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De Gaetano V, Pallozzi M, Cerrito L, Santopaolo F, Stella L, Gasbarrini A, Ponziani FR. Management of Portal Hypertension in Patients with Hepatocellular Carcinoma on Systemic Treatment: Current Evidence and Future Perspectives. Cancers (Basel) 2024; 16:1388. [PMID: 38611066 PMCID: PMC11011056 DOI: 10.3390/cancers16071388] [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: 02/21/2024] [Revised: 03/27/2024] [Accepted: 03/28/2024] [Indexed: 04/14/2024] Open
Abstract
The management of CSPH in patients undergoing systemic treatment for HCC has emerged as a critical concern due to the absence of reliable diagnostic criteria and uncertainties surrounding therapeutic approaches. This review aims to underscore the primary pathophysiological aspects linking HCC and PH, while also addressing the current and emerging clinical strategies for the management of portal hypertension. A review of studies from January 2003 to June 2023 was conducted using the PubMed database and employing MeSH terms, such as "hepatocellular carcinoma", "immune checkpoint inhibitors", "systemic therapy", "portal hypertension", "variceal bleeding" and "tyrosine kinase inhibitors". Despite promising results of tyrosine kinase inhibitors in animal models for PH and fibrosis, only Sorafenib has demonstrated similar effects in human studies, whereas Lenvatinib appears to promote PH development. The impact of Atezolizumab/Bevacizumab on PH remains uncertain, with an increasing risk of bleeding related to Bevacizumab in patients with prior variceal hemorrhage. Given the absence of specific guidelines, endoscopic surveillance during treatment is advisable, and primary and secondary prophylaxis of variceal bleeding should adhere to the Baveno VII recommendations. Furthermore, in patients with advanced HCC, refinement of diagnostic criteria for CSPH and guidelines for its surveillance are warranted.
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Affiliation(s)
- Valeria De Gaetano
- Liver Unit, Centro Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario GemelliIstituto di Ricovero e Cura a Carattere Scientifico, IRCCS, 00168 Rome, Italy; (V.D.G.); (M.P.); (L.C.); (F.S.); (L.S.); (F.R.P.)
| | - Maria Pallozzi
- Liver Unit, Centro Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario GemelliIstituto di Ricovero e Cura a Carattere Scientifico, IRCCS, 00168 Rome, Italy; (V.D.G.); (M.P.); (L.C.); (F.S.); (L.S.); (F.R.P.)
| | - Lucia Cerrito
- Liver Unit, Centro Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario GemelliIstituto di Ricovero e Cura a Carattere Scientifico, IRCCS, 00168 Rome, Italy; (V.D.G.); (M.P.); (L.C.); (F.S.); (L.S.); (F.R.P.)
| | - Francesco Santopaolo
- Liver Unit, Centro Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario GemelliIstituto di Ricovero e Cura a Carattere Scientifico, IRCCS, 00168 Rome, Italy; (V.D.G.); (M.P.); (L.C.); (F.S.); (L.S.); (F.R.P.)
| | - Leonardo Stella
- Liver Unit, Centro Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario GemelliIstituto di Ricovero e Cura a Carattere Scientifico, IRCCS, 00168 Rome, Italy; (V.D.G.); (M.P.); (L.C.); (F.S.); (L.S.); (F.R.P.)
| | - Antonio Gasbarrini
- Liver Unit, Centro Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario GemelliIstituto di Ricovero e Cura a Carattere Scientifico, IRCCS, 00168 Rome, Italy; (V.D.G.); (M.P.); (L.C.); (F.S.); (L.S.); (F.R.P.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Liver Unit, Centro Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario GemelliIstituto di Ricovero e Cura a Carattere Scientifico, IRCCS, 00168 Rome, Italy; (V.D.G.); (M.P.); (L.C.); (F.S.); (L.S.); (F.R.P.)
