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| 1 | Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer显示文摘AIM:To investigate human epidermal growth factor receptor 2(HER2)-phosphatidylinositol 3-kinase(PI3K)-vAkt murine thymoma viral oncogene homolog signaling pathway.METHODS:We analyzed 231 formalin-fixed,paraffinembedded gastric cancer tissue specimens from Japanese patients who had undergone surgical treatment.The patients' age,sex,tumor location,depth of invasion,pathological type,lymph node metastasis,and pathological stage were determined by a review of the medical records.Expression of HER2 was analyzed by immunohistochemistry(IHC) using the HercepTest TM kit.Standard criteria for HER2 positivity(0,1+,2+,and 3+) were used.Tumors that scored 3+ were considered HER2-positive.Expression of phospho Akt(pAkt) was also analyzed by IHC.Tumors were considered pAkt-positive when the percentage of positive tumor cells was 10% or more.PI3K,catalytic,alpha polypeptide(PIK3CA) mutations in exons 1,9 and 20 were analyzed by pyrosequencing.Epstein-Barr virus(EBV) infection was analyzed by in situ hybridization targeting EBV-encoded small RNA(EBER) with an EBER-RNA probe.Microsatellite instability(MSI) was analyzed by polymerase chain reaction using the mononucleotide markers BAT25 and BAT26.RESULTS:HER2 expression levels of 0,1+,2+ and 3+ were found in 167(72%),32(14%),12(5%) and 20(8.7%) samples,respectively.HER2 overexpression(IHC 3+) significantly correlated with intestinal histological type(15/20 vs 98 /205,P = 0.05).PIK3CA mutations were present in 20 cases(8.7%) and significantly correlated with MSI(10/20 vs 9/211,P < 0.01).The mutation frequency was high(21%) in T4 cancers and very low(6%) in T2 cancers.Mutations in exons 1,9 and 20 were detected in 5(2%),9(4%) and 7(3%) cases,respectively.Two new types of PIK3CA mutation,R88Q and R108H,were found in exon1.All PIK3CA mutations were heterozygous missense singlebase substitutions,the most common being H1047R(6/20,30%) in exon20.Eighteen cancers(8%) were EBV-positive and this positivity significantly correlated with a diffuse histological type(13/18 vs 93/198,P = 0.04).There were 7 cases of lymphoepithelioma-like carcinomas(LELC) and 6 of those cases were EBV-positive(percent/EBV:6/18,33%;percent/all LELC:6/7,86%).pAkt expression was positive in 119(53%) cases but showed no correlation with clinicopathological characteristics.pAkt expression was significantly correlated with HER2 overexpression(16/20 vs 103/211,P < 0.01) but not with PIK3CA mutations(12/20 vs 107/211,P = 0.37) or EBV infection(8/18 vs 103/211,P = 0.69).The frequency of pAkt expression was higher in cancers with exon20 mutations(100%) than in those with exon1(40%) or exon9(56%) mutations.One case showed both HER2 overexpression and EBV infection and 3 cases showed both PIK3CA mutations and EBV infection.However,no cases showed both PIK3CA mutations and HER2 overexpression.One EBVpositive cancer with PIK3CA mutation(H1047R) was MSI-positive.Three of these 4 cases were positive for pAkt expression.In survival analysis,pAkt expression significantly correlated with a poor prognosis(hazard ratio 1.75;95%CI:1.12-2.80,P = 0.02).CONCLUSION:HER2 expression,PIK3CA mutations and EBV infection in gastric cancer were characterized.pAkt expression significantly correlates with HER2 expression and with a poor prognosis. | Yasutaka Sukawa Hiroyuki Yamamoto Katsuhiko Nosho Hiroaki Kunimoto Hiromu Suzuki Yasushi Adachi Mayumi Nakazawa Takayuki Nobuoka Mariko Kawayama Masashi Mikami Takashi Matsuno Tadashi Hasegawa Koichi Hirata Kohzoh Imai Yasuhisa Shinomura | 2012 | World Journal of Gastroenterology2012，18，45： | 19 |
| 2 | The progression of comor- bidity in IL-18 transgenic chronic obstructive pulmonary disease mice model显示文摘 | Takenaka S Kawayama T Imaoka H | 2014 | Biochem Biophys Res Commun2014，445，3： | 1 |
| 3 | Interleukin-18 expression,CD8+T cells,and eosinophils in lungs of nonsmokers with fatal asthma显示文摘 | Oda H Kawayama T Imaoka H | 2014 | Ann Allergy Asthma Immunol2014，112，1： | 1 |
