Generic placeholder image

Current Cancer Therapy Reviews


ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Review Article

Liver Cancer: New Insights into Surgical and Nonsurgical Treatments

Author(s): Masoud Sharifian, Parastoo Baharvand and Alireza Moayyedkazemi*

Volume 17 , Issue 3 , 2021

Published on: 18 February, 2021

Page: [197 - 206] Pages: 10

DOI: 10.2174/1573394717666210219104201

Price: $65


Introduction: Hepatocellular carcinoma (HCC) is the most common type of liver cancer that has increased in recent years worldwide. Primary liver cancer or HCC is considered the 5th and 7th most common cancer among men and women, respectively. It is also the second leading cause of cancer death worldwide. Unfortunately, HCC is frequently diagnosed at an advanced stage when the majority of the patients do not have access to remedial therapies. Furthermore, current systemic chemotherapy shows low efficacy and minimum survival benefits. Liver cancer therapy is a multidisciplinary, multiple-choice treatment based on the complex interaction of the tumour stage, the degree of liver disease, and the patient's general state of health.

Methods: In this paper, we reviewed new insights into nonsurgical and surgical treatment of liver cancer in five English databases, including Scopus, PubMed, Web of Science, EMBASE, and Google Scholar up to December 2019.

Results: The results demonstrated, in addition to current therapies such as chemotherapy and surgical resection, new approaches, including immunotherapy, viral therapy, gene therapy, new ablation therapies, and adjuvant therapy, are widely used for the treatment of HCC. In recent years, biomaterials such as nanoparticles, liposomes, microspheres, and nanofibers are also regarded as reliable and innovative patents for the treatment and study of liver cancers.

Conclusion: Multidisciplinary and multi-choice treatments and therapies are available for this liver cancer, while there are differences in liver cancer management recommendations among specialties and geographic areas. Current results have shown that treatment strategies have been combined with the advancement of novel treatment modalities. In addition, the use of new approaches with greater efficacy, such as combination therapy, biomaterials, ablation therapy, etc. can be considered the preferred treatment for patients.

Keywords: Hepatocellular carcinoma, therapy, biomaterials, gene therapy, virus therapy, immunotherapy.

