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Liu H, Fan W, Li H, Qiao L, Liu Z, Zhu B, Guo J, Huang K, Tang Y, Wen J, Xue M, Wu Y, Zhao Y, Jiang Y, Liu K, Liang J, Cao M, Li J. Idarubicin versus Epirubicin in Transarterial Chemoembolization for Barcelona Clinic Liver Cancer Stage B Hepatocellular Carcinoma: An Open-label, Randomized, Phase IV Trial. Radiology 2025; 315:e242315. [PMID: 40326873 DOI: 10.1148/radiol.242315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/07/2025]
Abstract
Background Transarterial chemoembolization (TACE) is regarded as the first-line treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC). However, the optimal chemotherapeutic agent loaded in TACE remains controversial. Purpose To compare the efficacy and safety of idarubicin and epirubicin as loaded drugs in drug-eluting bead (DEB)-TACE in patients with BCLC stage B HCC. Materials and Methods In this open-label, phase IV trial, patients with BCLC stage B HCC were recruited from four centers from August 2020 to October 2022 and randomly assigned (at a one-to-one ratio) to undergo idarubicin DEB-TACE or epirubicin DEB-TACE. The primary end point was progression-free survival (PFS), which was measured from the time of randomization to the time of progression or death from any cause. The efficacy analysis was conducted on an intention-to-treat basis, and only participants who received treatment were included in the safety analysis. Results A total of 239 participants (median age, 57 years; IQR, 50-66 years; 210 male) were randomly assigned to the idarubicin group (n = 120) or the epirubicin group (n = 119). The primary analysis cutoff for PFS was March 1, 2023, with 167 events observed (70%; idarubicin group, 85 events; epirubicin group, 82 events). The median PFS was 10.8 months and 8.7 months in the idarubicin and epirubicin groups, respectively (hazard ratio [HR], 0.61; 95% CI: 0.44, 0.84; P = .002). The HR for median overall survival (OS) was 0.53 (95% CI: 0.31, 0.88), with OS rates of 81.5% and 77.3% at 12 months and 71.8% and 54.0% at 24 months for the idarubicin and epirubicin groups, respectively. The objective response rates were 70.8% and 57.1% for the idarubicin and epirubicin groups, respectively (P = .03). There was no evidence of a between-group difference in incidence of adverse events, including hematologic toxicity. No treatment-related deaths were observed. Conclusion Idarubicin DEB-TACE increased survival in participants with BCLC stage B HCC, without an increase in the incidence of any adverse events. Clinical trial registration no. ChiCTR2000034758 © RSNA, 2025 Supplemental material is available for this article.
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Affiliation(s)
- Haikuan Liu
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University No.58 Zhongshan 2nd Rd, Guangzhou 510080, China
| | - Wenzhe Fan
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University No.58 Zhongshan 2nd Rd, Guangzhou 510080, China
| | - Haiqing Li
- Department of Tumor Minimally Invasive, Taian City Central Hospital, Taian, China
| | - Liangliang Qiao
- Department of Interventional Oncology, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zhilong Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Bowen Zhu
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University No.58 Zhongshan 2nd Rd, Guangzhou 510080, China
| | - Jian Guo
- Department of Interventional Radiology, Guangdong Province Hospital-Zhuhai Hospital, Zhuhai, China
| | - Kun Huang
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University No.58 Zhongshan 2nd Rd, Guangzhou 510080, China
| | - Yiyang Tang
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University No.58 Zhongshan 2nd Rd, Guangzhou 510080, China
| | - Jie Wen
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University No.58 Zhongshan 2nd Rd, Guangzhou 510080, China
| | - Miao Xue
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University No.58 Zhongshan 2nd Rd, Guangzhou 510080, China
| | - Yanqin Wu
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University No.58 Zhongshan 2nd Rd, Guangzhou 510080, China
| | - Yue Zhao
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University No.58 Zhongshan 2nd Rd, Guangzhou 510080, China
| | - Yang Jiang
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University No.58 Zhongshan 2nd Rd, Guangzhou 510080, China
| | - Kangshou Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Junjie Liang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Mingrong Cao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Jiaping Li
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University No.58 Zhongshan 2nd Rd, Guangzhou 510080, China
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Zhao CH, Liu H, Pan T, Xiang ZW, Mu LW, Luo JY, Zhou CR, Li MA, Liu MM, Yan HZ, Huang MS. Idarubicin-transarterial chemoembolization combined with gemcitabine plus cisplatin for unresectable intrahepatic cholangiocarcinoma. World J Gastrointest Oncol 2025; 17:103776. [PMID: 40235888 PMCID: PMC11995345 DOI: 10.4251/wjgo.v17.i4.103776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 01/12/2025] [Accepted: 02/07/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (iCCA) is the second most common liver malignancy with poor prognosis and limited treatment options. AIM To identify the most effective drug for transarterial chemoembolization (TACE) in cholangiocarcinoma and evaluate the efficacy and safety of combining it with gemcitabine and cisplatin (GemCis) for unresectable iCCA. METHODS Cholangiocarcinoma cell lines (RBE, HuCC-T1) were treated with 10 chemotherapeutic drugs, and cytotoxicity was assessed by cell counting kit-8 assays. Tumor-bearing nude mice were treated with idarubicin or GemCis, and tumor growth was monitored. Clinical data from 85 iCCA patients were analyzed to evaluate the efficacy and safety of idarubicin-TACE combined with GemCis. RESULTS Idarubicin demonstrated the highest cytotoxicity, significantly outperforming GemCis, the standard first-line therapies. In tumor-bearing mouse models, idarubicin and GemCis treatments significantly slowed tumor growth, with idarubicin showing particularly pronounced effects on days 12 and 15 (P < 0.05). In retrospective analysis, the median overall survival (OS) and progression-free survival (PFS) in the combination therapy group were significantly longer than those in the GemCis alone group (median OS, 16.23 months vs 10.07 months, P = 0.042; median PFS, 7.73 months vs 6.30 months, P = 0.023). Additionally, major grade 3/4 adverse events (AEs) in the combination therapy group were abdominal pain (26.3% vs 6.5%, P = 0.049) and elevated transaminases (42.1% vs 12.9%, P = 0.038). Most AEs were mild to moderate and manageable. CONCLUSION Idarubicin demonstrated higher cytotoxicity than GemCis, significantly inhibiting tumor growth in tumor-bearing mouse models. Preliminary clinical results suggest that local idarubicin-TACE combined with GemCis may offer improved survival outcomes for iCCA patients with a manageable safety profile.
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Affiliation(s)
- Cheng-Hao Zhao
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Huan Liu
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Tao Pan
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Zhan-Wang Xiang
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Lu-Wen Mu
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Jun-Yang Luo
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Chu-Ren Zhou
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Ming-An Li
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Ming-Ming Liu
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Hu-Zheng Yan
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Ming-Sheng Huang
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
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Korsic S, Osredkar J, Smid A, Steblovnik K, Popovic M, Locatelli I, Trontelj J, Popovic P. Idarubicin-loaded drug-eluting microspheres transarterial chemoembolization for intermediate stage hepatocellular carcinoma: safety, efficacy, and pharmacokinetics. Radiol Oncol 2024; 58:517-526. [PMID: 39365794 DOI: 10.2478/raon-2024-0052] [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: 08/05/2024] [Accepted: 08/28/2024] [Indexed: 10/06/2024] Open
Abstract
BACKGROUND Transarterial chemoembolization (TACE) is the treatment of choice for the intermediate stage hepatocellular carcinoma (HCC). Doxorubicin remains the most used chemotherapeutic agent in TACE, although in vitro screening has demonstrated that idarubicin exhibits greater cytotoxicity against HCC. This study aimed to evaluate safety, efficacy, and pharmacokinetics of idarubicin-loaded drug-eluting microspheres TACE (DEMIDA-TACE) in intermediate stage HCC patients. PATIENTS AND METHODS Between September 2019 and December 2021, 31 consecutive intermediate stage HCC patients (96.8% cirrhotic) were included to this study. 2 mL of LifePearl™ microspheres (100 μm) loaded with 10 mg of 1 mg/mL idarubicin were used for treatment. The adverse events, objective response rate (ORR), progression free survival (PFS), time to TACE untreatable progression (TTUP), median overall survival (mOS), and pharmacokinetics were evaluated. RESULTS There were 68 TACE procedures performed. Adverse events grade ≥ 3 were noted after 29.4% procedures. The ORR was 83.9%, median PFS and TTUP were 10.5 months (95% CI: 6.8-14.3 months) and 24.6 months (95% CI: 11.6-37.6 months), respectively. Median OS was 36.0 months (95% CI: 21.1-50.9 months). Significant differences between patients achieving objective response (OR) and those with progressive disease were observed regarding idarubicinol and combined idarubicin-idarubicinol plasma concentrations at 72 hours post-procedure, higher plasma concentrations were observed in patients achieving OR (p = 0.014 and 0.014; cut-off values 1.2 and 1.29 ng/mL, respectively). CONCLUSIONS DEMIDA-TACE emerges as a safe and effective method of treatment for the intermediate stage HCC with low rates of adverse events alongside high tumor response, favourable disease control and overall survival. Idarubicinol and combined idarubicin-idarubicinol plasma concentrations at 72 hours post-procedure may serve as prognostic factors for achieving OR.
