[Show abstract][Hide abstract] ABSTRACT: Background:
Whether the mutant allele frequency (MAF) may also have predictive implications for tyrosine kinase inhibitor (TKI) therapy in patients with advanced epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma (AELAd) remains unknown.
Patients and methods:
Based on a biobanking system in conjunction with our institution, we assessed EGFR mutation status using pyrosequencing (Py) and by outsourcing laboratory tests, such as the Cycleave (Cy) and the Scorpion ARMS (A).
Out of 705 patients enrolled in the Shizuoka Lung Cancer Mutation Study between July 2011 and March 2013, 102 AELAd patients were identified as carrying the L858R mutation (L858Rm) using Py to analyze histological specimens. Of these 102 patients, the EGFR mutation status was assessed using both Py and Cy in 48 patients: the median MAF of L858R (MAFLR) was 18.5% (range: 8%-82%), and 45 patients (94%) were identified as having an L858Rm using both Py and Cy. Three patients (6%) with discrepant L858Rm findings were only identified using Py. The plotting of a receiver operating characteristic curve to identify the discordance in L858Rm findings showed that the area under the curve for MAFLR was 0.967 (95% confidence interval: 0.91-1) and that an MAFLR of 9% resulted in high sensitivity (100%) and specificity (99%). Also, 29 patients with AELAd, excluding those with postoperative recurrences, had their L858R status assessed using Cy or A. The median age, 69 years (range: 47-84 years); male/female, 14 (48%)/15 (52%); smokers/never-smokers 13 (45%)/16 (55%); ECOG PS 0-1/2-3, 26 (90%)/3 (10%); stage IIIB/IV, 4 (14%)/25 (86%); median MAFLR, 18% (range: 8%-63%). Patients with an MAFLR of ≤9% had a significantly shorter progression-free survival (PFS) period after TKI therapy than those with an MAFLR of >9% (mPFS: 92 versus 284 days, P = 0.0027).
The MAF may be a potential predictive factor of TKI treatment efficacy in patients with AELAd carrying the L858Rm.
[Show abstract][Hide abstract] ABSTRACT: One hundred and two kinds of coals from different countries were analyzed for Hg by an automatic mercury analyzer (AMA) based on an official method (heat vaporization atomic absorption spectrometry); the majority of those coals were bituminous coals with relatively low-sulfur content. Those coals are supplied in a powdery form as standard samples by a Japanese organization and called "SS-coals". Since the sample amount of coal used in the AMA measurement is usually small, the particle size of coal may greatly affect the measurement; however there have been no systematic studies on the matter. Some of the SS-coals showed a great deviation in data (relative standard deviation (RSD) is high) in the determination of Hg. For the determination of other trace elements, those coals did not show such a deviation in data. The unique character of Hg observed in the determination was discussed with the possibility of localization of Hg in coal body at a microscopic level. The content of Hg in coal (bituminous coals) somewhat correlated with that of ash (or Al) rather than that of sulfur. Also, it was found that the coals of low ash contents and those of high inherent moisture tended to have low Hg contents.
[Show abstract][Hide abstract] ABSTRACT: Recently, acid digestion assisted by microwave processing is popularly utilized for a pretreatment of the coal samples. It must be important to establish a proper protocol for coal in terms of the determination of trace elements by a joint-use of microwave assisted acid digestion (MW-AD) and atomic spectroscopy. In this study, the effect of MW-AD conditions on the determination of trace elements in coal by use of inductively coupled plasma-atomic emission spectrometry (ICP-AES) and inductively coupled plasma mass spectrometry (ICP-MS) was examined. When MW-AD was carried out by using with or without HF condition, the recovery of tested elements was not affected by the HF addition in the MW-AD acid mixture. After the optimization of MW-AD operation temperature and time, the concentration of major and trace elements in two certified reference coals (NIST 1632c and SARM 20) was examined and the good recoveries for each element were obtained. In addition, the determination of ultra-trace elements in coal sample, such as As, Se, Cd, and Hg were investigated by use of flow injection ICP-MS (FI-ICP-MS) method.
