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.

[EX Q]: Cadherins are calcium-dependent cell-to-cell adhesion glycoproteins playing a critical role in the formation and maintenance of normal tissue architecture. In normal mammary gland, E-cadherin is expressed by luminal epithelial cells, while P-cadherin is restricted to myoepithelial cells. Changes in the expression of classical E- and P-cadherins have been observed in mammary lesions and related to mammary carcinogenesis. P-cadherin and E-cadherin expressions were studied in a series of feline normal mammary glands, hyperplastic/dysplastic lesions, benign and malignant tumours by immunohistochemistry and double-label immunofluorescence.', 'In normal tissue and in the majority of hyperplastic/dysplastic lesions and benign tumours, P-cadherin was restricted to myoepithelial cells, while 80% of the malignant tumours expressed P-cadherin in luminal epithelial cells. P-cadherin expression was significantly related to high histological grade of carcinomas (p <0.0001), tumour necrosis (p = 0.001), infiltrative growth (p = 0.0051), and presence of neoplastic emboli (p = 0.0401). Moreover, P-cadherin positive carcinomas had an eightfold likelihood of developing neoplastic emboli than negative tumours. Cadherins expression profile in high grade and in infiltrative tumours was similar, the majority expressing P-cadherin, regardless of E-cadherin expression status. The two cadherins were found to be co-expressed in carcinomas with aberrant P-cadherin expression and preserved E-cadherin.
[EX A]: Is aberrant P-cadherin expression associated to aggressive feline mammary carcinomas?

[EX Q]: The Tonnis radiographic classification of developmental dysplasia of the hip (DDH) has been used as a prognostic indicator for patients with walking-age DDH. The International Hip Dysplasia Institute (IHDI) classification, a new radiographic classification system, has been proposed to be more reliable by its creators. We sought to validate its reliability using independent observers, to compare it to the Tonnis method, and to assess its prognostic significance in a large cohort of patients.', 'A consecutive series of walking-age DDH patients were examined radiographically and classified by the Tonnis and IHDI schemes by 3 independent observers. Interobserver agreement was determined using the Kappa method. Clinical data were collected on patients with regard to success of closed reduction, need for later pelvic osteotomy, and presence of subsequent radiographic avascular necrosis (AVN). The prognostic value of the Tonnis and IHDI classifications to predict these clinical outcomes was determined.', 'A total of 287 hips were available for analysis of the classification schemes. In total, 235 hips underwent attempted closed reduction and were eligible for analysis of successful closed reduction, and 131 hips had >4-year follow-up and were utilized for analysis of late pelvic osteotomy and AVN. Both classifications showed excellent interobserver reliability and in general, there was nonstatistically significant better reliability for the IHDI versus the Tonnis classification. In multivariate analysis, both IHDI and Tonnis classifications were found to be predictive of successful closed reduction and need for late pelvic osteotomy. Both methods showed trends toward being predictive of AVN rate, without statistical significance.
[EX A]: Is a New Radiographic Classification System for Developmental Hip Dysplasia Reliable and Predictive of Successful Closed Reduction and Late Pelvic Osteotomy?

[EX Q]: Irinotecan is used in the first-line treatment of metastatic colorectal cancer. The UGT1A1-metabolizing enzyme, expressed in liver and colon, is primarily involved in the inactivation of its active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). Herein, we explored the role of DNA methylation in the silencing of UGT1A1 gene expression in colon cancer and its influence on cellular SN-38 detoxification.', 'UGT1A1 mRNA was repressed in most primary tumors (41 of 50; 82%) and in three colon cancer cell lines (HCT-116, HCT-15, and COLO-320DM). Bisulfite sequencing of the UGT1A1 gene revealed the aberrant methylation of specific CpG islands in UGT1A1-negative cells. Conversely, hypomethylation was observed in HT-29, HT-115, and LOVO cells that overexpress UGT1A1. Direct methylation of the UGT1A1 promoter resulted in the complete repression of transcriptional activity. Treatment with demethylating and histone deacetylase inhibitor agents had the capacity to reverse aberrant hypermethylation and to restore UGT1A1 expression in hypermethylated UGT1A1-negative cells but not in hypomethylated cells. Loss of UGT1A1 methylation was further associated with an increase in UGT1A1 protein content and with an enhanced inactivation of SN-38 by 300% in HCT-116 cells.
[EX A]:
Is irinotecan inactivation modulated by epigenetic silencing of UGT1A1 in colon cancer?