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Affiliation(s)
- Spela Korsic
- Clinical Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Josko Osredkar
- Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
| | - Alojz Smid
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Department of Gastroenterology and Hepatology, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Klemen Steblovnik
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Department of Cardiology, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Mark Popovic
- Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia
| | - Igor Locatelli
- Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
| | - Jurij Trontelj
- Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
| | - Peter Popovic
- Clinical Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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Zaarour Y, Derbel H, Tran C, Saccentia L, Longère B, Blain M, Amaddeo G, Luciani A, Kobeiter H, Tacher V. Evaluation of a new beads reflux control microcatheter in drug-eluting bead transarterial chemoembolization. RESEARCH IN DIAGNOSTIC AND INTERVENTIONAL IMAGING 2024; 10:100048. [PMID: 39077730 PMCID: PMC11265494 DOI: 10.1016/j.redii.2024.100048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 04/01/2024] [Indexed: 07/31/2024]
Abstract
Rationale and objectives A new microcatheter was recently developed claiming to reduce beads reflux in drug-eluting bead transarterial chemoembolization (DEB-TACE). The aim of this study was to compare the reflux control microcatheter ability versus a standard microcatheter for TACE treatment in patients with hepatocellular carcinoma. Material and methods Patients were prospectively included between November 2017 and February 2022. They received a DEB-TACE treatment with charged radiopaque beads using standard microcatheters or the SeQure reflux control microcatheter (Guerbet, France) and were assigned respectively to a control and a test group. Beads distribution mismatch was evaluated between the targeted territory on treatment planning CBCT and beads' spontaneous opacities on the post-intervention CBCT and the 1-month CT scanner. Results Twenty-three patients (21 men, median age 64 years [12.5 years]) with 37 hepatocellular carcinoma nodules were treated. The control group consisted of 13 patients - 19 nodules, while the test group included ten patients - 18 nodules. Non target embolization (NTE) was found in 20 % (2/10) of patients in the test group and 85 % (11/13) in the control group. NTE involved only an adjacent segment in the test group while it affected the adjacent biliary sector or even the contralateral liver lobe in the control group. No complication linked to NTE was found in the test group, while it led to one case of ischemic cholangitis and another case of biloma in the control group. Conclusion The reflux control microcatheter may be efficient in reducing NTE and thus eventual adverse events in comparison to standard of care end-hole microcatheters.
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Affiliation(s)
- Youssef Zaarour
- Department of Radiology, CHU Henri-Mondor, Assistance publique – hôpitaux de Paris (AP-HP), 1, rue Gustave-Eiffel, 94010 Créteil, France
| | - Haytham Derbel
- Department of Radiology, CHU Henri-Mondor, Assistance publique – hôpitaux de Paris (AP-HP), 1, rue Gustave-Eiffel, 94010 Créteil, France
| | - Charles Tran
- Université Paris-Est Créteil (Upec), 94010 Créteil, France
| | - Laetitia Saccentia
- Department of Radiology, CHU Henri-Mondor, Assistance publique – hôpitaux de Paris (AP-HP), 1, rue Gustave-Eiffel, 94010 Créteil, France
- Université Paris-Est Créteil (Upec), 94010 Créteil, France
| | - Benjamin Longère
- Department of Radiology, CHU Henri-Mondor, Assistance publique – hôpitaux de Paris (AP-HP), 1, rue Gustave-Eiffel, 94010 Créteil, France
- Department of Cardiovascular Radiology, Institut Cœur-Poumon, CHU de Lille, 59037 Lille, France
| | - Maxime Blain
- Department of Radiology, CHU Henri-Mondor, Assistance publique – hôpitaux de Paris (AP-HP), 1, rue Gustave-Eiffel, 94010 Créteil, France
- Université Paris-Est Créteil (Upec), 94010 Créteil, France
| | - Giuliana Amaddeo
- Department of Hepatology, CHU Henri-Mondor, Assistance publique – hôpitaux de Paris (AP-HP), 94010 Créteil, France
| | - Alain Luciani
- Department of Radiology, CHU Henri-Mondor, Assistance publique – hôpitaux de Paris (AP-HP), 1, rue Gustave-Eiffel, 94010 Créteil, France
- Université Paris-Est Créteil (Upec), 94010 Créteil, France
- Unité Inserm U955, équipe n°18, IMRB, 94010 Créteil, France
| | - Hicham Kobeiter
- Department of Radiology, CHU Henri-Mondor, Assistance publique – hôpitaux de Paris (AP-HP), 1, rue Gustave-Eiffel, 94010 Créteil, France
- Université Paris-Est Créteil (Upec), 94010 Créteil, France
| | - Vania Tacher
- Department of Radiology, CHU Henri-Mondor, Assistance publique – hôpitaux de Paris (AP-HP), 1, rue Gustave-Eiffel, 94010 Créteil, France
- Université Paris-Est Créteil (Upec), 94010 Créteil, France
- Unité Inserm U955, équipe n°18, IMRB, 94010 Créteil, France
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Choi JW, Kim HC, Han J, Jang MJ, Chung JW. Transarterial Chemoembolization Using Idarubicin Versus Doxorubicin Chemoemulsion in Patients with Hepatocellular Carcinoma (IDADOX): Protocol for a Randomized, Non-inferiority, Double-Blind Trial. Cardiovasc Intervent Radiol 2024; 47:372-378. [PMID: 38147153 DOI: 10.1007/s00270-023-03621-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 11/07/2023] [Indexed: 12/27/2023]
Abstract
PURPOSE This study aims to test the hypothesis that idarubicin-based transarterial chemoembolization (IDA-TACE), using one of the most potent chemotherapeutic agents, could yield oncologic outcomes equivalent to or marginally improved over doxorubicin-based TACE (DOX-TACE). MATERIALS AND METHODS This single-center, prospective, phase II, randomized controlled, non-inferiority, double-blind trial will enroll 128 treatment-naïve patients with HCC (≤ 5 tumors, 1-5 cm in diameter) for conventional TACE. Participants will be randomly assigned (1:1) to either IDA-TACE or DOX-TACE, with stratification by Child-Pugh class. Superselective conventional TACE will be performed using cone-beam CT and small-bore microcatheters. Patient evaluations, including dynamic imaging and blood tests, will occur at 1, 3, and 6 months post-initial treatment. The primary outcome measure is the objective response rate (ORR) according to mRECIST at 6 months. Secondary outcomes include 3-month and 6-month tumor responses, time-to-progression, the incidence of treatment-related serious adverse events within 30 days, and the incidence and severity of any adverse events. STATISTICS Non-inferiority will be claimed if the upper limit of a one-sided 97.5% confidence interval for the proportion difference (i.e., "6-month ORR of DOX-TACE" - "6-month ORR of IDA-TACE") falls below 0.15 in both intention-to-treat and per-protocol analyses. The proportion difference and its confidence interval will be calculated by the Cochran-Mantel-Haenszel method to obtain a weighted average of stratum-specific proportion differences. EXPECTED GAIN OF KNOWLEDGE If IDA-TACE demonstrates outcomes comparable to DOX-TACE, this study could provide compelling evidence that various cytotoxic agents yield similar contributions in TACE, considering the minor role of chemotherapeutic agents in TACE. TRIAL REGISTRATION ClinicalTrials.gov ( https://clinicaltrials.gov/ ). Identifier: NCT06114082. World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) ( https://trialsearch.who.int/Default.aspx ). Identifier: KCT0008166.
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Affiliation(s)
- Jin Woo Choi
- Department of Radiology, Seoul National University Hospital, #101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University Hospital, #101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jiyeon Han
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Korea
| | - Myoung-Jin Jang
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Korea
| | - Jin Wook Chung
- Department of Radiology, Seoul National University Hospital, #101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
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Sun Z, Jiao D, Fang Y, Liu Y, Xu K, Zhang C, Huang Y, Han X. Efficacy and safety of raltitrexed-eluting CalliSpheres ® bead transarterial chemoembolization in patients with intermediate-stage hepatocellular carcinoma: a single-arm, prospective study. Ther Adv Med Oncol 2024; 16:17588359241229661. [PMID: 38362379 PMCID: PMC10868504 DOI: 10.1177/17588359241229661] [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: 04/09/2023] [Accepted: 01/10/2024] [Indexed: 02/17/2024] Open
Abstract
Background The most common loadable chemotherapeutic drugs in drug-eluting bead transarterial chemoembolization (DEB-TACE) include doxorubicin, epirubicin, etc. CalliSpheres® beads have exhibited efficient loadability and eluting characteristics for raltitrexed as well as in vitro and animal experiments. However, the efficacy and safety of raltitrexed-loaded DEB-TACE in patients with intermediate-stage hepatocellular carcinoma (HCC) remain unclear. Objectives To assess the efficacy and safety of raltitrexed-loaded DEB-TACE in patients with intermediate-stage HCC. Design The study was conducted as a single-arm prospective study. Methods This study was a prospective, single-arm trial conducted between June 2019 and June 2022. CalliSpheres® beads loaded with raltitrexed were used in the DEB-TACE procedure. The follow-up lasted for at least 1 year or until death. The primary endpoint was overall survival (OS), and the secondary endpoints were time to progression (TTP), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Results The 6-month ORR and disease control rates were 90.1% and 93.8%, respectively. The median OS was 33.0 months. The 1-, 2-, and 3-year survival rates were 95.1%, 82.1%, and 43.6%, respectively. Child-Pugh class and bilobar disease occurrence were identified as independent OS predictors. The median TTP and PFS were 22.7 and 19.8 months, respectively. Eleven (11.5%) patients experienced at least one grade 3 AE, and serious AEs were reported in five participants (5.2%). No patient experienced grade 4 or 5 AEs. Conclusion Raltitrexed-loaded DEB-TACE is feasible, safe, and effective in patients with intermediate-stage HCC. Trial registration This trial was registered at www.chictr.org.cn under the identifier: 1900024097 on 25 June 2019.
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Affiliation(s)
- Zhanguo Sun
- Department of Interventional Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Dechao Jiao
- Department of Interventional Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, Henan, China
| | - Yi Fang
- Department of Interventional Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yiming Liu
- Department of Interventional Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Kaihao Xu
- Department of Interventional Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Chengzhi Zhang
- Department of Interventional Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuanhao Huang
- Department of Interventional Medicine, Zhengzhou Central Hospital, Zhengzhou, China
| | - Xinwei Han
- Department of Interventional Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Caputo WL, de Souza MC, Basso CR, Pedrosa VDA, Seiva FRF. Comprehensive Profiling and Therapeutic Insights into Differentially Expressed Genes in Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:5653. [PMID: 38067357 PMCID: PMC10705715 DOI: 10.3390/cancers15235653] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 11/02/2023] [Accepted: 11/04/2023] [Indexed: 02/16/2024] Open
Abstract
Background: Drug repurposing is a strategy that complements the conventional approach of developing new drugs. Hepatocellular carcinoma (HCC) is a highly prevalent type of liver cancer, necessitating an in-depth understanding of the underlying molecular alterations for improved treatment. Methods: We searched for a vast array of microarray experiments in addition to RNA-seq data. Through rigorous filtering processes, we have identified highly representative differentially expressed genes (DEGs) between tumor and non-tumor liver tissues and identified a distinct class of possible new candidate drugs. Results: Functional enrichment analysis revealed distinct biological processes associated with metal ions, including zinc, cadmium, and copper, potentially implicating chronic metal ion exposure in tumorigenesis. Conversely, up-regulated genes are associated with mitotic events and kinase activities, aligning with the relevance of kinases in HCC. To unravel the regulatory networks governing these DEGs, we employed topological analysis methods, identifying 25 hub genes and their regulatory transcription factors. In the pursuit of potential therapeutic options, we explored drug repurposing strategies based on computational approaches, analyzing their potential to reverse the expression patterns of key genes, including AURKA, CCNB1, CDK1, RRM2, and TOP2A. Potential therapeutic chemicals are alvocidib, AT-7519, kenpaullone, PHA-793887, JNJ-7706621, danusertibe, doxorubicin and analogues, mitoxantrone, podofilox, teniposide, and amonafide. Conclusion: This multi-omic study offers a comprehensive view of DEGs in HCC, shedding light on potential therapeutic targets and drug repurposing opportunities.
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Affiliation(s)
- Wesley Ladeira Caputo
- Post Graduation Program in Experimental Pathology, State University of Londrina (UEL), Londrina 86057-970, PR, Brazil; (W.L.C.); (M.C.d.S.)
| | - Milena Cremer de Souza
- Post Graduation Program in Experimental Pathology, State University of Londrina (UEL), Londrina 86057-970, PR, Brazil; (W.L.C.); (M.C.d.S.)
| | - Caroline Rodrigues Basso
- Department of Chemical and Biological Sciences, Institute of Bioscience, São Paulo State University (UNESP), Botucatu 18610-034, SP, Brazil; (C.R.B.); (V.d.A.P.)
| | - Valber de Albuquerque Pedrosa
- Department of Chemical and Biological Sciences, Institute of Bioscience, São Paulo State University (UNESP), Botucatu 18610-034, SP, Brazil; (C.R.B.); (V.d.A.P.)
| | - Fábio Rodrigues Ferreira Seiva
- Post Graduation Program in Experimental Pathology, State University of Londrina (UEL), Londrina 86057-970, PR, Brazil; (W.L.C.); (M.C.d.S.)
- Department of Chemical and Biological Sciences, Institute of Bioscience, São Paulo State University (UNESP), Botucatu 18610-034, SP, Brazil; (C.R.B.); (V.d.A.P.)
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Takamoto T, Maruki Y, Kondo S. Recent updates in the use of pharmacological therapies for downstaging in patients with hepatocellular carcinoma. Expert Opin Pharmacother 2023; 24:1567-1575. [PMID: 37357809 DOI: 10.1080/14656566.2023.2229728] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 06/22/2023] [Indexed: 06/27/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, but only 20-30% of patients benefit from potentially curative treatments such as liver resection or transplantation. This article reviews conventional treatments and recent progress in pharmacotherapy for advanced HCC, with a focus on downstaging unresectable tumors to resectable status. AREAS COVERED In this article, conventional treatments and recent progress in pharmacotherapy for advanced HCC, aiming at downstaging from unresectable to resectable status, are reviewed. Future prospectives of combination therapies using immune checkpoint inhibitors were also introduced by reviewing recent clinical trials, paying attention to the objective response rate as its potential of downstaging treatments. EXPERT OPINION The newly developed pharmacological therapies showed higher responses. Although various tumor statuses in advanced HCC hamper detailed analysis of successful conversion rate, the novel combined immunotherapies are expected to provide more opportunities for subsequent curative surgery for initially unresectable advanced HCC. The conversion treatment strategies for unresectable HCC should be separately discussed for 'technically resectable but oncologically unfavorable' HCC and metastatic or invasive HCC beyond curative surgical treatments. The optimal downstaging treatment strategy for advanced HCC is awaited. Elucidation of preoperatively available factors that predict successful downstaging will allow the tailoring of promising initial treatments leading to conversion surgery.
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Affiliation(s)
- Takeshi Takamoto
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Yuta Maruki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Shunsuke Kondo
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
- Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan
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Zhao C, Yan H, Xiang Z, Wang H, Li M, Huang M. Idarubicin versus epirubicin in drug-eluting beads-transarterial chemoembolization for treating hepatocellular carcinoma: A real-world retrospective study. Invest New Drugs 2023; 41:617-626. [PMID: 37434023 DOI: 10.1007/s10637-023-01377-0] [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: 05/01/2023] [Accepted: 06/21/2023] [Indexed: 07/13/2023]
Abstract
The purpose of this study was to compare the efficacy and safety of idarubicin-loaded drug-eluting beads-transarterial chemoembolization (IDA-TACE) and epirubicin-loaded drug-eluting beads-TACE (EPI-TACE) in treating hepatocellular carcinoma (HCC). All patients with HCC treated with TACE in our hospital between June 2020 and January 2022 were screened. The included patients were divided into the IDA-TACE group and EPI-TACE group to compare overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events. There were 55 patients each in the IDA-TACE and EPI-TACE groups. Compared with the EPI-TACE group, the median TTP in the IDA-TACE group was not significantly different (10.50 vs. 9.23 months; HR 0.68; 95% CI 0.40-1.16; P = 0.154), whereas the survival status in the IDA-TACE group tended to be better (neither achieved; HR 0.47; 95% CI 0.22-1.02; P = 0.055). Based on the Barcelona Clinic Liver Cancer staging system for subgroup analysis, considering stage C patients, the IDA-TACE group performed significantly better in terms of ORR (77.1% vs. 54.3%, P = 0.044), median TTP (10.93 vs. 5.20 months; HR 0.46; 95% CI 0.24-0.89; P = 0.021), and median OS (not achieved vs. 17.80 months; HR 0.41; 95% CI 0.18-0.93; P = 0.033). Considering stage B patients, there were no significant differences between the IDA-TACE and EPI-TACE groups in terms of ORR (80.0% vs. 80.0%, P = 1.000), median TTP (10.20 vs. 11.2 months; HR 1.41; 95% CI 0.54-3.65; P = 0.483), or median OS (neither achieved, HR 0.47; 95% CI 0.04-5.24; P = 0.543). Notably, leukopenia was more common in the IDA-TACE group (20.0%, P = 0.052), and fever was more common in the EPI-TACE group (49.1%, P = 0.010). IDA-TACE was more effective than EPI-TACE in treating advanced-stage HCC and comparable in treating intermediate-stage HCC.
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Affiliation(s)
- Chenghao Zhao
- Department of Interventional Radiology, The 3rd Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Lu Road, Guangzhou, 510630, China
| | - Huzheng Yan
- Department of Interventional Radiology, The 3rd Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Lu Road, Guangzhou, 510630, China
| | - Zhanwang Xiang
- Department of Interventional Radiology, The 3rd Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Lu Road, Guangzhou, 510630, China
| | - Haofan Wang
- Department of Interventional Radiology, The 3rd Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Lu Road, Guangzhou, 510630, China
| | - Mingan Li
- Department of Interventional Radiology, The 3rd Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Lu Road, Guangzhou, 510630, China
| | - Mingsheng Huang
- Department of Interventional Radiology, The 3rd Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Lu Road, Guangzhou, 510630, China.