Graphical Abstract
Ober EA, Lemaigre FP. Development of the liver: Insights into organ and tissue morphogenesis. J Hepatol 2018; 68(5): 1049-62.
[] [PMID: 29339113]
Marengo A, Rosso C, Bugianesi E. Liver cancer: Connections with obesity, fatty liver, and cirrhosis. Annu Rev Med 2016; 67: 103-17.
[] [PMID: 26473416]
Bosch FX, Ribes J, Díaz M, Cléries R. Primary liver cancer: Worldwide incidence and trends. Gastroenterology 2004; 127(5): S5-S16.
[] [PMID: 15508102]
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127(12): 2893-917.
[] [PMID: 21351269]
Anbari K, Ahmadi SA, Baharvand P, Sahraei N. Investigation of breast cancer screening among the women of Khorramabad (west of Iran): a cross-sectional study. Epidemiology Biostatistics and Public Health 2017 Jan 10; 14(1): e12099-1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61(2): 69-90.
[] [PMID: 21296855]
Li L, Wang H. Heterogeneity of liver cancer and personalized therapy. Cancer Lett 2016; 379(2): 191-7.
[] [PMID: 26213370]
Cancer of the Liver Italian Program (CLIP) Investigators. A new prognostic system for hepatocellular carcinoma: A retrospective study of 435 patients: The Cancer of the Liver Italian Program (CLIP) investigators. Hepatology 1998; 28(3): 751-5.
[] [PMID: 9731568]
Llovet JM, Bruix J. Prospective validation of the Cancer of the Liver Italian Program (CLIP) score: A new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology 2000; 32(3): 679-80.
[] [PMID: 10991637]
Llovet JM, Fuster J, Bruix J. Barcelona-Clínic Liver Cancer Group. The Barcelona approach: Diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl 2004; 10(2): S115-20.
[] [PMID: 14762851]
Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: The BCLC staging classification. Semin Liver Dis 1999; 19(3): 329-38.
[] [PMID: 10518312]
Leung TW, Tang AM, Zee B, et al. Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program staging system: A study based on 926 patients. Cancer 2002; 94(6): 1760-9.
[] [PMID: 11920539]
Bruix J, Sherman M. Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology 2005; 42(5): 1208-36.
[] [PMID: 16250051]
Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006; 118(12): 3030-44.
[] [PMID: 16404738]
Bosetti C, Levi F, Boffetta P, Lucchini F, Negri E, La Vecchia C. Trends in mortality from hepatocellular carcinoma in Europe, 1980-2004. Hepatology 2008; 48(1): 137-45.
[] [PMID: 18537177]
Clark T, Maximin S, Meier J, Pokharel S, Bhargava P. Hepatocellular carcinoma: Review of epidemiology, screening, imaging diagnosis, response assessment, and treatment. Curr Prob Diagn Radiol 2015; 144(6): 479-86.
Zucman-Rossi J, Villanueva A, Nault JC, Llovet JM. Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology 2015; 149(5): 1226-39.
Bruix J, Reig M, Sherman M. Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology 2016; 150(4): 835-53.
[] [PMID: 26795574]
Verslype C, Van Cutsem E, Dicato M, et al. The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 10th World Congress on Gastrointestinal Cancer, Barcelona, 2008. Ann Oncol 2009; 20(Suppl. 7): vii1-6.
[] [PMID: 19497945]
Sun JH, Luo Q, Liu LL, Song GB. Liver cancer stem cell markers: Progression and therapeutic implications. World J Gastroenterol 2016; 22(13): 3547-57.
[] [PMID: 27053846]
Poon D, Anderson BO, Chen LT, et al. Asian Oncology Summit. Management of hepatocellular carcinoma in Asia: Consensus statement from the Asian Oncology Summit 2009. Lancet Oncol 2009; 10(11): 1111-8.
[] [PMID: 19880065]
Fong ZV, Tanabe KK. The clinical management of hepatocellular carcinoma in the United States, Europe, and Asia: A comprehensive and evidence-based comparison and review. Cancer 2014; 120(18): 2824-38.
[] [PMID: 24897995]
Dutta R, Mahato RI. Recent advances in hepatocellular carcinoma therapy. Pharmacol Ther 2017; 173: 106-17.
[] [PMID: 28174094]
Vyas M, Simbo DA, Mursalin M, Mishra V, Bashary R, Khatik GL. Drug delivery approaches for Doxorubicin in the management of cancers. Curr Cancer Ther Rev 2020; 16(4): 320-31.
Liu K, Wang LF, Wang FS, Shi M. Progress and prospects of clinical cell therapy for liver cirrhosis and liver cancer. Zhonghua Gan Zang Bing Za Zhi 2019; 27(11): 822-6.
[PMID: 31941234]
Yeo W, Mok TS, Zee B, et al. A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma. J Natl Cancer Inst 2005; 97(20): 1532-8.
[] [PMID: 16234567]
Kaur K, Khatik GL. Cancer immunotherapy: An effective tool in cancer control and treatment. Curr Cancer Ther Rev 2020; 16(1): 62-9.
Sangro B, Gomez-Martin C, de la Mata M, et al. A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C. J Hepatol 2013; 59(1): 81-8.
[] [PMID: 23466307]
Salem JE, Manouchehri A, Moey M, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors: An observational, retrospective, pharmacovigilance study. Lancet Oncol 2018; 19(12): 1579-89.
[] [PMID: 30442497]
Stein S, Pishvaian MJ, Lee MS, et al. Safety and clinical activity of 1L atezolizumab plus bevacizumab in a phase Ib study in hepatocellular carcinoma (HCC). J Clin Oncol 2018; 36: 4074.
Russell SJ, Peng KW, Bell JC. Oncolytic virotherapy. Nat Biotechnol 2012; 30(7): 658-70.
[] [PMID: 22781695]
Moehler M, Goepfert K, Heinrich B, et al. Oncolytic virotherapy as emerging immunotherapeutic modality: Potential of parvovirus h-1. Front Oncol 2014; 4: 92.
[] [PMID: 24822170]
Mohamadi A, Amini SM, Pagès G, Sadegh M. The important role of oncolytic viruses in common cancer treatments. Curr Cancer Ther Rev 2020; 16: 1-4.
Komori H, Nakatsura T, Senju S, et al. Identification of HLA-A2- or HLA-A24-restricted CTL epitopes possibly useful for glypican-3-specific immunotherapy of hepatocellular carcinoma. Clin Cancer Res 2006; 12(9): 2689-97.
[] [PMID: 16675560]
Iwama T, Uchida T, Sawada Y, et al. Vaccination with liposome- coupled glypican-3-derived epitope peptide stimulates cytotoxic T lymphocytes and inhibits GPC3-expressing tumor growth in mice. Biochem Biophys Res Commun 2016; 469(1): 138-43.
[] [PMID: 26616051]
Mizukoshi E, Nakagawa H, Kitahara M, et al. Phase I trial of multidrug resistance-associated protein 3-derived peptide in patients with hepatocellular carcinoma. Cancer Lett 2015; 369(1): 242-9.
[] [PMID: 26325606]
Yutani S, Ueshima K, Abe K, et al. Phase II study of personalized peptide vaccination with both a hepatitis c virus-derived peptide and peptides from tumor-associated antigens for the treatment of hcv-positive advanced hepatocellular carcinoma patients. J Immunol Res 2015; 2015: 473909.
[] [PMID: 26539554]
Kamimura K, Yokoo T, Abe H, Terai S. Gene therapy for liver cancers: Current status from basic to clinics. Cancers (Basel) 2019; 11(12): 1865.
[] [PMID: 31769427]
Vassaux G, Martin-Duque P. Use of suicide genes for cancer gene therapy: Study of the different approaches. Expert Opin Biol Ther 2004; 4(4): 519-30.
[] [PMID: 15102601]
Sangro B, Mazzolini G, Ruiz M, et al. A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma. Cancer Gene Ther 2010; 17(12): 837-43.
[] [PMID: 20689572]
Copolovici DM, Langel K, Eriste E, Langel Ü. Cell-penetrating peptides: Design, synthesis, and applications. ACS Nano 2014; 8(3): 1972-94.
[] [PMID: 24559246]
Taghizadeh E, Taheri F, Rostami D. MiR-492 as an important biomarker for early diagnosis and targeted treatment in different cancers. Curr Cancer Ther Rev 2020; 16(4): 269-75.
Kotipatruni RR, Dasari VR, Veeravalli KK, Dinh DH, Fassett D, Rao JS. p53- and Bax-mediated apoptosis in injured rat spinal cord. Neurochem Res 2011; 36(11): 2063-74.
[] [PMID: 21748659]
Bartel DP. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004; 116(2): 281-97.
[] [PMID: 14744438]
Farra R, Grassi M, Grassi G, Dapas B. Therapeutic potential of small interfering RNAs/micro interfering RNA in hepatocellular carcinoma. World J Gastroenterol 2015; 21(30): 8994-9001.
[] [PMID: 26290628]
