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.
    ###
    INPUT: PURPOSE : Acid ceramidase ( AC ) occupies an important place in the control of cancer cell proliferation . We tested the influence of AC inhibition on the effects of PSC 833 , a P-glycoprotein antagonist with potent ceramide-generating capacity , to determine whether AC could be a therapeutic target in pancreatic cancer . METHODS : Ceramide metabolism was followed using ( 3)H-palmitate , and molecular species were determined by mass spectroscopy . Apoptosis was measured by DNA fragmentation , autophagy by acridine orange staining , and cell cycle was assessed by flow cytometry and RB phosphorylation . AC was measured in intact cells using fluorescent substrate . RESULTS : Exposure of human PANC-1 or MIA-PaCa-2 cells to PSC 833 promoted increases in de novo ( dihydro)ceramides , ( dihydro)glucosylceramides , and ( dihydro)sphingomyelins , demarking ceramide generation and robust metabolism . Despite the multifold increases in ( dihydro)ceramide levels , cells were refractory to PSC 833 . However , PSC 833 produced a dose-dependent decrease in DNA synthesis and dose- and time-dependent decreases in RB phosphorylation , consistent with cell cycle arrest as demonstrated at G1 . Cytostatic effects of PSC 833 were converted to cytotoxic end-point by acid ceramidase inhibition . Cytotoxicity was accompanied by formation of acridine orange-stained acidic vesicles and an increase in LC3 expression , indicative of autophagic response . Cell death was not reversed by preexposure to myriocin , which blocks PSC 833-induced ceramide generation . CONCLUSION : Although the role of ceramide in end-point cytotoxicity is unclear , our results suggest that acid ceramidase is a viable target in pancreatic cancer . We propose that AC inhibition will be effective in concert with other anticancer therapies .
    OUTPUT:

agent
sustaining proliferative signaling;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.
    ###
    INPUT: PURPOSE : Acid ceramidase ( AC ) occupies an important place in the control of cancer cell proliferation . We tested the influence of AC inhibition on the effects of PSC 833 , a P-glycoprotein antagonist with potent ceramide-generating capacity , to determine whether AC could be a therapeutic target in pancreatic cancer . METHODS : Ceramide metabolism was followed using ( 3)H-palmitate , and molecular species were determined by mass spectroscopy . Apoptosis was measured by DNA fragmentation , autophagy by acridine orange staining , and cell cycle was assessed by flow cytometry and RB phosphorylation . AC was measured in intact cells using fluorescent substrate . RESULTS : Exposure of human PANC-1 or MIA-PaCa-2 cells to PSC 833 promoted increases in de novo ( dihydro)ceramides , ( dihydro)glucosylceramides , and ( dihydro)sphingomyelins , demarking ceramide generation and robust metabolism . Despite the multifold increases in ( dihydro)ceramide levels , cells were refractory to PSC 833 . However , PSC 833 produced a dose-dependent decrease in DNA synthesis and dose- and time-dependent decreases in RB phosphorylation , consistent with cell cycle arrest as demonstrated at G1 . Cytostatic effects of PSC 833 were converted to cytotoxic end-point by acid ceramidase inhibition . Cytotoxicity was accompanied by formation of acridine orange-stained acidic vesicles and an increase in LC3 expression , indicative of autophagic response . Cell death was not reversed by preexposure to myriocin , which blocks PSC 833-induced ceramide generation . CONCLUSION : Although the role of ceramide in end-point cytotoxicity is unclear , our results suggest that acid ceramidase is a viable target in pancreatic cancer . We propose that AC inhibition will be effective in concert with other anticancer therapies .
    OUTPUT:
