***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: AIM To investigate the prognostic role of thymidylate synthase ( TS ) and thymidine phosphorylase ( TP ) mRNA levels in T3 or T4 gastric cancer treated with 5-fluorouracil-based adjuvant chemotherapy .  METHODS Fifty-one patients with T3 or T4 gastric cancer received systemic 5-fluorouracil-based adjuvant chemotherapy  , and intratumoral expression of TS and TP in 51 gastric cancer tissue sample s was tested by real-time quantitative PCR . RESULTS The median disease-free survival ( DFS ) time was 10.2 mo in the patients . There were no significant differences in DFS between the groups with high and low levels of TP . However , the group with low level of TS had a longer DFS ( 14.4 mo vs 8.3 mo , P = 0.017 ) . The median overall survival ( OS ) time was 18.5 mo , and there were significant differences in OS between the groups with high and low levels of TS or TP ( for TS , 17.0 mo vs 21.3 mo , P = 0.010 ; for TP , 16.6 mo vs 22.5 mo , P = 0.009 ) . Moreover , the coupled low expression of these two genes was strongly associated with a longer survival time of patients as compared with that of a single gene . CONCLUSION Expression of TS and TP mRNA is a useful predictive parameter for the survival of postoperative gastric cancer patients after 5-fluorouracil-based adjuvant chemotherapy Purpose : We evaluated the expression of seven therapy-related genes to predict the clinical outcome of advanced gastric cancer patients treated with a neoadjuvant chemotherapeutic protocol .  Experimental Design : Pretherapeutic , formalin-fixed , and paraffin-embedded biopsies of 61 patients , who received a 5-fluorouracil (5-FU)– and cisplatin-based chemotherapy were studied . The expressions of the 5-FU – related genes TS , DPD , and TP and of the  cisplatin-related genes ERCC1 , ERCC4 , KU80 , and GADD45A were analyzed by quantitative real-time PCR . The expression levels of single genes and of various combinations were tested for an association with response and overall survival . Results : High DPD levels were more frequently found in nonresponding patients and were associated with worse survival . GADD45A and TP levels showed weak associations with response , but GADD45A expression correlated with survival . There was no association with response for TS expression , but tumors with a high TS level were associated with worse survival . The combination of GADD45A and TP revealed the strongest predictive effect . High expression values of TP and /or GADD45A were exclusively found in nonresponding patients ( P = 0.002 ) and were associated with a significantly poorer survival ( P = 0.04 ) . Conclusions : Combined gene expression levels of TP and GADD45A represent a new variable to predict the clinical outcome after neoadjuvant chemotherapy in gastric cancer . The association of DPD expression with response and survival underlines a predominant role of DPD to predict 5-FU sensitivity . The association of TS expression levels with survival but not with response suggests an importance of this gene for tumor progression We evaluated the expression of thymidylate synthase ( TS ) in locally advanced gastric cancer patients treated with adjuvant chemotherapy after curative resection and investigated the association between TS expression and clinicopathologic characteristics including prognosis of the patients . TS expression was evaluated by immunohistochemical staining using TS106 monoclonal antibody in 103 locally advanced gastric cancer patients ( stage IB – IV ) who underwent 5-fluorouracil ( 5-FU ) and doxorubicin-based adjuvant chemotherapy after curative resection .  