***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 establish the extent to which contrast enhancement with SonoVue in combination with quantitative evaluation of contrast-medium dynamics facilitates the detection of hepatic tumors . METHODS One hundred patients with histologically confirmed malignant or benign hepatic tumor ( maximum size 5 cm ) were analyzed .  Contrast-enhanced ultrasound ( bolus injection 2.5 mL SonoVue ) was carried out with intermittent breath-holding technique using a multifrequency transducer ( 2.5 - 4 MHz ) . Native vascularization was analyzed with power Doppler . The contrast-enhanced dynamic ultrasound investigation was carried out with contrast harmonic imaging in true detection mode during the arterial , portal venous and late phases . Mechanical index was set at 0.15 . Perfusion analysis was performed by post-processing of the raw data [ time intensity curve ( TIC ) analysis ] . The cut-off of the gray value differences between tumor and normal liver tissue was established using Receiver Operating Characteristic ( ROC ) analysis 64-line multi-slice computed tomography served as reference method in all cases . Magnetic resonance tomography was used additionally in 19 cases . RESULTS One hundred patients with 59 malignant ( 43 colon , 5 breast , 2 endocrine metastases , 7 hepatocellular carcinomas and 2 kidney cancers ) and 41 benign ( 15 hemangiomas , 7 focal nodular hyperplasias , 5 complicated cysts , 2 abscesses and 12 circumscribed fatty changes ) tumors were included . The late venous phase proved to be the most sensitive for classification of the tumor type . Fifty-eight of the 59 malignant tumors were classified as true positive , and one as false negative . This result ed in a sensitivity of 98.3 % . Of the 41 benign tumors , 37 were classified as true negative and 4 as false negative , which corresponds to a specificity of 90.2 % . Altogether , 95.0 % of the diagnoses were classified as correct on the basis of the histological classification . No investigator-dependency ( P = 0.23 ) was noted . CONCLUSION The results show the possibility of accurate prediction of malignancy of hepatic tumors with a positive prognostic value of 93.5 % using advanced contrast-enhanced ultrasound . Contrast enhancement with SonoVue in combination with quantitative evaluation of contrast-medium dynamics is a valuable tool to discriminate hepatic tumors OBJECTIVE To evaluate the tolerability and safety of frovatriptan 2.5 mg in patients with migraine . BACKGROUND Frovatriptan is a new , selective serotonin agonist ( triptan ) developed for the acute treatment of migraine . Dose range-finding studies identified 2.5 mg as the dose that conferred the optimal combination of efficacy and tolerability . METHODS The tolerability and safety of frovatriptan 2.5 mg were assessed during controlled , acute migraine treatment studies , including a study that compared frovatriptan 2.5 mg with sumatriptan 100 mg , as well as a 12-month open-label study during which patients could take up to three doses of frovatriptan 2.5 mg within a 24-hour period . Safety and tolerability were assessed through the collection of adverse events , monitoring of heart rate and blood pressure performance of 12-lead electrocardiogram , hematology screen , and blood chemistry studies . RESULTS In the short-term studies , 1554 patients took frovatriptan 2.5 mg and 838 took placebo .  In the 12-month study , 496 patients treated 13 878 migraine attacks . Frovatriptan was well tolerated in the short- and long-term studies with 1 % of patients in the short-term studies and 5 % of patients in the long-term study withdrawing due to lack of tolerability . The incidence of adverse events was higher in the frovatriptan-treated patients than in the patients who took placebo ( 47 % versus 34 % ) and the spectrum of adverse events was similar . When compared to sumatriptan 100 mg , significantly fewer patients taking frovatriptan experienced adverse events ( 43 % versus 36 % ; P=.03 ) and the number of adverse events was lower ( 0.62 versus 0.91 ) , there were also fewer adverse events suggestive of cardiovascular symptoms in the frovatriptan group . Analysis of the entire clinical data base ( n=2392 ) demonstrated that frovatriptan was well tolerated by the patients regardless of their age , gender , race , concomitant medication , or the presence of cardiovascular risk factors . No effects of frovatriptan on heart rate , blood pressure , 12-lead electrocardiogram , hematology screen , or blood chemistry were observed . No patient suffered any treatment-related serious adverse event . CONCLUSIONS Short- and long-term use of frovatriptan 2.5 mg was well tolerated by a wide variety of patients . Frovatriptan treatment produced an adverse events profile similar to that of placebo , and in a direct comparison study was better tolerated than sumatriptan 100 mg 
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However , pathways are still not fully understood as TLR2 up-regulation was also associated to enhanced tumorigenesis .
TLR3 has a well-known protective role influencing crucial processes like angiogenesis , cell growth or proliferation .
TLR4 works as an interesting epithelial-mesenchymal transition 's inducer and a promoter of cell survival probably inducing HCC carcinogenesis even though an anti-cancer role has already been observed .
Genetic polymorphisms in some TLRs have been found and its influence on the risk of HCC has been reported .
In conclusion , TLRs have been shown to be an interesting influence on the HCC 's microenvironment , with TLR3 clearly determining an anti-tumour influence .
TLR4 and TLR9 are considered to have a positive relationship with tumour development even though , in each of them anti-tumorigenic signals have been described .
TLR2 presents a more ambiguous role , possibly depending on the stage of the inflammation-HCC axis