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 Neuroblastoma ( NBL ) is a common pediatric solid tumor , and outcomes for patients with advanced neuroblastoma remain poor despite extremely aggressive treatment . Chemotherapy resistance at relapse contributes heavily to treatment failure . The poor survival of patients with high-risk NBL prompted this investigation into novel treatment options with the objective of gaining a better understanding of resistance mechanisms . On the basis of previous work and on data from publicly available studies , the authors hypothesized that human epidermal growth factor receptor 4 ( Her4 ) contributes to resistance . METHODS Her4 expression was reduced with small-hairpin RNA ( shRNA ) to over express intracellular HER4 , and the authors tested its impact on tumor cell survival under various culture conditions . The resulting changes in gene expression after HER4 knockdown were measured by using a messenger RNA ( mRNA ) array . RESULTS HER4 expression was up-regulated in tumor spheres compared with the expression in monolayer culture . With HER4 knockdown , NBL cells became less resistant to anoikis and serum starvation . Moreover , HER4 knockdown increased the chemosensitivity of NBL cells to cisplatin , doxorubicin , etoposide , and activated ifosfamide . In mRNA array analysis , HER4 knockdown predominately altered genes related to cell cycle regulation . In NBL spheres compared with monolayers , cell proliferation was decreased , and cyclin D expression was reduced . HER4 knockdown reversed cyclin D suppression . Overexpressed intracellular HER4 slowed the cell cycle and induced chemoresistance . CONCLUSIONS The current results indicated that HER4 protects NBL cells from multiple exogenous apoptotic stimuli , including anoikis , nutrient deficiency , and cytotoxic chemotherapy . The intracellular fragment of HER4 was sufficient to confer this phenotype . HER4 functions as a cell cycle suppressor , maintaining resistance to cellular stress . The current findings indicate that HER4 overexpression may be associated with refractory disease , and HER4 may be an important therapeutic target .
    OUTPUT:

agent
sustaining proliferative signaling;evading growth suppressors;resisting cell death
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 Neuroblastoma ( NBL ) is a common pediatric solid tumor , and outcomes for patients with advanced neuroblastoma remain poor despite extremely aggressive treatment . Chemotherapy resistance at relapse contributes heavily to treatment failure . The poor survival of patients with high-risk NBL prompted this investigation into novel treatment options with the objective of gaining a better understanding of resistance mechanisms . On the basis of previous work and on data from publicly available studies , the authors hypothesized that human epidermal growth factor receptor 4 ( Her4 ) contributes to resistance . METHODS Her4 expression was reduced with small-hairpin RNA ( shRNA ) to over express intracellular HER4 , and the authors tested its impact on tumor cell survival under various culture conditions . The resulting changes in gene expression after HER4 knockdown were measured by using a messenger RNA ( mRNA ) array . RESULTS HER4 expression was up-regulated in tumor spheres compared with the expression in monolayer culture . With HER4 knockdown , NBL cells became less resistant to anoikis and serum starvation . Moreover , HER4 knockdown increased the chemosensitivity of NBL cells to cisplatin , doxorubicin , etoposide , and activated ifosfamide . In mRNA array analysis , HER4 knockdown predominately altered genes related to cell cycle regulation . In NBL spheres compared with monolayers , cell proliferation was decreased , and cyclin D expression was reduced . HER4 knockdown reversed cyclin D suppression . Overexpressed intracellular HER4 slowed the cell cycle and induced chemoresistance . CONCLUSIONS The current results indicated that HER4 protects NBL cells from multiple exogenous apoptotic stimuli , including anoikis , nutrient deficiency , and cytotoxic chemotherapy . The intracellular fragment of HER4 was sufficient to confer this phenotype . HER4 functions as a cell cycle suppressor , maintaining resistance to cellular stress . The current findings indicate that HER4 overexpression may be associated with refractory disease , and HER4 may be an important therapeutic target .
    OUTPUT:
