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: Most solid human tumors exist in an acidic microenvironment, due in part to inefficient vasculature and a higher intrinsic rate of glycolysis. This leads to a tumor-selective pH gradient, which can be exploited therapeutically with antitumor agents such as the camptothecins (CPTs). Previous work in this laboratory has shown that camptothecin activity is enhanced 40- to 60-fold in monolayer cell culture by reducing the extracellular pH to 6.8. Three-dimensional histoculture has been shown to be a technique that allows human tumor tissue to grow in an in vivo-like way with maintenance of tissue histology and function and drug sensitivity for long periods of time.', 'In the current study, we utilized these features of histoculture to study new analogues of camptothecin that have superior pharmacological properties.', 'We evaluated six CPT analogues in histocultures of human brain, neuroblastoma, breast, colon, and prostate tumors. Fragments were exposed to 10,11-methylenedioxy-CPT (MDC), 7-chloromethyl-MDC, SN-38, topotecan (TPT), 9-amino-CPT, 10-amino-CPT, paclitaxel, 5-fluorouracil, 4-hydroperoxycyclophosphamide and doxorubicin, and antitumor activity was assessed. For in vivo tumor outgrowth studies, fragments were treated in parallel, implanted into nude mice, and monitored for development of tumors. RESULTS. Against 15 of 16 tumor xenografts and all primary tumor samples tested, all compounds were cytotoxic at pH 7.4 (IC(50) range 13-921 microM). MDC, SN-38, TPT, and 9-amino-CPT achieved an average 5-fold increase in activity (range 3-14) at pH 6.8, while 7-chloromethyl-MDC was enhanced 8-fold (range 6-14). The most potentiated analogue was 10-amino-CPT at 27-fold (range 17-49). In contrast, the other agents were active against one or more tumor types but were not enhanced by acidic pH. Importantly, the toxicity of MDC in histoculture of D54 glioma xenografts strongly correlated with the outgrowth of treated fragments subsequently implanted in vivo.
Answer: Evaluation of anticancer drug activity in native-state histoculture supports the concept that pH modulation may be an important approach to improve the selectivity and antitumor effectiveness of camptothecin-based chemotherapy.
[A]: Is the activity of camptothecin analogues enhanced in histocultures of human tumors and human tumor xenografts by modulation of extracellular pH?


[Q]: Context: Barrett esophagus (BE) is considered precursor condition of esophageal adenocarcinoma. Its incidence and prevalence are increasing in general population. Studies reported that metabolic syndrome (MS) or diabetes mellitus (DM) is related to increased risk of BE. Current study was to assess and better understand the relationship between MS /DM and BE.', "Electronic search was conducted in the database Pubmed/Medline (-December, 2015), Embase (-December, 2015), Cochrane Library (-December, 2015), and Web of Knowledge (-December, 2015). Studies included were assessed with summary odds ratios (ORs) with 95% confidence intervals (CIs) and compared exposure group with control group. The heterogeneity was examined by the funnel plot and the Egger's test. Subgroup analyses and sensitive analyses were performed for the detection of possible heterogeneity and impact on stability of analysis results.", "Twelve publications met the criteria and included 355,311 subjects were analyzed. The pooled results showed MS was closely associated with increased risk of BE (OR\u200a=\u200a1.23; 95%CI 1.03-1.47; P\u200a=\u200a0.024), and yet DM did not significantly increase the risk of BE (OR\u200a=\u200a1.07; 95%CI 0.82-1.38; P\u200a=\u200a0.627). Substantial heterogeneities were detected. No significant publication bias was detected by Egger's test (P\u200a=\u200a0.23).
Answer: Based on the results of current meta-analysis, MS is associated with increased risk of BE. Further long-term follow-up prospective study needs to verify the current results, and definite pathophysiological mechanism needs to be further investigated and clearly elucidated.
[A]: Is metabolic syndrome associated with increased risk of Barrett esophagus : A meta-analysis?


[Q]: Context: To determine the nature and extent of undersupply and the economic consequences of oversupply of medication among non-adherent patients.', 'This study used copies of repeat prescriptions (= multiple dispensations), collected during 1 week in 2002 at 16 Swedish community pharmacies. For patients with a refill adherence below 80%, treatment gaps were defined as the number of days they had no drug available. The cost of drug oversupply (i.e., refill adherence > 120%) was calculated from the prices of the drug packages dispensed.', 'The number of collected repeat prescriptions was 3,636. The median of treatment gaps among patients with a refill adherence below 80% was 53 days per 90-100 days treatment period and the corresponding median for oversupply was 40 days. The cost of oversupply for exempt patients (i.e., patients who have paid 1,800 SEK (Euro 196; US$ 243) per year for medicines) was 32,000 SEK (Euro 3,500; US$ 4,300) higher than for non-exempt patients. An extrapolation to all Sweden indicates that exemption from charges leads to an additional oversupply of about 142 million SEK (Euro 15 million; US$ 19 million) per year above that of non-exempt patients.
Answer: Both undersupply and oversupply of prescribed medicines are common in Sweden. Patients with a refill adherence below 80% seem to have less than half of the prescribed treatment available. Oversupply or drug stockpiling occurs more frequently among exempt than among non-exempt patients, and this oversupply leads to high unnecessary costs.
[A]:
Does refill non-adherence to repeat prescriptions lead to treatment gaps or to high extra costs?