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c-Met Expression (c-met + expression)
Selected AbstractsExpression of c-MET, low-molecular-weight cytokeratin, matrix metalloproteinases-1 and -2 in spinal chordomaHISTOPATHOLOGY, Issue 5 2009Takahiko Naka Aims:, In skull base chordoma, c-MET expression has been reported to correlate with younger patient age and favourable prognosis; however, it also contributes to tumour invasiveness, especially in recurrent lesions, suggesting variable roles for c-MET according to clinical status. The aim of this study was to investigate the significance of c-MET expression in spinal chordoma, which affects patients who are 10,20 years older than those with skull base chordoma. Methods and results:, Using immunohistochemical techniques, the expression of c-MET and its ligand, hepatocyte growth factor (HGF) was investigated in 34 primary spinal chordomas and compared with other clinicopathological parameters. Expression of c-MET and HGF was observed in 85.3 and 21.7% of lesions, respectively. c-MET expression correlated with the expression of an epithelial marker, low-molecular-weight cytokeratin (CAM5.2). Lesions with higher c-MET expression showed significantly stronger expression of proteinases, including matrix metalloproteinase (MMP)-1 and MMP-2. However, c-MET expression was not associated with patient age, proliferative ability estimated by MIB-1 labelling index, or prognosis. Conclusions:, c-MET expression was observed in most spinal chordomas and correlated with the expression of CAM5.2, suggesting a relationship to an epithelial phenotype. [source] Prognostic implications of ezrin expression in human hepatocellular carcinomaMOLECULAR CARCINOGENESIS, Issue 9 2010Yun Kyung Kang Abstract Ezrin is known to regulate cellular survival, adhesion, migration, and invasion and has been identified as one of the key components of tumor progression and metastasis. The authors investigated ezrin expression in human hepatocellular carcinoma (HCC) and sought to determine its relation with clinicopathologic parameters, patients' outcome, and interacting molecular markers. Ezrin expression was assessed by immunohistochemical staining in 100 surgically resected HCCs using the tissue microarray method. A total of 28 HCCs showed high ezrin immunoreactivity, mainly in cytoplasm. Ezrin expression exhibited a positive correlation with c-Met expression (P,=,0.001), but showed no correlation with the expression of CD44s or E-cadherin. HCCs expressing high level of ezrin were significantly associated with advanced TNM stage, poor Edmondson's histological grade, macroscopic portal vein invasion, tumor recurrence, and extrahepatic recurrence (P,<,0.05). Univariate analysis showed that HCCs with high ezrin immunoreactivity were strongly associated with unfavorable overall and disease-free survivals than HCCs with low or negative for ezrin immunoreactivity (P,=,0.0001 and 0.0011, respectively). Furthermore, multivariate analysis demonstrated that a high level of ezrin expression was independently associated with poor overall survival (hazard ratio, 1.905; P,=,0.011). The results suggest that ezrin expression could be a potential predictive marker of progression, metastasis, and prognosis in HCC. © 2010 Wiley-Liss, Inc. [source] Hepatocyte growth factor protects auditory hair cells from aminoglycosidesTHE LARYNGOSCOPE, Issue 10 2009Yayoi S. Kikkawa MD Abstract Objectives/Hypothesis: To examine the effect of hepatocyte growth factor (HGF) for protection of auditory hair cells against aminoglycosides and its molecular mechanisms. Study Design: Experimental study. Methods: We quantitatively assessed protective effects of HGF on mouse cochlear hair cells against neomycin toxicity using explant culture systems. To understand mechanisms of hair cell protection by HGF, we examined the expression of c-Met, HGF receptor, and 4-hydroxynonenal (a lipid peroxidation marker) in the cochlea by means of immunohistochemistry and Western blotting. Results: The application of HGF to cochlear explant cultures significantly reduced the hair cell loss induced by neomycin. Immunohistochemistry showed c-Met expression in normal auditory hair cells, and its increase in response to neomycin-induced damage. Immunostaining for 4-hydroxynonenal suggested that HGF acted by attenuating the lipid peroxidation of auditory epithelia induced by neomycin. Conclusions: These findings demonstrate that a functional HGF/c-Met coupling is present in the cochlea, and HGF application exerts protective effects on hair cells, indicating the potential of HGF as a therapeutic agent for sensorineural hearing loss. Laryngoscope, 2009 [source] Small molecule c-MET inhibitor PHA665752: Effect on cell growth and motility in papillary thyroid carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2008Chandrani Chattopadhyay PhD Abstract Background c-Met is upregulated in papillary thyroid carcinoma (PTC) and can be an attractive therapeutic target. We tested the effects of the small molecule c-met inhibitor PHA665752 in blocking c-met,dependent phenotypic effects in PTC cell lines. Methods PTC patient tissues and cell lines were evaluated for c-met expression. The effect of PHA665752 on c-met phosphorylation, downstream signaling, hepatocyte growth factor (HGF),dependent cell growth, and induction of apoptosis was studied. The IC50 of PHA665752 in c-met,expressing PTC cells was determined, and growth curves at 0.1×, 1×, and 10× IC50 concentrations were obtained. Poly(ADP-ribose) polymerase (PARP) and caspase-9-processing post-PHA665752 treatment were studied as markers of apoptosis, and assays analyzing HGF-dependent cell invasion and migration in the presence and absence of PHA665752 were done. Results c-Met was upregulated in most of the patient tissues with PTC and in many PTC cell lines. PHA665752 specifically inhibited c-met phosphorylation, c-met,dependent cell growth, signal transduction, cell survival, cell invasion, and migration in PTC cells with high c-met. Conclusions PHA665752 is an effective and specific inhibitor of c-met in PTC cells with high levels of c-met expression. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [source] | ||||||||||