Combined BRM270 and endostatin inhibit relapse of NSCLC while suppressing lung cancer stem cell proliferation induced by endostatin.

Endostatin (ES, ENDO) has been reported to suppress the growth of tumors while inducing the proliferation of lung cancer stem cells (LCSCs), causing a poor prognosis for lung cancer. In this study, we aimed to clarify whether BRM270 can inhibit the proliferation of cancer stem cells (CSCs). Endostatin + BRM270 showed anti-tumor effects by reducing tumor volume and increasing survival. Administration of BRM270 reduced the number of aldehyde dehydrogenase-positive (ALDH+) cells and the level of ALDH1A1 expression in tumors by increasing the level of miR-128 while decreasing the levels of BMI-1, ABCC-5, E2F3, and c-MET. The luciferase activity of miR-128 promoter was increased by an increasing concentration of BRM270. In addition, BMI-1, ABCC-5, E2F3, and c-MET were identified as candidate targets of miR-128, and the overexpression of miR-128 significantly reduced mRNA/protein levels of BMI-1, ABCC-5, E2F3, and c-MET in A549 and H460 cells. Administration of BRM270 inhibited the expression of BMI-1, ABCC-5, E2F3, and c-MET in a dose-dependent manner. In this study, we showed for the first time that the combined administration of endostatin and BRM270 achieved anti-tumor effects while suppressing the proliferation of stem cells.

Mitochondrial-Targeting Antioxidant SS-31 Suppresses Airway Inflammation and Oxidative Stress Induced by Cigarette Smoke.

This study investigated whether the mitochondrial-targeted peptide SS-31 can protect against cigarette smoke- (CS-) induced airway inflammation and oxidative stress in vitro and in vivo. Mice were exposed to CS for 4 weeks to establish a CS-induced airway inflammation model, and those in the experimental group were pretreated with SS-31 1 h before CS exposure. Pathologic changes and oxidative stress in lung tissue, inflammatory cell counts, and proinflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. The mechanistic basis for the effects of SS-31 on CS extract- (CSE-) induced airway inflammation and oxidative stress was investigated using BEAS-2B bronchial epithelial cells and by RNA sequencing and western blot analysis of lung tissues. SS-31 attenuated CS-induced inflammatory injury of the airway and reduced total cell, neutrophil, and macrophage counts and tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, and matrix metalloproteinase (MMP) 9 levels in BALF. SS-31 also attenuated CS-induced oxidative stress by decreasing malondialdehyde (MDA) and myeloperoxidase (MPO) activities and increasing that of superoxide dismutase (SOD). It also reversed CS-induced changes in the expression of mitochondrial fission protein (MFF) and optic atrophy (OPA) 1 and reduced the amount of cytochrome c released into the cytosol. Pretreatment with SS-31 normalized TNF-α, IL-6, and MMP9 expression, MDA and SOD activities, and ROS generation in CSE-treated BEAS-2B cells and reversed the changes in MFF and OPA1 expression. RNA sequencing and western blot analysis showed that SS-31 inhibited CS-induced activation of the mitogen-activated protein kinase (MAPK) signaling pathway in vitro and in vivo. Thus, SS-31 alleviates CS-induced airway inflammation and oxidative stress via modulation of mitochondrial function and regulation of MAPK signaling and thus has therapeutic potential for the treatment of airway disorders caused by smoking.

The Multifaceted Therapeutic Role of N-Acetylcysteine (NAC) in Disorders Characterized by Oxidative Stress.

Oxidative stress, which results in the damage of diverse biological molecules, is a ubiquitous cellular process implicated in the etiology of many illnesses. The sulfhydryl-containing tripeptide glutathione (GSH), which is synthesized and maintained at high concentrations in all cells, is one of the mechanisms by which cells protect themselves from oxidative stress. N-acetylcysteine (NAC), a synthetic derivative of the endogenous amino acid L-cysteine and a precursor of GSH, has been used for several decades as a mucolytic and as an antidote to acetaminophen (paracetamol) poisoning. As a mucolytic, NAC breaks the disulfide bonds of heavily cross-linked mucins, thereby reducing mucus viscosity. In vitro, NAC has antifibrotic effects on lung fibroblasts. As an antidote to acetaminophen poisoning, NAC restores the hepatic GSH pool depleted in the drug detoxification process. More recently, improved knowledge of the mechanisms by which NAC acts has expanded its clinical applications. In particular, the discovery that NAC can modulate the homeostasis of glutamate has prompted studies of NAC in neuropsychiatric diseases characterized by impaired glutamate homeostasis. This narrative review provides an overview of the most relevant and recent evidence on the clinical application of NAC, with a focus on respiratory diseases, acetaminophen poisoning, disorders of the central nervous system (chronic neuropathic pain, depression, schizophrenia, bipolar disorder, and addiction), cardiovascular disease, contrast-induced nephropathy, and ophthalmology (retinitis pigmentosa).

Microarray profiling of lung long non-coding RNAs and mRNAs in lipopolysaccharide-induced acute lung injury mouse model.

Long non-coding RNAs (lncRNAs) are involved in various biological processes as well as many respiratory diseases, while the role of lncRNAs in acute lung injury (ALI) remains unclear. The present study aimed to profile the expression of lung lncRNAs and mRNAs in lipopolysaccharide (LPS)-induced ALI mouse model. C57BL/6 mice were exposed to LPS or phosphate-buffered saline for 24 h, and lncRNAs and mRNAs were profiled by Arraystar mouse LncRNA Array V3.0. Bioinformatics analysis gene ontology including (GO) and pathway analysis and cell study in vitro was used to investigate potential mechanisms. Based on the microarray results, 2632 lncRNAs and 2352 mRNAs were differentially expressed between ALI and control mice. The microarray results were confirmed by the quantitative real-time PCR (qRT-PCR) results of ten randomized selected lncRNAs. GO analysis showed that the altered mRNAs were mainly related to the processes of immune system, immune response and defense response. Pathway analysis suggests that tumor necrosis factor (TNF) signaling pathway, NOD-like receptor pathway, and cytokine-cytokine receptor interaction may be involved in ALI. LncRNA-mRNA co-expression network analysis indicated that one individual lncRNA may interact with several mRNAs, and one individual mRNA may also interact with several lncRNAs. Small interfering RNA (siRNA) for ENSMUST00000170214.1, - ENSMUST00000016031.13 significantly inhibited LPS-induced TNF-α and interleukin (IL)-1ß production in murine RAW264.7 macrophages. Our results found significant changes of lncRNAs and mRNAs in the lungs of LPS-induced ALI mouse model, and intervention targeting lncRNAs may attenuate LPS-induced inflammation, which may help to elucidate the role of lncRNAs in the pathogenesis and treatment of ALI.

Mitochondrial peptides cause proinflammatory responses in the alveolar epithelium via FPR-1, MAPKs, and AKT: a potential mechanism involved in acute lung injury.

Acute lung injury (ALI) is characterized by alveolar epithelial damage and uncontrolled pulmonary inflammation. Mitochondrial damage-associated molecular patterns (DAMPs), including mitochondrial peptides [ N-formyl peptides (NFPs)], are released during cell injury and death and induce inflammation by unclear mechanisms. In this study, we have investigated the role of mitochondrial DAMPs (MTDs), especially NFPs, in alveolar epithelial injury and lung inflammation. In murine models of ALI, high levels of mitochondrial NADH dehydrogenase 1 in bronchoalveolar lavage fluid (BALF) were associated with lung injury scores and increased formyl peptide receptor (FPR)-1 expression in the alveolar epithelium. Cyclosporin H (CsH), a specific inhibitor of FPR1, inhibited lung inflammation in the ALI models. Both MTDs and NFPs upon intratracheal challenge caused accumulation of neutrophils into the alveolar space with elevated BALF levels of mouse chemokine KC, interleukin-1ß, and nitric oxide and increased pulmonary FPR-1 levels. CsH significantly attenuated MTDs or NFP-induced inflammatory lung injury and activation of MAPK and AKT pathways. FPR1 expression was present in rat primary alveolar epithelial type II cells (AECIIs) and was increased by MTDs. CsH inhibited MTDs or NFP-induced CINC-1/IL-8 release and phosphorylation of p38, JNK, and AKT in rat AECII and human cell line A549. Inhibitors of MAPKs and AKT also suppressed MTD-induced IL-8 release and NF-κB activation. Collectively, our data indicate an important role of the alveolar epithelium in initiating immune responses to MTDs released during ALI. The potential mechanism may involve increase of IL-8 production in MTD-activated AECII through FPR-1 and its downstream MAPKs, AKT, and NF-κB pathways.

