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| 1 | Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer显示文摘AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability(MSI) status in Japanese colorectal cancer(CRC) population.METHODS: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage Ⅰ-Ⅲ CRC and examined associations of these mutations with disease-free survival(DFS) and overall survival(OS) using uni- and multivariate Cox proportional hazards models.RESULTS: KRAS and BRAF mutations were detected in 312(38%) of 812 and 40(5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males(P = 0.02), while the presence of BRAF mutations was significantly associated with the female gender(P = 0.006), proximal tumor location(P < 0.001), mucinous or poorly differentiated histology(P < 0.001), and MSI-high tumors(P < 0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS(HR = 1.35; 95%CI: 1.03-1.75) and OS(HR = 1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS(HR = 2.20; 95%CI: 1.19-4.06) and OS(HR = 2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS.CONCLUSION: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, inJapanese patients with curatively resected CRC. | Shigenori Kadowaki Miho Kakuta Shuhei Takahashi Akemi Takahashi Yoshiko Arai Yoji Nishimura Toshimasa Yatsuoka Akira Ooki Kensei Yamaguchi Keitaro Matsuo Kei Muro Kiwamu Akagi | 2015 | World Journal of Gastroenterology2015，21，4： | 14 |
| 2 | Screening serum hepatocellular carcinoma-associated proteins by SELDI-based protein spectrum analysis显示文摘AIM:To find out potential serum hepatocellular carcinoma (HCC)-associated proteins with low molecular weight and low abundance by SELDI-based serum protein spectra analysis, that will have much application in the diagnosis or differentiated diagnosis of HCC, as well as giving a better understanding of the mechanism of hepato-carcinogenesis. METHODS:Total serum samples were collected with informed consent from 81 HCC patients with HBV(+)/ cirrhosis(+), 36 cirrhosis patients and 43 chronic hepatitis B patients. Serum protein fingerprint profiles were first generated by selected WCX2 protein chip capture integrating with SELDI-TOF-MS, then normalized and aligned by Ciphergen SELDI Software 3.1.1 with Biomarker Wizard. Comparative analysis of the intensity of corresponding protein fingerprint peaks in normalized protein spectra, some protein peaks with significant difference between HCC and cirrhosis or chronic hepatitis B were found. RESULTS:One hundred and twenty-eight serum protein peaks between 2000 and 30 000Da were identified under the condition of signal-to-noise > 5 and minimum threshold for cluster > 20%. Eighty-seven of these proteins were showed significant differences in intensity between HCC and cirrhosis (P < 0.05). Of the above differential proteins, 45 proteins had changes greater than two-fold, including 15 upregulated proteins and 30 downregulated proteins in HCC serum. Between HCC and chronic hepatitis B, 9 of 52 differential proteins (P < 0.05) had intensities of more than two-fold, including 2 upregulated proteins and 7 downregulated proteins in HCC serum. Between cirrhosis and chronic hepatitis B, 28 of 79 significant differential proteins (P < 0.05) changes greater than two-fold in intensity, including 17 upregulated proteins and 11 downregulated proteins in cirrhosis serum. For the analysis of these leading differential proteins in subtraction difference mode among three diseases, the five common downregulated proteins in HCC serum (M/Z 2870, 3941, 2688, 3165, 5483) and two common upregulated proteins (M/Z 3588, 2017) in HCC and cirrhosis serum were screened.CONCLUSION:Because the interference of unspecific secreted proteins from hepatitis B and cirrhosis could be eliminated partly in HCC serum under subtraction difference analysis, these seven common differential proteins have the obvious advantage of specificity for evaluating the pathological state of HCC and might become novel candidate biomarkers in the diagnosis of HCC. | Jie-Feng Cui Yin-Kun Liu Hai-Jun Zhou Xiao-Nan Kang Cheng Huang Yi-Feng He Zhao-You Tang Toshimasa Uemura | 2008 | World Journal of Gastroenterology2008，14，8： | 8 |
