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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 | Bone Marrow Origin of Endothelial Progenitor Cells Responsible for Postnatal Vasculogenesis in Physiological and Pathological Neovascularization显示文摘 | Takayuki Asahara Haruchika Masuda Tomono Takahashi Christoph Kalka Christopher Pastore Marcy Silver Marianne Kearne Meredith Magner Jeffrey M. Isner | 1999 | Circulation Research1999,,3: | 3 |
| 4 | Bone Marrow Origin of Endothelial Progenitor Cells Responsible for Postnatal Vasculogenesis in Physiological and Pathological Neovascularization显示文摘 | Takayuki Asahara Haruchika Masuda Tomono Takahashi Christoph Kalka Christopher Pastore Marcy Silver Marianne Kearne Meredith Magner Jeffrey M. Isner | 1999 | Circulation Research1999,,3: | 2 |
| 5 | Intracranial epidermoidcyst including elements of old hematoma显示文摘 | Tsurushima H Kamezaki T Tomono Y | 1997 | Neurol Med Chir(Tokyo)1997,37,11: | 1 |
| 6 | Effect of citrus flavonoids on HL60 cell differentiation显示文摘 | Kawaii S Tomono Y Katase E | 1999 | Anti Cancer Res1999,19,2: | 1 |
| 7 | Tie2 receptor ligands,angiopoietin-1 and angiopoietin-2 modulate VEGF-induced postnatal neovascularization显示文摘 | Donghui Chen Tomono Takahashi | 1998 | Cir Res1998,83,: | 1 |
| 8 | 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 |
| 9 | Combination therapy for chronic Pseudomonas aeruginosa respiratory infection associated with biofiom formation 显示文摘 | Tomono K Sawai T | 2000 | J Antimicrob Chemother2000,46,: | 1 |
| 10 | Immunohistochemica and ultrastructural study of clinically nonfunctioning pituitary adenomas 显示文摘 | Zhao D Tomono Y Tsuboi K | 2000 | Neurol Med Chir ( Tokyo)2000,40,9: | 1 |
| 11 | High throughput screening of 16 million serologically negative blood donors for hepatitis B virus, hepatitis C virus and human immunodeficiency virus type-1 by nucleic acid amplification testing with specific and sensitive multiplex reagent in Japan显示文摘 | Hideko Mine Hiroyuki Emura Masaki Miyamoto Tsugikazu Tomono Kiyoshi Minegishi Hiroyuki Murokawa Retsuji Yamanaka Akira Yoshikawa Kusuya Nishioka | 2003 | Journal of Virological Methods2003,,1: | 1 |
| 12 | Prevention of vascular injuryby combination of an ATI receptor blocker: olmesartan with variouscalcium antagonists显示文摘 | Inaba S Iwai M Tomono Y | 2009 | Am J Hypertens2009,22,2: | 1 |
| 13 | Acridones as inducers of HL-60 cell differentiation显示文摘 | Kawaii S Tomono Y Katase E | 1999 | Leuk Res1999,23,: | 1 |
| 14 | Terpenoids with antifouling activity against Barnacle larvae from the marine sponge Acanthella cavernosa 显示文摘 | HIROTA H TOMONO Y FUSETANI N | 1996 | Tetra- hedron1996,52,7: | 1 |
| 15 | Excess α‐tocopherol decreases extrahepatic phylloquinone in phylloquinone‐fed rats but not menaquinone‐4 in menaquinone‐4‐fed rats显示文摘 | Fumiaki Hanzawa Eri Sakuma Saki Nomura Tomono Uchida Hiroaki Oda Saiko Ikeda | 2014 | Mol. Nutr. Food Res2014,,: | 1 |
| 16 | Transcriptional control by A-factor of strR,the pathway-specific transcriptional activator for streptomycin biosynthesis in Streptomyces griseus显示文摘 | Tomono A Tsai Y Yamazaki H | 2005 | J Bacteriol2005,187,: | 1 |
| 17 | Surface property of polymer films with fluoroalkyl side chains显示文摘 | Tomono H Nakajima T | 1994 | Maromolecules1994,27,: | 1 |
| 18 | DNA-binding specificity of AdpA,a transcriptional activator in the A-factor regulatory cascade in Streptomyces griseus显示文摘 | Yamazaki H Tomono A Ohnishi Y | 2004 | Mol Microbiol2004,53,: | 1 |
| 19 | Interaction Between Cycloamylose and Various Drugs显示文摘 | Tomono K Mugishima A Suzuki T | 2002 | Journal of Inclusion Phenomena and Macrocyclic Chemistry2002,44,: | 1 |
| 20 | Four new steroids from two octocorals显示文摘 | Tomono Y Hirota H Imahara Y et a1 | 1999 | J Nat Prod1999,62,11: | 1 |