WNT/ß-catenin signaling regulates cigarette smoke-induced airway inflammation via the PPARδ/p38 pathway.

The mechanisms of WNT/ß-catenin signaling involved in airway inflammation of chronic obstructive pulmonary disease (COPD) remain unknown, although recent observations have suggested an important contribution of the pathway in pulmonary parenchymal tissue repair and airway epithelium differentiation. We investigated the role of WNT/ß-catenin signaling in cigarette smoke (CS)-related airway inflammation using patient lung tissues, human bronchial epithelial cells (16HBECs), and mouse models. Reduced activity of WNT/ß-catenin signaling was observed in the airway epithelium of smokers with or without COPD. The mRNA expression of WNT transcription factor TCF4 negatively correlated with the pack year. The mRNA levels of WNT receptor FZD4 negatively correlated with the mRNA levels of IL-1ß. CS exposure decreased the activity of WNT/ß-catenin signaling in both 16HBECs and mice. In vitro studies demonstrated the upregulation of inflammatory cytokines TNF-α and IL-1ß secretion induced by CS extract (CSE) could be attenuated by ß-catenin activator SB216763 and be exacerbated by ß-catenin small-interfering RNA (siRNA), respectively. Furthermore, the decrease in the expression of peroxisome proliferator-activated receptor (PPARδ) induced by CSE stimulation could be rescued by SB216763. SB216763 also attenuated the upregulation of phosphorylated p38 mitogen-activated protein kinase (MAPK) stimulated by CSE. Both PPARδ agonist and p38 MAPK inhibitor could suppress the TNF-α and IL-1ß release induced by CSE treatment. In addition, PPARδ activation could abolish ß-catenin siRNA-mediated aggravation of phosphorylated p38 MAPK in response to CSE. Finally, SB216763 treatment significantly ameliorated peribronchial inflammatory cell infiltration, leukocyte influx, and the release of TNF-α and IL-1ß in the bronchoalveolar lavage fluid of CS-exposed mice. Taken together, our findings indicate that the reduced activity of WNT/ß-catenin signaling induced by CS may promote inflammatory cytokine production in airway epithelium and have an essential role in airway inflammation in COPD by PPARδ/p38 MAPK pathway.

Clinical significance of airway mucus hypersecretion in chronic obstructive pulmonary disease.

Airway mucus hypersecretion is one of the most important features of chronic obstructive pulmonary disease (COPD). Airway mucus hypersecretion in COPD patients results in outcomes such as rapid decline of lung function, poor quality of life, and high rate of acute exacerbation, hospitalization and mortality. Nonpharmacologic treatments for airway mucus hypersecretion in COPD include smoking cessation and physical rehabilitation. Pharmacologic therapies include expectorants, mucolytics, methylxanthines, beta-adrenergic receptor agonists, anticholinergics, glucocorticoids, phosphodiesterase-4 inhibitors, antioxidants, and antibiotics. Novel drugs with promising prospects are currently under clinical trials.

Performance of osteopontin in the diagnosis of malignant pleural mesothelioma: a meta-analysis.

It is reported that osteopontin has shown promising diagnostic value for malignant pleural mesothelioma (MPM), this meta-analysis aimed to establish the overall diagnostic accuracy of the osteopontin measurement for diagnosing MPM. Based on a systematic review of English language studies, the sensitivity, specificity and other measures of accuracy of osteopontin in the diagnosis of MPM were pooled using random-effects model. Summary receiver operating characteristic curves were used to summarize overall test performance. Seven publications met our inclusion criteria, the pooled sensitivity was 0.57 (95%CI: 0.52-0.61), specificity was 0.81, 95%CI: 0.79-0.84). The PLR was 3.78 (95%CI: 2.23-6.41), the NLR was 0.51 (95%CI: 0.38-0.67) and the DOR was 9.04 (95%CI: 5.28-15.48), the area under the summary receiver operating characteristic curve was 0.80. Our data suggest that osteopontin is likely to be a useful diagnostic marker for MPM, considering for the limited studies and patients included, larger studies are needed to confirm these findings.

[Diammonium glycyrrhizinate promotes aquaporin-5 in LPS-induced acute lung injury via inactivation of NF-kappaB].

OBJECTIVE: To determine the therapeutic value and associated mechanism of diammonium glycyrrhizinate (DG) on the expression of AQP-5 in lipapolysacchairides (LPS)-induced acute lung injury in mice. METHODS: Thirty male BALB/c mice were randomly divided into three groups equally: Control, LPS+DG and LPS. HE staining and lung injury score system were used to evaluate the pathological changes in the lung tissues. Wet to dry ratio (W/D) was used to measure the degree of lung edema. RT-PCR and Western blot were obtained to measure AQP-5 expression. Total NF-kappaB p65 and phospho-NF-kappaB p65 (p-NF-kappaB p65) were evaluated by Western blot. RESULTS: After 3 days of LPS intratracheal injection, severe pathological changes, increased W/D, down-regulated AQP-5 expression and increased p-NF-kappaB p65/total NF-kappaB p65 were observed. Compared with mice in the LPS group, mice in the LPS+DG group had more significantly ameliorated pathological changes and increased W/ D, up-regulated AQP-5 expression, and reduced p-NF-kappaB p65/total NF-kappaB p65. CONCLUSION: DG up-regulates AQP-5 in vivo, possibly resulting from inactivation of NF-kappaB.

Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial.

BACKGROUND: Increased oxidative stress and inflammation has a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Drugs with antioxidant and anti-inflammatory properties, such as N-acetylcysteine, might provide a useful therapeutic approach for COPD. We aimed to assess whether N-acetylcysteine could reduce the rate of exacerbations in patients with COPD. METHODS: In our prospective, randomised, double-blind, placebo-controlled, parallel-group study, we enrolled patients aged 40-80 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <0·7 and FEV1 of 30-70% of predicted) at 34 hospitals in China. We stratified patients according to use of inhaled corticosteroids (regular use or not) at baseline and randomly allocated them to receive N-acetylcysteine (one 600 mg tablet, twice daily) or matched placebo for 1 year. The primary endpoint was the annual exacerbation rate in patients who received at least one dose of study drug and had at least one assessment visit after randomisation. This study is registered with the Chinese Clinical Trials Registry, ChiCTR-TRC-09000460. FINDINGS: Between June 25, 2009, and Dec 29, 2010, we screened 1297 patients, of whom 1006 were eligible for randomisation (504 to N-acetylcysteine and 502 to placebo). After 1 year, we noted 497 acute exacerbations in 482 patients in the N-acetylcysteine group who received at least one dose and had at least one assessment visit (1·16 exacerbations per patient-year) and 641 acute exacerbations in 482 patients in the placebo group (1·49 exacerbations per patient-year; risk ratio 0·78, 95% CI 0·67-0·90; p=0·0011). N-acetylcysteine was well tolerated: 146 (29%) of 495 patients who received at least one dose of N-acetylcysteine had adverse events (48 serious), as did 130 (26%) of 495 patients who received at least one dose of placebo (46 serious). The most common serious adverse event was acute exacerbation of COPD, occurring in 32 (6%) of 495 patients in the N-acetylcysteine group and 36 (7%) of 495 patients in the placebo group. INTERPRETATION: Our findings show that in Chinese patients with moderate-to-severe COPD, long-term use of N-acetylcysteine 600 mg twice daily can prevent exacerbations, especially in disease of moderate severity. Future studies are needed to explore efficacy in patients with mild COPD (GOLD I). FUNDING: Hainan Zambon Pharmaceutical.

Diagnostic accuracy of adenosine deaminase for tuberculous peritonitis: a meta-analysis.

INTRODUCTION: Tuberculous peritonitis remains a diagnostic challenge for clinicians. Many studies have investigated the usefulness of adenosine deaminase (ADA) in ascites for the diagnosis of tuberculous peritonitis; however, the overall diagnostic accuracy of ADA for tuberculous peritonitis remains unclear. The aim of the present meta-analysis was to determine the overall accuracy of ADA measurements in the diagnosis of tuberculous peritonitis. MATERIAL AND METHODS: We performed a systematic search in PubMed and Embase to identify published studies that evaluated the diagnostic role of ADA for tuberculous peritonitis. Quality was assessed according to standardized Quality Assessment of Diagnostic Accuracy Studies criteria. Sensitivity, specificity and other measures of accuracy of ADA assay in order to diagnose tuberculous peritonitis were pooled using random effects models. Summary receiver operating characteristic curve (SROC) was used to summarize overall test performance. RESULTS: Sixteen studies met inclusion criteria for the present meta-analysis. The pooled sensitivity and specificity for diagnosing tuberculous peritonitis were 0.93 (95% CI: 0.89-0.95) and 0.96 (95% CI: 0.94-0.97), respectively. The positive likelihood ratio was 15.80 (95% CI: 10.87-22.95), negative likelihood ratio was 0.09 (95% CI: 0.05-0.16) and diagnostic odds ratio was 249.28 (95% CI: 113.11-549.39). The area under the SROC was 0.98. CONCLUSIONS: Ascitic ADA determination is a relatively sensitive and specific test for the diagnosis of tuberculous peritonitis. Measurement of ADA in ascites is thus likely to be a useful diagnostic method for tuberculous peritonitis.

The 2518 A/G polymorphism in the MCP-1 gene and cancer risk: a meta-analysis.

BACKGROUND: The 2518 A/G polymorphism in the MCP-1 gene has been extensively studied for associations with cancer; however, results from replication studies have been inconsistent. The aim of this investigation was to determine links with risk of cancer by meta-analysis. METHODS: We searched Pubmed, Embase, CNKI, Weipu and Wanfang databases, covering all case-control studies until March, 2013. Statistical analyses were performed using the Revman 5.0 software. RESULTS: A total of 11 case-control studies met our inclusion criteria, including 1,422 cases and 2,237 controls. The results indicated that the MCP-1 2518 gene polymorphism had no association with cancer risk overall (GG vs.GA+ AA: OR = 0.89, 95%CI = 0.61-1.28, P = 0.52). However, in the subgroup analysis by ethnicity, a decrease of cancer risk was found in Asian populations (GG vs.GA+ AA: OR = 0.79, 95%CI = 0.63-0.99, P = 0.04). CONCLUSION: This meta-analysis suggested that the 2518A/G polymorphism of MCP-1 gene is associated with risk of cancer among Asian, but not in Caucasian populations.

Blocking of thromboxane A2 receptor attenuates airway mucus hyperproduction induced by cigarette smoke.

Cigarette smoking is one of the risk factors for chronic obstructive pulmonary disease (COPD). In this study, we investigated the effects of thromboxane A2 (TxA2) receptor antagonists on airway mucus production induced by cigarette smoke. Rats were exposed to cigarette smoke 1h/day, 6 days/week for 4 weeks. Seratrodast (2, 5, 10mg/kg day) was administered intragastrically prior to smoke exposure. Thromboxane B2 (TxB2) in the bronchoalveolar lavage fluid and lung tissues was determined by enzyme immunoassay. Airway mucus production was determined by alcin-blue/periodic acid sthiff (AB-PAS) staining, Muc5ac immunohistochemical staining, and RT-PCR. The phosphorylation of ERK and p38 was evaluated by Western blotting. Seratrodast reduced the overproduction of TxB2 in both bronchoalveolar lavage fluid and lung tissues. Cigarette smoke exposure markedly increased AB/PAS-stained goblet cells and rat Muc5ac expression in the airway, which was significantly attenuated by seratrodast administration. The induced phosphorylation of ERK and p38 was also attenuated by seratrodast. TxA2 receptor antagonist could reduce Muc5ac production induced by cigarette smoke in vivo, possibly through the mitogen-activated protein kinases (MAPK) signaling pathway.

Receptor for advanced glycation end products: a new theraputic target for chronic obstructive pulmonary disease?

Receptor for advanced glycation end products (RAGE), a multiligand receptor, has been suggested to be implicated in inflammatory response. However, its role in chronic obstructive pulmonary disease (COPD) has not been well elucidated. Recently, several studies reported RAGE and its common ligands were upregulated in airways and lung tissues from COPD smokers. Moreover, inhibition of RAGE activation significantly attenuated cigarette smoke extract or bacteria-induced pulmonary inflammation. Based on these findings, a conclusion could be made that ligand-activated RAGE may play a key role in COPD and thus RAGE could be a new therapeutic target for COPD.

