***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Nitric oxide ( NO ) is synthesized by inducible nitric oxide synthase ( iNOS ) and plays an important role in tumor growth and angiogenesis . NO generation by iNOS also influences the cytotoxicity of macrophages and tumor‐induced immunosuppression . Before now , the expression of iNOS in prostate carcinoma tissue had not been determined BACKGROUND Epidemiologic evidence indicates that diets high in carotenoid-rich fruits and vegetables , as well as high serum levels of vitamin E ( alpha-tocopherol ) and beta carotene , are associated with a reduced risk of lung cancer .  METHODS We performed a r and omized , double-blind , placebo-controlled primary -prevention trial to determine whether daily supplementation with alpha-tocopherol , beta carotene , or both would reduce the incidence of lung cancer and other cancers .  A total of 29,133 male smokers 50 to 69 years of age from southwestern Finl and were r and omly assigned to one of four regimens : alpha-tocopherol ( 50 mg per day ) alone , beta carotene ( 20 mg per day ) alone , both alpha-tocopherol and beta carotene , or placebo . Follow-up continued for five to eight years . RESULTS Among the 876 new cases of lung cancer diagnosed during the trial , no reduction in incidence was observed among the men who received alpha-tocopherol ( change in incidence as compared with those who did not , -2 percent ; 95 percent confidence interval , -14 to 12 percent ) . Unexpectedly , we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not ( change in incidence , 18 percent ; 95 percent confidence interval , 3 to 36 percent ) . We found no evidence of an interaction between alpha-tocopherol and beta carotene with respect to the incidence of lung cancer . Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol than among those who did not . Beta carotene had little or no effect on the incidence of cancer other than lung cancer . Alpha-tocopherol had no apparent effect on total mortality , although more deaths from hemorrhagic stroke were observed among the men who received this supplement than among those who did not . Total mortality was 8 percent higher ( 95 percent confidence interval , 1 to 16 percent ) among the participants who received beta carotene than among those who did not , primarily because there were more deaths from lung cancer and ischemic heart disease . CONCLUSIONS We found no reduction in the incidence of lung cancer among male smokers after five to eight years of dietary supplementation with alpha-tocopherol or beta carotene . In fact , this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects CONTEXT Secondary analyses of 2 r and omized controlled trials and supportive epidemiologic and pre clinical data indicated the potential of selenium and vitamin E for preventing prostate cancer . OBJECTIVE To determine whether selenium , vitamin E , or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men . DESIGN , SETTING , AND PARTICIPANTS A r and omized , placebo-controlled trial ( Selenium and Vitamin E Cancer Prevention Trial [ SELECT ] ) of 35,533 men from 427 participating sites in the United States , Canada , and Puerto Rico r and omly assigned to 4 groups ( selenium , vitamin E , selenium + vitamin E , and placebo ) in a double-blind fashion between August 22 , 2001 , and June 24 , 2004 . Baseline eligibility included age 50 years or older ( African American men ) or 55 years or older ( all other men ) , a serum prostate-specific antigen level of 4 ng/mL or less , and a digital rectal examination not suspicious for prostate cancer . INTERVENTIONS Oral selenium ( 200 microg/d from L-selenomethionine ) and matched vitamin E placebo , vitamin E ( 400 IU/d of all rac-alpha-tocopheryl acetate ) and matched selenium placebo , selenium + vitamin E , or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years . MAIN OUTCOME MEASURES Prostate cancer and prespecified secondary outcomes , including lung , colorectal , and overall primary cancer . RESULTS As of October 23 , 2008 , median overall follow-up was 5.46 years ( range , 4.17 - 7.33 years ) . Hazard ratios ( 99 % confidence intervals [ CIs ] ) for prostate cancer were 1.13 ( 99 % CI , 0.95 - 1.35 ; n = 473 ) for vitamin E , 1.04 ( 99 % CI , 0.87 - 1.24 ; n = 432 ) for selenium , and 1.05 ( 99 % CI , 0.88 - 1.25 ; n = 437 ) for selenium + vitamin E vs 1.00 ( n = 416 ) for placebo . There were no significant differences ( all P>.15 ) in any other prespecified cancer end points . There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group ( P = .06 ) and type 2 diabetes mellitus in the selenium group ( relative risk , 1.07 ; 99 % CI , 0.94 - 1.22 ; P = .16 ) but not in the selenium + vitamin E group . CONCLUSION Selenium or vitamin E , alone or in combination at the doses and formulations used , did not prevent prostate cancer in this population of relatively healthy men . TRIAL REGISTRATION clinical trials.gov identifier : NCT00006392 CONTEXT Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer , and vitamins E and C are among the most common individual supplements . A large-scale r and omized trial suggested that vitamin E may reduce risk of prostate cancer ; however , few trials have been powered to address this relationship . No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer . OBJECTIVE To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men . DESIGN , SETTING , AND PARTICIPANTS The Physicians ' Health Study II is a r and omized , double-blind , placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31 , 2007 . A total of 14,641 male physicians in the United States initially aged 50 years or older , including 1307 men with a history of prior cancer at r and omization , were enrolled . INTERVENTION Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily . MAIN OUTCOME MEASURES Prostate and total cancer . RESULTS During a mean follow-up of 8.0 years , there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers . Compared with placebo , vitamin E had no effect on the incidence of prostate cancer ( active and placebo vitamin E groups , 9.1 and 9.5 events per 1000 person-years ; hazard ratio [ HR ] , 0.97 ; 95 % confidence interval [ CI ] , 0.85 - 1.09 ; P = .58 ) or total cancer ( active and placebo vitamin E groups , 17.8 and 17.3 cases per 1000 person-years ; HR , 1.04 ; 95 % CI , 0.95 - 1.13 ; P = .41 ) . There was also no significant effect of vitamin C on total cancer ( active and placebo vitamin C groups , 17.6 and 17.5 events per 1000 person-years ; HR , 1.01 ; 95 % CI , 0.92 - 1.10 ; P = .86 ) or prostate cancer ( active and placebo vitamin C groups , 9.4 and 9.2 cases per 1000 person-years ; HR , 1.02 ; 95 % CI , 0.90 - 1.15 ; P = .80 ) . Neither vitamin E nor vitamin C had a significant effect on colorectal , lung , or other site-specific cancers . Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results . Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk . CONCLUSIONS In this large , long-term trial of male physicians , neither vitamin E nor C supplementation reduced the risk of prostate or total cancer . These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00270647 Background : Advanced glycation end products ( AGE ) accumulate in human tissue proteins during aging , particularly under hyperglycemia conditions . AGEs induce oxidative stress and inflammation via the receptor for AGEs ( RAGE ) and soluble RAGE ( sRAGE ) can neutralize the effects mediated by RAGE – lig and engagement . Methods : We examined the association between Nϵ-(carboxymethyl)lysine ( CML ) , a prominent AGE , and sRAGE and colorectal cancer risk in a prospect i ve case – cohort study nested within a cancer prevention trial among 29,133 Finnish male smokers . Among study subjects who were alive without cancer 5 years after baseline ( 1985–1988 ) , we identified 483 incident colorectal cancer cases and r and omly sample d 485 subcohort participants as the comparison group with the follow-up to April 2006  . Baseline serum levels of CML-AGE , sRAGE , glucose and insulin  were determined . Weighted Cox proportional hazard regression models were used to calculate relative risks ( RR ) and 95 % CI . Results : Comparing highest with lowest quintile of sRAGE , the RR for incident colorectal cancer was 0.65 ( 95 % CI , 0.39–1.07 ; Ptrend = 0.03 ) , adjusting for age , years of smoking , body mass index , and CML-AGE . Further adjustment for serum glucose strengthened the association ( RR = 0.52 ; 95 % CI , 0.30–0.89 ; Ptrend = 0.009 ) . Highest quintile of CML-AGE was not associated with an increased risk of colorectal cancer ( multivariate RR = 1.20 ; 95 % CI , 0.64–2.26 ) . Conclusions : Higher prediagnostic levels of serum sRAGE were associated with lower risk of colorectal cancer in male smokers . Impact : This is the first epidemiologic study to implicate the receptor for AGEs in colorectal cancer development . Cancer Epidemiol Biomarkers Prev ; 20(7 ) ; 1430–8 . © 2011 AACR Introduction Quality assessment of included studies is an important component of systematic review s. Objective The authors investigated inter-rater and test – retest reliability for quality assessment s conducted by inexperienced student raters . Design Student raters received a training session on quality assessment using the Jadad Scale for r and omised controlled trials and the Newcastle – Ottawa Scale ( NOS ) for observational studies . Raters were r and omly assigned into five pairs and they each independently rated the quality of 13–20 articles . These articles were drawn from a pool of 78 papers examining cognitive impairment following electroconvulsive therapy to treat major depressive disorder . The articles were r and omly distributed to the raters . Two months later , each rater re-assessed the quality of half of their assigned articles . Setting McMaster Integrative Neuroscience Discovery and Study Program . Participants 10 students taking McMaster Integrative Neuroscience Discovery and Study Program courses . Main outcome measures The authors measured inter-rater reliability using κ and the intraclass correlation coefficient type 2,1 or ICC(2,1 ) . The authors measured test – retest reliability using ICC(2,1 ) . Results Inter-rater reliability varied by scale question . For the six-item Jadad Scale , question -specific κs ranged from 0.13 ( 95 % CI −0.11 to 0.37 ) to 0.56 ( 95 % CI 0.29 to 0.83 ) . The ranges were −0.14 ( 95 % CI −0.28 to 0.00 ) to 0.39 ( 95 % CI −0.02 to 0.81 ) for the NOS cohort and −0.20 ( 95 % CI −0.49 to 0.09 ) to 1.00 ( 95 % CI 1.00 to 1.00 ) for the NOS case – control . For overall scores on the six-item Jadad Scale , ICC(2,1)s for inter-rater and test – retest reliability ( accounting for systematic differences between raters ) were 0.32 ( 95 % CI 0.08 to 0.52 ) and 0.55 ( 95 % CI 0.41 to 0.67 ) , respectively . Corresponding ICC(2,1)s for the NOS cohort were −0.19 ( 95 % CI −0.67 to 0.35 ) and 
    Output:
    
Upregulated OS profiles and impairment of antioxidant defense systems may play a role in men with PCa .