| 4 | IL- 18 induces air- way hyperresponsiveness and pulmonary inflammation via CD4 +T cell and IL- 13 显示文摘 | Sawada M Kawayama T Imaoka H | 2013 | PLoS One2013，8，54： | 1 |
| 5 | High plasma brain na- triuretic peptide levels in stable COPD without pulmonary hyper- tension or cor pulmonale 显示文摘 | Yuzuru Inoue Tomotaka Kawayama | 2009 | Inter Med2009，48，11： | 1 |
| 6 | High plasma brain na- triuretic peptide levels in stable COPD without pulmonary hyper- tension or corpulmonale 显示文摘 | Inoue Y Kawayama T Iwanaga T | 2009 | Intern Med2009，48，7： | 1 |
| 7 | Carbon nanotube terahertz polarizer 显示文摘 | ACS Applied PEN L PINT C L BOOSHEHRI L G RICE W I3 WANG X HILTON D J TAKEYA K KAWAYAMA I TONOUCHI M HAUGE R H KONO J | 2009 | Nano Letters2009，9，7： | 1 |
| 8 | Validation of symptom-based COPD questionnaires in Japanese subjects 显示文摘 | Kawayama T Minakata Y Matsunaga K | 2008 | Respirology2008，13，： | 1 |
| 9 | Clinical efficacy of the transdermal tulobuterol patch in patients with chronic obstructive pulmonary disease: a comparison with slow-release theophylline 显示文摘 | Minami S Kawayama T Iehiki M | 2008 | Intern Med2008，47，： | 1 |
| 10 | Study of photoexcited-carrier dynamics in GaAs photoconductive switches using dynamic terahertz emission microscopy显示文摘We propose dynamic terahertz(THz) emission microscopy(DTEM) to visualize temporal–spatial dynamics of photoexcited carriers in electronic materials. DTEM utilizes THz pulses emitted from a sample by probe pulses irradiated after pump pulse irradiation to perform time-resolved two-dimensional mapping of the THz pulse emission, reflecting various carrier dynamics. Using this microscopy, we investigated carrier dynamics in the gap region of low-temperature-grown Ga As and semi-insulating Ga As photoconductive switches of the identical-dipole type. The observed DTEM images are well explained by the change in the electric potential distribution between the electrodes caused by the screening effect of the photoexcited electron-hole pairs. | Hironaru Murakami Shogo Fujiwara Iwao Kawayama Masayoshi Tonouchi | 2016 | Photonics Research2016，4，3： | 1 |
| 11 | Decreased CTAL4+ and Foxp3 + cd25 (high)CD4 + ceils in induced sputum from patients with mild atopic asthma显示文摘 | Kawayama T Matsunaga K Kaku Y | 2013 | Allergol Int2013，62，2： | 1 |
| 12 | Effects of inhaled ciclesonide on circulating T-helper type 1/T-helper type 2 cells in atopic asthmatics after allergen challenge显示文摘 | Kawayama T O' byrne PM Watson RM | 2006 | Clin Exp Allergy2006，36，： | 1 |
| 13 | High plasma brain natriuretic peptide levels in stable COPD without pulmonary hypertension or Cor pulmonale显示文摘 | Inoue Y Kawayama T Iwanaga T | 2009 | Intern Med2009，48，7： | 1 |
| 14 | IL-18 induces airway hy- perresponsiveness and pulmonary inflammation via CD4 + T cell and IL-13显示文摘 | Sawada M Kawayama T Imaoka H | 2013 | PLoSOne2013，8，54： | 1 |
| 15 | Validation of symptom-based COPD questionnaires in Japanese subjects显示文摘 | Kawayama T Minakata Y Matsunaga K et ol | 2008 | Respirology2008，13，3： | 1 |
| 16 | High plasma brain natriuret-ic peptide levels in stable COPD without pulmonary hyper- tension orCor pulmonale 显示文摘 | Inoue Y Kawayama T Iwanaga T | 2009 | Intem Med2009，48，7： | 1 |
| 17 | High plasma brain na- triuretic peptide levels in stable COPD without pulmonary hyper- tension or cot pulmonale 显示文摘 | Inoue Y Kawayama T Iwanaga T | 2009 | Intern Med2009，48，7： | 1 |
| 18 | Depression,but not sleep disorder,is an independent factor affecting exacerbations and hospitalization in patients with chronic obstructive pulmonary disease显示文摘 | Ito K Kawayama T Shoji Y | 2012 | Respirology2012，17，6： | 1 |
| 19 | Clinical features of deep mycosis in critical care center-comparison of serological tests an d cultures for mycosis 显示文摘 | Kawayama T Oizumi K | 1999 | Kansenshogaku Zasshi1999，73，8： | 1 |
| 20 | Clinical efficacy of the transdermal tulobuterol patch in patients with chronic obstructive pulmonary disease:a comparison with slow-release theophylline显示文摘 | Minami S Kawayama T Ichiki M | 2008 | Intern Med2008，47，6： | 1 |
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