High-dose N-acetylcysteine in the prevention of COPD exacerbations: rationale and design of the PANTHEON Study.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation; from a pathophysiological point of view it involves many components, including mucus hypersecretion, oxidative stress and inflammation. N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. Long-term efficacy of NAC 600mg/d in COPD is controversial; a dose-effect relationship has been demonstrated, but at present it is not known whether a higher dose provides clinical benefits. The PANTHEON Study is a prospective, ICS stratified, randomized, double-blind, placebo-controlled, parallel-group, multi-center trial designed to assess the efficacy and safety of high-dose (1200 mg/daily) NAC treatment for one year in moderate-to-severe COPD patients. The primary endpoint is the annual exacerbation rate. Secondary endpoints include recurrent exacerbations hazard ratio, time to first exacerbation, as well as quality of life and pulmonary function. The hypothesis, design and methodology are described and baseline characteristics of recruited patients are presented. 1006 COPD patients (444 treated with maintenance ICS, 562 ICS naive, aged 66.27±8.76 yrs, average post-bronchodilator FEV1 48.95±11.80 of predicted) have been randomized at 34 hospitals in China. Final results of this study will provide objective data on the effects of high-dose (1200 mg/daily) long-term NAC treatment in the prevention of COPD exacerbations and other outcome variables.

Transcatheter arterial embolization followed by octreotide and celecoxib synergistically prolongs survival of rabbits with hepatic VX2 allografts.

OBJECTIVE: To validate the efficacy of an innovative multimodality therapy with transcatheter arterial embolization (TAE) plus octreotide and celecoxib in reducing neoangiogenesis and prolonging the survival of rabbits with hepatocellular carcinoma. METHODS: Rabbits with hepatic VX2 allografts were divided into four groups: control group, TAE group, octreotide + celecoxib (O + C) group and the multimodality therapy (TAE + O + C) group. Survival of the rabbits was analyzed using the Kaplan-Meier method and the expression of CD31 in tumor tissues was detected by immunohistochemistry. RESULTS: Rabbits in the TAE + O + C group lived nearly 20 days longer than those in the control group. The survival rate of the TAE + O + C group was 50% at day 80 and was the highest among the four groups (P < 0.05). No VX2 allograft-bearing rabbits in the control group lived longer than 60 days. Compared with the control group, the survival time of the other two intervention groups were not prolonged significantly (P > 0.05). The CD31 expression induced by TAE was reduced significantly in TAE + O + C group (P < 0.05). Less metastasis was detected in TAE + O + C group. CONCLUSION: TAE followed by the long-term administration of octreotide and celecoxib can synergistically prolong the survival of rabbits with hepatic VX2 allografts by inhibiting potential neoangiogenesis, tumor growth and metastasis.

Telomerase activity assay for the diagnosis of malignant pleural effusion: A meta-analysis.

The telomerase activity assay has been established for the detection of malignant pleural effusion (MPE), however, the overall diagnostic accuracy of the telomerase activity assay for MPE remains unclear. We performed a systematic search in the Pubmed, Embase and Cochrane databases to identify published studies that have evaluated the diagnostic role of the telomerase activity assay for MPE. Sensitivity, specificity and other measures of accuracy of the telomerase activity assay in the diagnosis of MPE were pooled using the random effects models. A summary receiver operating characteristic (SROC) curve was used to summarize overall test performance. A total of eight studies met the inclusion criteria for the meta-analysis. The pooled sensitivity and specificity for diagnosing MPE were 0.76 [95% confidence intervals (CI), 0.72-0.80] and 0.87 (95% CI, 0.83-0.91), respectively. The positive likelihood ratio was 5.19 (95% CI, 2.36-11.42), the negative likelihood ratio was 0.25 (95% CI, 0.11-0.53) and the diagnostic odds ratio was 23.18 (95% CI, 6.11-87.83). The area under the SROC curve was 0.92. The telomerase activity assay plays a role in the diagnosis of MPE with a relatively high specificity. The results of a telomerase activity assay should be interpreted together with the combination of other test results and clinical findings.