Given a passage, 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]: Large concentrations of meperidine inhibit N-methyl-D-aspartate-(NMDA) receptor channels by channel block mechanisms. Extracellular pH regulates the activity and drug sensitivity of NMDA-receptor channels. We examined the influence of extracellular pH on sensitivity to meperidine of epsilon/zeta heteromeric NMDA-receptor channels expressed in Xenopus oocytes. Inhibition of epsilon1/zeta1, epsilon2/zeta1, epsilon3/zeta1, and epsilon4/zeta1 channels by meperidine was dependent on pH, with more inhibition at acidic pH and less inhibition at alkaline pH. The degree of voltage-dependence of meperidine block was only slightly affected by changes in pH, whereas affinity for meperidine was greatly reduced at alkaline pH. Furthermore, interaction of meperidine with Mg(2+) block was reduced at alkaline pH. Because the percentage of the protonated form of meperidine is only slightly affected by pH, changes in properties of the meperidine binding site may be involved in mechanisms of alteration of meperidine potency by pH.
[A]: Is n-methyl-D-aspartate receptor channel block by meperidine dependent on extracellular pH?

[Q]: In patients presenting with a breast lesion, when initial core biopsy histology falls into the category of "uncertain malignant potential" (i.e. a B3 lesion), the next line of investigation has traditionally been a surgical biopsy (SBx). Vacuum-assisted biopsy (VAB) may be a viable minimally invasive alternative to SBx for B3 lesions. The primary aims of this study were to establish whether VAB reduces the need for surgical biopsy and determine VAB sensitivity for carcinoma following initial B3 histology.', 'B3 lesion data was collected from 2004 to 2013 retrospectively, from a single institution that utilises both VAB and SBx.', 'A total of 413 lesions were categorised B3 on initial biopsy. Mean age was 61 years (range: 24-91 years). Mean follow up was 52 months (range: 19-60 months). 156 patients (38%) underwent VAB. Only 20% of patients underwent VAB in 2004, with an increase to 95% by 2013. VAB histology revealed twelve carcinomas, all of which progressed to surgical excision. In six cases, a SBx was required following VAB in order to provide further diagnostic information. In one case, carcinoma was missed on VAB.
[A]: Is vacuum-assisted biopsy a viable alternative to surgical biopsy in the investigation of breast lesions of uncertain malignant potential?

[Q]: Local invasion is a common pattern of spread in uterine cervical squamous cell carcinoma (CSCC). Although transforming growth factor-beta (TGF-) facilitates invasion of various types of cancer cells, the role of the TGF- pathway in CSCC is unclear. In this study, we analyzed the role of TGF- signaling in the progression of CSCC.', 'Immunohistochemistry was used to examine the expression of TGF- pathway molecules in 67 CSCC samples with clinicopathological data. Activation of the TGF- pathway was investigated following co-culture of CSCC cells and cervical cancer-associated fibroblasts (CCAFs).', 'Clinicopathological analysis of CSCC samples revealed that prominent expression of TGF- receptor-2 was more frequent in CSCC with lymphovascular space invasion (LVSI) than without LVSI (p < 0.01). Lymph node metastasis was more frequent in cases in which phosphorylated SMAD3 (pSMAD3) was localized exclusively at the boundary of tumor clusters (n = 9, p < 0.05). Recombinant TGF-1 increased pSMAD3 expression and enhanced cellular invasion (p < 0.005) in CSCC cells, which was attenuated by an inhibitor of the TGF- receptor (p < 0.005). Enhanced pSMAD3 expression and invasion was also observed when conditioned media from CSCC cells co-cultured with CCAFs were administered. Luciferase assays showed that this medium contained a large amount of active TGF-. Along with TGF- activation, thrombospondin-1 was upregulated in both CSCC cells and CCAFs, while thrombospondin-1 silencing in either CSCC cells or CCAFs repressed the activity of TGF-. Thrombospondin-1 was prominently expressed in cases with pSMAD3 boundary staining (p < 0.05).
[A]:
Is invasion of uterine cervical squamous cell carcinoma cells facilitated by locoregional interaction with cancer-associated fibroblasts via activating transforming growth factor-beta?