instruction:
Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.
question:
FoxO transcription factors have been reported to play pivotal roles in tumorigenesis and drug resistance. The mechanisms underlying the tumor suppression function of FoxOs in human cancers remain largely unknown. Aberrant expression and activation of Nrf2 often correlate with chemoresistance and poor prognosis. Here, we report that FoxO3 directs the basal transcription of Kelch-like ECH-associated protein 1 (Keap1), an adaptor protein that bridges Nrf2 to Cul3 for degradation. FoxO3 depletion resulted in Keap1 down-regulation, thereby activating Nrf2 signaling. We further demonstrated that inhibition of the FoxO3-Keap1 axis accounts for Nrf2 induction and activation induced by constitutively active AKT signaling or tumor necrosis factor treatment. Unlike previous findings, FoxO3 silencing led to decreased reactive oxygen species production, therefore protecting cells from oxidative stress-induced killing in an Nrf2-dependent manner. Importantly, FoxO3 deficiency strongly potentiated tumor formation in nude mice and rendered cholangiocarcinoma xenografts resistant to cisplatin-induced cell death by activating Nrf2. Additionally, we found that clinical cholangiocarcinoma samples displayed FoxO3-Keap1 down-regulation and Nrf2 hyperactivation, underscoring the essential roles of these proteins in cholangiocarcinoma development.
answer:
0

question:
Previous research in fetuses with increased nuchal translucency (NT) showed abnormal lymphatic endothelial differentiation characteristics, including increased vascular endothelial growth factor (VEGF)-A expression, and aberrant smooth muscle cells (SMCs) surrounding enlarged jugular lymphatic sacs (JLS). We hypothesized that abnormal Sonic hedgehog (Shh) expression would result in altered VEGF-A signaling in the lymphatic endothelial cells of the JLS and that aberrant acquisition of SMCs could be caused by downregulation of forkhead transcription factor FOXC2 and upregulation of platelet-derived growth factor (PDGF)-B in the lymphatic endothelial cells of the JLS.', 'Five trisomy 21 fetuses and four controls were investigated using immunohistochemistry for Shh, VEGF-A, FOXC2 and PDGF-B expression in the lymphatic endothelial cells of the JLS.', 'An increased Shh, VEGF-A and PDGF-B expression, and decreased FOXC2 expression were shown in the lymphatic endothelial cells of the JLS of the trisomic fetuses.
answer:
1

question:
BTX-A is the standard treatment for glabellar furrows. However, some individuals have resting glabellar rhytides that are sufficiently deep that they respond poorly to BTX-A alone.', 'To compare the efficacy of BTX-A combined with intradermal Hylan B with the efficacy of BTX-A alone in individuals with moderate to severe glabellar rhytides.', 'This was a retrospective study of 16 subjects with moderate to severe glabellar rhytides. Their response to Hylan B plus BTX-A was compared clinically and photographically to their response to BTX-A alone.', 'All subjects had moderate or severe glabellar rhytides at rest before treatment. After BTX-A alone, none (0%) had achieved no or mild rhytides. After BTX-A and Hylan B injection, only 1 of 16 (6%) had moderate glabellar rhytides, with the remainder (94%) being mild.
answer:
1