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| 1 | Current and future directions for treating hepatitis B virus infection显示文摘Hepatitis B virus(HBV) persistently infects approximately 350 million people, and approximately 600000 liverrelated deaths are observed per year worldwide. HBV infection is also one of the major risk factors for hepatocellular carcinoma(HCC). The persistence of serum hepatitis B e antigen(HBe Ag) and high level of serum HBV DNA are thought to reflect a high HBV replication status in hepatocytes, causing cirrhosis, HCC and liver-related deaths. It has been reported that antiviral therapy, such as peginterferon and nucleos(t)ide analogues(NUCs), could suppress liver-related death by inhibiting the HBV DNA levels and inducing seroconversion from HBe Ag to antibody to HBe antigen. Currently, peginterferon is widely used, but there are also several disadvantages in the use of peginterferon, such as various adverse events, the administration route and duration. It is difficult to predict the effects of treatment and interferon is contraindicated for the patients with advanced fibrosis of the liver and cirrhosis. With respect to NUCs, entecavir and tenofovir disoproxil fumarate are current the first-choice drugs. NUCs can be administered orally, and their anti-viral effects are stronger than that of peginterferon. However, because cessation of NUC administration leads to high levels of viral replication and causes severe hepatitis, they must be administered for a long time. On the other hand, the use of both interferon and NUCs cannot eliminate covalently closed circular DNA of HBV. In this review, we evaluate the natural course of chronic HBV infection and then provide an outline of these representative drugs, such as peginterferon, entecavir and tenofovir disoproxil fumarate. | Akinobu Tawada Tatsuo Kanda Osamu Yokosuka | 2015 | World Journal of Hepatology2015，7，11： | 16 |
| 2 | Intragenic antagonistic roles of protein and circRNA in tumorigenesis显示文摘circRNAs arise from back splicing events during mRNA processing, and when deregulated can play an active role in cancer. Here we characterize a new circRNA (circPOK) encoded by the Zbtb7a gene (also kown as POKEMON, LRF) in the context of mesenchymal tumor progression. circPOK functions as a non-coding proto-oncogenic RNA independently and antithetically to its linear transcript counterpart, which acts as a tumor suppressor by encoding the Pokemon transcription factor. We find that circPOK regulates pro-proliferative and pro-angiogenic factors by co-activation of the ILF2/3 complex. Importantly, the expression of Pokemon protein and circRNA is aberrantly uncoupled in cancer through differential post-transcriptional regulation. Thus, we identify a novel type of genetic unit, the iRegulon, that yields biochemically distinct RNA products, circular and linear, with diverse and antithetical functions. Our findings further expand the cellular repertoire towards the control of normal biological outputs, while aberrant expression of such components may underlie disease pathogenesis including cancer. | Jlenia Guarnerio Yang Zhang Giulia Cheloni Riccardo Panella Jesse Mae Katon Mark Simpson Akinobu Matsumoto Antonella Papa Cristian Loretelli Andreas Petri Sakari Kauppinen Cassandra Garbutt Gunnlaugur Petur Nielsen Vikram Deshpande Mireia Castillo-Martin Carlos Cordon-Cardo Spentzos Dimitrios John G. Clohessy Mona Batish Pier Paolo Pandolfi | 2019 | Cell Research2019，29，8： | 15 |
| 3 | 艾地苯醌治疗缺血性脑血管疾病的药理作用及临床应用显示文摘动物实验证实艾地苯醌具有对发生脑卒中的大鼠脑线粒体功能有激活作用、对脑能量代谢及脑功能障碍有改善作用,艾地苯醌的T_(1/2)为7.69h,T_(max)3.31h,C_(max)为290ng/mL,24h尿中排泄率为32%。艾地苯醌治疗脑动脉硬化症和脑梗死后遗症30例(男24例,女6例;年龄67±23a)总改善率90%,情感障碍、智力低下、行动异常等改善率73%-81%,不良反应轻微。 | 杨学义 韩宝福 崔世贞 Akinobu Nagaoka | 1993 | 新药与临床1993，12，1： | 11 |
| 4 | Significance of functional hepatic resection rate calculated using 3D CT/^(99m)Tc-galactosyl human serum albumin singlephoton emission computed tomography fusion imaging显示文摘AIM: To evaluate the usefulness of the functional hepatic resection rate(FHRR) calculated using 3D computed tomography(CT)/^(99m)Tc-galactosyl-human serum albumin(GSA) single-photon emission computed tomography(SPECT) fusion imaging for surgical decision making. METHODS: We enrolled 57 patients who underwent bi- or trisectionectomy at our institution between October 2013 and March 2015. Of these, 26 patients presented with hepatocellular carcinoma, 12 with hilar cholangiocarcinoma, six with intrahepatic cholangiocarcinoma, four with liver metastasis, and nine with other diseases. All patients preoperatively underwent three-phase dynamic multidetector CT and ^(99m)Tc-GSA scintigraphy. We compared the parenchymal hepatic resection rate(PHRR) with the FHRR, which was defined as the resection volume counts per total liver volume counts on 3D CT/^(99m)Tc-GSA SPECT fusion images.RESULTS: In total, 50 patients underwent bisectionectomy and seven underwent trisectionectomy.Biliary reconstruction was performed in 15 patients, including hepatopancreatoduodenectomy in two. FHRR and PHRR were 38.6 ± 19.9 and 44.5 ± 16.0, respectively; FHRR was strongly correlated with PHRR. The regression coefficient for FHRR on PHRR was 1.16(P < 0.0001). The ratio of FHRR to PHRR for patients with preoperative therapies(transcatheter arterial chemoembolization, radiation, radiofrequency ablation, etc.), large tumors with a volume of > 1000 m L, and/or macroscopic vascular invasion was significantly smaller than that for patients without these factors(0.73 ± 0.19 vs 0.82 ± 0.18, P < 0.05). Postoperative hyperbilirubinemia was observed in six patients. Major morbidities(Clavien-Dindo grade ≥ 3) occurred in 17 patients(29.8%). There was no case of surgeryrelated death.CONCLUSION: Our results suggest that FHRR is an important deciding factor for major hepatectomy, because FHRR and PHRR may be discrepant owing to insufficient hepatic inflow and congestion in patients with preoperative therapies, macroscopic vascular invasion, and/or a tumor volume of > 1000 m L. | Yosuke Tsuruga Toshiya Kamiyama Hirofumi Kamachi Shingo Shimada Kenji Wakayama Tatsuya Orimo Tatsuhiko Kakisaka Hideki Yokoo Akinobu Taketomi | 2016 | World Journal of Gastroenterology2016，22，17： | 6 |
| 5 | Biological features and biomarkers in hepatocellular carcinoma显示文摘Similar to other cancers, a multistep process of carcinogenesis is observed in hepatocellular carcinoma(HCC). Although the mechanisms underlying the development of HCC have been investigated in terms of oncology, virology, and stem cell biology, the whole picture of hepatocarcinogenesis remains to be elucidated. Recent progress in molecular biology has provided clues to the underlying cause of various diseases. In particular, sequencing technologies, such as whole genome and exome sequencing analyses, have made an impact on genomic research on a variety of cancers including HCC. Comprehensive genomic analyses have detected numerous abnormal genetic alterations, such as mutations and copy number alterations. Based on these findings, signaling pathways and cancer-related genes involved in hepatocarcinogenesis could be analyzed in detail. Simultaneously, a number of novel biomarkers, both from tissue and blood samples, have been recently reported. These biomarkers have been successfully applied to early diagnosis and prognostic prediction of patients with HCC. In this review, we focus on the recent developments in molecular cancer research on HCC and explain the biological features and novel biomarkers. | Tetsuhiro Chiba Eiichiro Suzuki Tomoko Saito Sadahisa Ogasawara Yoshihiko Ooka Akinobu Tawada Atsushi Iwama Osamu Yokosuka | 2015 | World Journal of Hepatology2015，7，16： | 5 |