| 3 | Phase Ⅱ study of protracted irinotecan infusion and a low-dose cisplatin for metastatic gastric cancer显示文摘AIM: To test protracted irinotecan infusion plus a low-dose cisplatin in this Phase Ⅱ trial to decrease its toxic-ity. METHODS: The eligibility criteria were: (1) histologi-cally proven measurable gastric cancer; (2) performance status of 0 or 1; (3) no prior chemotherapy or comple-tion of prior therapy at least 4 wk before enrollment; (4) adequate function of major organs; (5) no other active malignancy; and (6) written informed consent. The regi-men consisted of irinotecan (60 mg/m2) on d 1 and 15 by 24-h infusion and cisplatin (10 mg/m2) on d 1, 2, 3, 15, 16, and 17. Treatment was repeated every 4 wk. RESULTS: Thirty-one patients were registered between April 2000 and January 2001. The response rate for all 31 patients, 20 patients without prior chemotherapy, and 11 patients with prior chemotherapy was 52% (16/31), 60% (12/20), and 36% (4/11), respectively. The median survival time was 378 d. The median number of courses given to all patients was 2. Grade 4 neutropenia oc-curred in 11 (35%) patients, while grade 3 to 4 diarrhea or nausea occurred in 1 (3%) and 3 (10%) patients, respectively. Fatigue was minimal as grade 1 fatigue was found only in 3 (10%) patients. Other adverse events were mild and no treatment-related deaths occurred.CONCLUSION: This regimen showed a high level of ac-tivity and acceptable toxicity in patients with metastatic gastric cancer. | Hiroshi Imamura Masataka Ikeda Hiroshi Furukawa Toshimasa Tsujinaka Kazumasa Fujitani Kenji Kobayashi Hiroyuki Narahara Michio Kato Haruhiko Imamoto Arimichi Takabayashi Hideaki Tsukuma | 2006 | World Journal of Gastroenterology2006，12，40： | 7 |
| 4 | Indicators of sorafenib efficacy in patients with advanced hepatocellular carcinoma显示文摘AIM:To determine significant indicators for the efficacy of sorafenib in patients with advanced hepatocellular carcinoma(HCC).METHODS:A total of 46 patients with Barcelona Clinic Liver Cancer stage C who received sorafenib for more than 30 d at the Iizuka Hospital from June 2009 to December 2012 were enrolled in this study.Multivariate and univariate analyses were performed to evaluate the associations of hepatic function according to Child-Pugh grade,location and size of the largest tumor and adverse events of sorafenib treatment,such as hand-foot syndrome(HFS),hypertension,diarrhea,and alopecia,with the efficacy of treatment,as measured by overall survival(OS)and time to progression(TTP).RESULTS:Patients included 39 men and 7 women whose ages ranged from 48 to 85 years(70.6±9.6years).HCC was classified according to etiology as follows:hepatitis C virus(n=26),hepatitis B virus(n=9),and other(n=11).Liver function in patients was categorized as Child-Pugh grade A(n=30)or B(n=16).Tumors were categorized by size[<5 cm(n=33)or>5 cm(n=13)]and the location of the largest tumor was used to categorize patients with intrahepatic(n=28)or extrahepatic(n=18)HCC.HFS,hypertension,diarrhea,and alopecia were present in22(47.8%),19(41.3%),15(32.6%)and 7 patients(15.2%),respectively.The median OS of all patients was 373 d and the median TTP was 112 d.The etiology of HCC