***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND & AIMS The effect of lycopene-containing foods in prostate cancer development remains undetermined . We tested whether a lycopene-rich tomato intervention could reduce the levels of prostate specific antigen ( PSA ) in prostate cancer patients . METHODS Prior to their curative treatment , 79 patients with prostate cancer were r and omized to a nutritional intervention with either 1 ) tomato products containing 30 mg lycopene per day ; 2 ) tomato products plus selenium , omega-3 fatty acids , soy isoflavones , grape/pomegranate juice , and green/black tea ( tomato-plus ) ; or 3 ) control diet for 3 weeks . RESULTS The main analysis , which included patients in all risk categories , did not reveal differences in changes of PSA-values between the intervention and control groups . Post-hoc , exploratory analyses within intermediate risk ( n = 41 ) patients based on tumor classification and Gleason score post-surgery , revealed that median PSA decreased significantly in the tomato group as compared to controls ( -2.9 % and + 6.5 % respectively , p = 0.016 ) . In separate post-hoc analyses , we observed that median PSA-values decreased by 1 % in patients with the highest increases in plasma lycopene , selenium and C20:5 n-3 fatty acid , compared to an 8.5 % increase in the patients with the lowest increase in lycopene , selenium and C20:5 n-3 fatty acid ( p = 0.003 ) . Also , PSA decreased in patients with the highest increase in lycopene alone ( p = 0.009 ) . CONCLUSIONS Three week nutritional interventions with tomato-products alone or in combination with selenium and n-3 fatty acids  lower PSA in patients with non-metastatic prostate cancer . Our observation suggests that the effect may depend on both aggressiveness of the disease and the blood levels of lycopene , selenium and omega-3 fatty acids Diets rich in lycopene from tomato products as well as greater concentrations of blood lycopene have been associated with a decreased risk for prostate cancer in epidemiologic studies . However , little is known about factors modulating lycopene absorption , metabolism and tissue distribution in humans and animal models of prostate cancer . A 2 x 4 factorial design was used to measure the effects of and rogen status ( castrated vs. intact ) , dietary lycopene concentration ( 0.00 - 5.00 g/kg lycopene ) and their interaction on tissue lycopene accumulation and isomer patterns in male F344 rats . Male F344 rats ( 14 wk old ; 44 castrated , 44 intact ) were r and omly assigned to one of four diets containing total lycopene concentrations of 0.00 , 0.05 , 0.50 or 5.00 g/kg as beadlets and fed for 8 wk . Tissue total lycopene and cis/trans lycopene profiles were determined by HPLC . Tissue and serum lycopene concentrations increased significantly ( P < 0.01 ) as dietary lycopene levels increased between 0.00 and 0.50 g/kg . No further increases in serum or tissue concentrations were seen in rats fed dietary lycopene between 0.50 and 5.00 g/kg . As dietary lycopene increased , so did the percentage of cis lycopene in the liver ( P < 0.05 ) , due primarily to an increase in the 5-cis isomer . Castrated rats accumulated twice ( P < 0.01 ) the liver lycopene as compared to intact controls , with no effect of castration on serum lycopene or adrenal , kidney , adipose , or lung tissue concentration . Livers from castrated rats had a greater proportion of cis-lycopene than those of intact rats ( P < 0.05 ) . A significant interaction between dietary lycopene concentration and and rogen status was seen for liver lycopene concentration ( P < 0.01 ) . We conclude that serum and tissue lycopene reaches a plateau between 0.05 and 0.50 g/kg dietary lycopene , the tissue cis/trans lycopene ratio increases with greater dietary lycopene and and rogens modulate hepatic lycopene metabolism We previously demonstrated that the castration of male rats profoundly increases hepatic lycopene compared with intact controls . Here we further characterized the role of testosterone in modulating hepatic lycopene accumulation and isomer patterns in male rats . Furthermore , because castration significantly decreases ad libitum food consumption , we investigated the influence of food restriction on lycopene metabolism .  Forty male F344 rats 8 wk of age were r and omly assigned to one of four treatments ( n = 10/group ) : 1 ) intact , free access to food , 2 ) castration , free access to food , 3 ) castration plus testosterone implants , free access to food and 4 ) intact , 20 % food restricted . All rats were fed an AIN-based diet with 0.25 g lycopene ( as 10 % water-soluble beadlets)/kg diet for 3 wk . Serum testosterone was 5.31 + /- 1.46 nmol/L in intact controls allowed free access to food , reduced in castrated animals ( 0.52 + /- 0.10 , P < 0.0001 versus controls ) and intact , food-restricted rats ( 1.53 + /- 0.49 nmol/L , P < 0.0001 versus controls ) and greater ( 17.23 + /- 3.09 nmol/L ) in castrated rats administered testosterone ( P < 0.0001 versus controls ) . Castrated rats accumulated approximately twice as much liver lycopene ( 74.5 + /- 8.5 nmol/g ; P < 0.01 versus controls ) as intact rats allowed free access to food ( 39.5 + /- 5.0 ) despite 13 % lower dietary lycopene intake ( P < 0.001 ; 3.38 + /- 0.07 versus 3.95 + /- 0.06 mg lycopene/d ) . Testosterone replacement in castrated rats returned liver lycopene concentrations ( 32.5 + /- 5.5 nmol lycopene/g with 3.76 + /- 0.05 mg dietary lycopene/d ) to those observed in intact rats . Food restriction result ed in a 20 % decrease in lycopene intake but significantly increased liver lycopene by 68 % ( 66.3 + /- 7.9 nmol lycopene/g with 3.38 + /- 0.00 mg lycopene/d ) compared with controls and castrated rats administered testosterone . These results suggest that and rogen depletion and 20 % food restriction increase hepatic lycopene accumulation . We hypothesize an endocrine and dietary interaction , where higher and rogen concentrations and greater energy intake may stimulate lycopene metabolism and degradation Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Individual studies have suggested that circulating carotenoids , retinol , or tocopherols may be associated with prostate cancer risk , but the studies have not been large enough to provide precise estimates of associations , particularly by stage and grade of disease . OBJECTIVE The objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids , retinol , α-tocopherol , and γ-tocopherol with risk of  prostate cancer  and to describe whether any associations differ by stage or grade of the disease or other factors . DESIGN Principal investigators of prospect i ve studies provided individual participant data for prostate cancer cases and controls . Risk by study -specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets . RESULTS Data were available for up to 11,239 cases ( including 1654 advanced stage and 1741 aggressive ) and 18,541 controls from 15 studies .  Lycopene was not associated with overall risk of prostate cancer , but there was statistically significant heterogeneity by stage of disease , and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 ( 95 % CI : 0.46 , 0.91 ; P-trend = 0.032 ) . No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease . For retinol , the OR for the highest compared with the lowest fifth was 1.13 ( 95 % CI : 1.04 , 1.22 ; P-trend = 0.015 ) . For α-tocopherol , the OR for the highest compared with the lowest fifth was 0.86 ( 95 % CI : 0.78 , 0.94 ; P-trend < 0.001 ) , with significant heterogeneity by stage of disease ; the OR for aggressive prostate cancer was 0.74 ( 95 % CI : 0.59 , 0.92 ; P-trend = 0.001 ) . γ-Tocopherol was not associated with risk . CONCLUSIONS Overall prostate cancer risk was positively associated with retinol and inversely associated with α-tocopherol , and risk of aggressive prostate cancer was inversely associated with lycopene and α-tocopherol . Whether these associations reflect causal relations is unclear BACKGROUND There is increasing interest in the role of dietary factors in both the development and behaviour of prostate cancer . This study was carried out to evaluate the impact of the dietary factor lycopene on DNA synthesis , activity and expression of the and rogen receptor gene element in prostate LnCaP cells and to report our pilot phase II study investigating its effect on prostate-specific antigen velocity over one year . METHODS LnCaP cells were grown with or without different concentrations of lycopene or tetrahydrofuran ( THF solvent ) added to the culture medium for 48 hours . DNA synthesis was measured by the incorporation of bromodeoxyuridine ( Brdu ) into DNA during a 4-hour pulse , followed by immunostaining and visualization of stained cells using fluorescence microscopy . A transient transfection of a plasmid DNA recombinant containing an and rogen receptor element-luciferase ( ARE-Luc ) report gene into LnCaP cells was developed and the impact of different concentrations of lycopene on the and rogen receptor element was reflected by quantitative analysis of the luciferase enzyme function . Expression of the and rogen gene was also studied by Western blotting . The phase II pilot study patients ( n=41 ) previously diagnosed with prostate cancer were enrolled and given lycopene supplement , 10 mg per day , and response was measured by observing changes in the plasma prostate-specific antigen ( PSA ) levels . RESULTS The addition of 0.5 micromol/L , 5 micromol/L , 10 micromol/L and 15 micromol/L of lycopene was shown to inhibit cell growth by 2.66 % , 4.29 % , 3.73 % and 13.66 % , respectively , compared with the THF solvent control sample s ( P=0.015 ) . As compared with the RPMI1640 medium group , cell proliferation in the presence of 5 micromol/L , 10 micromol/L , and 15 micromol/L  lycopene  was inhibited by 8.12 % , 6.33 % and 12.00 % , respectively ( P=0.024 ) . We showed for the first time that lycopene inhibited the activity of the and rogen receptor gene element in a dose-related manner . Inhibition was seen in the transcription of the luciferase construct and confirmed by and rogen receptor element expression assayed by Western blotting . Regression slopes of ( log ) PSA vs. time decreased in 26/37 ( 70 % , 95%CI 53%-84 % ) of the patients after supplementation and in eight cases ( 21 % ) the post-treatment slope was negative . For these eight patients , the average fall in PSA was equivalent to 2 % over 28 days ( i.e. an average slope/d of -0.000713 ) . The Wilcoxon rank-sum test showed an overall statistically significant decrease in slope ( P=0.0007 ) . Analysis of the PSA doubling time ( pretreatment vs. posttreatment ) showed a median increase after supplementation for 174 days ; however , this was not statistically significant ( P=0.18 ) . CONCLUSIONS Lycopene as an antioxidant dietary factor could significantly inhibit DNA synthesis in a dose-dependent pattern ; the result revealed lycopene might inhibit and rogen receptor gene element activity and expression . Dietary lycopene may play an important role in prostate cancer cell proliferation and further supports a large r and omized study into the role of lycopene supplementation in malignant prostate disease Background Epidemiological studies have shown that lycopene has anti‐prostate cancer effect . In vitro tests also confirmed that it can promote apoptosis of prostate cancer cells . We investigated the effect of whole‐tomato supplement lycopene on the prostate‐specific antigen velocity in selected prostate cancer patients . Methods Twenty selected 
    Output:
    
Strong mechanistic evidence was unable to be ascertained , but tomato and lycopene treatment appears to down-regulate and rogen metabolism and signaling in PCa