| 6 | Clinical impacts of mesothelin expression in gastrointestinal carcinomas显示文摘Mesothelin,C-ERC/mesothelin is a 40-kD a cell surface glycoprotein that is normally present on normal mesothelial cells lining the pleura,peritoneum,and pericardium.Moreover,mesothelin has been shown to be overexpressed in several human cancers,including virtually all mesothelioma and pancreatic cancer approximately 70% of ovarian cancer and extra bile duc cancer,and 50% of lung adenocarcinomas and gastric cancer.The full-length human mesothelin gene encodes the primary product,a 71-k Da precursor protein.The71-kD a mesothelin precursor is cleaved into two products40-k Da C-terminal fragment that remains membranebound via glycosylphosphatidylinositol anchor,and a31-kD a N-terminal fragment,megakaryocyte potentiating factor,which is secreted into the blood.The biologica functions of mesothelin remain largely unknown However,results of recent studies have suggested tha the mesothelin may play a role of cell proliferation and migration.In pancreatic cancer,mesothelin expression was immunohistochemically observed in all cases,bu absent in normal pancreas and in chronic pancreatitis Furthermore,the expression of mesothelin was correlated with an poorer patient outcome in severa human cancers.The limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer therapy.The present review discusses the expression and function o mesothelin in cancer cells and the utility of mesothelin as a target of cancer therapy. | Takahiro Einama Futoshi Kawamata Hirofumi Kamachi Hiroshi Nishihara Shigenori Homma Fumihiko Matsuzawa Tatsuzo Mizukami Yuji Konishi Munenori Tahara Toshiya Kamiyama Okio Hino Akinobu Taketomi Satoru Todo | 2016 | World Journal of Gastrointestinal Pathophysiology2016，7，2： | 4 |
| 7 | Control of oxidative stress in hepatocellular carcinoma: Helpful or harmful?显示文摘Oxidative stress is becoming recognized as a key factor in the progression of chronic liver disease(CLD) and hepatocarcinogenesis. The metabolically important liver is a major reservoir of mitochondria that serve as sources of reactive oxygen species, which are apparently responsible for the initiation of necroinflammation. As a result, CLD could be a major inducer of oxidative stress. Chronic hepatitis C is a powerful generator of oxidative stress, causing a high rate of hepatocarcinogenesis among patients with cirrhosis. Non-alcoholic steatohepatitis is also associated with oxidative stress although its hepatocarcinogenic potential is lower than that of chronic hepatitis C. Analyses of serum markers and histological findings have shown that hepatocellular carcinoma correlates with oxidative stress and experimental data indicate that oxidative stress increases the likelihood of developing hepatocarcinogenesis. However, the results of antioxidant therapy have not been favorable. Physiological oxidative stress is a necessary biological response, and thus adequate control of oxidative stress and a balance between oxidative and anti-oxidative responses is important. Several agents including metformin and L-carnitine can reportedly control mechanistic oxidative stress. This study reviews the importance of oxidative stress in hepatocarcinogenesis and of control strategies for the optimal survival of patients with CLD and hepatocellular carcinoma. | Akinobu Takaki Kazuhide Yamamoto | 2015 | World Journal of Hepatology2015，7，7： | 4 |
