Cross-fostering of the tammar wallaby (Macropus eugenii) pouch young accelerates fore-stomach maturation
MECHANISMS OF DEVELOPMENT
Authors: Kwek, Joly H. L.; De Iongh, Robbert; Digby, Matthew R.; Renfree, Marilyn B.; Nicholas, Kevin R.; Familari, Mary
Abstract
There are two phases of fore-stomach development during the first 200 days of pouch life in tammar wallaby For the first 170 days, the mucosa displays an immature gastric glandular phenotype that changes to a cardia glandular phenotype, which remains for the rest of the animal's life. During this 200-day period after birth, the pouch young (PY) is dependent on maternal milk, which progressively changes in composition. We showed previously that PY cross-fostered to host mothers at a later stage of lactation accelerated development. In this study, we investigated whether cross-fostering and exposure to late lactation stage milk affected the transition to cardia glandular phenotype. in fostered PY fore-stomach, there was increased apoptosis, but no change in cell proliferation. The parietal cell population was significantly reduced, and expression of gastric glandular phenotype marker genes (ATP4A, GKN2, GHRL and NDRG2) was down-regulated, suggesting down-regulation of gastric phenotype in fostered PY fore-stomach. The expression of cardia. glandular phenotype genes (MUC4, KRT20, CSTB, ITLN2 and LPLUNC1) was not changed in fostered PY. These data suggest that fore-stomach maturation proceeds via two temporally distinct processes: down-regulation of gastric glandular phenotype and initiation of cardia glandular phenotype. In fostered PY, these two processes appear uncoupled, as gastric glandular phenotype was down-regulated but cardia glandular phenotype was not initiated. We propose that milk from later stages of lactation and/or herbage consumed by the PY may play independent roles in regulating these two processes. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer
TRANSLATIONAL ONCOLOGY
Authors: Sikic, Danijel; Breyer, Johannes; Hartmann, Arndt; Burger, Maximilian; Erben, Philipp; Denzinger, Stefan; Eckstein, Markus; Stohr, Robert; Wach, Sven; Wullich, Bernd; Keck, Bastian; Wirtz, Ralph M.; Otto, Wolfgang
Abstract
INTRODUCTION: High-risk non-muscle-invasive bladder cancer (NMIBC) remains challenging given the high probability of progression. Given that the androgen receptor (AR) has been discussed as a possible factor in the development and progression of bladder cancer, we investigated the predictive value of AR in stage pT1 NMIBC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data and AR mRNA expression in 296 patients with stage pT1 NMIBC who underwent a transurethral resection of the bladder. The mRNA expression of the AR transcript variants 1 (AR1) and 2 (AR2) was measured by reverse transcription quantitative real-time polymerase chain reaction. AR expression was also correlated to KRT5 and KRT20 mRNA expression. RESULTS: Kaplan-Meier analysis indicated that high AR1 mRNA expression >= 35.47 is associated with statistically significant better recurrence-free survival (RFS) (P = .0007), progression-free survival (PFS) (P = .0420), and cancer-specific survival (CSS) (P = .0050). Multivariate Cox regression analysis revealed that high AR1 mRNA expression is an independent prognostic marker for RFS (P = .0029) and CSS (P = .0119). Spearman rank correlation revealed a significant positive association between mRNA expression of AR1 and KRT5 (r(s): 0.3171, P < .0001) as well as a negative association with multifocal tumors (r(s): 0.1478, P < .0109). No association was noted between AR1 expression and tumor grade, concomitant CIS, gender, tumor size, and KRT20 in patients with stage T1 NMIBC. CONCLUSIONS: AR mRNA expression can predict RFS and CSS in patients with stage T1 NMIBC. Further studies are necessary to refine the relevance of AR mRNA expression compared with immunohistochemically detectable AR expression.