Layzer JM, McCaffrey AP, Tanner AK, Huang Z, Kay MA, Sullenger BA. In vivo activity of nuclease-resistant siRNAs. RNA 2004; 10(5): 766-71.
[] [PMID: 15100431]
Hayes CN, Chayama K. MicroRNAs as biomarkers for liver disease and hepatocellular carcinoma. Int J Mol Sci 2016; 17(3): 280.
[] [PMID: 26927063]
Reza Mirzaei H, Sahebkar A, Mohammadi M, et al. Circulating microRNAs in hepatocellular carcinoma: Potential diagnostic and prognostic biomarkers. Current Pharmaceutical Design 2016; 22(34): 5257-5269..
Shahkarami K, Vousooghi N, Golab F, et al. Evaluation of dynorphin and kappa-opioid receptor level in the human blood lymphocytes and plasma: Possible role as a biomarker in severe opioid use disorder. Drug Alcohol Depend 2019 Dec 1; 205: 107638.
Deng X, Yin Z, Zhou Z, et al. Carboxymethyl dextran-stabilized polyethylenimine-poly (epsilon-caprolactone) nanoparticles-Mediated modulation of microRNA-34a expression via small-molecule modulator for hepatocellular carcinoma therapy. ACS Appl Mater Interfaces 2016; 8(27): 17068-79.
[] [PMID: 27300477]
Gu J, Liu X, Li J, He Y. MicroRNA-144 inhibits cell proliferation, migration and invasion in human hepatocellular carcinoma by targeting CCNB1. Cancer Cell Int 2019; 19(1): 15.
[] [PMID: 30651720]
Shen Q, Cicinnati VR, Zhang X, et al. Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion. Mol Cancer 2010; 9(1): 227.
[] [PMID: 20799954]
Yin XY, Lu MD. Percutaneous ablation for small hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2009; 3(2): 121-30.
[] [PMID: 19351283]
Kim SR, Imoto S, Nakajima T, et al. Well-differentiated hepatocellular carcinoma smaller than 15 mm in diameter totally eradicated with percutaneous ethanol injection instead of radiofrequency ablation. Hepatol Int 2009; 3(2): 411-5.
[] [PMID: 19669368]
Zhang YJ, Chen MS. The indications and application about radiofrequency ablation of liver cancer. J Hepatobiliary Surg 2010; 18: 9-10.
Waki K, Aikata H, Katamura Y, et al. Percutaneous radiofrequency ablation as first-line treatment for small hepatocellular carcinoma: Results and prognostic factors on long-term follow up. J Gastroenterol Hepatol 2010; 25(3): 597-604.
[] [PMID: 20074153]
Eisele RM, Denecke T, Glanemann M, Chopra SS. Minimal-invasive microwave coagulation therapy for liver tumours: Laparoscopic and percutaneous access. Zentralbl Chir 2014; 139(2): 235-43.
[PMID: 24241949]
Tang Y, Zhou XD. Research progress of ultrasound interventional therapy for primary liver carcinoma. Disi Junyi Daxue Xuebao 2008; 29: 89-92.
Kennedy JE. High-intensity focused ultrasound in the treatment of solid tumours. Nat Rev Cancer 2005; 5(4): 321-7.
[] [PMID: 15776004]
Orsi F, Zhang L, Arnone P, et al. High-intensity focused ultrasound ablation: Effective and safe therapy for solid tumors in difficult locations. AJR Am J Roentgenol 2010; 195(3): W245-52.
[] [PMID: 20729423]
Cormier JN, Thomas KT, Chari RS, Pinson CW. Management of hepatocellular carcinoma. J Gastrointest Surg 2006; 10(5): 761-80.
[] [PMID: 16713550]
Kerkar S, Carlin AM, Sohn RL, et al. Long-term follow up and prognostic factors for cryotherapy of malignant liver tumors. Surgery 2004; 136(4): 770-9.
[] [PMID: 15467661]
Georgiades CS, Hong K, D’Angelo M, Geschwind JF. Safety and efficacy of transarterial chemoembolization in patients with unresectable hepatocellular carcinoma and portal vein thrombosis. J Vasc Interv Radiol 2005; 16(12): 1653-9.
[] [PMID: 16371532]
Akamatsu N, Cillo U, Cucchetti A, et al. Surgery and hepatocellular carcinoma. Liver Cancer 2016; 6(1): 44-50.
[] [PMID: 27995087]
Samuel M, Chow PK, Chan Shih-Yen E, Machin D, Soo KC. Neoadjuvant and adjuvant therapy for surgical resection of hepatocellular carcinoma. Cochrane Database Syst Rev 2009; CD001199(1): CD001199.
[] [PMID: 19160192]
Xie F, Zhang X, Li H, et al. Adoptive immunotherapy in postoperative hepatocellular carcinoma: A systemic review. PLoS One 2012; 7(8): e42879.
[] [PMID: 22916174]
