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.

Acute promyelocytic leukemia (APL) is a sub-type of acute myeloid leukemia (AML) characterized by a block of myeloid differentiation at the promyelocytic stage and the predominant t(15:17) chromosomal translocation. We have previously determined that cells from APL patients show increased expression of genes regulated by hypoxia-inducible transcription factors (HIFs) compared to normal promyelocytes. HIFs regulate crucial aspects of solid tumor progression and are currently being implicated in leukemogenesis.', "To investigate the contribution of hypoxia-related signaling in APL compared to other AML sub-types, we reverse engineered a transcriptional network from gene expression profiles of AML patients' samples, starting from a list of direct target genes of HIF-1. A HIF-1-dependent subnetwork of genes specifically dysregulated in APL was derived from the comparison between APL and other AMLs.", 'Interestingly, this subnetwork shows a unique involvement of genes related to extracellular matrix interaction and cell migration, with decreased expression of genes involved in cell adhesion and increased expression of genes implicated in motility and invasion, thus unveiling the presence of characteristics of epithelial-mesenchymal transition (EMT). We observed that the genes of this subnetwork, whose dysregulation shows a peculiar pattern across different AML sub-types, distinguish malignant from normal promyelocytes, thus ruling out dependence on a myeloid developmental stage. Also, expression of these genes is reversed upon treatment of APL-derived NB4 cells with all-trans retinoic acid and cell differentiation.
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We aimed to investigate structural abnormalities in first-episode remitted geriatric depression (RGD) with optimized voxel-based morphometry (VBM) in closely matched patients and healthy control subjects and examine the relationship of performances on neuropsychological tests with regional gray matter volumes.', 'Nineteen subjects with first-episode RGD and 16 well-matched healthy control subjects were recruited for this study, and neuropsychological tests and magnetic resonance imaging were conducted on the subjects. The differences in regional gray matter volume were determined between these two groups by optimized VBM.', 'The volumes of right superior frontal cortex, left postcentral cortex, and right middle temporal gyrus were significantly smaller in patients with RGD relative to healthy control subjects. However, patients with RGD had larger left cingulate gyrus volume compared with healthy control subjects. There was a significant negative correlation between left cingulate gyrus volume and Rey Auditory Verbal Learning Test delayed recall raw score in patients with RGD.
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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 α 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.

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