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: Treatment for glioblastoma multiforme includes the alkylating agent temozolomide combined with ionizing radiation . Persistent O6-guanine methylation by temozolomide in O6-methylguanine methyl transferase negative tumors causes cytotoxic lesions recognized by DNA mismatch repair , triggering apoptosis . Resistance ( intrinsic or acquired ) presents obstacles to successful temozolomide treatment , limiting drug efficacy and life expectancy . Two glioma cell lines , SNB19 and U373 , sensitive to temozolomide ( GI(50) values 36 and 68 microM , respectively ) were exposed to increasing temozolomide concentrations ( 1-100 microM ) . Variant cell lines ( SNB19VR , U373VR ) were generated that displayed acquired temozolomide resistance ( GI(50) values 280 and 289 microM , respectively ) . Cross-resistance to mitozolomide was observed in U373VR cells only . In clonogenic and MTT assays , methylguanine methyltransferase ( MGMT ) depletion using O6-benzylguanine sensitized U373VR cells to temozolomide , indicating the resistance mechanism involves MGMT re-expression . Indeed , Western blot analyses revealed MGMT protein in cell lysates . In SNB19VR cells , down-regulation of MSH6 message and protein expression may confer temozolomide tolerance . Inhibition of poly(ADP-ribose) polymerase-1 ( a key base excision repair ( BER ) enzyme ) partially restored sensitivity , and DNA repair gene arrays demonstrated up-regulation ( &gt;5-fold ) of BER gene NTL1 in SNB19VR cells . In conclusion , we have developed two glioma cell lines whose distinct mechanisms of acquired resistance to temozolomide , involving expression of MGMT , or inactivation of DNA mismatch repair and recruitment of BER enzymes , are consistent with clinical observations . These cell lines provide valuable models for the development of strategies to combat temozolomide resistance .
    OUTPUT:

agent
genomic instability and mutation
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: Treatment for glioblastoma multiforme includes the alkylating agent temozolomide combined with ionizing radiation . Persistent O6-guanine methylation by temozolomide in O6-methylguanine methyl transferase negative tumors causes cytotoxic lesions recognized by DNA mismatch repair , triggering apoptosis . Resistance ( intrinsic or acquired ) presents obstacles to successful temozolomide treatment , limiting drug efficacy and life expectancy . Two glioma cell lines , SNB19 and U373 , sensitive to temozolomide ( GI(50) values 36 and 68 microM , respectively ) were exposed to increasing temozolomide concentrations ( 1-100 microM ) . Variant cell lines ( SNB19VR , U373VR ) were generated that displayed acquired temozolomide resistance ( GI(50) values 280 and 289 microM , respectively ) . Cross-resistance to mitozolomide was observed in U373VR cells only . In clonogenic and MTT assays , methylguanine methyltransferase ( MGMT ) depletion using O6-benzylguanine sensitized U373VR cells to temozolomide , indicating the resistance mechanism involves MGMT re-expression . Indeed , Western blot analyses revealed MGMT protein in cell lysates . In SNB19VR cells , down-regulation of MSH6 message and protein expression may confer temozolomide tolerance . Inhibition of poly(ADP-ribose) polymerase-1 ( a key base excision repair ( BER ) enzyme ) partially restored sensitivity , and DNA repair gene arrays demonstrated up-regulation ( &gt;5-fold ) of BER gene NTL1 in SNB19VR cells . In conclusion , we have developed two glioma cell lines whose distinct mechanisms of acquired resistance to temozolomide , involving expression of MGMT , or inactivation of DNA mismatch repair and recruitment of BER enzymes , are consistent with clinical observations . These cell lines provide valuable models for the development of strategies to combat temozolomide resistance .
    OUTPUT:
