[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.
Annals of Oncology 07/2014; 25(10). DOI:10.1093/annonc/mdu251 · 7.04 Impact Factor
[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.
Water Science & Technology Water Supply 02/2012; 12(1):24. DOI:10.2166/ws.2011.090 · 0.39 Impact Factor
[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.
[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.
International Journal of Oral and Maxillofacial Surgery 02/2009; 38(3):296-9. DOI:10.1016/j.ijom.2008.12.012 · 1.57 Impact Factor
[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.
British Journal of Cancer 02/2008; 98(4):742-8. DOI:10.1038/sj.bjc.6604235 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two low-rank coals, a sub-bituminous coal (BA) and a lignite (LY), were treated
by hot water extraction (HWE) and hydrothermal treatment (HTT), and the
environmental impacts of water-soluble matters eluted from coal by the HWE
and HTT processes were evaluated in terms of TOC, mutagenicity, and the acute
toxicity against freshwater organisms. When HWE was performed at 80°C, the
degree of TOC for LY was much higher than that for BA. However, for HTT,
the two coals gave comparable TOC values in L/S ratio of both 100 and 3. The
HWE and HTT eluents of two coals were assessed by the Ames mutagenicity
assay with Salmonella typhimurium TA100 and TA98 strains, and no notable
mutagenicity was observed in the presence or absence of metabolic activation.
When the mutagenicity of the 300ºC-HTT eluent of LY was analyzed, no notable
mutagenicity was also observed. For the HWE and HTT eluents of LY, the acute
toxicity test was carried out by use of Daphnia magna and Oryzias latipes. When
the 80°C-HWE eluent was tested, almost no toxicity was observed for D. magna
and O. latipes. However, when the HTT eluents were examined, the toxicity
increased as the elevation of the HTT temperature, and the toxicity of organic
matters dissolved in the 350°C-HTT eluent was comparable to that of reference
phenolic compounds. From the FTIR analysis of organic matters eluted in the
HTT eluents, it is found that the toxicity is caused by the presence of aromatic
compounds with hydrophilic substituents, such as carboxyl and hydroxyl groups.
Keywords: low-rank coal, wastewater, water-soluble organic matters,
mutagenicity, ames assay, acute toxicity.
[Show abstract][Hide abstract] ABSTRACT: The mutagen formation potential (MFP) was measured for the river water, the
raw sewage and the effluent of the sewage works by means of the Ames
Salmonella mutagenicity assay. MFP of the river water samples ranged from
1,200 to 22,000 net revertant colonies per liter of sample water. MFP of the
effluent was from 5,300 to 22,000 net revertant colonies per liter. This survey
showed that the removal percentages of dissolved organic carbon (DOC) at the
sewage works were 62.0-79.3%. It also showed that MFP reductions at the same
sewage works were 37.5-62.9%. There was no significant correlation observed
between MFP and organic matter concentration for the river water samples.
However, a weak correlation between ammonia nitrogen and MFP was observed
for the same river water samples. These results indicate that MFP cannot be
accurately estimated by use of the conventional water quality indices. When the
samples contain a high concentration of ammonia nitrogen, it is difficult to
control the amount of free chlorine dosages stoichiometrically, possibly resulting
in the overdose of chlorine. An overdose of chlorine may cause further formation
of mutagens. The isotherm of mutagen precursors adsorption onto the activated
carbon (OL 20x50), which was purchased from Calgon Mitsubishi Chemical
Corporation, was studied using river water in order to explore the means of
removing mutagen precursors from raw water used for the water supply. The
adsorption isotherm attained fit well into the Freundlich model.
Keywords: Ames Salmonella assay, chlorination, mutagenicity, mutagen
formation potential, river water, sewage, activated carbon, adsorption isotherm.
[Show abstract][Hide abstract] ABSTRACT: A novel adsorbent, which had been developed for phosphate adsorption, was adopted for arsenic removal from groundwater. Adsorption isotherm, pH dependence of the isotherm and adsorption rate were studied by batch method. Furthermore, by using a granular adsorbent of 1.8 mm diameter which is commercially available, lab-scale experiments of continuous adsorption treatment of actual groundwater containing arsenic at 50 mg m(-3) were conducted to examine the performance of the adsorbent. A large amount of arsenic, i.e., 10 g As kg(-1), was adsorbed at pH 7.0 and 10 mg As m(-3) in equilibrium concentration. It was only a 5% higher amount compared to conventional activated alumina. However, twice the bed volume, i.e., total volume of effluent divided by empty column volume, was achieved till breakthrough by using this novel adsorbent. This may be because the pH decrease, which enlarges apparent adsorption capacity of the adsorbent, is caused by a self-pH decrease function of the adsorbent. The self-pH decrease function must be delivered by dissociation of Al (III) aquoion. The proton release was clearly observed in batch experiments.
Water Science & Technology 02/2004; 50(8):23-32. · 1.11 Impact Factor