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10
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Abi-Jaoudeh N, Sadeghi B, Javan H, Na J, Beaton G, Tucci F, Ravula S, Imagawa DK. Drug-Eluting Embolic Loaded with Tyrosine Kinase Inhibitor Targeted Therapies for Transarterial Chemoembolization in a VX2 Model. Cancers (Basel) 2023; 15:3236. [PMID: 37370846 DOI: 10.3390/cancers15123236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 06/05/2023] [Accepted: 06/16/2023] [Indexed: 06/29/2023] Open
Abstract
Drug-eluting embolic transarterial chemoembolization (DEE-TACE) improves the overall survival of hepatocellular carcinoma (HCC), but the agents used are not tailored to HCC. Our patented liposomal formulation enables the loading and elution of targeted therapies onto DEEs. This study aimed to establish the safety, feasibility, and pharmacokinetics of sorafenib or regorafenib DEE-TACE in a VX2 model. DEE-TACE was performed in VX2 hepatic tumors in a selective manner until stasis using liposomal sorafenib- or regorafenib-loaded DEEs. The animals were euthanized at 1, 24, and 72 h timepoints post embolization. Blood samples were taken for pharmacokinetics at 5 and 20 min and at 1, 24, and 72 h. Measurements of sorafenib or regorafenib were performed in all tissue samples on explanted hepatic tissue using the same mass spectrometry method. Histopathological examinations were carried out on tumor tissues and non-embolized hepatic specimens. DEE-TACE was performed on 23 rabbits. The plasma concentrations of sorafenib and regorafenib were statistically significantly several folds lower than the embolized liver at all examined timepoints. This study demonstrates the feasibility of loading sorafenib or regorafenib onto commercially available DEEs for use in TACE. The drugs eluted locally without release into systemic circulation.
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Affiliation(s)
- Nadine Abi-Jaoudeh
- Department of Radiological Sciences, University of California Irvine, Orange, CA 92697, USA
| | - Ben Sadeghi
- Department of Radiological Sciences, University of California Irvine, Orange, CA 92697, USA
| | - Hanna Javan
- Department of Radiological Sciences, University of California Irvine, Orange, CA 92697, USA
| | - Jim Na
- Cullgen, Inc., San Diego, CA 92130, USA
| | | | - Fabio Tucci
- Epigen Biosciences, San Diego, CA 92121, USA
| | | | - David K Imagawa
- Department of Surgery, University of California Irvine, Orange, CA 92697, USA
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11
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Zhong BY, Jin ZC, Chen JJ, Zhu HD, Zhu XL. Role of Transarterial Chemoembolization in the Treatment of Hepatocellular Carcinoma. J Clin Transl Hepatol 2023; 11:480-489. [PMID: 36643046 PMCID: PMC9817054 DOI: 10.14218/jcth.2022.00293] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 08/17/2022] [Accepted: 08/22/2022] [Indexed: 01/18/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, transarterial chemoembolization (TACE) is the first-line recommendation for intermediate-stage HCC. In real-world clinical practice, TACE also plays an important role in early- and advanced-stage HCC. This review article by the experts from Chinese Liver Cancer Clinical Study Alliance (CHANCE) summarizes the available clinical evidence pertaining to the current application of TACE in patients with early-, intermediate-, and advanced-stage HCC. In addition, combination of TACE with other treatment modalities, especially immunotherapy, is reviewed.
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Affiliation(s)
- Bin-Yan Zhong
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Zhi-Cheng Jin
- Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, China
| | - Jian-Jian Chen
- Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, China
| | - Hai-Dong Zhu
- Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, China
- Correspondence to: Xiao-Li Zhu, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou, Jiangsu 215006, China; ORCID: https://orcid.org/0000-0002-5504-9528. Tel/Fax: +86-512-67780375, E-mail: ; Hai-Dong Zhu, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 DingjiaqiaoRoad, Nanjing, Jiangsu 210009, China. ORCID: https://orcid.org/0000-0003-1798-7641. Tel/Fax: +86-25-83792121, E-mail:
| | - Xiao-Li Zhu
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Correspondence to: Xiao-Li Zhu, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou, Jiangsu 215006, China; ORCID: https://orcid.org/0000-0002-5504-9528. Tel/Fax: +86-512-67780375, E-mail: ; Hai-Dong Zhu, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 DingjiaqiaoRoad, Nanjing, Jiangsu 210009, China. ORCID: https://orcid.org/0000-0003-1798-7641. Tel/Fax: +86-25-83792121, E-mail:
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12
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Jiang C, Sun XD, Qiu W, Chen YG, Sun DW, Lv GY. Conversion therapy in liver transplantation for hepatocellular carcinoma: What's new in the era of molecular and immune therapy? Hepatobiliary Pancreat Dis Int 2023; 22:7-13. [PMID: 36825482 DOI: 10.1016/j.hbpd.2022.10.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 10/18/2022] [Indexed: 11/04/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the sixth most common cancer globally, with limited therapies and unsatisfactory prognosis once in the advanced stages. With promising advances in locoregional and systematic treatments, fast development of targeted drugs, the success of immunotherapy, as well as the emergence of the therapeutic alliance, conversion therapy has recently become more well developed and an effective therapeutic strategy. This article aimed to review recent developments in conversion therapy in liver transplantation (LT) for HCC. DATA SOURCES We searched for relevant publications on PubMed before September 2022, using the terms "HCC", "liver transplantation", "downstaging", "bridging treatment" and "conversion therapy." RESULTS Conversion therapy was frequently represented as a combination of multiple treatment modalities to downstage HCC and make patients eligible for LT. Although combining various local and systematic treatments in conversion therapy is still controversial, growing evidence has suggested that multimodal combined treatment strategies downstage HCC in a shorter time, which ultimately increases the opportunities for LT. Moreover, the recent breakthrough of immunotherapy and targeted therapy for HCC also benefit patients with advanced-stage tumors. CONCLUSIONS In the era of targeted therapy and immunotherapy, applying the thinking of transplant oncology to benefit HCC patients receiving LT is a new topic that has shed light on advanced-stage patients. With the expansion of conversion therapy concepts, further investigation and research is required to realize the full potential of conversion treatment strategies, including accurately selecting candidates, determining the timing of surgery, improving the conversion rate, and guaranteeing the safety and long-term efficacy of treatment.
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Affiliation(s)
- Chao Jiang
- General Surgery Center, Department of Hepatobiliary and Pancreatic Surgery, the First Hospital of Jilin University, Changchun 130021, China
| | - Xiao-Dong Sun
- General Surgery Center, Department of Hepatobiliary and Pancreatic Surgery, the First Hospital of Jilin University, Changchun 130021, China
| | - Wei Qiu
- General Surgery Center, Department of Hepatobiliary and Pancreatic Surgery, the First Hospital of Jilin University, Changchun 130021, China
| | - Yu-Guo Chen
- General Surgery Center, Department of Hepatobiliary and Pancreatic Surgery, the First Hospital of Jilin University, Changchun 130021, China
| | - Da-Wei Sun
- General Surgery Center, Department of Hepatobiliary and Pancreatic Surgery, the First Hospital of Jilin University, Changchun 130021, China
| | - Guo-Yue Lv
- General Surgery Center, Department of Hepatobiliary and Pancreatic Surgery, the First Hospital of Jilin University, Changchun 130021, China.
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13
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Zheng Z, Ma M, Han X, Li X, Huang J, Zhao Y, Liu H, Kang J, Kong X, Sun G, Sun G, Kong J, Tang W, Shao G, Xiong F, Song J. Idarubicin-loaded biodegradable microspheres enhance sensitivity to anti-PD1 immunotherapy in transcatheter arterial chemoembolization of hepatocellular carcinoma. Acta Biomater 2023; 157:337-351. [PMID: 36509402 DOI: 10.1016/j.actbio.2022.12.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 11/23/2022] [Accepted: 12/02/2022] [Indexed: 12/13/2022]
Abstract
Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary hepatocellular carcinoma (HCC). However, conventional TACE formulations such as epirubicin-lipiodol emulsion are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. To overcome these limitations, we used biodegradable Idarubicin loaded microspheres (BILMs), which were prepared from gelatin and carrageenan and could be loaded with Idarubicin (IDA-MS). The morphology and the ability to load and release IDA of BILMs were characterized in vitro. We evaluated tumor changes and side effects after TACE treatment with IDA-MS in VX2 rabbit and C57BL/6 mice HCC models. In addition, the effect of IDA-MS on the tumor immune microenvironment of HCC tumors was elucidated via mass spectrometry and immunohistochemistry. Result showed that IDA-MS was developed as a new TACE formulation to overcome the poor delivery of drugs due to rapid elimination of the anticancer drug into the systemic circulation. We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment. STATEMENT OF SIGNIFICANCE: Conventional transarterial chemoembolization (TACE) formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in hepatocellular carcinoma (HCC). To overcome these limitations, we used biodegradable microspheres called BILMs, which could be loaded with Idarubicin (IDA-MS). We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment.
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Affiliation(s)
- Zhiying Zheng
- Hepatobiliary Center, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Mingxi Ma
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano-Science and Technology, Southeast University, Nanjing, China
| | - Xiuping Han
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Xiao Li
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jinxin Huang
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano-Science and Technology, Southeast University, Nanjing, China
| | - Yuetong Zhao
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Hanyuan Liu
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Junwei Kang
- Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiangyi Kong
- Hepatobiliary Center, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Guoqiang Sun
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Guangshun Sun
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jie Kong
- Department of Intervention, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
| | - Weiwei Tang
- Hepatobiliary Center, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
| | - Guoqiang Shao
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
| | - Fei Xiong
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano-Science and Technology, Southeast University, Nanjing, China.
| | - Jinhua Song
- Hepatobiliary Center, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
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14
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Burrel M, Bermúdez P. Drug-Eluting Embolic TACE (DEB-TACE). TRANSARTERIAL CHEMOEMBOLIZATION (TACE) 2023:57-64. [DOI: 10.1007/978-3-031-36261-3_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
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15
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Zhang Y, Wei W, Li C, Yan S, Wang S, Xiao S, He C, Li J, Qi Z, Li B, Yang K, Li C. Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein. Cell Death Dis 2022; 13:1034. [PMID: 36509750 PMCID: PMC9744908 DOI: 10.1038/s41419-022-05490-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 11/13/2022] [Accepted: 12/01/2022] [Indexed: 12/15/2022]
Abstract
Although second-generation therapies like abiraterone (ABI) and enzalutamide (ENZ) benefit patients with castration-resistant prostate cancer (CRPC), drug resistance frequently occurs, eventually resulting in therapy failure. In this study, we used two libraries, FDA-approved drug library and CRISP/Cas9 knockout (GeCKO) library to screen for drugs that overcome treatment resistance and to identify the potential drug-resistant genes involved in treatment resistance. Our screening results showed that the DNA-damaging agent idarubicin (IDA) overcame abiraterone and enzalutamide resistance in prostate cancer cells. IDA treatment inhibited the DNA repair protein XPA expression in a transcription-independent manner. Consistently, XPA knockout sensitized prostate cancer cells to abiraterone and enzalutamide treatment. In conclusion, IDA combats abiraterone and enzalutamide resistance by reducing XPA protein level in prostate cancer.
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Affiliation(s)
- Ying Zhang
- Institute of Precision Medicine, Jining Medical University, 272067, Jining, China
| | - Wei Wei
- Center for Experimental Medicine, School of Public Health, Jining Medical University, 272067, Jining, China
| | - Changying Li
- Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 300211, Tianjin, China
| | - Siyuan Yan
- Institute of Precision Medicine, Jining Medical University, 272067, Jining, China
| | - Shanshan Wang
- Institute of Precision Medicine, Jining Medical University, 272067, Jining, China
| | - Shudong Xiao
- Institute of Precision Medicine, Jining Medical University, 272067, Jining, China
| | - Chenchen He
- Department of Radiation Oncology, The First Affiliated Hospital, Xi'An Jiaotong University School of Medicine, 710061, Xi'An, China
| | - Jing Li
- Department of Histology and Embryology, School of Medicine, Nankai University, 300071, Tianjin, China
| | - Zhi Qi
- Department of Histology and Embryology, School of Medicine, Nankai University, 300071, Tianjin, China
| | - Benyi Li
- Department of Urology, The University of Kansas Medical Center, Kansas City, KS, 66160, USA
| | - Kuo Yang
- Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 300211, Tianjin, China.
| | - Changlin Li
- Institute of Precision Medicine, Jining Medical University, 272067, Jining, China.
- Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 300211, Tianjin, China.
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16
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Embolization therapy with microspheres for the treatment of liver cancer: State-of-the-art of clinical translation. Acta Biomater 2022; 149:1-15. [PMID: 35842035 DOI: 10.1016/j.actbio.2022.07.019] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 06/17/2022] [Accepted: 07/07/2022] [Indexed: 02/07/2023]
Abstract
Embolization with microspheres is a therapeutic strategy based on the selective occlusion of the blood vessels feeding a tumor. This procedure is intraarterially performed in the clinical setting for the treatment of liver cancer. The practice has evolved over the last decade through the incorporation of drug loading ability, biodegradability and imageability with the subsequent added functionality for the physicians and improved clinical outcomes for the patients. This review highlights the evolution of the embolization systems developed through the analysis of the marketed embolic microspheres for the treatment of malignant hepatocellular carcinoma, namely the most predominant form of liver cancer. Embolic microspheres for the distinct modalities of embolization (i.e., bland embolization, chemoembolization and radioembolization) are here comprehensively compiled with emphasis on material characteristics and their impact on microsphere performance. Moreover, the future application of the embolics under clinical investigation is discussed along with the scientific and regulatory challenges ahead in the field. STATEMENT OF SIGNIFICANCE: Embolization therapy with microspheres is currently used in the clinical setting for the treatment of most liver cancer conditions. The progressive development of added functionalities on embolic microspheres (such as biodegradability, imageability or drug and radiopharmaceutical loading capability) provides further benefit to patients and widens the therapeutic armamentarium for physicians towards truly personalized therapies. Therefore, it is important to analyze the possibilities that advanced biomaterials offer in the field from a clinical translational perspective to outline the future trends in therapeutic embolization.
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17
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Fan W, Zhu B, Yue S, Zheng X, Zou X, Li F, Qiao L, Wu Y, Xue M, Wang H, Tang Y, Li J. Idarubicin-Loaded DEB-TACE plus Lenvatinib versus Lenvatinib for patients with advanced hepatocellular carcinoma: A propensity score-matching analysis. Cancer Med 2022; 12:61-72. [PMID: 35698292 PMCID: PMC9844616 DOI: 10.1002/cam4.4937] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 05/25/2022] [Accepted: 05/29/2022] [Indexed: 01/27/2023] Open
Abstract
AIMS To investigate the efficacy and safety of lenvatinib and idarubicin-loaded drug-eluting beads transarterial chemoembolization (IDADEB-TACE) in primary advanced hepatocellular carcinoma (HCC). METHODS This retrospective study included patients with primary advanced HCC who received either lenvatinib monotherapy or lenvatinib plus IDADEB-TACE as first-line treatment from September 2019 to September 2020 at three institutes. Overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events were compared. Propensity score-matching was used to reduce the influence of confounding factors on the outcomes. RESULTS The study reviewed 118 patients who received lenvatinib plus IDADEB-TACE (LIDA group) and 182 who received lenvatinib alone (LEN group). After propensity score-matching, 78 pairs of patients remained. Compared to patients in the LEN group, those in the LIDA group had better post-treatment ORR (57.7% vs. 25.6%, p < 0.001, respectively), median OS and TTP (15.7 vs. 11.3 months, hazard ratio [HR] = 0.50, p < 0.001; 8.0 vs. 5.0 months, HR = 0.60, p = 0.003, respectively), 6- and 12-month OS rates (88.5% vs. 71.4%; 67.6% vs. 43.4%, respectively), and progression-free rates at 6 and 12 months (60.3% vs. 42.3%; 21.1% vs. 10.3%, respectively). Vascular invasion, α-fetoprotein level, and treatment type were independent OS predictors, and vascular invasion and treatment type were independent TTP predictors. Incidences of nausea/vomiting, fever, abdominal pain, and increased ALT/AST were higher in the LIDA group than in the LEN group. CONCLUSIONS Lenvatinib plus IDADEB-TACE is well-tolerated and more effective than lenvatinib monotherapy in patients with advanced HCC.
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Affiliation(s)
- Wenzhe Fan
- Department of Interventional OncologySun Yat‐sen University First Affiliated HospitalGuangzhouChina
| | - Bowen Zhu
- Department of Interventional OncologySun Yat‐sen University First Affiliated HospitalGuangzhouChina
| | - Shufan Yue
- Department of UltrasonicSun Yat‐sen University First Affiliated HospitalGuangzhouChina
| | - Xinlin Zheng
- Department of Interventional OncologySun Yat‐sen University First Affiliated HospitalGuangzhouChina
| | - Xinhua Zou
- Department of Interventional OncologySun Yat‐sen University First Affiliated HospitalGuangzhouChina
| | - Fuliang Li
- Liver and Gall Surgical DepartmentGaozhou People's HospitalGaozhouChina
| | - Liangliang Qiao
- Department of OncologyJinshazhou Hospital of Guangzhou University of Chinese MedicineGuangzhouChina
| | - Yanqin Wu
- Department of Interventional OncologySun Yat‐sen University First Affiliated HospitalGuangzhouChina
| | - Miao Xue
- Department of Interventional OncologySun Yat‐sen University First Affiliated HospitalGuangzhouChina
| | - Hongyu Wang
- Department of Interventional OncologySun Yat‐sen University First Affiliated HospitalGuangzhouChina
| | - Yiyang Tang
- Department of Interventional OncologySun Yat‐sen University First Affiliated HospitalGuangzhouChina
| | - Jiaping Li
- Department of Interventional OncologySun Yat‐sen University First Affiliated HospitalGuangzhouChina
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18
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Changes of Cell Adhesion Molecules and T Cell Subset Populations in Acute Myeloid Leukemia Patients Undergoing Intravenous Administration of Cytarabine Supplemented with Idarubicin. J CHEM-NY 2022. [DOI: 10.1155/2022/5507328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Objective. The present study aimed at investigating the efficacy and safety of intravenous administration of cytarabine supplemented with idarubicin in treating acute myeloid leukemia (AML) patients undergoing first attack and its effects on serum levels of cell adhesion molecules, cytokines in response to inflammation, and T cell subset populations in acute myeloid leukemia (AML) patients undergoing first attack. Methods. A total of 88 AML patients eligible for inclusion and exclusion criteria participated in the study and were randomly assigned into the control group (n = 44) in which the patients received intravenous administration of cytarabine and daunorubicin and the study group (n = 44) in which the patients received intravenous administration of cytarabine and idarubicin. Clinical response, incidence of adverse reactions, and quality of life 3 months after therapy were evaluated. Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), IL-10, and IL-35 were measured by ELISA methods. Phenotypic characteristics of T cell subsets including CD4+, CD8+, CD4+IL-10 Tregs, and CD4+CD25+CD127−Foxp3+ Tregs were analyzed by flow cytometry. Results. The clinical response rate of the study group was better than that of the control group (65.91% vs. 45.45%) (
). After treatment, the study group revealed significantly lower levels of sICAM-1, sVCAM-1, IL-10, and IL-35, a lower proportion of Tregs, a higher rate of CD4+/CD8+ T cells, along with increased scores of the Karnofsky Performance Scale (KPS) compared with the control group (
). The incidence rate of adverse reactions in the study group was lower than that in the control group (34.09% vs. 61.36%) (
). Conclusion. These findings demonstrate that intravenous administration of cytarabine supplemented with idarubicin can improve the immune function and quality of life of AML patients, and this combination drug therapy is effective and safe for AML.
