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.

Input: Consider Input: 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.

Output: Is the activity of camptothecin analogues enhanced in histocultures of human tumors and human tumor xenografts by modulation of extracellular pH?


Input: Consider Input: Context: Therapeutic angiogenesis is a promising strategy for treating ischemia. Our previous work showed that endogenous endothelial tissue factor (TF) expression induces intracrine signaling and switches-on angiogenesis in microvascular endothelial cells (mECs). We have hypothesized that activated mECs could exert a further paracrine regulation through the release of TF-rich microvascular endothelial microparticles (mEMPs) and induce neovascularization of ischemic tissues.', 'Here, we describe for the first time that activated mECs are able to induce reparative neovascularization in ischemic zones by releasing TF-rich microparticles. We show in vitro and in vivo that mEMPs released by both wild-type and TF-upregulated-mECs induce angiogenesis and collateral vessel formation, whereas TF-poor mEMPs derived from TF-silenced mECs are not able to trigger angiogenesis. Isolated TF-bearing mEMPs delivered to nonperfused adductor muscles in a murine hindlimb ischemia model enhance collateral flow and capillary formation evidenced by MRI. TF-bearing mEMPs increase angiogenesis operating via paracrine regulation of neighboring endothelial cells, signaling through the β1-integrin pathway Rac1-ERK1/2-ETS1 and triggering CCL2 (chemokine [C-C motif] ligand 2) production to form new and competent mature neovessels.
Answer: These findings demonstrate that TF-rich mEMPs released by microvascular endothelial cells can overcome the consequences of arterial occlusion and tissue ischemia by promoting postischemic neovascularization and tissue reperfusion.

Output: Do angiogenic microvascular endothelial cells release microparticles rich in tissue factor that promotes postischemic collateral vessel formation?


Input: Consider Input: Context: This large cross-sectional, multi-centre study evaluated the association of body composition measurements by a novel dual frequency bioimpedance device (BIA-ACC) with chronic stress/inflammation biomarkers and the presence of medically unexplained symptoms (MUS).', 'Participants were adult Caucasians of both sexes and included 10,416 lean subjects with no MUS (Group A), 58,710 lean subjects with MUS (Group B) and 30,445 overweight/obese subjects with no MUS and excessive fat mass (FM) (Group C).', 'Total body extracellular water (ECW) was higher, while intracellular water (ICW) was lower in Group B than both other groups (P < 0.01). Group A had significantly lower FM and higher skeletal mass (SK) and phase angle (PA) than Group B and lower circulating high sensitivity (hs) CRP levels than both other groups. hsCRP was higher in Group C than Group A though (P < 0.01). Salivary cortisol in Group B was lower in the morning and higher in the evening than both other groups (P < 0.001), indicating circadian rhythm obliteration or reversal in this group. ECW correlated positively with serum hsCRP and 8 p.m. salivary cortisol, but negatively with 8 a.m. salivary cortisol, while PA correlated positively with 8 a.m. and negatively with 8 p.m. salivary cortisol and serum hsCRP. Both 8 a.m. and 8 p.m. salivary cortisol and serum hsCRP were associated with the presence of MUS and BIA-ACC measurements, including ECW, ICW, FM, SK and PA.
Answer: MUS is an index of chronic stress and inflammation and BIA-ACC may provide a useful, bloodless and rapid tool in the clinical setting, distinguishing patients with chronic stress/inflammation from healthy subjects and monitoring their response to treatment.


Output: Are stress and inflammatory biomarkers and symptoms associated with bioimpedance measures?