Biomedical subjects

Veronica Mason

Publications and source records attributed to Veronica Mason.

4 recordsLinked to original sources

PubMed2006

Overexpression of NDRG1 is an indicator of poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma is a highly lethal cancer that typically has poor prognosis. Prognostic markers can help in its clinical management and in understanding the biology of poor prognosis. Through an earlier gene expression study, we identified N-Myc downregulated gene 1 (NDRG1) to be significantly highly expressed in hepatocellular carcinoma compared to nontumor liver. As NDRG1 is a differentiation-related gene with putative metastasis suppressor activity, we investigated the clinical significance of its overexpression. Quantitative real-time polymerase chain reaction using an independent set of patient samples confirmed the significant overexpression of NDRG1 in hepatocellular carcinoma compared to nontumor liver samples (P<0.001). Additionally, high levels of NDRG1 transcript correlated with shorter overall survival (P<0.001), late tumor stage (P=0.001), vascular invasion (P=0.003), large tumor size (P=0.011), and high Edmondson-Steiner histological grade (P=0.005). Using immunohistochemistry, NDRG1 protein was found to be significantly overexpressed in hepatocellular carcinoma samples compared to nontumor liver or cirrhotic and benign liver lesions (P<0.001). Among the hepatocellular carcinoma samples, those which are moderately and poorly differentiated express higher levels of NDRG1 protein than those which are well-differentiated (P<0.005). Additionally, hepatocellular carcinomas with vascular invasion also express elevated levels of NDRG1 protein compared to those without vascular invasion (significant at P<0.005). Our results suggest NDRG1 to be a likely tumor marker for hepatocellular carcinoma, the overexpression of which is correlated with tumor differentiation, vascular invasion, and overall survival. Its significantly elevated expression in hepatocellular carcinoma could be a useful indicator of tumor aggressiveness and therefore patient prognosis.

Biomarkers, Tumor↗

PubMed2006

Sprouty 2, an inhibitor of mitogen-activated protein kinase signaling, is down-regulated in hepatocellular carcinoma.

The Sprouty proteins are increasingly being recognized to be deregulated in various types of cancers. This deregulation is often associated with aberrant signaling of receptor tyrosine kinases and its downstream effectors, leading to the mitogen-activated protein kinase (MAPK) signaling pathway. In human hepatocellular carcinoma, where the MAPK activity is enhanced via multiple hepatocarcinogenic factors, we observed a consistent reduced expression of the sprouty 2 (Spry2) transcript and protein in malignant hepatocytes compared with normal or cirrhotic hepatocytes. The expression pattern of Spry2 in hepatocellular carcinoma resembles that of several potential tumor markers of hepatocellular carcinoma and also that of several angiogenic factors and growth factor receptors. In contrast to previous studies of Spry2 down-regulation in other cancers, we have ruled out loss of heterozygosity or the methylation of promoter sites, two common mechanisms responsible for the silencing of genes with tumor suppressor properties. Functionally, we show that Spry2 inhibits both extracellular signal-regulated kinase signaling as well as proliferation in hepatocellular carcinoma cell lines, whereas knocking down Spry2 levels in NIH3T3 cells causes mild transformation. Our study clearly indicates a role for Spry2 in hepatocellular carcinoma, and an understanding of the regulatory controls of its expression could provide new means of regulating the angiogenic switch in this hypervascular tumor, thereby potentially controlling tumor growth.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Novel endothelial cell markers in hepatocellular carcinoma.

Hepatocellular carcinoma is characterized by hypervascularity and a propensity for vascular invasion. Detailed analysis of complementary DNA (cDNA) microarray global gene expression data and further validation on a smaller independent sample set by reverse transcription-polymerase chain reaction established the presence of two endothelial gene clusters in hepatocellular carcinoma. Cluster I, consists of 20 cDNA clones, representing 15 unique genes. Cluster II consists of nine unique genes. The expression of the cluster I genes appeared to be significantly upregulated in hepatocellular carcinoma compared with normal liver, cirrhotic liver, or nontumor liver tissues adjacent to the hepatocellular carcinoma. The pattern of gene expression of cluster I genes correlated positively with the 'proliferation gene cluster' and 'stromal cells cluster 2'. Expression of cluster II genes, in contrast, was not significantly different between hepatocellular carcinoma and non-neoplastic liver tissues. Studies conducted to localize the protein products of these genes by immunohistochemical staining of tissue arrays with up to 350 cores of tissues, and by in situ hybridization led to the discovery of novel sinusoidal endothelial cell markers in hepatocellular carcinoma: podocalyxin-like and regulator of G protein signaling-5. Our results underscore fundamental differences not only between neoplastic vs non-neoplastic liver cells but also between the hepatic sinusoidal endothelium of hepatocellular carcinoma and normal liver.

Antigens, CD34↗

PubMed2003

Gene expression in the normal adult human kidney assessed by complementary DNA microarray.

The kidney is a highly specialized organ with a complex, stereotyped architecture and a great diversity of functions and cell types. Because the microscopic organization of the nephron, the functional unit of the kidney, has a consistent relationship to the macroscopic anatomy of the kidney, knowledge of the characteristic patterns of gene expression in different compartments of the kidney could provide insight into the functions and functional organization of the normal nephron. We studied gene expression in dissected renal lobes of five adult human kidneys using cDNA microarrays representing approximately 30,000 different human genes. Total RNA was isolated from sections of the inner and outer cortex, inner and outer medulla, papillary tips, and renal pelvis and from glomeruli isolated by sieving. The results revealed unique and highly distinctive patterns of gene expression for glomeruli, cortex, medulla, papillary tips, and pelvic samples. Immunohistochemical staining using selected antisera confirmed differential expression of several cognate proteins and provided histological localization of expression within the nephron. The distinctive patterns of gene expression in discrete portions of the kidney may serve as a resource for further understanding of renal physiology and the molecular and cellular organization of the nephron.

Adult↗