Nā huahana

Ma luna o 70% o nā gliomas haʻahaʻa haʻahaʻa e lawe i kahi hoʻololi R132H heterozygous i ka gene coding no isocitrate dehydrogenase 1 (IDH1).Hāʻawi kēia i ka enzyme me ka mana hou e hoʻololi i ka α-ketoglutarate i 2-hydroxyglutarate, e alakaʻi ana i ka tumorigenesis.ʻO ke kumu nui o ka hana 2-hydroxyglutarate he glutamine, ʻo ia hoʻi, i ka maʻi kanesa, he kumu no ka tricarboxylic acid cycle (TCA) anaplerosis.ʻO kahi kumu ʻē aʻe o ka anaplerosis he pyruvate flux ma o pyruvate carboxylase (PC), he ala maʻamau i nā astrocytes maʻamau.ʻO ka pahuhopu o kēia noiʻi ʻana ʻo ia ka hoʻoholo inā lawelawe ʻo PC ma ke kumu o TCA anaplerosis i loko o nā pūnaewele mutant IDH1 kahi i hoʻohana ʻia ai ka glutamine no ka hana 2-hydroxyglutarate.Ua hoʻoholo ʻia ke kahe o ka pyruvate ma o PC a ma o ka pyruvate dehydrogenase (PDH) ma o ka hoʻohana ʻana i ka spectroscopy resonance magnetic e ʻimi i ka lepili o [2-¹³C] glucose i loaʻa i ka ¹³C-labe alakaʻi i ka glutamate a me ka glutamine.Ua hoʻohana ʻia nā hoʻāʻo hana, RT-PCR a me ke komohana blotting e ʻimi i ka ʻōlelo a me ka hana o nā enzyme pili.Ua kālailai ʻia ka ʻikepili Cancer Genome Atlas (TCGA) no ka loiloi ʻana i ka hōʻike ʻana o nā enzymes i loko o nā ʻano glioma kanaka.Ua pili kēia me ka piʻi nui ʻana o ka hana PC a me ka ʻōlelo.I ka manawa like, ua emi nui ka hana PDH, ua hoʻopili ʻia paha e ka nui o ka inhibitory PDH phosphorylation e PDH kinase 3. E like me ka nānā ʻana i loko o nā pūnaewele, hōʻike ʻia ka ʻikepili o TCGA i ka piʻi nui ʻana o ka ʻōlelo PC ma ka mutant IDH-expressing human glioma samples like me wild- ʻano IDH. ʻO kā mākou mau ʻike e hōʻike ana he mea nui paha ka hoʻololi ʻana i ka PC a me ka PDH i ka hoʻololi ʻana o ke kelepona i ka mutation IDH1 a hiki ke lilo i mau pahuhopu therapeutic kūpono.