[Show abstract][Hide abstract] ABSTRACT: The effects of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with non-small cell lung cancer (NSCLC). We examined whether progression-free survival (PFS), post-progression survival (PPS), or tumor response could be valid surrogate endpoints for OS after first-line chemotherapies in advanced NSCLC by using individual-level data, given the lack of research in this area. Between April 2009 and June 2011, 50 patients with advanced non-squamous NSCLC treated with cisplatin and pemetrexed as first-line chemotherapy were analyzed. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.89, P < 0.05, R2 = 0.79), PFS was moderately correlated with OS (r = 0.67, P < 0.05, R2 = 0.39), and tumor shrinkage was weakly correlated with OS (r = 0.36, P < 0.05, R2 = 0.14). Performance status at the beginning of second-line treatment, the best response to second-line treatment, and number of regimens used after progression following first-line chemotherapy were significantly associated with PPS (P < 0.05). Analysis of individual-level data suggested that PPS could be used as a surrogate for OS in patients with advanced non-squamous NSCLC with unknown oncogenic driver mutations and therefore limited options for subsequent chemotherapy. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS. These results should be validated in other larger populations. Keywords: non-small cell lung cancer, overall survival, post-progression survival, progression-free survival, tumor response.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to examine the relationship between the expression level of excision repair cross-complementation group 1 (ERCC1) and of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) in various thoracic neoplasm.Three hundreds-eight patients [non-small cell lung cancer (NSCLC)(n=56), malignant pleural mesothelioma (MPM)(n=21), pulmonary metastatic tumors (PMT)(n=148), thymic epithelial tumors (n=49) and pulmonary neuroendocrine tumor (n=34)] who underwent 18F-FDG PET before treatment were included in this study. Tumors sections were stained by immunohistochemistry for ERCC1, glucose transporter 1(Glut1), vascular endothelial growth factor (VEGF) and microvessel density (MVD) by determinate by CD34. The expression of ERCC1 in thoracic neoplasms had a positivity of 49% (152/308), and the positive rates of ERCC1 expression in NSCLC, PMT, thymic epithelial tumor, pulmonary neuroendocrine tumor and MPM were 52, 43, 53, 47 and 85%, respectively. The positivity of ERCC1 expression was significantly higher in MPM and SQC than in the other histological types. A statistically significant correlation between ERCC1 expression and 18F-FDG uptake was observed in thymic epithelial tumors, especially thymoma. Moreover, ERCC1 expression was also closely associated with the expression of Glut1, VEGF and MVD.Our results indicated that 18F-FDG uptake may be an alternative biomarker for predicting ERCC1 expression in patients with thymoma.
[Show abstract][Hide abstract] ABSTRACT: A new method for the removal of arsenite [As(III)] and selenate [Se(VI)], which are difficult to remove by conventional water treatment methods from aqueous media, was investigated. This method involves the use of photocatalytic oxidation of As(III) and photocatalytic reduction of Se(VI). Also, a novel TiO2-adsorbent hybrid (HYB) which has photocatalyst sites and adsorbent sites on the same particle was developed. When the removal of As(III) by use of photocatalyst adsorbent system and the HYB system was carried out, As(III) was effectively removed from aqueous phase. Moreover, with the removal of Se(VI) by using photocatalytic reduction, Se(VI) could also be removed from aqueous phase under the photocatalyst-adsorbent system and the HYB system, even if the concentration of a hole scavenger formic acid was reduced.