| 8 | Hepatic osteodystrophy complicated with bone fracture in early infants with biliary atresia显示文摘Biliary atresia(BA) is one of the major hepatobiliary abnormalities in infants and one of the causes of hepatic osteodystrophy.Bone disease may be caused by the malabsorption of calcium and magnesium by vitamin D in hepatobiliary diseases in which bile flow into the intestines is deficient or absent.Bone fracture before Kasai hepatic portoenterostomy or within one month after the procedure in an infant with BA is very rare.We herein report two infants:one infant with BA who initially presented with a bone fracture before Kasai hepatic portoenterostomy,and the other at 4 wk after Kasai hepatic portoenterostomy,and also provide a review of the literature.Moreover,we conclude that clinicians should consider BA in infants with bone fracture during early infancy. | Tadao Okada Shohei Honda Hisayuki Miyagi Masashi Minato Akinobu Taketomi | 2012 | World Journal of Hepatology2012，4，10： | 3 |
| 9 | Alpha-fetoprotein before and after pegylated interferon therapy for predicting hepatocellular carcinoma development显示文摘AIM: To investigate factors that accurately predict hepatocellular carcinoma(HCC) development after antiviral therapy in chronic hepatitis C(CHC) patients. METHODS: CHC patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein(AFP) to predict HCC development after interferon(IFN) therapy. RESULTS: Of 1255 patients enrolled, 665 developed sustained virological response(SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients were included. Proportional hazard models showed that HCC occurred in SVR patients showing AFP ≥ 5 ng/m L before therapy and in non-SVR patients showing AFP ≥ 5 ng/m L before and 1 year after therapy besides older age, and low platelet counts. SVR patients showing AFP ≥ 5 ng/m L before therapy and no decrease in AFP to < 5 ng/m L 1 year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP ≥ 5 ng/m L before therapy and decreased AFP(P = 0.043). AFP ≥ 5 ng/m L before therapy was significantly associated with low platelet counts and high values of alanine aminotransferase(ALT) in stepwise logistic regression analysis. After age, gender, platelet count, and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP < 5 ng/m L before therapy than in those showing AFP ≥ 5 ng/m L.CONCLUSION: The criteria of AFP < 5 ng/m L before and 1 year after IFN therapy is a benefical predictor for HCC development in CHC patients. | Yasuto Takeuchi Fusao Ikeda Toshiya Osawa Yasuyuki Araki Kouichi Takaguchi Youichi Morimoto Noriaki Hashimoto Kousaku Sakaguchi Tatsuro Sakata Masaharu Ando Yasuhiro Makino Shuji Matsumura Hiroki Takayama Hiroyuki Seki Shintarou Nanba Yuki Moritou Tetsuya Yasunaka Hideki Ohnishi Akinobu Takaki Kazuhiro Nouso Yoshiaki Iwasaki Kazuhide Yamamoto | 2015 | World Journal of Hepatology2015，7，19： | 3 |
| 10 | THE GREATER VULNERABILITY OF BILE DUCT CELLS TO REOXYGENATION INJURY THAN TO ANOXIA显示文摘 | KEITH NOACK STEVEN F. BRONK AKINOBU KATO GREGORY J. GORES | 1993 | Transplantation1993，，3： | 3 |
| 11 | Predictors of Extrahepatic Recurrence After Curative Hepatectomy for Hepatocellular Carcinoma显示文摘 | Akinobu Taketomi Takeo Toshima Dai Kitagawa Takashi Motomura Kazuki Takeishi Yohei Mano Hiroto Kayashima Keishi Sugimachi Shinichi Aishima Yoichi Yamashita Toru Ikegami Tomonobu Gion Hideaki Uchiyama Yuji Soejima Takashi Maeda Ken Shirabe Yoshihiko Maehar | 2010 | Annals of Surgical Oncology2010，，10： | 2 |
| 12 | Rituximab, IVIG, and Plasma Exchange Without Graft Local Infusion Treatment: A New Protocol in ABO Incompatible Living Donor Liver Transplantation显示文摘 | Toru Ikegami Akinobu Taketomi Yuji Soejima Tomoharu Yoshizumi Hideaki Uchiyama Noboru Harada Tomohiro Iguchi Naotaka Hashimoto Yoshihiko Maehara | 2009 | Transplantation2009，，3： | 2 |
