Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The WW domain-containing oxidoreductase (WWOX) gene, located on chromosome 16q23.3-24.1 in the region recognized as the common fragile site FRA16D is considered to be a tumor suppressor gene involved in various carcinomas. The present study was to investigate the alterations of WWOX expression and its correlation with polymorphism, the level of WWOX loss of heterozygosity (LOH), and methylation status in esophageal squamous cell carcinoma (ESCC). Immunohistochemistry and RT-PCR methods were used, respectively, to examine the protein and mRNA expression of WWOX in ESCC tissues. PCR-RFLP, PCR-SSLP, and MSP approach were used, respectively, to detect polymorphisms of rs3764340, rs2548861, and rs1079635 site, the level of LOH, and WWOX methylation status. Family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC. Protein and mRNA expression of WWOX was reduced in ESCC tumor tissues and was associated with LOH and hypermethylation of the gene. The G allele of rs3764340 significantly elevated the risk of developing ESCC and was associated with TNM stage. LOH at the WWOX loci was observed in 41.4% tumors. The hypermethylation of promoter and exon1 of WWOX was found to be occurred in dysplastic tissues and the methylation frequency of WWOX in ESCC tumor tissues was significantly higher than that in corresponding normal tissues and was associated with UGIC family history. In all, these results indicate that the WWOX gene may play an important role in the development of ESCC especially in individuals with UGIC family history.
Mol Carcinog 2013 Apr
PMID:Decreased expression of WWOX in the development of esophageal squamous cell carcinoma. 2221 16

Matrix metalloproteinases (MMPs) are elevated in patients with squamous cell carcinoma (SCC) over either the head and neck (HNSCC) or the esophagus (ESCC). Synchronous SCC with both HNSCC and ESCC predispose to worse survival. This study tested if serum MMP levels correlate with clinical features and predict survival for HNSCC, ESCC, and synchronous SCC. One hundred and thirty patients with SCCs in upper aero-digestive tract (70 ESCC, 20 HNSCC, and 40 synchronous SCC) and 74 healthy controls were assessed for serum MMP-3, -7, and -9 titers by enzyme-linked immunosorbent assay. The titers were validated to their correlations to clinical features and survival rates of the different SCC groups. Patients with SCCs had significantly higher serum MMP-3, -7, and -9 titers than the controls (P < 0.001) but there was no difference among the three SCC groups. Based on the optimal MMP cut-off values by ROC curve, elevated MMP-3 and MMP-9, but not MMP-7, correlated with distant metastasis and poor survival (P < 0.05). Concomitantly elevated MMP-3 (>14 ng/mL) and MMP-9 (>329.3 ng/mL) independently correlated with poor two-year survival (P = 0.002, by log rank test). Cox regression confirmed that such concomitant elevation was superior to the tumor stage of either ESCC or HNSCC in predicting survival for synchronous SCC. Serum MMPs are elevated in SCC of the upper aero-digestive tract. Especially for synchronous SCC, concomitantly elevated MMP-3 and MMP-9 levels serve as better biomarkers to predict prognosis than TNM staging of ESCC or HNSCC.
Mol Carcinog 2013 Jun
PMID:Concomitantly elevated serum matrix metalloproteinases 3 and 9 can predict survival of synchronous squamous cell carcinoma of the upper aero-digestive tract. 2224 50

Abnormalities in signal transducer and activator of transcription (STAT) signaling, especially STAT3 and STAT5, are involved in the oncogenesis of several human cancers, including gastric cancer (GC). However, the downstream targets of STAT3 and STAT5 are not fully identified, and the precise roles and the prognostic value of STAT3 and STAT5 in GC have not been fully characterized. In this study, we used ChIP-on-chip to identify STAT3 and STAT5 target genes on a whole genome scale in AGS cells, a human GC cell line. A total of 2,514 and 1,314 genes were identified as STAT3 and STAT5 target genes, which were mainly related to cell growth, metabolism, differentiation, adhesion, immune response, and stress response. Furthermore, we depleted STAT3 and STAT5 with a small interfering RNA, respectively. Our results demonstrate that STAT3, but not STAT5, is involved in GC cell growth and cell cycle progression through regulation of gene expression, such as Bcl-2, p16(ink4a) and p21(waf1/cip1). Moreover, expression of pSTAT3(Tyr705) correlates with TNM stage, differentiation and survival, and is a significant prognostic factor in GC. Therefore, our findings provide novel evidence that STAT3 may be a potential therapeutic target for GC treatment and pSTAT3(Tyr705) expression can predict prognosis in GC.
J Mol Med (Berl) 2012 Sep
PMID:Constitutive activation of STAT3 is predictive of poor prognosis in human gastric cancer. 2232 12

