Therapeutic Effects and Adverse Drug Reactions are Affected by Icotinib Exposure and CYP2C19 and EGFR Genotypes in Chinese Non-Small Cell Lung Cancer Patients

Chen, Jia,Zheng, Xin,Liu, Dong-Yang,Zhao, Qian,Wu, Yi-Wen,Tan, Fen-Lai,Wang, Yin-Xiang,Jiang, Ji,Hu, Pei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17

Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

Systematic review: total knee arthroplasty (TKA) in patients with pigmented villonodular synovitis (PVNS)

( Yi Chuen Tan ),( Jia Yin Tan ),( Konstantinos Tsitskaris ) 대한슬관절학회 2021 대한슬관절학회지 Vol.33 No.-

Background: To determine the functional outcomes, complications and revision rates following total knee arthroplasty (TKA) in patients with pigmented villonodular synovitis (PVNS). Materials and methods: We conducted a systematic review of the literature. Five studies with a total of 552 TKAs were included for analysis. The methodological quality of the articles was evaluated using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) scale. Functional outcomes, complications and revision rates were assessed. The mean age was 61 years (range 33-94 years) and the mean follow-up period was 61.1 months (range 0.2-35 years). Results: All the studies reported improvement in knee function following TKA. Post-operative stiffness was the most frequently reported complication, affecting 32.7% (n = 32) of patients in our review. Symptomatic recurrence of PVNS, component loosening, tibial-component fracture, instability and periprosthetic infection were the main factors leading to the need for revision TKA. Conclusion: The findings of this review support the use of TKA to alleviate the functional limitations and pain due to knee degeneration in patients with PVNS. The operating surgeon should be aware of the increased risk of postoperative stiffness, as well as a potentially higher risk of infection. Implant survival should also be considered inferior to the one expected for the general population undergoing TKA.

Oecophyllibacter saccharovorans gen. nov. sp. nov., a bacterial symbiont of the weaver ant Oecophylla smaragdina

Chua Kah-Ooi,See-Too Wah-Seng,Tan Jia-Yi,Song Sze-Looi,Yong Hoi-Sen,Yin Wai-Fong,Chan Kok-Gan 한국미생물학회 2020 The journal of microbiology Vol.58 No.12

In this study, bacterial strains Ha5T, Ta1, and Jb2 were isolated from different colonies of weaver ant Oecophylla smaragdina. They were identified as bacterial symbionts of the ant belonging to family Acetobacteraceae and were distinguished as different strains based on distinctive random-amplified polymorphic DNA (RAPD) fingerprints. Cells of these bacterial strains were Gram-negative, rod-shaped, aerobic, non-motile, catalase-positive and oxidase-negative. They were able to grow at 15–37°C (optimum, 28–30°C) and in the presence of 0–1.5% (w/v) NaCl (optimum 0%). Their predominant cellular fatty acids were C18:1 ω7c, C16:0, C19:0 ω8c cyclo, C14:0, and C16:0 2-OH. Strains Ha5T, Ta1, and Jb2 shared highest 16S rRNA gene sequence similarity (94.56–94.63%) with Neokomagataea tanensis NBRC106556T of family Acetobacteraceae. Both 16S rRNA gene sequence-based phylogenetic analysis and core gene-based phylogenomic analysis placed them in a distinct lineage in family Acetobacteraceae. These bacterial strains shared higher than species level thresholds in multiple overall genome-relatedness indices which indicated that they belonged to the same species. In addition, they did not belong to any of the current taxa of Acetobacteraceae as they had low pairwise average nucleotide identity (< 71%), in silico DNA-DNA hybridization (< 38%) and average amino acid identity (< 67%) values with all the type members of the family. Based on these results, bacterial strains Ha5T, Ta1, and Jb2 represent a novel species of a novel genus in family Acetobacteraceae, for which we propose the name Oecophyllibacter saccharovorans gen. nov. sp. nov., and strain Ha5T as the type strain.

Single-cell RNA sequencing reveals B cell–related molecular biomarkers for Alzheimer’s disease

Xiong Liu-Lin,Xue Lu-Lu,Du Ruo-Lan,Niu Rui-Ze,Chen Li,Chen Jie,Hu Qiao,Tan Ya-Xin,Shang Hui-Fang,Liu Jia,Yu Chang-Yin,Wang Ting-Hua 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

In recent years, biomarkers have been integrated into the diagnostic process and have become increasingly indispensable for obtaining knowledge of the neurodegenerative processes in Alzheimer’s disease (AD). Peripheral blood mononuclear cells (PBMCs) in human blood have been reported to participate in a variety of neurodegenerative activities. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 in the early stage, 2 in the late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease in B cells was detected in the blood of AD patients. Furthermore, we further examined PBMCs from 43 AD patients and 41 normal subjects by fluorescence activated cell sorting (FACS), and combined with correlation analysis, we found that the reduction in B cells was closely correlated with the patients’ Clinical Dementia Rating (CDR) scores. To confirm the role of B cells in AD progression, functional experiments were performed in early-stage AD mice in which fibrous plaques were beginning to appear; the results demonstrated that B cell depletion in the early stage of AD markedly accelerated and aggravated cognitive dysfunction and augmented the Aβ burden in AD mice. Importantly, the experiments revealed 18 genes that were specifically upregulated and 7 genes that were specifically downregulated in B cells as the disease progressed, and several of these genes exhibited close correlation with AD. These findings identified possible B cell-based AD severity, which are anticipated to be conducive to the clinical identification of AD progression.

Synthesis of N-Azaaryl Anilines: An Efficient Protocol via Smiles Rearrangement

Shuai Xia,Li-Ying Wang,Heng-Zhi Sun,Huan Yue,Xiu-Hua Wang,Jia-Lian Tan,Yin Wang,Di Hou,Xiao-Yan He,Ki-Cheol Mun,B. Prem kumar,Hua Zuo,신동수 대한화학회 2013 Bulletin of the Korean Chemical Society Vol.34 No.2

An efficient process for the synthesis of N-azaaryl anilines via Smiles rearrangement as a tool. A variety of Nazaaryl anilines were generated by the reaction of substituted phenols, substituted anilines, aminopyridines and chloroacetyl chloride or pyridols, under base condition in good to excellent yields.

Synthesis of N-Azaaryl Anilines: An Efficient Protocol via Smiles Rearrangement

Xia, Shuai,Wang, Li-Ying,Sun, Heng-Zhi,Yue, Huan,Wang, Xiu-Hua,Tan, Jia-Lian,Wang, Yin,Hou, Di,He, Xiao-Yan,Mun, Ki-Cheol,Kumar, B. Prem,Zuo, Hua,Shin, Dong-Soo Korean Chemical Society 2013 Bulletin of the Korean Chemical Society Vol.34 No.2

An efficient process for the synthesis of N-azaaryl anilines via Smiles rearrangement as a tool. A variety of N-azaaryl anilines were generated by the reaction of substituted phenols, substituted anilines, aminopyridines and chloroacetyl chloride or pyridols, under base condition in good to excellent yields.