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: Heparin-binding epidermal growth factor-like growth factor ( HB-EGF ) is a member of the epidermal growth factor family and has a variety of physiological and pathological functions . Modulation of HB-EGF activity might have a therapeutic potential in the oncology area . We explored the therapeutic possibilities by characterizing the in vitro biological activity of anti-HB-EGF monoclonal antibody Y-142 . EGF receptor ( EGFR ) ligand and species specificities of Y-142 were tested . Neutralizing activities of Y-142 against HB-EGF were evaluated in EGFR and ERBB4 signaling . Biological activities of Y-142 were assessed in cancer cell proliferation and angiogenesis assays and compared with the anti-EGFR antibody cetuximab , the HB-EGF inhibitor CRM197 , and the anti-vascular endothelial growth factor ( VEGF ) antibody bevacizumab . The binding epitope was determined with alanine scanning . Y-142 recognized HB-EGF as well as the EGFR ligand amphiregulin , and bound specifically to human HB-EGF , but not to rodent HB-EGF . In addition , Y-142 neutralized HB-EGF-induced phosphorylation of EGFR and ERBB4 , and blocked their downstream ERK1/2 and AKT signaling . We also found that Y-142 inhibited HB-EGF-induced cancer cell proliferation , endothelial cell proliferation , tube formation , and VEGF production more effectively than cetuximab and CRM197 and that Y-142 was superior to bevacizumab in the inhibition of HB-EGF-induced tube formation . Six amino acids in the EGF-like domain were identified as the Y-142 binding epitope . Among the six amino acids , the combination of F115 and Y123 determined the amphiregulin cross-reactivity and that F115 accounted for the species selectivity . Furthermore , it was suggested that the potent neutralizing activity of Y-142 was derived from its recognition of R142 and Y123 and its high affinity to HB-EGF . Y-142 has a potent HB-EGF neutralizing activity that modulates multiple biological activities of HB-EGF including cancer cell proliferation and angiogenic activities . Y-142 may have a potential to be developed into a therapeutic agent for the treatment of HB-EGF-dependent cancers .
    OUTPUT:

agent
inducing angiogenesis;sustaining proliferative signaling
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: Heparin-binding epidermal growth factor-like growth factor ( HB-EGF ) is a member of the epidermal growth factor family and has a variety of physiological and pathological functions . Modulation of HB-EGF activity might have a therapeutic potential in the oncology area . We explored the therapeutic possibilities by characterizing the in vitro biological activity of anti-HB-EGF monoclonal antibody Y-142 . EGF receptor ( EGFR ) ligand and species specificities of Y-142 were tested . Neutralizing activities of Y-142 against HB-EGF were evaluated in EGFR and ERBB4 signaling . Biological activities of Y-142 were assessed in cancer cell proliferation and angiogenesis assays and compared with the anti-EGFR antibody cetuximab , the HB-EGF inhibitor CRM197 , and the anti-vascular endothelial growth factor ( VEGF ) antibody bevacizumab . The binding epitope was determined with alanine scanning . Y-142 recognized HB-EGF as well as the EGFR ligand amphiregulin , and bound specifically to human HB-EGF , but not to rodent HB-EGF . In addition , Y-142 neutralized HB-EGF-induced phosphorylation of EGFR and ERBB4 , and blocked their downstream ERK1/2 and AKT signaling . We also found that Y-142 inhibited HB-EGF-induced cancer cell proliferation , endothelial cell proliferation , tube formation , and VEGF production more effectively than cetuximab and CRM197 and that Y-142 was superior to bevacizumab in the inhibition of HB-EGF-induced tube formation . Six amino acids in the EGF-like domain were identified as the Y-142 binding epitope . Among the six amino acids , the combination of F115 and Y123 determined the amphiregulin cross-reactivity and that F115 accounted for the species selectivity . Furthermore , it was suggested that the potent neutralizing activity of Y-142 was derived from its recognition of R142 and Y123 and its high affinity to HB-EGF . Y-142 has a potent HB-EGF neutralizing activity that modulates multiple biological activities of HB-EGF including cancer cell proliferation and angiogenic activities . Y-142 may have a potential to be developed into a therapeutic agent for the treatment of HB-EGF-dependent cancers .
    OUTPUT:
