scholarly journals Relationship between E-cadherin, matrix metalloproteinase-7 gene expression and clinicopathological features in gastric carcinoma

2006 ◽  
Author(s):  
Kyung Lee ◽  
Sang Shin ◽  
Kyeong Kim ◽  
Min Kim ◽  
Myung Hyun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Carcinoma ◽  
Matrix Metalloproteinase ◽  
Clinicopathological Features ◽  
Matrix Metalloproteinase 7 ◽  
E Cadherin

Decline in serum soluble E-cadherin and low baseline matrix metalloproteinase-9 are associated with response to combination celecoxib and erlotinib therapy in advanced non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7640-7640
Author(s):  
K. L. Reckamp ◽  
B. K. Gardner ◽  
R. A. Figlin ◽  
D. Elashoff ◽  
K. Krysan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Combination Therapy ◽  
Matrix Metalloproteinase ◽  
Epithelial To Mesenchymal Transition ◽  
Advanced Nsclc ◽  
Mesenchymal Transition ◽  
Best Response ◽  
Cox 2 ◽  
E Cadherin

7640 Background: Cyclooxygenase-2 (COX-2) overexpression may mediate resistance to EGFR TK inhibition through prostaglandin E2 (PGE2)-dependent promotion of epithelial to mesenchymal transition (EMT). Thomson, et al. reported that the suppression of epithelial markers such as E-cadherin led to resistance to erlotinib (Cancer Res 2005;65:9455). In addition, PGE2 downregulates E-cadherin expression by upregulating transcriptional repressors including ZEB1 and Snail, as described by Dohadwala et al (Cancer Res 2006;66:5338). These findings suggest that COX-2 inhibition may enhance the efficacy of EGFR TKI therapy in NSCLC. Methods: A phase I, dose escalation trial to was performed investigating the combination of celecoxib and erlotinib in pts with advanced NSCLC. Soluble E-cadherin (sEC) was evaluated by ELISA in pt serum at baseline and weeks 4 and 8 of treatment. Other markers of COX-2 gene expression were evaluated by ELISA, including matrix metalloproteinase (MMP)-9, MMP-2 and tissue inhibitor of MMP (TIMP1). Results: 22 pts were enrolled and 21 were evaluable for the determination of the optimal dose, toxicity assessment and response (reported in Clin Cancer Res 2006;12:3381). Here we report serum sEC and MMP-9 levels, which were analyzed according to best response (PR, SD or PD) in 21 pts. SEC was analyzed according to best response (PR, SD or PD). We found a significant decrease in sEC between baseline and week 8 in pts with PR when compared to those with SD or PD (p = 0.021). In pts who responded to the combination therapy, baseline MMP-9 was significantly lower compared to non-responders (p = 0.006). Conclusions: SEC, MMP-9 and other downstream markers of COX-2 gene expression may be useful for assessing response to combination celecoxib and erlotinib in pts with advanced NSCLC. A randomized Phase II trial is planned comparing erlotinib and celecoxib with erlotinib plus placebo in advanced NSCLC, to evaluate the efficacy of this combination therapy and to assess these and other biomarkers in both serum and tumor tissue. Supported by ASCO Young Investigator Award, UCLA Lung Cancer SPORE NCI P50 CA 90388 and GLAVAHS Career Development Award. No significant financial relationships to disclose.

scholarly journals Prognostic Significance of Matrix Metalloproteinase-7 (MMP-7) Expression at the Invasive Front in Gastric Carcinoma

2002 ◽  
Vol 93 (3) ◽  
pp. 291-295 ◽  
Author(s):  
Xiu Ping Liu ◽  
Shigeto Kawauchi ◽  
Atsunori Oga ◽  
Kureo Tsushimi ◽  
Mutsuo Tsushimi ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Matrix Metalloproteinase ◽  
Prognostic Significance ◽  
Invasive Front ◽  
Matrix Metalloproteinase 7

scholarly journals Matrix Metalloproteinase-7 Induces E-Cadherin Cleavage in Acid-Exposed Primary Human Pharyngeal Epithelial Cells Via The ROS/ERK/c-Jun Pathway

2021 ◽  
Author(s):  
Nu-Ri IM ◽  
Byoungjae Kim ◽  
Kwang-Yoon Jung ◽  
Seung-Kuk Baek
Keyword(s):  
Epithelial Cells ◽  
Matrix Metalloproteinase ◽  
Laryngopharyngeal Reflux ◽  
Mucosal Damage ◽  
Acid Exposure ◽  
Mitogen Activated Protein Kinase ◽  
Signaling Mechanism ◽  
Transepithelial Permeability ◽  
Matrix Metalloproteinase 7 ◽  
E Cadherin

Abstract Introduction Laryngopharyngeal reflux disease (LPRD) is caused by pharyngeal mucosal damage due to the reflux of gastric contents, including acid, pepsin, and bile juice. Our previous study has demonstrated that LPRD is associated with the cleavage of E-cadherin, which is facilitated by the acid-activated matrix metalloproteinase-7 (MMP-7); however, the mechanism by which the acid activates MMP-7 remains unclear. The purpose of this study was to investigate the mechanism by which MMP-7 is activated in the pharyngeal epithelial cells that are exposed to acid. Methods The levels of reactive oxygen species (ROS) were measured in the epithelial cells exposed to acid. To investigate the signaling mechanism of ROS in the expression of MMP-7, the mechanism of action of the mitogen-activated protein kinase was examined. The expression of various signaling factors were determined, according to the presence or absence of each inhibitor in the acid-exposed pharyngeal epithelial cells. To identify changes in the cleavage of E-cadherin, the integrity of the mucosal membrane was assessed using a transepithelial permeability test.ResultsWe found that acid exposure increased the levels of ROS, phosphorylated-extracellular signal-regulated kinase (p-ERK) 1/2, and phosphorylated-c-Jun (p-c-Jun) in pharyngeal epithelial cells. The ROS inhibitor reduced the expression of p-ERK and MMP-7, while the ERK inhibitor reduced the expression of p-c-Jun and MMP-7. Moreover, the c-Jun inhibitor reduced the expression of MMP-7 and blocked the degradation of E-cadherin. In addition, decrease in the levels of immunostained E-cadherin and increase in transepithelial permeability after acid exposure were collectively alleviated by the inhibitors of ROS, ERK, and c-Jun. Conclusions The degradation of E-cadherin that occurs after human mucosal cells are exposed to acid appears to be caused by an increase in the expression of MMP-7 via the ROS/ERK/c-Jun pathway, which is thought to be an important mechanism associated with the development of LPRD.

Clinical Significance of Matrix Metalloproteinase-7 and Ets-1 Gene Expression in Patients with Lung Cancer

2001 ◽  
Vol 101 (2) ◽  
pp. 242-247 ◽  
Author(s):  
Hidefumi Sasaki ◽  
Haruhiro Yukiue ◽  
Satoru Moiriyama ◽  
Yoshihiro Kobayashi ◽  
Yoshiaki Nakashima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Matrix Metalloproteinase ◽  
Clinical Significance ◽  
Matrix Metalloproteinase 7
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