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Decreased Protein Expression (decreased + protein_expression)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Differential stress-induced alterations of colonic corticotropin-releasing factor receptors in the Wistar Kyoto rat

NEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2010
D. O'malley
Abstract Background, A growing body of data implicates increased life stresses with the initiation, persistence and severity of symptoms associated with functional gut disorders such as irritable bowel syndrome (IBS). Activation of central and peripheral corticotropin-releasing factor (CRF) receptors is key to stress-induced changes in gastrointestinal (GI) function. Methods, This study utilised immunofluorescent and Western blotting techniques to investigate colonic expression of CRF receptors in stress-sensitive Wistar Kyoto (WKY) and control Sprague Dawley (SD) rats. Key Results, No intra-strain differences were observed in the numbers of colonic CRFR1 and CRFR2 positive cells. Protein expression of functional CRFR1 was found to be comparable in control proximal and distal colon samples. Sham levels of CRFR1 were also similar in the proximal colon but significantly higher in WKY distal colons (SD: 0.38 ± 0.14, WKY: 2.06 ± 0.52, P < 0.01). Control levels of functional CRFR2 were similar between strains but sham WKYs samples had increased CRFR2 in both the proximal (SD: 0.88 ± 0.21, WKY: 1.8 ± 0.18, P < 0.001) and distal (SD: 0.18 ± 0.08, WKY: 0.94 ± 0.32, P < 0.05) regions. Exposure to open field (OF) and colorectal distension (CRD) stressors induced decreased protein expression of CRFR1 in SD proximal colons, an effect that was blunted in WKYs. CRD stimulated decreased expression of CRFR2 in WKY rats alone. Distally, CRFR1 is decreased in WKY rats following CRD but not OF stress without any apparent changes in SD rats. Conclusions & Inferences, This study demonstrates that psychological and physical stressors alter colonic CRF receptor expression and further support a role for local colonic CRF signalling in stress-induced changes in GI function. [source]

Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer

THE PROSTATE, Issue 3 2006
Zheng Fu
Abstract BACKGROUND Diminished expression of Raf kinase inhibitor protein (RKIP), an inhibitor of the Raf signaling cascade, promotes prostate cancer (PCa) metastasis in a murine model, suggesting that it is a metastasis suppressor gene. However, the prognostic significance of RKIP expression and its association with metastasis in PCa patients is unknown. METHODS To investigate RKIP protein expression is a prognostic marker in PCa we performed immunohistochemical staining for RKIP expression in tissue microarrays consisting of 758 non-neoplastic prostate tissues, primary tumors and metastases from 134 PCa patients. The Cox proportional-hazards model was used to adjust for covariates including Gleason score, tumor volume, tumor weight, clinical stage, digital rectal exam findings, serum PSA level and surgical margins. RESULTS RKIP expression was low in approximately 5%, 48%, and 89%of non-neoplastic prostate, primary tumors and metastases, respectively. Low RKIP expression in primary tumors was a strong positive predictive factor for PCa recurrence based on PSA levels. In patients whose primary tumors expressed high RKIP levels, the 7-year PSA recurrence rate was <,10%; whereas in patients with tumors with low RKIP expression the recurrence rate was 50% (P,<,0.001). Multivariate analysis revealed RKIP was an independent prognostic factor (P,<,0.001). CONCLUSION In contrast to increased expression of pro-tumorigenic genes, these results demonstrate decreased protein expression of a gene, for example, RKIP, can serve as a prognostic marker in PCa patients. © 2005 Wiley-Liss, Inc. [source]

HLA-DR expression and differential trafficking of monocyte subsets following low to intermediate risk surgery,

ANAESTHESIA, Issue 1 2010
J. M. Handy
Summary Reduced HLA-DR expression on monocytes has been suggested as a predictive marker of immunosuppression following very high risk surgery, but there are few reports in lower risk surgery. In 32 patients undergoing low to intermediate risk surgery, blood samples were analysed by flow cytometry for HLA-DR expression and numbers in both CD14high and CD14lowCD16+ monocyte subsets. The numbers of CD14high monocytes increased at 24 h (mean (SD), 5.0 (2.2) vs 7.6 (3.9) × 105 cells.ml,1; p < 0.01) while CD14lowCD16+ monocytes decreased (0.68 (0.36) vs 0.44 (0.36) × 105 cells.ml,1; p < 0.01). HLA-DR expression was significantly reduced in both subsets by 24 h (mean (SD) fluorescent intensity 440 (310) vs 160 (130) for CD14high and 1000 (410) vs 560 (380) for CD14lowCD16+ subsets; p < 0.01). This reduction of monocyte HLA-DR expression 24 h following lower risk surgery raises questions about the purported clinical utility of this biomarker as an early predictor of postoperative complications. Our results also suggest that surgery induces significant trafficking (i.e. mobilisation, margination and extravasation) of monocyte subsets, and that monocyte HLA-DR depression is the result of a down-regulatory phenomenon (decreased protein expression on each cell) rather than the differential trafficking of monocyte subsets. [source]

Didox, a ribonucleotide reductase inhibitor, induces apoptosis and inhibits DNA repair in multiple myeloma cells

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2006
N. Raje
Summary Ribonucleotide reductase (RR) is the enzyme that catalyses the rate-limiting step in DNA synthesis, the production of deoxynucleotides. RR activity is markedly elevated in tumour tissue and is crucial for cell division. It is therefore an excellent target for cancer chemotherapy. This study examined the anti-myeloma activity of Didox (3,4-Dihydroxybenzohydroxamic acid), a novel RR inhibitor (RRI). Our data showed that Didox induced caspase-dependent multiple myeloma (MM) cell apoptosis. Didox, unlike other RRIs that mainly target the pyrimidine metabolism pathway, targets both purine and pyrimidine metabolism pathways in MM, as demonstrated by transcriptional profiling using the Affymetrix U133A 2·0 gene chip. Specifically, a ,2-fold downregulation of genes in these anabolic pathways was shown as early as 12 h after exposure to Didox. Furthermore, apoptosis was accompanied by downregulation of bcl family proteins including bcl-2, bclxl, and XIAP. Importantly, RR M1 component transcript was also downregulated, associated with decreased protein expression. Genes involved in DNA repair mechanisms, specifically RAD 51 homologue, were also downregulated. As Didox acts on MM cells by inhibiting DNA synthesis and repair, combination studies with melphalan, an agent commonly used in MM, were performed. A strong in vitro synergism was shown, with combination indices of <0·7 as determined by the Chou,Talalay method. These studies therefore provide the preclinical rationale for evaluation of Didox, alone and in combination with DNA-damaging agents, to improve patient outcome in MM. [source]