1.Effect of PAK4-LIMK1-cofilin signaling on non-small-cell lung cancer mi-gration and invasion
Dongxia LI ; Yongling WANG ; Songwang CAI
Chinese Journal of Pathophysiology 2015;(12):2130-2135
AIM:To explore the mechanism of p21-activated kinase 4 (PAK4) on non-small-cell lung cancer (NSCLC) migration and invasion.METHODS:After A549 and NCI-H520 cell lines were transfected with PAK4-siRNA or negative control , the expression of PAK4 at mRNA and protein levels was detected by real-time PCR and Western blot , re-spectively .The invasion and migration of A 549 cells and NCI-H520 cells were measured by Matrigel invasion assay and Transwell migration assay.LIMK1, cofilin, and their respective phosphorylation were examined by Western blot .The inter-action of PAK4 and LIMK1 was investigated by co-immunoprecipitation assay .The relationship between PAK4 and LIMK1 phosphorylation was examined by a protein kinase assay in the A 549 cells and NCI-H520 cells.The expression of PAK4 and p-LIMK1 in 10 human NSCLC tissues was examined by Western blot .A549 cells and NCI-H520 cells were individually or commonly transfected with PAK4-siRNA or LIMK1 plasmid in order to observe the cell migration and invasion .RE-SULTS:After A549 cells and NCI-H520 cells were transfected with PAK4-siRNA for 48 h, the expression of PAK4 at mR-NA and protein levels , and the numbers of invasion and migration cells in PAK 4-siRNA group were lower than those in con-trol group.Compared with control group , the phosphorylation of LIMK1 and cofilin was lower in PAK4-siRNA group, whereas the total expression levels of LIMK 1 and cofilin did not change .The results of co-immunoprecipitation assays showed that PAK4 specifically interacted with LIMK1 in A549 and NCI-H520 cells.LIMK1 phosphorylation in the presence of PAK4 (K350M) was significantly lower than that in the presence of PAK 4 (WT) or PAK4 (S445N) in the protein ki-nase assay.The PAK4 upregulation was positively correlated with the level of p-LIMK1 (P<0.05).After A549 cells and NCI-H520 cells were co-transfected with PAK4-siRNA and LIMK1 plasmid, the migration and invasion cell numbers in co-transfection group were higher than those in PAK 4-siRNA transfection group .CONCLUSION: PAK4 promotes the inva-sive and migratory abilities of NSCLC , which is mediated by LIMK 1 phosphorylation .
2.The usefulness of color Doppler ultrasound in diagnosing venous diseases of lower extremity: a comparison with DSA
Yamei ZHANG ; Shuzhi WANG ; Jianping GU ; Songwang CHEN ; Yan HUANG
Journal of Interventional Radiology 2009;18(12):904-907
Objective To evaluate the color Doppler ultrasound in diagnosing venous diseases of lower extremity, and to compare it with DSA. Methods By using color Doppler ultrasound (CDUS)apparatus, two-dimensional spectrum, color Doppler flow image, pulse wave Doppler and Valsalva examination were performed in 48 patients with suspected venous diseases of lower extremity. The CDUS findings were compared with DSA findings. Results Of 48 cases with suspected lower extremity venous diseases, deep vein thrombosis formation was confirmed in 27, among them 15 were accompanied with lower extremity deep venous valvular incompetence, 8 were complicated by lower extremity varicosity and 2 were associated with both conditions. Another one had cyst in the left popliteal fossa and popliteal venous thrombosis. Decreased blood flow in iliac veins was found in some cases. Pure lower extremity venous valvular incompetence was seen in 5 cases and pure lower extremity superficial varicosity in 6 cases. Six cases suffered both valvular incompetence and superficial varicosity. CDUS showed normal findings in 4 cases, of them DSA demonstrated compressed iliac vein in 2. When taking DSA as golden standard, the accuracy of CDUS was 95.83%. By using the uniformity test, Kappa value was 0.65. Conclusion CDUS is of great clinical usefulness in diagnosing venous diseases of lower extremity as well as in evaluating the therapeutic effect.
3.The Current Status of Informatization Construction and Application in Provincial Disease Prevention and Control Institutions
Songwang WANG ; Yujie MENG ; Yanfei LI ; Qiang CHEN ; Rui ZHANG ; Xiaopeng QI
Journal of Medical Informatics 2017;38(7):46-50
The paper issues questionnaires to investigate the current status of informatization construction and application in 32 provincial disease prevention and control institutions of China,summarizes the current status of informatization organization and management,standard planning,capital input and allocation,analyzes the problems existing in the process of disease control informatization construction,focuses on the discussion of imbalanced regional development,insufficient capital input,lack of informatization personnel,and lack of informatization security awareness,and proposes corresponding suggestions and countermeasures.
4.Inhibitory effect of small interference RNA targeting hypoxia-inducible factor 1 alpha nanospheres on human esophageal squamous carcinoma TE-1 cell growth
Hongying LIAO ; Jiangping SONG ; Lijia GU ; Yimin WENG ; Yun LI ; Jian ZHANG ; Songwang CAI ; Chao YU ; Huiguo CHEN ; Cuiping WANG
Chinese Journal of Tissue Engineering Research 2009;13(38):7493-7497
BACKGROUND: Nanosphere, an ideal nonviral gene delivery vector, is not excellence of immunogenicity and oncogenicity. Nanotechnology and gene interference are used to block hypoxia-inducible factor 1 alpha (HIF-1α) expression in esophageal squamous carcinoma tissue and decrease tolerance of malignant cells to chemotherapeutics. Theoretically, they become effective methods to inhibit malignant cell growth of esophageal squamous carcinoma. OBJECTIVE: To study the inhibitory effect of small interference RNA targeting HIF-1α (siRNA-HIF-1α) nanospheres on human esophageal squamous cancer TE-1 cell growth. DESIGN, TIME AND SETTING: Based on in vitro cultured esophageal squamous cancer TE-1 cells, a completely randomized controlled study was performed at the Central Laboratory, the Third Hospital Affiliated to Sun Yat-sen University from January 2007 to December 2008. MATERIALS: siRNA-HIF-1α was synthesized by Shanghai Bioengineering Company; siRNA-HIF-1α nanospheres were prepared using solvent evaporation technique; human esophageal squamous cancer TE cell strain was provided by Shanghai Cell Bank of the Chinese Academy of Sciences. METHODS: TE-1 cells cultured in vitro were assigned into four groups: saline, gene-free nanospheres, siRNA-HIF-1α, and siRNA-HIF-1α nanospheres groups. MAIN OUTCOME MEASURES: HIF-1α mRNA expression was detected by RT-PCR; HIF-1α protein expression was detected by Western blot; apoptosis of TE-1 cells was determined by flow cytometry; TE-1 cell growth was examined by MTT. RESULTS: At 72 hours after treatment, both HIF-1α mRNA expression and HIF-1α protein expression in the siRNA-HIF-1α nanospheres group were significantly less than other three groups (P < 0.01), but apoptotic rate was significantly greater than other three groups (P < 0.01). TE-1 cell growth was remarkably inhibited in the siRNA-HIF-1α nanospheres group, which was significantly different compared with other three groups (P < 0.01).CONCLUSION: siRNA-HIF-1α nanospheres can specifically reduce both HIF-1α mRNA and HIF-1α protein expressions in esophageal squamous carcinoma TE-1 cells, significantly increase tumor cell apoptosis, and remarkably inhibit TE-1 cell growth.
5.GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer.
Qiwei JIANG ; Yong LI ; Songwang CAI ; Xingyuan SHI ; Yang YANG ; Zihao XING ; Zhenjie HE ; Shengte WANG ; Yubin SU ; Meiwan CHEN ; Zhesheng CHEN ; Zhi SHI
Acta Pharmaceutica Sinica B 2024;14(2):698-711
Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.