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.

Q: 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.

A: Is a multitargeted , metronomic , and maximum-tolerated dose '' chemo-switch '' regimen antiangiogenic , producing objective responses and survival benefit in a mouse model of cancer?
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Q: Endoscopic snare papillectomy (ESP) is a viable alternative to surgical treatment of ampullary adenomas and T1N0 stage ampullary carcinomas. The main drawback of this technique is the high risk of acute pancreatitis post procedure.The aim of this study was to assess the efficacy, safety, and long-term results of this procedure, and to determine whether routine pancreatic intubation facilitated by intraductal methylene blue (MB) injection reduces the risk for pancreatitis.', 'Between 2004 and 2011, 56 consecutive patients underwent ESP. Before resection, the pancreatic duct was cannulated, and MB was injected intraductally to facilitate stent placement after ampullectomy.', 'ESP was performed en bloc in 45 patients with histological findings of low-grade dysplasia (39%), high-grade dysplasia (25%), carcinoma (32.5%), and others (3.5%). The morbidity rate was 19.5%: acute pancreatitis (n=6), bleeding (n=4), perforation (n=1), and sepsis (n=1). Pancreatic intubation was performed in 89% of the patients. Postprocedure pancreatitis occurred significantly less in the patients with a pancreatic stent than in those without: 3/49 versus 3/6, P=0.013. ESP was considered as curative in 39 patients (75%). Of the 12 recurrences (25%), 10 were managed endoscopically, but with higher morbidity (acute pancreatitis=40%).

A: Does pancreatic intubation facilitated by methylene blue injection decrease the risk for postpapillectomy acute pancreatitis?
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Q: Thermal angioplasty methods heat the arterial wall. We related platelet adhesion to the temperature to which subendothelium and purified adhesive proteins had been exposed.', 'Cultured subendothelium, purified von Willebrand factor, collagen types I and III, or fibronectin was applied to glass coverslips. Coverslips were mounted on a heating device that applied a temperature gradient from 30 to 100 degrees C. De-endothelialized umbilical arteries were heated by immersion in phosphate-buffered saline. After cooling to room temperature, the surfaces were perfused with blood at 37 degrees C (shear rate, 1600 sec-1). Compared with 37 degrees C, platelet adhesion to endothelial cell matrix was significantly reduced by 25%, 50% or 75% after heating to 69 +/- 1 degree C (mean +/- SEM, P < .05), 72 +/- 1 degree C, or 75 +/- 1 degree C, respectively. Platelet coverage to umbilical artery subendothelium was in the same way significantly reduced after heating to 71 +/- 1 degree C, or 77 +/- 1 degree C, respectively. In contrast to endothelial cell matrix, however, heating to about 55 degrees C increased platelet coverage from 30 +/- 5% to 54 +/- 6% (P < .05). Both platelet adhesion to von Willebrand factor and monoclonal antibody binding against the GpIb binding site of von Willebrand factor showed a comparable temperature dependence as platelet adhesion to subendothelium, provided the proper von Willebrand factor concentration was used. Platelet adhesion to heated collagen types I and III was increased and maximal at 57 +/- 2 degrees C and 62 +/- 2 degrees C, respectively. Preincubation of collagen III with proteins resulted in decreased platelet adhesion with increasing temperatures. Heating did not affect the reactivity of fibronectin.

A:
Is both increased and decreased platelet adhesion to thermally injured subendothelium caused by denaturation of von Willebrand factor?
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