TASK DEFINITION: Given a passage with a context and an answer, 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: Context: The authors previously described the complete regression of established neuroblastoma (NB) by the adoptive transfer of syngeneic interleukin-12 transduced dendritic cells (DC) from naive mice. However, some malignancies, like NB, abrogate DC immunostimulation. The authors hypothesize that IL-12 transduction of DC from NB-bearing mice will have the same antitumor properties.', 'A/J mice (n = 32) with established NB received peritumoral injection of 1 x 10(6) DC (DC, IL-12 DC, day 7 IL-12 DC or day 14 IL-12 DC) on day 7. Tumor growth, phenotype, and ability to induce NK and T cell activity were measured.', 'Vaccination with naive admIL-12 DC resulted in 100% tumor regression and prolonged survival. Transduced DC induced only partial responses in 75% (day 7) and 25% (day 14) of animals. No differences in phenotype or effector cell activation were noted between admIL-12DC in tumor-bearing or naive mice.
Answer: IL-12 DC from tumor-bearing animals have a decreased ability to induce antitumor activity against established murine NB. This decreased capacity appears to be related to the duration of exposure to tumor because day 14 transduced DC had less of an effect than day 7 DC, despite similar phenotypes and ability to activate immune effector cells.

SOLUTION: Does advanced neuroblastoma impair dendritic cell function in adoptive immunotherapy?

PROBLEM: Context: Preterm delivery and sub-optimal fetal growth are associated with each other and affect both mother and infant. Our aim was to determine (i) whether there are detectable differences in DNA methylation between early and late gestation and (ii) whether changes in DNA methylation from entry are associated with spontaneous preterm delivery with and without reduced fetal growth.', 'We conducted a case-control study nested within a large prospective cohort. Gene specific methylation was measured by Methyl-Profiler PCR Array in a Human Breast Cancer Signature Panel of 24 genes from maternal peripheral leukocytes genomic DNA at entry and 3', 'There was significantly decrease in DNA methylation in 15 of 24 genes during the 3
Answer: These data suggest that epigenetic modification is associated with an increased risk of spontaneous preterm delivery, spontaneous preterm delivery with reduced fetal growth in particular.

SOLUTION: Is spontaneous Preterm Delivery , Particularly with Reduced Fetal Growth , Associated with DNA Hypomethylation of Tumor Related Genes?

PROBLEM: Context: During short-term hypoxia, Hypoxia Inducible Factors (particular their subunits HIF-1α and HIF-2α) regulate the expression of many genes including the potent angiogenesis stimulator VEGF. However, in some pathological conditions chronic hypoxia occurs and is accompanied by reduced angiogenesis.', 'We investigated the effect of prolonged hypoxia on the proliferation and sprouting ability of human microvascular endothelial cells and the involvement of the HIFs and Dll4/Notch signaling.', 'Human microvascular endothelial cells (hMVECs), cultured at 20% oxygen for 14 days and seeded on top of 3D fibrin matrices, formed sprouts when stimulated with VEGF-A/TNFα. In contrast, hMVECs precultured at 1% oxygen for 14 days were viable and proliferative, but did not form sprouts into fibrin upon VEGF-A/TNFα stimulation at 1% oxygen. Silencing of HIF-2α with si-RNA partially restored the inhibition of endothelial sprouting, whereas HIF-1α or HIF-3α by si-RNA had no effect. No involvement of Dll4/Notch pathway in the inhibitory effect on endothelial sprouting by prolonged hypoxia was found. In addition, hypoxia decreased the production of urokinase-type plasminogen activator (uPA), needed for migration and invasion, without a significant effect on its inhibitor PAI-1. This was independent of HIF-2α, as si-HIF-2α did not counteract uPA reduction.
Answer: Prolonged culturing of hMVECs at 1% oxygen inhibited endothelial sprouting into fibrin. Two independent mechanisms contribute. Silencing of HIF-2α with si-RNA partially restored the inhibition of endothelial sprouting pointing to a HIF-2α-dependent mechanism. In addition, reduction of uPA contributed to reduced endothelial tube formation in a fibrin matrix during prolonged hypoxia.

SOLUTION:
Does hIF-2α Expression regulate Sprout Formation into 3D Fibrin Matrices in Prolonged Hypoxia in Human Microvascular Endothelial Cells?