A large strand of research supports the idea of implementing a population-based lung cancer screening program using low-dose computer tomography to reduce lung cancer mortality. It has been recognized that one of the key factors contributing a successful lung screening program is its combination with smoking cessation intervention. This study provides results of smoking cessation intervention in a population-based lung cancer screening trial. Korean Lung Cancer Screening Project (K-LUCAS) is a single arm prospective nationwide lung cancer screening trial. In K-LUCAS, all currently smoking participants were provided with mandatory smoking cessation counselling. Smoking status of 5,144 currently smoking participants in K-LUCAS were surveyed by telephone 6 months after participation. There were some variations in the intervention; the department of which counselling is provided within; publicly or privately operated smoking clinics; and whether or not counselling is provided simultaneously with screening results. The impact of such variations on smoking cessation is also reported. Participant’s motivation to quit smoking increased by 9.4% on average after participating in lung cancer screening. The smoking cessation rate was 24.7% and over 80% of quitters said that participation in lung cancer screening motivated them to quit smoking. The smoking cessation counselling was more effective when the smoking clinics are operated by national health insurance services than when operated privately by hospital and when counselling was provided simultaneously with screening results than when provided separately with screening results. The screening results itself also affected smoking cessation. The probability of quitting smoking for participants with positive screening results were significantly higher than participants with negative results. Smoking cessation intervention combined with lung cancer screening program encourages smoking cessation for screening participants. Our results the highlights the importance of incorporating smoking cessation intervention in lung cancer screening program which would further enhance the effectiveness of lung cancer screening program.
Administering the best treatment after acquiring resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) requires the knowledge of the resistance status. In this trial, the treatment efficacy of osimertinib (AZD9291) was assessed in patients with non-small-cell lung carcinoma (NSCLC) harboring T790M resistance mutation, which was detected in the circulating tumor DNA (CtDNA) without re-biopsy of the tumor tissue. To prove 60% response rate of osimertinib compared to 30% as null hypothesis, and considering 10% drop out rate, 19 subjects were recruited. To extract CtDNA, 15 mL of peripheral blood was withdrawn and centrifuged immediately before storage. Cobas® v2 RUO (Roche diagnostics) and PANA mutyper® (Pangene, Korea) were used to detect the EGFR mutations from CtDNA. Osimertinib was prescribed as an 80 mg tablet once in a day irrespective of the food intake. Eighty patients with acquired resistance to prior EGFR TKIs were screened for T790M resistance mutation, and the CtDNA of 21 subjects (26.3%) showed T790M mutation. T790M mutation was detected by both PANA mutyper® and Cobas® in 13 cases, T790M was detected only by PANA mutyper® in 4 cases, and only by Cobas® in 4 cases. Nineteen subjects (age: 64.4 ± 11.6 years old, 14 women, 5 men) were enrolled in this prospective single arm trial from September 2016 to April 2017. Prior EGFR TKIs were afatinib (n=3), erlotinib (n=4), gefitinib (n=10), erlotinib and afatinib (n=1), and gefitinib and afatinib (n=1). Twelve subjects had exon 19 deletion of EGFR gene, 4 had L858R point mutation, one showed exon 19 deletion and L858R, 1 had G719X, and 1 case showed no activating mutation. The response to osimertinib was evaluable in 15 subjects; 4 subjects dropped out from this trial before response evaluation. Among the 15 subjects (efficacy analysis set), partial remission was observed in 10 cases (66.7%). Assuming 40% of screened patients are harboring T790M mutation, sensitivity of CtDNA testing is 65% using both tests, and 53% with either test. Toxicity and survival analyzes will be followed. (ClinicalTrials.gov Identifier: NCT02769286)
Background: The aim of this study is to investigate the feasibility of liquid biopsy using plasma and platelets for detection of ALK rearrangement. Methods: FISH was performed in 664 patients between January 2015 and May 2017. We retrospectively analyzed the FFPE tissue and blood sample to detect ALK rearrangement using multiplex RT-PCR from 30 advanced NSCLC patients who had available tissue specimen. Total RNA were extracted from FFPE cell blocks, plasma and platelets, respectively. EML4-ALK fusion RNA was detected using PANAqPCR™ EML4-ALK fusion gene detection kit. Results: 28 patients were FISH positive and 2 were negative. In a validation data compared with FISH, RT-PCR using FFPE tissue demonstrated 57.1% sensitivity and 69.2% accuracy. Liquid biopsy (plasma or platelets-positive) had higher sensitivity (96.4%) and accuracy (93.3%). Among the specimen of liquid biopsy, platelets showed slightly higher sensitivity and accuracy than plasma (82.1 and 83.3% vs 78.6 and 76.7%). Compared with FFPE tissue using RT-PCR, liquid biopsy showed 100% sensitivity, 20.0% specificity and 69.2% accuracy. Median proportion of positive cells in FISH was higher in subgroups of liquid biopsy with positive result (Plasma, 30.0 vs 15.0%, p = 0.062; Platelets 30.0 vs 20.0%, p = 0.104). In 18 patients with crizotinib treatment, platelets-positive subgroup showed a tendency of longer duration of treatment (7.2 vs 1.5 months, p = 0.071) and higher response rate (57.1 vs 0.0%, p = 0.092). However, plate-lets-positive subgroup showed significantly higher disease control rate than platelets-negative subgroup when they were treated with crizotinib (85.7 vs 25.0%, p = 0.044). Conclusions: Plasma and platelets are valuable sources for liquid biopsy using RT-PCR technique in detection of ALK rearrangement, and could play a supplementary role in diagnosis of ALK-positive NSCLC. Furthermore, platelets may be useful for predicting the treatment outcome of crizotinib. Legal entity responsible for the study: Legal entity responsible for the study Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest.
(-)-Epigallocatechin-3-gallate (EGCG), a main constituent of tea catechins, affects Gram-positive and Gram-negative bacteria differently; however, the underlying mechanisms are not clearly understood. Atomic force microscopy (AFM) was used to compare morphological alterations in Gram-positive and Gram-negative bacteria induced by EGCG and by H(2)O(2) at sub-minimum inhibitory concentrations (MICs). EGCG initially induced aggregates in the cell envelopes of Staphylococcus aureus and eventually caused cell lysis, which was not observed in cells treated with H(2)O(2). It initially induced nanoscale perforations or microscale grooves in the cell envelopes of Escherichia coli O157:H7 which eventually disappeared, similar to E. coli cells treated with H(2)O(2). An E. coli O157:H7 tpx mutant, with a defect in thioredoxin-dependent thiol peroxidase (Tpx), was more severely damaged by EGCG when compared with its wild type. Similar differing effects were observed in other Gram-positive and Gram-negative bacteria when exposed to EGCG; it caused aggregated in Streptococcus mutans, while it caused grooves in Pseudomonas aeruginosa. AFM results suggest that the major morphological changes of Gram-negative bacterial cell walls induced by EGCG depend on H(2)O(2) release. This is not the case for Gram-positive bacteria. Oxidative stress in Gram-negative bacteria induced by EGCG was confirmed by flow cytometry.
Testicular torsion is a urologic emergency. A testis injury produced by reperfusion can be more severe than that induced by ischemia. The reperfusion component typically involves the generation of toxic reactive oxygen species (ROS) with the return of blood following a period of ischemia. The present study was designed to determine whether KRG protected the rat testis against dysfunction and oxidative stress induced by I-R injury.
Cytology examination is currently standard non-invasive method for bladder cancer detection, while its sensitivity is low. Therefore, biomarker-based more sensitive and reliable non-invasive methods are currently required for detection of bladder cancer. Aberrant DNA hypermethylation is a major mechanism for inactivating tumor suppressor genes and other cancer-associated genes in various cancers. Promoter hypermethylation is an important early event in the development of bladder cancer and could be used as a promising diagnostic biomarker. To identify potential methylation biomarkers in bladder cancers, we performed genome-wide methylation scanning and assessed methylation status in DNA from exfoliated urine cytology specimens.
8-hydroxydeoxyguanosine (8-oxo-dG), a nucleoside of 8-oxo-Gua, has anti-inflammatory properties. We investigated the inhibitory mechanism of 8-oxo-dG in mouse allergic asthma. BALB/c mice were sensitized and challenged with OVA to induce asthma. OVA-specific serum IgE levels or expressions of cytokine proteins were measured by ELISA, recruitment of inflammatory cells into bronchoalveolar lavage (BAL) fluid or lung tissues by Diff-Quik or haematoxylin and eosin staining, epithelial hyperplasia by periodic acid-Schiff staining, the expressions of CD40, CD40L, and VCAM-1 by immunohistochemistry, the mRNA of cytokines by RT-PCR, and the activation of small G proteins, PKCs, MAP kinases, STAT1 on serine 727, and nuclear factor-kappa B (NF-κB) in BAL cells or lung tissues by Western blot or EMSA. 8-oxo-dG reduced the level of OVA-specific IgE, the number of inflammatory cells infiltrating BAL fluid or lung tissues, the number of goblet cells, the expression of CD40, CD40L or VCAM-1, the mRNA and protein levels of cytokines, the activation of small G proteins, PKC isoforms, MAP kinases, STAT1 on serine 727 and NF-κB, all which were increased in BAL cells or lung tissues of OVA-induced mouse allergic asthma.The data suggest that 8-oxo-dG may have a therapeutic effect in allergic asthma by reducing various allergic responses through regulation of small G-proteins/PKCs/MAP kinases/STAT1 on serine 727/NF-κB. 8-hydroxydeoxyguanosine (8-oxo-dG), a nucleoside of 8-oxo-Gua, has anti-inflammatory properties. We investigated the inhibitory mechanism of 8-oxo-dG in mouse allergic asthma. BALB/c mice were sensitized and challenged with OVA to induce asthma. OVA-specific serum IgE levels or expressions of cytokine proteins were measured by ELISA, recruitment of inflammatory cells into bronchoalveolar lavage (BAL) fluid or lung tissues by Diff-Quik or haematoxylin and eosin staining, epithelial hyperplasia by periodic acid-Schiff staining, the expressions of CD40, CD40L, and VCAM-1 by immunohistochemistry, the mRNA of cytokines by RT-PCR, and the activation of small G proteins, PKCs, MAP kinases, STAT1 on serine 727, and nuclear factor-kappa B (NF-κB) in BAL cells or lung tissues by Western blot or EMSA. 8-oxo-dG reduced the level of OVA-specific IgE, the number of inflammatory cells infiltrating BAL fluid or lung tissues, the number of goblet cells, the expression of CD40, CD40L or VCAM-1, the mRNA and protein levels of cytokines, the activation of small G proteins, PKC isoforms, MAP kinases, STAT1 on serine 727 and NF-κB, all which were increased in BAL cells or lung tissues of OVA-induced mouse allergic asthma. The data suggest that 8-oxo-dG may have a therapeutic effect in allergic asthma by reducing various allergic responses through regulation of small G-proteins/PKCs/MAP kinases/STAT1 on serine 727/NF-κB.
In this study, we characterized the two-dimensional lattice of bovine serum albumin (BSA) as a chemical and physical barrier against bacterial adhesion, using fluorescence microscopy and atomic force microscopy (AFM). The lattice of BSA on glass surface was fabricated by micro-contact printing (μCP), which is a useful way to pattern a wide range of molecules into microscale features on different types of substrates. The contact-mode AFM measurements showed that the average height of the printed BSA monolayer was 5–6 nm. Escherichia coli adhered rapidly on bare glass slide, while the bacterial adhesion was minimized on the lattices in the range of 1–3 μm2. Especially, the bacterial adhesion was completely inhibited on a 1 μm2 lattice. The results suggest that the anti-adhesion effects are due by the steric repulsion forces exerted by BSA.
Korean red ginseng (KRG) is a potent antioxidant, and a free radical scavenger. The aim of this study was to investigate the possible effects of KRG on the oxidant damage after ischemia/reperfusion (I/R) of rat urinary bladder.
This study is to compare the usefulness of saline infusion sonogram (SIS) or small diameter outpatients flexible minihysteroscopy for first-step accurate diagnosis of intrauterine mass on acceptability of patients.
TRUS guided biopsy of the prostate is the standard diagnostic modality for prostate cancer. The hypoechoic lesion is the most common finding of prostate cancer, but diagnostic value of hypoechoic lesion itself is debating. We evaluated the diagnostic significance of hypoechoic lesion and increased blood flow in TRUS for prostate cancer detection.
To evaluate the outcome and complications of a prospective comparative trial between the SPARC (SPARC sling system, suprapubic arc, American Medical System) and the MONARC (MONARC subfascial hammock, American Medical System) sling systems for the treatment of female stress urinary incontinence.