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19
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Ebeling Barbier C, Heindryckx F, Lennernäs H. Limitations and Possibilities of Transarterial Chemotherapeutic Treatment of Hepatocellular Carcinoma. Int J Mol Sci 2021; 22:ijms222313051. [PMID: 34884853 PMCID: PMC8658005 DOI: 10.3390/ijms222313051] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 11/26/2021] [Accepted: 11/29/2021] [Indexed: 02/07/2023] Open
Abstract
Because diagnostic tools for discriminating between hepatocellular carcinoma (HCC) and advanced cirrhosis are poor, HCC is often detected in a stage where transarterial chemoembolization (TACE) is the best treatment option, even though it provides a poor survival gain. Despite having been used worldwide for several decades, TACE still has many limitations. First, there is a vast heterogeneity in the cellular composition and metabolism of HCCs as well as in the patient population, which renders it difficult to identify patients who would benefit from TACE. Often the delivered drug does not penetrate sufficiently selectively and deeply into the tumour and the drug delivery system is not releasing the drug at an optimal clinical rate. In addition, therapeutic effectiveness is limited by the crosstalk between the tumour cells and components of the cirrhotic tumour microenvironment. To improve this widely used treatment of one of our most common and deadly cancers, we need to better understand the complex interactions between drug delivery, local pharmacology, tumour targeting mechanisms, liver pathophysiology, patient and tumour heterogeneity, and resistance mechanisms. This review provides a novel and important overview of clinical data and discusses the role of the tumour microenvironment and lymphatic system in the cirrhotic liver, its potential response to TACE, and current and possible novel DDSs for locoregional treatment.
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Affiliation(s)
| | - Femke Heindryckx
- Department of Medical Cell Biology, Uppsala University, 751 23 Uppsala, Sweden;
| | - Hans Lennernäs
- Department of Pharmaceutical Biosciences, Uppsala University, 751 23 Uppsala, Sweden
- Correspondence: ; Tel.: +46-18-471-4317; Fax: +46-18-471-4223
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20
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Lucatelli P, Burrel M, Guiu B, de Rubeis G, van Delden O, Helmberger T. CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation. Cardiovasc Intervent Radiol 2021; 44:1851-1867. [PMID: 34694454 DOI: 10.1007/s00270-021-02968-1] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 09/04/2021] [Indexed: 12/15/2022]
Abstract
This CIRSE Standards of Practice document is aimed at interventional radiologists and provides best practices for performing transarterial chemoembolisation. It has been developed by an expert writing group under the guidance of the CIRSE Standards of Practice Committee. It will encompass all technical details reflecting European practice of different TACE procedures (Lp-TACE, DEM-TACE, DSM-TACE, b-TACE) as well as revising the existing literature on the various clinical indications (HCC, mCRC, ICC, NET). Finally, new frontiers of development will also be discussed.
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Affiliation(s)
- Pierleone Lucatelli
- Vascular and Interventional Radiology Unit, Department of Radiological Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy.
| | - Marta Burrel
- Radiology Department, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Boris Guiu
- Department of Radiology, Montpellier School of Medicine, St-Eloi University Hospital, Montpellier, France
| | - Gianluca de Rubeis
- Vascular and Interventional Radiology Unit, Department of Radiological Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy
- Department of Diagnostic Radiology, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
| | - Otto van Delden
- Department of Interventional Radiology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Thomas Helmberger
- Institute for Diagnostic and Interventional Radiology and Neuroradiology, Bogenhausen Hospital, Munich, Germany
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21
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Bucalau AM, Tancredi I, Verset G. In the Era of Systemic Therapy for Hepatocellular Carcinoma Is Transarterial Chemoembolization Still a Card to Play? Cancers (Basel) 2021; 13:5129. [PMID: 34680278 PMCID: PMC8533902 DOI: 10.3390/cancers13205129] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/30/2021] [Accepted: 10/07/2021] [Indexed: 02/07/2023] Open
Abstract
Conventional transarterial embolization (cTACE) has been proven to be effective for intermediate stage hepatocellular carcinoma (HCC), with a recent systematic review showing an overall survival (OS) of 19.4 months. Nevertheless, due to the rapid development of the systemic therapeutic landscape, the place of TACE is becoming questionable. Is there still a niche for TACE in the era of immunotherapy and combination treatments such as atezolizumab-bevacizumab, which has shown an OS of 19.2 months with excellent tolerance? The development of drug-eluting microspheres (DEMs) has led to the standardization of the technique, and along with adequate selection, it showed an OS of 48 months in a retrospective study. In order to increase treatment selectivity, new catheters have also been added to the TACE arsenal as well as the use of cone-beam CT (CBCT), which provides three-dimensional volumetric images and guidance during procedures. Moreover, the TACE indications have also widened. It may serve as a "bridging therapy" for liver transplantation candidates while they are on the waiting list, and it represents a valuable downstaging tool to transplantation criteria. The aim of this review is to explore the current data on the advancements of TACE and its future place amongst the growing panel of treatments.
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Affiliation(s)
- Ana-Maria Bucalau
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Hôpital Erasme, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium;
| | - Illario Tancredi
- Department of Interventional Radiology, Hôpital Erasme, 1070 Brussels, Belgium;
| | - Gontran Verset
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Hôpital Erasme, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium;
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22
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Fohlen A, Bordji K, Assenat E, Gongora C, Bazille C, Boulonnais J, Naveau M, Breuil C, Pérès EA, Bernaudin M, Guiu B. Anticancer Drugs for Intra-Arterial Treatment of Colorectal Cancer Liver Metastases: In-Vitro Screening after Short Exposure Time. Pharmaceuticals (Basel) 2021; 14:ph14070639. [PMID: 34358065 PMCID: PMC8308869 DOI: 10.3390/ph14070639] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 06/25/2021] [Accepted: 06/26/2021] [Indexed: 12/24/2022] Open
Abstract
To treat colorectal liver metastases, intra-arterial chemotherapies may complete therapeutic arsenal. Drugs using intra-arterially are very heterogeneous. The aim of this study was to select the most efficient drug on a panel of colorectal cancer (CRC) cell lines (Caco-2, HCT 116, HT 29, SW 48, SW 480, SW 620) exposed for 30 min to 12 cytotoxic agents (doxorubicin, epirubicin, idarubicin, 5-FU, raltitrexed, gemcitabine, cisplatin, oxaliplatin, mitomycin C, irinotecan, streptozocin, paclitaxel) at different concentrations. The effect on cell viability was measured using the WST-1 cell viability assay. For each drug and cell line, the IC50 and IC90 were calculated, which respectively correspond to the drug concentration (mg/mL) required to obtain 50% and 90% of cell death. We also quantified the cytotoxic index (CyI90 = C Max/IC90) to compare drug efficacy. The main findings of this study are that idarubicin emerged as the most cytotoxic agent to most of the tested CRC cell lines (Caco-2, HT29, HCT116, SW620 and SW480). Gemcitabine seemed to be the most efficient chemotherapy for SW48. Interestingly, the most commonly used cytotoxic agents in the systemic and intra-arterial treatment of colorectal liver metastasis (CRLM) (oxaliplatin, 5-FU, irinotecan) showed very limited cytotoxicity to all the cell lines.
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Affiliation(s)
- Audrey Fohlen
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
- Urodigestive Imagery and Interventional Radiology Department, University Hospital of Caen, CEDEX, 14000 Caen, France
- Correspondence: ; Tel.: +33-616702414
| | - Karim Bordji
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
| | - Eric Assenat
- Medical Oncology Department, Montpellier School of Medicine, Saint-Eloi University Hospital, 80 Avenue Augustin Fliche, 34295 Montpellier, France;
| | - Céline Gongora
- IRCM, Montpellier Cancerology Research Center, INSERM U1194, Montpellier University, Montpellier Regional Institute of Cancer, 34298 Montpellier, France;
| | - Céline Bazille
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
- Department of Pathology, University Hospital of Caen, CEDEX, 14000 Caen, France
| | - Jérémy Boulonnais
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
| | - Mikaël Naveau
- UNICAEN, CNRS, UMS 3408, GIP CYCERON, Normandie University, 14000 Caen, France;
| | - Cécile Breuil
- Pharmacy Department, University Hospital of Caen, CEDEX, 14000 Caen, France;
| | - Elodie A. Pérès
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
| | - Myriam Bernaudin
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
| | - Boris Guiu
- Radiology Department, Montpellier School of Medicine, Saint-Eloi University Hospital, 80 Avenue Augustin Fliche, 34295 Montpellier, France;
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23
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Zhang Y, Tang Y, Guo C, Li G. Integrative analysis identifies key mRNA biomarkers for diagnosis, prognosis, and therapeutic targets of HCV-associated hepatocellular carcinoma. Aging (Albany NY) 2021; 13:12865-12895. [PMID: 33946043 PMCID: PMC8148482 DOI: 10.18632/aging.202957] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 03/23/2021] [Indexed: 02/05/2023]
Abstract
Hepatitis C virus-associated HCC (HCV-HCC) is a prevalent malignancy worldwide and the molecular mechanisms are still elusive. Here, we screened 240 differentially expressed genes (DEGs) of HCV-HCC from Gene expression omnibus (GEO) and the Cancer Genome Atlas (TCGA), followed by weighted gene coexpression network analysis (WGCNA) to identify the most significant module correlated with the overall survival. 10 hub genes (CCNB1, AURKA, TOP2A, NEK2, CENPF, NUF2, CDKN3, PRC1, ASPM, RACGAP1) were identified by four approaches (Protein-protein interaction networks of the DEGs and of the significant module by WGCNA, and diagnostic and prognostic values), and their abnormal expressions, diagnostic values, and prognostic values were successfully verified. A four hub gene-based prognostic signature was built using the least absolute shrinkage and selection operator (LASSO) algorithm and a multivariate Cox regression model with the ICGC-LIRI-JP cohort (N =112). Kaplan-Meier survival plots (P = 0.0003) and Receiver Operating Characteristic curves (ROC = 0.778) demonstrated the excellent predictive potential for the prognosis of HCV-HCC. Additionally, upstream regulators including transcription factors and miRNAs of hub genes were predicted, and candidate drugs or herbs were identified. These findings provide a firm basis for the exploration of the molecular mechanism and further clinical biomarkers development of HCV-HCC.
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MESH Headings
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/virology
- Computational Biology
- Datasets as Topic
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Gene Regulatory Networks
- Hepatitis C, Chronic/genetics
- Hepatitis C, Chronic/pathology
- Hepatitis C, Chronic/virology
- Humans
- Kaplan-Meier Estimate
- Liver/pathology
- Liver/virology
- Liver Neoplasms/diagnosis
- Liver Neoplasms/genetics
- Liver Neoplasms/mortality
- Liver Neoplasms/virology
- MicroRNAs/metabolism
- Predictive Value of Tests
- Prognosis
- Protein Interaction Maps/genetics
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Risk Assessment/methods
- Transcription Factors/metabolism
- Transcriptome/genetics
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Affiliation(s)
- Yongqiang Zhang
- Molecular Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, P.R. China
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610041, P.R. China
| | - Yuqin Tang
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P.R. China
| | - Chengbin Guo
- Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, P.R. China
| | - Gen Li
- Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, P.R. China
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24
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Guan MC, Wang MD, Liu SY, Ouyang W, Liang L, Pawlik TM, Xu QR, Huang DS, Shen F, Zhu H, Yang T. Early diagnosis and therapeutic strategies for hepatocellular carcinoma: From bench to bedside. World J Gastrointest Oncol 2021; 13:197-215. [PMID: 33889272 PMCID: PMC8040062 DOI: 10.4251/wjgo.v13.i4.197] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/14/2021] [Accepted: 03/11/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. The prognosis of patients with HCC remains poor largely due to the late diagnosis and lack of effective treatments. Despite being widely used, alpha-fetoprotein serology and ultrasonography have limited diagnostic performance for early-stage HCC. The emergence of omics strategies has contributed to significant advances in the development of non-invasive biomarkers for the early diagnosis of HCC including proteins, metabolites, circulating tumor deoxyribonucleic acid, and circulating non-coding ribonucleic acid. Early diagnosis is beneficial to patients as it increases the proportion who can be treated with curative treatment, thus prolonging survival outcomes. Currently, multiple clinical trials involving locoregional, systemic therapies, and combinations of these modalities are changing therapeutic strategies for different stage HCC. Success in several preclinical trials that involve immunotherapeutic innovations has created the potential to complement and enforce other treatment strategies in the future. This review summarizes the most recent advances in non-invasive early molecular detection, current therapy strategies, and potential immunotherapeutic innovations of HCC.
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Affiliation(s)
- Ming-Cheng Guan
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai 200438, China
| | - Si-Yu Liu
- Department of Laboratory, Lishui Municipal Central Hospital, Lishui 323000, Zhejiang Province, China
| | - Wei Ouyang
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Lei Liang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310000, Zhejiang Province, China
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
| | - Timothy M Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH 43210, United States
| | - Qiu-Ran Xu
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310000, Zhejiang Province, China
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
| | - Dong-Sheng Huang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310000, Zhejiang Province, China
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai 200438, China
| | - Hong Zhu
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai 200438, China
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310000, Zhejiang Province, China
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
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Golfieri R, Bezzi M, Verset G, Fucilli F, Mosconi C, Cappelli A, Paccapelo A, Lucatelli P, Magand N, Rode A, De Baere T. Retrospective European Multicentric Evaluation of Selective Transarterial Chemoembolisation with and without Balloon-Occlusion in Patients with Hepatocellular Carcinoma: A Propensity Score Matched Analysis. Cardiovasc Intervent Radiol 2021; 44:1048-1059. [PMID: 33709273 PMCID: PMC8189964 DOI: 10.1007/s00270-021-02805-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 02/10/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE The aim of this retrospective multicentric study was to compare the tumour response rates of Balloon-occluded Transarterial Chemoembolisation (B-TACE) to non-B-TACE using propensity score matching (PSM) in patients with hepatocellular carcinoma and to investigate the clinical benefit, such as lower rates of TACE re-intervention achieved using B-TACE. MATERIAL AND METHODS The B-TACE procedures (n = 96 patients) were compared with a control group of non-B-TACE treatments (n = 434 pts), performed with conventional (cTACE) or drug-eluting microspheres TACE (DEM-TACE). Data were collected from six European centres from 2015 to 2019. Objective responses (OR) and complete response (CR) rates after the first session and the number of TACE re-interventions were evaluated using PSM (91 patients per arm). RESULTS The best target OR after PSM were similar for both B-TACE and non-B-TACE (90.1% and 86.8%, p = 0.644); however, CR at 1-6 months was significantly higher for B-TACE (59.3% vs. 41.8%, p = 0.026). Patients treated with B-TACE had a significantly lower retreatment rate during the first 6 months (9.9%% vs. 22.0%, p = 0.041). Post-embolisation syndrome (PES) rates were 8.8% in non-B-TACE and 41.8% in B-TACE (p < 0.001), with no significant differences between groups regarding major adverse events. CONCLUSION B-TACE is safe and effective, achieving higher CR rates than non-B-TACE. Patients undergoing B-TACE had a significantly lower retreatment rate within the first 6 months but higher PES rates. LEVEL OF EVIDENCE III Level 3, retrospective study.
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Affiliation(s)
- Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, via Albertoni 15, 40138, Bologna, Italy. .,Università Degli Studi Di Bologna, Bologna, Italy.