No preview · Article · Feb 2012 · Water Science & Technology Water Supply
[Show abstract][Hide abstract] ABSTRACT: Several coals were tested in a pilot plant of coal combustion facility, and a slurry supernatant water from the wet flue gas desulfurization (FGD) system was obtained. The determination of trace elements in those FGD water samples was done by ICP-AES, ICP-MS, and other methods, while the analysis of major cations and anions was conducted by ICP-AES and ion chromatography, respectively. The levels of B, Se, and Hg in the FGD water samples sometimes exceeded the Japanese national effluent standards for terrestrial water (10, 0.1, and 0.005 mg/L for B, Se, and Hg, respectively). When oxy-fuel combustion was carried out by use of the same combustion facility, the concentrations of trace elements in the FGD water samples tended to be lower than those for the normal combustion. The removal of these hazardous trace elements was attempted by adsoption method and phocatalytic reduction method.
[Show abstract][Hide abstract] ABSTRACT: The mutagens produced through chemical reaction between chlorine and the insecticide fenitrothion were studied by using a quadrupole GC-MS. The mutagenicity and the mutagen formation potential (MFP) of the identified by-products were evaluated by the Ames assay (preincubation method) using Salmonella typhimurium TA100 without exogenous activation by S9 mix (TA100-S9). Before conducting GC/MS analyses, six compounds were presumed to be produced in chlorinated fenitrothion. These compounds were confirmed to be produced by the GC/MS analyses, but none of them were mutagenic. One of the chlorination by-products, 3-methyl-4-nitrophenol, has 19 times greater MFP than that of fenitrothion. This result suggests that a major mutagen in chlorinated fenitrothion will be produced via a chemical reaction between chlorine and 3-methyl-4-nitrophenol.
No preview · Article · Jul 2010 · Water Science & Technology
[Show abstract][Hide abstract] ABSTRACT: A case of large cell neuroendocrine carcinoma (LCNEC) of the tongue base is described. It was characterized by solid tumor nests with central necrosis and rosette formation resembling basaloid squamous cell carcinoma. Immunohistochemical examination revealed that this tumor had neuroendocrine differentiation. It was diagnosed as LCNEC of the tongue base. Pulmonary LCNEC is a well-established entity, but LCNEC also occurs in other organs. This is the first report of mucosal LCNEC in the oral cavity. Basal cells in the normal squamous epithelium around the tumor indicated positivity for neural cell adhesion molecule and N-cadherin. These cells were considered neuroendocrine-related cells in the lingual squamous epithelium, which are related to the tumorigenesis of mucosal LCNEC in the tongue base.
No preview · Article · Feb 2009 · International Journal of Oral and Maxillofacial Surgery
[Show abstract][Hide abstract] ABSTRACT: The clinical significance of L-type amino acid transporter 1 (LAT1) expression remains unclear, whereas many experimental studies have demonstrated that LAT1 is associated with the proliferation of cancer cells. The purpose of this study was to evaluate the prognostic value of LAT1 in patients with nonsmall cell lung cancer (NSCLC). A total of 321 consecutive patients with completely resected pathologic stage I-III NSCLC were retrospectively reviewed. Expression of LAT1 and proliferative activity, as determined by the Ki-67 labelling index, was also evaluated immunohistochemically and correlated with the prognosis of patients who underwent complete resection of the tumour. Expression of LAT1 was positive in 163 patients (51%) (29% of adenocaricnoma (58 of 200 patients), 91% of squamous cell carcinoma (91 of 100 patients), and 67% of large cell carcinoma (14 of 21 patients)). The 5-year survival rate of LAT1-positive patients (51.8%) was significantly worse than that of LAT1-negative patients (87.8%; P<0.001). L-type amino acid transporter 1 expression was significantly associated with lymph node metastasis and disease stage. Multivariate analysis confirmed that positive expression of LAT1 was an independent factor for predicting a poor prognosis. There was a significant correlation between LAT1 expression and Ki-67 labelling index. LAT1 expression is a promising pathological factor to predict the prognosis in patients with resectable stage I-III NSCLC.
Full-text · Article · Feb 2008 · British Journal of Cancer