12:792781. [PMID: 34975896 PMCID: PMC8714655 DOI: 10.3389/fimmu.2021.792781] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 11/25/2021] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and is increasing in incidence. Local ablative therapy plays a leading role in HCC treatment. Radiofrequency (RFA) is one of the first-line therapies for early local ablation. Other local ablation techniques (e.g., microwave ablation, cryoablation, irreversible electroporation, phototherapy.) have been extensively explored in clinical trials or cell/animal studies but have not yet been established as a standard treatment or applied clinically. On the one hand, single treatment may not meet the needs. On the other hand, ablative therapy can stimulate local and systemic immune effects. The combination strategy of immunotherapy and ablation is reasonable. In this review, we briefly summarized the current status and progress of ablation and immunotherapy for HCC. The immune effects of local ablation and the strategies of combination therapy, especially synergistic strategies based on biomedical materials, were discussed. This review is hoped to provide references for future researches on ablative immunotherapy to arrive to a promising new era of HCC treatment.
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Affiliation(s)
- Kunpeng Wang
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Cong Wang
- Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, China
| | - Hao Jiang
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Yaqiong Zhang
- Department of Clinical Laboratory, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Weidong Lin
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Jinggang Mo
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Chong Jin
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
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25
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Orloff LA, Noel JE, Stack BC, Russell MD, Angelos P, Baek JH, Brumund KT, Chiang FY, Cunnane MB, Davies L, Frasoldati A, Feng AY, Hegedüs L, Iwata AJ, Kandil E, Kuo J, Lombardi C, Lupo M, Maia AL, McIver B, Na DG, Novizio R, Papini E, Patel KN, Rangel L, Russell JO, Shin J, Shindo M, Shonka DC, Karcioglu AS, Sinclair C, Singer M, Spiezia S, Steck JH, Steward D, Tae K, Tolley N, Valcavi R, Tufano RP, Tuttle RM, Volpi E, Wu CW, Abdelhamid Ahmed AH, Randolph GW. Radiofrequency ablation and related ultrasound-guided ablation technologies for treatment of benign and malignant thyroid disease: An international multidisciplinary consensus statement of the American Head and Neck Society Endocrine Surgery Section with the Asia Pacific Society of Thyroid Surgery, Associazione Medici Endocrinologi, British Association of Endocrine and Thyroid Surgeons, European Thyroid Association, Italian Society of Endocrine Surgery Units, Korean Society of Thyroid Radiology, Latin American Thyroid Society, and Thyroid Nodules Therapies Association. Head Neck 2021; 44:633-660. [PMID: 34939714 DOI: 10.1002/hed.26960] [Citation(s) in RCA: 126] [Impact Index Per Article: 31.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 12/02/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The use of ultrasound-guided ablation procedures to treat both benign and malignant thyroid conditions is gaining increasing interest. This document has been developed as an international interdisciplinary evidence-based statement with a primary focus on radiofrequency ablation and is intended to serve as a manual for best practice application of ablation technologies. METHODS A comprehensive literature review was conducted to guide statement development and generation of best practice recommendations. Modified Delphi method was applied to assess whether statements met consensus among the entire author panel. RESULTS A review of the current state of ultrasound-guided ablation procedures for the treatment of benign and malignant thyroid conditions is presented. Eighteen best practice recommendations in topic areas of preprocedural evaluation, technique, postprocedural management, efficacy, potential complications, and implementation are provided. CONCLUSIONS As ultrasound-guided ablation procedures are increasingly utilized in benign and malignant thyroid disease, evidence-based and thoughtful application of best practices is warranted.
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Affiliation(s)
- Lisa A Orloff
- Department of Otolaryngology - Head & Neck Surgery, Stanford University School of Medicine, Stanford, California, USA
| | - Julia E Noel
- Department of Otolaryngology - Head & Neck Surgery, Stanford University School of Medicine, Stanford, California, USA
| | - Brendan C Stack
- Department of Otolaryngology - Head & Neck Surgery, Southern Illinois University School of Medicine, Springfield, Illinois, USA
| | - Marika D Russell
- Department of Otolaryngology - Head & Neck Surgery, San Francisco School of Medicine, University of California, San Francisco, California, USA
| | - Peter Angelos
- Department of Surgery, University of Chicago, Chicago, Illinois, USA
| | - Jung Hwan Baek
- Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Kevin T Brumund
- Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of California, San Diego, San Diego, California, USA
| | - Feng-Yu Chiang
- Department of Otolaryngology - Head and Neck Surgery, E-Da Hospital, School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Mary Beth Cunnane
- Department of Radiology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA
| | - Louise Davies
- The Section of Otolaryngology, The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA
| | - Andrea Frasoldati
- Department of Endocrinology and Metabolism, Arcispedale Santa Maria Nuova IRCCS-ASL, Reggio Emilia, Italy
| | - Anne Y Feng
- Department of Otolaryngology - Head and Neck Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Laszlo Hegedüs
- Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark
| | - Ayaka J Iwata
- Department of Otolaryngology - Head & Neck Surgery, Kaiser Permanente, Santa Clara, California, USA
| | - Emad Kandil
- Department of Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA
| | - Jennifer Kuo
- Department of Surgery, Columbia University Irving Medical Center, New York, New York, USA
| | - Celestino Lombardi
- Division of Endocrine and Metabolic Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Mark Lupo
- Thyroid & Endocrine Center of Florida, Sarasota, Florida, USA
| | - Ana Luiza Maia
- Unidade de Tireoide, Hospital de Clínicas de Porto Alegre, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Bryan McIver
- Department of Head and Neck-Endocrine Oncology, H. Lee Moffitt Cancer Center, Research Institute, Tampa, Florida, USA
| | - Dong Gyu Na
- Department of Radiology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, South Korea
| | | | - Enrico Papini
- Department of Endocrinology and Metabolism, Regina Apostolorum Hospital, Rome, Italy
| | - Kepal N Patel
- Department of Surgery, New York University, New York, New York, USA
| | - Leonardo Rangel
- Division of Otorhinolaryngology - Head and Neck Surgery, State University of Rio de Janeiro, Rio de Janiero, Brazil
| | - Jonathon O Russell
- Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jennifer Shin
- Department of Otolaryngology - Head and Neck Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Maisie Shindo
- Department of Otolaryngology - Head and Neck Surgery, Oregon Health and Science University, Portland, Oregon, USA
| | - David C Shonka
- Department of Otolaryngology - Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia, USA
| | - Amanda S Karcioglu
- Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, NorthShore University Health System, Evanston, Illinois, USA.,Clinician Educator, Pritzker School of Medicine, Chicago, Illinois, USA
| | - Catherine Sinclair
- Department of Otolaryngology - Head and Neck Surgery, Mount Sinai West Hospital, New York, New York, USA
| | - Michael Singer
- Department of Otolaryngology - Head and Neck Surgery, Henry Ford Health System, Detroit, Michigan, USA
| | - Stefano Spiezia
- Endocrine Surgery, Ospedale del Mare, ASL NA1 Centro, Naples, Italy
| | - Jose Higino Steck
- Department of Otorhinolaryngology - Head and Neck Surgery, University of Campinas, Campinas, Brazil
| | - David Steward
- Department of Otolaryngology - Head and Neck Surgery, University of Cincinnati, Cincinnati, Ohio, USA
| | - Kyung Tae
- Department of Otolaryngology - Head and Neck Surgery, College of Medicine, Hanyang University, Seoul, South Korea
| | - Neil Tolley
- Hammersmith Hospital, Imperial College NHS Healthcare Trust, London, UK
| | | | - Ralph P Tufano
- Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - R Michael Tuttle
- Endocrine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Erivelto Volpi
- Oncology Center, Oswaldo Cruz German Hospital, Sao Paulo, Brazil
| | - Che Wei Wu
- Department of Otolaryngology - Head and Neck Surgery, Kaohsiung Medical University Hospital, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Amr H Abdelhamid Ahmed
- Department of Otolaryngology - Head and Neck Surgery, Division of Thyroid and Parathyroid Endocrine Surgery, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA
| | - Gregory W Randolph
- Department of Otolaryngology - Head and Neck Surgery, Division of Thyroid and Parathyroid Endocrine Surgery, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA
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26
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Wang Z, Jiang L, Wang J, Chai Z, Xiong W. Morphine promotes angiogenesis by activating PI3K/Akt/HIF-1α pathway and upregulating VEGF in hepatocellular carcinoma. J Gastrointest Oncol 2021; 12:1761-1772. [PMID: 34532126 DOI: 10.21037/jgo-20-394] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Accepted: 05/16/2021] [Indexed: 12/24/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) is characterized by the neo-angiogenesis induced by tumor and adjacent cells. It is a leading cancer-related cause of death. Morphine has effects on angiogenesis with pro-angiogenic or anti-angiogenic phonotypes. This study explores the function of morphine on cancer cell growth, angiogenesis and the underlying mechanism in HCC. Methods Morphine was used to treat BEL-7402 or HCC-LM3 cells and human umbilical vein endothelial cells (HUVECs) were subsequently incubated in the conditioned media (CM) of HCC cells. The potential effects of cell proliferation, migration and tube formation of CM-treated HUVECs were investigated. Furthermore, the angiogenesis regulated factors of VEGFA, PIGF, ANG-1, ANG-2, FGF-1 and FGF-2 were assessed. siRNA and LY294002 were further used to explore the mechanism mediating the effects of morphine on the angiogenesis pathway. The neovascularization effect by morphine was confirmed through the use of human HCC cancer heterotopic mouse model in vivo. Results A significantly increased cell proliferation, migration, and tube formation effect of HUVECs induced by the CM from HCC cell lines treated with morphine was observed. More VEGFA secretion in CM from LM3 or BEL-7402 cell lines was found than the controls (P=0.03 and P=0.027, respectively). VEGFA knock-down could significantly reverse cell proliferation, migration and tube formation induced by the CM from HCC cell lines with morphine treatment. Further molecular experiments indicated that VEGFA secretion was activated by morphine potentially through the PI3K/Akt/HIF-1α pathway. Morphine-induced neovascularization was also observed by the IHC of CD31 and VEGFA. Conclusions Morphine promotes angiogenesis in hepatocellular carcinoma possibly through the activation of the PI3K/Akt/HIF-1α pathway and VEGFA stimulation.