did not correlate with the median OS and TPP.The median OS of patients with tumors<5 cm was significantly longer than those with larger tumors(496 vs 245 d;HR=0.19,95%CI:0.07-0.48;P<0.01).According to the results of a multivariate analysis,the size of the largest tumor affected OS(HR=0.22,95%CI:0.08-0.59;P<0.01).The median TTP was significantly longer in patients with extrahepatic compared to intrahepatic major HCC(224 vs 98 d;HR=0.32;95%CI:0.14-0.67;P<0.01).The median TTP of patients with HFS was significantly longer than those without it(195 d vs 83 d;HR=0.41,95%CI:0.20-0.82;P<0.05),and the median TTP was significantly longer in patients with hypertension(195 d vs84 d;HR=0.43,95%CI:0.21-0.84;P<0.05).According to the results of the multivariate analysis,extrahepatic major HCC(HR=0.36,P<0.01)and HFS(HR=0.44,P<0.05)prolonged TTP.CONCLUSION:Extrahepatic major HCC and HFS are associated with prolonged TTP and are useful indicators for judging the efficacy of sorafenib treatment. | Masayoshi Yada Akihide Masumoto Kenta Motomura Hirotaka Tajiri Yusuke Morita Hideo Suzuki Takeshi Senju Toshimasa Koyanagi | 2014 | World Journal of Gastroenterology2014，20，35： | 7 |
| 5 | 他克莫司诱导的骨髓间充质干细胞成骨细胞分化和体内骨形成显示文摘目的研究免疫抑制剂他克莫司(FK506)对大鼠骨髓来源的间充质干细胞(MSC)的成骨细胞分化诱导,及对 MSCs 结合多孔β三磷酸钙(β-TCP)的体内成骨作用。方法原代 MSCs 按实验目的随机分组。对照组生长培养液中加入 L-抗坏血酸-2-磷酸(AsAp)和β-甘油磷酸(β-GP);FK506处理组在对照组基础上加入50 nmol/L FK506。实验分成体外体内两部分相继进行。体外实验细胞分别于培养第4、8、12、16大时行碱件磷酸酶(APase)活性,钙含量,扫描电镜和骨钙素 mRNANorthern 印迹分析;体内实验将细胞载入多孔β-TCP 立方块形成 MSCs/β-TCP 复合物,继续成骨诱导培养2周后植入大鼠背部皮下,4周和8周后取出复合物作组织学检查。结果 FK506处理组碱性磷酸酶活性、钙含量、骨钙素 mRNA 均明显高于对照组(均 P<0.05);体内成骨情况亦明显优于对照组。结论免疫抑制剂 FKS06能显著促进大鼠骨髓来源间充质干细胞(MSCs)的体外成骨细胞分化和动物体内继续成骨的作用,并提示 FK506可作为一种新型成骨生长因子,在临床有潜在的应用价值。 | 董健 戴文达 方涛林 林红 Toshimasa Uemura | 2007 | 中华医学杂志2007，87，3： | 6 |
| 6 | A low-voltage low-power CMOS voltage reference based on subthreshold MOSFETs显示文摘This paper describes a CMOS voltage reference using only resistors and transistors working in weak inversion,without the need for any bipolar transistors.The voltage reference is designed and fabricated by a 0.18μm CMOS process.The experimental results show that the proposed voltage reference has a temperature coefficient of 370 ppm/℃at a 0.8 V supply voltage over the temperature range of-35 to 85℃and a 0.1%variation in supply voltage from 0.8 to 3 V.Furthermore,the supply current is only 1.5μA at 0.8 V supply voltage. | 王洪来 张小兴 戴宇杰 吕英杰 Toshimasa Matsuoka Wang Jun Kenji Taniguchi | 2011 | Journal of Semiconductors2011，32，8： | 5 |
| 7 | Adiponectin and Adiponectin Receptors显示文摘 | Takashi Kadowaki Toshimasa Yamauchi | 2005 | Endocrine Reviews2005，，3： | 5 |
| 8 | FK506对骨髓间充质干细胞体外成骨活性的诱导显示文摘目的研究免疫抑制剂FKS06在体外对大鼠骨髓来源的间充质干细胞(MSCs)成骨诱导能力以及FK506成骨诱导的量效关系。方法MSCs在不同条件下培养16d:(1)对照组(C组)- (基础培养液):含L-抗坏血酸-2-磷酸(AsAp)和β-甘油磷酸(β-GP)的α-MEM培养液;(2)基础培养液加入地塞米松(D组);(3)基础培养液加入FK506(F组);(4)基础培养液加入地塞米松和FKS06(FD组)。通过测定干细胞形态、细胞增殖、碱性磷酸酶(ALP)活性、钙化结节染色和骨钙素基因表达等,评价FK506对MSCs的成骨诱导能力。结果FK506能促进大鼠MSCs增殖、成骨细胞分化,明显诱导钙化结节形成,显著提高ALP活性和骨钙素mRNA的表达。FK506与地塞米松具有协同成骨诱导作用,当α-MEM中含0.25mmol/L AsAp、10mmol/Lβ-甘油磷酸、10nmol/L地塞米松和50nmol/L FK506时可获得最佳成骨效应。结论FK506具有强大成骨诱导能力,可以用作骨诱导因子。 | 董健 方涛林 孙源 戴文达 李云飞 Toshimasa Uemura | 2006 | 中华创伤杂志2006，22，10： | 4 |
| 9 | Prediction of acute left main coronary artery obstruction by 12-lead electrocardiography显示文摘 | Hirosuke Yamaji Kohichiro Iwasaki Shozo Kusachi Takashi Murakami Ryouichi Hirami Hiromi Hamamoto Kazuyoshi Hina Toshimasa Kita Noburu Sakakibara Takao Tsuji | 2001 | Journal of the American College of Cardiology2001，，5： | 3 |
