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.
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Question: Context: To explore the role of SCF/c-Kit signaling in the invasion of bladder cancer T24 cells.', 'Western blotting was used to detect the expression of c-Kit and PI3K pathway activation stimulated by stem cell factor (SCF) in T24 cells. The invasiveness of T24 cells before and after SCF stimulation and Wortmannin (aspecific PI3K inhibitor) treatment was evaluated using Transwell invasion assay (direct and indirect counting methods).', 'T24 cells expressed c-Kit protein and showed obvious Akt phosphorylation after stimulation with SCF (1 ng/ml) for 24 h. Compared to the control group, SCF stimulation (1 ng/ml) caused a greater number of T24 cells to migrate through the polycarbonate film (P<0.01), and this effect was blocked by the application of Wortmannin before the stimulation.
Answer: SCF/c-Kit signaling promotes the invasiveness of T24 cells, and this effect is mediated by the PI3K pathway.

Answer: Does [ SCF/c-Kit signaling promote invasion of T24 cells via PI3K pathway ]?


Question: 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.

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


Question: Context: This study characterizes ovariectomized (OVX)-induced osteoporotic fracture healing with focus on estrogen receptors (ERs). Callus formation plays a critical role in fracture healing, and ERs are well-known mechanosensors in osteogenic pathways. It was hypothesized that callus formation was related to and partially determined by the difference in expression patterns of ERs in both normal and OVX-induced osteoporotic fractures.', 'Closed femoral fracture in SHAM and ovariectomized rats were used in this study. Weekly callus width (CW) and area (CA), endpoint mechanical properties, gene expressions of Col-1, BMP-2, ER-α, ER-β and ER-α:ER-β ratios (ER-ratios), and correlations were assessed at 2, 4 and 8 weeks post-fracture.', 'CW and CA results confirmed that OVX-induced osteoporotic fracture was delayed at 2-4 weeks with impaired endpoint mechanical properties. Gene expressions of ER-α and ER-β were higher in the SHAM group at week 2 (p < 0.05) and later lowered at week 8; whereas the OVX group showed an opposing trend. Moderate correlation existed between ER-α and BMP-2 (0.545, p = 0.003), and ER-ratio and BMP-2 (0.601, p = 0.001), and BMP-2 to CW and CA (r = 0.709, p = 0.000 and r = 0.588, p = 0.001, respectively). ER-α and ER-β proteins expressions were confirmed by immunohistochemistry at the fracture callus in reparative progenitor cells, osteoblasts- and osteoclasts-like cells.
Answer: We conclude that the delayed healing rate and impaired callus quality in OVX-induced osteoporotic fracture is related to the delayed expression of ERs. A high ER-α:ER-β ratio favors callus formation.

Answer:
Is callus formation related to the expression ratios of estrogen receptors-alpha and -beta in ovariectomy-induced osteoporotic fracture healing?