Nuclear factor-κB (NF-κB) has a vital role in cell survival. Inhibition of NF-κB has been proven to be an efficient therapeutic pathway for various cancers. Activation of NF-κB is mainly through serine residues' phosphorylation of inhibitor of κBα (IκBα) by IKK complex. Phosphorylation at tyrosine 42 is an alternative pathway in regulation of IκBα and NF-κB signaling, though little is known about the underlying mechanism. Here we identified regulator of calcineurin 1 (RCAN1) as a novel endogenous inhibitor of NF-κB signaling pathway. RCAN1 can interact with IκBα and affect the phosphorylation of IκBα at tyrosine 42. Overexpression of RCAN1 by adenovirus reduced cell viability in lymphoma Raji cells and restrained the growth of lymphoma transplants in mice. We further found that N terminus 1–103aa of RCAN1 is sufficient to inhibit NF-κB and reduce cell viability of lymphoma cells. Our study implicated a novel therapeutic approach for lymphoma by RCAN1 through inhibition of NF-κB signaling.
OBJECTIVE: Retrospective study to investigate levels of components of the urokinase-type plasminogen activator (uPA) system in patients with chronic obstructive pulmonary disease (COPD). METHODS: Peripheral lung tissue was obtained from patients who underwent surgical resection for benign lung diseases: 16 patients with COPD, 10 controls without lung function impairment who were smokers, and 10 controls without lung function impairment who were nonsmokers.Immunohisto chemical staining for uPA, uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) was quantified. Airway remodelling (collagen; detected by Sirius red staining), lung function (determined by spirometry) and emphysema (alveolar destruction; percentage of low attenuation areas on computed tomography scan) were evaluated. RESULTS: uPA, uPAR and PAI-1 were significantly different in structural lung cells and pulmonary macrophages from patients with COPD compared with controls. There were significant positive correlations between collagen levels and uPA and PAI-1, and between uPA and degree of emphysema. There were significant inverse correlations between lung function and uPA, uPAR and PAI-1. CONCLUSION: Correlations between components of the uPA system and lung function, small airway fibrosis and emphysema indicate a role for the uPA system in COPD.
ABSTRACT. The specific correlation between CXCR4 expression and survival in non-small cell lung cancer (NSCLC) has been investigated independently; however, these have yielded inconsistent results. Therefore, we examined the exact relationship between CXCR4 expression and NSCLC in this meta-analysis. The bibliographic databases in English and Chinese were carefully searched and data regarding the prognostic value of CXCR4 and its association with pathological parameters of NSCLC were collected. Pooled odds ratios (OR) with 95% confidence interval (CI) were applied. A total of twelve studies (CXCR4 positive cases = 565, CXCR4 negative = 755; 2003-2013) that matched our predefined criteria were finally incorporated into our study. The pooled OR revealed that expression of CXCR4 in NSCLC patients was apparently correlated with lymphatic (2015) metastasis, distant metastasis, and TNM stages (lymphatic metastasis: OR = 1.91, 95%CI = 1.21-3.27, P = 0.018; distant metastasis: OR = 4.81, 95%CI = 1.69-13.66, P = 0.003; TNM stages: OR = 3.91, 95%CI = 1.22-12.55, P = 0.022). Positive expression of CXCR4 was also strongly correlated with a shorter overall survival (OS) rate in NSCLC patients (hazard ratio = 2.10, 95%CI = 1.21-2.99, P < 0.05). Further stratification by ethnicity indicated a negative association between CXCR4 expression and NSCLC development and prognosis in Asians NSCLC patients in all four models (P < 0.05). This indicated that elevated CXCR4 expression may be correlated with aggressive metastasis, advanced TNM stages, and shorter OS rate in NSCLC patients, suggesting a poor prognostic outcome of this disease.
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