***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: Background MicroRNA-10b ( miR-10b ) has a prominent role in regulating tumor invasion and metastasis by targeting the HOXD10 transcriptional repressor and has been found up-regulated in several tumor types . Methods We evaluated the expression of miR-10b  in paired tumor and normal specimens obtained from a prospect i ve cohort of breast cancer patients with at least 36 months follow-up enrolled according to the REMARK guidelines ( n = 150 ) . RNA quality was measured and only sample s with RNA Integrity Number ( RIN ) ≥7.0 were analyzed . Results The relative expression of miR-10b  in tumor as compared to its normal counterpart ( RER ) was determined by RT-qPCR  . miR-10b RERs were higher in the subgroup of patients with synchronous metastases ( n = 11 , Median 0.25 ; IQR 0.11 - 1.02 ) as compared with patients without metastases ( n = 90 , Median 0.09 ; IQR 0.04 - 0.29 ) ( p = 0.028 ) . In the subgroup of patients without synchronous metastases ( n = 90 ) , higher miR-10b RERs were associated with increased risk of disease progression and death in both univariable ( HR 1.16 , p = 0.021 and HR 1.20 , p = 0.015 respectively for 0.10 unitary increase of miR-10b RERs levels ) and multivariable ( HR1.30 , p < 0.001 , and HR 1.31 , p = 0.003 respectively for 0.10 unitary increase of miR-10b RERs levels ) Cox regression models . The addition of miR-10b RERs to the Nottingham Prognostic Index ( NPI ) provided an improvement in discrimination power and risk reclassification abilities for the clinical outcomes at 36 months . Survival C-indices significantly increased from 0.849 to 0.889 ( p = 0.009 ) for OS and from 0.735 to 0.767 ( p = 0.050 ) for DFS . Conclusions Our results provide evidence s that the addition of miR-10b RERs to the prognostic factors used in clinical routine could improve the prediction abilities for both overall mortality and disease progression in breast cancer patients Purpose : HER-2/neu oncogene is overexpressed in 10–30 % of epithelial ovarian cancers and is associated with a poor prognosis . The E1A gene product of adenovirus type 5 down-regulates HER-2/neu and causes tumor regression in animal models . In the current study , we sought to determine the toxicity and biological activity of E1A-lipid complex in ovarian cancer patients . Experimental Design : A Phase I trial involving intraperitoneal ( i.p . ) administration of E1A-lipid complex was initiated in ovarian cancer patients to assess biological activity ( E1A gene transfer/transcription/translation and HER-2/neu expression ) and to determine the maximum tolerated dose . Successive cohorts received E1A-lipid complex at doses of 1.8 , 3.6 , and 7.2 mg DNA/m2 , given as weekly i.p . infusions for 3 of 4 weeks ( each cycle ) up to a maximum of six cycles . Peritoneal fluid was sample d at baseline and twice monthly for cellularity , cytology , CA-125 , and biological activity Results : Fifteen patients , with a median age of 57 years ( range , 43–81 ) were recruited . Three ( 1.8 mg DNA/m2 ) , 4 ( 3.6 mg DNA/m2 ) , and 8 patients ( 7.2 mg DNA/m2 ) received i.p . E1A . A total of 91 infusions ( range , 1–18 ) was administered . Abdominal pain was the dose-limiting toxicity , and the maximum-tolerated dose was 3.6 mg DNA/m2 . E1A gene transfer and expression was observed in all of the patients and at all of the dose levels . HER-2/neu down-regulation could be demonstrated in the tumor cells of 2 patients ( 18 % ) . There was no correlation between dose and biological activity . Conclusions : I.P. EIA-lipid complex gene therapy is feasible and safe . Future studies , either alone or in combination with chemotherapy , particularly in patients with minimal residual disease , should be evaluated PURPOSE We conducted a Phase 1 study to determine the maximal tolerated dose and maximum biologically active dose of the E1A gene delivered by intratumoral injection as a lipid complex with 3 beta[N-(n',n'-dimethylaminoethane)-carbamoyl ] cholesterol/dioleoylphosphatidyl-ethanolamine ( tgDCC-E1A ) . The E1A adenovirus gene functions as a tumor inhibitor gene by repressing oncogene transcription ; modulating gene expression , result ing in cellular differentiation ; and inducing apoptosis of cancer cells . E1A also sensitizes cancer cells to chemotherapeutic drugs such as etoposide , cisplatin , and taxol . EXPERIMENTAL DESIGN Nine patients with recurrent and unresectable breast cancer and nine patients with head and neck cancer were enrolled . One tumor nodule in each patient was injected with tgDCC-E1A .  Safety , tumor response , E1A gene transfer , and down-regulation of HER-2/neu were evaluated . RESULTS No dose-limiting toxicity was observed in the four dose groups ( 15 , 30 , 60 , and 120 microg DNA/cm of tumor ) . All patients tolerated the injections , although several experienced pain and bleeding at the injection site . A maximally tolerated dose was not reached in this study . E1A gene transfer was demonstrated in 14 of 15 tumor sample s tested , and down-regulation of HER-2/neu was demonstrated in two of the five patients who overexpressed HER-2/neu at baseline . HER-2/neu could not be assessed in other posttreatment tumor sample s because of extensive necrosis . In one breast cancer patient , no pathological evidence of tumor was found on biopsy of the treated tumor site at week 12 . In 16 patients evaluable for tumor response , 2 had minor responses , 8 had stable disease , and 6 had progressive disease . CONCLUSIONS Gene therapy with an E1A gene : lipid complex appears to be safe and warrants further testing 
    Output:
    
Interestingly , the mRNA of Twist1 represents a downstream target of miRNAs , indicating an intricate network between miRNAs and Twist1 .
This network was shown to play multiple roles in cancer cell migration , invasion , and metastasis .