PDLIM2 acts as a cancer suppressor gene in non-small cell lung cancer via the down regulation of NF-κB signaling.

PDZ and LIM domain containing protein 2 (PDLIM2) has been identified as a vital tumor-associated gene that is aberrantly expressed in various types of tumors. Yet, the involvement of PDLIM2 in non-small cell lung cancer (NSCLC) is currently undetermined. The design of the current study was to evaluate whether PDLIM2 plays a role in NSCLC. We found that PDLIM2 expression was commonly decreased in NSCLC tissues. Moreover, low expression of PDLIM2 was also detected in NSCLC cell lines and demethylation treatment restored PDLIM2 expression. The re-expression of PDLIM2 impeded the proliferative, colony-forming, and invasive capabilities of NCLCL cells. In contrast, depletion of PDLIM2 markedly enhanced the malignant behaviors of NSCLC cells. Notably, PDLIM2 overexpression downregulated the expression of nuclear factor (NF)-κB p65 subunit and repressed NF-κB transcription reporter activity in NSCLC cells. The overexpression of p65 significantly reversed PDLIM2-mediated antitumor effects in NSCLC cells. Additionally, the Xenograft tumor formation assay revealed that the overexpression of PDLIM2 markedly restricted the tumor growth of NSCLC in vivo. Overall, our study confirms that PDLIM2 acts as a tumor-inhibitor in NSCLC through the inactivation of NF-κB, suggesting PDLIM2 as a candidate therapeutic target for NSCLC.

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.

Diagnostic value and safety of medical thoracoscopy for pleural effusion of different causes.

BACKGROUND: Pleural effusions occur for various reasons, and their diagnosis remains challenging despite the availability of different diagnostic modalities. Medical thoracoscopy (MT) can be used for both diagnostic and therapeutic purposes, especially in patients with undiagnosed pleural effusion. AIM: To assess the diagnostic efficacy and safety of MT in patients with pleural effusion of different causes. METHODS: Between January 1, 2012 and April 30, 2021, patients with pleural effusion underwent MT in the Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University (Shaanxi, China). According to the discharge diagnosis, patients were divided into malignant pleural effusion (MPE), tuberculous pleural effusion (TBPE), and inflammatory pleural effusion (IPE) groups. General information, and tuberculosis- and effusion-related indices of the three groups were analyzed. The diagnostic yield, diagnostic accuracy, performance under thoracoscopy, and complications of patients were compared among the three groups. Then, the significant predictive factors for diagnosis between the MPE and TBPE groups were analyzed. RESULTS: Of the 106 patients enrolled in this 10-year study, 67 were male and 39 female, with mean age of 57.1 ± 14.184 years. Among the 74 thoracoscopy-confirmed patients, 41 (38.7%) had MPE, 21 had (19.8%) TBPE, and 32 (30.2%) were undiagnosed. Overall diagnostic yield of MT was 69.8% (MPE: 75.9%, TBPE: 48.8%, and IPE: 75.0%, with diagnostic accuracies of 100%, 87.5%, and 75.0%, respectively). Under thoracoscopy, single or multiple pleural nodules were observed in 81.1% and pleural adhesions in 34.0% with pleural effusions. The most common complication was chest pain (41.5%), followed by chest tightness (11.3%) and fever (10.4%). Multivariate logistic regression analyses showed effusion appearance [odds ratio (OR): 0.001, 95%CI: 0.000-0.204; P = 0.010] and carcinoembryonic antigen (OR: 0.243, 95%CI: 0.081-0.728; P = 0.011) as significant for differentiating MPE and TBPE, with area under the receiver operating characteristic curve of 0.977 (95%CI: 0.953-1.000; P < 0.001). CONCLUSION: MT is an effective, safe, and minimally invasive procedure with high diagnostic yield for pleural effusion of different causes.

Comparison of metagenomic next-generation sequencing using cell-free DNA and whole-cell DNA for the diagnoses of pulmonary infections.

Although the fast-growing metagenomic next-generation sequencing (mNGS) has been used in diagnosing infectious diseases, low detection rate of mNGS in detecting pathogens with low loads limits its extensive application. In this study, 130 patients with suspected pulmonary infections were enrolled, from whom bronchoalveolar lavage fluid (BALF) samples were collected. The conventional tests and mNGS of cell-free DNA (cfDNA) and whole-cell DNA (wcDNA) using BALF were simultaneously performed. mNGS of cfDNA showed higher detection rate (91.5%) and total coincidence rate (73.8%) than mNGS of wcDNA (83.1% and 63.9%) and conventional methods (26.9% and 30.8%). A total of 70 microbes were detected by mNGS of cfDNA, and most of them (60) were also identified by mNGS of wcDNA. The 31.8% (21/66) of fungi, 38.6% (27/70) of viruses, and 26.7% (8/30) of intracellular microbes can be only detected by mNGS of cfDNA, much higher than those [19.7% (13/66), 14.3% (10/70), and 6.7% (2/30)] only detected by mNGS of wcDNA. After in-depth analysis on these microbes with low loads set by reads per million (RPM), we found that more RPM and fungi/viruses/intracellular microbes were detected by mNGS of cfDNA than by mNGS of wcDNA. Besides, the abilities of mNGS using both cfDNA and wcDNA to detect microbes with high loads were similar. We highlighted the advantage of mNGS using cfDNA in detecting fungi, viruses, and intracellular microbes with low loads, and suggested that mNGS of cfDNA could be considered as the first choice for diagnosing pulmonary infections.

Essential role for STAT3/FOXM1/ATG7 signaling-dependent autophagy in resistance to Icotinib.

BACKGROUND: The contribution of autophagy to cancer therapy resistance remains complex, mainly owing to the discrepancy of autophagy mechanisms in different therapy. However, the potential mechanisms of autophagy-mediated resistance to icotinib have yet to be elucidated. METHODS: The effect of autophagy in icotinib resistance was examined using a series of in vitro and in vivo assays. The results above were further verified in biopsy specimens of lung cancer patients before and after icotinib or gefitinib treatment. RESULTS: Icotinib increased ATG3, ATG5, and ATG7 expression, but without affecting Beclin-1, VPS34 and ATBG14 levels in icotinib-resistant lung cancer cells. Autophagy blockade by 3-MA or silencing Beclin-1 had no effects on resistance to icotinib. CQ effectively restored lung cancer cell sensitivity to icotinib in vitro and in vivo. Notably, aberrantly activated STAT3 and highly expressed FOXM1 were required for autophagy induced by icotinib, without the involvement of AMPK/mTOR pathway in this process. Alterations of STAT3 activity using genetic and/or pharmacological methods effectively affected FOXM1 and ATG7 levels increased by icotinib, with altering autophagy and icotinib-mediated apoptosis in resistant cells. Furthermore, silencing FOXM1 impaired up-regulated ATG7 induced by STAT3-CA and icotinib. STAT3/FOXM1 signalling blockade also reversed resistance to icotinib in vivo. Finally, we found a negative correlation between STAT3/FOXM1/ATG7 signalling activity and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) treatment efficacy in patients undergoing EGFR-TKIs treatment. CONCLUSIONS: Our findings support that STAT3/FOXM1/ATG7 signalling-induced autophagy is a novel mechanism of resistance to icotinib, and provide insights into potential clinical values of ATG7-dependent autophagy in icotinib treatment.

Pretreatment HDL-C and ApoA1 are predictive biomarkers of progression-free survival in patients with EGFR mutated advanced non-small cell lung cancer treated with TKI.

