Association between serum CCL-18 and IL-23 concentrations and disease progression of chronic obstructive pulmonary disease.

This study aimed to investigate the association between serum concentrations of chemokine (C-C Motif) ligand 18 (CCL-18) and interleukin 23 (IL-23) and clinical parameters of chronic obstructive pulmonary disease (COPD). The serum concentrations of CCL-18 and IL-23 were tested by enzyme linked immunosorbent assay (ELISA). The association between their concentrations and clinical parameters of COPD patients were analyzed by linear regression, logistic regression and ROC curve. The results showed that the serum concentrations of CCL-18 and IL-23 in COPD patients were increased compared with healthy people (P < 0.001) and that patients with acute exacerbation of COPD (AECOPD) had higher serum CCL-18 and IL-23 concentrations than stable patients (P < 0.001). Synergistic increase of CCL-18 and IL-23 in COPD patients was positively correlated with COPD patients' higher GOLD grade (P < 0.001), higher mMRC score (P < 0.001) and longer medical history (P < 0.001), but negatively correlated with the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) (P < 0.001) and FEV1% predicted (P < 0.001). The serum concentrations of CCL-18 and IL-23 were most related to the GOLD grade (OR = 2.764 for CCL-18 and OR = 4.215 for IL-23) and detection of both showed considerable sensitivity (72.57% for CCL-18 and 76.92% for IL-23) and specificity (92.50% for CCL-18 and 77.5% for IL-23) in identifying COPD. Increased serum concentrations of CCL-18 and IL-23 correlated with the disease progression of COPD and they could be used as biomarkers for disease evaluation of COPD.

Correlation between serum IL-32 concentration and clinical parameters of stable COPD: a retrospective clinical analysis.

This study was to investigate the association between serum interleukin 32 (IL-32) concentration and clinical parameters in patients with stable chronic obstructive pulmonary disease (COPD). One hundred and sixteen patients with stable COPD and 70 healthy subjects were included in the study. The serum concentration of IL-32 was detected by enzyme-linked immunosorbent assay. The correlation between serum IL-32 and clinical parameters of patients with COPD was analyzed by T-test, one-way analysis of variance, multiple linear regression and receiver operating characteristic curve. The serum concentration of IL-32 in patients with stable COPD was higher than that in healthy control group (p < 0.001) and increased serum IL-32 was positively correlated with GOLD grading (p = 0.026), mMRC score (p = 0.004) and clinical medical history (p = 0.005), but negatively related to FEV1/FVC (p = 0.001) and FEV1% predicted (p = 0.001). Patient's COPD grading (p = 0.001), clinical medical history (p < 0.001) and FEV1/FVC (p = 0.001) exerted a significant impact on serum IL-32. The sensitivity and specificity of serum IL-32 for discerning COPD patients from healthy individuals were 85.34% and 64.29%, and the area under the curve was 0.808 (p < 0.001). Increased IL-32 is involved in the chronic disease progression of COPD, suggesting that IL-32 may be a molecular biomarker that reflects the severity of COPD and contributes to the disease diagnosis.

Reduced Serum Concentration of CC16 Is Associated with Severity of Chronic Obstructive Pulmonary Disease and Contributes to the Diagnosis and Assessment of the Disease.

Background: The aim of this study was to reveal the correlations between serum concentration of Clara cell secretory protein (CC16) and clinical parameters of stable chronic obstructive pulmonary disease (COPD). Patients and Methods: Serum concentration of CC16 was determined by enzyme-linked immunosorbent assay (ELISA). The correlations between serum concentration of CC16 and clinical parameters was performed by linear correlation analysis and multiple linear regression analysis. The sensitivity and specificity of serum CC16 for differential diagnosis of COPD were determined by receiver operator characteristic curve (ROC). Results: The serum concentration of CC16 was down-regulated in stable COPD patients compared with healthy control group (p < 0.05). The decreased serum CC16 was negatively related to smoking (p < 0.05), GOLD grading (p < 0.005), mMRC score (p < 0.05) and medical history (p < 0.05) of patients, but positively correlated with pulmonary function (p < 0.05). The smoking, FEV1/FVC values, COPD grading and mMRC scores all affected the concentration of CC16 (p < 0.05). The decreased CC16 was an independent risk factor in the process of deterioration of lung function. The sensitivity and specificity of serum CC16 for identifying COPD reached to 65.3% and 75%. Conclusion: Decreased serum concentration of CC16 correlated with the disease progression of COPD, suggesting that it can be used as an indicator contributing to the diagnosis and assessment of COPD.

