UNASSIGNED: As uncontrolled cell proliferation requires @entity4334 biosynthesis, inhibiting enzymes that mediate @entity4334 biosynthesis constitutes a rational approach to the management of oncological diseases. In practice, however, results of this strategy are mixed and thus elucidation of the mechanisms by which @entity5 cells evade the effect of @entity4334 biosynthesis restriction is urgently needed. Here we explored the notion that intrinsic differences in @entity5 cell cycle velocity are important in the resistance towards inhibition of @entity15129 dehydrogenase (IMPDH) by @entity3442 ( @entity3443 ). In short-term experiments, @entity3443 treatment of fast-growing @entity5 cells effectively elicited G0/G1 arrest and provoked apoptosis thus inhibiting cell proliferation and colony formation. Forced expression of a mutated @entity21940 , lacking a binding site for @entity3443 but retaining enzymatic activity, resulted in complete resistance of @entity5 cells to @entity3443 . In @entity19 subcutaneously engrafted with HeLa cells, @entity3443 moderately delayed @entity5 formation by inhibiting cell proliferation and inducing apoptosis. Importantly, we developed a lentiviral vector-based Tet-on label-retaining system that enables to identify, isolate and functionally characterize slow-cycling or so-called label-retaining cells (LRCs) in vitro and in vivo. We surprisingly found the presence of LRCs in fast-growing @entity5 . LRCs were superior in colony formation, @entity5 initiation and resistance to @entity3443 as compared to fast-cycling cells. Thus, the slow-cycling compartment of @entity5 seems predominantly responsible for resistance to @entity3443 .

Differential Sensitivities of Fast- and Slow-cycling Cancer Cells to XXXX Dehydrogenase 2 Inhibition by @entity3442 .

@entity3442 :: ('MESH:D009173', 'Chemical') :: ['mycophenolic acid'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer', 'tumors'] @entity19 :: ('10090', 'Species') :: ['nude mice'] @entity3443 :: ('D015097', 'Chemical') :: ['MPA'] @entity21940 :: ('3615', 'Gene') :: ['IMPDH2'] @entity15129 :: ('MESH:D007291', 'Chemical') :: ['inosine monophosphate'] @entity4334 :: ('D009711', 'Chemical') :: ['nucleotide']
@entity15129 :: (MESH:D007291,Chemical) :: ['Inosine Monophosphate']
