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: Recent studies have shown that the transcription factor , nuclear factor kappaB ( NF-kappaB ) , regulates critical survival pathways in a variety of different cell types , including human pancreatic cancer cells . The activation of NF-kappaB is controlled by proteasome-mediated degradation of its endogenous polypeptide inhibitor , inhibitor of nuclear factor kappaBalpha . We investigated the effects of PS-341 , a peptide boronate inhibitor of the proteasome in human pancreatic cancer cells in vitro and in vivo . Comparison of PS-341's effects on the growth of eight different human pancreatic cancer cell lines revealed marked heterogeneity in drug responsiveness , ranging from highly resistant ( IC50 &gt ; 10 microM ; Panc-48 , HS766T , and Mia-PaCa-2 ) to extremely sensitive ( IC50 &lt ; 40 nM ; L3.6pl , Hpaf2 , and BxPC3 ) . However , these effects did not correlate with differential inhibition of NF-kappaB activation . Direct quantification of apoptosis revealed that PS-341's effects on cell growth largely correlated with sensitivity to programmed cell death . Evaluation of PS-341's effects on established orthotopic tumor xenografts demonstrated that biweekly intravenous administration of the maximum-tolerated dose of the drug ( 1 mg/kg ) led to significant reductions in the volumes of L3.6pl tumors but not Mia-PaCa-2 tumors . Laser scanning cytometer-mediated quantification of drug-induced apoptosis in the xenografts confirmed that PS-341 induced DNA fragmentation and activation of caspase-3 in L3.6pl tumors but not in Mia-PaCa-2 tumors . However , histological examination of drug-treated tumors revealed extensive central necrosis and reductions in microvessel density and VEGF expression in both tumor types . Taken together , our results demonstrate that PS-341 inhibits the growth of human pancreatic tumors via direct effects on tumor cells and indirect effects on the tumor vasculature .
    OUTPUT:

agent
resisting cell death;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.
    ###
    INPUT: Recent studies have shown that the transcription factor , nuclear factor kappaB ( NF-kappaB ) , regulates critical survival pathways in a variety of different cell types , including human pancreatic cancer cells . The activation of NF-kappaB is controlled by proteasome-mediated degradation of its endogenous polypeptide inhibitor , inhibitor of nuclear factor kappaBalpha . We investigated the effects of PS-341 , a peptide boronate inhibitor of the proteasome in human pancreatic cancer cells in vitro and in vivo . Comparison of PS-341's effects on the growth of eight different human pancreatic cancer cell lines revealed marked heterogeneity in drug responsiveness , ranging from highly resistant ( IC50 &gt ; 10 microM ; Panc-48 , HS766T , and Mia-PaCa-2 ) to extremely sensitive ( IC50 &lt ; 40 nM ; L3.6pl , Hpaf2 , and BxPC3 ) . However , these effects did not correlate with differential inhibition of NF-kappaB activation . Direct quantification of apoptosis revealed that PS-341's effects on cell growth largely correlated with sensitivity to programmed cell death . Evaluation of PS-341's effects on established orthotopic tumor xenografts demonstrated that biweekly intravenous administration of the maximum-tolerated dose of the drug ( 1 mg/kg ) led to significant reductions in the volumes of L3.6pl tumors but not Mia-PaCa-2 tumors . Laser scanning cytometer-mediated quantification of drug-induced apoptosis in the xenografts confirmed that PS-341 induced DNA fragmentation and activation of caspase-3 in L3.6pl tumors but not in Mia-PaCa-2 tumors . However , histological examination of drug-treated tumors revealed extensive central necrosis and reductions in microvessel density and VEGF expression in both tumor types . Taken together , our results demonstrate that PS-341 inhibits the growth of human pancreatic tumors via direct effects on tumor cells and indirect effects on the tumor vasculature .
    OUTPUT:
