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WJH 6^(th) Anniversary Special Issues(2): hepatocellular carcinoma Mammalian target of rapamycin inhibition in hepatocellular carcinoma

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World Journal of hepatology 2014年第11期6卷 776-782页

作者： René E Ashworth Jennifer Wu Hematology and Medical Oncology Pro-gram NYU School of Medicine Perlmutter Cancer Center NYU Langone Medical Center Division of Hematology and Oncology NYU School of Medicine Subdivision of GI Oncology Perlmutter Cancer Center NYU Langone Medical Center Division of Hematology and Oncology

hepatocellular carcinoma(HCC) is one of the leading causes of cancer-related death worldwide. It is associated with a poor prognosis and has limited treatment options. Sorafenib, a multi-targeted kinase inhibitor, is the only available systemic agent for treatment of HCC that improves overall survival for patients with advanced stage disease; unfortunately, an effective second-line agent for the treatment of progressive or sorafenib-resistant HCC has yet to be identified. This review focuses on components of the mammalian target of rapamycin(mTOR) pathway, its role in HCC pathogenesis, and dual mTOR inhibition as a therapeutic option with potential efficacy in advanced HCC. There are several important upstream and downstream signals in the mTOR pathway, and alternative tumor-promoting pathways are known to exist beyond mTORC1 inhibition in HCC. This review analyzes the relationships of the upstream and downstream regulators of mTORC1 and mTORC2 signaling; it also provides a comprehensive global picture of the interaction between mTORC1 and mTORC2 which demonstrates the pre-clinical relevance of the mTOR pathway in HCC pathogenesis and progression. Finally, it provides scientific rationale for dual mTORC1 and mTORC2 inhibition in the treatment of HCC. Clinical trials utilizing mTORC1 inhibitors and dual mTOR inhibitors in HCC are discussed as well. The mTOR pathway is comprised of two main components, mTORC1 and mTORC2; each has a unique role in the pathogenesis and progression of HCC. In phase Ⅲ studies, mTORC1 inhibitors demonstrate anti-tumor ac-tivity in advanced HCC, but dual mTOR(mTORC1 and mTORC2) inhibition has greater therapeutic potential in HCC treatment which warrants further clinical investigation.

关键词： Mammalian target of rapamycin hepato-cellular carcinoma Mammalian target of rapamycin complex 1 Mammalian target of rapamycin complex 2 PI3K/AKT/mTOR signaling pathway Sorafenib Everoli-mus Sirolimus Liver transplantation CC-223

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hepatocellular carcinoma and focal nodular hyperplasia of the liver in a glycogen storage disease patient

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World Journal of hepatology 2012年第6期4卷 191-195页

作者： Yoshihiro Mikuriya Akihiko Oshita Hirotaka Tashiro Hironobu Amano Tsuyoshi Kobayashi Kouji Arihiro Hideki Ohdan Division of Frontier Medical Science Department of Surgery Graduate School of Biomedical Sciences Hiroshima University 1-2-3 Kasumi Minami-ku Hiroshima 734-8551 Japan Department of Pathology Hiroshima University Hospital1-2-3 Kasumi Minami-ku Hiroshima 734-8551 Japan

Glycogen storage disease type Ia (GSD-Ia; also called von Gierke disease) is an autosomal recessive disorder of carbohydrate metabolism caused by glucose-6-phosphatase deficiency. There have been many reports describing hepatic tumors in GSD patients; however, most of these reports were of hepatocellular adenomas, whereas there are only few reports describing focal nodular hyperplasia (FNH) or hepatocellular carcinoma (HCC). We report a case with GSD-Ia who had undergone a partial resection of the liver for FNH at 18 years of age and in whom moderately differentiated HCC had developed. Preoperative imaging studies, including ultrasonography, dynamic computer tomography (CT) and magnetic resonance imaging, revealed benign and malignant features. In particular, fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT revealed the atypical findings that FDG accumulated at high levels in the non-tumorous hepatic parenchyma and low levels in the tumor. Right hemihepatectomy was performed. During the perioperative period, high-dose glucose and sodium bicarbonate were administered to control metabolic acidosis. He had multiple recurrences of HCC at 10 mo after surgery and was followed-up with transcatheter arterial chemoembolization. The tumor was already highly advanced when it was found by chance; therefore, a careful follow-up should be mandatory for GSD-I patients as they are at a high risk for HCC, similar to hepatitis patients.