| | - Mario Bezzi
- Vascular and Interventional Radiology Unit, Department of Diagnostic Service, Sapienza University of Rome, Rome, Italy
| | - Gontran Verset
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Fabio Fucilli
- Radiology Unit, S. De Bellis National Institute of Gastroenterology Research Hospital, Castellana Grotte (BARI), Bari, Italy
| | - Cristina Mosconi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, via Albertoni 15, 40138, Bologna, Italy
| | - Alberta Cappelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, via Albertoni 15, 40138, Bologna, Italy
| | - Alexandro Paccapelo
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, via Albertoni 15, 40138, Bologna, Italy
| | - Pierleone Lucatelli
- Vascular and Interventional Radiology Unit, Department of Diagnostic Service, Sapienza University of Rome, Rome, Italy
| | - Nicolas Magand
- Diagnostic and Interventional Radiology Department, Croix Rousse Hospital, Hospices Civils de, Lyon, France
| | - Agnes Rode
- Diagnostic and Interventional Radiology Department, Croix Rousse Hospital, Hospices Civils de, Lyon, France
| | - Thierry De Baere
- Department of Interventional Radiology, Gustave Roussy Cancer Center, Villejuif, France
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26
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Guiu B, Assenat E. Doxorubicin for the treatment of hepatocellular carcinoma: GAME OVER! ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1693. [PMID: 33490205 PMCID: PMC7812160 DOI: 10.21037/atm-2020-131] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Boris Guiu
- Department of Radiology, St-Eloi University Hospital, Montpellier, France
| | - Eric Assenat
- Department of Oncology, St-Eloi University Hospital, Montpellier, France
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27
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Real Life Prospective Evaluation of New Drug-Eluting Platform for Chemoembolization of Patients with Hepatocellular Carcinoma: PARIS Registry. Cancers (Basel) 2020; 12:cancers12113405. [PMID: 33212917 PMCID: PMC7698357 DOI: 10.3390/cancers12113405] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 11/07/2020] [Accepted: 11/10/2020] [Indexed: 02/08/2023] Open
Abstract
Simple Summary Hepatocellular carcinoma treatment options depend on stage of disease. In intermediate stage transarterial chemoembolization with drug-eluting microspheres (DEM-TACE) is recommended. DEM-TACE is simultaneous embolization of tumour feeding arteries and local delivery of anticancer drugs. We assessed real-life practice, safety, toxicity and efficacy of this therapy using new embolization microspheres in 97 patients. Toxicity of the treatment in our study was within or below rates reported so far, and the healthy liver parenchyma, the bile ducts and the portal vein were well preserved when compared with previous study using other type of DEM. Tumour response rate was high, achieving disease control in almost all patients. Hepatocellular carcinoma was controlled during 16.7 months with DEM-TCE as the only treatment. At one year 81% and at two years 66% of patients were alive. Our study showed that DEM-TACE in patients from every-day clinical practice is safe and efficient treatment modality. Abstract Background and aim: Transarterial chemoembolization with drug-eluting microspheres (DEM-TACE) is recommended for patients with BCLC stage B hepatocellular carcinoma (HCC) and stage 0-A unsuitable for curative treatments. We assessed efficacy and safety along with hepatobiliary toxicities (HBT) of DEM-TACE using a novel microsphere, LifePearlTM, loaded with anthracyclines. Materials and methods: 97 patients diagnosed with HCC were prospectively enrolled and treated using LifePearlTM loaded with doxorubicin (77%) or idarubicin (23%). Safety and tolerability were assessed using CTCAE, HBT by CT/MRI scans, and tumor response by applying modified Response Evaluation Criteria in Solid Tumors (mRECIST). Follow-up was after 2 years. Results: Adverse events (AE) were reported in 73.2% of patients, majority being Grade 1–2. Grade ≥ 3 AE reported in 13.4% of patients were mainly related to postembolization syndrome. HBT were observed after 15.5% (29/187) of the DEM-TACEs. Objective response and disease control rates were 81% and 99%, respectively, as the best responses. Survival rates at one and two years were 81% and 66%, respectively, while the median overall survival (OS) was not reached. Median progression free survival was 13.7 months (95% CI: 11.3; 15.6) and median time to TACE untreatable progression was 16.7 months (95% CI: 12.7; not estimable (n.e.)). Conclusions: DEM-TACE using LifePearlTM provides a high tumor response rate in HCC patients. HBT rates within or below previously reported results for cTACE and DEM-TACE indicate a good safety profile for LifePearlTM. The trial was registered in National Library of Medicine (ID: NCT03053596).
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TACE mit Idarubicin-Beads. ROFO-FORTSCHR RONTG 2020. [DOI: 10.1055/a-0999-7302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Roth GS, Teyssier Y, Abousalihac M, Seigneurin A, Ghelfi J, Sengel C, Decaens T. Idarubicin vs doxorubicin in transarterial chemoembolization of intermediate stage hepatocellular carcinoma. World J Gastroenterol 2020; 26:324-334. [PMID: 31988592 PMCID: PMC6969879 DOI: 10.3748/wjg.v26.i3.324] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 11/29/2019] [Accepted: 12/22/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver cancer is the fifth most common cancer and the second cause of cancer-related deaths worldwide. Transarterial chemoembolization (TACE) is the best treatment of intermediate hepatocellular carcinoma (HCC). Doxorubicin is the most commonly used drug despite a low level of evidence.
AIM To compare the objective response rate of idarubicin-based TACE (Ida-TACE) against doxorubicin-based TACE (Dox-TACE) in intermediate stage HCC.
METHODS Between January 2012 and December 2014, all patients treated with TACE at our academic hospital were screened. Inclusion criteria were patients with Child-Pugh score A or B, a performance status below or equal to 1, and no prior TACE. Either lipiodol TACE or drug-eluting beads TACE could be performed with 10 mg of idarubicin or 50 mg of doxorubicin. Each patient treated with idarubicin was matched with two doxorubicin-treated patients. The TACE response was assessed by independent radiologists according to the mRECIST criteria.
RESULTS Sixty patients were treated with doxorubicin and thirty with idarubicin. There were 93% and 87% of cirrhotic patients and 87% and 70% of Child-Pugh A in the doxorubicin and idarubicin groups, respectively. The median number of HCC per patient was two in both groups with 31% and 26% of single nodules in doxorubicin and idarubicin groups, respectively. Objective response rate after first TACE was 76.7% and 73.3% (P = 0.797) with 41.7% and 40.0% complete response in doxorubicin and idarubicin groups, respectively. Progression-free survival was 7.7 mo in both groups, and liver transplant-free survival was 24.9 mo and 21.9 mo in doxorubicin and idarubicin groups, respectively. Safety profiles were similar in both groups, with grade 3-4 adverse events in 35% of Dox-TACE and 43% of Ida-TACEs.
CONCLUSION Ida-TACE and Dox-TACE showed comparable results in terms of efficacy and safety. Ida-TACE may represent an interesting alternative to Dox-TACE in the management of patients with intermediate stage HCC.
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Affiliation(s)
- Gaël Stéphane Roth
- Clinique Universitaire d’Hépato-Gastroentérologie et Oncologie Digestive, CHU Grenoble-Alpes, Grenoble 38043, France
- Faculté de Médicine, Université Grenoble-Alpes, Domaine de la Merci, La Tronche 38700, France
- Institute for Advanced Biosciences - INSERM U1209/CNRS UMR 5309/Université Grenoble-Alpes, Site Santé - Allée des Alpes, La Tronche 38700, France
| | - Yann Teyssier
- Faculté de Médicine, Université Grenoble-Alpes, Domaine de la Merci, La Tronche 38700, France
- Clinique Universitaire de Radiologie et Imagerie Médicale, CHU Grenoble-Alpes, Grenoble 38043, France
| | - Mélodie Abousalihac
- Clinique Universitaire d’Hépato-Gastroentérologie et Oncologie Digestive, CHU Grenoble-Alpes, Grenoble 38043, France
| | - Arnaud Seigneurin
- Faculté de Médicine, Université Grenoble-Alpes, Domaine de la Merci, La Tronche 38700, France
- Département de Santé Publique - CHU Grenoble-Alpes, Grenoble 38043, France
| | - Julien Ghelfi
- Clinique Universitaire de Radiologie et Imagerie Médicale, CHU Grenoble-Alpes, Grenoble 38043, France
| | - Christian Sengel
- Clinique Universitaire de Radiologie et Imagerie Médicale, CHU Grenoble-Alpes, Grenoble 38043, France
| | - Thomas Decaens
- Clinique Universitaire d’Hépato-Gastroentérologie et Oncologie Digestive, CHU Grenoble-Alpes, Grenoble 38043, France
- Faculté de Médicine, Université Grenoble-Alpes, Domaine de la Merci, La Tronche 38700, France
- Institute for Advanced Biosciences - INSERM U1209/CNRS UMR 5309/Université Grenoble-Alpes, Site Santé - Allée des Alpes, La Tronche 38700, France
- Department of Hepatology and Gastroenterology, Grenoble-Alpes University Hospital, Grenoble 38043, France
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Fu X, Luo RG, Qiu W, Ouyang L, Fan GQ, Liang QR, Tang Q. Sustained release of arsenic trioxide benefits interventional therapy on rabbit VX2 liver tumor. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2019; 24:102118. [PMID: 31678180 DOI: 10.1016/j.nano.2019.102118] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 10/01/2019] [Accepted: 10/13/2019] [Indexed: 11/28/2022]
Abstract
The benefit of chemotherapy as a constituent of transcatheter arterial chemoembolization (TACE) is still in debate. Recently we have developed arsenic trioxide nanoparticle prodrug (ATONP) as a new anticancer drug, but its systemic toxicity is a big issue. In this preclinical TACE study, ATONP emulsified in lipiodol behaved as drug-eluting bead manner. Sustained release of arsenic from ATONP within occluded tumor caused very low arsenic level in plasma, avoiding the "rushing out" effect as ATO did. Correspondingly, intratumoral arsenic accumulation and inorganic phosphate deprivation were simultaneously observed, and arsenic concentration was much higher as ATONP was transarterially administered than ATO, or intravenously injected. Tumor necrosis and apoptosis were remarkably more severe in ATONP group than ATO, but no significant hepatic and renal toxicity was perceived. In brief, ATONP alleviated arsenic toxicity and boosted the therapeutic effect of TACE via Pi-activated drug sustainable release.
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Affiliation(s)
- Xin Fu
- Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, China
| | - Rong-Guang Luo
- Department of Medical Imaging and Interventional Radiology, the First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Wei Qiu
- Department of Interventional and Vascular Radiology, Chaohu Hospital of Anhui Medical University, Chaohu, China
| | - Lu Ouyang
- Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, China
| | - Guang-Qin Fan
- Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, China
| | - Qing-Rong Liang
- Institute for Advanced Study, Nanchang University, Nanchang, China
| | - Qun Tang
- Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, China; Institute for Advanced Study, Nanchang University, Nanchang, China.
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Chemoembolization of HCC: Time for Technical Standardization, or Is It Too Late? Cardiovasc Intervent Radiol 2019; 42:1329-1330. [DOI: 10.1007/s00270-019-02268-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 06/11/2019] [Accepted: 06/11/2019] [Indexed: 10/26/2022]
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Affiliation(s)
- Siddharth A Padia
- From the Section of Interventional Radiology, Department of Radiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, Calif
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