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.

Input: Consider Input: Formation of branching tubes is a fundamental step in the development of glandular organs. To identify extracellular cues that orchestrate epithelial tubulogenesis, we employed an in vitro assay in which EpH4-J3B1A mammary epithelial cells form spheroidal cysts when grown in collagen gels under serum-free conditions, but form branching tubules in the presence of fetal calf serum (FCS).', 'Initial experiments showed that the tubulogenesis-inducing activity of FCS was markedly increased by heating (70 degrees C) or transient acidification to pH3. We therefore hypothesized that the tubulogenic agent was transforming growth factor-beta (TGF-beta), a cytokine that is present in serum in latent form and can be activated by heat or acid treatment. We found indeed that the tubulogenic activity of acidified FCS is abrogated by addition of either SB-431542, a selective inhibitor of the TGF-beta type I receptor, or a neutralizing antibody to TGF-beta-1. On the other hand, addition of low concentrations (20-100 pg/ml) of exogenous TGF-beta-1 recapitulated the effect of acidified FCS in inducing morphogenesis of hollow tubes. In contrast, higher concentrations of TGF-beta-1 induced the formation of thin cellular cords devoid of a detectable lumen. To gain insight into the mechanisms underlying TGF-beta-1-induced tube formation, we assessed the potential role of matrix metalloproteinases (MMPs). By western blot and gelatin zymography, we observed a dose-dependent increase in MMP-9 upon TGF-beta-1 treatment. Tube formation was suppressed by a synthetic broad-spectrum metalloproteinase inhibitor, by recombinant tissue inhibitor of metalloproteinases-2 (TIMP-2) and by a selective inhibitor of MMP-9, indicating that this morphogenetic process requires the activity of MMP-9.

Output: Do low concentrations of transforming growth factor-beta-1 induce tubulogenesis in cultured mammary epithelial cells?


Input: Consider Input: Neuroendocrine (NE) differentiation in prostate cancer (PCa), promoted by NE cell secreted products, appears to be associated with tumor progression, poor prognosis, and hormone-refractory disease. We recently reported secretagogin, a hexa-EF-hand Ca(2+) binding protein, as a novel NE marker in carcinoid tumors of the lung and the gastrointestinal tract. The present study analyzes the expression of secretagogin in normal and malign prostate tissue.', 'We analyzed immunoreactivity for secretagogin, chromogranin A (CgA), neuron specific enolase (NSE), and synaptophysin (SYN) in consecutive sections from 87 formalin-fixed paraffin-embedded (FFPE) benign hyperplastic (n = 10) and prostate adenocarcinoma (n = 77) specimens. The intracellular distribution of secretagogin, CgA, and NSE was examined by confocal fluorescent microscopy, and we characterized secretagogin in eight samples by Western blotting.', 'Secretagogin is cytoplasmic and nuclear expressed in NE and NE differentiated cells, and to a lesser extent in epithelial cells, in the benign prostate and prostate adenocarcinoma cells. Secretagogin stained 82% (46/56) of benign and 71% (48/68) of prostate adenocarcinomas and co-localized with the NE markers CgA and NSE. The expression of secretagogin is significantly correlated to CgA (P < 0.001) and NSE (P < 0.048) in prostate adenocarcinoma and to CgA in normal epithelium (P < 0.028).

Output: Is secretagogin a new neuroendocrine marker in the human prostate?


Input: Consider Input: The aim of the study is to investigate whether body mass index (BMI) affected pathological characteristics and biochemical recurrence (BCR) of prostate cancer after radical prostatectomy in Chinese men.', 'Medical records of 211 Chinese patients who underwent radical prostatectomy between 2006 and 2014 were retrospectively reviewed, with follow-up time of 24.5\u2009±\u200927.0\xa0months. Multivariate logistic and Cox regression analyses were applied to address the impact of BMI on adverse pathological outcomes and BCR following prostatectomy. A meta-analysis of published studies from MEDLINE or EMBASE was conducted to determine the relationship between BMI and BCR following prostatectomy among Asian populations.', 'Higher BMI was positively correlated with higher biopsy Gleason score (odds ratios (OR) 1.163, 95\xa0% confidence interval (CI) 1.023-1.322, P\u2009=\u20090.021) and pathological Gleason score (OR 1.220, 95\xa0% CI 1.056-1.410, P\u2009=\u20090.007) in multivariate analysis. BCR was detected in 48 patients (22.7\xa0%). Multivariate Cox proportional hazards analysis revealed that higher BMI (hazard ratio (HR) 1.145, 95\xa0% CI 1.029-1.273, P\u2009=\u20090.013) and prostate-specific antigen (HR 1.659, 95\xa0% CI 1.102-2.497, P\u2009=\u20090.015) levels were independent predictors of BCR. The meta-analysis enrolled eight Asian studies of 4145 patients treated by radical prostatectomy. Based on random-effects approach, a 5\xa0kg/m(2) increase in BMI was correlated with 28\xa0% higher risk of BCR (HR 1.22, 95\xa0% CI 0.86-1.72) without statistical significance.


Output: Is body mass index associated with higher Gleason score and biochemical recurrence risk following radical prostatectomy in Chinese men : a retrospective cohort study and meta-analysis?