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Huang J, Wu Q, Geller DA, Yan Y. Macrophage metabolism, phenotype, function, and therapy in hepatocellular carcinoma (HCC). J Transl Med 2023; 21:815. [PMID: 37968714 PMCID: PMC10652641 DOI: 10.1186/s12967-023-04716-0] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 11/09/2023] [Indexed: 11/17/2023] Open
Abstract
The pivotal role of the tumor microenvironment (TME) in the initiation and advancement of hepatocellular carcinoma (HCC) is widely acknowledged, as it fosters the proliferation and metastasis of HCC cells. Within the intricate TME of HCC, tumor-associated macrophages (TAMs) represent a significant constituent of non-malignant cells. TAMs engage in direct communication with cancer cells in HCC, while also exerting influence on other immune cells to adopt a tumor-supportive phenotype that facilitates tumor progression. Among the multifaceted mechanisms at play, the metabolic reprogramming of both tumor cells and macrophages leads to phenotypic alterations and functional modifications in macrophages. This comprehensive review elucidates the intricate interplay between cellular metabolism and macrophage phenotype/polarization, while also providing an overview of the associated signaling molecules and potential therapeutic strategies for HCC.
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Affiliation(s)
- Jingquan Huang
- Department of General Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, Guangxi, China
| | - Qiulin Wu
- Department of General Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, Guangxi, China
| | - David A Geller
- Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, 15260, USA.
| | - Yihe Yan
- Department of General Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, Guangxi, China.
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Parikh ND, Girvan A, Coulter J, Gable J, Poon JL, Kim S, Chatterjee A, Boeri M. Risk thresholds for patients to switch between daily tablets and biweekly infusions in second-line treatment for advanced hepatocellular carcinoma: a patient preference study. BMC Cancer 2023; 23:66. [PMID: 36658529 PMCID: PMC9851100 DOI: 10.1186/s12885-022-10388-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 11/30/2022] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Historically, high hepatocellular carcinoma (HCC)-related mortality has been, in part, due to lack of effective therapies; however, several systemic therapies have been recently approved for HCC treatment, including regorafenib and ramucirumab. These two treatments utilize different routes of administration (four daily tablets and biweekly intravenous infusions, respectively) and have different risks of adverse events (AEs). However, we lack data on patient preferences in balancing the route of administration and risk of AEs in patients with HCC. We aimed to determine patient preferences and trade-offs for second-line treatment in patients with HCC. METHODS: Patients with advanced or metastatic HCC were recruited through their physicians for this study. Patient preferences were assessed by using a modified threshold technique (TT) design in which respondents were asked two direct-elicitation questions before (assuming same safety and efficacy and only varying mode of administration) and after (incorporating the safety profiles of ramucirumab and regorafenib) the TT series on seven risks of clinically relevant AEs. RESULTS In total, of the 157 patients recruited by their physicians, 150 were eligible and consented to participate. In the first elicitation question (assuming risk and efficacy were equivalent), 61.3% of patients preferred daily tablets. However, 76.7% of patients preferred the biweekly infusion when the safety profiles of the two available second-line therapies were included. The TT analysis confirmed that preferences for oral administration were not strong enough to balance out the risk of AEs that differentiate the two therapies. DISCUSSION We found that when patients were asked to choose between a daily, oral medication and a biweekly IV medication for HCC, they were more likely to choose a daily, oral medication if efficacy and safety profiles were the same. However, when risks of AEs representing the safety profiles of two currently available second-line treatments were introduced in a second direct-elicitation question, respondents often selected an IV administration with a safety profile similar to ramucirumab, rather than oral tablets with a safety profile similar to regorafenib. Our findings indicate that the risk profile of a second-line treatment for HCC may be more important than the mode of administration to patients.
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Affiliation(s)
- Neehar D. Parikh
- grid.412590.b0000 0000 9081 2336Division of Gastroenterology and Hepatology, University of Michigan Health System, Ann Arbor, MI USA
| | - Allicia Girvan
- grid.417540.30000 0000 2220 2544Eli Lilly and Company, Indianapolis, IN USA
| | - Joshua Coulter
- grid.62562.350000000100301493RTI Health Solutions, Research Triangle Park, NC USA
| | - Jonathon Gable
- grid.417540.30000 0000 2220 2544Eli Lilly and Company, Indianapolis, IN USA
| | - Jiat Ling Poon
- grid.417540.30000 0000 2220 2544Eli Lilly and Company, Indianapolis, IN USA
| | - Sangmi Kim
- grid.417540.30000 0000 2220 2544Eli Lilly and Company, Indianapolis, IN USA
| | - Anindya Chatterjee
- grid.417540.30000 0000 2220 2544Eli Lilly and Company, Indianapolis, IN USA
| | - Marco Boeri
- RTI Health Solutions, 123B Forsyth House, Cromac Square, Belfast, BT2 8LA UK
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Cammarota A, Zanuso V, D’Alessio A, Pressiani T, Personeni N, Rimassa L. Cabozantinib plus atezolizumab for the treatment of advanced hepatocellular carcinoma: Shedding light on the preclinical rationale and clinical trials. Expert Opin Investig Drugs 2022; 31:401-413. [DOI: 10.1080/13543784.2022.2032641] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Antonella Cammarota
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan,Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Valentina Zanuso
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan,Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Antonio D’Alessio
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan,Italy
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospitalc, London, W120HS, United Kingdom
| | - Tiziana Pressiani
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Nicola Personeni
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan,Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan,Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
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Li H. Angiogenesis in the progression from liver fibrosis to cirrhosis and hepatocelluar carcinoma. Expert Rev Gastroenterol Hepatol 2021; 15:217-233. [PMID: 33131349 DOI: 10.1080/17474124.2021.1842732] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Introduction: Persistent inflammation and hypoxia are strong stimulus for pathological angiogenesis and vascular remodeling, and are also the most important elements resulting in liver fibrosis. Sustained inflammatory process stimulates fibrosis to the end-point of cirrhosis and sinusoidal portal hypertension is an important feature of cirrhosis. Neovascularization plays a pivotal role in collateral circulation formation of portal vein, mesenteric congestion, and high perfusion. Imbalance of hepatic artery and portal vein blood flow leads to the increase of hepatic artery inflow, which is beneficial to the formation of nodules. Angiogenesis contributes to progression from liver fibrosis to cirrhosis and hepatocellular carcinoma (HCC) and anti-angiogenesis therapy can improve liver fibrosis, reduce portal pressure, and prolong overall survival of patients with HCC. Areas covers: This paper will try to address the difference of the morphological characteristics and mechanisms of neovascularization in the process from liver fibrosis to cirrhosis and HCC and further compare the different efficacy of anti-angiogenesis therapy in these three stages. Expert opinion: More in-depth understanding of the role of angiogenesis factors and the relationship between angiogenesis and other aspects of the pathogenesis and transformation may be the key to enabling future progress in the treatment of patients with liver fibrosis, cirrhosis, and HCC.
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Affiliation(s)
- Hui Li
- Central Laboratory, Hospital of Chengdu University of Traditional Chinese Medicine , Chengdu, Sichuan Province, P. R. China
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Patel K, Lamm R, Altshuler P, Dang H, Shah AP. Hepatocellular Carcinoma-The Influence of Immunoanatomy and the Role of Immunotherapy. Int J Mol Sci 2020; 21:ijms21186757. [PMID: 32942580 PMCID: PMC7555667 DOI: 10.3390/ijms21186757] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 09/09/2020] [Accepted: 09/14/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality worldwide. Most patients are diagnosed with advanced disease, limiting their options for treatment. While current treatments are adequate for lower staged disease, available systemic treatments are limited, with marginal benefit at best. Chimeric antigen receptor (CAR) T cell therapy, effective in treating liquid tumors such as B-cell lymphoma, presents a potentially promising treatment option for advanced HCC. However, new challenges specific to solid tumors, such as tumor immunoanatomy or the immune cell presence and position anatomically and the tumor microenvironment, need to be defined and overcome. Immunotherapy currently in use must be re-engineered and re-envisioned to treat HCC with the hopes of ushering in an answer to advanced stage solid tumor disease processes. Future therapy options must address the uniqueness of the tumors under the umbrella of HCC. This review strives to summarize HCC, its staging system, current therapy and immunotherapy medications currently being utilized or studied in the treatment of HCC with the hopes of highlighting what is being done and suggesting what needs to be done in the future to champion this therapy as an effective option.
