UNASSIGNED: Cancer stem cells (CSCs) appear to explain many aspects of the neoplastic evolution of @entity5 and likely account for enhanced therapeutic resistance following treatment. Dysregulated Notch signaling, which affects CSCs plays an important role in @entity788 progression. We have determined the ability of @entity69141 to inhibit CSCs and the Notch signaling pathway. @entity69141 treatment resulted in significant inhibition of proliferation and colony formation in @entity788 cell lines, but not in normal pancreatic epithelial cells. Moreover, @entity69141 affected pancreatosphere formation. The compound also decreased the expression of CSC marker proteins @entity16252 , @entity3844 , @entity26720 and @entity27947 . In addition, flow cytometry studies demonstrated that @entity69141 reduced the number of @entity16252 + cells. Furthermore, levels of Notch 1-4 receptors, their ligands @entity5239 , @entity30732 , @entity13186 , @entity69142 , @entity5237 and the downstream target protein @entity10351 were reduced. The y-secretase complex proteins, @entity20933 , @entity69143 , @entity19035 , and @entity69144 , required for Notch activation also exhibited decreased expression. Ectopic expression of the Notch Intracellular Domain (NICD) partially rescued the cells from @entity69141 mediated growth suppression. To determine the effect of @entity69141 on @entity5 growth in vivo, @entity19 carrying @entity5 xenografts were administered @entity69141 intraperitoneally every day for 21 days. Treatment with the compound significantly inhibited @entity5 xenograft growth, coupled with significant reduction in the expression of CSC markers and Notch signaling proteins. Together, these data suggest that @entity69141 is a potent inhibitor of @entity788 that targets the stem cells by inhibiting Notch signaling proteins.

Quinomycin A targets Notch signaling pathway in XXXX stem cells.

@entity788 :: ('MESH:D010190', 'Disease') :: ['pancreatic cancer'] @entity20933 :: ('19164(Tax:10090)', 'Gene') :: ['Presenilin 1'] @entity69143 :: ('59287(Tax:10090)', 'Gene') :: ['Nicastrin'] @entity13186 :: ('13388(Tax:10090)', 'Gene') :: ['DLL1'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors'] @entity10351 :: ('15205(Tax:10090)', 'Gene') :: ['Hes-1'] @entity19 :: ('10090', 'Species') :: ['nude mice'] @entity69144 :: ('103979(Tax:10090)', 'Gene') :: ['APH-1'] @entity27947 :: ('17075(Tax:10090)', 'Gene') :: ['EPCAM'] @entity26720 :: ('12484(Tax:10090)', 'Gene') :: ['CD24'] @entity69142 :: ('13389(Tax:10090)', 'Gene') :: ['DLL3'] @entity16252 :: ('13175(Tax:10090)', 'Gene') :: ['DCLK1'] @entity5239 :: ('16449(Tax:10090)', 'Gene') :: ['Jagged1'] @entity30732 :: ('16450(Tax:10090)', 'Gene') :: ['Jagged2'] @entity69141 :: ('MESH:C010777', 'Chemical') :: ['Quinomycin'] @entity19035 :: ('66340(Tax:10090)', 'Gene') :: ['Pen2'] @entity3844 :: ('12505(Tax:10090)', 'Gene') :: ['CD44'] @entity5237 :: ('54485(Tax:10090)', 'Gene') :: ['DLL4']
@entity788 :: (MESH:D010190,Disease) :: ['pancreatic cancer']
