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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 | Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial显示文摘 | Ronald P DeMatteo Karla V Ballman Cristina R Antonescu Robert G Maki Peter WT Pisters George D Demetri Martin E Blackstein Charles D Blanke Margaret von Mehren Murray F Brennan Shreyaskumar Patel Martin D McCarter Jonathan A Polikoff Benjamin R Tan Kouros | 2009 | The Lancet2009，，9669： | 2 |
| 3 | Efficient string matching:An aid to bibliographic search显示文摘 | Alfred V A Margaret J C | 1975 | Communication of ACM1975，18，6： | 1 |
| 4 | End-stage renal disease and economic incentives:The international study of health care organization and fi- nancing显示文摘 | AviDor Mark V Pauly Margaret A Eichleay Philip J Held | 2007 | International Journal of Health Care Finance and Economics2007，，2： | 1 |
| 5 | Corasick Efficient String Matching显示文摘 | Aho A V Margaret J | 1975 | An Aid to Biographic Search Communications of the ACM1975，18，6： | 1 |
| 6 | Induction of labor in women with previors cesarean section using the double balloon drvice显示文摘 | Samia K Margaret V Liadya T | 2001 | Acta Obstet Gynecol Scand2001，80，11： | 1 |
| 7 | Effect of Two-and Three-locus linkage disequilibrium on the power to detect marker/phenotype associations显示文摘 | Dahila M N Margaret G E Dmitri V Z | 2004 | Genetics2004，168，： | 1 |
| 8 | Pulmonary Pressures and Death in Heart Failure显示文摘 | Francesca Bursi Sheila M. McNallan Margaret M. Redfield Vuyisile T. Nkomo Carolyn S.P. Lam Susan A. Weston Ruoxiang Jiang Véronique L. Roger | 2012 | Journal of the American College of Cardiology2012，，： | 1 |
| 9 | Benign Breast Disease:Diagnosis and Assessment显示文摘 | Margaret Thompson V Suzanne Klimberg | | 0，，： | 1 |
| 10 | Classification of deep-sea, fine-grained sediments 显示文摘 | WALTER E D MARGARET L DORRIK A V S | 1985 | Journal of Sedimentary Petrology1985，55，： | 1 |
| 11 | Characterizing the relationships between soil organic matter components and micro- bial function and composition along a tillage disturbance gradient 显示文摘 | COOKSON W R DANIEL V M MARGARET M R | 2008 | Soil Biology & Biochemistry2008，40，： | 1 |
| 12 | Chemical screening:A simple approach to visualizing Streptomyces diversity for drugdiscovery and further research 显示文摘 | Antonieta T Margaret V Juan G | 2006 | Research in Microbiology2006，157，3： | 1 |
| 13 | Scmliki Forest virusbased vaccines: persistence, distribution and pathological analysis in two animal systems 显示文摘 | Margaret M Morris-Dowries Kerry V | 2001 | Vaccine2001，19，： | 1 |
| 14 | Comparisons and dynamic incentives显示文摘 | MARGARET A M JOHN V | 1997 | Journal of Political Economy1997，105，： | 1 |
| 15 | Induction of labor in women with previous cesarean section using the double balloon device显示文摘 | Samia K Margaret V Lidya T | 2001 | Acta Obstet Gynecol Seand2001，80，11： | 1 |
| 16 | Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction显示文摘 | Carolyn S.P. Lam Véronique L. Roger Richard J. Rodeheffer Barry A. Borlaug Felicity T. Enders Margaret M. Redfield | 2009 | Journal of the American College of Cardiology2009，，13： | 1 |
| 17 | Dynamic ca- pabilities deconstructed; A bibliographical investi- gation into the origin, development, and future di- rections of the research domain显示文摘 | Giada D S Margaret P Gianmario V | 2010 | Industrial and Corporate Change2010，19，4： | 1 |
| 18 | Distribution of NADPH-d and nNOS-IR in the thoracolumbar and sacrococcygeal spinal cord of the guinea pig显示文摘 | Garth V Doone Nicole Pelissier Thomas Manchester Margaret A Vizzard | 1999 | Journal of the Autonomic Nervous System1999，，2： | 1 |
| 19 | Performance comparisons and dynamic incentives显示文摘 | Margaret A John V | 1997 | Journal of Political Economy1997，105，3： | 1 |
| 20 | Patient - reported outcomes to as- sess the efficacy of extended - release guaifenesin for the treatment of acute respiratory tract infection symptoms显示文摘 | Helmut A Margaret V Gall S | 2013 | Respir Res2013，13，： | 1 |
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