Circulating miR-17-5p and miR-20a (miR-17-5p/20a) have been demonstrated to be elevated in the plasma of gastric cancer patients. However, the clinical significance of the circulating levels of these microRNAs (miRNAs), the predictive power for prognosis and application for monitoring of chemotherapeutic effects remain unclear. To this end, we measured plasma miR-17-5p/20a levels in unpaired pre-operative (n=65), post-operative (n=16) and relapse (n=6) gastric cancer patient groups. The 3-year overall survival rate for the unpaired pre-operative patients was recorded. The circulating levels of miR-17-5p/20a were also tested in paired pre-operative and post-operative plasma from 14 gastric cancer patients. We found that the concentrations of miR-17-5p/20a were significantly associated with the differentiation status and TNM stages of gastric cancer. The miRNA levels in the different groups reflected pathological tumor progression. Kaplan-Meier curve analysis revealed that high expression levels of miR-17-5p/20a were significantly correlated with poor overall survival. Cox regression analysis demonstrated that the level of plasma miR-20a was an independent risk predictor for prognosis. An in vivo mouse tumor model was established and antagomirs against miR-17-5p/20a were applied as chemotherapeutics to perform tumor treatment. An assay of serum miR-17-5p/20a levels showed that the levels of serum miRNAs were notably reduced in post-treated mice with tumor volume regression. Taken together, the levels of circulating miR-17-5p/20a may be a promising non-invasive molecular marker for pathological progression, prediction of prognosis and monitoring of chemotherapeutic effects for gastric cancer.
Mol Med Rep 2012 Jun
PMID:Circulating miR-17-5p and miR-20a: molecular markers for gastric cancer. 2240 28

Survivin and Bcl-2 are generally considered to be inhibitors of apoptosis and are frequently overexpressed in several types of human cancers. However, their role in regulating the biological behavior of non-small cell lung carcinoma (NSCLC) remains controversial. We aimed to determine the expression of survivin and Bcl-2 and explore their correlation with clinicopathological features and prognosis. The expression of survivin and Bcl-2 proteins in 62 specimens of NSCLC tissues and 30 specimens of tumor adjacent tissues was detected using immunohistochemistry. The correlation between protein expression and clinicopathological features and prognosis was analyzed. The percentage of survivin-positive samples obtained from NSCLC tissues was 58.06% (36/62), which was significantly higher compared to that in normal lung tissues (10%, 3/30; P<0.05). Similarly, the percentage of Bcl-2-positive samples obtained from NSCLC tissues was statistically higher compared to that from normal lung tissues (51.61%, 32/62 vs. 6.67%, 2/30; P<0.05). Survivin expression was closely correlated with tumor differentiation, lymph node metastasis and TNM stage (P<0.05), while Bcl-2 expression was only associated with TNM stage (P<0.05). The expression of survivin was positively correlated with that of Bcl-2 (P<0.05). A five-year follow-up study revealed that the expression of survivin and Bcl-2 was negatively correlated with post-operative survival duration. Our findings suggest that survivin and Bcl-2 may act synergistically in the occurrence, development, invasion and metastasis of NSCLC, both of which are up-regulated in NSCLC tissues. The co-expression of survivin and Bcl-2, which is closely related to malignancy, may serve as a biomarker for predicting prognosis.
Mol Med Rep 2012 Jun
PMID:Influence of survivin and Bcl-2 expression on the biological behavior of non-small cell lung cancer. 2244 32

A20 protein plays essential roles in tumorigenesis, but its value for diagnosis of pancreatic cancer remains unclear. Our aim was to determine whether A20 is a potential biomarker for the diagnosis of pancreatic cancer. The pancreatic cancer tissue microarray contained pancreatic cancer tissues (n = 40) and normal tissues (n = 10) was immunohistochemically assessed for A20 expression. The association of A20 expression with the tumor grade, lymph node metastasis, age and gender in pancreatic cancer patients were estimated by ANOVA. Stronger staining of A20 was observed in the normal tissues compared with that in the pancreatic cancer tissues (P = 0.003). ANOVA analysis showed that the A20 expression was not deeply associated with tumor grade, gender, age or TNM stages. The results implied that low A20 expression is significantly associated with the pancreatic cancer behavior, but is not the sole determinant of pancreatic cancer progression.
J Mol Histol 2012 Jun
PMID:Expression of A20 is reduced in pancreatic cancer tissues. 2246 Nov 93

The aim of this study was to investigate the expression of ZEB1 in gastric carcinoma, its correlation with the clinicopathology of gastric carcinoma, and the role of ZEB1 in invasion and metastasis in gastric carcinoma. ZEB1 expression was analyzed by immunohistochemistry and Western blot in 45 gastric carcinoma tissue samples that contained the adjacent gastric mucosa. The correlation between ZEB1 expression, the occurrence and development of gastric cancer, and clinical pathology was investigated. ZEB1 expression in the human gastric carcinoma cell line AGS was downregulated by RNA interference, and changes in ZEB1 expression corresponded with changes in the invasive and metastatic ability of AGS cells. Immunohistochemistry revealed that ZEB1 protein expression in gastric carcinoma tissues was significantly higher than in normal gastric mucosa tissues (p < 0.001). A lower degree of differentiation of gastric cancer (p = 0.009), a higher TNM (tumor, node, and metastasis) stage (p = 0.010), and a larger scope of invasion were correlated with higher expression of ZEB1 (p = 0.041, 0.002). However, the expression of ZEB1 in gastric carcinoma tissue was independent of gender, age, and tumor size (p > 0.05). Western blot results also showed that ZEB1 protein expression was significantly higher in gastric carcinoma tissue than in the adjacent normal gastric mucosa tissue (p = 0.008). A lower degree of differentiation of the gastric carcinoma correlated with a higher TNM stage, and a larger scope of invasion correlated with increased ZEB1 expression (p = 0.023). Transfection of ZEB1 siRNA in AGS cells significantly decreased the expression level of ZEB1 protein (p = 0.035). Furthermore, the number of cells that could pass through the Transwell chamber was significantly lower in the transfected group than in the non-transfected control group (p = 0.039), indicating that the suppression of ZEB1 expression could significantly reduce the invasive and metastatic ability of AGS cells (p = 0.005). Concluding, in gastric carcinoma tissue, overexpression of ZEB1 may be related to the occurrence and development as well as invasion and metastasis of gastric carcinoma.
Mol Cell Biochem 2012 Jul
PMID:Overexpression of ZEB1 associated with metastasis and invasion in patients with gastric carcinoma. 2246 58

Breast cancer (BC) is the most common neoplasm among women in most developed countries, including Egypt. Elevated levels of certain proteins in human BC are associated with unfavorable prognosis and progressive stages of the disease. The aim of our study was to evaluate the protein expression profile and prognostic significance of cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2), MMP-9 and membrane type 1-MMP (MT1-MMP) and their interaction in operable BC patients. The protein expression of COX-2, MMP-2 and MT1-MMP were evaluated by western blot technique, whereas enzymatic activity of MMP-2 and MMP-9 was determined by zymography in 47 breast cancer patients as well as normal adjacent tissues. Also, the correlation between these proteins and age, tumor size, LN stage, TNM stage, estrogen receptor, progesterone receptor, disease-free survival, and overall survival (OS) has been investigated. As compared to adjacent normal tissues, COX-2, MMP-2 and MT1-MMP were over-expressed in 43, 64, and 60 % of tumor tissues, respectively. In the same pattern, the activity of MMP-2 (62 %) and MMP-9 (45 %) was elevated in BC tissues. Multivariate analysis showed a positive correlation between the protein expression of COX-2, MMP-2, and MT1-MMP and the activity of MMP-2 and MMP-9 in BC patients. However, the enzymatic activity showed no correlation with clinicopathological features. This study confirms the preclinical evidence that COX-2 increased the expression of MT1-MMP, which in turn activates MMP-2. The lack of correlation with clinicopathological features, OS or disease-free survival ascertains the complexity of tumor progression and metastasis with many pro- and counter regulatory factors.
Mol Cell Biochem 2012 Jul
PMID:Clinical relevance of cyclooxygenase-2 and matrix metalloproteinases (MMP-2 and MT1-MMP) in human breast cancer tissue. 2252 32

The objective of this study was to identify new diagnostic, prognostic or therapeutic molecules for non-small- cell lung cancer (NSCLC). We investigated the expression of EphB4, a tyrosine kinase receptor which has been shown to act as a tumor promoter in other cancers. Using immunohistochemistry, we visualized EphB4 expression in 28 samples of NSCLC and 12 samples of adjacent normal tissues. Additionally, we assessed a single-nucleotide polymorphism in EphB4 to determine its effect on protein expression. The correlation of both genotype and protein expression with disease severity was determined. EphB4 was expressed in 53.6% of patients with lung cancer, a significant increase compared to control lung samples (0.0%, P<0.05). Furthermore, EphB4 expression was correlated with differentiation, lymph node metastasis and TNM stage of tumors (P<0.05). Additionally, the polymorphism in EphB4 at rs314310 appeared to correspond to protein expression and disease susceptibility. While the frequencies of CC, CA and AA genotypes were not different between lung cancer patients and healthy controls, the frequencies of C and A alleles were significantly different between these groups (P<0.05). Further analysis showed that the positive rate of EphB4 expression in patients with the AA genotype was significantly higher compared to that in patients with other genotypes (P<0.05). Overexpression of EphB4 plays a role in the occurrence and development of NSCLC, and the polymorphism at rs314310 may predispose individuals to this disease.
Mol Med Rep 2012 Aug
PMID:EphB4 gene polymorphism and protein expression in non-small-cell lung cancer. 2268 42

Breast cancer (BC) screening is important for early detection, but conventional tumor markers lack the desired sensitivity. Aberrant microRNA (miRNA) expression plays an important role in tumor formation and development. Thus, serum miRNAs represent potential BC biomarkers. microRNA-181a (miR-181a) is deregulated in many types of human cancer and is a key oncogenic regulator, but the relationship between serum miR-181a and BC diagnosis has not been investigated. This study investigated serum miR-181a levels in BC patients and healthy controls and compared the diagnostic value of serum miR-181a as a BC tumor marker with the conventional tumor markers CA153 and CEA. Serum miR-181a and miR-16 (as a control) were quantified by real-time quantitative RT-PCR in 20 plasma samples. The promising results prompted analysis of 227 additional samples. The levels of CA153 and CEA were measured using electrochemiluminescence assays. Median miR-181a levels were significantly lower in patients with BC compared to healthy controls (P=0.001). ROC analysis demonstrated the sensitivity and specificity of miR-181a for BC diagnosis at 70.7 and 59.9%, respectively, whereas the sensitivities of CA153 and CEA were 10.53 and 9.21%. As a tumor marker, serum miR-181a expressed a higher level of sensitivity [55.28% (68/123)] in the early stage of BC diagnosis (ductal carcinoma in situ, TNM I and II) than the CA153 and CEA markers (8.13 and 7.32%, respectively). There were no significant associations between miR-181a levels and other clinicopathological parameters. These results suggest that serum miR-181a may represent a novel biomarker for primary BC as well as for early stage BC diagnosis. In combination with other markers, serum miR-181a may improve the sensitivity of BC screening.
Int J Mol Med 2012 Sep
PMID:Decreased serum miR-181a is a potential new tool for breast cancer screening. 2269 39


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