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| 1 | Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma显示文摘AIM: To assess the clinical features and prognosis of 151 patients with extrahepatic metastases from primary hepatocellular carcinoma (HCC), and describe the treatment strategy for such patients. METHODS: After the diagnosis of HCC, all 995 consecutive HCC patients were followed up at regular intervals and 151 (15.2%) patients were found to have extrahepatic metastases at the initial diagnosis of primary HCC or developed such tumors during the follow-up period. We assessed their clinical features, prognosis, and treatment strategies. RESULTS: The most frequent site of extrahepatic metastases was the lungs (47%), followed by lymph nodes (45%), bones (37%), and adrenal glands (12%). The cumulative survival rates after the initial diagnosis of extrahepatic metastases at 6, 12, 24, and 36 mo were 44.1%, 21.7%, 14.2%, 7.1%, respectively. The median survival time was 4.9 mo (range, 0-37 mo). Fourteen patients (11%) died of extrahepatic HCC, others died of primary HCC or liver failure. CONCLUSION: The prognosis of HCC patients with extrahepatic metastases is poor. With regard to the cause of death, many patients would die of intrahepatic HCC and few of extrahepatic metastases. Although most of HCC patients with extrahepatic metastases should undergo treatment for the primary HCC mainly, treatment of extrahepatic metastases in selected HCC patients who have good hepatic reserve, intrahepatictumor stage (T0-T2), and are free of portal venous invasion may improve survival. | Kiminori Uka Hiroshi Aikata Shintaro Takaki Hiroo Shirakawa Soo Cheol Jeong Keitaro Yamashina Akira Hiramatsu Hideaki Kodama Shoichi Takahashi Kazuaki Chayama | 2007 | World Journal of Gastroenterology2007，13，3： | 44 |
| 2 | Molecular diagnosis and therapy for occult peritoneal metastasis in gastric cancer patients显示文摘To apply an individualized oncological approach to gastric cancer patients,the accurate diagnosis of disease entities is required.Peritoneal metastasis is the most frequent mode of metastasis in gastric cancer,and the tumor-node-metastasis classification includes cytological detection of intraperitoneal cancer cells as part of the staging process,denoting metastatic disease.The accuracy of cytological diagnosis leaves room for improvement;therefore,highly sensitive molecular diagnostics,such as an enzyme immunoassay,reverse transcription polymerase chain reaction,and virusguided imaging,have been developed to detect minute cancer cells in the peritoneal cavity.Molecular targeting therapy has also been spun off from basic research in the past decade.Although conventional cytologyis still the mainstay,novel approaches could serve as practical complementary diagnostics to cytology in near future. | Shunsuke Kagawa Kunitoshi Shigeyasu Michihiro Ishida Megumi Watanabe Hiroshi Tazawa Takeshi Nagasaka Yasuhiro Shirakawa Toshiyoshi Fujiwara | 2014 | World Journal of Gastroenterology2014，20，47： | 11 |
| 3 | Progress in researches about focal adhesion kinase in gastrointestinal tract显示文摘Focal adhesion kinase(FAK)is a 125-kDa non-receptor protein tyrosine.Growth factors or the clustering of integrins facilitate the rapid phosphorylation of FAK at Tyr-397 and this in turn recruits Src-family protein tyrosine kinases,resulting in the phosphorylation of Tyr-576 and Tyr-577 in the FAK activation loop and full catalytic FAK activation.FAK plays a critical role in the biological processes of normal and cancer cells including the gastrointestinal tract.FAK also plays an important role in the restitution,cell survival and apoptosis and carcinogenesis of the gastrointestinal tract.FAK is over-expressed in cancer cells and its over-expression and elevated activities are associated with motility and invasion of cancer cells.FAK has been proposed as a potential target in cancer therapy.Small molecule inhibitors effectively inhibit the kinase activity of FAK and show a potent inhibitory effect for the proliferation and migration of tumor cells,indicating a high potential for application in cancer therapy. | Hui Fang Hao Yoshio Naomoto Xiao-Hong Bao Nobuyuki Watanabe Kazufumi Sakurama Kazuhiro Noma Yasuko Tomono Takuya Fukazawa Yasuhiro Shirakawa Tomoki Yamatsuji Junji Matsuoka Munenori Takaoka | 2009 | World Journal of Gastroenterology2009，15，47： | 8 |
