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| 1 | Apoptosis and non-alcoholic fatty liver diseases显示文摘The number of patients with nonalcoholic fatty liver diseases(NAFLD) including nonalcoholic steatohepatitis(NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma(HCC) and is one of the most serious health problems in the world. The mechanism through which NASH progresses is still largely unknown. Activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD/NASH. Apoptotic hepatocytes stimulate immune cells and hepatic stellate cells toward the progression of fibrosis in the liver through the production of inflammasomes and cytokines. Abnormalities in glucose and lipid metabolism as well as microbiota accelerate these processes. The production of reactive oxygen species, oxidative stress, and endoplasmic reticulum stress is also involved. Cell death, including apoptosis, seems very important in the progression of NAFLD and NASH. Recently, inhibitors of apoptosis have been developed as drugs for the treatment of NASH and may prevent cirrhosis and HCC. Increased hepatocyte apoptosis may distinguish NASH from NAFLD, and the improvement of apoptosis could play a role in controlling the development of NASH. In this review, the association between apoptosis and NAFLD/NASH are discussed. This review could provide their knowledge, which plays a role in seeing the patients with NAFLD/NASH in daily clinical practice. | Tatsuo Kanda Shunichi Matsuoka Motomi Yamazaki Toshikatsu Shibata Kazushige Nirei Hiroshi Takahashi Tomohiro Kaneko Mariko Fujisawa Teruhisa Higuchi Hitomi Nakamura Naoki Matsumoto Hiroaki Yamagami Masahiro Ogawa Hiroo Imazu Kazumichi Kuroda Mitsuhiko Moriyama | 2018 | World Journal of Gastroenterology2018，24，25： | 32 |
| 2 | Importance of adequate immunosuppressive therapy for the recovery of patients with 'life-threatening' severe exacerbation of chronic hepatitis B显示文摘AIM: Hepatitis B virus (HBV) re-activation often occurs spontaneously or after withdrawal of immunosuppressive therapy in patients with chronic hepatitis B. Severe exacerbation, sometimes developing into fulminant hepatic failure, is at high risk of mortality. The efficacy of corticosteroid therapy in 'clinically severe' exacerbation of chronic hepatitis B has not been well demonstrated. In this study we evaluated the efficacy of early introduction of high-dose corticosteroid therapy in patients with lifethreatening severe exacerbation of chronic hepatitis B.METHODS: Twenty-two patients, 14 men and 8 women,were defined as 'severe' exacerbation of chronic hepatitis B using uniform criteria and enrolled in this study. Eleven patients were treated with corticosteroids at 60 mg or more daily with or without anti-viral drugs within 10 d after the diagnosis of severe disease ('early high-dose'group) and 11 patients were either treated more than 10 d or untreated with corticosteroids ('non-early high-dose'group).RESULTS: Mean age, male-to-female ratio, mean prothrombin time (PT) activity, alanine transaminase (ALT)level, total bilirubin level, positivity of HBeAg, mean IgMHBc titer, and mean HBV DNA polymerase activity did not differ between the two groups. Ten of 11 patients of the 'early high-dose' group survived, while only 2 of 11 patients of the 'non-early high-dose' group survived (P<0.001). During the first 2 wk after the introduction of corticosteroids, improvements in PT activities and total bilirubin levels were observed in the 'early high-dose'group. Both ALT levels and HBV DNA polymerase levels fell in both groups.CONCLUSION: The introduction of high-dose corticosteroid can reverse deterioration in patients with 'clinically lifethreatening' severe exacerbation of chronic hepatitis B,when used in the early stage of illness. | Keiichi Fujiwara Osamu Yokosuka Hiroshige Kojima Tatsuo Kanda Hiromitsu Saisho Hiroyuki Hirasawa Hiroshi Suzuki | 2005 | World Journal of Gastroenterology2005，11，8： | 20 |
| 3 | Antiviral therapies for chronic hepatitis C virus infection with cirrhosis显示文摘Patients who are infected with hepatitis C virus(HCV) and also have advanced fibrosis or cirrhosis have beenrecognized as 'difficult-to-treat' patients during an era when peginterferon and ribavirin combination therapy is the standard of care. Recent guidelines have clearly stated that treatment should be prioritized in this population to prevent complications such as decompensation and hepatocellular carcinoma. Recent advances in the treatment of chronic hepatitis C have been achieved through the development of direct-acting antiviral agents(DAAs). Boceprevir and telaprevir are first-generation DAAs that inhibit the HCV NS3/4A protease. Boceprevir or telaprevir, in combination with peginterferon and ribavirin, improved the sustained virological response rates compared with peginterferon and ribavirin alone and were tolerated in patients with HCV genotype 1 infection without cirrhosis or compensated cirrhosis. However, the efficacy is lower especially in prior non-responders with or without cirrhosis. Furthermore, a high incidence of adverse events was observed in patients with advanced liver disease, including cirrhosis, in real-life settings. Current guidelines in the United States and in some European countries no longer recommend these regimens for the treatment of HCV. Next-generation DAAs include second-generation HCV NS3/4A protease inhibitors, HCV NS5 A inhibitors and HCV NS5 B inhibitors, which have a high efficacy and a lower toxicity. These drugs are used in interferon-free or in interferon-based regimens with or without ribavirin in combination with different classes of DAAs. Interferon-based regimens, such as simeprevir in combination with peginterferon and ribavirin, are well tolerated and are highly effective especially in treatmentnave patients and in patients who received treatment but who relapsed. The efficacy is less pronounced in nullresponders and in patients with cirrhosis. Interferonfree regimens in combination with ribavirin and/or two or more DAAs could be used for treatment-nave, treatment-experienced and even for interferon-ineligible or interferon-intolerant patients. Some clinical trials have demonstrated promising results, and have shown that the efficacy and safety were not different between patients with and without cirrhosis. There are also promising regimens for genotypes other than genotype 1. Interferonis contraindicated in patients with decompensated cirrhosis, and further studies are needed to establish the optimal treatment regimen for this population. In the future, interferon-free and ribavirin-free regimens with high efficacy and improved safety are expected for HCVinfected patients with advanced liver diseases. | Shingo Nakamoto Tatsuo Kanda Hiroshi Shirasawa Osamu Yokosuka | 2015 | World Journal of Hepatology2015，7，8： | 17 |
| 4 | Hepatitis C virus NS5A inhibitors and drug resistance mutations显示文摘Some direct-acting antiviral agents for hepatitis C virus(HCV),such as telaprevir and boceprevir have been available since 2011.It was reported that HCV NS5A is associated with interferon signaling related to HCV replication and hepatocarcinogenesis.HCV NS5A inhibitors efficiently inhibited HCV replication in vitro.Human studies showed that dual,triple and quad regimens with HCV NS5A inhibitors,such as daclatasvir and ledipasvir,in combination with other direct-acting antiviral agents against other regions of HCV with or without peginterferon/ribavirin,could efficiently inhibit HCV replication according to HCV genotypes.These combinations might be a powerful tool for'difficult-to-treat'HCV-infected patients.'First generation'HCV NS5A inhibitors such as daclatasvir,ledipasvir and ABT-267,which are now in phaseⅢclinical trials,could result in resistance mutations.'Second generation'NS5A inhibitors such as GS-5816,ACH-3102,and MK-8742,have displayed improvements in the genetic barrier while maintaining potency.HCV NS5A inhibitors are safe at low concentrations,which make them attractive for use despite low genetic barriers,although,in fact,HCV NS5A inhibitors should be used with HCV NS3/4A inhibitors,HCV NS5B inhibitors or peginterferon plus ribavirin.This review article describes HCV NS5A inhibitor resistance mutations and recommends that HCV NS5A inhibitors be used in combination regimens potent enough to prevent the emergence of resistant variants. | Shingo Nakamoto Tatsuo Kanda Shuang Wu Hiroshi Shirasawa Osamu Yokosuka | 2014 | World Journal of Gastroenterology2014，20，11： | 12 |
| 5 | Long-term results of elective hepatectomy for the treatment of ruptured hepatocellular carcinoma显示文摘 | Hiroshi Yoshida Yasuhiro Mamada Nobuhiko Taniai Yoshiaki Mizuguchi Daisuke Kakinuma Yoshinori Ishikawa Tomohiro Kanda Satoshi Matsumoto Koich Bando Koho Akimaru Takashi Tajiri | 2008 | Journal of Hepato - Biliary - Pancreatic Surgery2008，，2： | 2 |
| 6 | Postoperative long-term evaluation of interposition reconstruction compared with Roux-en-Y after total gastrectomy in gastric cancer: prospective randomized controlled trial显示文摘 | Sumiya Ishigami Shoji Natsugoe Shuichi Hokita Teruaki Aoki Hideyuki Kashiwagi Kosei Hirakawa Tetsuji Sawada Yoshitaka Yamamura Seiji Itoh Koichi Hirata Keiichiro Ohta Kenichi Mafune Yasushi Nakane Tatsuo Kanda Hiroshi Furukawa Iwao Sasaki Tetsuro Kubota M | 2011 | The American Journal of Surgery2011，，3： | 2 |
| 7 | Nuclear receptor mRNA expression by HBV in human hepatoblastoma cell lines显示文摘 | Shuang Wu Tatsuo Kanda Fumio Imazeki Shingo Nakamoto Hiroshi Shirasawa Osamu Yokosuka | 2011 | Cancer Letters2011，，1： | 2 |
| 8 | Colour changes produced in natural brown diamonds by high-pressure, high-temperature treatment显示文摘 | Alan T Collins Hisao Kanda Hiroshi Kitawaki | 2000 | Diamond & Related Materials2000，，2： | 1 |
| 9 | EXPRESSION OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR, UROKINASE-TYPE PLASMINOGEN ACTIVATOR RECEPTOR AND PLASMINOGEN ACTIVATOR INHIBITORS IN PATIENTS WITH RENAL CELL CARCINOMA: CORRELATION WITH TUMOR ASSOCIATED MACROPHAGE AND PROGNOSIS显示文摘 | KOJIRO OHBA YASUYOSHI MIYATA SHIGERU KANDA SHIGEHIKO KOGA TOMAYOSHI HAYASHI HIROSHI KANETAKE | 2005 | The Journal of Urology2005，，2： | 1 |
| 10 | NY-ESO-1 expression and its serum immunoreactivity in esophageal cancer显示文摘 | Argun Akcakanat Tatsuo Kanda Yu Koyama Michitoshi Watanabe Eiji Kimura Yutaka Yoshida Shintarou Komukai Satoru Nakagawa Shoji Odani Hiroshi Fujii Katsuyoshi Hatakeyama | 2004 | Cancer Chemotherapy and Pharmacology2004，，1： | 1 |
| 11 | Pitavastatin Reduces Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Ligands in Hypercholesterolemic Humans显示文摘 | Tetsuya Matsumoto Masatoshi Fujita Tatsuya Sawamura Akemi Kakino Yuko Sato Yoshiko Fujita Haruo Matsuda Mamoru Nakanishi Kagehiro Uchida Izuru Nakae Hiroshi Kanda Akira Yoshida Kunihisa Miwa Hideki Hayashi Kenichi Mitsunami Minoru Horie | 2010 | Lipids2010，，4： | 1 |
| 12 | Klotho insufficiency causes decrease of ribosomal RNA gene transcription activity, cytoplasmic RNA and rough ER in the spinal anterior horn cells显示文摘 | Yorito Anamizu Hiroshi Kawaguchi Atsushi Seichi Shinji Yamaguchi Emiko Kawakami Naotoshi Kanda Shiro Matsubara Makoto Kuro-o Yoichi Nabeshima Kozo Nakamura Kiyomitsu Oyanagi | 2005 | Acta Neuropathologica2005，，5： | 1 |
| 13 | Hepatoid adenocarcinoma: A distinctive histological subtype of alpha-fetoprotein-producing lung carcinoma显示文摘 | Hiroshi Ishikura Makoto Kanda Motohiko Ito Kenji Nosaka Kazuya Mizuno | 1990 | Virchows Archiv A Pathological Anatomy and Histopathology1990，，1： | 1 |
| 14 | Identification of putative metabolites of docosahexaenoic acid as potent PPARγ agonists and antidiabetic agents显示文摘 | Keiko Yamamoto Toshimasa Itoh Daijiro Abe Masato Shimizu Tomoatsu Kanda Takatoshi Koyama Masazumi Nishikawa Tadakazu Tamai Hiroshi Ooizumi Sachiko Yamada | 2004 | Bioorganic & Medicinal Chemistry Letters2004，，3： | 1 |
| 15 | Characterization of Trichoderma polysporum from Spitsbergen, Svalbard archipelago, Norway, with species identity, pathogenicity to moss, and polygalacturonase activity显示文摘 | Yusuke Yamazaki Motoaki Tojo Tamotsu Hoshino Kenichi Kida Tatsuji Sakamoto Hideshi Ihara Isao Yumoto Anne Marte Tronsmo Hiroshi Kanda | 2010 | Fungal Ecology2010，，1： | 1 |
| 16 | Colour changes produced in natural brown diamonds by high-pressure and high-temperature treatment显示文摘 | Alan T Collins Hisao Kanda Hiroshi Kitawaki | 2000 | Diamond and Related Materials2000，9，2： | 1 |
| 17 | Reduction of Pneumonia Risk by an Angiotensin I–Converting Enzyme Inhibitor in Elderly Japanese Inpatients According to Insertion/Deletion Polymorphism of the Angiotensin I–Converting Enzyme Gene显示文摘 | Takashi Takahashi Shigeto Morimoto Kohya Okaishi Tsugiyasu Kanda Takeshi Nakahashi Masashi Okuro Hiroshi Murai Yukiharu Nishimura Kunimitsu Iwai Masayuki Matsumoto | 2005 | American Journal of Hypertension2005，，10： | 1 |
| 18 | Analysis of Noise Sources and Their Transfer Paths in Diesel Engines显示文摘 | Hiroshi Kanda | | SAE0，，： | 1 |
| 19 | Dietary unripe apple polyphenol inhibits the development of food allergies in murine models显示文摘 | Hiroshi Akiyama Yuji Sato Takahiro Watanabe Megumi H. Nagaoka Yasuo Yoshioka Toshihiko Shoji Tomomasa Kanda Kiyoshi Yamada Mamoru Totsuka Reiko Teshima Jun-ichi Sawada Yukihiro Goda Tamio Maitani | 2005 | FEBS Letters2005，，20： | 1 |
| 20 | Colour changes produced in natural brown diamonds by high-pressure, high-temperature treatment显示文摘 | Alan T Collins Hisao Kanda Hiroshi Kitawaki | 2000 | Diamond & Related Materials2000，，2： | 1 |
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