Conversion Surgery for Hepatocellular Carcinoma Following Molecular Therapy

Abstract Recent developments in systemic chemotherapy for advanced hepatocellular carcinoma have been outstanding. However, reports on conversion surgery after lenvatinib therapy are scarce. We present the first case of advanced hepatocellular carcinoma with tumor thrombus in the suprahepatic vena cava close to the right atrium, which shrank after 12 weeks’ administration of lenvatinib, thereby leading to successful conversion surgery without using total vascular exclusion or extracorporeal circulation. The treatment strategy for hepatocellular carcinoma with macroscopic hepatic vein tumor thrombus is controversial, however, from a Japanese nationwide survey, surgical resection has been accepted as one of the treatment options for advanced hepatocellular carcinoma with hepatic vein tumor thrombus in Japan. However, the survival rate after resection of hepatocellular carcinoma having inferior vena cava tumor thrombus with extracorporeal circulation was reported to be worse than without extracorporeal circulation, and some preoperative down-sizing therapy for inferior vena cava tumor thrombus was advocated. Preoperative lenvatinib therapy might be a promising option among the multidisciplinary treatments for hepatocellular carcinoma with macroscopic tumor thrombus in the hepatic veins.

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Molecular therapy for the treatment of hepatocellular carcinoma

British Journal of Cancer ◽

10.1038/sj.bjc.6604784 ◽

2008 ◽

Vol 100 (1) ◽

pp. 19-23 ◽

Cited By ~ 51

Author(s):

T F Greten ◽

F Korangy ◽

M P Manns ◽

N P Malek

Keyword(s):

Hepatocellular Carcinoma ◽

Molecular Therapy

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Complete Response for Advanced Hepatocellular Carcinoma by Conversion Surgery Therapy Following a Good Response of Regorafenib Despite Rapid Progressive Disease with Sorafenib

Internal Medicine ◽

10.2169/internalmedicine.5870-20 ◽

2021 ◽

Vol 60 (13) ◽

pp. 2047-2053

Author(s):

Kenji Yamaoka ◽

Tomokazu Kawaoka ◽

Hiroshi Aikata ◽

Yuwa Ando ◽

Yumi Kosaka ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Progressive Disease ◽

Complete Response ◽

Advanced Hepatocellular Carcinoma ◽

Conversion Surgery

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Synergistic Effect of MiR-146a Mimic and Cetuximab on Hepatocellular Carcinoma Cells

BioMed Research International ◽

10.1155/2014/384121 ◽

2014 ◽

Vol 2014 ◽

pp. 1-15 ◽

Cited By ~ 7

Author(s):

Suning Huang ◽

Rongquan He ◽

Minhua Rong ◽

Yiwu Dang ◽

Gang Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Growth ◽

Synergistic Effect ◽

Vital Role ◽

Molecular Therapy ◽

Therapy Strategy ◽

Formalin Fixed Paraffin Embedded ◽

Ffpe Tissues ◽

Hcc Cells

Previously, we found that the expression of microRNA-146a (miR-146a) was downregulated in hepatocellular carcinoma (HCC) formalin-fixed paraffin-embedded (FFPE) tissues compared to the adjacent noncancerous hepatic tissues. In the current study, we have explored thein vitroeffect of miR-146a on the malignant phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by spectrophotometry, fluorimetry, and fluorescence microscopy, respectively. Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2, and stat5 signalings. These effects were less potent compared to that of a siRNA targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various EGFR targeting agents. The most potent combination was miR-146a mimic with cetuximab, presenting a synergistic effect. In conclusion, miR-146a plays a vital role in the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a critical targeted molecular therapy strategy for HCC.

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Perspectives of Molecular Therapy-Targeted Mitochondrial Fission in Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2020/1039312 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Hanwen Zhang ◽

Yanshuo Ye ◽

Wei Li

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Dynamic Equilibrium ◽

Mitochondrial Fission ◽

Molecular Therapy ◽

Eukaryotic Cells ◽

Molecular Targeting ◽

Molecular Pathways ◽

Ros Homeostasis ◽

Dynamic Equilibrium State

Current advances of molecular-targeting therapies for hepatocellular carcinoma (HCC) have improved the overall survival significantly, whereas the results still remain unsatisfied. Recently, much attention has been focused on organelles, such as the mitochondria, to reveal novel strategies to control the cancers. The mitochondria are vital organelles which supply energy and maintain metabolism in most of the eukaryotic cells. They not only execute critical bioenergetic and biosynthetic functions but also regulate ROS homeostasis and apoptosis. Existing in a dynamic equilibrium state, mitochondria constantly undergo the fission and fusion processes in normal situation. Increasing evidences have showed that mitochondrial fission is highly related to the diseases and cancers. Distinctive works have proved the significant effects of mitochondrial fission on HCC behaviors and the crosstalks with other molecular pathways. Here, we provide an overview of the mitochondrial fission and the link with HCC, emphasizing on the underlying molecular pathways and several novel materials that modulate HCC behaviors.

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Role of ATP-binding Cassette Transporters in Sorafenib Therapy for Hepatocellular Carcinoma: an overview

Current Drug Targets ◽

10.2174/1389450122666210412125018 ◽

2021 ◽

Vol 22 ◽

Author(s):

Maria Manuela Estevinho ◽

Carlos Fernandes ◽

João Carlos Silva ◽

Ana Catarina Gomes ◽

Edgar Afecto ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Multidrug Resistance ◽

Abc Transporters ◽

Current Knowledge ◽

Molecular Therapy ◽

Resistance Factors ◽

Sorafenib Therapy ◽

Online Databases ◽

Associated Proteins

Background: Molecular therapy with sorafenib remains the mainstay for advanced-stage hepatocellular carcinoma. Notwithstanding, treatment efficacy is low, with few patients obtaining long-lasting benefits due to the high chemoresistance rate. Objective: To perform, for the first time, an overview of the literature concerning the role of adenosine triphosphate-binding cassette (ABC) transporters in sorafenib therapy for hepatocellular carcinoma. Methods: Three online databases (PubMed, Web of Science and Scopus) were searched, from inception to October 2020. Studies selection, analysis and data collection was independently performed by two authors. Results: The search yielded 224 results; 29 were selected for inclusion. Most studies were pre-clinical, using HCC cell lines; three used human samples. Studies highlight the effect of sorafenib in decreasing ABC transporters expression. Conversely, it is described the role of ABC transporters, particularly multidrug resistance protein 1 (MDR-1), multidrug resistance-associated proteins 1 and 2 (MRP-1 and MRP-2) and ABC subfamily G member 2 (ABCG2) in sorafenib pharmacokinetics and pharmacodynamics, being key resistance factors. Combination therapy with naturally available or synthetic compounds that modulate ABC transporters may revert sorafenib resistance, by increasing absorption and intracellular concentration. Conclusion: A deeper understanding of ABC transporters’ mechanisms may provide guidance for developing innovative approaches for hepatocellular carcinoma. Further studies are warranted to translate the current knowledge into practice and paving the way to individualized therapy.

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