De Novo T790M Mutation in an L858R Epidermal Growth Factor Receptor Mutant-Associated Lung Adenocarcinoma
CANCERS
Authors: Fujiwara, Takumi; Kobayashi, Tetsu; Yasuma, Taro; D'Alessandro-Gabazza, Corina N.; Toda, Masaaki; Fujimoto, Hajime; Fujiwara, Kentaro; Takeshita, Atsuro; Nishihama, Kota; Okano, Tomohito; D'Alessandro, Valeria Fridman; Takei, Yoshiyuki; Hataji, Osamu; Gabazza, Esteban C.
Abstract
Simple Summary Lung adenocarcinomas caused by (L858R) somatic mutation in the epidermal growth factor receptor (EGFR) show good therapeutic response to tyrosine kinase inhibitors. These tumors develop resistance to therapy mainly after acquired T790M mutation. However, whether the T790M mutation occurred before or after therapy is unknown. To demonstrate this, we developed mice with tetracycline-inducible lung-specific expression of the full-length genomic DNA of the human epidermal growth factor receptor containing an L858R mutation or both L858R and T790M mutations and evaluated de novo T790M mutation in untreated transgenic mice carrying a single L858R EGFR mutation. The results showed that lung tumors spontaneously acquire T790M mutation without any drug-related selective pressure. Background: Lung cancer is the leading cause of mortality for cancer worldwide. A point mutation in exon 21 of the epidermal growth factor receptor resulting in the substitution of arginine for leucine at position 858 (L858R) is a frequent cause of lung adenocarcinoma. Tyrosine kinase inhibitors are effective for treating patients with lung cancer associated with mutant epidermal growth factor receptors but most tumors become resistant shortly after treatment. The substitution of methionine for threonine at position 790 (T790M) on exon 20 is the most frequently acquired mutation leading to resistance to tyrosine kinase inhibitors. Whether the T790M mutation occurred after tyrosine kinase inhibitor therapy or it already existed before therapy is unclear. Methods: Here, we developed mice with tetracycline-inducible lung-specific expression of the full-length genomic DNA of the human epidermal growth factor receptor containing an L858R mutation or both L858R and T790M mutations and evaluated de novo T790M mutation in untreated transgenic mice carrying a single L858R EGFR mutation. Results: The L858R mutation-associated lung adenocarcinoma acquired de novo T790 mutation without previous therapy. Conclusions: The results of this study suggest that lung tumors may spontaneously acquire T790M mutations without any drug-related selective pressure.
Visible-light-driven AgBr-TiO2-Palygorskite photocatalyst with excellent photocatalytic activity for tetracycline hydrochloride
JOURNAL OF CLEANER PRODUCTION
Authors: Shi, Yingying; Yan, Zhuan; Xu, Yingtao; Tian, Tian; Zhang, Jing; Pang, Jianfeng; Peng, Xihua; Zhang, Qianghua; Shao, Mingli; Tan, Wenyi; Li, Hailun; Xiong, Qingping
Abstract
Tetracycline hydrochloride (TC) wastewater has complex components, high concentration of organic matter and certain biological toxicity. Photocatalytic degradation is of great application prospect due to its green, thorough and efficient removal of TC. In this study, heterojunction photocatalyst supported on Palygorskite (Pal) AgBr-TiO2-Pal with visible light response was successfully prepared via sol-gel and liquid deposition method successfully. Taking TC as the target pollutant, the photocatalytic performance of AgBr-TiO2-Pal photocatalys excited by visible light was studied. The spreading/grafting of AgBr-TiO2 on the surface of Pal was improved by a series of structural characterization and composition analysis. The results also demonstrated that the specific surface area of AgBr-TiO2-Pal was about 48.06 m(2).g(-1) with uniform mesoporous slit. The AgBr-TiO2-Pal catalyst was very effective for the degradation of TC, and it still retained its high stability and reusability after five cycles. The results showed that under the best reaction conditions (initial concentration of tetracycline 10 mg,L-1, catalyst dosage 0.5 g.L-1, pH value 9), with the excitation of visible light, the maximum removal ratio of TC was 90%, and the mineralization ratio was 67%. The removal efficiency and degradation rate of TC by AgBr-TiO2-Pal catalyst were 2.17 and 4.75 times as much as those of TiO2 respectively. The outstanding photocatalytic performance of heterogeneous AgBr-TiO2-Pal catalyst was obtained by fully participate in the reaction by photoinduced charge. This study could be expected to be used in photocatalytic degradation of antibiotic pollutants in wastewater treatment. (C) 2020 Elsevier Ltd. All rights reserved.