| 13 | Russell body gastritis with Dutcher bodies evaluated using magnification endoscopy显示文摘Russell body gastritis(RBG) is an unusual type of chronic gastritis characterized by marked infiltration of Mott cells,which are plasma cells filled with spherical eosinophilic bodies referred to as Russell bodies.It was initially thought that Helicobacter pylori(H.pylori) infection was a major cause of RBG and that the infiltrating Mott cells were polyphenotypic;however,a number of cases of RBG without H.pylori infection or with monoclonal Mott cells have been reported.Thus,diagnostic difficulty exists in distinguishing RBG with monoclonal Mott cells from malignant lymphoma.Here,we report an unusual case of an 86-year-old-Japanese man with H.pylori-positive RBG.During the examination of melena,endoscopic evaluation confirmed a 13-mm whitish,flat lesion in the gastric antrum.Magnification endoscopy with narrowband imaging suggested that the lesion was most likely a poorly differentiated adenocarcinoma.Biopsy findings were consistent with chronic gastritis with many Mott cells with intranuclear inclusions referred to as Dutcher bodies.Endoscopic submucosal dissection confirmed the diagnosis of RBG with kappa-restricted monoclonal Mott cells.Malignant lymphoma was unlikely given the paucity of cytological atypia and Ki-67 immunoreactivity of monoclonal Mott cells.This is the first reported case of RBG with endoscopic diagnosis of malignant tumor and the presence of Dutcher bodies. | Kenji Yorita Takehiro Iwasaki Kunihisa Uchita Naoto Kuroda Koji Kojima Shinichi Iwamura Yutaka Tsutsumi Akinobu Ohno Hiroaki Kataoka | 2017 | World Journal of Gastrointestinal Endoscopy2017，9，8： | 2 |
| 14 | Tumor-Associated Macrophage Promotes Tumor Progression via STAT3 Signaling in Hepatocellular Carcinoma显示文摘 | Mano Yohei Aishima Shinichi Fujita Nobuhiro Tanaka Yuki Kubo Yuichiro Motomura Takashi Taketomi Akinobu Shirabe Ken Maehara Yoshihiko Oda Yoshinao | 2013 | Pathobiology2013，，3： | 2 |
| 15 | One‐step venous reconstruction for a right lobe graft with multiple venous orifices in living donor liver transplantation显示文摘 | Yuji Soejima Naoyuki Ueda Takasuke Fukuhara Tomoharu Yoshizumi Toru Ikegami Yoichi Yamashita Keishi Sugimachi Akinobu Taketomi Yoshihiko Maehara | 2008 | Liver Transpl2008，，5： | 2 |
| 16 | A Simple Hilar Dissection Technique Preserving Maximum Blood Supply to the Bile Duct in Living Donor Liver Transplantation显示文摘 | Yuji Soejima Takasuke Fukuhara Kazutoyo Morita Tomoharu Yoshizumi Toru Ikegami Yoichi Yamashita Keishi Sugimachi Akinobu Taketomi Yoshihiko Maehara | 2008 | Transplantation2008，，10： | 2 |
| 17 | Risk factors for recurrence after transarterial chemoembolization for early-stage hepatocellular carcinoma显示文摘 | Hideaki Kinugasa Kazuhiro Nouso Yasuto Takeuchi Tetsuya Yasunaka Hideki Onishi Shin-ichiro Nakamura Hidenori Shiraha Kenji Kuwaki Hiroaki Hagihara Fusao Ikeda Yasuhiro Miyake Akinobu Takaki Kazuhide Yamamoto | 2012 | Journal of Gastroenterology2012，，4： | 2 |
| 18 | Role of tumor-associated macrophages in the progression of hepatocellular carcinoma显示文摘 | Ken Shirabe Yohei Mano Jun Muto Rumi Matono Takashi Motomura Takeo Toshima Kazuki Takeishi Hidekaki Uchiyama Tomoharu Yoshizumi Akinobu Taketomi Masaru Morita Shunichi Tsujitani Yoshihisa Sakaguchi Yoshihiko Maehara | 2012 | Surgery Today2012，，1： | 2 |
| 19 | Extended Indication for Living Donor Liver Transplantation in Patients With Hepatocellular Carcinoma显示文摘 | Yuji Soejima Akinobu Taketomi Tomoharu Yoshizumi Hideaki Uchiyama Shinich Aishima Takahiro Terashi Mitsuo Shimada Yoshihiko Maehara | 2007 | Transplantation2007，，7： | 2 |
| 20 | Zero mortality in more than 300 hepatic resections: validity of preoperative volumetric analysis显示文摘 | Shinji Itoh Ken Shirabe Akinobu Taketomi Kazutoyo Morita Norifumi Harimoto Eiji Tsujita Keishi Sugimachi Yo-ichi Yamashita Tomonobu Gion Yoshihiko Maehara | 2012 | Surgery Today2012，，5： | 2 |
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