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: Testicular Germ Cell Tumors ( TGCT ) and patient-derived cell lines are extremely sensitive to cisplatin and other interstrand cross-link ( ICL ) inducing agents . Nevertheless , a subset of TGCTs are either innately resistant or acquire resistance to cisplatin during treatment . Understanding the mechanisms underlying TGCT sensitivity/resistance to cisplatin as well as the identification of novel strategies to target cisplatin-resistant TGCTs have major clinical implications . Herein , we have examined the proficiency of five embryonal carcinoma ( EC ) cell lines to repair cisplatin-induced ICLs . Using γH2AX staining as a marker of double strand break formation , we found that EC cell lines were either incapable of or had a reduced ability to repair ICL-induced damage . The defect correlated with reduced Homologous Recombination ( HR ) repair , as demonstrated by the reduction of RAD51 foci formation and by direct evaluation of HR efficiency using a GFP-reporter substrate . HR-defective tumors cells are known to be sensitive to the treatment with poly(ADP-ribose) polymerase ( PARP ) inhibitor . In line with this observation , we found that EC cell lines were also sensitive to PARP inhibitor monotherapy . The magnitude of sensitivity correlated with HR-repair reduced proficiency and with the expression levels and activity of PARP1 protein . In addition , we found that PARP inhibition strongly enhanced the response of the most resistant EC cells to cisplatin , by reducing their ability to overcome the damage . These results point to a reduced proficiency of HR repair as a source of sensitivity of ECs to ICL-inducing agents and PARP inhibitor monotherapy , and suggest that pharmacological inhibition of PARP can be exploited to target the stem cell component of the TGCTs ( namely ECs ) and to enhance the sensitivity of cisplatin-resistant TGCTs to standard treatments .
    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: Testicular Germ Cell Tumors ( TGCT ) and patient-derived cell lines are extremely sensitive to cisplatin and other interstrand cross-link ( ICL ) inducing agents . Nevertheless , a subset of TGCTs are either innately resistant or acquire resistance to cisplatin during treatment . Understanding the mechanisms underlying TGCT sensitivity/resistance to cisplatin as well as the identification of novel strategies to target cisplatin-resistant TGCTs have major clinical implications . Herein , we have examined the proficiency of five embryonal carcinoma ( EC ) cell lines to repair cisplatin-induced ICLs . Using γH2AX staining as a marker of double strand break formation , we found that EC cell lines were either incapable of or had a reduced ability to repair ICL-induced damage . The defect correlated with reduced Homologous Recombination ( HR ) repair , as demonstrated by the reduction of RAD51 foci formation and by direct evaluation of HR efficiency using a GFP-reporter substrate . HR-defective tumors cells are known to be sensitive to the treatment with poly(ADP-ribose) polymerase ( PARP ) inhibitor . In line with this observation , we found that EC cell lines were also sensitive to PARP inhibitor monotherapy . The magnitude of sensitivity correlated with HR-repair reduced proficiency and with the expression levels and activity of PARP1 protein . In addition , we found that PARP inhibition strongly enhanced the response of the most resistant EC cells to cisplatin , by reducing their ability to overcome the damage . These results point to a reduced proficiency of HR repair as a source of sensitivity of ECs to ICL-inducing agents and PARP inhibitor monotherapy , and suggest that pharmacological inhibition of PARP can be exploited to target the stem cell component of the TGCTs ( namely ECs ) and to enhance the sensitivity of cisplatin-resistant TGCTs to standard treatments .
    OUTPUT:
