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: BACKGROUND Expression of epidermal growth factor receptor ( EGFR ) , a potent regulator of cellular homeostasis , is associated with aggressive tumor behavior . The mechanism by which EGFR inhibition functions is unclear , with controversial results demonstrating an effect on the tumor cells , endothelial cells , or pericytes . EGFR activation has been linked to the expression of vascular endothelial growth factor ( VEGF ) , a known mitogen of angiogenesis , but the relationship between these factors and their effect on tumor vessel development is vague . We hypothesized that using an EGFR inhibitor on a human Ewing's sarcoma model would inhibit tumor growth by suppressing vessel proliferation . METHODS A cell proliferation assay was performed on the Ewing's sarcoma ( SK-NEP-1 ) cell line . Tumor cells were implanted intrarenally in athymic mice . Animals received daily gavage with vehicle or gefitinib 1 wk following implantation . Mice ( n = 12/cohort ) were euthanized 6 wk following implantation . Remaining mice were maintained without treatment for 2 wk . Vascular changes were assessed by angiography and immunohistochemically . EGFR and vascular endothelial growth factor ( VEGF ) expression were quantified using quantitative polymerase chain reaction ( qPCR ) . RESULTS Gefitinib suppressed in vitro cell growth with an IC(50) = 1.36 Î¼M . Minimal tumor growth suppression was noted at 6 wk ( 6.01 ï¿½ 1.2 g in control versus 4.61 ï¿½ 0.9 g treated , P = 0.36 ) . After cessation of gefitinib , tumor growth was increased in both groups ( 7.37 ï¿½ 1.62 g versus 6.77 ï¿½ 1.53 g , P = 0.79 ) . Microvessel density was unchanged despite EGFR inhibition ( 161,000 ï¿½ 16,000 pixels versus 135,000 ï¿½ 18,000 pixels , P = 0.31 ) . At 6 wk , the vascular maturity index was similar in both groups ( 3.63 ï¿½ 1.12 versus 4.09 ï¿½ 1.71 , P = 0.83 ) . A downward trend in EGFR expression ( 49% of control ) and an upward trend in VEGF levels ( 50% of control ) occurred in the treated group . CONCLUSIONS EGFR expression was suppressed in cultured cells and xenograft tumors . Despite a cytotoxic effect on cell lines , gefitinib had little effect on tumor growth . No effects on the tumor vasculature were noted in the setting of EGFR suppression , suggesting that angiogenesis induced by SK-NEP-1 cells is refractory to EGFR inhibition . Interestingly , the resulting increase in VEGF expression following EGFR blockade , provides an alternative pro-angiogenic pathway promoting tumor survival .
    OUTPUT:

agent
sustaining proliferative signaling;inducing angiogenesis
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: BACKGROUND Expression of epidermal growth factor receptor ( EGFR ) , a potent regulator of cellular homeostasis , is associated with aggressive tumor behavior . The mechanism by which EGFR inhibition functions is unclear , with controversial results demonstrating an effect on the tumor cells , endothelial cells , or pericytes . EGFR activation has been linked to the expression of vascular endothelial growth factor ( VEGF ) , a known mitogen of angiogenesis , but the relationship between these factors and their effect on tumor vessel development is vague . We hypothesized that using an EGFR inhibitor on a human Ewing's sarcoma model would inhibit tumor growth by suppressing vessel proliferation . METHODS A cell proliferation assay was performed on the Ewing's sarcoma ( SK-NEP-1 ) cell line . Tumor cells were implanted intrarenally in athymic mice . Animals received daily gavage with vehicle or gefitinib 1 wk following implantation . Mice ( n = 12/cohort ) were euthanized 6 wk following implantation . Remaining mice were maintained without treatment for 2 wk . Vascular changes were assessed by angiography and immunohistochemically . EGFR and vascular endothelial growth factor ( VEGF ) expression were quantified using quantitative polymerase chain reaction ( qPCR ) . RESULTS Gefitinib suppressed in vitro cell growth with an IC(50) = 1.36 Î¼M . Minimal tumor growth suppression was noted at 6 wk ( 6.01 ï¿½ 1.2 g in control versus 4.61 ï¿½ 0.9 g treated , P = 0.36 ) . After cessation of gefitinib , tumor growth was increased in both groups ( 7.37 ï¿½ 1.62 g versus 6.77 ï¿½ 1.53 g , P = 0.79 ) . Microvessel density was unchanged despite EGFR inhibition ( 161,000 ï¿½ 16,000 pixels versus 135,000 ï¿½ 18,000 pixels , P = 0.31 ) . At 6 wk , the vascular maturity index was similar in both groups ( 3.63 ï¿½ 1.12 versus 4.09 ï¿½ 1.71 , P = 0.83 ) . A downward trend in EGFR expression ( 49% of control ) and an upward trend in VEGF levels ( 50% of control ) occurred in the treated group . CONCLUSIONS EGFR expression was suppressed in cultured cells and xenograft tumors . Despite a cytotoxic effect on cell lines , gefitinib had little effect on tumor growth . No effects on the tumor vasculature were noted in the setting of EGFR suppression , suggesting that angiogenesis induced by SK-NEP-1 cells is refractory to EGFR inhibition . Interestingly , the resulting increase in VEGF expression following EGFR blockade , provides an alternative pro-angiogenic pathway promoting tumor survival .
    OUTPUT:
