ABSTRACT
Objective Toexploretheprognosticvalueofpreoperativeneutrophil-to-lymphocyteratioandderived neutrophil-to-lymphocyteratioincolorectalcancer(CRC)individuals.Methods Theclinicalpathologicaldataand preoperative blood routine test results were collected from medical records,and 5 year follow up was performed in a total of 555 surgically resected CRC cases.Receiver operative curve (ROC)was used to calculate NLR and d -NLR cut-off value,and Kaplan-Meier curve and multiple COX regression were selected to evaluate the influence of preoperative NLR and d -NLR on clinical outcome of CRC cases and prognostic predictive nomogram was established to evaluate the predictivevalueofNLRandd-NLR.Results Usingoverallsurvival(OS)asanendpoint,theoptimalcut-offvaluesof NLR and d-NLR were 3.21 (Sensitivity=0.752,specificity=0.753,AUC=0.762)and 2.12 (sensitivity=0.721, specificity=0.683,AUC=0.720),respectively.Preoperative NLR and d-NLR were significantly associated with free-recurrent survival (RFS)and OS(P<0.01).NLR and d-NLR were independent factors for prediction of RFS (HRNLR=2.53,HRd-NLR=1.60)and OS (HRNLR=2.75,HRd-NLR=2.11)in II-III stage preoperative CRC patients.The C-indexes of RFS and OS predictive nomograms including NLR and d-NLR were 0.851 and 0.836,and C-indexes without NLRandd-NLRwere0.801and0.793,respectively.Conclusion ThisresultsindicatedthatRFSandOSofthe patients with preoperative high NLR and d-NLR were significantly shorter than those with relative low NLR and d-NLR, and they were independent prognostic predictive factors for RFS and OS,and nomograms including NLR and d-NLR could significantly improve the prognostic predictive efficacy in postoperative CRC individuals.
ABSTRACT
In patients with advanced cancer, cancer-induced bone pain (CIBP) is a severe and common problem that is difficult to manage and explain. As c-Jun N-terminal kinase (JNK) and chemokine (C-X-C motif) ligand 1 (CXCL1) have been shown to participate in several chronic pain processes, we investigated the role of JNK and CXCL1 in CIBP and the relationship between them. A rat bone cancer pain model was established by intramedullary injection of Walker 256 rat gland mammary carcinoma cells into the left tibia of Sprague-Dawley rats. As a result, intramedullary injection of Walker 256 carcinoma cells induced significant bone destruction and persistent pain. Both phosphorylated JNK1 (pJNK1) and pJNK2 showed time-dependent increases in the ipsilateral spinal cord from day 7 to day 18 after tumor injection. Inhibition of JNK activation by intrathecal administration of SP600125, a selective pJNK inhibitor, attenuated mechanical allodynia and heat hyperalgesia caused by tumor inoculation. Tumor cell inoculation also induced robust CXCL1 upregulation in the ipsilateral spinal cord on day 18 after tumor injection. Inhibition of CXCL1 by intrathecal administration of CXCL1 neutralizing antibody showed a stable analgesic effect. Intrathecal administration of SP600125 reduced CXCL1 increase in the spinal cord, whereas inhibition of CXCL1 in the spinal cord showed no influence on JNK activation. Taken together, these results suggested that JNK activation in spinal cord contributed to the maintenance of CIBP, which may act through modulation of CXCL1. Inhibition of the pJNK/CXCL1 pathway may provide a new choice for treatment of CIBP.
Subject(s)
Animals , Female , Rats , Antibodies, Neutralizing , Allergy and Immunology , Therapeutic Uses , Bone Neoplasms , Metabolism , Cancer Pain , Drug Therapy , Metabolism , Cell Line, Tumor , Chemokine CXCL1 , Allergy and Immunology , Metabolism , JNK Mitogen-Activated Protein Kinases , Metabolism , Protein Kinase Inhibitors , Pharmacology , Therapeutic Uses , Rats, Sprague-Dawley , Spinal Cord , MetabolismABSTRACT
To better understand the outcomes of small cell lung cancer (SCLC), we examined the clinical features and prognostic factors of SCLC in this study. A total of 148 patients who were diagnosed as having SCLC between January 2009 and December 2013 in Cancer Center of Union Hospital, Wuhan, China, were enrolled and their clinical features and prognostic factors were retrospectively analyzed. Log-rank test and Cox regression model were employed for analysis of prognostic factors. The 1- and 2-year overall survival (OS) rates were 59.7% and 25.7%, respectively, for limited disease (LD) patients whose median survival time (MST) was 16 months. The 1- and 2-year OS rates were 29.5% and 5.3%, respectively, for extensive disease (ED) patients whose MST was 10 months. The univariate analysis and multivariate analysis revealed that age, tumor stage, serum CEA and Ki-67 antigen were significantly correlated to the outcomes of SCLC, and they were significant prognostic factors for SCLC.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Ki-67 Antigen , Blood , Lung Neoplasms , Blood , Epidemiology , Pathology , Neoplasm Staging , Small Cell Lung Carcinoma , Blood , Epidemiology , Pathology , Survival AnalysisABSTRACT
In patients with advanced cancer, cancer-induced bone pain (CIBP) is a severe and common problem that is difficult to manage and explain. As c-Jun N-terminal kinase (JNK) and chemokine (C-X-C motif) ligand 1 (CXCL1) have been shown to participate in several chronic pain processes, we investigated the role of JNK and CXCL1 in CIBP and the relationship between them. A rat bone cancer pain model was established by intramedullary injection of Walker 256 rat gland mammary carcinoma cells into the left tibia of Sprague-Dawley rats. As a result, intramedullary injection of Walker 256 carcinoma cells induced significant bone destruction and persistent pain. Both phosphorylated JNK1 (pJNK1) and pJNK2 showed time-dependent increases in the ipsilateral spinal cord from day 7 to day 18 after tumor injection. Inhibition of JNK activation by intrathecal administration of SP600125, a selective pJNK inhibitor, attenuated mechanical allodynia and heat hyperalgesia caused by tumor inoculation. Tumor cell inoculation also induced robust CXCL1 upregulation in the ipsilateral spinal cord on day 18 after tumor injection. Inhibition of CXCL1 by intrathecal administration of CXCL1 neutralizing antibody showed a stable analgesic effect. Intrathecal administration of SP600125 reduced CXCL1 increase in the spinal cord, whereas inhibition of CXCL1 in the spinal cord showed no influence on JNK activation. Taken together, these results suggested that JNK activation in spinal cord contributed to the maintenance of CIBP, which may act through modulation of CXCL1. Inhibition of the pJNK/CXCL1 pathway may provide a new choice for treatment of CIBP.
ABSTRACT
<p><b>OBJECTIVE</b>To determine the effect of exogenous GM3 on proliferation, apoptosis and VEGF expression in human lung adenocarcinoma cell line A549 cells.</p><p><b>METHODS</b>A549 cells were treated with GM3 at different concentrations for 48 hours. MTT assay was used to detect the cell proliferation and flow cytometry was applied to analyze cell apoptosis. RT-PCR was used to detect the expression level of VEGF mRNA and confocal laser scanning microscopy was applied to observe the localization and fluorescence intensity of VEGF.</p><p><b>RESULTS</b>Comparing with the control, being treated with higher than 10 µmol/L GM3 significantly inhibited A549 cell proliferation (P < 0.05), and the suppressive effect could be enhanced following increasing doses. The IC(50) was 412 µmol/L. Comparing with the control, being treated with higher than 40 µmol/L GM3 significantly promoted the apoptotic rate of A549 cells (P < 0.05). Comparing with the control, being treated with higher than 40 µmol/L GM3 significantly decreased the VEGF mRNA level of A549 cells (P < 0.05), and the fluorescence intensity of VEGF distinctly weakened.</p><p><b>CONCLUSIONS</b>Exogenous ganglioside GM3 can inhibit the proliferation, promote apoptosis, and down-regulate the VEGF expression level in A549 cells. This may be considered as two mechanisms of GM3 for its anti-tumor effect by modulating cell apoptosis and angiogenesis.</p>