title: Combination of branched-chain amino acids and angiotensin-converting enzyme inhibitor suppresses the cumulative recurrence of hepatocellular carcinoma: a randomized control trial.
abstract: Insulin resistance (IR) is reportedly involved in the progression of hepatocellular             carcinoma (HCC). Since neovascularization plays an important role in hepatocarcinogenesis             and IR, an angiostatic therapy may be considered as one of the promising approaches             for chemoprevention against HCC. The aim of the current study was to examine the             combination effect of a clinically used branched-chain amino acid (BCAA) and an             angiotensin-converting enzyme inhibitor (ACE-I), both reportedly possess anti-angiogenic             and IR-improving activities, on the cumulative recurrence after curative therapy.             BCAA granules (Livact; 12 g/day) and/or ACE-I (perindopril; 4 mg/day) were administered             after the curative therapy for HCC, and several indices were analyzed. A 48-month             follow-up revealed that the combination treatment with BCAA and ACE-I markedly             inhibited the cumulative recurrence of HCC under IR conditions, whereas neither             single treatment exerted a significant inhibition. The soluble form of the vascular             endothelial growth factor (VEGF; a central angiogenic factor) receptor-2 (sVEGFR2)             was significantly decreased only three months after the treatment without recurrence.             We also observed that IR, determined by the homeostasis model assessment (HOMA-IR),             was significantly improved by this regimen, indicating that an inhibitory effect             was achieved, at least partly, by coordinated effects of anti-angiogenesis and             IR improvement. In conclusion, since both BCAA and ACE-I are widely used in clinical             practice with safety, this combination therapy may represent a potential new strategy             for chemoprevention against IR-based HCC recurrence in the future. Moreover, sVEGFR2             may become a useful clinical predictive marker of this combination treatment.
authors.affiliation: Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8522, Japan. yoshijih@naramed-u.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshiji
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Noguchi
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Ikenaka
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kaji
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Aihara
authors.forename: Masaharu
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Junichi
authors.initials: J
authors.lastname: Yamao
authors.forename: Masahisa
authors.initials: M
authors.lastname: Toyohara
authors.forename: Akira
authors.initials: A
authors.lastname: Mitoro
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Sawai
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Chie
authors.initials: C
authors.lastname: Morioka
authors.forename: Masao
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Masahito
authors.initials: M
authors.lastname: Uemura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukui
mesh_terms: D000368:Aged; D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000517:prevention & control*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008113:Liver Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000517:prevention & control*; D020913:Perindopril / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000597:Amino Acids, Branched-Chain; D000806:Angiotensin-Converting Enzyme Inhibitors; D014408:Biomarkers, Tumor; D020913:Perindopril