***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: Diffuse large B-cell lymphoma ( DLBCL ) is a heterogeneous entity , with patients exhibiting a wide range of outcomes . The addition of rituximab to CHOP chemotherapy (R-CHOP)has led to a marked improvement in survival and has called into question the significance of previously recognized prognostic markers . Since r and omized controlled trials of R-CHOP in DLBCL have included select subgroups of patients , the utility of the International Prognostic Index ( IPI ) has not been reassessed . We performed a retrospective analysis of patients with DLBCL treated with R-CHOP in the province of British Columbia to assess the value of the IPI in the era of immunochemotherapy . The IPI remains predictive , but it identifies only 2 risk groups . Redistribution of the IPI factors into a revised IPI ( R-IPI ) provides a more clinical ly useful prediction of outcome . The R-IPI identifies 3 distinct prognostic groups with a very good ( 4-year progression-free survival [ PFS ] 94 % , overall survival [ OS ] 94 % ) , good ( 4-year PFS 80 % , OS 79 % ) , and poor ( 4-year PFS 53 % , OS 55 % ) outcome , respectively ( P < .001 ) . The IPI ( or R-IPI ) no longer identifies a risk group with less than a 50 % chance of survival . In the era of R-CHOP treatment , the R-IPI is a clinical ly useful prognostic index that may help guide treatment planning and interpretation of clinical trials The BCL6 ( B-Cell Lymphoma 6 ) gene is a proto-oncogene that is often expressed in diffuse large B-cell lymphomas ( DLBCLs ) . BCL6 loss of function can kill DLBCL cells , demonstrating that BCL6 is necessary for the survival of DLBCL cells and could be a therapeutic target . In this study , we found that BCL6 protein levels were consistently upregulated in DLBCL tissues , whereas its mRNA levels varied r and omly in tissues , suggesting that a post-transcriptional mechanism was involved in BCL6 regulation . We used bioinformatics analysis to search for miRNAs , which potentially target BCL6 , and identified specific targeting sites for miR-10a in the 3′-untranslated region ( 3′-UTR ) of BCL6 . We further identified an inverse correlation between miR-10a levels and BCL6 protein levels , but not mRNA levels , in DLBCL tumor tissue sample s. By overexpressing or knocking down miR-10a in DLBCL cells , we experimentally vali date d that miR-10a directly recognizes the 3′-UTR of the BCL6 transcript and regulated BCL6 expression . Furthermore , we demonstrated that negatively regulating BCL6 by miR-10a suppressed the proliferation and promoted apoptosis of DLBCL cells BACKGROUND Although many patients with intermediate- grade or high- grade ( aggressive ) non-Hodgkin 's lymphoma are cured by combination chemotherapy , the remainder are not cured and ultimately die of their disease . The Ann Arbor classification , used to determine the stage of this disease , does not consistently distinguish between patients with different long-term prognoses . This project was undertaken to develop a model for predicting outcome in patients with aggressive non-Hodgkin 's lymphoma on the basis of the patients ' clinical characteristics before treatment . METHODS Adults with aggressive non-Hodgkin 's lymphoma from 16 institutions and cooperative groups in the United States , Europe , and Canada who were treated between 1982 and 1987 with combination-chemotherapy regimens containing doxorubicin  were evaluated for clinical features predictive of overall survival and relapse-free survival . Features that remained independently significant in step-down regression analyses of survival were incorporated into models that identified groups of patients of all ages and groups of patients no more than 60 years old with different risks of death . RESULTS In 2031 patients of all ages , our model , based on age , tumor stage , serum lactate dehydrogenase concentration , performance status , and number of extranodal disease sites , identified four risk groups with predicted five-year survival rates of 73 percent , 51 percent , 43 percent , and 26 percent . In 1274 patients 60 or younger , an age-adjusted model based on tumor stage , lactate dehydrogenase level , and performance status identified four risk groups with predicted five-year survival rates of 83 percent , 69 percent , 46 percent , and 32 percent . In both models , the increased risk of death was due to both a lower rate of complete responses and a higher rate of relapse from complete response . These two indexes , called the international index and the age-adjusted international index , were significantly more accurate than the Ann Arbor classification in predicting long-term survival . CONCLUSIONS The international index and the age-adjusted international index should be used in the design of future therapeutic trials in patients with aggressive non-Hodgkin 's lymphoma and in the selection of appropriate therapeutic approaches for individual patients 
    Output:
    
In this review , we have identified miR-155 - 5p and miR-21 - 5p as miRNAs of potential utility for diagnosis , while miR-155 - 5p and miR-221 - 3p could be useful for classification .