| 10 | Effect of binder amount on the development of coal-binder interface and its relationship with the strength of the carbonized coal-binder composite显示文摘Production of high-strength carbonized coal composites from non-caking coals only with possible application as coke is presented.A binder and a non-caking coal were mixed in different ratios and carbonized at 1000C to produce coal-binder composites.Two binders,one from coal origin and other from oil origin were used.Effect of coal-binder mixing ratio and base coal particle size on the fracture strength of composites was investigated.Bonding of binder with the coal particles at coal-binder interface and development of connected carbon matrix were primarily responsible for the strength of the carbonized coal composites.The trend of change in fracture strength as a function of coal-binder fraction was similar for both the binders.However,for same coal-binder mixing ratio,binder type strongly affected the maximum strength achieved.Fracture strength was found to be primarily dependent on the coal-binder mixing ratio and base coal particle size.The main finding of this study is that the irrespective of binder type,for a given base coal particle size there was only one coal-binder mixing ratio at which the maximum strength was obtained.The binder fraction at which the highest strength observed was correlated to the carbon matrix connectivity index. | Atul Sharma Naoto Sakimoto Toshimasa Takanohashi | 2018 | Carbon Resources Conversion2018，1，2： | 3 |
| 11 | Clinical benefit of surgery for stage IV colorectal cancer with synchronous peritoneal metastasis显示文摘 | Hirotoshi Kobayashi Kenjiro Kotake Kimihiko Funahashi Kazuo Hase Koichi Hirata Tsuneo Iiai Shingo Kameoka Yukihide Kanemitsu Koutarou Maeda Akihiko Murata Masayuki Ohue Kazuo Shirouzu Keiichi Takahashi Toshiaki Watanabe Hideaki Yano Toshimasa Yatsuoka Yoj | 2014 | Journal of Gastroenterology2014，，4： | 2 |
| 12 | Bottom-up estimate of biomass burning in mainland China显示文摘 | Xiaoyuan Yan Toshimasa Ohara Hajime Akimoto | 2006 | Atmospheric Environment2006，，27： | 2 |
| 13 | Mesophilic methane fermentation of chicken manure at a wide range of ammonia concentration: Stability, inhibition and recovery显示文摘 | Qigui Niu Wei Qiao Hong Qiang Toshimasa Hojo Yu-You Li | 2013 | Bioresource Technology2013，，： | 2 |
| 14 | Biliary Complications after Duct-to-duct Biliary Reconstruction in Living-donor Liver Transplantation: Causes and Treatment显示文摘 | Hirotaka Tashiro Toshiyuki Itamoto Tamito Sasaki Hideki Ohdan Yasuhiro Fudaba Hironobu Amano Saburo Fukuda Hideki Nakahara Kohei Ishiyama Akihiko Ohshita Toshihiko Kohashi Hiroshi Mitsuta Kazuaki Chayama Toshimasa Asahara | 2007 | World Journal of Surgery2007，，11： | 2 |
| 15 | Adiponectin Receptor Signaling: A New Layer to the Current Model显示文摘 | Takashi Kadowaki Toshimasa Yamauchi | 2011 | Cell Metabolism2011，，2： | 2 |
| 16 | Molecular simulation of relaxation behaviors of coal-aggregated structures显示文摘 | Toshimasa Takanohashi Takahiro Yoshida Hiroyuki Kawashima | 2002 | Fuel Processing Technology2002，7778，： | 2 |
| 17 | Adiponectin and adiponectin recaptors in insulin resistance,diabetes,and the metabolic syndrome显示文摘 | Takashi K Toshimasa Y Naoto K | 2006 | J Clin Invest2006，116，7： | 1 |
| 18 | Partitioning of Boron during the Generation of Uhraclean Fuel ( Hyper Coal) by Solvent Extraction of Coal显示文摘 | Lian Zhang Hiroyuki Kawashima Toshimasa Takanohashi | 2008 | Energy and Fuels2008，22，： | 1 |
| 19 | Disruption of adiponectin causes insulin resistance and neoinimal formation 显示文摘 | Naoto K Yasuo T Toshimasa Y | 2002 | J Biol Chem2002，277，25： | 1 |
| 20 | Adiponectin and adiponectin receptors in insulin resistance diabetes and the metabolic syndrome 显示文摘 | Tskashi K Toshimasa Y Naoto K | 2006 | The Journal of Clinical Investigation2006，116，7： | 1 |
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