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: The aim of this study was to determine the clinical significance and prognostic impact of extranodal metastasis (EM) in gastric carcinoma.', 'The study included 1023 patients who underwent gastrectomy with lymphadenectomy for primary gastric carcinoma between January 1993 and December 1996. EM was defined as the presence of tumour cells in extramural soft tissue that was discontinuous with either the primary lesion or locoregional lymph nodes.', "EM was detected in 146 (14.3 per cent) of the 1023 patients and in 1060 (3.0 per cent) of the 35 811 nodules that were retrieved as 'lymph nodes' from adipose connective tissues. The incidence of EM was significantly higher in patients with tumours that were large (diameter 10 cm or more), infiltrative, deeply invading or undifferentiated and in those with lymph node, peritoneal or liver metastases, or lymphatic or vascular involvement. After curative operation overall survival was significantly worse for patients with EM than those without (P < 0.001). Multivariate analysis identified EM as an independent prognostic factor (hazard ratio 1.82 (95 per cent confidence interval 1.23 to 2.71); P = 0.003).
Answer: EM is an independent prognostic factor and should therefore be included in the tumour node metastasis (TNM) staging system.
[A]: Is extranodal metastasis an indicator of poor prognosis in patients with gastric carcinoma?


[Q]: Context: Vessel formation is a crucial event in tissue repair after injury. Thus, one assumption of innovative therapeutic approaches is the understanding of its molecular mechanisms. Notwithstanding our knowledge of the role of Protein Kinase C epsilon (PKCε) in cardio-protection and vascular restenosis, its role in vessel progenitor differentiation remains elusive.', 'Given the availability of PKCε pharmacological modulators already tested in clinical trials, the specific aim of this study is to unravel the role of PKCε in vessel progenitor differentiation, with implications in vascular pathology and vasculogenesis.', 'Mouse Peri-Vascular Adipose Tissue (PVAT) was used as source of mesenchymal vessel progenitors. VEGF-induced differentiation of PVAT cells down-regulates both PKCε and p-PAK1 protein expression levels. PKCε overexpression and activation: i) reduced the expression levels of SMA and PECAM in endothelial differentiation of PVAT cells; ii) completely abrogated tubules formation in collagen gel assays; iii) increased the expression of p-PAK1.
Answer: PKCε negatively interferes with vessel progenitor differentiation via interaction with PAK-1.
[A]: Is pKCε a negative regulator of PVAT-derived vessel formation?


[Q]: Context: Distant prostate cancers are commonly hormone refractory and exhibit increased growth no longer inhibited by androgen deprivation therapy. Understanding all molecular mechanisms contributing to uncontrolled growth is important to obtain effective treatment strategies for hormone refractory prostate cancers (HRPC). The aryl hydrocarbon receptor (AhR) affects a number of biological processes including cell growth and differentiation. Several studies have revealed that exogenous AhR ligands inhibit cellular proliferation but recent evidence suggests AhR may possess intrinsic functions that promote cellular proliferation in the absence of exogenous ligands.', 'qRT-PCR and western blot analysis was used to determine AhR mRNA and protein expression in hormone sensitive LNCaP cells as well as hormone refractory DU145, PC3 and PC3M prostate cancer cell lines. LNCaP cells express AhR mRNA and protein at a much lower level than the hormone refractory cell models. Cellular fractionation and immunocytochemistry revealed nuclear localization of AhR in the established hormone refractory cell lines while LNCaP cells are devoid of nuclear AhR protein. qRT-PCR analysis used to assess basal CYP1B1 levels and a xenobiotic responsive element binding assay confirmed ligand independent transcriptional activity of AhR in DU145, PC3 and PC3M cells. Basal CYP1B1 levels were decreased by treatment with specific AhR inhibitor, CH223191. An in vitro growth assay revealed that CH223191 inhibited growth of DU145, PC3 and PC3M cells in an androgen depleted environment. Immunohistochemical staining of prostate cancer tissues revealed increased nuclear localization of AhR in grade 2 and grade 3 cancers compared to the well differentiated grade 1 cancers.
Answer: Together, these results show that AhR is constitutively active in advanced prostate cancer cell lines that model hormone refractory prostate cancer. Chemical ablation of AhR signaling can reduce the growth of advanced prostate cancer cells, an effect not achieved with androgen receptor inhibitors or growth in androgen depleted media.
[A]:
Is the aryl hydrocarbon receptor constitutively active in advanced prostate cancer cells?