| 4 | The inverse association between tuberculin responses and atopic disorder显示文摘 | Shirakawa T Enomoto T Shimazu S | | 0，，： | 6 |
| 5 | Facile and Scalable Synthesis of a Highly Hydroxylated Water-Soluble Fullerenol as a Single Nanoparticle显示文摘水溶性的 polyhydroxylated fullerene,即 fullerenol 与 44 个氢氧根组和 8 个第二等的界限水分子一起, C60 (哦) | Ken Kokubo Shogo Shirakawa Naoki Kobayashi Hisae Aoshima Takumi Oshima | 2011 | Nano Research2011，4，2： | 5 |
| 6 | Glutamine depletion induces murine neonatal melena with increased apoptosis of the intestinal epithelium显示文摘AIM:To investigate the possible biological outcome and effect of glutamine depletion in neonatal mice and rodent intestinal epithelial cells.METHODS:We developed three kinds of artificial milk with different amounts of glutamine;Complete amino acid milk (CAM),which is based on maternal mouse milk,glutamine-depleted milk (GDM),and glutaminerich milk (GRM).GRM contains three-fold more glutamine than CAM.Eighty-seven newborn mice were divided into three groups and were fed with either of CAM,GDM,or GRM via a recently improved nipple-bottle system for seven days.After the feeding period,the mice were subjected to macroscopic and microscopic observations by immunohistochemistry for 5-bromo-2'deoxyuridine (BrdU) and Ki-67 as markers of cell proliferation,and for cleaved-caspase-3 as a marker of apoptosis.Moreover,IEC6 rat intestinal epithelial cells were cultured in different concentrations of glutamine and were subject to a 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)2H-5-tetrazolio]-1,3-benzene disulfonate cell proliferation assay,flow cytometry,and western blotting to examine the biological effect of glutamine on cell growth and apoptosis.RESULTS:During the feeding period,we found colonic hemorrhage in six of 28 GDM-fed mice (21.4%),but not in the GRM-fed mice,with no differences in body weight gain between each group.Microscopic examination showed destruction of microvilli and the disappearance of glycocalyx of the intestinal wall in the colon epithelial tissues taken from GDM-fed mice.Intake of GDM reduced BrdU incorporation (the average percentage of BrdU-positive staining;GRM:13.8%,CAM:10.7%,GDM:1.14%,GRM vs GDM:P < 0.001,CAM vs GDM:P < 0.001) and Ki-67 labeling index (the average percentage of Ki67-positive staining;GRM:24.5%,CAM:22.4% GDM:19.4%,GRM vs GDM:P=0.001,CAM vs GDM:P =0.049),suggesting that glutamine depletion inhibited cell proliferation of intestinal epithelial cells.Glutamine deprivation further caused the deformation of the nuclear membrane and the plasma membrane,accompanied by chromatin degeneration and an absence of fat droplets from the colonic epithelia,indicating that the cells underwent apoptosis.Moreover,immunohistochemical analysis revealed the appearance of cleaved caspase-3 in colonic epithelial cells of GDM-fed mice.Finally,when IEC6 rat intestinal epithelial cells were cultured without glutamine,cell proliferation was significantly suppressed after 24 h (relative cell growth;4 mmol/L:100.0% ± 36.1%,0 mmol/L:25.3% ± 25.0%,P < 0.05),with severe cellular damage.The cells underwent apoptosis,accompanied by increased cell population in sub-G0 phase (4 mmol/L:1.68%,0.4 mmol/L:1.35%,0 mmol/L:5.21%),where dying cells are supposed to accumulate.CONCLUSION:Glutamine is an important alimentary component for the maintenance of intestinal mucosa.Glutamine deprivation can cause instability of the intestinal epithelial alignment by increased apoptosis. | Takayuki Motoki Yoshio Naomoto Junji Hoshiba Yasuhiro Shirakawa Tomoki Yamatsuji Junji Matsuoka Munenori Takaoka Yasuko Tomono Yasuhiro Fujiwara Hiroshi Tsuchita Mehmet Gunduz Hitoshi Nagatsuka Noriaki Tanaka Toshiyoshi Fujiwara | 2011 | World Journal of Gastroenterology2011，17，6： | 4 |
| 7 | Impairment of IFN-a production capacity in patients with hepatitis C virus and the risk of the development of hepatocellular carcinoma显示文摘AIM: To determine the utility of interferon (IFN) -αproduction capacity in patients with hepatitis C virus (HCV) infection for the measurement of immunosurveillance potential and for the early detection of hepatocellular carcinoma (HCC) by investigating the Sendai virus (HVJ) stimulated IFN-α production capacity of patients with HCV infection.METHODS: HVJ stimulated IFN-α production was determined in a large number of patients with HCV infection and the development of HCC was monitored for 3 years in patients with liver cirrhosis (LC).RESULTS: IFN-α production capacity decreases gradually with the progression of liver disease from chronic hepatitis (CH) to HCC. A significant correlation between the duration of HCV infection and impaired IFN-α production capacity was observed. IFN-α production in patients who developed HCC within 3 years was significantly lower than that of patients who remained in LC without developing HCC.CONCLUSION: Measurement of IFN-α production in LC patients may be useful for the early detection of HCC. | Kazuko Uno Yoshiki Suginoshita Kazuhiro Kakimi Fuminori Moriyasu Mayumi Hirosaki Taro Shirakawa Tsunataro Kishida | 2005 | World Journal of Gastroenterology2005，11，46： | 3 |
| 8 | A ruptured large extraluminal ileal gastrointestinal stromal tumor causing hemoperitoneum显示文摘We describe an 87-year-old woman with a large ileal gastrointestinal stromal tumor (GIST) causing hemoperitoneum. A CT scan demonstrated a large heterogeneous mass measuring about 13 cm × 11 cm in the pelvis and hemoperitoneum, with a non-uniform enhancement pattern. The mass was diagnosed as a GIST originating from the gastrointestinal tract. She underwent an urgent laparotomy and an ileal GIST with a rupture was found 130 cm from the anal to the Treitz’s ligament. Hemoperitoneum caused by ileal GIST rupture is a rare condition. Bleeding in the large tumor leading to rupture of the capsule might cause hemoperitoneum in the present case. | Shoji Hirasaki Kohei Fujita Minoru Matsubara Hiromitsu Kanzaki Hiromichi Yamane Masato Okuda Seiyuu Suzuki Atsuko Shirakawa Hideyuki Saeki | 2008 | World Journal of Gastroenterology2008，14，18： | 3 |
| 9 | Effects of a 24-week course of interferon-αtherapy after curative treatment of hepatitis C virus-associated hepatocellular carcinoma显示文摘AIM:To assess whether a 24-wk course of interferon (IFN)could prevent hepatocellular carcinoma(HCC) recurrence and worsening of liver function in patients with hepatitis C virus(HCV)-infected patients after receiving curative treatment for primary HCC. METHODS:Outcomes in 42 patients with HCV infection treated with IFN-α,after curative treatment for primary HCC(IFN group),were compared with 42 matched curatively treated historical controls not given IFN(non- IFN group). RESULTS:Although the rate of initial recurrence did not differ significantly between IFN group and non-IFN group (0%,44%,61%,and 67% vs 4.8%,53%,81%,and 87% at 1,3,5,and 7 years,P=0.153,respectively), IFN group showed a lower rate than the non-IFN group for second recurrence(0%,10.4%,28%,and 35% vs 0%,30%,59%,and 66% at 1,3,5 and 7 years, P=0.022,respectively).Among the IFN group,patients with sustained virologic response(SVR)were less likely to have a second HCC recurrence than IFN patients without an SVR,or non-IFN patients.Multivariate analysis identified the lack of SVR as the only independent risk factor for a second recurrence,while SVR and Child-Pugh class A independently favored overall survival. CONCLUSION:Most intrahepatic recurrences of HCV- related HCC occurred during persistent viral infection. Eradication of HCV is essential for the prevention of HCC recurrence and improvement of survival. | Soo Cheol Jeong Hiroshi Aikata Yoshio Katamura Takahiro Azakami Tomokazu Kawaoka Hiromi Saneto Kiminori Uka Nami Mori Shintaro Takaki Hideaki Kodama Koji Waki Michio Imamura Hiroo Shirakawa Yoshiiku Kawakami Shoichi Takahashi Kazuaki Chayama | 2007 | World Journal of Gastroenterology2007，13，40： | 3 |