Post-discharge extended care contributes to the disease control of patients with COPD: a Chinese study.

BACKGROUND: The aim of this study was to evaluate the efficacy of extended care in patients with COPD. PATIENTS AND METHODS: A total of 140 patients with GOLD-2 to -4 of COPD were included in final analysis. The care efficacy was evaluated by the St George's Respiratory Questionnaire 12-item General Health Questionnaire (GHQ-12), pulmonary function test and blood gas analysis. RESULTS: The extended care improved the activity ability of COPD patients, relieved the clinical symptoms as well as reduced the impact degree of COPD to daily life (P<0.05). In addition, the extended care improved the mental health condition of patients with COPD compared with usual care (P<0.05). Moreover, the extended care improved the ventilation function of COPD patients, reduced the acute exacerbation rate and improved the blood gas levels compared with the usual care (P<0.05). CONCLUSION: The extended care improves the quality of life, respiratory function and the mental health condition of patients with COPD after discharge, indicating that it contributes to the disease control of patients with COPD.

Correlation of serum levels of HIF-1α and IL-19 with the disease progression of COPD: a retrospective study.

BACKGROUND: The aim of this study was to disclose the correlation between the serum levels of hypoxia-inducible factor 1 alpha (HIF-1α) and IL-19 and stable COPD. METHODS: The serum levels of HIF-1α and IL-19 were tested by ELISA. The relationships between their levels and clinical parameters of stable COPD patients were analyzed by linear regression methods. RESULTS: Patients with stable COPD showed higher serum levels of HIF-1α and IL-19 compared with healthy control group (P<0.001), and serum levels of HIF-1α and IL-19 had a positive linear correlation (P<0.05). In stable COPD patients, increased serum levels of HIF-1α and IL-19 were positively correlated with the GOLD grading (P<0.005), modified British Medical Research Council (mMRC) score (P<0.05), and medical history (P<0.05) but negatively related to the pulmonary function (P<0.05). The serum level of HIF-1α (P<0.05) was affected by the patient's FEV1/FVC value and COPD grading, and the serum level of IL-19 was associated with the mMRC scores and the serum level of HIF-1α (P<0.05). CONCLUSION: Increased serum levels of HIF-1α and IL-19 correlated with the disease progression of COPD, suggesting that they can be used as indicators to help us understand the COPD.

Molecular mechanism and targeted therapy of Hsp90 involved in lung cancer: New discoveries and developments (Review).

The exploration of the molecular mechanisms and signaling pathways on lung cancer is very important for developing new strategies of diagnosis and treatment to this disease, such as finding valuable lung cancer markers and molecularly targeted therapies. Previously, a number of studies disclose that heat shock protein 90 (Hsp90) is upregulated in cancer cells, tissues and serum of lung cancer patients, and its upregulation intimately correlates with the occurrence, development and outcome of lung cancer. On the contrary, inhibition of Hsp90 can suppress cell proliferation, motility and metastasis of lung cancer and promote apoptosis of lung cancer cells via complex signaling pathways. In addition, a series of Hsp90 inhibitors have been investigated as effective molecular targeted therapy tactics fighting against lung cancer. This review, systematically summarizes the role of Hsp90 in lung cancer, the molecular mechanisms and development of anti-Hsp90 treatment in lung cancer.

Increased stathmin correlates with advanced stage and poor survival of non-small cell lung cancer.