BACKGROUND: We aimed to explore the correlation between blood lipids (high density lipoprotein cholesterol [HDL-C] and apolipoprotein A1 [ApoA1]) and epidermal growth factor receptor (EGFR) T790M mutation, as well as its predictive role in clinical efficacy and progression-free survial (PFS) in advanced non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKI). METHODS: We retrospectively collected information of 153 patients with advanced NSCLC harboring exon EGFR mutation and receiving EGFR-TKI. RESULTS: The best cutoff value for HDL-C and ApoA1 was determined to be 1.15 and 1.14 mmol/l. The overall response rate (ORR) was 67.7% in the high HDL-C group and 46.6% in the low HDL-C group, respectively. The ORR of the high ApoA1 group showed a significant increase than that of the low ApoA1 group (68.1% vs. 38.5%). The mean ApoA1 level of the EGFR T790M mutation-positive group was significantly higher than that of the EGFR T790M mutation-negative group (1.13 g/l vs. 1.01 g/l). Patients with high ApoA1 levels were related to the EGFR T790M mutation (r = 0.324). (3) The median progression-free survival (PFS) of the high HDL-C group and low HDL-C group were 13.00 months and 10.20 months. The median PFS of the high ApoA1 group and the low ApoA1 group were 12.10 and 10.00 months, respectively. Multivariate Cox stepwise regression model analysis demonstrated ECOG PS, pathological type and HDL-C were confirmed as critical and independent predictors of PFS. CONCLUSIONS: Patients with EGFR T790M mutations often show higher ApoA1 levels. Peripheral serum HDL-C and ApoA1 before treatment can be used as potential significant factors for predicting clinical efficacy and PFS in advanced NSCLC patients treated with EGFR-TKI.

Molecular Characteristics of the Uncommon EGFR Exon 21 T854A Mutation and Response to Osimertinib in Patients With Non-Small Cell Lung Cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) T854A is an uncommon exon 21 mutation in patients with non-small cell lung cancer (NSCLC). It was first reported in samples collected after first generation EGFR tyrosine kinase inhibitor (TKI) treatment as an acquired resistant mutation to first generation EGFR-TKI. The efficacy of osimertinib, a third generation EGFR-TKI, in these patients was not clear. METHODS: In this study, a total of 8932 NSCLC patients with NGS data were retrospectively analyzed to investigate the molecular characteristics and clinical outcomes of patients with EGFR T854A mutation. RESULTS: Eight of 8932 patients (0.09%) had EGFR T854A mutation, and 5 of them (62.5%) were treatment-naïve. Interestingly, all EGFR T854A mutations were co-occurred with EGFR L858R mutation in cis. TP53 was the most common concomitant mutation and no other driver mutation was found. Five of the 8 patients received treatment of osimertinib. Four patients achieved partial response, and one had stable disease, resulting in an overall objective response rate of 80% and disease control rate of 100%. The median progression-free survival of patients who received osimertinib was 10 months. Moreover, EGFR C797S mutation was detected in 1 patient after resistant to osimertinib treatment. CONCLUSION: Presence of EGFR T854A mutation was rare in NSCLC patients and our retrospective study provides clinical evidence that osimertinib may be an effective treatment to improve survival outcomes in patients with EGFR T854A.

[Value of Combined Detection of Cytokines and Tumor Markers in the 
Differential Diagnosis of Benign and Malignant Solitary Pulmonary Nodules].

BACKGROUND: Solitary pulmonary nodule has received increasing attention in recent years. A couple of lung nodules have been recognized as primary malignant tumors, which leads to an urgent need in enhancing the diagnosis of benign/malignant lung nodules at clinical settings. This study aims to explore the value of the combined detection of cytokines and tumor markers in differencing benign and malignant solitary pulmonary nodules in diagnose. METHODS: With 81 solitary pulmonary nodules cases with a clear diagnosis, the general clinical data, nodule imaging features, pathological diagnosis data, serological index cytokine series and tumor marker expression levels were collected in groups. Both single factor and multi-factors analysis were conducted to screen out the serum influence indexes that can predict the malignant probability of lung nodules, and mean while binary logistic regression analysis was used to construct joint indexes; After receiver operating characteristic curve (ROC) was drawn, the area under the curve and the corresponding sensitivity, specificity and positive of each index predicted value, negative predicted value and accuracy could be calculated with a view to determine the statistical significance of area under the curve (AUC). RESULTS: There are differences in the distribution of malignant solitary pulmonary nodules at different locations, with the highest proportion of the right upper lobe (40.4%). The serum levels of carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA21-1), interleukin-6 (IL-6), interleukin-8 (IL-8) in the malignant nodule group were higher than those in the benign nodule group. Logistic regression analysis suggests that CEA, IL-6 and IL-8 are independent risk factors for predicting malignant nodules. ROC curve analysis shows that the areas under the curve of the individual indicators CEA, IL-6 and IL-8 are 0.642, 0.684 and 0.749. The comparison result of the test efficiency of the area under the curve suggests that CEA+IL-6+IL-8 has a larger area under the curve and higher detection efficiency. CONCLUSIONS: CEA, IL-6 and IL-8 are independent risk factors for malignant solitary pulmonary nodules. The combined detection of cytokines and tumor markers has played a role in the differential diagnosis of benign and malignant lung nodules. The diagnostic value of the combined detection of CEA+IL-6+IL-8 is the highest.

Overexpression of BCCIP predicts an unfavorable prognosis and promotes the proliferation and migration of lung adenocarcinoma.

BACKGROUND: Lung cancer accounts for the highest rate of cancer-related diagnosis and mortality. Lung adenocarcinoma (LUAD) is the most common histopathological type. BCCIP was originally identified as a BRCA2 and CDKN1A interacting protein. In different cancers, BCCIP plays different roles. The role of BCCIP in LUAD is still unknown. METHODS: The expression and prognostic value of BCCIP was analyzed using public databases, including LCE, GEPIA, TCGA, and clinical specimens. Bioinformatic analysis and vitro experiments were conducted to explore the biological functions of BCCIP in LUAD. By using the GEPIA and TIMER databases, we investigated the correlations between LUAD expression and immune infiltration in LUAD. RESULTS: Compared with normal tissue, LUAD tissue had a higher expression level of BCCIP and high expression level of BCCIP was detrimental to LUAD patient survival. The suppression of BCCIP inhibited LUAD cell proliferation, migration and resulted in G1/S phase arrest in vitro. Bioinformatic analysis demonstrated that BCCIP could be associated with cell cycle, DNA repair and E2F transcription factor family. There were significant correlations between BCCIP expression and immune infiltrates, including B cell, CD4+ T cell, macrophage, neutrophil and dendritic cells. Furthermore, BCCIP expression showed strong correlations with diverse immune marker sets in LUAD, such as B cell, macrophage and DC. CONCLUSIONS: Overexpression of BCCIP predicts an unfavorable prognosis and promotes the proliferation and migration of lung adenocarcinoma cells. BCCIP is correlated with immune infiltration in LUAD. Suppression of BCCIP may be a potential approach in the prevention and treatment of LUAD.

CircPVT1 promotes proliferation of lung squamous cell carcinoma by binding to miR-30d/e.

BACKGROUND: Circular RNAs (circRNAs) are a new type of extensive non-coding RNAs that regulate the activation and progression of different human diseases, including cancer. However, information on the underlying mechanisms and clinical significance of circRNAs in lung squamous cell carcinoma (LUSC) remains scant. METHODS: The expression profile of RNAs in 8 LUSC tissues, and 9 healthy lung tissues were assayed using RNA sequencing (RNA-seq) techniques. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to profile the expression of circPVT1 and its relationship with the prognosis of LUSC, i.e., survival analysis. Moreover, in vitro and in vivo experiments were performed to evaluate the impacts of circPVT1 on the growth of tumors. RNA pull-down tests, mass spectrometry, dual-luciferase reporter assessment, and RNA immune-precipitation tests were further conducted to interrogate the cross-talk between circPVT1, HuR, or miR-30d/e in LUSC. RESULTS: Our data showed that circPVT1 was upregulated in LUSC tissues, serum, and cell lines. LUSC patients with higher circPVT1 expression exhibited shorter survival rates. The in vivo and in vitro data revealed that circPVT1 promotes the proliferation of LUSC cells. Additionally, mechanistic analysis showed that HuR regulated circPVT1. On the other hand, circPVT1 acted as a competing endogenous RNA (ceRNA) of miR-30d and miR-30e in alleviating the suppressive influences of miR-30d and miR-30e on its target cyclin F (CCNF). CONCLUSION: CircPVT1 promotes LUSC progression via HuR/circPVT1/miR-30d and miR-30e/CCNF cascade. Also, it acts as a novel diagnostic biomarker or treatment target of individuals diagnosed with LUSC.

Genomic Landscape and Tumor Mutational Burden Determination of Circulating Tumor DNA in Over 5,000 Chinese Patients with Lung Cancer.

PURPOSE: Having emerged as a noninvasive and clinically applicable approach for molecular determination of lung cancer, a genomic overview of circulating tumor DNA (ctDNA) of large-scale cohort may be helpful in novel biomarker development and therapeutic innovation. EXPERIMENTAL DESIGN: Primary cohort encompasses 5,671 blood samples from 4,892 patients with lung cancer. Pair-wise tissue samples from 579 patients and additional 358 sample pairs were collected to evaluate the correlation between blood and tissue tumor mutational burden (TMB). Parallel sequencing with plasma/tissue and white blood cells was performed using a 1,021-gene panel. RESULTS: Histologic subtyping was the most relevant to ctDNA detectability independent of other demographic characteristics, with small cell lung cancer showing the highest detectability, ctDNA abundance, and blood TMB (bTMB). Mutational landscape demonstrated significant differences, and integrated clonality analysis highlighted distinct driver-pattern and functional pathway interaction among various subtypes. The clonality and concurrent genes of EGFR mutations could predict the therapeutic efficacy of tyrosine kinase inhibitors (TKI), and RB1 mutations in non-small cell lung cancer characterized a subset with high bTMB, elevated ctDNA level, and potential small cell transformation. Most importantly, we developed an adjusted algorithm for bTMB in samples with extremely low ctDNA level and validated its correlation with tissue TMB in an independent cohort. CONCLUSIONS: ctDNA could serve as a promising alternative in genomic profiling for lung cancer. The novel identification of ctDNA clonality and adjusted bTMB might improve therapeutic and prognostic evaluation. This dataset was also a valuable resource for the development of new therapeutic targets and new genomically guided clinical trials.

Inhibition of TrxR2 suppressed NSCLC cell proliferation, metabolism and induced cell apoptosis through decreasing antioxidant activity.

AIMS: This study aims to analyze the effect of thioredoxin reductase 2 (TrxR2) on lung cancer cell proliferation, apoptosis, invasion and migration in vitro. MAIN METHODS: Real-time PCR was used to measure the expression of TrxR2 in NSCLC tumor tissues. After pAd-TrxR2 or shRNA-TrxR2 was transfected into A549 or NCI-H1299 cells, the cell proliferation was measured by CCK-8 method; cell apoptosis was measured by flow cytometry; cell invasion and migration was measured by Transwell method. The production of ROS was measured by DCFH-DA method; the activity of SOD, CAT and GSH-Px was measured by relative ELISA kit. KEY FINDINGS: The results showed that TrxR2 was up-regulated in NSCLC tumor tissues. Inhibition of TrxR2 suppressed NSCLC cell proliferation and induced apoptosis, and inhibited cell invasion and migration. However, overexpression of TrxR2 showed the opposite effect. Furthermore, when cells were transfected with shRNA-TrxR2, the production of ROS was significantly increased, and SOD, CAT and GSH-Px activity was decreased. Conversely, pAd-TrxR2 transfection showed the opposite effect. SIGNIFICANCE: Taken together, our results suggest that TrxR2 acts as an oncogenic gene in the context of lung cancer progression. The inhibition of TrxR2 suppressed lung cancer cell proliferation, invasion and migration and induced cell apoptosis by inducing ROS production and decreasing antioxidant activity. TrxR2 may be a potential target for NSCLC treatment.

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.].

D-dimer as a potential biomarker for the progression of COPD.

BACKGROUND: D-dimer is a manifestation of endogenous fibrinolytic activity and associated with inflammation process. Despite chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by a hypercoagulable state, D-dimer levels in COPD patients are still conflicting. METHODS: Forty-three participants were investigated at admission for an acute exacerbation of COPD, and reassessed when stable. Forty-three controls were matched for age, gender, body mass index, smoking index, comorbidities and medication use. Participants underwent pulmonary function and laboratory testing, including the measurements of D-dimer and high-sensitivity C-reactive protein (hsCRP). RESULTS: The median of D-dimer was 2839 µg/l (IQR: 2078-4389 µg/l) and 1799 µg/l (IQR: 1205-2196 µg/l) in exacerbated and stable COPD patients respectively. The median of D-dimer in the control subjects was 433 µg/l (IQR: 369-456 µg/l). D-dimer level was significantly increased in stable COPD patients compared with healthy controls, and further increased in those patients with an acute exacerbation (both P<0.001). D-dimer was positively correlated with the well-known inflammatory marker hsCRP both in the exacerbated and stable phases of COPD (r=0.392 P=0.009 and r=0.411 P=0.006, respectively), and negatively correlated with FEV1% predicted and FEV1/FVC in stable COPD (r=-0.409 P=0.006 and r=-0.343 P=0.024, respectively). CONCLUSIONS: D-dimer is increased in COPD patients, and could be considered as an inflammatory marker for the assessment of inflammation in the progression of COPD.

The role of JAK/STAT3 signaling pathway on apoptosis of lung adenocarcinoma cell line PC-9 induced by icotinib.

OBJECTIVE: The aim of this study is to estimate the role of JAK/STAT3 signaling pathway on apoptosis of lung adenocarcinoma induced by icotinib. METHODS: EGFR mutation was detected in lung adenocarcinoma cell line PC-9 by ARMS assay; The inhibitory rates of cell proliferation of PC-9 cells which were exposed to different concentrations of icotinib (0~100 µMol/L) for different time (24~72 h) respectively were evaluated by MTT assay; Apoptosis of PC-9 cells exposed to different concentrations of icotinib (0, 0.1, 1 and 10 µMol/L) for 48 h were evaluated by TUNEL assay; JAK2, STAT3, Bcl-2, Bax mRNA expressions were evaluated by Real-time PCR assay; The protein levels of P-STAT3 and IL-6 were evaluated by Western-blot assay. RESULTS: Human lung adenocarcinoma cell line PC-9 had an exon 19 deletion mutation in EGFR gene; Followed by treatment of icotinib, the proliferation of PC-9 cells were all inhibited significantly, especially in 48 and 72 h (P<0.01) in all concentrations; The inhibitory rates of cell proliferation in different treating time had statistical significance (P<0.01); Cell apoptosis in different concentrations were increased significantly (P<0.05); Along with the increasing concentrations, gene expression levels of JAK2, STAT3 and Bcl-2 decreased significantly (P<0.05), Bax increased significantly (P<0.05), JAK2/STAT3 ratios increased significantly (P<0.01), and Bcl-2/bax ratios decreased significantly (P<0.01); P-STAT3 and IL-6 protein levels were inhibited significantly in higher concentration. CONCLUSIONS: JAK/STAT3 signaling pathway participates in apoptosis of PC-9 cells induced by icotinib. The most likely mechanism is icotinib inhibited the gene expression levels of JAK2, STAT3 and Bcl-2, so with the P-STAT3 and IL-6 protein levels, and mediated gene Bax overexpression.

Serum Cystatin C as an Inflammatory Marker in Exacerbated and Convalescent COPD Patients.

Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease with high morbidity and mortality rates. Cystatin C (Cys C) is a sensitive indicator for various chronic inflammatory diseases. In this study, we aimed to evaluate the role of Cys C in COPD patients comparing with the other well-known inflammatory markers. Ninety patients with acute exacerbated COPD were studied and were reassessed when convalescent. Ninety controls were matched for age, gender, body mass index, smoking index, and comorbidity. Serum Cys C was significantly increased in convalescent COPD patients compared with healthy controls and further increased in COPD patients with an acute exacerbation. Serum Cys C was positively correlated with hsCRP both in the exacerbation and convalescence periods of COPD and negatively correlated with FEV1% predicted and FEV1/FVC in the convalescent COPD patients. In conclusion, serum Cys C is a positive acute-phase reactant in COPD patients and might indicate systemic inflammation during the progression of COPD.

Sex-determining region of Y chromosome-related high-mobility-group box 2 in malignant tumors: current opinions and anticancer therapy.

OBJECTIVE: To gain insight into the mechanism by which sex-determining region of Y chromosome (SRY)-related high-mobility-group box 2 (SOX2) involved in carcinogenesis and cancer stem cells (CSCs). DATA SOURCES: The data used in this review were mainly published in English from 2000 to present obtained from PubMed. The search terms were "SOX2," "cancer," "tumor" or "CSCs." STUDY SELECTION: Articles studying the mitochondria-related pathologic mechanism and treatment of glaucoma were selected and reviewed. RESULTS: SOX2, a transcription factor that is the key in maintaining pluripotent properties of stem cells, is a member of SRY-related high-mobility group domain proteins. SOX2 participates in many biological processes, such as modulation of cell proliferation, regulation of cell death signaling, cell apoptosis, and most importantly, tumor formation and development. Although SOX2 has been implicated in the biology of various tumors and CSCs, the findings are highly controversial, and information regarding the underlying mechanism remains limited. Moreover, the mechanism by which SOX2 involved in carcinogenesis and tumor progression is rather unclear yet. CONCLUSIONS: Here, we review the important biological functions of SOX2 in different tumors and CSCs, and the function of SOX2 signaling in the pathobiology of neoplasia, such as Wnt/ß-catenin signaling pathway, Hippo signaling pathway, Survivin signaling pathway, PI3K/Akt signaling pathway, and so on. Targeting towards SOX2 may be an effective therapeutic strategy for cancer therapy.

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.

Long-term survival for 93 months of limited-stage small cell lung cancer: A case report and literature review.

A 49-year-old man was diagnosed with small cell lung cancer in May 2005. Chemotherapy was started with 60 mg/day cisplatin iv drip (from days one to three), 2 mg topotecan (TP) hydrochloride iv drip (from days one to four), and traditional Chinese medicine (TCM) AiDi injection for anti-tumor. After four cycles, he underwent conformal radiotherapy with 56Gy/28 fractions in October 2005. In April 2006, a mass on the right supraclavicular area was found. Therefore, he underwent another course of radiotherapy. The fields included the right supraclavicular area and the radiation dose was 50Gy/25 fractions. After completion of chemoradiotherapy, the patient achieved complete remission. Subsequently, the patient received prophylactic cranial irradiation (PCI). Until April of 2012, he had been followed up regularly. Since the SCLC diagnosis, he had received TCM for seven years. In April 2012, the patient complained of coughing again. Subsequently, the patient was given five cycles of an etoposide carboplatin regimen. A computed tomography (CT) scan was performed for review, which showed no obvious change. The patient underwent a second-line chemotherapy irinotecan cisplatin three times. However, the symptoms and CT of this patient showed no significant improvement. We changed the chemotherapy regimen to TP (topotecan 1.2 mg iv drip, days one to five; carboplatin 100 mg iv drip, days one to five). After two TP regimens, the patient died in his sleep on 3 March 2013. In this case, the standardized sequential chemotherapy and radiotherapy treatment, PCI, TCM, and good compliance may have contributed to the patient's longer survival.

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.