Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We sought to evaluate the biological function of the receptor tyrosine kinase EphB4 in bladder cancer. All of the nine bladder cancer cell lines examined express EphB4 and the receptor could be phosphorylated following stimulation with its cognate ligand, EphrinB2. Out of the 15 fresh bladder cancer specimens examined, 14 expressed EphB4 with a mean sevenfold higher level of expression compared to adjacent normal urothelium. EphB4 expression was regulated by several mechanisms: EPHB4 gene locus was amplified in 27% tumor specimens and 33% cell lines studied; inhibition of EGFR signaling downregulated EphB4 levels; and forced expression of wild-type p53 reduced EphB4 expression. EphB4 knockdown using specific siRNA and antisense oligodeoxynucleotides molecules led to a profound inhibition in cell viability associated with apoptosis via activation of caspase-8 pathway and downregulation of antiapoptotic factor, bcl-xl. Furthermore, EphB4 knockdown significantly inhibited tumor cell migration and invasion. EphB4 knockdown in an in vivo murine tumor xenograft model led to a nearly 80% reduction in tumor volume associated with reduced tumor proliferation, increased apoptosis and reduced tumor microvasculature. EphB4 is thus a potential candidate as a predictor of disease outcome in bladder cancer and as target for novel therapy.
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PMID:EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival. 1620 42

The receptor tyrosine kinase EphB4 and its ligand EphrinB2 play critical roles in blood vessel maturation, and are frequently overexpressed in a wide variety of cancers. We studied the aberrant expression and biological role of EphB4 in head and neck squamous cell carcinoma (HNSCC). We tested the effect of EphB4-specific siRNA and antisense oligonucleotides (AS-ODN) on cell growth, migration and invasion, and the effect of EphB4 AS-ODN on tumor growth in vivo. All HNSCC tumor samples express EphB4 and levels of expression correlate directly with higher stage and lymph node metastasis. Six of 7 (86%) HNSCC cell lines express EphB4, which is induced either by EGFR activation or by EPHB4 gene amplification. EphrinB2 was expressed in 65% tumors and 5 of 7 (71%) cell lines. EphB4 provides survival advantage to tumor cells in that EphB4 siRNA and AS-ODN significantly inhibit tumor cell viability, induce apoptosis, activate caspase-8, and sensitize cells to TRAIL-induced cell death. Furthermore, EphB4-specific AS-ODN significantly inhibits the growth of HNSCC tumor xenografts in vivo. Expression of EphB4 in HNSCC tumor cells confers survival and invasive properties, and thereby provides a strong rationale for targeting EphB4 as novel therapy for HNSCC.
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PMID:EphB4 provides survival advantage to squamous cell carcinoma of the head and neck. 1661 13

The upregulation of EPH receptor B4 (EPHB4) results in a survival advantage for tumor cells via the inhibition of the casapse-8-mediated apoptotic pathway, which begins from the cell membrane. The present study investigated the expression patterns of EPHB4, ephrin B2 (EFNB2) and caspase-8 in patients with esophageal squamous cell carcinoma (ESCC). The association between the expression patterns and certain clinicopathological characteristics of the patients was also determined. mRNA levels of EPHB4, EFNB2 and caspase-8 in paired primary ESCC samples and adjacent esophageal tissues collected from 96 patients with ESCC were quantified using quantitative PCR. Upregulation of EPHB4 and EFNB2 mRNA expression, and downregulation of caspase-8 mRNA were detected in ESCC samples compared with that in the adjacent esophageal tissues. The expression levels of EPHB4 and EFNB2 were positively correlated with each other, whereas the mRNA levels of both EPHB4 and EFNB2 exhibited a negative correlation with that of caspase-8. The mRNA levels of both EPHB4 and EFNB2 demonstrated a significant positive association with certain clinicopathological features of patients with ESCC, including family history, tumor size, metastasis and stage. Conversely, a negative association was revealed between the expression level of caspase-8 and clinicopathological features of patients with ESCC. Moreover, mRNA expression levels of EPHB4 and EFNB2 were negatively associated with survival times of patients with ESCC, whereas the level of caspase-8 was positively associated with patient outcome. The results from the present study suggested that EPHB4, EFNB2 and caspase-8 may be implicated in the tumorigenesis and progression of ESCC, and that consequently, they may serve as useful prognostic markers, as well as potential therapeutic targets.
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PMID:Expression levels of EPHB4, EFNB2 and caspase-8 are associated with clinicopathological features and progression of esophageal squamous cell cancer. 3188 20