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| 1 | 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 |
| 2 | 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 |
| 3 | Primar7 malignam melanoma of tile esophagus: report of case successfullv treated with pre- and post-operative adjuvant hormone-chemolherapy 显示文摘 | Naomoto Y Perdomo JA Kamikawa Y | 1998 | Jpn Clin 0neo11998，28，12： | 1 |
| 4 | Localization of hep- aranase in esophageal cancer cells: respective roles in prognosis and differ - entiation 显示文摘 | Ohkawa T Naomoto Y Takaoka M | 2004 | Lab Invest2004，84，10： | 1 |
| 5 | Effect of 5 - fluoroura- cil on cell cycle regulatory proteins in human colon cancer cell line 显示文摘 | Takeda It Haisa M Naomoto Y | 1999 | Jpn J Cancer Res1999，90，： | 1 |
| 6 | Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer显示文摘 | Hui-fang Hao Munenori Takaoka Xiao-hong Bao Zhi-gang Wang Yasuko Tomono Kazufumi Sakurama Toshiaki Ohara Takuya Fukazawa Tomoki Yamatsuji Toshiyoshi Fujiwara Yoshio Naomoto | 2012 | Biochemical and Biophysical Research Communications2012，，： | 1 |
| 7 | Anti-tumor effect in human breast cancer by TAE226, a dual inhibitor for FAK and IGF-IR in vitro and in vivo显示文摘 | Naito Kurio Tsuyoshi Shimo Takuya Fukazawa Munenori Takaoka Tatsuo Okui Nur Mohammad Monsur Hassan Tatsuki Honami Shinji Hatakeyama Masahiko Ikeda Yoshio Naomoto Akira Sasaki | 2011 | Experimental Cell Research2011，，： | 1 |
| 8 | Free jejunal graft for hypopharyngeal and esophageal reconstruction显示文摘 | Yasuhiro Shirakawa Yoshio Naomoto Kazuhiro Noma Ryoko Ono Tetsuji Nobuhisa Masahiko Kobayashi Toshiya Fujiwara Hirofumi Noguchi Takaomi Ohkawa Tomoki Yamatsuji Minoru Haisa Junji Matsuoka Mehmet Gunduz Noriaki Tanaka | 2004 | Langenbeck’s Archives of Surgery2004，，5： | 1 |
| 9 | Heparanase Expression correlates with malignant potential in human colon cancer显示文摘 | Nobuhisa T Naomoto Y Ohkawa T | 2005 | J Cancer Res Clin Oncol2005，131，4： | 1 |
| 10 | Focal adhesion kinase as potential target for cancer therapy (Review) 显示文摘 | Hao H Naomoto Y Bao X | 2009 | Oncol Rep2009，22，5： | 1 |
| 11 | Heparanase expression correlates with invasion and poor prognosis in gastric cancers 显示文摘 | Takaoka M Naomoto Y Ohkawa T | 2005 | Lab Invest2005，83，5： | 1 |
| 12 | Focal adhesion kinase as potentialtarget for cancer therapy(Review)显示文摘 | Hao H Naomoto Y Bao X | 2009 | Oncol Rep2009，22，5： | 1 |
| 13 | Topological analysis of P21 Waf1/cip expression in esophagea1 squamous dysplasia显示文摘 | Shirakawa Y Naomoto Y Kimura M | 2000 | Clin Cancer Res2000，6，2： | 1 |
| 14 | Heparanase expression correlates with invasion and poor prognosis in gastric caneers显示文摘 | Takaoka M Naomoto Y Ohkawa T | 2003 | J Lab Invest2003，83，： | 1 |
| 15 | Suppression of tumor growth and downregulation of platelet-derivede endothelial cell growth factor/thymidine phosphorylase in tumor cells by angiogenesis inhibitor TNP-470显示文摘 | Mori J Haisa M Naomoto Y | 2000 | Jpn J Cancer Res2000，91，6： | 1 |
| 16 | Translocation of heparanase into nucleus results in cell differentiation 显示文摘 | Nobuhisa T Naomoto Y Okawa T | 2007 | Cancer Sci2007，98，4： | 1 |
| 17 | Focal adhe- sion kinase as potential target for cancer therapy (Re- view)显示文摘 | HAO H NAOMOTO Y BAO X | 2009 | OncolRep2009，22，： | 1 |
| 18 | Heparanase expression correlates with invasion and poor prognosis in gastric cancers显示文摘 | Takaoka M Naomoto Y Ohkawa T | 2003 | Lab Invest2003，83，5： | 1 |
| 19 | Basaloid-squamous cell carcinoma of the esophagus:diagnosis based on immunohistochemical analysis显示文摘 | Nishimura W Naomoto Y Hamaya K | 2001 | J Gastroenterol Hepatol2001，16，5： | 1 |
| 20 | Heparanase expression correlates with invasion and poor prognosis in gastric cancers 显示文摘 | Takaoka M Naomoto Y Ohkawa T | 2003 | Lab Invest2003，83，5： | 1 |
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