Furtado R, Crawford M, Sandroussi C. Systematic review and meta-analysis of adjuvant i(131) lipiodol after excision of hepatocellular carcinoma. Ann Surg Oncol 2014; 21(8): 2700-7.
[] [PMID: 24743904]
Hackl C, Schlitt HJ, Kirchner GI, Knoppke B, Loss M. Liver transplantation for malignancy: Current treatment strategies and future perspectives. World J Gastroenterol 2014; 20(18): 5331-44.
[] [PMID: 24833863]
Baharvand P. Responsiveness of the health system towards patients admitted to west of Iran hospitals. Electronic J General Med 2019; 16(2): 121.
Sugawara Y, Tamura S, Makuuchi M. Living donor liver transplantation for hepatocellular carcinoma: Tokyo University series. Dig Dis 2007; 25(4): 310-2.
[] [PMID: 17960065]
Niazi M, Veiskaramian A, Mokhayeri Y. Toward nonalcoholic fatty liver treatment; A review on herbal medicine treatment. J Crit Rev 2020; 7: 554-64.
Zhang C, An T, Wang D, et al. Stepwise pH-responsive nanoparticles containing charge-reversible pullulan-based shells and poly(β-amino ester)/poly(lactic-co-glycolic acid) cores as carriers of anticancer drugs for combination therapy on hepatocellular carcinoma. J Control Release 2016; 226: 193-204.
[] [PMID: 26896737]
Wang Y, Chen H, Liu Y, et al. pH-sensitive pullulan-based nanoparticle carrier of methotrexate and combretastatin A4 for the combination therapy against hepatocellular carcinoma. Biomaterials 2013; 34(29): 7181-90.
[] [PMID: 23791500]
Upadhyay T, Ansari VA, Ahmad U, Sultana N, Akhtar J. Exploring nanoemulsion for liver cancer therapy. Curr Cancer Ther Rev 2020; 16(4): 260-8.
Yanhua W, Hao H, Li Y, Zhang S. Selenium-substituted hydroxyapatite nanoparticles and their in vivo antitumor effect on hepatocellular carcinoma. Colloids Surf B Biointerfaces 2016; 140: 297-306.
[] [PMID: 26764116]
Xu Y, Wen Z, Xu Z. Chitosan nanoparticles inhibit the growth of human hepatocellular carcinoma xenografts through an antiangiogenic mechanism. Anticancer Res 2009; 29(12): 5103-9.
[PMID: 20044623]
Qi L, Xu Z, Chen M. In vitro and in vivo suppression of hepatocellular carcinoma growth by chitosan nanoparticles. Eur J Cancer 2007; 43(1): 184-93.
[] [PMID: 17049839]
Bu L, Gan LC, Guo XQ, et al. Trans-resveratrol loaded chitosan nanoparticles modified with biotin and avidin to target hepatic carcinoma. Int J Pharm 2013; 452(1-2): 355-62.
[] [PMID: 23685116]
Cheng M, Zhu W, Li Q, Dai D, Hou Y. Anti-cancer efficacy of biotinylated chitosan nanoparticles in liver cancer. Oncotarget 2017; 8(35): 59068-85.
[] [PMID: 28938619]
Liu Y, Li L, Li L, et al. Programmed drug delivery system based on optimized “size decrease and hydrophilicity/hydrophobicity transformation” for enhanced hepatocellular carcinoma therapy of doxorubicin. Nanomedicine (Lond) 2018; 14(4): 1111-22.
[] [PMID: 29458212]
Paino IM, Marangoni VS, de Oliveira RdeC, Antunes LM, Zucolotto V. Cyto and genotoxicity of gold nanoparticles in human hepatocellular carcinoma and peripheral blood mononuclear cells. Toxicol Lett 2012; 215(2): 119-25.
[] [PMID: 23046612]
Xue HY, Liu Y, Liao JZ, et al. Gold nanoparticles delivered miR-375 for treatment of hepatocellular carcinoma. Oncotarget 2016; 7(52): 86675-86.
[] [PMID: 27880727]
Tomuleasa C, Soritau O, Orza A, et al. Gold nanoparticles conjugated with cisplatin/doxorubicin/capecitabine lower the chemoresistance of hepatocellular carcinoma-derived cancer cells. J Gastrointestin Liver Dis 2012; 21(2): 187-96.
[PMID: 22720309]
Shen Z, Wei W, Tanaka H, et al. A galactosamine-mediated drug delivery carrier for targeted liver cancer therapy. Pharmacol Res 2011; 64(4): 410-9.
[] [PMID: 21723392]
Li M, Zhao P, Fan T, et al. Biocompatible co-loading vehicles for delivering both nanoplatin cores and siRNA to treat hepatocellular carcinoma. Int J Pharm 2019; 572: 118769.
[] [PMID: 31669557]
Liang HF, Chen CT, Chen SC, et al. Paclitaxel-loaded poly(γ-glutamic acid)-poly(lactide) nanoparticles as a targeted drug delivery system for the treatment of liver cancer. Biomaterials 2006; 27(9): 2051-9.
[] [PMID: 16307794]
Zhou K, Nguyen LH, Miller JB, et al. Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model. Proc Natl Acad Sci USA 2016; 113(3): 520-5.
[] [PMID: 26729861]
Wei M, Guo X, Tu L, et al. Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma. Int J Nanomedicine 2015; 10: 5123-37.
[PMID: 26316745]
Wang J, Wu Z, Pan G, et al. Enhanced doxorubicin delivery to hepatocellular carcinoma cells via CD147 antibody-conjugated immunoliposomes. Nanomedicine (Lond) 2018; 14(6): 1949-61.
[] [PMID: 29045824]
Wang XM, Yin ZY, Yu RX, Peng YY, Liu PG, Wu GY. Preventive effect of regional radiotherapy with phosphorus-32 glass microspheres in hepatocellular carcinoma recurrence after hepatectomy. World J Gastroenterol 2008; 14(4): 518-23.
[] [PMID: 18203282]
Che HL, Lee HJ, Uto K, et al. Simultaneous drug and gene delivery from the biodegradable poly (-caprolactone) nanofibers for the treatment of liver cancer. J Nanosci Nanotechnol 2015; 15(10): 7971-5.
[] [PMID: 26726449]
Lazzeri L, Cascone MG, Danti S, Serino LP, Moscato S, Bernardini N. Gelatine/PLLA sponge-like scaffolds: Morphological and biological characterization. J Mater Sci Mater Med 2007; 18(7): 1399-405.
[] [PMID: 17277980]
Leung M, Kievit FM, Florczyk SJ, et al. Chitosan-alginate scaffold culture system for hepatocellular carcinoma increases malignancy and drug resistance. Pharm Res 2010; 27(9): 1939-48.
[] [PMID: 20585843]
Kundu B, Saha P, Datta K, Kundu SC. A silk fibroin based hepatocarcinoma model and the assessment of the drug response in hyaluronan-binding protein 1 overexpressed HepG2 cells. Biomaterials 2013; 34(37): 9462-74.
[] [PMID: 24016853]
She Z, Jin C, Huang Z, Zhang B, Feng Q, Xu Y. Silk fibroin/chitosan scaffold: Preparation, characterization, and culture with HepG2 cell. J Mater Sci Mater Med 2008; 19(12): 3545-53.
[] [PMID: 18622765]
Xu XX, Liu C, Liu Y, et al. Encapsulated human hepatocellular carcinoma cells by alginate gel beads as an in vitro metastasis model. Exp Cell Res 2013; 319(14): 2135-44.
[] [PMID: 23707395]
Yip D, Cho CH. A multicellular 3D heterospheroid model of liver tumor and stromal cells in collagen gel for anti-cancer drug testing. Biochem Biophys Res Commun 2013; 433(3): 327-32.
[] [PMID: 23501105]
Moriyama K, Naito S, Wakabayashi R, Goto M, Kamiya N. Enzymatically prepared redox-responsive hydrogels as potent matrices for hepatocellular carcinoma cell spheroid formation. Biotechnol J 2016; 11(11): 1452-60.
[] [PMID: 27617786]
Bokhari M, Carnachan RJ, Cameron NR, Przyborski SA. Culture of HepG2 liver cells on three dimensional polystyrene scaffolds enhances cell structure and function during toxicological challenge. J Anat 2007; 211(4): 567-76.
[] [PMID: 17711423]
Mazza G, Rombouts K, Rennie Hall A, et al. Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation. Sci Rep 2015; 5: 13079.
[] [PMID: 26248878]
Sarkar J, Kumari J, Tonello JM, Kamihira M, Kumar A. Enhanced hepatic functions of genetically modified mouse hepatoma cells by spheroid culture for drug toxicity screening. Biotechnol J 2017; 12(10): 1700274.
[] [PMID: 28834334]
Moscato S, Ronca F, Campani D, Danti S. Poly (vinyl alcohol)/gelatin hydrogels cultured with HepG2 cells as a 3D model of hepatocellular carcinoma: A morphological study. J Funct Biomater 2015; 6(1): 16-32.
[] [PMID: 25590431]
Liang Y, Jeong J, DeVolder RJ, et al. A cell-instructive hydrogel to regulate malignancy of 3D tumor spheroids with matrix rigidity. Biomaterials 2011; 32(35): 9308-15.
[] [PMID: 21911252]
He X, He Q, Wang L, He X. New researches about combinatorial therapeutic regimen on cancer treatment. Curr Cancer Ther Rev 2020; 16(2): 97-109.
Mohamed AA, Ghanem HM, Kamal MM, et al. Dickkopf-1 and β-catenin as biomarkers for early diagnosis of hepatocellular carcinoma. Curr Cancer Ther Rev 2020; 16(2): 136-44.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy