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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 | Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial显示文摘 | Kris V Kowdley Eric Lawitz Israel Crespo Tarek Hassanein Mitchell N Davis Michael DeMicco David E Bernstein Nezam Afdhal John M Vierling Stuart C Gordon Jane K Anderson Robert H Hyland Hadas Dvory-Sobol Di An Robert G Hindes Efsevia Albanis William T Symo | 2013 | The Lancet2013，，9883： | 3 |
| 3 | Robust stability for sampled-data system显示文摘 | BERNSTEIN D S HOLLOT C V | 1989 | System & Control Letters1989，，13： | 2 |
| 4 | AML1,AML2 and AML3,the human members of the runt domain gene-family:cDNA structure,expression and chromosomal localization显示文摘 | Levanon D Negreanu V Bernstein Y | 1994 | Genomics1994，23，： | 1 |
| 5 | A method of uniform stratification of risk for evaluating the results of surgery in acquired adultheartdisease显示文摘 | Parsonnet V Dean D Bernstein A D | 1989 | Circulation1989，79，62： | 1 |
| 6 | Development and Validation of a New Index to Measure Emergency Department Crowding显示文摘 | Bernstein S L Verghese V Leung W Lunney A T Perez I | 2003 | Acad Emerg Med2003，10，9： | 1 |
| 7 | A fundamental approach to grate coolers显示文摘 | BERNSTEIN V G L MOLES F D | 1995 | ZKG-international1995，，3： | 1 |
| 8 | Value of dual energy CT in differentiating focal fatty infiltration of the liver from low density masses显示文摘 | Raptopoulos V Karellas A Bernstein J | 1991 | AJR1991，157，： | 1 |
| 9 | AML1,AML2 and AML3,the human members of the runt domain gene-family;cDNA structure,expression,and chromosomal localization显示文摘 | Levanon D Negreanu V Bernstein Y | 1994 | Genomics1994，23，2： | 1 |
| 10 | Pathophysi-ologic and therapeutic importance of tissue ACE : a con-sensus report显示文摘 | Dzau V J Bernstein K Celermajer D | 2002 | Cardiovasc Drugs Ther2002，16，2： | 1 |
| 11 | Adaptive autocentefing control for an active magnetic bearing supporting a rotor with unknown mass imbalance显示文摘 | LUM K Y COPPOLA V T BERNSTEIN D S | 1996 | IEEE Transaction on Control System Technology1996，4，5： | 1 |
| 12 | Pacermaker- implantation complication rates: an analysis of some contributing factors 显示文摘 | Parsonnet V Bernstein A Lindsay B | 1989 | J Am Coll Cardiol1989，13，4： | 1 |
| 13 | Ananal ysis of freezing rain, freezing drizzle, and ice pellets across the United States and Canada: 1976- 90显示文摘 | Cortinas Jr J V Bernstein B C Robbins C C | 2004 | Wea Forecas ring2004，19，： | 1 |
| 14 | Purification and characterization of heparinase from Flavobacterium heparinum显示文摘 | Linhardt R J Bernstein H | 1985 | J Biological Chemistry1985，260，： | 1 |
| 15 | The diagnosis and management of rhinitis: an updated practice parameter显示文摘 | WALLACE D V DYKEWICZ M S BERNSTEIN D I | 2008 | J Allergy Clin Im- munol2008，122，2： | 1 |
| 16 | Adaptive autocentering control for an active mag-netic bearing supporting a rotor with unknown mass imbalance 显示文摘 | LUM K Y COPPOLA V T BERNSTEIN D S | 1996 | IEEE Transactions on Control Sys- tems Technology1996，4，5： | 1 |
| 17 | Value of dual-energy CT in differentiating focal fatty infiltration of the liver from low-density masses显示文摘 | Raptopoulos V Karellas A Bernstein J | 1991 | AJR1991，157，： | 1 |
| 18 | AML1,AML2 and AML3, the human members of the runt domaingene-family: cDNA structure, expression and chromosomallocalization 显示文摘 | Levanon D Negreanu V Bernstein Y | 1994 | Genomics1994，23，2： | 1 |
| 19 | Adaptive au- tocentering control for an active magnetic bearing sup- porting a rotor with unknown mass imbalance显示文摘 | Lum K Y Coppola V T Bernstein D S | 1996 | IEEE Transactions on Control Systems Technology1996，4，5： | 1 |
| 20 | The diagnosis and management of rhinitis:an updated practice parameter显示文摘 | Wallace D V Dykewicz M S Bernstein D I | 2008 | J Allergy Clin Immunol2008，122，2： | 1 |
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