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.

[Q]: Context: We analyzed the involvement of thromboxane (TX) A2/prostaglandin (PG) H2 (TP) receptor in ischemia-induced neovascularization in mice.', 'Unilateral hindlimb ischemia was induced by right femoral artery ligature in male C57BL/6J mice (n=7 per group). Animals were then treated with or without TP receptor antagonist (S18886, 5 or 10 mg/kg per day; ramatroban, 10 mg/kg per day) or aspirin (30 mg/kg per day) in drinking water for 21 days. Hindlimb ischemia raised plasma level of TXB2, the stable metabolite of TXA2, by 4.7-fold. This increase was blocked by aspirin treatment whereas S18886 (5 or 10 mg/kg per day) had no effect. However, neither S 18886 nor aspirin affected postischemic neovascularization. We next assessed the putative involvement of TXA2 signaling in angiotensin II (Ang II) proangiogenic pathway. Ang II (0.3 mg/kg per day) enhanced TXB2 plasma levels by 2.6-fold over that of control (P<0.01). Ang II-induced TXB2 upregulation was reduced by cotreatment with Ang II type I receptor antagonist (candesartan, 20 mg/kg per day). Angiographic score, capillary number, and foot perfusion were improved by 1.7-, 1.7-, and 1.4-fold, respectively, in Ang II-treated mice compared with controls (P<0.05). Ang II proangiogenic effect was associated with a 1.6-fold increase in VEGF-A protein content (P<0.05) and a 1.4-fold increase in the number of Mac-3-positive cells (ie, macrophages) in ischemic areas (P<0.05). Interestingly, treatments with TP receptor antagonists or aspirin hampered the proangiogenic effects of Ang II.
Answer: Endogenous activation of TXA2 receptor by eicosanoids did not modulate spontaneous neovascularization in the setting of ischemia. Conversely, TXA2 signaling is involved in Ang II-induced AT1-dependent vessel growth.
[A]: Does thromboxane A2/prostaglandin H2 receptor activation mediate angiotensin II-induced postischemic neovascularization?


[Q]: Context: Biliary tract cancers (BTCs) are uncommon and are associated with a dismal prognosis. Combinations of gemcitabine and platinum chemotherapy (gemcitabine and platinum-based therapy [GP]) form the standard approach for treating advanced BTC. To characterize the spectrum of mutations and to identify potential biomarkers for a GP response in BTC, this study evaluated the genomic landscape and assessed whether mutations affecting DNA repair were associated with GP resistance.', 'Pretreatment, formalin-fixed, paraffin-embedded samples from 183 BTC patients treated with GP were analyzed. Cox regression models were used to determine the association between mutations, progression-free survival (PFS), and overall survival (OS).', 'When genes with an incidence\u2009>\u200910% were considered, no individual gene was independently predictive of a GP response. In patients with unresectable BTC who received GP as their first-line therapy, the joint status of cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein 53 (TP53), and AT-rich interaction domain 1A (ARID1A) was associated with PFS (P\u2009=\u2009.0004) and OS (P\u2009≤\u2009.0001). Patients with mutations in CDKN2A and TP53 were identified as a poor-prognosis cohort with a median PFS of 2.63 months and a median OS of 5.22 months. Patients with mutant ARID1A, regardless of the single-mutation status of TP53 or CDKN2A, had similar outcomes. A patient who exhibited mutations in all 3 genes had a median PFS of 20.37 months, and OS was not reached.
Answer: In the largest exploratory analysis of this kind for BTC, 3 prevalent, mutually exclusive mutations represent distinct patient cohorts. These mutations are prognostic and may represent a predictive biomarker for a GP response. Prospective studies to validate these findings are needed, and they should include the incorporation of therapies that exploit the genomic instability observed with these mutations in BTC. Cancer 2016;122:3657-66. © 2016 American Cancer Society.
[A]: Does next-generation sequencing survey of biliary tract cancer reveal the association between tumor somatic variants and chemotherapy resistance?


[Q]: Context: Patients with type 2 diabetes mellitus (T2DM) have a high risk of fracture although they have slightly higher bone mineral density (BMD). There is no evidence that dipeptidyl peptidase-4 (DPP-4) is involved in the bone fragility of the patients. The aim of this study was to investigate the association between serum DPP-4 levels and vertebral fractures (VFs) in men with T2DM.', 'We conducted a cross-sectional study and investigated the relationships between serum DPP-4 levels vs BMD at lumbar spine, femoral neck and radius, bone turnover markers and presence of VFs in 204 Japanese male patients.', 'Multiple regression analyses adjusted for confounders such as age, duration of diabetes, body mass index, serum creatinine, HbA1c, serum albumin, log(alanine transaminase), and log(C-reactive protein) showed that serum DPP-4 was positively associated with bone formation markers (bone-specific alkaline phosphatase and osteocalcin) as well as a bone resorption marker [tartrate-resistant acid phosphatase 5b (TRACP-5b)] (β = 0·25, P < 0·01; β = 0·17, P < 0·05; and β = 0·30, P < 0·01, respectively), but not BMD at each site. Multivariate logistic regression analyses adjusted for the confounders described above revealed that serum DPP-4 levels were associated with the presence of multiple VFs (odds ratio 1·61, 95% confidential interval 1·05-2·49 per SD increase, P < 0·05). This association was still significant after additional adjustment for any sites of BMD or bone turnover markers except for TRACP-5b.
Answer: We firstly showed that high level of serum DPP-4 is associated with prevalent multiple VFs independently of BMD and bone formation in men with T2DM.
[A]:
Is serum dipeptidyl peptidase-4 associated with multiple vertebral fractures in type 2 diabetes mellitus?