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| 1 | Novel diet-related mouse model of colon cancer parallels human colon cancer显示文摘AIM:To investigate the close parallels between our novel diet-related mouse model of colon cancer and human colon cancer.METHODS:Twenty-two wild-type female mice(ages 6-8 wk)were fed the standard control diet(AIN-93G)and an additional 22 female mice(ages 6-8 wk)were fed the control diet supplemented with 0.2%deoxycho-lic acid[diet+deoxycholic acid(DOC)]for 10 mo.Tu-mors occurred in the colons of mice fed diet+DOC and showed progression to colon cancer[adenocarcinoma(AC)].This progression is through the stages of tubular adenoma(TA),TA with high grade dysplasia or ad-enoma with sessile serrated morphology,intramucosal AC,AC stage T1,and AC stage T2.The mouse tumors were compared to human tumors at the same stages by histopathological analysis.Sections of the small and large intestines of mice and humans were evaluated for glandular architecture,cellular and nuclear morphology including cellular orientation,cellular and nuclear atyp-ia,pleomorphism,mitotic activity,frequency of goblet cells,crypt architecture,ulceration,penetration of crypts through the muscularis mucosa and presence of malignant crypts in the muscularis propria.In addition,preserved colonic tissues from genetically similar male mice,obtained from a prior experiment,were analyzed by immunohistochemistry.The male mice had been fed the control diet or diet+DOC.Four molecular markers were evaluated:8-OH-dG,DNA repair protein ERCC1,autophagy protein beclin-1 and the nuclear location of beta-catenin in the stem cell region of crypts.Also,male mice fed diet+DOC plus 0.007%chlorogenic acid(diet+DOC+CGA)were evaluated for ERCC1,beclin-1 and nuclear location of beta-catenin.RESULTS:Humans with high levels of diet-relatedDOC in their colons are at a substantially increased riskof developing colon cancer.The mice fed diet+DOChad levels of DOC in their colons comparable to that ofhumans on a high fat diet.The 22 mice without addedDOC in their diet had no colonic tumors while 20 ofthe 22 mice(91%)fed diet+DOC developed colonictumors.Furthermore,the tumors in 10 of these mice(45%of mice)included an adenocarcinoma.All micewere free of cancers of the small intestine.Histopatho-logically,the colonic tumor types in the mice werevirtually identical to those in humans.In humans,char-acteristic aberrant changes in molecular markers can be detected both in field defects surrounding cancers(from which cancers arise)and within cancers.In thecolonic tissues of mice fed diet+DOC similar changesin biomarkers appeared to occur.Thus,8-OH-dG wasincreased,DNA repair protein ERCC1 was decreased,autophagy protein beclin-1 was increased and,in thestem cell region at the base of crypts there was sub-stantial nuclear localization of beta-catenin as well asincreased cytoplasmic beta-catenin.However,in micefed diet+DOC+CGA(with reduced frequency ofcancer)and evaluated for ERCC1,beclin-1,and beta-catenin in the stem cell region of crypts,mouse tissueshowed amelioration of the aberrancies,suggestingthat chlorogenic acid is protective at the molecular levelagainst colon cancer.This is the first diet-related modelof colon cancer that closely parallels human progressionto colon cancer,both at the histomorphological level aswell as in its molecular profile.CONCLUSION:The diet-related mouse model of coloncancer parallels progression to colon cancer in humans,and should be uniquely useful in model studies of pre-vention and therapeutics. | Anil R Prasad Shilpa Prasad Huy Nguyen Alexaner Facista Cristy Lewis Beryl Zaitlin Harris Bernstein Carol Bernstein | 2014 | World Journal of Gastrointestinal Oncology2014，6，7： | 2 |
| 2 | Naval threat and countermeasure simulator 显示文摘 | VAITEKUNAS D A ALEXAN K BIRK A M | 1994 | SPIE1994，2269，： | 1 |
| 3 | Observations of insects and birds with a polarimetric radar显示文摘 | Dusan S Zmic Alexaner V Ryzhkov | 1998 | IEEE Transactions on Geoscience and Remote Sensing1998，36，2： | 1 |
| 4 | Markers of inflamation and cardivascular disease显示文摘 | Pearson TA Mensah GA Alexaner RW | 2003 | Circulation2003，107，3： | 1 |
| 5 | Supported gold catalysts prepared from a gold phosphine precursor and as-precipitated metal-hydroxide precursors: Effect of preparation conditions on the catalytic performance显示文摘 | ALEXAN DER I K ANGUELINA P K KIYOTAKA A | 2000 | Journal of Catalysis2000，196，1： | 1 |
| 6 | SHIPIR /NTCS:a naval ship infrared signature counterm easure and threat engagement simulator显示文摘 | Vaitekunas D A Alexan K Law rence O E | | 0，，： | 1 |
| 7 | Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study显示文摘 | Martin J Elliott Paolo De Coppi Simone Speggiorin Derek Roebuck Colin R Butler Edward Samuel Claire Crowley Clare McLaren Anja Fierens David Vondrys Lesley Cochrane Christopher Jephson Samuel Janes Nicholas J Beaumont Tristan Cogan Augustinus Bader Alexan | 2012 | The Lancet2012，，9846： | 1 |
| 8 | Clinical rating systems for the ankle-hindfoot,midfoot,hallux,and lessertoes显示文摘 | Kitaoka HB Alexan der IJ Adelaar RS | | 0，，07： | 1 |
| 9 | Snutibox arterovenous fistula for hemo-dialysis显示文摘 | Mehigan JT Alexan der RA | | 0，，02： | 1 |
| 10 | Transcriptional gene expression profiles of colorectal adenoma,adenocarcinoma,and normal tissue examined by oligonucleotide arrays显示文摘 | Daniel A Notterman N Alexaner J | 2001 | Cancer Res2001，61，4： | 1 |
| 11 | Constitutive modelling finite thermoviscoplasticity:a physical approach based on nonlinear rheological models 显示文摘 | Alexan L | 2000 | International Journal of Plasticity2000，16，3： | 1 |
| 12 | Hepatitis B virus genotypes and HBsAg subtypes in refugees and injection drug users in the United States determined by LiPA and monoclonal EIA显示文摘 | Swenson PD Van Geyt C Alexan der ER et a1 | 2001 | Med Virol2001，64，3： | 1 |
| 13 | SHIPIR/ NTCS: a naval ship infrared signature countermeasure and threat engagement simulator显示文摘 | Vaitekunas D A Alexan K Lawrence O E | 1996 | SPIE1996，2744，： | 1 |
| 14 | Inhibit ion of NR2B phosphorylat ion rest ores alt erat ions in NMDA recept or ex-pression and im proves functional recovery f ollow ing t raumat ic brain injury in mice显示文摘 | Schumann J Alexan drovich GA Biegon A | | 0，，08： | 1 |
| 15 | Magnetic resonance classification of lumbar intervertebral disc degeneration显示文摘 | Christian W A Alexan der M Marco Z | | 0，，： | 1 |
| 16 | SHIPIRINTCS: a naval ship infrared signature countermeasure and threat engagement simulator显示文摘 | Vaitekunas D A Alexan K Lawerence O E | 1996 | Proceeding of the SPIE1996，2744，： | 1 |
| 17 | SHIPIR/NTCS: A naval ship infrared signature countermeasure and threat engagement simulator 显示文摘 | Vaitekunas D A Alexan K Lawrence O E | 1996 | SPIE1996，2744，： | 1 |
| 18 | Markers of inflamation and cardi-vascular disease显示文摘 | PearsonTA Mensah GA Alexaner RW | 2003 | Circulation2003，107，3： | 1 |
| 19 | Lipoxygenase-structure and reaction mechanism 显示文摘 | Alexan'dra Andreou Ivo Feussner | 2009 | Phytochemistry2009，，70： | 1 |
| 20 | Transcriptional gene expression profiles of colorectal adenoma, adenocarcinoma, and normal tissue examined by oligonucleotide arrays 显示文摘 | Daniel A Notterman N Alexaner J | 2001 | Cancer Res2001，61，4： | 1 |
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