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Affiliation(s)
- Keyur Patel
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19144, USA; (K.P.); (R.L.); (P.A.)
| | - Ryan Lamm
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19144, USA; (K.P.); (R.L.); (P.A.)
| | - Peter Altshuler
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19144, USA; (K.P.); (R.L.); (P.A.)
| | - Hien Dang
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19144, USA; (K.P.); (R.L.); (P.A.)
- Sidney Kimmel Cancer Center, Philadelphia, PA 19107, USA
- Correspondence: (H.D.); (A.P.S.)
| | - Ashesh P. Shah
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19144, USA; (K.P.); (R.L.); (P.A.)
- Correspondence: (H.D.); (A.P.S.)
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Tang Y, Cao J, Cai Z, An H, Li Y, Peng Y, Chen N, Luo A, Tao H, Li K. Epigallocatechin gallate induces chemopreventive effects on rats with diethylnitrosamine‑induced liver cancer via inhibition of cell division cycle 25A. Mol Med Rep 2020; 22:3873-3885. [PMID: 33000276 PMCID: PMC7533491 DOI: 10.3892/mmr.2020.11463] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 07/03/2020] [Indexed: 02/06/2023] Open
Abstract
Epigallocatechin gallate (EGCG), the most active monomer in green tea (GT), has demonstrated potential therapeutic and preventive effects on various tumors, including liver cancer. However, the anticancer mechanisms of EGCG in liver cancer remain to be elucidated. The abnormal expression of cell division cycle 25A (CDC25A) has been identified in liver cancer and is closely associated with malignancy and poor prognosis in patients with hepatocellular carcinoma (HCC). The present study used human hepatoma cell lines and rats with diethylnitrosamine (DEN)-induced HCC as models to investigate the association between the effect of EGCG on liver cancer and regulation of the p21waf1/Cip1/CDC25A axis. The results demonstrated that EGCG can inhibit the proliferation of HepG2 and Huh7 cells, reduce the expression of CDC25A and increase the expression of p21waf1/Cip1 in HepG2. In vivo, HCC was induced by DEN in Sprague-Dawley rats. EGCG significantly reduced tumor volume and improved the survival rates of rats with HCC. The expression levels of CDC25A mRNA and protein in liver tissues and the level of serum γ glutamyl transpeptidase in rats treated with EGCG were significantly decreased, while p21waf1/Cip1 mRNA and protein expression levels were increased compared with the HCC group, in the process of DEN-induced HCC. No significant difference in the chemopreventive effects on liver cancer was observed between GT extract and EGCG under an EGCG equivalence condition. Thus, EGCG can suppress human hepatoma cell proliferation and prolong the survival of rats with HCC, and the potential mechanism may be involved in EGCG-induced upregulation of p21waf1/Cip1 and downregulation of CDC25A.
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Affiliation(s)
- Yanping Tang
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, P.R. China
| | - Ji Cao
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, P.R. China
| | - Zhengmin Cai
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, P.R. China
| | - Huihua An
- Department of Clinical Medicine, College of Basic Medicine, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Yuqun Li
- Department of Clinical Medicine, College of Basic Medicine, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Yan Peng
- Department of Clinical Medicine, College of Basic Medicine, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Ni Chen
- Department of Clinical Medicine, College of Basic Medicine, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Anqiang Luo
- Department of Clinical Medicine, College of Basic Medicine, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Hao Tao
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, P.R. China
| | - Kezhi Li
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, P.R. China
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Rizzo A, Nannini M, Novelli M, Dalia Ricci A, Scioscio VD, Pantaleo MA. Dose reduction and discontinuation of standard-dose regorafenib associated with adverse drug events in cancer patients: a systematic review and meta-analysis. Ther Adv Med Oncol 2020; 12:1758835920936932. [PMID: 32684988 PMCID: PMC7343359 DOI: 10.1177/1758835920936932] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Accepted: 05/22/2020] [Indexed: 12/12/2022] Open
Abstract
Background Regorafenib (REG) is an oral multikinase inhibitor used in colorectal cancer, gastrointestinal stromal tumour and hepatocellular carcinoma. Several adverse events (AEs) are commonly reported during REG administration, and strategies for managing AEs in everyday clinical practice include supportive care, dose modifications and, when necessary, treatment withdrawal. We performed a systematic review and meta-analysis to assess the schedule treatment modifications of REG associated with AEs across randomized controlled clinical trials (RCTs). Methods Eligible studies included RCTs assessing standard dose REG versus placebo. Outcomes of interest included: AE-related permanent discontinuation, dose interruptions and dose reductions. Results We retrieved all the relevant RCTs through PubMed/Med, Cochrane library and EMBASE: 7 eligible studies involving a total of 2099 patients (Regorafenib: 1362; placebo: 737) were included in our analysis. The use of REG was associated with higher incidence and risk of all outcomes of interest when compared with placebo. The incidences of permanent discontinuation, dose interruptions and dose reductions in patients receiving REG were 9.7%, 57.2% and 47%, respectively, versus 3.3%, 16.7% and 7.7% of placebo group; compared with placebo, the summary relative risks (RRs) of permanent discontinuation, dose interruptions and dose reductions in REG arm were 2.80 (95% CI 1.85-4.22), 3.21 (95% CI 2.59-3.99) and 6.02 (95% CI 3.28-11.03), respectively. Conclusions Treatment with REG at the standard dose of 160 mg is associated with a significant increase in AE-related permanent discontinuation, dose interruptions and dose reductions. Prompt identification and management of AEs seem mandatory to obtain maximal benefit from REG treatment. In the current landscape, dose personalization of REG may have the potential to improve quality of life, minimize treatment discontinuation and maximize patient outcomes.
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Affiliation(s)
- Alessandro Rizzo
- Department of Specialized, Experimental and Diagnostic Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Margherita Nannini
- Medical Oncology Unit, Sant’Orsola-Malpighi University Hospital, via Massarenti 9, Bologna, 40138, Italy
| | | | - Angela Dalia Ricci
- Department of Specialized, Experimental and Diagnostic Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | | | - Maria Abbondanza Pantaleo
- Department of Specialized, Experimental and Diagnostic Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
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Wu B, Li A, Zhang Y, Liu X, Zhou S, Gan H, Cai S, Liang Y, Tang X. Resistance of hepatocellular carcinoma to sorafenib can be overcome with co-delivery of PI3K/mTOR inhibitor BEZ235 and sorafenib in nanoparticles. Expert Opin Drug Deliv 2020; 17:573-587. [PMID: 32056461 DOI: 10.1080/17425247.2020.1730809] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Binquan Wu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Amin Li
- Biochemistry Department, Medical School, Anhui University of Science & Technology, Huainan, China
| | - Yinci Zhang
- Biochemistry Department, Medical School, Anhui University of Science & Technology, Huainan, China
| | - Xueke Liu
- Biochemistry Department, Medical School, Anhui University of Science & Technology, Huainan, China
| | - Shuping Zhou
- Biochemistry Department, Medical School, Anhui University of Science & Technology, Huainan, China
| | - Huaiyong Gan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Shiyu Cai
- Biochemistry Department, Medical School, Anhui University of Science & Technology, Huainan, China
| | - Yong Liang
- Central Laboratory, Huai’an Hospital Affiliated of Xuzhou Medical College and Huai’an Second Hospital, Huai’an, P. R. China
| | - Xiaolong Tang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Biochemistry Department, Medical School, Anhui University of Science & Technology, Huainan, China
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