TASK DEFINITION: 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.
PROBLEM: To determine the origin of the neoplastic cell in central nervous system (CNS) hemangioblastomas in von Hippel-Lindau disease (VHL) and its role in tumor formation and distribution, we characterized and differentiated neoplastic cells from hemangioblastomas removed from VHL patients.', 'A total of 31 CNS hemangioblastomas from 25 VHL patients were resected and analyzed. Tumor cells from the hemangioblastomas were characterized, grown, and differentiated into multiple lineages. Resected hemangioblastomas were located in the cerebellum (11 tumors), brainstem (five tumors), and spinal cord (15 tumors). Consistent with an embryologically derived hemangioblast, the neoplastic cells demonstrated coexpression of the mesodermal markers brachyury, Flk-1 (vascular endothelial growth factor-2), and stem cell leukemia (Scl). The neoplastic cells also expressed hematopoietic stem cell antigens and receptors including CD133, CD34, c-kit, Scl, erythropoietin, and erythropoietin receptor. Under specific microenvironments, neoplastic cells (hemangioblasts) were expanded and differentiated into erythrocytic, granulocytic, and endothelial progenitors. Deletion of the wild-type VHL allele in the hematopoietic and endothelial progeny confirmed their neoplastic origin.

SOLUTION: Are von Hippel-Lindau disease-associated hemangioblastomas derived from embryologic multipotent cells?

PROBLEM: Pituitary tumor-transforming gene (PTTG) is a multifunctional protein involved in several tumorigenic mechanisms, including angiogenesis. PTTG has been shown to promote angiogenesis, a key rate-limiting step in tumor progression, by up-regulation of fibroblast growth factor-2 and vascular endothelial growth factor.', 'To investigate whether PTTG regulates other angiogenic genes in thyroid cells, we performed angiogenesis-specific cDNA arrays after PTTG transfection. Two of the genes [inhibitor of DNA binding-3 (ID3) and thrombospondin-1 (TSP-1)] which showed differential expression in primary thyroid cells were validated in vitro and in vivo.', 'TSP-1 showed a 2.5-fold reduction and ID3 showed a 3.5-fold induction in expression in response to PTTG overexpression in vitro. Conversely, suppression of PTTG with small interfering RNA was associated with a 2-fold induction of TSP-1 and a 2.2-fold reduction in ID3 expression. When we examined TSP-1 and ID3 expression in 34 differentiated thyroid cancers, ID3 was significantly increased in tumors compared with normal thyroid tissue. Furthermore, ID3 expression was significantly higher in follicular thyroid tumors than in papillary tumors. Although mean TSP-1 expression was not altered in cancers compared with normal thyroids, we observed a significant independent association between TSP-1 expression and early tumor recurrence, with recurrent tumors demonstrating 4.2-fold lower TSP-1 expression than normal thyroid tissues.

SOLUTION: Does pituitary tumor-transforming gene regulate multiple downstream angiogenic genes in thyroid cancer?

PROBLEM: Intravenous oxygen infusions have been introduced in complementary medicine for treatment of atherosclerosis and inflammatory diseases. As atherosclerosis and inflammation are causally related to oxidative stress and as intravenous supply with oxygen causes oxidative stress, it was suggested that the clinical success of intravenous oxygen therapy is biochemically based on an enhancement of endogenous antioxidative mechanisms. The anti-atherogenic enzyme paraoxonase-1 (PON1) is is part of this system.', 'To evaluate the effect of repeated intravenous oxygen infusions on serum PON1 activity.', 'A total of 45 patients were treated with intravenous oxygen. During treatment oxygen dosage was increased from 15 to 50 ml (1-2 ml/min). Before treatments 1 and 10 blood was obtained for measurement of PON1 activities. From 20 patients blood was additionally obtained after 20 days of treatment and 2 weeks post treatment. Serum PON1 activity was measured spectrophotometrically using the synthetic substrates paraoxon, phenylacetate, and p-nitrophenyl-acetate.', 'Using the substrate paraoxon PON1 activity significantly increased by 38% above basal levels 24 hours after intravenous oxygen infusion 9 (p < 0.001). Adverse effects were not observed.

SOLUTION:
Does [ Intravenous oxygen therapy increase the activity of the antioxidative and antiatherogenic serum enzyme paraoxonase 1 ]?