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pRb Expression (prb + expression)
Selected AbstractsRetinoblastoma gene expression in human non-melanoma skin cancerJOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2003Malcolm J. Edwards Background:, The aberrant expression of both the retinoblastoma and p53 tumor suppressor genes has been associated with more aggressive tumors, metastasis and lower survival. Methods:, We have evaluated immunohistochemically the expression of pRB in a panel of non-melanoma skin cancers containing p53 somatic mutations. Results:, Nuclear anti-p53 staining was detected in 18 (72%) differentiated squamous cell carcinomas, six (100%) undifferentiated squamous cell carcinomas and seven (28%) basal cell carcinomas. A correlation was observed between p53 expression and the proliferative activity of differentiated squamous cell carcinomas (P < 0.066), undifferentiated squamous cell carcinomas (P < 0.05) and basal cell carcinomas (P < 0.01). Tumors were selected for mutant p53 expression by PCR-directed DNA sequencing and pRB expression measured immunohistochemically. Anti-pRB reactivity was detected in the nuclei of basal and suprabasal layer cells of normal epidermis, and in the proliferative compartment of all the differentiated squamous cell carcinomas, and basal cell carcinomas. A correlation was observed between pRB expression and the proliferative activity of the differentiated squamous cell carcinomas (P < 0.01) and basal cell carcinomas (P < 0.025). However, anti-pRB reactivity was not detected in the six anti-p53 reactive undifferentiated squamous cell carcinomas. [source] Abnormal Expression of p16INK4a, Cyclin D1, Cyclin-Dependent Kinase 4 and Retinoblastoma Protein in Gastric Carcinomas,JOURNAL OF SURGICAL ONCOLOGY, Issue 1 2008Ichiro Kishimoto MD Abstract Background and Objectives The p16INK4a (p16), cyclin D1, cyclin-dependent kinase (CDK) 4 and retinoblastoma (Rb) genes are components of the Rb pathway that controls the G1-S checkpoint of the cell cycle. The aim of this study was to assess the relationship between their abnormalities and clinicopathological features in gastric carcinomas. Mehtods Immunohistochemical analysis of the encoded proteins was performed on a series of 158 cases. Results Loss of p16/Rb protein (pRb) expression and overexpression of cyclin D1/CDK4 were observed in 49%/40% and 37%/37% of gastric carcinomas, respectively. At least 1 of these abnormalities was found in 86% of the cases and a positive correlation was noted between p16 and pRb (P,=,0.009). Cyclin D1 (P,=,0.042) and CDK4 (P,=,0.008) overexpession was inversely associated with lymph node metastasis and depth of invasion, respectively. Loss of pRb expression was more frequently in diffuse type lesions than in the intestinal type (P,=,0.022). The patients with p16+/pRb,/cyclin D1,/CDK4, or p16,/pRb+/cyclin D1,/CDK4, tumors demonstrated particularly poor survival. With multivariate survival analysis, only depth of invasion and TNM stage could be proven as independent predictors. Conclusions The Rb pathway is disrupted in the vast majority of gastric carcinomas. This study also identified specific immunohistochemical marker profiles for prognosis. J. Surg. Oncol. 2008;98:60,66. © 2008 Wiley-Liss, Inc. [source] Levamisole induced apoptosis in cultured vascular endothelial cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2000Michaela Artwohl To better understand the anticancer activity of Levamisole (LMS), which serves as an adjuvant in colon cancer therapy in combination with 5-Fluorouracil, this study analyses LMS' ability to induce apoptosis and growth arrest in cultured human micro- and macrovascular endothelial cells (ECs) and fibroblasts. Cells exposed (24 h) to Levamisole (range: 0.5,2 mmol l,1) alone or in combination with antioxidants (10 mmol l,1 glutathione or 5 mmol l,1 N-Acetylcysteine or 0.1 mmol l,1 Tocopherol) were evaluated for apoptosis (3H-thymidine assays, in situ staining), mRNA/protein expression (Northern/Western blot), and proliferation (3H-thymidine incorporation). Levamisole dose-dependently increased apoptosis in ECs to 230% (HUVECs-human umbilical vein ECs), 525% (adult human venous ECs) and 600% (human uterine microvascular ECs) but not in fibroblasts compared to control cells (set as 100%). Levamisole increased in ECs integrin-dependent matrix adhesion, inhibited proliferation (,70%), reduced expression of survival factors such as clusterin (,30%), endothelin-1 (,43%), bcl-2 (,34%), endothelial NO-synthase (,32%) and pRb (Retinoblastoma protein: ,89%), and increased that of growth arrest/death signals such as p21 (+73%) and bak (+50%). LMS (2 mmol l,1)-induced apoptosis was inhibited by glutathione (,50%) and N-Acetylcysteine (,36%), which also counteracted reduction by Levamisole of pRb expression, suggesting reactive oxygen species and pRb play a role in these processes. The ability of LMS to selectively induce apoptosis and growth arrest in endothelial cells potentially hints at vascular targeting to contribute to Levamisole's anticancer activity. British Journal of Pharmacology (2000) 131, 1577,1583; doi:10.1038/sj.bjp.0703660 [source] A novel form of pRb expressed during normal myelopoiesis and in tumour-associated macrophagesCELL PROLIFERATION, Issue 1 2005H. P. Liu We have identified a novel myeloid-specific form of retinoblastoma protein (pRb), termed ,Rb-p70, that exists in vivo as an N-terminally truncated form of full-length pRb. ,Rb-p70 appears to be the product of alternative translation and is expressed in primary myeloid cells in fetal liver, bone marrow and spleen. It is also expressed in the human myelomonocytic cell line U937 and is down-regulated as U937s are induced to differentiate. We have also detected ,Rb-p70 expression in primary human breast tumours and we have determined that ,Rb-p70 is specifically expressed in tumour-associated macrophages. These data identify a novel mechanism for regulating pRb expression that is unique to the myeloid system. [source] | ||||||||||