BACKGROUND: Previous studies show that overexpression of stathmin involved in the malignant biological behavior of lung cancer. This investigation is to disclose the expression status of stathmin in non-small cell lung cancer (NSCLC) and its clinical value for the diagnosis and prognosis to lung cancer. METHODS: The expression of stathmin in cells and tissues of NSCLC was examined using immunohistochemistry (IHC), in-situ hybridization (ISH), and Western blot. The correlation between stathmin expression and survival of lung cancer patients was evaluated by a Kaplan-Meier method and the multiple regression analysis. RESULTS: NSCLC tissues and cells showed an overexpression of stathmin compared with normal lung tissues and cells (p< 0.05). And the expression level of stathmin was significantly associated with lung adenocarcinoma (LAC) (p< 0.05), lymphatic invasion (p< 0.05) and advanced stages of NSCLC (p< 0.05). Moreover, overexpression of stathmin predicted a reduced survival (p<0.05). CONCLUSION: Increased stathmin correlated with pathologic grade, lymphatic invasion, advanced stage and poor survival of NSCLC, which indicated that stathmin could serve as a potential biomarker of NSCLC.

Increased level of Hsp90-beta in bronchoalveolar lavage fluid correlates with lymphatic invasion and advanced stage of lung cancer patients.

BACKGROUND: The purpose of this work is to explore the correlation between Hsp90-beta level in broncheoalveolar lavage fluid (BALF) and lung cancer. METHODS: Hsp90-beta level was measured by immunohistochemistry and enzyme-linked immunosorbent assay. Sensitivity and specificity of Hsp90-beta were calculated by receiver operator characteristic curve. RESULTS: BALF in patients with lung cancer showed a higher expression of Hsp90-beta than those with benign lung disease (P<0.05). Elevated Hsp90-beta was closely related to lymphatic invasion and advanced stage of patients with lung cancer (P<0.05). The sensitivity of BALF Hsp90-beta for discerning lung cancer from patients with benign disease was 82.56% and specificity was 97.56%. CONCLUSION: Increased BALF Hsp90-beta correlates with lymphatic invasion and advanced stage of patients with lung cancer, suggesting it could be a diagnostic indicator for patients with lung cancer.

Erratum: Identification and verification of Hsp90-beta as a potential serum biomarker for lung cancer.

[This corrects the article on p. 874 in vol. 4, PMID: 25520875.].

Matrine promotes the efficacy and safety of platinum-based doublet chemotherapy for advanced non-small cell lung cancer.

PURPOSE: Many studies have investigated the efficacy of matrine combined with platinum-based doublet chemotherapy (PBDC) versus PBDC alone for treating advanced non-small cell lung cancer (NSCLC). This study is an analytic value of available evidence. METHODS: twenty-two studies reporting matrine combined with PBDC versus PBDC alone for treating advanced NSCLC were reviewed. Pooled odds ratios and hazard ratio with 95% confidence intervals were calculated using either the fixed effects model or random effects model. RESULTS: The overall response rate (ORR) and disease control rate (DCR) of matrine combined with PBDC for treating NSCLC were significantly higher than those of PBDC alone, with 15.1% and 19.7% improvement, respectively (P < 0.00001). In addition, the mean survival time (MST) and quality of life (QOL) were improved after the treatment of matrine combined with PBDC (P < 0.00001). The main adverse effects found in this review were hematological reactions, nausea and vomiting. Matrine combined with PBDC had a lower incidence of adverse reactions compared with PBDC alone (P < 0.05). CONCLUSIONS: Matrine combined with PBDC was associated with higher RR, DCR, and MST as well as superior QOL profiles compared with PBDC alone. Matrine combined with PBDC decrease the incidence of adverse reactions compared with PBDC alone.

Identification and verification of Hsp90-beta as a potential serum biomarker for lung cancer.

BACKGROUND: Hsp90-beta was investigated as prognostic factor because of its apparent association with tumorigenesis. The aim of this study was to investigate the expression of Hsp90-beta in lung cancer patients, to analyze the relationship with respect to the clinicopathological features and to assess whether Hsp90-beta as a potential serum marker for lung cancer. METHODS: Expression of Hsp90-beta was examined using immunohistochemistry, in-situ hybridization, western blot and enzyme-linked immunosorbent assay. Sensitivities and specificities for Hsp90-beta serum test were determined using receiver operator characteristic curve and cutoff was defined based on 95% and 85% sensitivities. RESULTS: Lung cancer tissues exhibited higher expression of Hsp90-beta than the normal tissues (P < 0.05) and the serum Hsp90-beta of lung cancer patients also exhibited higher level than control groups (P < 0.05). Moreover, increased serum Hsp90-beta was significantly associated with the pathological grade and clinical stage of lung cancer patients (P < 0.05). Using receiver operator characteristic curve analysis, the cutoffs for distinguishing lung cancer from normal and benign groups were 1.155 and 1.158 ng/ml respectively. The sensitivities of Hsp90-beta for distinguishing lung cancer from normal and benign groups were 98.77% and 95.9%, and specificities were 88.33% and 72.7%. CONCLUSION: Up-regulation of serum Hsp90-beta was associated with pathological grade and clinical stage of lung cancer patients, which indicated that it could be considered molecular biomarker for diagnosis and prognosis of lung cancer.

Elevated serum annexin A1 as potential diagnostic marker for lung cancer: a retrospective case-control study.

BACKGROUND: Annexin A1 was investigated as prognostic factor because of its apparent association with tumorigenesis. The aim of this study was to investigate the expression of annexin A1 in lung cancer patients, and analysed the relationship with respect to the clinico-pathological features and assessed whether annexin A1 as a potential serum marker for lung cancer. METHODS: Expression of annexin A1 was examined using immunohistochemistry, in-situ hybridization, western blot and enzyme-linked immunosorbent assay. Sensitivities and specificities for annexin A1 serum test were determined using receiver operator characteristic curve and cutoff was defined based on 95% and 85% sensitivities. RESULTS: Lung cancer tissues exhibited higher expression of annexin A1 than the normal tissues (P < 0.05) and the serum annexin A1 of lung cancer patients also exhibited higher level than control groups (P < 0.05). Moreover, increased serum annexin A1 was significantly associated with the pathological grade and clinical stage of lung cancer patients (P < 0.05). Using receiver operator characteristic curve analysis, the cutoffs for distinguishing lung cancer from normal and benign groups were 4.77 and 4.84 ng/ml respectively. The sensitivities of annexin A1 for distinguishing lung cancer from normal and benign groups were 98.9% and 97.4%, and specificities were 88.3% and 66.4%. CONCLUSIONS: Up-regulation of serum annexin A1 was associated with pathological grade and clinical stage of lung cancer patients, which indicated that it could be considered molecular biomarker for diagnosis and prognosis of lung cancer.

Differential mitochondrial proteome analysis of human lung adenocarcinoma and normal bronchial epithelium cell lines using quantitative mass spectrometry.

BACKGROUND: Lung cancer is one of the higher incidences of malignant tumors around the world. At present, tumor markers CEA, CA19-9, and CA-125 in serum are used for the diagnosis of lung cancer, however, fewer studies have shown tumor markers for early diagnosis. Therefore, using quantitative mass spectrometry, differential mitochondrial proteome analysis was performed, comparing human lung adenocarcinoma and normal bronchial epithelium cells. METHODS: A human lung adenocarcinoma cell line A549 and a normal human bronchial epithelial cell line 16HBE were cultured in vitro. The cell mitochondria of the two cell lines were extracted and purified by differential centrifugation and percoll density gradient centrifugation. The integrity and purity of mitochondria were validated by electron microscopy and Western-blot. The proteins/peptides from lung cancer cells and normal cells were marked by the same amount of relative and absolute quantification of ectopic tags (iTRAQ). The mixed samples were analyzed and identified by two-dimensional liquid chromatography - tandem mass spectrometry (2D-LC-MS/MS). The proteome was analyzed with different bioinformatic tools. RESULTS: One hundred and sixty-one mitochondrial proteins were identified. One hundred and fifty-three mitochondrial proteins, which were expressed differently between 16HBE cells and A549 cells, were identified. Sixty-seven proteins were high expression, while 86 proteins were lower expression. Expression of three proteins: ornithine aminotransferase (OAT), heat shock protein beta90 (HSP90), and vimentin (VIM), was increased more than twice. Our results, in combination with the literature review, suggest that HSP90 and Vimentin may be the new tumor markers of lung cancer.

Systematic review and meta-analysis of Endostar (rh-endostatin) combined with chemotherapy versus chemotherapy alone for treating advanced non-small cell lung cancer.

BACKGROUND: Many studies have investigated the efficacy of Endostar combined with platinum-based doublet chemotherapy (PBDC) versus PBDC alone for treating advanced non-small cell lung cancer (NSCLC). This study is a meta-analysis of available evidence. METHODS: Fifteen studies reporting Endostar combined with PBDC versus PBDC alone for treating advanced NSCLC were reviewed. Pooled odds ratios and hazard ratio with 95% confidence intervals were calculated using either the fixed effects model or random effects model. RESULTS: The overall response rate (ORR) and disease control rate (DCR) of Endostar combined with PBDC for treating NSCLC were significantly higher than those of PBDC alone, with 14.7% and 13.5% improvement, respectively (P < 0.00001). In addition, the time to progression (TTP) and quality of life (QOL) were improved after the treatment of Endostar combined with PBDC (P < 0.00001). The main adverse effects found in this review were hematological reactions, hepatic toxicity, and nausea/vomiting. Endostar combined with PBDC had a similar incidence of adverse reactions compared with PBDC alone (P < 0.05). CONCLUSIONS: Endostar combined with PBDC was associated with higher RR, DCR, and TTP as well as superior QOL profiles compared with PBDC alone. Endostar combined with PBDC had a similar incidence of adverse reactions compared with PBDC alone.

Study of differential proteins in lung adenocarcinoma using laser capture microdissection combined with liquid chip-mass spectrometry technology.

BACKGROUND: In recent years the proportion of lung adenocarcinoma (adCA) which occurs in lung cancer patients has increased. Using laser capture microdissection (LCM) combined with liquid chip-mass spectrometry technology, we aimed to screen lung cancer biomarkers by studying the proteins in the tissues of adCA. METHODS: We used LCM and magnetic bead based weak cation exchange (MB-WCX) to separate and purify the homogeneous adCA cells and normal cells from six cases of fresh adCA and matched normal lung tissues. The proteins were analyzed and identified by matrix assisted laser desorption/ionization time-of-fight mass spectrometry (MALDI-OF-MS). We screened for the best pattern using a radial basic function neural network algorithm. RESULTS: About 2.895 × 10(6) and 1.584 × 10(6) cells were satisfactorily obtained by LCM from six cases of fresh lung adCA and matched normal lung tissues, respectively. The homogeneities of cell population were estimated to be over 95% as determined by microscopic visualization. Comparing the differentially expressed proteins between the lung adCA and the matched normal lung group, 221 and 239 protein peaks, respectively, were found in the mass-to-charge ration (M/Z) between 800 Da and 10 000 Da. According to t test, the expression of two protein peaks at 7521.5 M/Z and 5079.3 M/Z had the largest difference between tissues. They were more weakly expressed in the lung adCA compared to the matched normal group. The two protein peaks could accurately separate the lung adCA from the matched normal lung group by the sample distribution chart. A discriminatory pattern which can separate the lung adCA from the matched normal lung tissue consisting of three proteins at 3358.1 M/Z, 5079.3 M/Z and 7521.5 M/Z was established by a radial basic function neural network algorithm with a sensitivity of 100% and a specificity of 100%. CONCLUSIONS: Differential proteins in lung adCA were screened using LCM combined with liquid chip-mass spectrometry technology, and a biomarker model was established. It is possible that this technology is going to become a powerful tool in screening and early diagnosis of lung adCA.