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Affiliation(s)
- Zhiyao Wang
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Linghui Jiang
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jie Wang
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zongtao Chai
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wanxia Xiong
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China
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Li Z, Yu Q, Lu X, Liu Y, Ji B. Efficacy of radiofrequency ablation versus laparoscopic liver resection for hepatocellular carcinoma in China: a comprehensive meta-analysis. Wideochir Inne Tech Maloinwazyjne 2021; 16:455-471. [PMID: 34691297 PMCID: PMC8512513 DOI: 10.5114/wiitm.2021.105377] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 01/08/2021] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) has been the second leading cause of cancer-related death in China. Radiofrequency ablation is a relatively novel treatment that may improve the treatment of HCC. AIM To evaluate and compare the efficacy and safety of radiofrequency ablation (RFA) versus laparoscopic liver resection (LLR) in the treatment of HCC. MATERIAL AND METHODS We searched for relevant published studies in English (PubMed, Cochrane Library, EMBASE) and in Chinese (CBM, CNKI and Wanfang) from their inception until September 23, 2019. The quality of included studies was evaluated by the Newcastle-Ottawa Scale. RESULTS A total of 19 retrospective studies including 2038 patients were eligible for the meta-analysis. The results of the meta-analysis demonstrated that LLR was superior to RFA in terms of 3-year overall survival rate (OR = 0.62), 1 to 3-year disease-free survival rates (OR = 0.57; OR = 0.41, respectively) and local recurrence rates (OR = 2.71). CONCLUSIONS The meta-analysis demonstrates that laparoscopic liver resection should be preferred in tumors of size 3-5 cm, while for < 3 cm the long term results are equal.
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Affiliation(s)
- Zhijun Li
- Department of Hepatobiliary and Pancreatic Surgery, the First Hospital, Jilin University, Changchun, China
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Qiong Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Xiaozheng Lu
- Department of Hepatobiliary and Pancreatic Surgery, the First Hospital, Jilin University, Changchun, China
| | - Yahui Liu
- Department of Hepatobiliary and Pancreatic Surgery, the First Hospital, Jilin University, Changchun, China
| | - Bai Ji
- Department of Hepatobiliary and Pancreatic Surgery, the First Hospital, Jilin University, Changchun, China
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Kong J, Yao C, Dong S, Wu S, Xu Y, Li K, Ji L, Shen Q, Zhang Q, Zhan R, Cui H, Zhou C, Niu H, Li G, Sun W, Zheng L. ICAM-1 Activates Platelets and Promotes Endothelial Permeability through VE-Cadherin after Insufficient Radiofrequency Ablation. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2021; 8:2002228. [PMID: 33643788 PMCID: PMC7887603 DOI: 10.1002/advs.202002228] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Revised: 11/06/2020] [Indexed: 06/02/2023]
Abstract
Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) often leads to aggressive local recurrence and increased metastasis, and vascular integrity and platelets are implicated in tumor metastasis. However, whether interactions between endothelial cells and platelets induce endothelial permeability in HCC after insufficient RFA remains unclear. Here, significantly increased CD62P-positive platelets and sP-selectin in plasma are observed in HCC patients after RFA, and tumor-associated endothelial cells (TAECs) activate platelets and are susceptible to permeability after heat treatment in the presence of platelets in vitro. In addition, tumors exhibit enhanced vascular permeability after insufficient RFA in mice; heat treatment promotes platelets-induced endothelial permeability through vascular endothelial (VE)-cadherin, and ICAM-1 upregulation in TAECs after heat treatment results in platelet activation and increased endothelial permeability in vitro. Moreover, the binding interaction between upregulated ICAM-1 and Ezrin downregulates VE-cadherin expression. Furthermore, platelet depletion or ICAM-1 inhibition suppresses tumor growth and metastasis after insufficient RFA in an orthotopic tumor mouse model, and vascular permeability decreases in ICAM-1-/- mouse tumor after insufficient RFA. The findings suggest that ICAM-1 activates platelets and promotes endothelial permeability in TAECs through VE-cadherin after insufficient RFA, and anti-platelet and anti-ICAM-1 therapy can be used to prevent progression of HCC after insufficient RFA.
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Affiliation(s)
- Jian Kong
- Department of Hepatobiliary SurgeryBeijing Chaoyang HospitalCapital Medical UniversityBeijing100043P. R. China
| | - Changyu Yao
- Department of Hepatobiliary SurgeryBeijing Chaoyang HospitalCapital Medical UniversityBeijing100043P. R. China
| | - Shuying Dong
- Department of Hepatobiliary SurgeryBeijing Chaoyang HospitalCapital Medical UniversityBeijing100043P. R. China
| | - Shilun Wu
- Department of Hepatobiliary SurgeryBeijing Chaoyang HospitalCapital Medical UniversityBeijing100043P. R. China
| | - Yangkai Xu
- The Institute of Cardiovascular Sciences and Institute of Systems BiomedicineSchool of Basic Medical SciencesPeking University Health Science CenterKey Laboratory of Molecular Cardiovascular Sciences of Ministry of EducationKey Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of HealthBeijing Key Laboratory of Cardiovascular Receptors ResearchBeijing100191P. R. China
| | - Ke Li
- Beijing Tiantan HospitalChina National Clinical Research Center for Neurological DiseasesAdvanced Innovation Center for Human Brain ProtectionCapital Medical UniversityBeijing100050P. R. China
| | - Liang Ji
- The Institute of Cardiovascular Sciences and Institute of Systems BiomedicineSchool of Basic Medical SciencesPeking University Health Science CenterKey Laboratory of Molecular Cardiovascular Sciences of Ministry of EducationKey Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of HealthBeijing Key Laboratory of Cardiovascular Receptors ResearchBeijing100191P. R. China
| | - Qiang Shen
- The Institute of Cardiovascular Sciences and Institute of Systems BiomedicineSchool of Basic Medical SciencesPeking University Health Science CenterKey Laboratory of Molecular Cardiovascular Sciences of Ministry of EducationKey Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of HealthBeijing Key Laboratory of Cardiovascular Receptors ResearchBeijing100191P. R. China
| | - Qi Zhang
- The Institute of Cardiovascular Sciences and Institute of Systems BiomedicineSchool of Basic Medical SciencesPeking University Health Science CenterKey Laboratory of Molecular Cardiovascular Sciences of Ministry of EducationKey Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of HealthBeijing Key Laboratory of Cardiovascular Receptors ResearchBeijing100191P. R. China
| | - Rui Zhan
- The Institute of Cardiovascular Sciences and Institute of Systems BiomedicineSchool of Basic Medical SciencesPeking University Health Science CenterKey Laboratory of Molecular Cardiovascular Sciences of Ministry of EducationKey Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of HealthBeijing Key Laboratory of Cardiovascular Receptors ResearchBeijing100191P. R. China
| | - Hongtu Cui
- The Institute of Cardiovascular Sciences and Institute of Systems BiomedicineSchool of Basic Medical SciencesPeking University Health Science CenterKey Laboratory of Molecular Cardiovascular Sciences of Ministry of EducationKey Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of HealthBeijing Key Laboratory of Cardiovascular Receptors ResearchBeijing100191P. R. China
| | - Changping Zhou
- The Institute of Cardiovascular Sciences and Institute of Systems BiomedicineSchool of Basic Medical SciencesPeking University Health Science CenterKey Laboratory of Molecular Cardiovascular Sciences of Ministry of EducationKey Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of HealthBeijing Key Laboratory of Cardiovascular Receptors ResearchBeijing100191P. R. China
| | - Haigang Niu
- Department of Hepatobiliary SurgeryBeijing Chaoyang HospitalCapital Medical UniversityBeijing100043P. R. China
| | - Guoming Li
- Department of Hepatobiliary SurgeryBeijing Chaoyang HospitalCapital Medical UniversityBeijing100043P. R. China