65 patients ( 63 % ) had primary tumours with high TS expression ( ≥ 25 % of tumour cells positive ) , and 38 patients ( 37 % ) demonstrated low TS expression ( < 25 % of tumour cells positive or no staining ) . High TS expression was associated with male gender ( P=0.002 ) , poorly differentiated histology ( P=0.015 ) , and mixed type in Lauren 's classification ( P=0.027 ) . There were no statistically significant differences in 4-year disease-free survival ( 60.0 % vs 57.2 % , P=0.548 ) and overall survival ( 59.6 % vs 59.3 % , P=0.792 ) between high-TS group and low-TS group . In conclusion , although high TS expression was associated with poorly differentiated histology and mixed type in Lauren 's classification , it did not predict poor disease-free and overall survival  in gastric cancer patients treated with 5-FU and doxorubicin-based adjuvant chemotherapy  after curative resection . Further prospect i ve studies including the evaluation of other biological markers associated with the resistance to 5-FU and doxorubicin are necessary . © 2001 Cancer Research Campaign The predictive values of thymidylate synthase ( TS ) and dihydropyrimidine dehydrogenase ( DPD ) gene expressions were retrospectively evaluated in patients with gastric cancer treated by a regimen containing S-1 .  The study population consisted of 53 patients registered into different two phase II studies for metastatic gastric cancer ; 27 patients treated by S-1-alone study : 26 patients treated with S-1 combined with irinotecan ( CPT-11 ) .  TS and DPD gene expressions in primary tumours were measured by the real-time reverse transcription PCR method . There was no statistical difference in DPD gene expression in terms of response in cases treated with S-1 alone and those treated with S-1 plus CPT-11 .  TS mRNA of responding tumours was lower than that of nonresponding ones when treated with S-1 ( P<0.005 ) . In the S-1-alone group , taking TS cutoff as the median values , the response rate in the low TS group was 50 % , but only 8 % in the high TS group ( P<0.05 ) . Patients with low TS gene expression survived longer than those with high TS gene expression ( P<0.0001 ) . However , there was no statistically significant difference in response rate and survival between patients with low TS tumours and those with high TS tumours , when the cutoff was taken as the median value of TS gene expression in the group treated with S-1 plus CPT-11 . In conclusion , treatment effects of S-1 monotherapy for gastric cancer were determined by the status of TS gene expression , regardless of DPD gene expression . TS predictive power was overcome by CPT-11 combination therapy with S-1 We investigated the utility of examining biological markers to predict chemoresponse and survival . The subjects consisted of 39 unresectable gastric cancer patients treated with a combination of 5-fluorouracil and cis-platinum .  The expression of p53 , bcl-2 , thymidylate synthase ( TS ) , glutathione S-transferase pi ( GST-pi ) , and vascular endothelial growth factor ( VEGF ) in the formalin-fixed biopsy sample s of primary tumors before chemotherapy was examined immunohistochemically . The positive rate for VEGF , bcl-2 , TS , p53 , and GST-pi was 51 , 10 , 46 , 38 , and 69 % , respectively . VEGF-positive cases showed a higher response rate than did negative cases ( 11 of 20 versus 2 of 19 cases ; P = 0.0057 ) . The cases that were negative for p53 , TS , bcl-2 , and GST-pi were more likely to respond to chemotherapy than the cases that were positive for these markers . The 10 cases having 4 or 5 favorable phenotypes ( VEGF positive , p53 negative , bcl-2 negative , TS negative , and GST-pi negative ) survived longer than the remaining 29 cases ( P = 0.0069 ) . Multivariate analysis revealed that the number of favorable phenotypes ( > or = 4 versus < or = 3 ) had a greater impact on survival than performance status ( 0 versus 1 or 2 ) , age ( > 60 years versus < or = 60 years ) , macroscopic type ( scirrhous versus nonscirrhous ) , histological type ( intestinal versus diffuse ) , or tumor extent ( locally advanced versus metastatic ) . Immunohistochemical examination of biological markers in biopsy sample s may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum PURPOSE We have previously shown that relative thymidylate synthase ( TS ) mRNA levels in primary gastric adenocarcinomas treated with fluorouracil ( 5-FU ) and cisplatin are inversely associated with response and survival . This is a presumed function of TS as a target for 5-FU activity . We now test the hypotheses that the relative mRNA level of the excision repair cross-complementing ( ERCC1 ) gene is inversely associated with response and survival as an independent function of cisplatin efficacy . PATIENTS AND METHODS Patients had intact , untreated , primary gastric adenocarcinoma cancer and were evaluated for eligibility on a preoperative cisplatin infusion-5-FU protocol . cDNA , derived from primary gastric tumors before chemotherapy , was used to determine ERCC1 mRNA levels , expressed as the ratio of polymerase chain reaction ( PCR ) product of the ERCC1 gene and the beta-actin gene . RESULTS The median ERCC1 mRNA level from 38 primary gastric cancers ( 33 assessable for response ) was 5.8 x 10(-3 ) ( range , 1.8 x 10(-3 ) to 19.5 x 10(-3 ) ) . Of 17 responding patients , 13 ( 76 % ) were less than or equal to 5.8 x 10(-3 ) and four were greater than 5.8 x 10(-3 ) ( P = .003 ) . The median survival for patients with ERCC1 mRNA levels less than or equal to 5.8 x 10(-3 ) has not been reached , whereas for those greater than 5.8 x 10(-3 ) it was 5.4 months ( P = .034 ) . The median TS mRNA level , 3.7 x 10(-3 ) ( range , 0.9 to 18.9 ) also segregated responsive versus resistant tumors ( P = .024 ) . With both ERCC1 and TS mRNA levels below their medians , 11 of 13 patients ( 85 % ) responded ; with both ERCC1 and TS mRNA levels above their medians , two of 10 patients ( 20 % ) responded ( P = .003 ) . CONCLUSION Considered separately , either ERCC1 or TS mRNA levels in a primary gastric adenocarcinoma has a statistically significant relationship to response . ERCC1 mRNA levels have a statistically significant association with survival ; in this cohort TS mRNA levels did not reach statistically significant association with survival as in our previous publication . Whether these molecular parameters are independent of each other as predictors of outcome remains to be determined In the past 4 years , the weekly 24‐hour infusion of high dose 5‐fluorouracil ( 5‐FU ) and leucovorin in the treatment of patients with advanced gastric carcinoma has been prospect ively studied at the authors ' institution . This has enabled them to explore the possibility that the level of expression of thymidylate synthase ( TS ) , the target enzyme of 5‐FU , is related to the drug sensitivity of gastric carcinoma to 5‐FU‐based chemotherapy Purpose We investigated whether the intensity of thymidylate synthase ( TS ) staining in tissue sample s obtained from gastric cancer ( GC ) patients undergoing gastrectomy could predict response to 5-FU-based adjuvant chemotherapy after gastrectomy . Method and material sClinicopathological features of 124 patients with histologically proven GC who underwent radical gastrectomy  were retrospectively review ed . Tissue sample s obtained from these patients were immunohistochemically stained for assessing TS expression . We arbitrarily classified the TS staining results as low ( < 20 % cytoplasmic immunostaining ) and high ( ≥20 % cytoplasmic immunostaining ) TS expression . Results The clinicopathological features of the low TS expression group patients were typically similar to those of the high TS expression group patients . However , multivariate forward stepwise logistic regression analysis revealed that low TS expression was independently associated with females and responders to 5-FU-based adjuvant chemotherapy . The median follow-up duration for the 124 GC patients who had undergone curative resection was 41.3 months . The GC patients who showed poor tumor differentiation and high TS expression had short disease-free survival ( DFS ) and overall survival ( OS ) . Conclusions Low TS expression is significantly associated with female GC patients and responders to 5-FU-based adjuvant chemotherapy . It predicts longer DFS and OS in selected GC patients treated with 5-FU-based adjuvant chemotherapy after curative resection . The results suggest that prospect i ve assessment of TS staining intensity in tissue sample s obtained from GC patients undergoing gastrectomy would be useful to predict the patients who would be benefited from 5-FU-based adjuvant chemotherapy after gastrectomy 
    Output:
    
High levels of TS expression were associated with a poorer OS for advanced GC patients compared with low levels .
In the adjuvant setting , high TS expression was also associated with a worse EFS .