PMC:7426526 / 34020-36368
Annnotations
TEST0
{"project":"TEST0","denotations":[{"id":"32849491-82-89-3396413","span":{"begin":429,"end":432},"obj":"[\"29428447\"]"},{"id":"32849491-167-174-3396414","span":{"begin":602,"end":605},"obj":"[\"29950146\"]"},{"id":"32849491-66-72-3396415","span":{"begin":920,"end":922},"obj":"[\"19342894\"]"},{"id":"32849491-141-146-3396416","span":{"begin":995,"end":996},"obj":"[\"11689955\"]"},{"id":"32849491-144-150-3396417","span":{"begin":998,"end":1000},"obj":"[\"16651403\"]"},{"id":"32849491-148-155-3396418","span":{"begin":1002,"end":1005},"obj":"[\"29389522\"]"},{"id":"32849491-144-151-3396419","span":{"begin":1152,"end":1155},"obj":"[\"28321124\"]"},{"id":"32849491-149-156-3396420","span":{"begin":1157,"end":1160},"obj":"[\"26657156\"]"},{"id":"32849491-154-161-3396421","span":{"begin":1162,"end":1165},"obj":"[\"28933312\"]"},{"id":"32849491-112-119-3396422","span":{"begin":1280,"end":1283},"obj":"[\"28933312\"]"},{"id":"32849491-166-172-3396423","span":{"begin":1452,"end":1454},"obj":"[\"25749979\"]"},{"id":"32849491-69-75-3396424","span":{"begin":1526,"end":1528},"obj":"[\"19342894\"]"},{"id":"32849491-73-79-3396425","span":{"begin":1530,"end":1532},"obj":"[\"25749979\"]"},{"id":"32849491-140-147-3396426","span":{"begin":1597,"end":1600},"obj":"[\"28905209\"]"},{"id":"32849491-145-152-3396427","span":{"begin":1602,"end":1605},"obj":"[\"25889765\"]"},{"id":"32849491-119-124-3396428","span":{"begin":1727,"end":1728},"obj":"[\"11689955\"]"},{"id":"32849491-122-128-3396429","span":{"begin":1730,"end":1732},"obj":"[\"21376230\"]"},{"id":"32849491-126-132-3396430","span":{"begin":1734,"end":1736},"obj":"[\"16651403\"]"},{"id":"32849491-85-91-3396431","span":{"begin":2071,"end":2073},"obj":"[\"21376230\"]"}],"text":"Intracellular Biomarkers as Regulators of Stemness in Hematological Cancers\nThe core-network of pluripotency associated transcription factors as well as signaling pathways have also been analyzed in hematological cancers. Fifty AML patients have been analyzed for the expression of Sox proteins, which are overexpressed in 10–22% of the patients. The analysis showed that high levels of Sox proteins may have a prognostic value (432). The analysis of Oct-3/4 expression correlated with an unfavorable prognosis and is associated with FMS-like tyrosine kinase 3-internal tandem duplications (FLT3-ITD) (430).\nActivation of stemness-associated pathways especially in CML has been shown to promote extensive proliferation and has been linked to the onset of blast crisis, which is associated with a loss of differentiation of the leukemia initiating cells. An important impact on this effect has the Wnt/ß-catenin pathway (46) that promotes HSC proliferation, independent of the bone marrow niche (5, 22, 499). Especially, resistance to the tyrosine kinase inhibitor imatinib has been shown to correlate to an increased nuclear localization of ß-catenin (454, 458, 500). Inhibitors targeting the Wnt pathway have been shown to be of advantage for example in long-term cell cultures (500). Additionally, the hedgehog pathway has been suggested to be involved in chemotherapeutic resistance in CML, which is also characteristic for chronic phase CML cells (47). Mouse studies also indicate the involvement of the hedgehog pathway (46, 47), which has been implicated as a therapeutic biomarker for CML (456, 461).\nTo summarize, CSCs at tumor initiation originate from either differentiated cells or adult tissue resident stem cells (5, 19, 22). Several data indicate that the origin strongly correlates to the aggressiveness of the tumor. Therefore, extra- and intracellular biomarkers that characterize CSCs have been identified and implemented to be of diagnostic and prognostic advantage. However, stem cells are subject to a high degree of plasticity modulated by the TME (19), that is significantly changed by chemo- and radiotherapies and composed of several different cell types. In the following section, focus will be laying on senescent tumor cells as part of the TME as they have long-term influence on TME and CSC development and progression."}
MyTest
{"project":"MyTest","denotations":[{"id":"32849491-29428447-34970793","span":{"begin":429,"end":432},"obj":"29428447"},{"id":"32849491-29950146-34970794","span":{"begin":602,"end":605},"obj":"29950146"},{"id":"32849491-19342894-34970795","span":{"begin":920,"end":922},"obj":"19342894"},{"id":"32849491-11689955-34970796","span":{"begin":995,"end":996},"obj":"11689955"},{"id":"32849491-16651403-34970797","span":{"begin":998,"end":1000},"obj":"16651403"},{"id":"32849491-29389522-34970798","span":{"begin":1002,"end":1005},"obj":"29389522"},{"id":"32849491-28321124-34970799","span":{"begin":1152,"end":1155},"obj":"28321124"},{"id":"32849491-26657156-34970800","span":{"begin":1157,"end":1160},"obj":"26657156"},{"id":"32849491-28933312-34970801","span":{"begin":1162,"end":1165},"obj":"28933312"},{"id":"32849491-28933312-34970802","span":{"begin":1280,"end":1283},"obj":"28933312"},{"id":"32849491-25749979-34970803","span":{"begin":1452,"end":1454},"obj":"25749979"},{"id":"32849491-19342894-34970804","span":{"begin":1526,"end":1528},"obj":"19342894"},{"id":"32849491-25749979-34970805","span":{"begin":1530,"end":1532},"obj":"25749979"},{"id":"32849491-28905209-34970806","span":{"begin":1597,"end":1600},"obj":"28905209"},{"id":"32849491-25889765-34970807","span":{"begin":1602,"end":1605},"obj":"25889765"},{"id":"32849491-11689955-34970808","span":{"begin":1727,"end":1728},"obj":"11689955"},{"id":"32849491-21376230-34970809","span":{"begin":1730,"end":1732},"obj":"21376230"},{"id":"32849491-16651403-34970810","span":{"begin":1734,"end":1736},"obj":"16651403"},{"id":"32849491-21376230-34970811","span":{"begin":2071,"end":2073},"obj":"21376230"}],"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":"Intracellular Biomarkers as Regulators of Stemness in Hematological Cancers\nThe core-network of pluripotency associated transcription factors as well as signaling pathways have also been analyzed in hematological cancers. Fifty AML patients have been analyzed for the expression of Sox proteins, which are overexpressed in 10–22% of the patients. The analysis showed that high levels of Sox proteins may have a prognostic value (432). The analysis of Oct-3/4 expression correlated with an unfavorable prognosis and is associated with FMS-like tyrosine kinase 3-internal tandem duplications (FLT3-ITD) (430).\nActivation of stemness-associated pathways especially in CML has been shown to promote extensive proliferation and has been linked to the onset of blast crisis, which is associated with a loss of differentiation of the leukemia initiating cells. An important impact on this effect has the Wnt/ß-catenin pathway (46) that promotes HSC proliferation, independent of the bone marrow niche (5, 22, 499). Especially, resistance to the tyrosine kinase inhibitor imatinib has been shown to correlate to an increased nuclear localization of ß-catenin (454, 458, 500). Inhibitors targeting the Wnt pathway have been shown to be of advantage for example in long-term cell cultures (500). Additionally, the hedgehog pathway has been suggested to be involved in chemotherapeutic resistance in CML, which is also characteristic for chronic phase CML cells (47). Mouse studies also indicate the involvement of the hedgehog pathway (46, 47), which has been implicated as a therapeutic biomarker for CML (456, 461).\nTo summarize, CSCs at tumor initiation originate from either differentiated cells or adult tissue resident stem cells (5, 19, 22). Several data indicate that the origin strongly correlates to the aggressiveness of the tumor. Therefore, extra- and intracellular biomarkers that characterize CSCs have been identified and implemented to be of diagnostic and prognostic advantage. However, stem cells are subject to a high degree of plasticity modulated by the TME (19), that is significantly changed by chemo- and radiotherapies and composed of several different cell types. In the following section, focus will be laying on senescent tumor cells as part of the TME as they have long-term influence on TME and CSC development and progression."}
2_test
{"project":"2_test","denotations":[{"id":"32849491-29428447-34970793","span":{"begin":429,"end":432},"obj":"29428447"},{"id":"32849491-29950146-34970794","span":{"begin":602,"end":605},"obj":"29950146"},{"id":"32849491-19342894-34970795","span":{"begin":920,"end":922},"obj":"19342894"},{"id":"32849491-11689955-34970796","span":{"begin":995,"end":996},"obj":"11689955"},{"id":"32849491-16651403-34970797","span":{"begin":998,"end":1000},"obj":"16651403"},{"id":"32849491-29389522-34970798","span":{"begin":1002,"end":1005},"obj":"29389522"},{"id":"32849491-28321124-34970799","span":{"begin":1152,"end":1155},"obj":"28321124"},{"id":"32849491-26657156-34970800","span":{"begin":1157,"end":1160},"obj":"26657156"},{"id":"32849491-28933312-34970801","span":{"begin":1162,"end":1165},"obj":"28933312"},{"id":"32849491-28933312-34970802","span":{"begin":1280,"end":1283},"obj":"28933312"},{"id":"32849491-25749979-34970803","span":{"begin":1452,"end":1454},"obj":"25749979"},{"id":"32849491-19342894-34970804","span":{"begin":1526,"end":1528},"obj":"19342894"},{"id":"32849491-25749979-34970805","span":{"begin":1530,"end":1532},"obj":"25749979"},{"id":"32849491-28905209-34970806","span":{"begin":1597,"end":1600},"obj":"28905209"},{"id":"32849491-25889765-34970807","span":{"begin":1602,"end":1605},"obj":"25889765"},{"id":"32849491-11689955-34970808","span":{"begin":1727,"end":1728},"obj":"11689955"},{"id":"32849491-21376230-34970809","span":{"begin":1730,"end":1732},"obj":"21376230"},{"id":"32849491-16651403-34970810","span":{"begin":1734,"end":1736},"obj":"16651403"},{"id":"32849491-21376230-34970811","span":{"begin":2071,"end":2073},"obj":"21376230"}],"text":"Intracellular Biomarkers as Regulators of Stemness in Hematological Cancers\nThe core-network of pluripotency associated transcription factors as well as signaling pathways have also been analyzed in hematological cancers. Fifty AML patients have been analyzed for the expression of Sox proteins, which are overexpressed in 10–22% of the patients. The analysis showed that high levels of Sox proteins may have a prognostic value (432). The analysis of Oct-3/4 expression correlated with an unfavorable prognosis and is associated with FMS-like tyrosine kinase 3-internal tandem duplications (FLT3-ITD) (430).\nActivation of stemness-associated pathways especially in CML has been shown to promote extensive proliferation and has been linked to the onset of blast crisis, which is associated with a loss of differentiation of the leukemia initiating cells. An important impact on this effect has the Wnt/ß-catenin pathway (46) that promotes HSC proliferation, independent of the bone marrow niche (5, 22, 499). Especially, resistance to the tyrosine kinase inhibitor imatinib has been shown to correlate to an increased nuclear localization of ß-catenin (454, 458, 500). Inhibitors targeting the Wnt pathway have been shown to be of advantage for example in long-term cell cultures (500). Additionally, the hedgehog pathway has been suggested to be involved in chemotherapeutic resistance in CML, which is also characteristic for chronic phase CML cells (47). Mouse studies also indicate the involvement of the hedgehog pathway (46, 47), which has been implicated as a therapeutic biomarker for CML (456, 461).\nTo summarize, CSCs at tumor initiation originate from either differentiated cells or adult tissue resident stem cells (5, 19, 22). Several data indicate that the origin strongly correlates to the aggressiveness of the tumor. Therefore, extra- and intracellular biomarkers that characterize CSCs have been identified and implemented to be of diagnostic and prognostic advantage. However, stem cells are subject to a high degree of plasticity modulated by the TME (19), that is significantly changed by chemo- and radiotherapies and composed of several different cell types. In the following section, focus will be laying on senescent tumor cells as part of the TME as they have long-term influence on TME and CSC development and progression."}