The functions of oxytocin in the female are thought to be confined to the processes of milk ejection and parturition. In this study the role of oxytocin in the body’s response to stressful stimuli has been examined. Physical immobilization of rats and forced swimming caused large increases in the secretion of the hormone, whereas vasopressin levels remained unchanged. These findings classify oxytocin, in contrast to vasopressin, as a so-called ‘stress hormone’ and suggest its importance in processes other than those related to reproduction.
Purpose: The aim of the present study was to identify human genes that might prove useful in the diagnosis and therapy of primary breast cancer. Experimental Design: Twenty-four matched pairs of invasive ductal breast cancer and corresponding benign breast tissue were investigated by a combination of laser microdissection and gene expression profiling. Differential expression of candidate genes was validated by dot blot analysis of cDNA in 50 pairs of matching benign and malignant breast tissue. Cellular expression of candidate genes was further validated by RNA in situ hybridization, quantitative reverse transcription-PCR, and immunohistochemistry using tissue microarray analysis of 272 nonselected breast cancers. Multivariate analysis of factors on overall survival and recurrence-free survival was done. Results: Fifty-four genes were found to be up-regulated and 78 genes were found to be downregulated. Dot blot analysis reduced the number of up-regulated genes to15 candidate genes that showed at least a 2-fold overexpression in >15 of 50 (30%) tumor/normal pairs. We selected phosphatidic acid phosphatase type 2 domain containing 1A (PPAPDC1A) and karyopherin a2 (KPNA2) for further validation. PPAPDC1A and KPNA2 RNA was up-regulated (fold change >2) in 84% and 32% of analyzed tumor/normal pairs, respectively. Nuclear protein expression of KPNA2 was significantly associated with shorter overall survival and recurrence-free survival. Testing various multivariate Cox regression models, KPNA2 expression remained a highly significant, independent and adverse risk factor for overall survival. Conclusions: Gene expression profiling of laser-microdissected breast cancer tissue revealed novel genes that may represent potential molecular targets for breast cancer therapy and prediction of outcome.
The missing link in the evidence for an active endogenous renin angiotensin system in the brain has been the demonstration of local angiotensin synthesis in the central nervous system in vivo. In this report the extraction and characterization of angiotensin I and angiotensin II from the brain of rats is described. The accumulation of angiotensin I was enhanced in hypertensive rats when the conversion to angiotensin II was blocked in vivo by the converting enzyme inhibitor captopril.
Common fragile sites (CFSs) are seen as chromosomal gaps and breaks brought about by inhibition of replication, and it is thought that they cluster with tumor breakpoints. This study presents a comprehensive analysis using conventional and molecular cytogenetic mapping of CFSs and their expression frequencies in two mouse strains, BALB/c and C57BL/6, and in human probands. Here we show that induced mouse CFSs relate to sites of spontaneous gaps and breaks and that CFS expression levels in chromosome bands are conserved between the two mouse strains and between syntenic mouse and human DNA segments. Furthermore, four additional mouse CFSs were found to be homologous to human CFSs on the molecular cytogenetic level (Fra2D-FRA2G, Fra4C2-FRA9E, Fra6A3
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