关键词： Glycogen storage disease type Ia hepato-cellular carcinoma Focal nodular hyperplasia Hepatectomy Metachronous

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Protein induced by vitamin K absence or antagonist Ⅱ-producing gastric cancer

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World Journal of Gastrointestinal Pathophysiology 2010年第4期1卷 129-136页

作者： Yoshihisa Takahashi Tohru Inoue Toshio Fukusato Department of Pathology Teikyo University School of Medicine Department of Pathology Tokyo Kousei-Nenkin Hospital

Protein induced by vitamin K absence or antagonist Ⅱ(PIVKA-Ⅱ) is a putative specific marker of hepatocellular carcinoma(HCC),but it may also be produced by asmall number of gastric *** date,16 cases of PIVKA-Ⅱ-producing gastric cancer have been reported,2 of which were reported by us and all of which were identified in *** are no symptoms specific to PIVKA-Ⅱ-producing gastric cancer,and the representative clinical symptoms are general fatigue,appetite loss,and upper abdominal *** alpha-feto-protein(AFP)levels are also increased in almost *** metastasis is observed in approximately 80% of cases and portal vein tumor thrombus is ob-served in approximately 20% of *** diagnosis between metastatic liver tumor and HCC is often ***,almost all cases appear as advanced gastric ***,a hepatoid pattern is observed in many cases,in addition to a moderately to poorly differentiated adenocarcinoma *** production of PIVKA-Ⅱ and AFP is usually confirmed using immunohistochemical *** and prognosis largely depends on the existence of liver meta-stasis,and the prognosis of patients with liver metas-tasis is very ***-Ⅱ may be produced during the hepatocellular metaplasia of the tumor cells.

关键词： Protein induced by vitamin K absence or antagonist Ⅱ Gastric cancer Alpha-fetoprotein hepato-cellular carcinoma hepatoid carcinoma

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Role of the contrast-enhanced ultrasoud in the diagnosis of HCC in cirrhotic liver

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hepatoma Research 2018年第9期4卷 111-122页

作者： Francesco Loria AntoneIIo ParIati Giuseppe Loria Luciano Frosina Giuseppe Crea SaIvatore BasiIe Caterina AIessio Giuseppe Di Leo AdeIe De Caridi Vittorio Maschio NicoIa Zizzi Orazio Trapuzzano SaIvatore Giuseppe GaIea Deptartment of Radiology Giovanni Paolo II HospitalLamezia Terme ZC 89015Italy Deptartment of Radiology Policlinico G.Martino University of MessinaMessina ZC 98100Italy Deptartment of Radiology Palmi HospitalASP RCPalmi ZC 89015Italy

The development of second generation ultrasound (US) contrast-medium and specific imaging techniques with dedicated softwares, allows to observe the liver perfusion in real time, becoming an useful and less invasive method to describe precisely the vascularization of hepatic lesions. This significantly increased the ability of US to detect and characterize focal liver lesions. The aim of this review article is to evaluate the role of contrast enhancement US in the diagnosis of hepatocellular carcinoma in cirrhotic liver, with reference to the guidelines of American Association for the Study of Liver Diseases, European Association for the Study of the Liver and European Federation of Societies for Ultrasound in Medicine and Biology.

关键词： Contrast-enhanced ultrasound hepato-cellular carcinoma cirrhotic liver

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Certainty of patient survival with reference to game information dynamic model

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Open Journal of Preventive Medicine 2012年第4期2卷 490-498页

作者： Hiroyuki Iida Takeo Nakagawa Nathan Nossal School of Information Science Japan Advanced Institute of Science and Technology Nomi Japan

This paper is concerned with hepato-cellular Carcinoma (HCC) patients treated naturopathic agents. Patients treated with ≥4 agents survived significantly longer than patients treated with ≤3 agents. The great effect is seen in patients treated with at least 4 agents that include Cordyceps sinensis. This greater certainty of patient survival without toxic side effects is significant benefit comparing with the conventional therapy. Treatment of HCC with a regimen of ≥4 agents prepared from natural products is associated with greater certainty of patient survival in a substantial portion of patients. The information dynamic model for certainty of patient survival is derived based on fluid mechanics, where a series of approximate solutions of the flow between two parallel flat walls, one of which is at rest, the other is suddenly accelerated from the rest to a constant velocity are used. The kinetic energy of certainty of patient survival decreases with increasing time, while the potential energy increases with increasing time. Total mechanical energy of patients treated with 4 or more agents is smaller than that treated with 3 or fewer agents. The kinetic energy (potential energy) of patients treated with 4 or more agents decreases (increases) more slower than the kinetic energy (potential energy) of patients treated with 3 or fewer agents.

关键词： Certainty of Patient Survival Game Information Dynamic Model Naturopathic Therapy Herbal Treatment Natural Antioxidants hepato-cellular Carcinoma

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