PMC:7426526 / 48017-49267 JSONTXT

{"project":"TEST0","denotations":[{"id":"32849491-147-154-3396559","span":{"begin":147,"end":150},"obj":"[\"30556601\"]"},{"id":"32849491-152-159-3396560","span":{"begin":152,"end":155},"obj":"[\"22737629\"]"},{"id":"32849491-157-164-3396561","span":{"begin":157,"end":160},"obj":"[\"22080947\"]"},{"id":"32849491-211-218-3396562","span":{"begin":385,"end":388},"obj":"[\"22737629\"]"},{"id":"32849491-216-223-3396563","span":{"begin":390,"end":393},"obj":"[\"22080947\"]"},{"id":"32849491-127-134-3396564","span":{"begin":523,"end":526},"obj":"[\"20858887\"]"},{"id":"32849491-132-139-3396565","span":{"begin":528,"end":531},"obj":"[\"26302802\"]"},{"id":"32849491-137-144-3396566","span":{"begin":533,"end":536},"obj":"[\"30556601\"]"},{"id":"32849491-150-157-3396567","span":{"begin":689,"end":692},"obj":"[\"26302802\"]"},{"id":"32849491-214-221-3396568","span":{"begin":909,"end":912},"obj":"[\"20858887\"]"},{"id":"32849491-219-226-3396569","span":{"begin":914,"end":917},"obj":"[\"30556601\"]"},{"id":"32849491-232-239-3396570","span":{"begin":1245,"end":1248},"obj":"[\"30556601\"]"}],"text":"As mentioned above, cells undergoing senescence can still escape the senescence program and become malignant while acquiring additional mutations (519, 535, 536) (Figure 2). In our studies, we observed a spontaneous mutation [a deficiency in p19 (Arf)] in Ras-expressing hepatocytes, which resulted in a full-blown HCC development using a Ras-induced precancerous liver disease model (535, 536). The reversibility of TIS can be caused through the inactivation of tumor suppressors p53, p16 (Ink4A), p19 (Ink4d), and/or RB (504, 507, 519). Additionally, the over-expression of CDC2/CDK1 and survivin can promote cancer stem cell survival and can also promote the development of polyploidy (507). In general, mutations in CDKN2A, coding for p16 (Ink4a, CDKN2A), p21 (Waf1, CDKN1A), and p27 (Kip1, CDKN1B) as well as E2F3 and EZH2, and a high c-MYC expression might result in low percentages of senescent cells (504, 519). Moreover, particular mutations completely protect melanoma cells from cell cycle arrest upon chemotherapy: DMBC29 melanoma cells that carried a EZH2S412C mutation, expressed c-MYC at a low level and a wild type of CDKN2A did not undergo senescence, in contrast to many melanoma cells treated with vemurafenib and trametinib (519)."}

{"project":"MyTest","denotations":[{"id":"32849491-30556601-34970939","span":{"begin":147,"end":150},"obj":"30556601"},{"id":"32849491-22737629-34970940","span":{"begin":152,"end":155},"obj":"22737629"},{"id":"32849491-22080947-34970941","span":{"begin":157,"end":160},"obj":"22080947"},{"id":"32849491-22737629-34970942","span":{"begin":385,"end":388},"obj":"22737629"},{"id":"32849491-22080947-34970943","span":{"begin":390,"end":393},"obj":"22080947"},{"id":"32849491-20858887-34970944","span":{"begin":523,"end":526},"obj":"20858887"},{"id":"32849491-26302802-34970945","span":{"begin":528,"end":531},"obj":"26302802"},{"id":"32849491-30556601-34970946","span":{"begin":533,"end":536},"obj":"30556601"},{"id":"32849491-26302802-34970947","span":{"begin":689,"end":692},"obj":"26302802"},{"id":"32849491-20858887-34970948","span":{"begin":909,"end":912},"obj":"20858887"},{"id":"32849491-30556601-34970949","span":{"begin":914,"end":917},"obj":"30556601"},{"id":"32849491-30556601-34970950","span":{"begin":1245,"end":1248},"obj":"30556601"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"As mentioned above, cells undergoing senescence can still escape the senescence program and become malignant while acquiring additional mutations (519, 535, 536) (Figure 2). In our studies, we observed a spontaneous mutation [a deficiency in p19 (Arf)] in Ras-expressing hepatocytes, which resulted in a full-blown HCC development using a Ras-induced precancerous liver disease model (535, 536). The reversibility of TIS can be caused through the inactivation of tumor suppressors p53, p16 (Ink4A), p19 (Ink4d), and/or RB (504, 507, 519). Additionally, the over-expression of CDC2/CDK1 and survivin can promote cancer stem cell survival and can also promote the development of polyploidy (507). In general, mutations in CDKN2A, coding for p16 (Ink4a, CDKN2A), p21 (Waf1, CDKN1A), and p27 (Kip1, CDKN1B) as well as E2F3 and EZH2, and a high c-MYC expression might result in low percentages of senescent cells (504, 519). Moreover, particular mutations completely protect melanoma cells from cell cycle arrest upon chemotherapy: DMBC29 melanoma cells that carried a EZH2S412C mutation, expressed c-MYC at a low level and a wild type of CDKN2A did not undergo senescence, in contrast to many melanoma cells treated with vemurafenib and trametinib (519)."}

{"project":"2_test","denotations":[{"id":"32849491-30556601-34970939","span":{"begin":147,"end":150},"obj":"30556601"},{"id":"32849491-22737629-34970940","span":{"begin":152,"end":155},"obj":"22737629"},{"id":"32849491-22080947-34970941","span":{"begin":157,"end":160},"obj":"22080947"},{"id":"32849491-22737629-34970942","span":{"begin":385,"end":388},"obj":"22737629"},{"id":"32849491-22080947-34970943","span":{"begin":390,"end":393},"obj":"22080947"},{"id":"32849491-20858887-34970944","span":{"begin":523,"end":526},"obj":"20858887"},{"id":"32849491-26302802-34970945","span":{"begin":528,"end":531},"obj":"26302802"},{"id":"32849491-30556601-34970946","span":{"begin":533,"end":536},"obj":"30556601"},{"id":"32849491-26302802-34970947","span":{"begin":689,"end":692},"obj":"26302802"},{"id":"32849491-20858887-34970948","span":{"begin":909,"end":912},"obj":"20858887"},{"id":"32849491-30556601-34970949","span":{"begin":914,"end":917},"obj":"30556601"},{"id":"32849491-30556601-34970950","span":{"begin":1245,"end":1248},"obj":"30556601"}],"text":"As mentioned above, cells undergoing senescence can still escape the senescence program and become malignant while acquiring additional mutations (519, 535, 536) (Figure 2). In our studies, we observed a spontaneous mutation [a deficiency in p19 (Arf)] in Ras-expressing hepatocytes, which resulted in a full-blown HCC development using a Ras-induced precancerous liver disease model (535, 536). The reversibility of TIS can be caused through the inactivation of tumor suppressors p53, p16 (Ink4A), p19 (Ink4d), and/or RB (504, 507, 519). Additionally, the over-expression of CDC2/CDK1 and survivin can promote cancer stem cell survival and can also promote the development of polyploidy (507). In general, mutations in CDKN2A, coding for p16 (Ink4a, CDKN2A), p21 (Waf1, CDKN1A), and p27 (Kip1, CDKN1B) as well as E2F3 and EZH2, and a high c-MYC expression might result in low percentages of senescent cells (504, 519). Moreover, particular mutations completely protect melanoma cells from cell cycle arrest upon chemotherapy: DMBC29 melanoma cells that carried a EZH2S412C mutation, expressed c-MYC at a low level and a wild type of CDKN2A did not undergo senescence, in contrast to many melanoma cells treated with vemurafenib and trametinib (519)."}