Diagnostic predictability of serum miR-4793-3p and miR-1180-3p expression in community-acquired pneumonia.

Background: Early identification of community-acquired pneumonia (CAP) is crucial to prevent severe progression. Methods: The authors enrolled 150 hospitalized CAP patients and collected clinicopathologic features and blood indicators. Plasma miRNA profiling was conducted using microarray detection, and selected miRNAs were tested with reverse transcription quantitative PCR. Predictive models were built using least shrinkage and selection operator regression. Results: Least shrinkage and selection operator regression identified two miRNAs (miR-4793-3p and miR-1180-3p) that distinguished mild from severe CAP patients (area under the curve = 0.948). The miRNA model outperformed D-dimer, platelet and procalcitonin (max area under the curve = 0.729). Conclusion: Increased levels of miR-4793-3p and miR-1180-3p may indicate severe pneumonia development. Plasma miRNA profiling enables early prediction of severe CAP, aiding therapeutic decisions.

A prediction model for risk of low oxygen saturation in patients with post-tuberculosis tracheobronchial stenosis during bronchoscopy.

BACKGROUND: Low oxygen saturation (LOS) is a frequent occurrence for patients with post-tuberculosis tracheobronchial stenosis (PTTS) during bronchoscopic procedures. However, there are currently no systematic assessment tools to predict LOS risk in PTTS patients during bronchoscopy. OBJECTIVES: This study aimed to develop an effective preoperative predictive model to guide clinical practice. DESIGN: Retrospective cohort study. METHODS: Data was retrospectively collected from PTTS patients who underwent bronchoscopic interventions between January 2017 and December 2022. Among all patients included in this study, patients between January 2017 and December 2021 were used as training cohort for the logistic regression model, and patients between January 2022 and December 2022 were utilized as validation cohort for internal validation. We used consistency index (C-index), goodness-of-fit test and calibration plot to evaluate the model performance. RESULTS: A total of 465 patients who met the inclusion criteria were enrolled in the study. The overall incidence of LOS was 26.0% (121/465). Comorbidity, degree of stenosis, bronchoscopist level, thermal ablation therapy, balloon dilation, and airway stenting, as independent risk factors for the presence of LOS, were used to construct the nomogram prediction model. The C-index of training cohort was 0.827 (95% CI, 0.786-0.869), whereas that of validation cohort was 0.836 (95% CI, 0.757-0.916), combining with the results of the calibration plot and goodness-of-fit test, demonstrating that this model had good predictive ability. CONCLUSION: The predictive model and derived nomogram with good predictive ability has been developed to preoperatively predict the risk of LOS in PTTS patients during bronchoscopy, allowing for individualized interventions for high-risk patients.

PLEKHG2 Promotes NSCLC Cell Growth by Increasing Glycolysis via Activated PI3K/AKT Pathway.

Purpose: PLEKHG2 is a member of the diffuse B-cell lymphoma family. The function of PLEKHG2 in NSCLC was still unclear. This study aimed to investigate the relationship between the upregulated expression of PLEKHG2 and the prognosis of NSCLC and to revealed its mechanisms. Materials and methods: The expression of PLEKHG2 in NSCLC patients and its relationship with prognosis were first determined by analyzing public databases. Validation was performed in NSCLC cell lines and patient`s tumor tissues. PLEKHG2-silenced H1299 cells and PLEKHG2 overexpressing PC9 cells were constructed and used to validate its function. Glycolysis was evaluated by assaying cellular metabolites, glucose uptake and the expression levels of biomarkers of glycolysis. The relationship of PLEKHG2 and the PI3K/Akt pathway was demonstrated by small molecule inhibitors. The function of PLEKHG2 was evaluated in vivo by a H1299 cell derived xenograft (CDX) model. Results: PLEKEHG2 was highly expressed in NSCLC tissues and associated with poor prognosis. In PLEKHG2 knockdown H1299 cells, ATP and lactate production and glucose uptake were significantly inhibited. The opposite results were observed in PC9 cells with PLEKHG2 overexpression. The increased glycolysis following PLEKHG2 overexpression was abolished by adding the PI3K/AKT pathway inhibitor LY294002, suggesting that PLEKHG2 promotes glycolysis in NSCLC cells via activation of the PI3K/AKT pathway. Finally, we found that PLEKHG2 knockdown inhibited the tumor growth in the H1299 CDX model. Conclusion: PLEKHG2 contributed to NSCLC development by promoting glycolysis via activation of the PI3K/AKT pathway. PLEKHG2 was a potential therapeutic target and biomarker for poor prognosis of NSCLC.

Predictive value of the resistance of the probe to pass through the lesion in the diagnosis of peripheral pulmonary lesions using radial probe endobronchial ultrasound with a guide sheath.

Background: Transbronchial lung biopsy guided by radial probe endobronchial ultrasonography with a guide sheath (EBUS-GS-TBLB) is becoming a significant approach for diagnosing peripheral pulmonary lesions (PPLs). We aimed to explore the clinical value of the resistance of the probe to pass through the lesion in the diagnosis of PPLs when performing EBUS-GS-TBLB, and to determine the optimum number of EBUS-GS-TBLB. Methods: We performed a prospective, single-center study of 126 consecutive patients who underwent EBUS-GS-TBLB for solid and positive-bronchus-sign PPLs where the probe was located within the lesion from September 2019 to May 2022. The classification of probe resistance for each lesion was carried out by two bronchoscopists independently, and the final result depended on the bronchoscopist responsible for the procedures. The primary endpoint was the diagnostic yield according with the resistance pattern. The secondary endpoints were the optimum number of EBUS-GS-TBLB and factors affecting diagnostic yield. Procedural complications were also recorded. Results: The total diagnostic yield of EBUS-GS-TBLB was 77.8%, including 83.8% malignant and 67.4% benign diseases (P=0.033). Probe resistance type II displayed the highest diagnostic yield (87.5%), followed by type III (81.0%) and type I (61.1%). A significant difference between the diagnostic yield of malignant and benign diseases was detected in type II (P = 0.008), whereas others did not. Although most of the malignant PPLs with a definitive diagnosis using EBUS-GS-TBLB in type II or type III could be diagnosed in the first biopsy, the fourth biopsy contributed the most sufficient biopsy samples. In contrast, considerably limited tissue specimens could be obtained for each biopsy in type I. The inter-observer agreement of the two blinded bronchoscopists for the classification of probe resistance was excellent (κ = 0.84). Conclusion: The probe resistance is a useful predictive factor for successful EBUS-GS-TBLB diagnosis of solid and positive-bronchus-sign PPLs where the probe was located within the lesion. Four serial biopsies are appropriate for both probe resistance type II and type III, and additional diagnostic procedures are needed for type I.

Anoikis-related genes combined with single cell sequencing: Insights into model specification of lung adenocarcinoma and applicability for prognosis and therapy.

Background: Anoikis has therapeutic potential against different malignancies including lung adenocarcinoma. This study used anoikis and bioinformatics to construct a prognostic model for lung adenocarcinoma and explore new therapeutic strategies. Methods: Several bioinformatic algorithms (co-expression analysis, univariate Cox analysis, multivariate Cox analysis, and cross-validation) were used to screen anoikis-related genes (ARGs) to construct a risk model. Lung adenocarcinoma patients were divided into training and testing groups at a ratio of 1:1. The prognostic model was validated by risk score comparison between high- and low-risk groups using receiver operating characteristic curve (ROC), nomograms, independent prognostic analysis and principal component analysis. In addition, two anoikis-related genes patterns were classified utilizing consensus clustering method and were compared with each other in survival time, immune microenvironment, and regulation in pathway. Single cell sequencing was applied to analyze anoikis-related genes constructed the model. Results: This study demonstrated the feasibility of the model based on seven anoikis-related genes, as well as identifying axitinib, nibtinib and sorafenib as potential therapeutic strategies for LUAD. Risk score based on this model had could be used as an independent prognostic factor for lung adenocarcinoma (HR > 1; p < 0.001) and had the highest accuracy to predict survival compared with the clinical characteristics. Single cell sequencing analysis discovered Keratin 14 (KRT14, one of the seven anoikis-related genes) was mainly expressed in malignant cells in various cancers. Conclusion: We identified seven anoikis-related genes and constructed an accurate risk model based on bioinformatics analysis that can be used for prognostic prediction and for the design of therapeutic strategies in clinical practice.

5-methyladenosine regulators play a crucial role in development of chronic hypersensitivity pneumonitis and idiopathic pulmonary fibrosis.

5-methyladenosine (m5C) modification regulates gene expression and biological functions in oncologic areas. However, the effect of m5C modification in chronic hypersensitivity pneumonitis (CHP) and idiopathic pulmonary fibrosis (IPF) remains unknown. Expression data for 12 significant m5C regulators were obtained from the interstitial lung disease dataset. Five candidate m5C regulators, namely tet methylcytosine dioxygenase 2, NOP2/Sun RNA methyltransferase 5, Y-box binding protein 1, tRNA aspartic acid methyltransferase 1, and NOP2/Sun RNA methyltransferase 3 were screened using random forest and nomogram models to predict risks of pulmonary fibrosis. Next, we applied the consensus clustering method to stratify the samples with different m5C patterns into two groups (cluster A and B). Finally, we calculated immune cell infiltration scores via single-sample gene set enrichment analysis, then compared immune cell infiltration, related functions as well as the expression of programmed cell death 1 (PD-1, PDCD1) and programmed death protein ligand-1 (PD-L1, CD274) between the two clusters. Principal component analysis of m5C-related scores across the 288 samples revealed that cluster A had higher immune-related expression than B. Notably, T helper cell (Th) 2 type cytokines and Th1 signatures were more abundant in clusters A and B, respectively. Our results suggest that m5C is associated with and plays a crucial role in development of pulmonary fibrosis. These m5C patterns could be potential biomarkers for identification of CHP and IPF, and guide future development of immunotherapy or other new drugs strategies for pulmonary fibrosis.

A narrative review of progress in airway stents.

Background and Objective: Airway stents, used to restore airway patency, are mostly utilized by patients with malignant airway strictures, and are occasionally used in a range of other airway related diseases, including conditions which result in benign stenosis, malacia, and fistula. There has been an increasing number of airway stents that are being developed thanks to improvements in interventional therapy. However, the method of promoting airway stents for clinical application remains undetermined. Herein, we describe the recent advances in airway stents by reviewing the published studies, providing the reference for clinical decision-making and further research on airway stents. Methods: Relevant articles between January 1964 and November 2021 were obtained from PubMed, Web of Science, and EMBASE databases. The terms "metallic", "silicone", "drug-eluting", "biodegradable", "radioactive", "three-dimensional (3D)", and "stents" were searched in different combinations.Key Content and Findings: In this review, we focus on the latest evidence in terms of the application of various stents with novel materials and designs including novel metallic, novel silicone, drug-eluting, biodegradable, radioactive, and 3D stents for airway stenosis. Despite reducing the well-known complications of all current commercially available stents, novel stents are still in their infancy without a long track record of utility and safety, and remain some limitations. There are more steps to be taken before such stents enter routine clinical practice. Conclusions: A combination of 3D-printing method and biodegradable material may present a promising avenue of solving the existing problems pertaining to "classic" stents and has potential to become the main trend in the future.

Priority of PET-CT vs CT Thorax for EBUS-TBNA 22G vs 19G: Mesothorax Lymphadenopathy.

Introduction: Lung lesions and undiagnosed mesothorax lymphadenopathy is an issue that several doctors face in the everyday clinical practice. PET-CT and CT of the thorax are usually the first examinations to identify characteristics of the lesions before biopsy. Patients and Methods: We performed a retrospective study with 450 patients that had EBUS-TBNA with 22G, Upgraded 22G and 19G needles with and without PET-CT in order to identify the cost effeteness of performing EBUS-TBNA before or after PET-CT. All centers used the same PET-CT equipment and EBUS-TBNA system. Three types of needle were used for the endoscopy in order to identify similarities and differences for the cost-effectiveness. The costs in every center for every examination and materials were the same. Results: There were more block slices for 19G>22Gupgraded>21G>22G and there was cost-effectiveness when in general PET-CT was performed prior to biopsy of any lesion. 19G needle was more effective for lymphomas, while 22Gupgraded and 21G needles were more cost-effective when used for smaller lesions for primary lung cancer of metastatic disease. Conclusions: We have been using PET-CT and EBUS-TBNA in the everyday clinical practice according to the current guidelines for initial disease staging and re-staging. However; we can also use both in a cost effective method based on the initial radiologic findings.

Application of a Simulator-Based Teaching Method in the Training of the Flexible Bronchoscope-Guided Intubation.

BACKGROUND: The study aimed to explore the effect of a bronchoscopic simulator-based comprehensive teaching method in the training of flexible bronchoscope-guided intubation for suspected lung cancer patients for doctors without bronchofibroscopic operation background. METHODS: We designed a prospective self-control study involved in 35 trainees from the Navy Military Medical University's affiliated hospital to evaluate flexible bronchoscope-guided intubation's training outcome. Before and after the practice training, we recorded the flexible bronchoscope passing time from nasal to visible glottis and carina, tracheal placement tube, and ventilation. RESULTS: All 35 trainees could complete flexible bronchoscope-guided intubation independently after training. CONCLUSIONS: The bronchial diagnosis for suspected lung cancer patients and treatment-based model can be widely applied in tracheal intubation training.

Inflammation accelerates copper-mediated cytotoxicity through induction of six-transmembrane epithelial antigens of prostate 4 expression.

Copper is an essential trace metal, but imbalance in copper homeostasis can induce oxidative damage. Inflammation is a fundamental element of various pulmonary diseases. Although a positive relationship between copper and chronic pulmonary diseases has been reported, the underlying reasons are still not clear. The copper level in the sputum of patients with various pulmonary diseases was measured. An inflammatory model was established to evaluate the impact of inflammation on copper uptake in the lung. We found that the level of sputum copper was increased in patients with various pulmonary diseases, especially chronic obstructive pulmonary disease and asthma. Then, we confirmed that mice with pulmonary inflammation were susceptible to copper-mediated oxidative damage because of copper overload in lung tissue. Further investigation demonstrated that interleukin (IL)-17 and tumor necrosis factor (TNF)-α exerted synergistic effects in airway epithelial cells by upregulating the expression of six-transmembrane epithelial antigens of prostate 4 (STEAP4), a metalloreductase that reduces extracellular copper ions from the cupric state to the cuprous state and facilitates copper uptake. Inhibition of STEAP4 decreased the copper uptake of cells and inhibited copper-mediated oxidative damage. Moreover, we demonstrated that the upregulation of STEAP4 by IL-17 and TNF-α was largely dependent on TNF receptor-associated factor 4 (TRAF4). Traf4-/- mice were resistant to copper-mediated oxidative damage. Our data suggest a novel IL-17/TNF-α-TRAF4-STEAP4 axis that regulates copper homeostasis.

The development of bronchoscopy in China: a national cross-sectional study.

Objective: To investigate the development of bronchoscopy in China and compare it with its application in the early 21st century. Methods: The data collection was based on questionnaires. Three hundred and nineteen hospitals, which distributed across 30 provinces and 130 cities, were included in the study. Data about the application of bronchoscopy in Shanghai and Hunan province in the early 21st century are also involved for comparison. Results: The median period of performing diagnostic and therapeutic bronchoscopy was 19.7±11.0 and 7.4±7.0 years, respectively. On average, about 155.2 cases and 28.4 cases received diagnostic and therapeutic bronchoscopy in each hospital per month. The average area and number of the examination room was 122.7m2 and 2.2m2, respectively. More examination items were performed in specialty hospitals than those in general hospitals (P<0.05) and specialty hospitals owned more rooms exclusively for bronchoscopy (P<0.05), while no difference of the number of allocated doctors was found (P>0.05). On the other side, the whole amount of diagnosis and therapeutic items in teaching hospitals was slightly higher than that in non-teaching hospitals (P<0.01). Comparison of diagnosis and therapeutic endoscopy in Shanghai and Hunan province shows that the number of flexible bronchoscopy increased by 5.8 times in Shanghai from 2002 to 2017, while that increased by 3.4 times in Hunan province from 2005 to 2017. Furthermore, the average number of allocated doctors increased by 0.85 times in Shanghai, which was more rapidly compared with that of Hunan province (0.66 times) (P<0.05). Besides, the development rate of the diagnosis and therapeutic projects in Shanghai was significantly higher than that in Hunan province (P<0.05). Conclusion: All different classes of hospitals in China are capable of carrying out conventional bronchoscopy diagnosis and therapeutic projects, and newly developed bronchoscopy technology has gradually spread in high-level hospitals since 21st century. The higher class the hospital was, the earlier bronchoscopy was performed. Respiratory endoscopy in China has developed rapidly since the early 21st century and the construction of respiratory endoscopy center and the personnel training are on the right track, but it is also faced with inadequate equipment, unbalanced regional development and insufficient personnel allocation.

Exosomes from mmu_circ_0001359-Modified ADSCs Attenuate Airway Remodeling by Enhancing FoxO1 Signaling-Mediated M2-like Macrophage Activation.

Asthma is the most common chronic disease and is characterized by airway remodeling and chronic inflammation. Increasingly, studies have found that the activation and M1 phenotypic transformation of macrophages play important roles in asthma progress, including airway remodeling. However, the reversal of M1 macrophages to the M2 phenotype has been shown to attenuate airway remodeling. Exosomes are nano-sized extracellular vesicles derived from endosomes; they play direct roles in governing physiological and pathological conditions by the intracellular transfer of bioactive cargo, such as proteins, enzymes, nucleic acids (microRNA [miRNA], mRNA, DNA), and metabolites. However, transfer mechanisms are unclear. To uncover potential therapeutic mechanisms, we constructed an ovalbumin-induced asthma mouse model and lipopolysaccharide-induced RAW264.7 macrophages cells. High-throughput sequencing showed that mmu_circ_0001359 was downregulated in asthmatic mice when compared with normal mice. Adipose-derived stem cell (ADSC)-exosome treatment suppressed inflammatory cytokine expression by the conversion of M1 macrophages to the M2 phenotype, under lipopolysaccharide-induced conditions. Exosomes from mmu_circ_0001359 overexpression in ADSCs increased therapeutic effects, in terms of cytokine expression, when compared with wild-type exosomes. Luciferase reporter assays confirmed that exosomes from mmu_circ_0001359-modified ADSCs attenuated airway remodeling by enhancing FoxO1 signaling-mediated M2-like macrophage activation, via sponging miR-183-5p. In conclusion, mmu_circ_0001359-enriched exosomes attenuated airway remodeling by promoting M2-like macrophages.

Bibliometric analysis of scientific publications in respiratory journals from China and other top-ranking countries between 2007 and 2017.

INTRODUCTION: Respiratory disease remains one of the leading causes of mortality and morbidity worldwide. OBJECTIVES: In this study, we aimed to compare the quantity and quality of scientific publications in the field of respirology from the United States, the United Kingdom, Germany, Canada and China. METHODS: Articles published in 58 respiratory journals from 2007 to 2017 were screened with Science Citation Index Expanded database. The number of total and annual articles, article types, impact factor (IF), h-index, citations and articles in the high-impact journals from the corresponding country were collected for quantity and quality comparisons. The correlation of socioeconomic factors and annual publications was also analysed. RESULTS: A total of 93078 articles were published worldwide in respiratory journals from 2007 to 2017. The United States contributed the largest proportion (34399 (37.0%)), followed by the United Kingdom (9494 (10.2%)), Germany (6918 (7.4%)) and Canada (6574 (7.1%)). Publications from China represented the 6th, but this quantity is rapidly increasing. The United States occupies the dominant place in all kinds of article types under investigation in the study, except in the category of meta-analysis. For total and average citations, China still lags behind the other 4 countries in the study. The annual numbers of articles from China, Canada and the United States were positively correlated with gross domestic product (P < 0.05). CONCLUSIONS: The United States has played predominant role in respiratory research for the last 11 years. Although China has made great progress in the number of published articles over the past decade, the quality of these publications needs further improvement.

The 100 most influential publications in asthma from 1960 to 2017: A bibliometric analysis.

BACKGROUND: The area of asthma medicine has produced a large volume of important clinical and scientific papers that can be found in those most influential journals. The purpose of our study was to identify the 100 most cited papers in asthma research and to analyze their characteristics. METHODS: We used the Institute for Scientific Information Web of Knowledge Database to identify the most frequently cited articles published from 1960 to December 2017. Original articles and reviews were included in the study. The 100 top-cited articles were then analyzed with regard to number of citations, publication year, journals, institution, research type and field, authors and countries of authors of publications. RESULTS: The 100 top-cited articles in asthma were published between 1960 and 2011 with a median of 933 citations per article (range, 701-2947). The number of citations per article was greatest for articles published in the 1990s. The United States of America contributed most of the classic articles, followed by England. The leading institutions were Imperial College London, McMaster University, Erasmus University Rotterdam. The 100 top-cited articles were published in twenty-five journals, led by The New England Journal of Medicine (21 articles), followed by American Journal of Respiratory and Critical Care Medicine (19 articles), Lancet (11 articles), respectively. Among the 100 classics, 50% articles were clinical research articles. CONCLUSIONS: Our study provides a historical perspective on the progress of research on asthma. Studies conducted in well-developed European countries and North America, published in high-impact journals had the highest citations.

A case report of tongue metastasis from lung squamous cell carcinoma and literature review.

RATIONALE: Tongue metastasis from lung cancer is extremely rare, and the prognosis of these patients is rather poor. PATIENT CONCERS: A 56-year-old man was found a 4-cm cavity lesion in the left upper lobe, which was initially misdiagnosed as tuberculosis. DIAGNOSES: A case of lung squamous cell carcinoma that metastasized to the base of a patient's tongue. INTERVATIONS: We send the biopsy of the lung and the tongue lesions for gene sequencing. OUTCOMES: He received systemic chemotherapy, but continued to have pain at the base of his tongue and died 7 months later. LESSONS: From sequencing data, mutations in KRAS proto-oncogene, GTPase (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and tumor protein p53 (TP53) were found in the tumor biopsy of the patient. All of these were indicators of poor prognosis.

Underexpression of LKB1 tumor suppressor is associated with enhanced Wnt signaling and malignant characteristics of human intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a rare and highly aggressive malignancy. In this study, we identified the presence of gene deletion and missense mutation leading to inactivation or underexpression of liver kinase B1 (LKB1) tumor suppressor and excluded the involvement of LKB1 gene hypermethylation in ICC tissues. Immunohistochemical analysis showed that LKB1 was underexpressed in a portion of 326 ICC tissues compared to their adjacent normal tissues. By statistical analysis underexpression of LKB1 in ICC tissues significantly correlated with poor survival and malignant disease characteristics in ICC patients. Moreover, we showed that knockdown of LKB1 significantly enhanced growth, migration, and invasion of three LKB1-competent ICC cell lines. Global transcriptional profiling analysis identified multiple malignancy-promoting genes, such as HIF-1α, CD24, Talin1, Vinculin, Wnt5, and signaling pathways including Hedgehog, Wnt/ß-catenin, and cell adhesion as novel targets of LKB1 underexpression in ICC cells. Furthermore, knockdown of LKB1 gene expression dramatically enhanced Wnt/ß-catenin signaling in ICC cells, while an inverse correlation between LKB1 and nuclear ß-catenin was observed in ICC tissues. Our findings suggest a novel mechanism for ICC carcinogenesis in which LKB1 underexpression enhances multiple signaling pathways including Wnt/ß-catenin to promote disease progression.

Malignant pleural effusion supernatants are substitutes for metastatic pleural tumor tissues in EGFR mutation test in patients with advanced lung adenocarcinoma.

BACKGROUND: Though the possibility of using malignant pleural effusions (MPEs) as alternatives for metastatic pleural tumor tissues (MPTTs) in epidermal growth factor receptor (EGFR) mutation test has been examined, due to the lack of studies comparing the results in matching MPEs and MPTTs, the clinical value of MPEs for advanced adenocarcinoma patients with pleural effusions is not confirmed. METHODS: EGFR mutation statuses in matching MPTTs, MPE supernatants and cell blocks, of 41 patients with advanced lung adenocarcinoma as diagnosed by thoracoscopy were analyzed using amplification refractory mutation system (ARMS). RESULTS: EGFR mutations were detected in 46.3% (19/41) of MPTTs, 43.9% (18/41) of MPE supernatants and 56.3% (18/32) of MPE cell blocks by ARMS analysis. Generally, the same EGFR statuses were identified in both MPTTs and matching MPE cell blocks of 81.3% patients (26/32), whereas MPTTs and matching MPE supernatants of 87.8% (36/41) patients shared the same EGFR status. Compared with EGFR mutation detection in MPTTs, the sensitivity of EGFR mutation detection in MPE-cell blocks was 87.5% (14/16), specificity was 75.0% (12/16), while the sensitivity of EGFR mutation detection in MPE-supernatants was 84.2% (16/19), specificity was 90.9% (20/22). CONCLUSIONS: The high concordance of EGFR mutation statuses between MPEs and MPTTs in lung adenocarcinoma patients with pleural metastasis as determined by ARMS analysis suggests that MPEs, particularly MPE supernatants, may be substitutes for MPTTs in EGFR mutation test.

Anticancer activity of oncolytic adenoviruses carrying p53 is augmented by 11R in gallbladder cancer cell lines in vitro and in vivo.

Gallbladder cancer (GBC) is a rare disease associated with an extremely poor patient prognosis, and occasionally, aberrant expression of p53 is present. Considering that p53 is one of the most widely studied tumor­suppressor genes, we used a cell-penetrating peptide, 11R, to enhance the transferring efficiency of the oncolytic adenovirus carrying the p53 gene by constructing SG7605-11R-p53, a gene-viral therapy system which has higher specificity, enhanced safety, and efficacy. After infection with SG7605-11R-p53 at a multiplicity of infection (MOI) of 1 PFU/cell in vitro, the survival rate of EH-GB1 cells was lower than 50%, and that of EH-GB2 cells was lower than 40%, while the survival rate was higher than 90% for BJ human fibroblast cells, demonstrating that SG7605-11R-p53 has potent specific cytotoxicity against GBC cells. The tumor growth was greatly inhibited in nude mice bearing EH-GB2 xenografts when the total dose of SG7605-11R-p53 was 1x109 PFU, and terminal dUTP nick end-labeling (TUNEL) revealed that the apoptotic rate of cancer cells was 66.75±6.702%. Compared with existing gene therapy with long-standing shortcomings, our new system offers an additional option for patients with advanced GBC and other cancers who may not be suitable for chemotherapy, radiotherapy or who are not indicated for surgical treatment.

Gemcitabine plus oxaliplatin for the treatment of leptomeningeal metastases of non-small cell lung cancer: A case report and review of the literature.

A 62-year-old male presented with stage IV lung adenocarcinoma with leptomeningeal metastases (LM). Gemcitabine (1000 mg/m2 i.v.) was administered on days 1 and 8 while oxaliplatin (100/m2 i.v.) was administered on day 1 and repeated for 4 cycles every 3 weeks. Computerized tomography (CT) and cerebrospinal fluid (CSF) were used to evaluate the response of the LM and the primary tumor to drug therapy. Following the administration of chemotherapy, headaches were observed to be notably reduced 6 days later and absent after 14 days. The symptoms of coughing and chest pain were alleviated. Subsequent to 4 cycles of treatment, the patient had a partial response (PR) and the CSF pressure was normal. Analysis of the CSF revealed that it was colorless, positive for protein, had a total cell number of 0/l and contained no cancer cells. However, the primary lung tumor progressed for 1 year. This may suggest that first-line therapies, including the use of gemcitabine and oxalipaltin, may be appropriate for the treatment of non-small cell lung carcinoma (NSCLC) with LM involvement.

Identification of novel mutations of TP53, ALK and RET gene in metastatic thymic squamous cell carcinoma and its therapeutic implication.

Thymic tumors are epithelial tumors of the thymus for which multimodal therapies are often ineffective because of a lack of standardized regimens. Due to the low incidence, the molecular pathology and genomic abnormalities of thymic epithelial tumors are largely unknown. In this study, we report our comprehensively genomic study on a case of metastatic thymic tumor. Using next generation deep DNA sequencing technology, we sequenced 190 segments of 46 cancer genes of the cancer genome to cover 739 COSMIC mutations in 604 loci. Among these sequenced cancer genes, we identified that three low frequency (~10% of cells) mutations in the TP53 gene (c.782+1G>T), ALK gene (c.3551C>T), and RET gene (c.2651A>T). To the best of our knowledge, this is the first study to show those mutations in thymic tumor. Of note, our study further indicates comprehensive molecular analysis may facilitate development of novel diagnostic and therapeutic strategies for thymic tumors.