Relationships among MTHFR a1298c Gene Polymorphisms and Methylation Status of Dact1 Gene in Transitional Cell Carcinomas

Cheng, Huan,Lu, Meng,Mao, Li-Jun,Wang, Jun-Qi,Li, Wang,Wen, Ru-Min,Chen, Jia-Cun Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.10

Objectives: The purpose of this study was to determine the relationship between methylation status of the Dact1 gene and MTHFR a1298c polymorphic forms in transitional cell carcinoma tissues in a Chinese population. Methods: Polymorphisms of folate metabolism enzyme gene MTHFR were assessed by restrictive fragment length polymorphism (RFLP) methods and PCR-based DNA methylation analysis was used to determine the CpG island methylation status of the Dact1 gene. Associations between the methylation status of the Dact1 gene and clinical characteristics, as well as MTHFR a1298c polymorphisms, were analyzed. Results: aberrant methylation of the Dact1 gene was found in 68.3% of cancer tissues and 12.4% of normal tissues,. The methylation rate of the Dact1 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis (46.3% vs. 17.2%, P = 0.018). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables, variant allele of MTHFR a1298c was found to be associated with methylation of the Dact1 gene. Compared with wild type CC, the odds ratio was 4.33 (95% CI: 1.06-10.59) for AC and 4.95 (95% CI: 1.18-12.74) for AA. The N stage in TNM staging and the occurrence of lymph node metastasis were associated with an MTHFR 1298 AA+AC genotype (P<0.05). Conclusion: MTHFR 1298 AC and AA genotypes might help maintain a normal methylation status of the Dact1 gene, aberrant CpG island methylation of which is closely related to the genesis and progression of transitional cell carcinoma.

The Pattern of Time to Onset and Resolution of Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors in Cancer: A Pooled Analysis of 23 Clinical Trials and 8,436 Patients

Si-Qi Tang,Ling-Long Tang,Yan-Ping Mao,Wen-Fei Li,Lei Chen,Yuan Zhang,Ying Guo,Qing Liu,Ying Sun,Cheng Xu,Jun Ma 대한암학회 2021 Cancer Research and Treatment Vol.53 No.2

Purpose The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear. Materials and Methods Phase II-III clinical trials that evaluated ICI-based treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software.Results Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031).Conclusion This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.

Molecular Dynamics Simulation to Investigate the Rake Angle Effects on Nanometric Cutting of Single Crystal Ni3Al

Rui-cheng Feng,Yong-nian Qi,Zong-xiao Zhu,Wen-yuan Song,Hai-yan Li,Mao-mao Wang,Zhi-yuan Rui,Feng-shou Gu 한국정밀공학회 2020 International Journal of Precision Engineering and Vol.21 No.4

Molecular dynamics, an eff ective method to gain an insight into nanometric behaviour of materials, was employed to studythe nano-cutting behaviour of single crystal Ni 3 Al in nanometric scale. In this paper, comparisons were made for compressive/tensile stress, subsurface damage and surface roughness with three rake angles of a diamond tool. Subsurface damage waspartitioned by region and studied with work hardening in detail. A model for precise characterization of surface roughnesswas established with consideration of local surface fl uctuation. Simulation results showed that the chip thickness increasedas rake angle changed from negative to positive, and the boundary formed between tensile and compressive stress was inconsistent with the glide direction of stacking fault. Subsurface damage decreased as the increase of rake angle, and regularglide planes of stacking faults were found in front of the cutting tool. Further, the pinned dissociated 1/2 < 110 > superpartialdislocation with anti-phase boundary was demonstrated. The model was tested and characterized by implanted pits onperfect surface. Results showed that surface roughness can be well characterized, and an evident discrepancy was observedamong three rake angles, especially for 30° rake angle, which showed an distinct smooth surface compared with the others.

Micro-gap DBD Plasma and Its Applications

( Zhitao Zhang ),( Cheng Liu ),( Mindi Bai ),( Bo Yang ),( Cheng Qi Mao ) 한국동굴학회 2006 동굴 Vol.76 No.-

The Dielectric Barrier Discharge (DBD) is a nonequilibrium gas discharge that is generated in the space between two electrodes, which are separated by an insulating dielectric layer. The dielectric layer can be put on either of the two electrodes or be inserted in the space between two electrodes. If an AC or pulse high voltage is applied to the electrodes that is operated at applied frequency from 50Hz to several MHz and applied voltages from a few to a few tens of kilovolts rms, the breakdown can occur in working gas, resulting in large numbers of micro-discharges across the gap, the gas discharge is the so called DBD. Compared with most other means for nonequilibrium discharges, the main advantage of the DBD is that active species for chemical reaction can be produced at low temperature and atmospheric pressure without the vacuum set up, it also presents many unique physical and chemical process including light, heat, sound and electricity. This has led to a number of important applications such as ozone synthesizing, UV lamp house, CO2 lasers, et al. In recent years, due to its potential applications in plasma chemistry, semiconductor etching, pollution control, nanometer material and large area flat plasma display panels, DBD has received intensive attention from many researchers and is becoming a hot topic in the field of non-thermal plasma.

IL-33 promotes IL-10 production in macrophages: a role for IL-33 in macrophage foam cell formation

Hai-Feng Zhang,Mao-Xiong Wu,Yong-Qing Lin,Shuang-Lun Xie,Tu-Cheng Huang,Pin-Ming Liu,Ru-Qiong Nie,Qin-Qi Meng,Nian-Sang Luo,Yang-Xin Chen,Jing-Feng Wang 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and sitespecific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the − 2000 to − 1752 bp segment of the 5′-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the − 1997 to − 1700 and − 1091 to − 811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.

Hypoxia-Inducible Factor 1 Promoter-Induced JAB1 Overexpression Enhances Chemotherapeutic Sensitivity of Lung Cancer Cell Line A549 in an Anoxic Environment

Hu, Ming-Dong,Xu, Jian-Cheng,Fan, Ye,Xie, Qi-Chao,Li, Qi,Zhou, Chang-Xi,Mao, Mei,Yang, Yu Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

The presence of lung cancer cells in anoxic zones is a key cause od chemotherapeutic resistance. Thus, it is necessary to enhance the sensitivity of such lung cancer cells. However, loss of efficient gene therapeutic targeting and inefficient objective gene expression in the anoxic zone in lung cancer are dilemmas. In the present study, a eukaryotic expression plasmid pUC57-HRE-JAB1 driven by a hypoxia response elements promoter was constructed and introduced into lung cancer cell line A549. The cells were then exposed to a chemotherapeutic drug cis-diamminedichloroplatinum (C-DDP). qRT-PCR and western blotting were used to determine the mRNA and protein level and flow cytometry to examine the cell cycle and apoptosis of A549 transfected pUC57-HRE-JAB1. The results showed that JAB1 gene in the A549 was overexpressed after the transfection, cell proliferation being arrested in G1 phase and the apoptosis ratio significantly increased. Importantly, introduction of pUC57-HRE-JAB1 significantly increased the chemotherapeutic sensitivity of A549 in an anoxic environment. In conclusion, JAB1 overexpression might provide a novel strategy to overcome chemotherapeutic resistance in lung cancer.