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:Sorafenib is the only drug approved for the treatment of hepatocellular carcinoma ( HCC ) . The bioenergetic propensity of cancer cells has been correlated to anticancer drug resistance , but such correlation is unclear in sorafenib resistance of HCC.Methods:Six sorafenib-naive HCC cell lines and one sorafenib-resistant HCC cell line ( Huh-7R ; derived from sorafenib-sensitive Huh-7 ) were used . The bioenergetic propensity was calculated by measurement of lactate in the presence or absence of oligomycin . Dichloroacetate ( DCA ) , a pyruvate dehydrogenase kinase ( PDK ) inhibitor , and siRNA of hexokinase 2 ( HK2 ) were used to target relevant pathways of cancer metabolism . Cell viability , mitochondrial membrane potential , and sub-G1 fraction were measured for in vitro efficacy . Reactive oxygen species ( ROS ) , adenosine triphosphate ( ATP ) and glucose uptake were also measured . A subcutaneous xenograft mouse model was used for in vivo efficacy.Results:The bioenergetic propensity for using glycolysis correlated with decreased sorafenib sensitivity ( R(2)=0.9067 , among sorafenib-naive cell lines ; P=0.003 , compared between Huh-7 and Huh-7âR ) . DCA reduced lactate production and increased ROS and ATP , indicating activation of oxidative phosphorylation ( OXPHOS ) . DCA markedly sensitised sorafenib-resistant HCC cells to sorafenib-induced apoptosis ( sub-G1 ( combination vs sorafenib ) : Hep3B , 65.4Â±8.4% vs 13Â±2.9% ; Huh-7âR , 25.3Â± 5.7% vs 4.3Â±1.5% ; each P&lt;0.0001 ) , whereas siRNA of HK2 did not . Sorafenib ( 10âmgâkg(-1) per day ) plus DCA ( 100âmgâkg(-1) per day ) also resulted in superior tumour regression than sorafenib alone in mice ( tumour size : -87% vs -36% , P&lt;0.001).Conclusion:The bioenergetic propensity is a potentially useful predictive biomarker of sorafenib sensitivity , and activation of OXPHOS by PDK inhibitors may overcome sorafenib resistance of HCC.British Journal of Cancer advance online publication , 20 December 2012 ; doi:10.1038/bjc.2012.559 www.bjcancer.com .
    OUTPUT:

agent
cellular energetics;tumor promoting inflammation;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:Sorafenib is the only drug approved for the treatment of hepatocellular carcinoma ( HCC ) . The bioenergetic propensity of cancer cells has been correlated to anticancer drug resistance , but such correlation is unclear in sorafenib resistance of HCC.Methods:Six sorafenib-naive HCC cell lines and one sorafenib-resistant HCC cell line ( Huh-7R ; derived from sorafenib-sensitive Huh-7 ) were used . The bioenergetic propensity was calculated by measurement of lactate in the presence or absence of oligomycin . Dichloroacetate ( DCA ) , a pyruvate dehydrogenase kinase ( PDK ) inhibitor , and siRNA of hexokinase 2 ( HK2 ) were used to target relevant pathways of cancer metabolism . Cell viability , mitochondrial membrane potential , and sub-G1 fraction were measured for in vitro efficacy . Reactive oxygen species ( ROS ) , adenosine triphosphate ( ATP ) and glucose uptake were also measured . A subcutaneous xenograft mouse model was used for in vivo efficacy.Results:The bioenergetic propensity for using glycolysis correlated with decreased sorafenib sensitivity ( R(2)=0.9067 , among sorafenib-naive cell lines ; P=0.003 , compared between Huh-7 and Huh-7âR ) . DCA reduced lactate production and increased ROS and ATP , indicating activation of oxidative phosphorylation ( OXPHOS ) . DCA markedly sensitised sorafenib-resistant HCC cells to sorafenib-induced apoptosis ( sub-G1 ( combination vs sorafenib ) : Hep3B , 65.4Â±8.4% vs 13Â±2.9% ; Huh-7âR , 25.3Â± 5.7% vs 4.3Â±1.5% ; each P&lt;0.0001 ) , whereas siRNA of HK2 did not . Sorafenib ( 10âmgâkg(-1) per day ) plus DCA ( 100âmgâkg(-1) per day ) also resulted in superior tumour regression than sorafenib alone in mice ( tumour size : -87% vs -36% , P&lt;0.001).Conclusion:The bioenergetic propensity is a potentially useful predictive biomarker of sorafenib sensitivity , and activation of OXPHOS by PDK inhibitors may overcome sorafenib resistance of HCC.British Journal of Cancer advance online publication , 20 December 2012 ; doi:10.1038/bjc.2012.559 www.bjcancer.com .
    OUTPUT:
