Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
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Question: A transgenic mouse model has revealed parameters of the angiogenic switch during multistep tumorigenesis of pancreatic islets, and demonstrated efficacy of antiangiogenic therapies. Pericytes have been revealed as functionally important for tumor neovasculature, using kinase inhibitors targeting their platelet-derived growth factor receptors (PDGFRs). Additionally, vascular endothelial growth factor receptor (VEGFR) inhibitors and metronomic chemotherapy show modest benefit against early- but not late-stage disease.', 'Seeking to improve efficacy against otherwise intractable end-stage pancreatic islet tumors, two receptor tyrosine kinase inhibitors, imatinib and SU11248, were used to disrupt PDGFR-mediated pericyte support of tumor endothelial cells in concert with maximum-tolerated dose (MTD) or metronomic chemotherapy and/or VEGFR inhibition.', 'Imatinib, despite equivocal efficacy as monotherapy, reduced pericyte coverage of tumor vessels and enhanced efficacy in combination with metronomic chemotherapy or VEGFR inhibition. A regimen involving all three was even better. MTD using cyclophosphamide caused transitory regression, but then rapid regrowth, in contrast to metronomic cyclophosphamide plus imatinib, which produced stable disease. The MTD regimen elicited apoptosis of tumor cells but not endothelial cells, whereas the other regimens increased endothelial cell apoptosis concordant with efficacy. A "chemo-switch" protocol, involving sequential MTD and then metronomic chemotherapy, overlaid with multitargeted inhibition of PDGFR and VEGFR, gave complete responses and unprecedented survival advantage in this model.

Answer: Is a multitargeted , metronomic , and maximum-tolerated dose '' chemo-switch '' regimen antiangiogenic , producing objective responses and survival benefit in a mouse model of cancer?

Question: Diastolic runoff in the abdominal aorta, with subsequent circulatory mesenteric insufficiency, has been postulated as a cause of necrotizing enterocolitis in term infants with congenital heart disease. With this study we sought to determine whether Doppler-flow characteristics in the abdominal aorta can predict which infants are at specific risk, independent of gestational age and type of congenital heart disease.', 'We conducted a case-control study of term infants with congenital heart disease and proven necrotizing enterocolitis (n = 18) compared with gestational age-matched and diagnosis-matched control subjects (n = 20). Abdominal aortic Doppler velocities, time intervals, and reversals were analyzed. Groups were compared, and independent risk factors for necrotizing enterocolitis were determined.', 'The groups were similar with regard to weight, pulse pressure, use of prostaglandins or inotropes, presence of a patent ductus arteriosus, and systolic function. However, 47% of the case subjects with necrotizing enterocolitis had persistent retrograde diastolic flow in the abdominal aorta compared with 15% of the control subjects. When adjusting for multiple risk factors, persistent diastolic flow reversal remained the only factor significantly associated with necrotizing enterocolitis.

Answer: Is persistent diastolic flow reversal in abdominal aortic Doppler-flow profiles associated with an increased risk of necrotizing enterocolitis in term infants with congenital heart disease?

Question: Leucine-rich-alpha-2-glycoprotein 1 (LRG1) has been reported to be involved in several tumors, whether it participates in colorectal cancer (CRC) progression remains unclear. Here, we investigated the biological function and underlying molecular mechanisms of LRG1 in CRC.', 'The mRNA and protein levels of LRG1 were assessed in CRC tissues through RT-PCR and immunohistochemistry, respectively. HCT116 and SW480 cells were treated with LRG1 siRNA, control siRNA, or recombinant LRG1. Transwell invasion assays and wound healing assays were performed to evaluate the invasion and migration of CRC cells. Epithelial-to-mesenchymal transition (EMT) markers of E-cadherin, VDR, N-cadherin, -SMA, Vimentin and Twist1 were detected by RT-PCR and western blot. Enzyme-linked immunosorbent assay was used to measure the secretion level of VEGF-A. Conditioned medium from CRC cells was collected for endothelial cell migration, tube formation and aortic ring sprouting assays.', 'LRG1 was overexpressed in CRC tissues and associated with cancer aggressiveness. LRG1 was further found to induce the EMT process, as well as CRC cell migration and invasion capacity. In addition, LRG1 promoted VEGF-A expression in CRC cells and contributed to tumor angiogenesis. Furthermore, HIF-1 could be induced by LRG1 in a concentration- and time-dependent manner, which was responsible for LRG1-induced VEGF-A expression and EMT.

Answer:
Does lRG1 modulate epithelial-mesenchymal transition and angiogenesis in colorectal cancer via HIF-1 activation?