human
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: Cytokeratin ( CK ) 19-positive hepatocellular carcinoma ( HCC ) has been reported to have a poor prognosis . The mechanism of the development of CK19-positive HCC remains to be studied . To clarify this , in vitro experiments were performed using human HCC cell lines ( PLC-5 , HepG2 ) , and the phenotypic changes after stimulation with several growth factors were examined using quantitative reverse transcriptase PCR , western blotting , and immunofluorescence staining . In vivo experiments using human HCC specimens obtained from a total of 78 patients and clinicopathological analysis were also performed . Among the growth factors tested , epidermal growth factor ( EGF ) had prominent effects on inducing CK19 expression in PLC-5 and HepG2 , which was accompanied by the reduced expression of Î±-fetoprotein in PLC-5 . The induction of CK19 expression after EGF stimulation was accompanied by the phosphorylation of c-Jun-N-terminal kinase ( JNK)/stress-activated protein kinase , which was blocked by the addition of JNK inhibitors . EGF also increased proliferative abilities and invasive properties of the HCC cell lines . In vivo , 9 ( 12% ) of 78 HCC cases showed positive immunohistochemical staining of CK19 . The extent of positive immunohistochemical signals of EGF , EGF receptor ( EGFR ) , and JNK expression was significantly intense in CK-19-positive HCC than those of CK19-negative HCC . Clinicopathological analysis showed that CK19-positive HCC had a high incidence of portal vein invasion , extrahepatic metastasis and an early relapse , which was associated with the worsened 2-year disease free survival . These results indicate that the activation of the EGF-EGFR signaling pathway is associated with the development of CK19-positive HCC , and the EGF-induced increase in growth abilities of HCC may account for the poor prognosis of the patients .
    OUTPUT:

agent
sustaining proliferative signaling;activating invasion and metastasis
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
    ###
    INPUT: Cytokeratin ( CK ) 19-positive hepatocellular carcinoma ( HCC ) has been reported to have a poor prognosis . The mechanism of the development of CK19-positive HCC remains to be studied . To clarify this , in vitro experiments were performed using human HCC cell lines ( PLC-5 , HepG2 ) , and the phenotypic changes after stimulation with several growth factors were examined using quantitative reverse transcriptase PCR , western blotting , and immunofluorescence staining . In vivo experiments using human HCC specimens obtained from a total of 78 patients and clinicopathological analysis were also performed . Among the growth factors tested , epidermal growth factor ( EGF ) had prominent effects on inducing CK19 expression in PLC-5 and HepG2 , which was accompanied by the reduced expression of Î±-fetoprotein in PLC-5 . The induction of CK19 expression after EGF stimulation was accompanied by the phosphorylation of c-Jun-N-terminal kinase ( JNK)/stress-activated protein kinase , which was blocked by the addition of JNK inhibitors . EGF also increased proliferative abilities and invasive properties of the HCC cell lines . In vivo , 9 ( 12% ) of 78 HCC cases showed positive immunohistochemical staining of CK19 . The extent of positive immunohistochemical signals of EGF , EGF receptor ( EGFR ) , and JNK expression was significantly intense in CK-19-positive HCC than those of CK19-negative HCC . Clinicopathological analysis showed that CK19-positive HCC had a high incidence of portal vein invasion , extrahepatic metastasis and an early relapse , which was associated with the worsened 2-year disease free survival . These results indicate that the activation of the EGF-EGFR signaling pathway is associated with the development of CK19-positive HCC , and the EGF-induced increase in growth abilities of HCC may account for the poor prognosis of the patients .
    OUTPUT:
