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| 1 | Cancer and age related colonic crypt deficiencies in cytochrome c oxidase Ⅰ显示文摘AIM: To investigate whether defi ciency of expressionof cytochrome c oxidase I (CcOI) in colonic crypts is associated with colon cancer.METHODS: The pattern and level of expression of CcOI in non-neoplastic colonic crypts,and in dysplastic tissues,was assessed using standard immunohis-tochemical methods.Biopsies were obtained from individuals undergoing colonoscopies for screening purposes or for a medically indicated reason.Tissue samples were also obtained from surgical colonic resections.Samples from resections were taken from colonic mucosa 1 and 10 cm from tumors and from the tumors themselves.Samples were evaluated for frequency of crypts with reduced or absent expression of CcOI.In most crypts the loss was apparent throughout the entire crypt,while in a small minority the loss was segmental.The strong immunoreactivity using this monoclonal antibody makes the scoring unambiguous.The percent of crypts with reduced or absent expression of CcOI or (infrequent) segmented loss of expression was then calculated.Data analyses were performed using SPSS statistical package 17.0.RESULTS: The average frequency of CcOI deficient crypts (CcOI-DC) is low in individuals between 20 and 39 years of age,with 0.48% ± 0.40% CcOI-DC for women and 1.80% ± 0.35% for men.CcOI-DC increases after age 40 years,so that between the ages of 40 and 44 years the average frequency of CcOI- DC goes up to 5.89% ± 0.84% in women and 2.15% ± 1.27% in men.By 80-84 years of age,the average frequency of CcOI-DC goes up in women to 15.77% ± 0.97% and in men to 22.6% ± 0.65%.The increases in CcOI-DC from ages 40-44 years compared to 80-84 years in women and men are significantly different with P < 0.01.For women over age 60 years,deficiency of CcOI expression is greater in those women who have had a cancer in their colon.The frequency of CcOI-DC,measured in men,increased in tissues adjacent to colon cancer,being 4.03% ± 0.27% in individuals free of neoplasia in the age range 55-64 yearsand 14.13% ± 0.35% in resected histologically normal tissue of men with cancer in the same age range,P < 0.001.Similar signifi cant differences were noted in older age ranges.The frequency of CcOI-DC crypts in the cecum and sigmoid colon of an individual are signifi cantly correlated,with an R2 = 0.414 for women and R2 = 0.528 for men,P < 0.001.This suggests that the factors determining the level of CcOI deficiency act throughout the colon.Most defective crypts are in clusters of two or more,a likely consequence of crypt fission.In the non-neoplastic margins of cancers,crypts are frequently defi cient for CcOI,and such crypts may appear in large clusters,some containing more than 100 defi cient crypts.CcOI defi ciency is also apparent in colon cancers and sometimes involves a large section of the tumor.Overall,CcOI deficient cells can be visualized in segments of crypts,in whole crypts that increase in frequency with age,in crypts undergoing f ission,in clusters of crypts where the clusters increase in size with age,in increased frequency near tumors,in large clusters in the intimate margins of tumors,and in the tumors themselves.There is no clear dividing line between early stages that can be considered aspects of aging and later stages that can be considered aspects of the progression to cancer.This ambiguity may re ect a rather general situation leading to adult cancer where the early stages of cellular change appear to be relatively innocuous features of the aging process but over decades may evolve into malignancy.CONCLUSION: CcOI defi cient crypts increase in frequency with age,and clusters of defi cient crypts are associated with,and may give rise to,colon cancer. | Carol Bernstein Alexander Facista Huy Nguyen Beryl Zaitlin Nadia Hassounah Cristy Loustaunau Claire Margaret Payne Bhaskar Banerjee Steve Goldschmid V Liana Tsikitis Robert Krouse Harris Bernstein | 2010 | World Journal of Gastrointestinal Oncology2010，2，12： | 5 |
| 2 | 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 |
| 3 | 高校实验室里的隐性杀手显示文摘23岁的谢哈巴诺·“谢里”·桑吉(sheharbano“Sheir”Sangji)决不会想到.一次实验竟为她的生命画上了句号。2008年12月底的一个下午.这位美国加利福尼亚大学洛杉矶分校(UCLA)的女技术员在做人生中的最后一个实验时,身穿的是运动T恤.而非正规实验服。 | 贝丽尔·利夫·本德尔利(Beryl Lieff Benderly) 严田青(译) | 2010 | 环球科学2010，，9： | 2 |
| 4 | Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings显示文摘 | Christopher A. Lipinski Franco Lombardo Beryl W. Dominy Paul J. Feeney | 2012 | Advanced Drug Delivery Reviews2012，，： | 1 |
| 5 | Clinical correlates of advanced retinopathy in type 2 diabetic patients 显示文摘 | Cecile D Beryl VL Francoise VK | 1996 | J Clin Epidemiol1996，49，6： | 1 |
| 6 | Experimental and computational approaches to estimate solubility and permeability in drug discovery and developmentq settings显示文摘 | Christopher A L Franco L Beryl W D | 2001 | Adv Drug Deliver Rev2001，46，5： | 1 |
| 7 | Actinomycetes in relation to taste and odour in drinking water:Myths,tenets and truths显示文摘 | BERYL Z SUSAN B W | 2006 | Wa- ter Res2006，40，9： | 1 |
| 8 | The history of the second‐trimester sonographic markers for detecting fetal Down syndrome, and their current role in obstetric practice显示文摘 | Beryl R.Benacerraf | 2010 | Prenat Diagn2010，，7： | 1 |
| 9 | A systematic approach to evaluate the modification of lens proteins by glycation-induced crossllnking 显示文摘 | Kwang-Won L Gregory S Beryl O | 1999 | Biochimica et Biophysica Acta1999，1453，： | 1 |
| 10 | The Government Performance and Results Act and the Tradition of Federal Management Reform:Square Pegs in Round Holes?显示文摘 | Radin Beryl A | 2000 | Journal of Public Administration Research and Theory2000，，： | 1 |
| 11 | Aetinomycetes in relation to taste and odour in drinking water: Myths, tenets and truths 显示文摘 | Beryl Z Susan B W | 2006 | Water Research2006，40，： | 1 |
| 12 | Actinomycetes in relation to taste and odour in dringking water: Myths, tenets and truths显示文摘 | Beryl Z Susan B W | 2006 | Water Research2006，40，9： | 1 |
| 13 | An integrative review of infection prevention and control programs for multidrug-resistant organisms in acute care hospitals: A socio-ecological perspective显示文摘 | Chantal Backman Geoffrey Taylor Anne Sales Patricia Beryl Marck | 2011 | AJIC: American Journal of Infection Control2011，，5： | 1 |
| 14 | The history of the second‐trimester sonographic markers for detecting fetal Down syndrome, and their current role in obstetric practice显示文摘 | Beryl R.Benacerraf | 2010 | Prenat. Diagn2010，，： | 1 |
| 15 | Second trimester ultrasound screening for chromosomal abnormalities显示文摘 | Thomas D Beryl RB | 2002 | Prenat Diagn2002，22，： | 1 |
| 16 | High -risk behaviors among men who have sex with men in 6 US cities: Baseline data from the EXPLORE Study显示文摘 | Beryl A Kolin Margaret A Chesney Marla J Husnik | 2003 | American Journal of Public Health2003，93，6： | 1 |
| 17 | What Does Magnetic Resonance Imaging Add to the Prenatal Sonographic Diagnosis of Ventriculomegaly? 显示文摘 | Beryl RB Thomas DS Bryann B | 2007 | J Ultrasound Med2007，26，11： | 1 |
| 18 | High prevalence of HIV infection among young men who have sex with men in New York City 显示文摘 | Beryl A Koblin Lucia V Torian Vince GuiUin | 2000 | AIDS2000，14，： | 1 |
| 19 | Common toxicity criteria: version 2.0. an improved reference for grading the acute effects of cancer treatment: impact on radiotherapy显示文摘 | Andy Trotti Roger Byhardt Joanne Stetz Clement Gwede Benjamin Corn Karen Fu Leonard Gunderson Beryl McCormick Mitchell Morris∫ Tyvin Rich William Shipley Walter Curran | 2000 | International Journal of Radiation Oncology Biology Physics2000，，1： | 1 |
| 20 | Sonography should be the first imaging examination done to evaluate patients with suspected endometriosis显示文摘 | Beryl RB Yvette G | 2012 | Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine2012，31，4： | 1 |
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