Concurrent Hypermethylation of SFRP2 and DKK2 Activates the Wnt/β-Catenin Pathway and Is Associated with Poor Prognosis in Patients with Gastric Cancer

Hao Wang,Xiang-Long Duan,Xiao-Li Qi,Lei Meng,Yi-Song Xu,Tong Wu,Peng-Gao Dai 한국분자세포생물학회 2017 Molecules and cells Vol.40 No.1

Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer. Moreover, concurrent hypermethylation of SFRP2 and DKK2 was observed in gastric cancer and this was significantly associated with increased expression of -catenin, indicating that the joint inactivation of these two genes promoted the activation of the Wnt signaling pathway. Further analysis using a multivariate Cox proportional hazards model showed that DKK2 methylation was an independent prognostic factor for poor overall survival, and the predictive value was markedly enhanced when the combined methylation status of SFRP2 and DKK2 was con-sidered. In addition, the methylation level of SFRP4 and DKK2 was correlated with the patient’s age and tumor differentiation, respectively. In conclusion, epigenetic silencing of Wnt antagonists was associated with gastric carcinogenesis, and concurrent hypermethylation of SFRP2 and DKK2 could be a potential marker for a prognosis of poor overall survival.

Concurrent Hypermethylation of SFRP2 and DKK2 Activates the Wnt/β-Catenin Pathway and Is Associated with Poor Prognosis in Patients with Gastric Cancer

Wang, Hao,Duan, Xiang-Long,Qi, Xiao-Li,Meng, Lei,Xu, Yi-Song,Wu, Tong,Dai, Peng-Gao Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.1

Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer. Moreover, concurrent hypermethylation of SFRP2 and DKK2 was observed in gastric cancer and this was significantly associated with increased expression of ${\beta}-catenin$, indicating that the joint inactivation of these two genes promoted the activation of the Wnt signaling pathway. Further analysis using a multivariate Cox proportional hazards model showed that DKK2 methylation was an independent prognostic factor for poor overall survival, and the predictive value was markedly enhanced when the combined methylation status of SFRP2 and DKK2 was considered. In addition, the methylation level of SFRP4 and DKK2 was correlated with the patient's age and tumor differentiation, respectively. In conclusion, epigenetic silencing of Wnt antagonists was associated with gastric carcinogenesis, and concurrent hypermethylation of SFRP2 and DKK2 could be a potential marker for a prognosis of poor overall survival.

Serum Insulin-Like Growth Factor Binding Protein 7 as a Potential Biomarker in the Diagnosis and Prognosis of Esophagogastric Junction Adenocarcinoma

Can-Tong Liu,Yi-Wei Xu,Hong Guo,Chao-Qun Hong,Xin-Yi Huang,Yu-Hao Luo,Shi-Han Yang,Ling-Yu Chu,En- Min Li,Yu-Hui Peng 거트앤리버 소화기연관학회협의회 2020 Gut and Liver Vol.14 No.6

Background/Aims: Esophagogastric junction adenocarcinoma (EJA) is a malignant tumor associated with high morbidity and has attracted increasing attention due to a rising incidence and low survival rate. Pathological biopsy is the gold standard for diagnosis, but noninvasive and effective tests are lacking, resulting in diagnoses at advanced stages. This study explored the diagnostic value of insulin-like growth factor binding protein 7 (IGFBP7) in EJA. Methods: A total of 120 EJA patients and 88 normal controls were recruited, and their serum levels of IGFBP7 were measured by enzymelinked immunosorbent assay. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value, and Pearson chi-square analysis was used to evaluate the correlation between IGFBP7 and clinical parameters. Kaplan- Meier survival analysis was carried out to assess the effect of IGFBP7 on overall survival (OS). Results: The levels of IGFBP7 were higher in both early- and late-stage EJA patients than in normal controls (p<0.001). The area under the ROC curve for EJA patients was 0.794 (95% confidence interval [CI], 0.733 to 0.854), with a cutoff value of 2.716 ng/mL, a sensitivity of 63.3% (95% CI, 54.0% to 71.8%) and a specificity of 90.9% (95% CI, 82.4% to 95.7%). For the diagnosis of early-stage EJA, the same cutoff value and specificity were obtained, but the sensitivity of IGFBP7 was 54.3% (95% CI, 36.9% to 70.8%). Patients with low IGFBP7 protein expression had lower OS than those with high expression (p=0.034). The multivariate analysis showed that IGFBP7 is an independent prognostic factor for EJA (p=0.011). Conclusions: Serum IGFBP7 acts as a potential diagnostic and prognostic marker for EJA.

