***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: Deficiencies of selenium have been associated with an increased cancer risk , and several clinical and animal trials have suggested that improved selenium nutrition may reduce the incidence of several kinds of cancer , including lung , colorectal , and breast . Results from recent trials also show an anticarcinogenic effect of selenium in the prostate . There is converging evidence from epidemiologic , experimental animal , and molecular biology studies for an antitumor effect of selenium . Evidence suggests there are two modes of action of selenium affecting cancer risk : first , by functioning as an essential nutrient that provides the catalytic centers of a number of selenoenzymes , including some with antioxidant and redox functions ; second , by serving as a source of selenium metabolytes that affect carcinogenesis in other ways . The first mechanism appears most relevant to protection against cancer initiation , the second against cancer progression . There is conclusive evidence of the increased risk of prostate cancer for a male with a family history of the disease . As a result of this evidence , and the evidence supporting the chemopreventive properties of selenium , this study proposed that a trial to test the effect of selenium on men at high risk for development of prostate cancer is appropriate . This article describes the Australian Prostate Cancer Prevention Trial Using Selenium ( APPOSE ) trial to test the hypothesis that daily dietary supplementation with selenium will reduce prostate cancer incidence in a population of men who are at increased risk because of a first-degree relative with prostate cancer PURPOSE Treatment of advanced Non small cell lung cancer ( NSCLC ) often produces dismal results . Combination of available treatment modalities has reportedly improved the outcome . A prospect ively r and omized trial was conducted , comparing combined treatment modalities versus radiotherapy alone , in treatment of unresectable NSCLC . MATERIAL S AND METHODS A total of 103 patients were r and omized to three groups . In group ' A ' , 32 patients received radiotherapy alone ( 6500 cGy/30 fraction ) . In group ' B ' , 35 patients received neoadjuvant chemotherapy ( Cisplatin 80 mg/m2 on day 1 and Etoposide 100 mg/m day 1 - 3 intravenously q3 weeks for 3 cycles ) , followed by radiotherapy ( 6000 cGy/30 fractions ) and 3 more cycles of Chemotherapy , with the same regimen . In group ' C ' , 36 patients received radiotherapy ( 5000 cGy/25 fractions ) with concurrent chemotherapy ( cisplatin 20 mg/m2 + Etoposide 75 mg/m2 intravenously on day 1 - 5 and day 22 - 26 ) , followed by 2 more cycles of chemotherapy , q3 weeks with the same regimen . RESULTS Initial treatment responses were significantly higher in group ' B ' ( P < 0.05 ) and ' C ' ( P < 0.03 ) , compared to group ' A ' . Follow-up observations showed , that addition of chemotherapy brought down distant metastasis 's from 62.5 % ( group ' A ' ) to 48.6 % ( group ' B ' ) and 44.4 % ( group ' C ' ) . The median time to tumour progression also improved from 16 months ( Group ' A ' ) to 21 months ( Group ' B ' and ' C ' ) . But 2 year follow up did not show any survival benefit . Acute toxicities were more frequent in group ' B ' and ' C ' , but were manageable . CONCLUSION Addition of chemotherapy with radiation in unresectable NSCLC improves response rates , time to tumour progression and disease free survival , though the same effect is not translated in overall survival 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 PURPOSE Growing evidence implies that selenium and vitamin E may decrease the risk of prostate cancer .  The Selenium and Vitamin E Cancer Prevention Trial ( SELECT ) is a r and omized prospect i ve double-blind study design ed to determine whether selenium and vitamin E decrease the risk of prostate cancer in healthy men . MATERIAL S AND METHODS The pre clinical and epidemiological evidence regarding chemoprevention with selenium and vitamin E were review ed . Secondary analyses from r and omized trials of the 2 agents were included in the current analysis . Data from these analyses as well as evidence from the Prostate Cancer Prevention Trial were used to develop the SELECT schema . RESULTS Pre clinical , epidemiological and phase III data imply that selenium and vitamin E have potential efficacy for prostate cancer prevention . The experience of the Prostate Cancer Prevention Trial shows the interest and dedication of healthy men to long-term studies of cancer prevention . A total of 32,400 men are planned to be r and omized in SELECT . CONCLUSIONS SELECT is the second large-scale study of chemoprevention for prostate cancer . Enrollment in the study is planned to begin in 2001 with final results anticipated in 2013 This is a report of research efforts underway at the Arizona Cancer Center . These efforts build upon Larry Clark 's unanticipated clinical prevention trial results : those results indicated that 200 microg/day of selenium in selenized yeast decreased prostate cancer risk by almost 60 % . The trials underway address various phases of the possible preventive activity of selenium . The first of these , for men who are suspected to have prostate cancer but who have had a biopsy revealing no evidence of cancer , will test the ability of selenium to prevent the development of clinical prostate cancer . The second is for men with high- grade prostatic intraepithelial neoplasia ; the trial will test whether selenium will prevent the development of prostatic cancer in this high-risk group . The third trial is for men who have been diagnosed with prostate cancer and are scheduled for prostatectomy : the trial is design ed to test whether evidence of selenium-linked changes can be identified in the tissue removed at prostatectomy . The fourth trial is for men who have been diagnosed with prostate cancer but who have chosen neither surgery nor irradiation ; this trial will evaluate whether treatment with selenium will inhibit the progress of prostate cancer . Together , these trials will provide important information as to the prostate cancer chemopreventive potential of selenium Selenium supplementation has been shown for many years to work as an anticarcinogenic agent both in epidemiology and in in vitro studies . Selenium supplementation has recently been shown to decrease total cancer incidence . However , the mechanism of action of selenium as an anticarcinogenic agent has yet to be eluci date d. Selenomethionine was the predominant form of selenium in the dietary supplement in the study by Clark et al. ( Clark , L.C. , Combs , G.F. , Turnbull , W.B. , Slate , E.H. , Chalker , D.K. , Chow , J. , Davis , L.S. , Glover , R.A. , Graham , G.F. , Gross , E.G. , Krongrad , A. , Lesher , J.L. , Park , H.K. , S and ers , B.B. , Smith , C.L. , Taylor , J.R. and The Nutritional Prevention of Cancer Study Group ( 1996 ) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin : a r and omized controlled trial . J. Am . Med . Assoc . , 276 ( 24 ) , 1957 - 1963 ) and therefore we evaluated the growth inhibitory effects of selenomethionine against human tumor cells .  Selenomethionine was tested against each of three human tumor cell lines ( MCF-7/S breast carcinoma , DU-145 prostate cancer cells and UACC-375 melanoma ) and against normal human diploid fibroblasts . All cell lines demonstrated a dose-dependent manner of growth inhibition by selenomethionine . Selenomethionine inhibited the growth of all of the human tumor cell lines in the micromolar ( microM ) range ( ranging from 45 to 130 microM ) while growth inhibition of normal diploid fibroblasts required 1 mM selenomethionine , approximately 1000-fold higher than for the cancer cell lines . In short , normal diploid fibroblasts were less sensitive than the cancer cell lines to the growth inhibitory effects of selenomethionine . Furthermore , we show that selenomethionine administration to these cancer cell lines results in apoptotic cell death and aberrant mitoses . These results demonstrate the differential sensitivity of tumor cells and normal cells to selenomethionine The Nutritional Prevention of Cancer Trial was a double-blind , r and omized , placebo-controlled clinical trial design ed to test whether selenium as selenized yeast ( 200 microg daily ) could prevent nonmelanoma skin cancer among 1312 patients from the Eastern United States who had previously had this disease . Results from September 15 , 1983 , through December 31 , 1993 , showed no association between treatment and the incidence of basal and squamous cell carcinomas of the skin . This report summarizes the entire blinded treatment period , which ended on January 31 , 1996 . The association between treatment and time to first nonmelanoma skin cancer diagnosis and between treatment and time to multiple skin tumors overall and within subgroups , defined by baseline characteristics , was evaluated . Although results through the entire blinded period continued to show that selenium supplementation was not statistically significantly associated with the risk of basal cell carcinoma ( hazard ratio [ HR ] = 1.09 , 95 % confidence interval [ CI ] = 0.94 to 1.26 ) , selenium supplementation was associated with statistically significantly elevated risk of squamous cell carcinoma ( HR = 1.25 , 95 % CI = 1.03 to 1.51 ) and of total nonmelanoma skin cancer ( HR = 1.17 , 95 % CI = 1.02 to 1.34 ) . Results from the Nutritional Prevention of Cancer Trial conducted among individuals at high risk of nonmelanoma skin cancer continue to demonstrate that selenium supplementation is ineffective at preventing basal cell carcinoma and that it increases the risk of squamous cell carcinoma and total nonmelanoma skin cancer OBJECTIVE To determine whether a nutritional supplement of selenium will decrease the incidence of cancer . DESIGN A multicenter , double-blind , r and omized , placebo-controlled cancer prevention trial . SETTING Seven dermatology clinics in the eastern United States . PATIENTS A total of 1312 patients ( mean age , 63 years ; range , 18 - 80 years ) with a history of basal cell or squamous cell carcinomas of the skin were r and omized from 1983 through 1991 . Patients were treated for a mean ( SD ) of 4.5 ( 2.8 ) years and had a total follow-up of 6.4 ( 2.0 ) years . INTERVENTIONS Oral administration of 200 microg of selenium per day or place 
    Output:
    
This systematic review provides the first evidence that antioxidant supplementation during chemotherapy holds potential for reducing dose-limiting toxicities .