http://rdf.ncbi.nlm.nih.gov/pubchem/patent/US-2021023107-A1
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_afdb934a233081ca4d6ed3d1b0702a80 http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_d21cbff64022f95c237c0bd3ec8656ca http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_4d5de9a1dac6b033c4643bb236ef4df3 |
| classificationCPCAdditional | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K45-06 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P35-04 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P35-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-708 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K45-06 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-708 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61P35-00 |
| filingDate | 2019-03-22-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_e3d8ac068068f8ee613a41de6907839e http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_dcaa9e2ec9584e76e088a227d7e02964 |
| publicationDate | 2021-01-28-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | US-2021023107-A1 |
| titleOfInvention | USE OF 6-THIO-dG TO TREAT THERAPY-RESISTANT TELOMERASEPOSITIVE PEDIATRIC BRAIN TUMORS |
| abstract | Brain tumors remain the leading cause of cancer-related deaths in children and often are associated with long-term sequelae among survivors of current therapies. Telomerase and telomeres play important roles in cancer, representing attractive therapeutic targets to treat children with poor-prognosis brain tumors such as diffuse intrinsic pontine glioma (DIPG), high-grade glioma (HGG) and high-risk medulloblastoma (MB). It has shown that DIPG, HGG and MB frequently express telomerase activity. It is now shown that the telomerase-dependent incorporation of 6-thio-2′deoxyguanosine (6-thio-dG), a telomerase substrate precursor analog, into telomeres leads to telomere dysfunction-induced foci (TIFs) along with extensive genomic DNA damage, cell growth inhibition and cell death of primary stem-like cells derived from patients with DIPG, HGG and MB. Importantly, the effect of 6-thio-dG is persistent even after drug withdrawal. Treatment with 6-thio-dG elicits a sequential activation of ATR and ATM pathways and induces G2/M arrest. In vivo, treatment of mice bearing MB xenografts with 6-thio-dG delays tumor growth, increases in-tumor TIFs and apoptosis. Furthermore, 6-thio-dG crosses the blood-brain barrier and specifically targets tumor cells in an orthotopic mouse model of DIPG. Together, these findings suggest that 6-thio-dG is a promising approach to treat therapy-resistant telomerase-positive pediatric brain tumors. |
| priorityDate | 2018-03-22-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
Incoming Links
Total number of triples: 571.