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Chemoprevention of obesity-related liver carcinogenesis by using pharmaceutical and nutraceutical agents

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World Journal of Gastroenterology 2016年第1期22卷 394-406页

作者： Hiroyasu Sakai Yohei shirakami Masahito Shimizu Department of Gastroenterology/Internal Medicine Gifu University Graduate School of Medicine

Obesity and its related metabolic disorders are serious health problems worldwide,and lead to various healthrelated complications,including *** human cancers,hepatocellular carcinoma(HCC)is one of the most common malignancies affected by ***,obesity and its related disorders might be a key target for the prevention of ***,new research indicates that the molecular abnormalities associated with obesity,including insulin resistance/hyperinsulinemia,chronic inflammation,adipokine imbalance,and oxidative stress,are possible molecular mechanisms underlying the pathogenesis of obesityrelated *** tea catechins and branched-chain amino acids,both of which are classified as nutraceutical agents,have been reported to prevent obesity-related HCC development by improving metabolic *** administration of acyclic retinoid,a pharmaceutical agent,reduced the incidence of HCC in obese and diabetic mice,and was also associated with improvements in insulin resistance and chronic *** this article,we review the detailed molecular mechanisms that link obesity to the development of HCC in obese *** also summarize recent evidence from experimental and clinical studies using either nutraceutical or pharmaceutical agents,and suggest that nutraceutical and pharmaceutical approaches targeting metabolic abnormalities might be a promising strategy to prevent the development of obesity-related HCC.

关键词： Hepatocellular carcinoma Obesity Greentea catechins Branched-chain amino acids Acyclicretinoid

Strategies to prevent hypertrophic scar formation:a review of therapeutic interventions based on molecular evidence

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Burns & Trauma 2020年第1期8卷 433-440页

作者： Eri shirakami Sho Yamakawa Kenji Hayashida Division of Plastic and Reconstructive Surgery Shimane University Faculty of Medicine89-1 Enya-choIzumoShimane 693-8501Japan

Once scar tissues mature,it is impossible for the surrounding tissue to regenerate normal dermal ***,it is essential to understand the fundamental mechanisms and establish effective strategies to inhibit aberrant scar *** scar formation is considered a result of the imbalance between extracellular matrix synthesis and degradation during wound ***,the underlying mechanisms of hypertrophic scar development are poorly *** purpose of this review was to outline the management in the early stage after wound healing to prevent hypertrophic scar formation,focusing on strategies excluding therapeutic agents of internal *** aimed at molecular targets,including cytokines,will be future options to prevent and treat hypertrophic *** basic studies and clinical trials,including combination therapy,are required to investigate the mechanisms and prevent hypertrophic scar formation.

关键词： Hypertrophic scar Therapy Intervention Cytokines

Chemoprevention of colorectal cancer by targeting obesity-related metabolic abnormalities

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World Journal of Gastroenterology 2014年第27期20卷 8939-8946页

作者： Yohei shirakami Masahito Shimizu Masaya Kubota Hiroshi Araki Takuji Tanaka Hisataka Moriwaki Mitsuru Seishima Department of Informative Clinical Medicine Gifu University Graduate School of Medicine Department of Gastroenterology Gifu University Graduate School of Medicine Department of Tumor Pathology Gifu University Graduate School of Medicine

Obesity and its related metabolic disorders, including insulin resistance and chronic inflammation, increase the risk of colorectal cancer(CRC). This observation suggests that the metabolic abnormalities associated with obesity can be effective targets for preventing the development of CRC in obese individuals. In recent years, many studies using obese and diabetic animal models have been conducted to investigate the chemoprevention of CRC using pharmaceutical or nutritional interventions. Pitavastatin, a medicine used to treat hyperlipidemia, prevents the development of obesityrelated colorectal carcinogenesis by attenuating chronic inflammation. Anti-hypertensive medicines, such as captopril and telmisartan, also suppress the formation of colonic preneoplastic lesions in obese and diabetic mice. In addition, several phytochemicals, including green tea catechins, have been reported to improve metabolic disorders and prevent the development of various cancers, including CRC. Moreover, the administration of branched-chain amino acids, which improves protein malnutrition and prevents the progression of hepatic failure, is effective for suppressing obesityrelated colon carcinogenesis, which is thought to be associated with improvements in insulin resistance. In the present article, we summarize the detailed relationship between metabolic abnormalities and the development of CRC. This review also outlines recent evidence, in particular drawing from basic and clinical examinations using either pharmaceutical or nutritional intervention that suggests that targeting metabolic alterations may be an effective strategy for preventing the development of CRC in obese individuals.

关键词： Colorectal cancer Obesity Green tea catechin Branched-chain amino acid Chemoprevention

Esophageal Carcinogenesis

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Open Journal of Pathology 2014年第4期4卷 151-170页

作者： Naoki Watanabe Masahito Shimizu Takahiro Kochi Yohei shirakami Takuji Tanaka Department of Diagnostic Pathology (DDP) & Research Center of Diagnostic Pathology (RC-DiP) Gifu Municipal Hospital Gifu Japan Department of Internal Medicine/Gastroenterology Gifu University Graduate School of Medicine Gifu Japan Department of Tumor Pathology Gifu University Graduate School of Medicine Gifu Japan

Esophageal cancer is the sixth leading cause of cancer death and remains one of the least survivable cancers. Esophageal cancers show wide variations in incidence in different population, suggesting that environmental or lifestyle risk factors could be controlled to reduce risk of these diseases. There are two major histopathologic types (squamous cell carcinoma and adenocarcinoma) of esophageal epithelial malignancy. Recently, the rate of adenocarcinoma is increasing in developed countries: in the United States, 50% or more is adenocarcinoma and, in about 70%, the increase especially in a white male serves as adenocarcinoma. Esophageal adenocarcinoma develops in the lower esophagus. In contrast, in Japan, the increase in adenocarcinoma is not clear and most (90%) of esophageal cancers are squamous cell carcinoma. Such squamous cell carcinoma occurs onto the middle part esophagus mostly, and 60% or more of the whole esophagus cancer also develops in the middle and upper parts. These differences also influence the treatment results. The scope of this article is to discuss carcinogenesis in the esophagus by giving an overview about its histopathological characteristics and molecular mechanisms.

关键词： Esophageal Neoplasms Preneoplastic Lesions Squamous Cell Carcinoma Adenocarcinoma Risk Factor