| 10 | Synthesis of electrically conducting organic polymers: halogen derivatives of polyacetylene, (CH)x 显示文摘 | Shirakawa H Louis E J MacDiarmid A G | 1977 | Chemical Communication1977，，： | 2 |
| 11 | Low-dose intermittent interferon-alpha therapy for HCV-related liver cirrhosis after curative treatment of hepatocellular carcinoma显示文摘AIM: To assess the efficacy of low-dose intermittent interferon (IFN) therapy in patients with hepatitis C virus (HCV)-related compensated cirrhosis who had received curative treatment for primary hepatocellular carcinoma (HCC). METHODS: We performed a prospective case controlled study. Sixteen patients received 3 MIU of natural IFN- alpha intramuscularly 3 times weekly for at least 48 wk (IFN group). They were compared with 16 matched historical controls (non-IFN group). RESULTS: The cumulative rate of first recurrence of HCC was not significantly different between the IFN group and the non-IFN group (0% vs 6.7% and 68.6% vs 80% at 1- and 3-year, P = 0.157, respectively). The cumulative rate of second recurrence was not also significantly different between the IFN group and the non-IFN group (0% vs 6.7% and 35.9% vs 67% at 1- and 3-year, P = 0.056, respectively). Although the difference in the Child-Pugh classification score between the groups at initial treatment of HCC was not signifi cant, the score was signifi cantly worse at the time of data analysis in the non-IFN group than IFN group (7.19 ± 1.42 vs 5.81 ± 0.75, P = 0.0008). The cumulative rate of deviation from objects of any treatment for recurrentHCC was also higher in the non-IFN group than IFN group (6.7% and 27% vs 0 and 0% at 1- and 3-year, P = 0.048, respectively). CONCLUSION: Low-dose intermittent IFN-alpha therapy for patients with HCV-related compensated cirrhosis after curative HCC treatment was effective by making patients tolerant to medical or surgical treatment for recurrent HCC in the later period of observation. | Soocheol Jeong Hiroshi Aikata Yoshio Katamura Takahiro Azakami Tomokazu Kawaoka Hiromi Saneto Kiminori Uka Nami Mori Shintaro Takaki Hideaki Kodama Koji Waki Michio Imamura Hiroo Shirakawa Yoshiiku Kawakami Shoichi Takahashi Kazuaki Chayama | 2007 | World Journal of Gastroenterology2007，13，39： | 2 |
| 12 | Vasculogenic mimicry and pseudo-comedo formation in breast cancer显示文摘 | Shirakawa K Wakasugi H Heike Y | 2002 | International Journal of Cancer2002，，06： | 2 |
| 13 | Isolated spontaneous dissection of the splanchnic arteries显示文摘 | Toshio Takayama Tetsuro Miyata Motoaki Shirakawa Hirokazu Nagawa | 2008 | Journal of Vascular Surgery2008，，2： | 2 |
| 14 | Vasculogenic mimicry and pseudo-comedo formation in breast cancer显示文摘 | Shirakawa K Wakasugi H Heike Y | 2002 | Int J Cancer2002，99，6： | 1 |
| 15 | Engineering for LNG-BOG management 显示文摘 | Shirakawa Yutaka | 2006 | Energy and Resources2006，27，5： | 1 |
| 16 | Y-chromosomemicrodeletion and phenotype in cytogenetically normal menwith idiopathic azoospermia显示文摘 | Fujisawa M Shirakawa T Kanzaki M | 2001 | Fertil Steril2001，76，3： | 1 |
| 17 | An Automatic Routing System for Single-Layer Printed Wiring Boards 显示文摘 | S Futagami I Shirakawa H Ozaki | 1982 | IEEE Transactions on Circuits and Systems1982，29，1： | 1 |
| 18 | Etodolac, a selective cyclooxygenase-2 inhibitor, induces upregulation of E- cadherin and has antitumor effect on human bladder cancer cell- sin vitroandin vivo 显示文摘 | OKAMOTO A SHIRAKAWA T BITO T | 2008 | Urology2008，71，： | 1 |
| 19 | Isolated spontaneous dissection of the splanchnic arteries显示文摘 | Takayama T Miyata T Shirakawa M | | 0，，： | 1 |
| 20 | Identification and Dynamics of Arabidopsis Adaptor Protein-2 Complex and Its Involvement in Floral Organ Development[W]显示文摘 | Shohei Yamaoka Yuki Shimono Makoto Shirakawa Yoichiro Fukao Takashi Kawase Noriyuki Hatsugai Kentaro Tamura Tomoo Shimada Ikuko Hara-Nishimura | 2013 | The Plant Cell2013，，8： | 1 |
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