Thermal, Mechanical and Rheological Properties of Poly(lactic acid) Chain Extended with Polyaryl Polymethylene Isocyanate

Yanping Hao,Yi Li,Zhigang Liu,Xiangyu Yan,Yi Tong,Huiliang Zhang 한국섬유공학회 2019 Fibers and polymers Vol.20 No.9

In this study, polyaryl polymethylene isocyanate (PAPI) was used as a chain extender for poly(lactic acid) (PLA)to produce a high molecular weight material with better rheological, thermal and mechanical properties. The reactionbetween PLA chains and PAPI was proved by FTIR during reactive blending. The results showed that the molecular weightand molecular weight distribution were increased with the addition of PAPI content due to the chain extension. Chainextension was also responsible for the increased modulus and complex viscosity. The glass transition temperature (Tg) andthermal stability increased by incorporating with PAPI. The results of mechanical properties showed that a considerablyhigher tensile strength and Young’s modulus of the reactive blends compared with neat PLA.

Induction of Indoleamine 2,3-dioxygenase (IDO) Enzymatic Activity Contributes to Interferon-Gamma Induced Apoptosis and Death Receptor 5 Expression in Human Non-small Cell Lung Cancer Cells

Chung, Ting Wen,Tan, Kok-Tong,Chan, Hong-Lin,Lai, Ming-Derg,Yen, Meng-Chi,Li, Yi-Ron,Lin, Sheng Hao,Lin, Chi-Chen Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.18

Interferon-gamma (IFN-${\gamma}$) has been used to treat various malignant tumors. However, the molecular mechanisms underlying the direct anti-proliferative activity of IFN-${\gamma}$ are poorly understood. In the present study, we examined the in vitro antitumor activity of IFN-${\gamma}$ on two human non-small-cell lung carcinoma (NSCLC) cell lines, H322M and H226. Our findings indicated that IFN-${\gamma}$ treatment caused a time-dependent reduction in cell viability and induced apoptosis through a FADD-mediated caspase-8/tBid/mitochondria-dependent pathway in both cell lines. Notably, we also postulated that IFN-${\gamma}$ increased indoleamine 2,3-dioxygenase (IDO) expression and enzymatic activity in H322M and H226 cells. In addition, inhibition of IDO activity by the IDO inhibitor 1-MT or tryptophan significantly reduced IFN-${\gamma}$-induced apoptosis and death receptor 5 (DR5) expression, which suggests that IDO enzymatic activity plays an important role in the anti-NSCLC cancer effect of IFN-${\gamma}$. These results provide new mechanistic insights into interferon-${\gamma}$ antitumor activity and further support IFN-${\gamma}$ as a potential therapeutic adjuvant for the treatment of NCSLC.

Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5–24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study

Wang Lu,Dai Ying-Jie,Cui Yu,Zhang Hong,Jiang Chang-Hao,Duan Ying-Jie,Zhao Yong,Feng Ye-Fang,Geng Shi-Mei,Zhang Zai-Hui,Lu Jiang,Zhang Ping,Zhao Li-Wei,Zhao Hang,Ma Yu-Tong,Song Cheng-Guang,Zhang Yi,Ch 대한뇌졸중학회 2023 Journal of stroke Vol.25 No.3

Background and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; <i>P</i>=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, <i>P</i>=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Polyethersulfone membrane modified by zwitterionic groups for improving anti-fouling and antibacterial properties

Wei Jin,Yu-Fei Lin,Zhen-Liang Xu,Ping-Ping Li,Jia-Yue Dai,Yi-Hao Tong,Xin Zhang 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.122 No.-

Ultrafiltration (UF) membranes are commonly confronted with threats from pollutants during long-termoperation. The zwitterions with high hydrophilicity are expected to be the critical material to improve theanti-fouling and antibacterial abilities of membranes. Herein, a new zwitterionic polyethersulfone (PES)(zwitterionic PES - ZPES) was synthesized. The as-prepared ZPES was used to fabricate a zwitterionic UFmembrane via the non-solvent induced phase inversion (NIPS) method. Zwitterionic polymer skeletonenhanced the hydrophilicity, permeability and anti-fouling properties of the material. As a result, theZPES membrane exhibited doubled water flux growth (269.6 Lm2h1) compared with that of the PES(125.3 Lm2h1) and high protein rejection (98.6%). Besides, the ZPES membrane could maintain anexcellent flux recovery rate (94.1%) and antibacterial effect (more than 95%). Therefore, the excellentanti-fouling and antibacterial abilities of the ZPES membrane broaden its application scope further.