Abstract
Angiogenesis is a complex and critical process essential for supporting the growth of hepatocellular carcinoma (HCC) as well as hepatocarcinogenesis. Recent studies have revealed that renin-angiotensin system (RAS) is involved in many types of cancer including HCC. Some studies have proven that suppression of angiotensin-II (AT-II) by a clinically used angiotensin-converting enzyme inhibitor (ACE-I) significantly attenuated the HCC growth and hepatocarcinogenesis along with down-regulation of a potent angiogenic factor; namely, the vascular endothelial growth factor (VEGF). When used in combination with the clinical available drugs such as interferon (IFN) and vitamin K (VK), ACE-I exerted more potent anti-tumor activities as compared with either single agent in addition to suppression of the intra-tumoral angiogenesis both in experimental models and clinical practice. It is well known that AT-II plays an important role in the insulin resistance (IR), and IR is reportedly involved in the progression of HCC. The combination of ACE-I and branched-chain amino acids (BCAA) exerted a marked chemopreventive effect against HCC under the condition of IR. In addition to AT-II, aldosterone (Ald), which plays a role in the downstream of AT-II, is also involved in the HCC development, and a clinically used selective Ald blocker (SAB) significantly suppressed the HCC growth and hepatocarcinogenesis. Since ACE-I, IFN, VK, BCAA, and SAB are already in widespread clinical use without any serious adverse effects, they may represent a potential new strategy for cancer therapy and chemoprevention against HCC especially in combination with other angiostatic agents.
Keywords: Angiogenesis, angiotensin-converting enzyme, angiotensin-II, hepatocellular carcinoma, vascular endothelial growth factor, aldosterone, nonalcoholic steatohepatitis, radiofrequency ablation, calcium channels blockers, 5-fluorouracil, lectin-reactive -fetoprotein, imatinibmesylate, tyrosine kinase inhibitor
Current Cancer Drug Targets
Title: Impact of Renin-Angiotensin System in Hepatocellular Carcinoma
Volume: 11 Issue: 4
Author(s): H. Yoshiji, R. Noguchi, Y. Ikenaka, K. Kaji, Y. Aihara and H. Fukui
Affiliation:
Keywords: Angiogenesis, angiotensin-converting enzyme, angiotensin-II, hepatocellular carcinoma, vascular endothelial growth factor, aldosterone, nonalcoholic steatohepatitis, radiofrequency ablation, calcium channels blockers, 5-fluorouracil, lectin-reactive -fetoprotein, imatinibmesylate, tyrosine kinase inhibitor
Abstract: Angiogenesis is a complex and critical process essential for supporting the growth of hepatocellular carcinoma (HCC) as well as hepatocarcinogenesis. Recent studies have revealed that renin-angiotensin system (RAS) is involved in many types of cancer including HCC. Some studies have proven that suppression of angiotensin-II (AT-II) by a clinically used angiotensin-converting enzyme inhibitor (ACE-I) significantly attenuated the HCC growth and hepatocarcinogenesis along with down-regulation of a potent angiogenic factor; namely, the vascular endothelial growth factor (VEGF). When used in combination with the clinical available drugs such as interferon (IFN) and vitamin K (VK), ACE-I exerted more potent anti-tumor activities as compared with either single agent in addition to suppression of the intra-tumoral angiogenesis both in experimental models and clinical practice. It is well known that AT-II plays an important role in the insulin resistance (IR), and IR is reportedly involved in the progression of HCC. The combination of ACE-I and branched-chain amino acids (BCAA) exerted a marked chemopreventive effect against HCC under the condition of IR. In addition to AT-II, aldosterone (Ald), which plays a role in the downstream of AT-II, is also involved in the HCC development, and a clinically used selective Ald blocker (SAB) significantly suppressed the HCC growth and hepatocarcinogenesis. Since ACE-I, IFN, VK, BCAA, and SAB are already in widespread clinical use without any serious adverse effects, they may represent a potential new strategy for cancer therapy and chemoprevention against HCC especially in combination with other angiostatic agents.
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Yoshiji H., Noguchi R., Ikenaka Y., Kaji K., Aihara Y. and Fukui H., Impact of Renin-Angiotensin System in Hepatocellular Carcinoma, Current Cancer Drug Targets 2011; 11 (4) . https://dx.doi.org/10.2174/156800911795538084
DOI https://dx.doi.org/10.2174/156800911795538084 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
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