| | - Wenbing Sun
- Department of Hepatobiliary SurgeryBeijing Chaoyang HospitalCapital Medical UniversityBeijing100043P. R. China
| | - Lemin Zheng
- The Institute of Cardiovascular Sciences and Institute of Systems BiomedicineSchool of Basic Medical SciencesPeking University Health Science CenterKey Laboratory of Molecular Cardiovascular Sciences of Ministry of EducationKey Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of HealthBeijing Key Laboratory of Cardiovascular Receptors ResearchBeijing100191P. R. China
- Beijing Tiantan HospitalChina National Clinical Research Center for Neurological DiseasesAdvanced Innovation Center for Human Brain ProtectionCapital Medical UniversityBeijing100050P. R. China
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Jiang AN, Liu JT, Zhao K, Wu H, Wang S, Yan K, Yang W. Specific Inhibitor of Matrix Metalloproteinase Decreases Tumor Invasiveness After Radiofrequency Ablation in Liver Tumor Animal Model. Front Oncol 2020; 10:561805. [PMID: 33330030 PMCID: PMC7709861 DOI: 10.3389/fonc.2020.561805] [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: 05/13/2020] [Accepted: 10/19/2020] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVE To determine whether the specific inhibitor of matrix metalloproteinase (MMP)-batimastat (BB-94)-could decrease the progression of liver tumor after radiofrequency ablation (RFA) and achieve better therapeutic efficacy in an animal model. METHODS In vitro experiments, the proliferation of H22 liver tumor cells was detected by CCK 8 assay and cell migration was detected by Transwell method. In vivo experiments, H22 murine liver tumors were used. First, 32 mice with one tumor were randomized into four groups (n = 8 each group): control (PBS only), RFA alone (65°C, 5 min), BB-94 (30 mg/kg), RFA+BB-94. The growth rate of the residual tumor and the end point survival were calculated and the pathologic changes were evaluated. Secondly, a total of 48 tumors in 24 animals (paired tumors) were randomized into three groups (n = 8 each group): control, RFA alone, RFA+BB-94. Each mouse was implanted with two tumors subcutaneously, one tumor was treated by RFA and the other was evaluated for distant metastasis after applying BB-94. RESULTS In vitro, the proliferation assay demonstrated higher proliferation ability after heat treatment (0.82 ± 0.07 vs 1.27 ± 0.08, P = 0.008), and it could be inhibited by BB-94 (1.27 ± 0.08 vs 0.67 ± 0.06, P = 0.001). In the cell migration assay, the H22 cells demonstrated enhanced tumor invasiveness in the heat group than the control group (33.7 ± 2.1 vs 19.7 ± 4.9, P = 0.011). And it could be significantly suppressed after BB-94 incubation (33.7 ± 2.1 vs 23.0 ± 4.6, P = 0.009). With one tumor animal, the growth rate of the residual tumor in the BB-94+RFA group was slower than that in the RFA alone group (P = 0.003). And combination of BB-94 could significantly prolong the survival of the mice (40.3 ± 1.4d vs 47.1 ± 1.3d, P = 0.002). The expression of CD31 and VEGF at the coagulation margin were decreased after combined with BB-94. With two tumors animal, the growth of metastasis tumor in the BB-94+RFA group was slower than that in the RFA group (P < 0.001). CONCLUSION BB-94 combined with RFA reduced the invasiveness of the liver tumor and improved the end-point survival. Our data suggested that targeting the MMP process with the specific inhibition could help to increase overall ablation efficacy.
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Affiliation(s)
- An-Na Jiang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jing-Tao Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pharmacy, Peking University Cancer Hospital & Institute, Beijing, China
| | - Kun Zhao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Hao Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Song Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Kun Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Wei Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
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Amarogentin Inhibits Liver Cancer Cell Angiogenesis after Insufficient Radiofrequency Ablation via Affecting Stemness and the p53-Dependent VEGFA/Dll4/Notch1 Pathway. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5391058. [PMID: 33145353 PMCID: PMC7596460 DOI: 10.1155/2020/5391058] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 07/18/2020] [Accepted: 08/21/2020] [Indexed: 01/14/2023]
Abstract
Background Whether and how amarogentin suppresses the angiogenesis effect in liver cancer cells after insufficient radiofrequency ablation (iRFA) are still poorly studied. Methods The number of liver cancer stem cells (LCSCs) and the level of vascular endothelial growth factor A (VEGFA) were assessed in liver cancer tissue after iRFA. Then, CD133-positive cells were detected in iRFA models of HepG2 and Huh7 cell lines treated with amarogentin. Tube formation assays were applied to observe the antiangiogenesis effects of amarogentin. In addition, the angiogenesis-related molecules p53, delta-like ligand 4 (Dll4), and Notch1 were detected in the iRFA cells and mouse models treated with amarogentin. Results The mRNA and protein expression levels of CD133 and VEGFA were significantly higher in the residual liver cancer tissue than in the liver cancer tissues treated by hepatectomy. Amarogentin then markedly decreased the percentage of CD133-positive cells in the iRFA model in both HepG2 and Huh7 cell lines. The number of tubules formed by human umbilical vein endothelial cells (HUVECs) was significantly decreased by amarogentin. Inversely, the antiangiogenesis effect of amarogentin was counteracted after p53 silencing in the iRFA cell models. Conclusion Amarogentin prevents the malignant transformation of liver cancer after iRFA via affecting stemness and the p53-dependent VEGFA/Dll4/Notch1 pathway to inhibit cancer cell angiogenesis.
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Lu X, Li Z, Liu Y, Wang Z, Peng F, Yu Q, Fu X, Ji B. The Long-Term Efficacy of Radiofrequency Ablation Versus Laparoscopic Hepatectomy for Small Hepatocellular Carcinoma in East Asia: A Systematic Review and Meta-Analysis. IRANIAN RED CRESCENT MEDICAL JOURNAL 2020; 22. [DOI: 10.5812/ircmj.102876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 06/21/2020] [Accepted: 07/19/2020] [Indexed: 07/28/2023]
Abstract
Context: Hepatocellular carcinoma (HCC) is a common malignant cancer and the second leading cause of cancer-related deaths around the world. Radiofrequency ablation (RFA) and laparoscopic hepatectomy (LH) have been adopted for the treatment of HCC. The aim of the meta-analysis was to explore the long-term efficacy of RFA compared with LH for small HCC (sHCC) patients in the East Asian population. Evidence Acquisition: We performed a systematic review and meta-analysis by the literature search on PubMed, Cochrane Library, EMBASE, Chinese Biological Medical Literature (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang from their inception until October 10, 2019, for comparing the long-term efficacy outcomes of RFA with LH. Results: Fourteen retrospective studies with 1,390 subjects were included in the meta-analysis. Compared with the LH-treated group, RFA could raise the local recurrence rate under median follow-up duration and reduce disease-free survival (DFS) rates at 1 - 3 years. However, it failed to affect 5-year overall survival (OS) and DFS rates. In the subgroup analyses, different RFA approaches had significantly higher local recurrence rates than the LH group. A similar effect on OS and DFS rates within five years for single early (≤ 3 cm) HCCs and on the 1- and 5-year DFS rates for nodules ≤ 5 cm were observed between the two groups, but RFA approaches could reduce the 3-y OS and DFS rates for single nodules ≤ 5 cm. The percutaneous radiofrequency ablation (PRFA) group had significantly lower 3- and 5-year OS and the 1- and 3-year DFS rates than the LH group, while no significant difference in OS and DFS rates in the laparoscopic radiofrequency ablation (LRFA) approach. The RFA approach improved the 3-year OS compared with the LH group in Japan, but reduced the 3-year OS and DFS rates within 3 years in China. Conclusions: Our results support that LH treating sHCC had a better long-term efficacy and a lower local recurrence rate than RFA in the East Asian population. Further high-quality prospective studies are required to confirm the long-term efficacy.
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Kong J, Yao C, Ding X, Dong S, Wu S, Sun W, Zheng L. ATPase Inhibitory Factor 1 Promotes Hepatocellular Carcinoma Progression After Insufficient Radiofrequency Ablation, and Attenuates Cell Sensitivity to Sorafenib Therapy. Front Oncol 2020; 10:1080. [PMID: 32670888 PMCID: PMC7330926 DOI: 10.3389/fonc.2020.01080] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Accepted: 05/29/2020] [Indexed: 12/20/2022] Open
Abstract
Epithelial-mesenchymal transition (EMT) and angiogenesis is involved in tumor progression after radiofrequency ablation (RFA). ATPase inhibitory factor 1 (IF1) is a bad predictor of prognosis. Sorafenib inhibited EMT of hepatocellular carcinoma (HCC) after RFA. Whether IF1 promotes the EMT and angiogenesis of HCC and attenuates the effect of sorafenib after insufficient RFA is investigated. In this study, higher expression of IF1 was found in residual tumor after insufficient RFA. Hep3B or Huh7 cells after insufficient RFA were designated as Hep3B-H or Huh7-H cells in vitro. Hep3B-H or Huh7-H cells exhibited enhanced capacities of colony formation, migration, and increased expression of EMT associated markers and IF1 compared with Hep3B or Huh7 cells. IF1 knockdown in Hep3B-H or Huh7-H cells decreased the colony formation and migratory capacity, and IF1 overexpression in Hep3B or Huh7 cells increased these capacities. IF1 in HCC cells directly and indirectly affected angiogenesis of TAECs after insufficient RFA. IF1 promoted HCC cells growth and metastasis after insufficient RFA. IF1 increased HCC cells resistance after insufficient RFA to sorafenib. Higher IF1 expression indicated poor disease survival in HCC patients after sorafenib therapy. NF-κB activation induced by IF1 attenuated the effect of sorafenib on HCC cells after insufficient RFA. Our results demonstrated that IF1 promotes the EMT and angiogenesis, and attenuates HCC cell sensitivity to sorafenib after insufficient RFA through NF-κB signal pathway.
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Affiliation(s)
- Jian Kong
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Changyu Yao
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xuemei Ding
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Shuying Dong
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Shilun Wu
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Wenbing Sun
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Lemin Zheng
- Key Laboratory of Molecular Cardiovascular Science of Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of Health, Beijing Key Laboratory of Cardiovascular Receptors Research, School of Basic Medical Sciences, The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Tiantan Hospital, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
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Chen L, Ying X, Zhang D, Lai L, Wu F, Tu J, Ji J. Iodine-125 Brachytherapy Can Prolong Progression-Free Survival of Patients with Locoregional Recurrence and/or Residual Hepatocellular Carcinoma After Radiofrequency Ablation. Cancer Biother Radiopharm 2020; 36:820-826. [PMID: 32551979 DOI: 10.1089/cbr.2020.3647] [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: 12/21/2022] Open
Abstract
Background: Radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC) is limited by locoregional recurrence and/or residual tumors caused by incomplete ablation. Iodine-125 brachytherapy can achieve a high local control rate in solid carcinoma, but few studies have assessed the efficacy of this treatment for locoregional recurrence and/or residual HCC after RFA. Objective: To investigate the effectiveness and safety of iodine-125 brachytherapy for treating locoregional recurrence and/or residual HCC in patients treated with RFA. Methods: Eligible study patients were those with locoregional recurrence and/or residual HCC on abdominal imaging performed 1 month after RFA at this institution between February 2009 and September 2014 retrospectively. Patients were divided into either the control group (no treatment until the tumor progressed) or the treatment group (underwent iodine-125 brachytherapy). Progression-free survival (PFS), overall survival (OS), and complications of iodine-125 brachytherapy were evaluated. Results: A total of 42 patients were included in the final analysis, including 29 in the control group and 13 in the treatment group. A total of 457 iodine-125 particles were used (mean 32.8 ± 21.3 mCi per case). The median follow-up time was 25 months. Median PFS was 9 months in the control group and 18 months in the treatment group (p = 0.026). The median OS was 28 months in the control group and 33 months in the treatment group (p = 0.441). There were no major complications observed in patients treated with iodine-125 brachytherapy. Conclusion: Iodine-125 brachytherapy can prolong PFS in patients with locoregional recurrence and/or residual HCC after RFA.
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Affiliation(s)
- Li Chen
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Lishui, China
| | - Xihui Ying
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Lishui, China
| | - Dengke Zhang
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Lishui, China
| | - Linqiang Lai
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Lishui, China
| | - Fazong Wu
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Lishui, China
| | - Jianfei Tu
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Lishui, China
| | - Jiansong Ji
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Lishui, China
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Shi L, Wang J, Ding N, Zhang Y, Zhu Y, Dong S, Wang X, Peng C, Zhou C, Zhou L, Li X, Shi H, Wu W, Long X, Wu C, Liao W. Inflammation induced by incomplete radiofrequency ablation accelerates tumor progression and hinders PD-1 immunotherapy. Nat Commun 2019; 10:5421. [PMID: 31780645 PMCID: PMC6883042 DOI: 10.1038/s41467-019-13204-3] [Citation(s) in RCA: 188] [Impact Index Per Article: 31.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 10/28/2019] [Indexed: 02/07/2023] Open
Abstract
Radiofrequency ablation (RFA) promotes tumor antigen-specific T cell responses and enhances the effect of immunotherapy in preclinical settings. Here we report that the existence of remnant tumor masses due to incomplete RFA (iRFA) is associated with earlier new metastases and poor survival in patients with colorectal cancer liver metastases (CRCLM). Using mouse models, we demonstrate that iRFA promotes tumor progression and hinders the efficacy of anti-PD-1 therapy. Immune analysis reveals that iRFA induces sustained local inflammation with predominant myeloid suppressor cells, which inhibit T cell function in tumors. Mechanistically, tumor cell-derived CCL2 is critical for the accumulation of monocytes and tumor-associated macrophages (TAMs). The crosstalk between TAMs and tumor cells enhances the CCL2 production by tumor cells. Furthermore, we find that administration of a CCR2 antagonist or the loss of CCL2 expression in tumor cells enhances the antitumor activity of PD-1 blockade, providing a salvage alternative for residual tumors after iRFA. Radiofrequency ablation is used to treat metastatic colorectal cancer. In this study, the authors show that incomplete ablation of tumours results in metastases and show in mouse models that the chemokine CCL2 recruits myeloid cells to the partially ablated tumours, which can block T cell function.
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Affiliation(s)
- Liangrong Shi
- Radiological Intervention Center, Department of Radiology, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China.,Center for Molecular Imaging, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China
| | - Junjun Wang
- Department of Oncology, the Third Affiliated Hospital, Soochow University, Changzhou, 213003, Jiangsu, China
| | - Nianhua Ding
- Radiological Intervention Center, Department of Radiology, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China.,Center for Molecular Imaging, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China
| | - Yi Zhang
- Dept. of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Yibei Zhu
- Institute of Biotechnology, Key Laboratory of Clinical Immunology of Jiangsu Province, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Shunli Dong
- Dept. of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Xiaohui Wang
- Dept. of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Changli Peng
- Radiological Intervention Center, Department of Radiology, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China
| | - Chunhui Zhou
- Radiological Intervention Center, Department of Radiology, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China
| | - Ledu Zhou
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China
| | - Xiaodong Li
- Department of Oncology, the Third Affiliated Hospital, Soochow University, Changzhou, 213003, Jiangsu, China
| | - Hongbing Shi
- Department of Oncology, the Third Affiliated Hospital, Soochow University, Changzhou, 213003, Jiangsu, China
| | - Wei Wu
- National Clinical Research Center for Geriatric Disorder, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China
| | - Xueyin Long
- Radiological Intervention Center, Department of Radiology, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China.,Center for Molecular Imaging, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China
| | - Changping Wu
- Department of Oncology, the Third Affiliated Hospital, Soochow University, Changzhou, 213003, Jiangsu, China.
| | - Weihua Liao
- Radiological Intervention Center, Department of Radiology, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China. .,Center for Molecular Imaging, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China.
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Xu WL, Wang SH, Sun WB, Gao J, Ding XM, Kong J, Xu L, Ke S. Insufficient radiofrequency ablation-induced autophagy contributes to the rapid progression of residual hepatocellular carcinoma through the HIF-1α/BNIP3 signaling pathway. BMB Rep 2019. [PMID: 30940322 PMCID: PMC6507849 DOI: 10.5483/bmbrep.2019.52.4.263] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Currently speaking, it is noted that radiofrequency ablation (RFA) has been the most widely used treatment for hepatocellular carcinoma (HCC) occurring in patients. However, accumulating evidence has demonstrated that the incidence of insufficient RFA (IRFA) may result in the identified rapid progression of residual HCC in the patient, which can greatly hinder the effectiveness and patient reported benefits of utilizing this technique. Although many efforts have been proposed, the underlying mechanisms triggering the rapid progression of residual HCC after IRFA have not yet been fully clarified through current research literature reviews. It was shown in this study that cell proliferation, migration and invasion of residual HepG2 and SMMC7721 cells were significantly increased after the IRFA was simulated in vitro. In other words, it is noted that IRFA could do this by enhancing the image of autophagy of the residual HCC cell via the HIF-1α/BNIP3 pathway. Consequently, the down-regulation of BNIP3 may result in the inhibition of the residual HCC cell progression and autophagy after IRFA. Our present study results suggest that IRFA could promote residual HCC cell progression in vitro by enhancing autophagy via the HIF-1α/BNIP3 pathway. For this reason, it is noted that the targeting of the BNIP3 may be useful in preventing the rapid growth and metastasis of residual HCC after IRFA.
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Affiliation(s)
- Wen-Lei Xu
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital Affiliated to Capital Medical University, Beijing 100043, China
| | - Shao-Hong Wang
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital Affiliated to Capital Medical University, Beijing 100043, China
| | - Wen-Bing Sun
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital Affiliated to Capital Medical University, Beijing 100043, China
| | - Jun Gao
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital Affiliated to Capital Medical University, Beijing 100043, China
| | - Xue-Mei Ding
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital Affiliated to Capital Medical University, Beijing 100043, China
| | - Jian Kong
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital Affiliated to Capital Medical University, Beijing 100043, China
| | - Li Xu
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital Affiliated to Capital Medical University, Beijing 100043, China
| | - Shan Ke
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital Affiliated to Capital Medical University, Beijing 100043, China
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Zhang N, Zhu H, Dong YH, Wang L. Establishment of an insufficient radiofrequency ablation orthotopic nude mouse model of hepatocellular carcinoma to study the invasiveness and metastatic potential of residual cancer. Oncol Lett 2019; 18:2548-2553. [PMID: 31402950 DOI: 10.3892/ol.2019.10552] [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] [Received: 05/31/2018] [Accepted: 02/19/2019] [Indexed: 12/13/2022] Open
Abstract
In order to assess the metastatic potential of residual hepatocellular carcinoma (HCC) following insufficient radiofrequency ablation (RFA) and to improve the current animal model, an insufficient RFA orthotopic nude mouse model of HCC was developed in the present study. A human HCC orthotopic nude mouse model was established using HCCLM3 cells, which has a high metastatic potential, labeled with green fluorescent protein. A total of 12 nude mice within the RFA group received insufficient RFA and 12 mice in the control group received RFA needle electrode puncture of the tumor without ablation, 3 weeks after implantation. To investigate tumor growth and metastasis, 4 weeks after RFA, six mice in each group were sacrificed and the remaining mice in each group were maintained until death to evaluate their life span. No mice died following insufficient RFA and the success rate was 100%. Compared with the control group, the intrahepatic and lung metastasis rates were higher in the RFA group, despite the mice having smaller tumor volumes and longer survival times. Lung and intrahepatic metastasis rates in the insufficient RFA group were 100% (6/6) and 66.67% (4/6), respectively, compared with 33.33% (2/6) and 0% (0/6), respectively, in the control group. As part of the study, a safe and reliable method to establish an insufficient RFA orthotopic nude mouse model was developed. The present study revealed that residual cancer following insufficient RFA had exhibited increased invasiveness and metastatic potential.
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Affiliation(s)
- Ning Zhang
- Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
| | - Hua Zhu
- Department of Oncology, The First People's Hospital of Jining, Jining, Shandong 272000, P.R. China
| | - Ye-Hao Dong
- Reproductive Medicine Center, The Affiliated Hospital of Jining Medical College, Jining, Shandong 272000, P.R. China
| | - Lu Wang
- Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
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Jiang J, Chen S, Li K, Zhang C, Tan Y, Deng Q, Chai Y, Wang X, Chen G, Feng K, Zhang L, Xie CM, Ma K. Targeting autophagy enhances heat stress-induced apoptosis via the ATP-AMPK-mTOR axis for hepatocellular carcinoma. Int J Hyperthermia 2019; 36:499-510. [PMID: 31007109 DOI: 10.1080/02656736.2019.1600052] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Affiliation(s)
- Jiayun Jiang
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Shihan Chen
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Kun Li
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Chang Zhang
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Yunhua Tan
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Qingsong Deng
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Yuelong Chai
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Xiaofei Wang
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Geng Chen
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Kai Feng
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Leida Zhang
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Chuan-Ming Xie
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Kuansheng Ma
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
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Thompson SM, Jondal DE, Butters KA, Knudsen BE, Anderson JL, Roberts LR, Callstrom MR, Woodrum DA. Heat Stress and Thermal Ablation Induce Local Expression of Nerve Growth Factor Inducible (VGF) in Hepatocytes and Hepatocellular Carcinoma: Preclinical and Clinical Studies. Gene Expr 2018; 19:37-47. [PMID: 29973305 PMCID: PMC6290322 DOI: 10.3727/105221618x15305531034617] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
The purposes of this study were to test the hypothesis that heat stress and hepatic thermal ablation induce nerve growth factor inducible (VGF) and to determine intrahepatic versus systemic VGF expression induced by thermal ablation in vivo and in patients. Hepatocytes and HCC cells were subjected to moderate (45°C) or physiologic (37°C) heat stress for 10 min and assessed for VGF expression at 0-72 h post-heat stress (n ≥ 3 experiments). Orthotopic N1S1 HCC-bearing rats were randomized to sham or laser thermal ablation (3 W × 90 s), and liver/serum was harvested at 0-7 days postablation for analysis of VGF expression (n ≥ 6 per group). Serum was collected from patients undergoing thermal ablation for HCC (n = 16) at baseline, 3-6, and 18-24 h postablation and analyzed for VGF expression. Data were analyzed using ordinary or repeated-measures one-way analysis of variance and post hoc pairwise comparison with Dunnett's test. Moderate heat stress induced time-dependent VGF mRNA (3- to 15-fold; p < 0.04) and protein expression and secretion (3.1- to 3.3-fold; p < 0.05). Thermal ablation induced VGF expression at the hepatic ablation margin at 1 and 3 days postablation but not remote from the ablation zone or distant intrahepatic lobe. There was no detectable serum VGF following hepatic thermal ablation in rats and no increase in serum VGF following HCC thermal ablation in patients at 3-6 and 18-24 h postablation compared to baseline (0.71- and 0.63-fold; p = 0.27 and p = 0.16, respectively). Moderate heat stress induces expression and secretion of VGF in HCC cells and hepatocytes in vitro, and thermal ablation induces local intrahepatic but not distant intrahepatic or systemic VGF expression in vivo.
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Affiliation(s)
- Scott M. Thompson
- *Department of Radiology, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Danielle E. Jondal
- *Department of Radiology, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Kim A. Butters
- *Department of Radiology, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Bruce E. Knudsen
- *Department of Radiology, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Jill L. Anderson
- *Department of Radiology, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Lewis R. Roberts
- †Division of Gastroenterology and Hepatology, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Matthew R. Callstrom
- *Department of Radiology, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA
| | - David A. Woodrum
- *Department of Radiology, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA
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Zhang N, Wang LR, Li DD, Ma DN, Wang CH, He XG, Gao DM, Wang L, Tang ZY. Interferon-α Combined With Herbal Compound "Songyou Yin" Effectively Inhibits the Increased Invasiveness and Metastasis by Insufficient Radiofrequency Ablation of Hepatocellular Carcinoma in an Animal Model. Integr Cancer Ther 2018; 17:1260-1269. [PMID: 30234394 PMCID: PMC6247542 DOI: 10.1177/1534735418801525] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Objective: We had previously proved that insufficient radiofrequency
ablation (RFA) could enhance invasiveness and metastasis of hepatocellular
carcinoma (HCC) through epithelial-mesenchymal transition (EMT), which is
mediated by activating β-catenin signaling. Thus, the aim of the present study
was to demonstrate whether the combined treatment of interferon-α (IFN-α) and
“Songyou Yin” (SYY) minimizes the pro-metastatic effects of insufficient RFA, as
well as to explore its underlying mechanism. Methods: Insufficient
RFA was performed in an orthotopic nude mice model of HCCLM3 with high
metastatic potential. The effects of IFN-α, SYY, and combined IFN-α and SYY were
observed in the animal model. Tumor sizes, lung metastasis, and survival time
were assessed. Immunochemistry staining, real-time polymerase chain reaction,
and Western blot were used to examine gene expression related to metastasis and
angiogenesis in residual cancer after insufficient RFA. Results:
For up to 8 weeks of treatment, the combined therapy significantly decreased the
residual cancer sizes, minimized the lung metastasis rate, and prolonged the
survival time of nude mice, which might be due to suppression of the EMT via
β-catenin signal blockade, in addition to attenuating angiogenesis in residual
cancer after insufficient RFA. Conclusion: IFN-α combined with SYY
significantly weakened the enhanced metastatic potential of residual cancer
after insufficient RFA by attenuating EMT, which is mediated through inhibiting
activation of β-catenin. In addition, decreasing angiogenesis of residual cancer
might also play a certain role.
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Affiliation(s)
- Ning Zhang
- 1 Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.,2 Zhongshan Hospital, Liver Cancer Institute, Fudan University, Shanghai, People's Republic of China
| | - Long-Rong Wang
- 1 Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
| | - Dou-Dou Li
- 1 Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
| | - De-Ning Ma
- 3 Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People's Republic of China
| | - Cheng-Hao Wang
- 1 Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.,2 Zhongshan Hospital, Liver Cancer Institute, Fudan University, Shanghai, People's Republic of China
| | - Xi-Gan He
- 1 Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
| | - Dong-Mei Gao
- 2 Zhongshan Hospital, Liver Cancer Institute, Fudan University, Shanghai, People's Republic of China
| | - Lu Wang
- 1 Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
| | - Zhao-You Tang
- 2 Zhongshan Hospital, Liver Cancer Institute, Fudan University, Shanghai, People's Republic of China
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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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Jondal DE, Thompson SM, Butters KA, Knudsen BE, Anderson JL, Carter RE, Roberts LR, Callstrom MR, Woodrum DA. Heat Stress and Hepatic Laser Thermal Ablation Induce Hepatocellular Carcinoma Growth: Role of PI3K/mTOR/AKT Signaling. Radiology 2018; 288:730-738. [PMID: 29737948 DOI: 10.1148/radiol.2018172944] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Purpose To determine if heat stress and hepatic laser thermal ablation induce hepatocellular carcinoma (HCC) growth and to identify growth factors induced by heat stress. Materials and Methods Non-heat-stressed HCC cells were cocultured with HCC cells or hepatocytes that were heat stressed at 37°C (physiologic), 45°C (moderate), or 50°C (severe) for 10 minutes and proliferation monitored with bioluminescence imaging for up to 6 days after heat stress (three experiments). Rats bearing orthotopic N1S1 HCC were randomly assigned to undergo immediate sham or laser thermal (3 W for 60 or 90 seconds; hereafter, 3W×60s and 3W×90s, respectively) ablation of the median (local) or left (distant) hepatic lobe, and tumor growth was monitored with magnetic resonance imaging for up to 18 days after ablation (six or more rats per group). Experiments were repeated with rats randomly assigned to receive either the adjuvant phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor (NVP-BEZ235) or the vehicle control. Heat-stressed HCC cells and hepatocytes were analyzed by using microarray or quantitative real-time polymerase chain reaction analysis for growth factor expression (three or more experiments). Groups were compared by using one- or two-way analysis of variance, and post hoc pairwise comparison was performed with the Dunnett test. Results There were more non-heat-stressed HCC cells when cells were cocultured with cells subjected to moderate but not physiologic or severe heat stress (P < .001 for both). Local intrahepatic N1S1 tumors were larger at day 18 in the 3W×60s (mean, 3102 mm3 ± 463 [standard error]; P = .004) and 3W×90s (mean, 3538 mm3 ± 667; P < .001) groups than in the sham group (mean, 1363 mm3 ± 361) but not in distant intrahepatic tumors (P = .31). Adjuvant BEZ235 resulted in smaller N1S1 tumors in the BEZ235 and laser thermal ablation group than in the vehicle control and laser thermal ablation group (mean, 1731 mm3 ± 1457 vs 3844 mm3 ± 2400, P < .001). Moderate heat stress induced expression of growth factors in HCC cells and hepatocytes, including heparin-binding growth factor, fibroblast growth factor 21, and nerve growth factor (range, 2.9-66.9-fold; P < .05). Conclusion Moderate heat stress and laser thermal ablation induce hepatocellular carcinoma growth, which is prevented with adjuvant PI3K/mTOR/protein kinase B inhibition.
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Affiliation(s)
- Danielle E Jondal
- From the Department of Radiology (D.E.J., S.M.T., K.A.B., B.E.K., J.L.A., M.R.C., D.A.W.) and Division of Gastroenterology and Hepatology (L.R.R.), Mayo Clinic School of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; and Department of Health Sciences Research, Mayo Clinic School of Medicine, Jacksonville, Fla (R.E.C.)
| | - Scott M Thompson
- From the Department of Radiology (D.E.J., S.M.T., K.A.B., B.E.K., J.L.A., M.R.C., D.A.W.) and Division of Gastroenterology and Hepatology (L.R.R.), Mayo Clinic School of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; and Department of Health Sciences Research, Mayo Clinic School of Medicine, Jacksonville, Fla (R.E.C.)
| | - Kim A Butters
- From the Department of Radiology (D.E.J., S.M.T., K.A.B., B.E.K., J.L.A., M.R.C., D.A.W.) and Division of Gastroenterology and Hepatology (L.R.R.), Mayo Clinic School of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; and Department of Health Sciences Research, Mayo Clinic School of Medicine, Jacksonville, Fla (R.E.C.)
| | - Bruce E Knudsen
- From the Department of Radiology (D.E.J., S.M.T., K.A.B., B.E.K., J.L.A., M.R.C., D.A.W.) and Division of Gastroenterology and Hepatology (L.R.R.), Mayo Clinic School of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; and Department of Health Sciences Research, Mayo Clinic School of Medicine, Jacksonville, Fla (R.E.C.)
| | - Jill L Anderson
- From the Department of Radiology (D.E.J., S.M.T., K.A.B., B.E.K., J.L.A., M.R.C., D.A.W.) and Division of Gastroenterology and Hepatology (L.R.R.), Mayo Clinic School of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; and Department of Health Sciences Research, Mayo Clinic School of Medicine, Jacksonville, Fla (R.E.C.)
| | - Rickey E Carter
- From the Department of Radiology (D.E.J., S.M.T., K.A.B., B.E.K., J.L.A., M.R.C., D.A.W.) and Division of Gastroenterology and Hepatology (L.R.R.), Mayo Clinic School of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; and Department of Health Sciences Research, Mayo Clinic School of Medicine, Jacksonville, Fla (R.E.C.)
| | - Lewis R Roberts
- From the Department of Radiology (D.E.J., S.M.T., K.A.B., B.E.K., J.L.A., M.R.C., D.A.W.) and Division of Gastroenterology and Hepatology (L.R.R.), Mayo Clinic School of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; and Department of Health Sciences Research, Mayo Clinic School of Medicine, Jacksonville, Fla (R.E.C.)
| | - Matthew R Callstrom
- From the Department of Radiology (D.E.J., S.M.T., K.A.B., B.E.K., J.L.A., M.R.C., D.A.W.) and Division of Gastroenterology and Hepatology (L.R.R.), Mayo Clinic School of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; and Department of Health Sciences Research, Mayo Clinic School of Medicine, Jacksonville, Fla (R.E.C.)
| | - David A Woodrum
- From the Department of Radiology (D.E.J., S.M.T., K.A.B., B.E.K., J.L.A., M.R.C., D.A.W.) and Division of Gastroenterology and Hepatology (L.R.R.), Mayo Clinic School of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; and Department of Health Sciences Research, Mayo Clinic School of Medicine, Jacksonville, Fla (R.E.C.)
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Zhu K, Huang J, Lai L, Huang W, Cai M, Zhou J, Guo Y, Chen J. Medium or Large Hepatocellular Carcinoma: Sorafenib Combined with Transarterial Chemoembolization and Radiofrequency Ablation. Radiology 2018; 288:300-307. [PMID: 29688153 DOI: 10.1148/radiol.2018172028] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Purpose To determine the safety and efficacy of sorafenib combined with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) (hereafter, S-TACE-RFA) in patients with medium or large (range, 3.1-7.0 cm in diameter) hepatocellular carcinoma (HCC). Materials and Methods This retrospective study evaluated the medical records of consecutive patients with medium or large HCC who underwent S-TACE-RFA or combined TACE and RFA (hereafter, TACE-RFA) from January 2010 to December 2014. Sorafenib was started 3-5 days after TACE, and RFA was performed 1-2 weeks after TACE. Treatment complications, recurrence-free survival (RFS), and overall survival (OS) in patients who underwent S-TACE-RFA were compared with those in patients who underwent TACE-RFA. Results Of the 174 patients who underwent S-TACE-RFA or TACE-RFA, 106 who met the eligibility criteria were included in this study. Among them, 40 underwent S-TACE-RFA and 66 underwent TACE-RFA. The patients who underwent S-TACE-RFA had longer RFS (median, 24.0 vs 10.0 months; P = .04) and better OS (median, 63.0 vs 36.0 months, P = .048) than those who underwent TACE-RFA. S-TACE-RFA and α-fetoprotein level were independent prognostic factors for survival in uni- and multivariable analyses. The rate of complications in patients who underwent S-TACE-RFA was similar to that in patients who underwent TACE-RFA (22.5% vs 18.2%, P = .59). Conclusion S-TACE-RFA resulted in longer RFS and better OS than did TACE-RFA in patients with medium or large HCC. © RSNA, 2018 Online supplemental material is available for this article.
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Affiliation(s)
- Kangshun Zhu
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
| | - Jingjun Huang
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
| | - Lisha Lai
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
| | - Wensou Huang
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
| | - Mingyue Cai
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
| | - Jingwen Zhou
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
| | - Yongjian Guo
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
| | - Junwei Chen
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
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Benedicto A, Romayor I, Arteta B. Role of liver ICAM-1 in metastasis. Oncol Lett 2017; 14:3883-3892. [PMID: 28943897 DOI: 10.3892/ol.2017.6700] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Accepted: 07/07/2017] [Indexed: 12/15/2022] Open
Abstract
Intercellular adhesion molecule (ICAM)-1, is a transmembrane glycoprotein of the immunoglobulin (Ig)-like superfamily, consisting of five extracellular Ig-like domains, a transmembrane domain and a short cytoplasmic tail. ICAM-1 is expressed in various cell types, including endothelial cells and leukocytes, and is involved in several physiological processes. Furthermore, it has additionally been reported to be expressed in various cancer cells, including melanoma, colorectal cancer and lymphoma. The majority of studies to date have focused on the expression of the ICAM-1 on the surface of tumor cells, without research into ICAM-1 expression at sites of metastasis. Cancer cells frequently metastasize to the liver, due to its unique physiology and specialized liver sinusoid capillary network. Liver sinusoidal endothelial cells constitutively express ICAM-1, which is upregulated under inflammatory conditions. Furthermore, liver ICAM-1 may be important during the development of liver metastasis. Therefore, it is necessary to improve the understanding of the mechanisms mediated by this adhesion molecule in order to develop host-directed anticancer therapies.
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Affiliation(s)
- Aitor Benedicto
- Department of Cell Biology and Histology, School of Medicine and Nursing, University of The Basque Country, UPV/EHU, Leioa, E-48940 Vizcaya, Spain
| | - Irene Romayor
- Department of Cell Biology and Histology, School of Medicine and Nursing, University of The Basque Country, UPV/EHU, Leioa, E-48940 Vizcaya, Spain
| | - Beatriz Arteta
- Department of Cell Biology and Histology, School of Medicine and Nursing, University of The Basque Country, UPV/EHU, Leioa, E-48940 Vizcaya, Spain
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Deng Q, Chen S, Fu C, Jiang J, Zou M, Tan Y, Wang X, Xia F, Feng K, Ma K, Bie P. Long noncoding RNA expression profiles in sub-lethal heat-treated hepatoma carcinoma cells. World J Surg Oncol 2017; 15:136. [PMID: 28732507 PMCID: PMC5521104 DOI: 10.1186/s12957-017-1194-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Accepted: 06/22/2017] [Indexed: 02/06/2023] Open
Abstract
Background Sub-lethal heat treatment characterizes a transition zone of radiofrequency ablation (RFA) which explains hepatocellular carcinoma (HCC) residual cancer occurrence in this area after RFA treatment. The biochemistry of residual cancer cell recurrence is poorly understood, but long noncoding RNAs (lncRNAs) may have aberrant expression that is associated with diverse cancers. Thus, we measured lncRNA gene expression in sub-lethally heat-treated HCC cells using microarray. Method Differentially expressed lncRNA and mRNA were measured with an Agilent Human lncRNA + mRNA Array V4.0 (4 × 180 K format) containing 41,000 lncRNAs and 34,000 mRNAs. Bioinformatics analysis was used to assess differentially expressed lncRNA and mRNA. Seven lncRNA and seven mRNA were validated by qRT-PCR analysis in HCC cells. Results Genome-wide lncRNA and mRNA expression data in sub-lethal heat-treated SMMC-7721 HCC cells 558 lncRNA and 250 mRNA were significantly up-regulated and 224 lncRNA and 1031 mRNA down-regulated compared to normal cultured SMMC-7721 cells. We demonstrated for the first time that ENST00000570843.1, ENST00000567668.1, ENST00000582249.1, ENST00000450304.1, TCONS_00015544, ENST00000602478.1, TCONS_00001266 and ARC, IL12RB1, HSPA6 were upregulated, whereas STAT3, PRPSAP1, MCU, URB2 were down-regulated in sub-lethally heat-treated HCC cells. Conclusions lncRNA expression data in sub-lethally heat-treated HCC cells will provide important insights about lncRNAs’ contribution to HCC recurrence after RFA treatment. Electronic supplementary material The online version of this article (doi:10.1186/s12957-017-1194-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Qingsong Deng
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Shihan Chen
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Chunchuan Fu
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Jiayun Jiang
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Mengda Zou
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Yunhua Tan
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Xiaofei Wang
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Feng Xia
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Kai Feng
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
| | - Kuansheng Ma
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
| | - Ping Bie
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
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Li W, Zhou X, Huang Z, Zhang K, Luo X, Zhong J, Chen Y. Short-term and long-term outcomes of laparoscopic hepatectomy, microwave ablation, and open hepatectomy for small hepatocellular carcinoma: a 5-year experience in a single center. Hepatol Res 2017; 47:650-657. [PMID: 27487979 DOI: 10.1111/hepr.12785] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Revised: 06/28/2016] [Accepted: 07/26/2016] [Indexed: 12/12/2022]
Abstract
AIM Laparoscopic hepatectomy (LH), microwave ablation (MWA), and open hepatectomy (OH) are three widely used methods to treat small hepatocellular carcinoma (HCC). However, few studies have compared the short- and long-term outcomes of these three treatments. The aim of this study was to investigate their effectiveness. METHODS The data were reviewed from 280 patients with HCCs measuring ≤3 cm (Barcelona Clinic Liver Cancer stage 0 or A) who received LH (n = 133), OH (n = 87), or MWA (n = 60) in our research center from 2005 to 2010. Short-term outcomes included intraoperative blood loss, operation time, and length of hospital stay. The disease-free survival and overall survival rates were analyzed as long-term outcomes. RESULTS The patients in the MWA and LH groups showed better short-term outcomes compared with those in the OH group. There were no significant differences in overall survival rates among the three treatments. The LH group showed significantly lower recurrence rates than the MWA group (P = 0.0146). CONCLUSIONS Laparoscopic hepatectomy may be a better option for patients with small HCC located on the liver surface and left lateral lobe. The short-term outcome of MWA is promising, although the high risk of local recurrence after the operation should be considered when planning treatment.
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Affiliation(s)
- Wenda Li
- Department of Hepatobiliary Surgery, The Sun Yat-sen memorial Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xue Zhou
- Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zejian Huang
- Department of Hepatobiliary Surgery, The Sun Yat-sen memorial Hospital of Sun Yat-sen University, Guangzhou, China
| | - Kelin Zhang
- Department of Surgical Intensive Care Unit, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xuan Luo
- Department of Hepatobiliary Surgery, The Sun Yat-sen memorial Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jinyi Zhong
- Department of Hepatobiliary Surgery, The Sun Yat-sen memorial Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yajin Chen
- Department of Hepatobiliary Surgery, The Sun Yat-sen memorial Hospital of Sun Yat-sen University, Guangzhou, China
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Napoleone M, Kielar AZ, Hibbert R, Saif S, Kwan BY. Local tumor progression patterns after radiofrequency ablation of colorectal cancer liver metastases. Diagn Interv Radiol 2017; 22:548-554. [PMID: 27705879 DOI: 10.5152/dir.2016.15543] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
PURPOSE We aimed to evaluate patterns of local tumor progression (LTP) after radiofrequency ablation (RF ablation) of colorectal cancer liver metastases (CRCLM) and to highlight the percentage of LTP not attributable to lesion size or RF ablation procedure-related factors (heat sink or insufficient ablation margin). METHODS CRCLM treated by RF ablation at a single tertiary care center from 2004-2012, with a minimum of six months of postprocedure follow-up, were included in this retrospective study. LTP morphology was classified as focal nodular (<90° of ablation margin), circumferential (>270°), or crescentic (90°-270°). Initial metastasis size, minimum ablation margin size, morphology of LTP, presence of a heat sink, and time to progression were recorded independently by two radiologists. RESULTS Thirty-two of 127 RF ablation treated metastases (25%) with a mean size of 23 mm (standard deviation 12 mm) exhibited LTP. Fifteen of 32 LTPs (47%) were classified as focal nodular, with seven having no procedure-related factor to explain recurrence. Ten of 32 LTPs (31%) were circumferential, with four having no procedure-related factor to explain recurrence. Seven of 32 LTPs (22%) were crescentic, with two having no procedure-related factor to explain recurrence. Of the 13 lesions without any obvious procedure-related reason for LTP, six (46%) were <3 cm in size. CONCLUSION Although LTP in RF ablation treated CRCLM can often be explained by procedure-related factors or size of the lesion, in this study up to six (5%) of the CRCLM we treated showed LTP without any reasonable cause.
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Affiliation(s)
- Marc Napoleone
- Department of Radiology, University of Ottawa, Canada and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
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Han Y, Yan D, Xu F, Li X, Cai JQ. Radiofrequency Ablation versus Liver Resection for Colorectal Cancer Liver Metastasis: An Updated Systematic Review and Meta-analysis. Chin Med J (Engl) 2017; 129:2983-2990. [PMID: 27958231 PMCID: PMC5198534 DOI: 10.4103/0366-6999.195470] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background: Controversial results about the therapeutic value of radiofrequency ablation (RFA) and liver resection (LR) in the treatment of colorectal cancer liver metastasis (CRCLM) have been reported. Thus, we performed the present meta-analysis to summarize the related clinical evidences. Methods: A systematic literature search was conducted using PubMed (Medline), EMBASE, Cochrane Library, and Web of Science, for all years up to April 2016. Pooled analyses of the overall survival (OS), progression-free survival (PFS), and morbidity rates were performed. Results: A total of 14 studies were finally enrolled in the meta-analysis. Patients treated by LR gained a longer OS and PFS than those of patients treated by RFA. Patients in the RFA group had lower morbidity rates than those of patients in the LR group. Publication bias analysis revealed that there was no significant publication bias in the meta-analysis. Conclusions: Patients with CRCLM gained much more survival benefits from LR than that from RFA. RFA rendered lower rates of morbidities. More well-designed randomized controlled trails comparing the therapeutic value of LR and RFA are warranted.
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Affiliation(s)
- Yue Han
- Department of Interventional Therapies, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dong Yan
- Department of Interventional Therapies, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Fei Xu
- Department of Interventional Therapies, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xiao Li
- Department of Interventional Therapies, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jian-Qiang Cai
- Department of Abdominal Surgical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Fitian AI, Cabrera R. Disease monitoring of hepatocellular carcinoma through metabolomics. World J Hepatol 2017; 9:1-17. [PMID: 28105254 PMCID: PMC5220267 DOI: 10.4254/wjh.v9.i1.1] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 09/20/2016] [Accepted: 10/24/2016] [Indexed: 02/06/2023] Open
Abstract
We elucidate major pathways of hepatocarcinogenesis and accurate diagnostic metabolomic biomarkers of hepatocellular carcinoma (HCC) identified by contemporary HCC metabolomics studies, and delineate a model HCC metabolomics study design. A literature search was carried out on Pubmed for HCC metabolomics articles published in English. All relevant articles were accessed in full text. Major search terms included “HCC”, “metabolomics”, “metabolomics”, “metabonomic” and “biomarkers”. We extracted clinical and demographic data on all patients and consolidated the lead candidate biomarkers, pathways, and diagnostic performance of metabolomic expression patterns reported by all studies in tables. Where reported, we also extracted and summarized the metabolites and pathways most highly associated with the development of cirrhosis in table format. Pathways of lysophospholipid, sphingolipid, bile acid, amino acid, and reactive oxygen species metabolism were most consistently associated with HCC in the cited works. Several studies also elucidate metabolic alterations strongly associated with cirrhosis, with γ-glutamyl peptides, bile acids, and dicarboxylic acids exhibiting the highest capacity for stratifying cirrhosis patients from appropriately matched controls. Collectively, global metabolomic profiles of the referenced works exhibit a promising diagnostic capacity for HCC at a capacity greater than that of conventional diagnostic biomarker alpha-fetoprotein. Metabolomics is a powerful strategy for identifying global metabolic signatures that exhibit potential to be leveraged toward the screening, diagnosis, and management of HCC. A streamlined study design and patient matching methodology may improve concordance among metabolomic datasets in future works.
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Zhou B, Ren C, Zu L, Zheng L, Guo L, Gao W. Elevated plasma migration inhibitory factor in hypertension-hyperlipidemia patients correlates with impaired endothelial function. Medicine (Baltimore) 2016; 95:e5207. [PMID: 27787379 PMCID: PMC5089108 DOI: 10.1097/md.0000000000005207] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Migration inhibitory factor (MIF) has been shown to be critical in the pathology of early artherosclerosis; this article aim to investigate the plasma levels of MIF in hypertension plus hyperlipidemia patients.A total of 39 hypertension plus hyperlipidemia patients without any previous treatment were enrolled (HTN-HLP). Twenty-five healthy subjects were enrolled as the healthy control group (HEALTHY). Plasma MIF was measured by ELISA; laboratory and clinical characteristics were analyzed. HUVECs were treated with pooled plasma from HTN-HLP and HEALTHY groups, and the protein levels of adhesion molecules VCAM-1 and ICAM-1 were determined by ELISA. We found that plasma MIF was significantly elevated in the HTN-HLP group. Serum NO and eNOS levels were significantly lower; serum ET-1 (endothelin) levels were significantly higher in the HTN-HLP group. Furthermore, blood pressure, baPWV (brachial-ankle pulse wave velocity), and serum ET-1 level were significantly positively; serum NO and eNOS levels were negatively correlated with plasma MIF levels. Plasma from HTN-HLP significantly stimulated VCAM-1 and ICAM-1 protein expression on the surface of HUVECs.Plasma MIF was elevated in HTN-HLP patients and correlates with impaired endothelial function.
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Affiliation(s)
- Boda Zhou
- Department of Cardiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Peking University Third Hospital
| | - Chuan Ren
- Department of Cardiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Peking University Third Hospital
| | - Lingyun Zu
- Department of Cardiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Peking University Third Hospital
- Correspondence: Lingyun Zu, Department of Cardiovascular Medicine, Peking University Third Hospital, Beijing, China (e-mail: )
| | - Lemin Zheng
- The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Peking University Health Science Center, Beijing, China
| | - Lijun Guo
- Department of Cardiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Peking University Third Hospital
| | - Wei Gao
- Department of Cardiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Peking University Third Hospital
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Bimonte S, Leongito M, Piccirillo M, de Angelis C, Pivonello C, Granata V, Izzo F. Radio-frequency ablation-based studies on VX2rabbit models for HCC treatment. Infect Agent Cancer 2016; 11:38. [PMID: 27525037 PMCID: PMC4981963 DOI: 10.1186/s13027-016-0082-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Accepted: 05/30/2016] [Indexed: 12/15/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide with high morbidity, mortality and increasing incidence. It is of note that the main curative therapies for HCC are hepatic resection and transplantation although the majority of patients at the time of presentation are not eligible for resection or orthotopic liver transplantation (OLT) due to the underlying cirrhosis. Currently, a variety of loco-regional therapies, including radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), microwave coagulation therapy (MCT), transarterial chemoembolization (TACE) and others, have been developed as alternative treatment options for HCC. Among these techniques, RFA is currently the most widely used treatment, due to its several advantages, such as safety and efficacy. To date, the effectiveness of RFA for HCC is reduced by the presence of residual tumor as a consequence of insufficient treatment. In order to ameliorate the effects of RFA on HCC, several in vivo studies, have been performed on its application as single or in combination treatment with drugs or others loco-regional therapies, by using rabbit VX2 liver model. This represents an ideal model of liver cancers and is widely used for imaging and other experimental studies due to the rapid growth of these tumors and their similarity to human hepatocellular carcinoma. In order to elucidate the therapeutic potential of RFA with adjuvant treatments for HCC, we reviewed the latest findings on the RFA-based studies in rabbit VX2 hepatocarcinoma models.
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Affiliation(s)
- Sabrina Bimonte
- Division of Abdominal Surgical Oncology, Hepatobiliary Unit, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", - IRCCS, Via Mariano Semmola, 80131 Naples, Italy
| | - Maddalena Leongito
- Division of Abdominal Surgical Oncology, Hepatobiliary Unit, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", - IRCCS, Via Mariano Semmola, 80131 Naples, Italy
| | - Mauro Piccirillo
- Division of Abdominal Surgical Oncology, Hepatobiliary Unit, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", - IRCCS, Via Mariano Semmola, 80131 Naples, Italy
| | | | - Claudia Pivonello
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università di Napoli Federico II, Naples, Italy
| | - Vincenza Granata
- Division of Abdominal Surgical Oncology, Hepatobiliary Unit, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", - IRCCS, Via Mariano Semmola, 80131 Naples, Italy
| | - Francesco Izzo
- Division of Abdominal Surgical Oncology, Hepatobiliary Unit, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", - IRCCS, Via Mariano Semmola, 80131 Naples, Italy
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