3.Current situation and progress in the comprehensive treatment of locally advanced gastroesophageal junction adenocarcinoma
Wei LIU ; Yudong WANG ; Long WANG
Chinese Journal of Clinical Oncology 2014;(3):149-152
Based on special biological characteristics and prognosis, the incidence of gastroesophageal junction adenocarcinoma (GEJA) has rapidly increased over recent years, and its diagnosis and treatment remain controversial. Compared with simple surgery, neo-adjuvant and adjuvant therapies can improve the survival of patients with locally advanced GEJA. Under neo-adjuvant therapy, neo-adjuvant chemoradiation is superior to neo-adjuvant chemotherapy alone for improving the resectability, maintaining loco-regional control, and improving the quality of life of the patient. The combination of this therapy with targeted drugs may further increase the ef-ficacy of GEJA. Most data on GEJA-treated patients were obtained from randomized clinical studies on esophageal cancer or gastric cancer. Thus, prospective randomized controlled studies with a large sample size should be performed to optimize the strategy of neo-adjuvant and adjuvant therapies, and further improve the treatment outcome. In this article, studies on the comprehensive treatment of GEJA were reviewed.
4.Clinical research progress in adenocarcinoma of the esophagogas-tric junction
Long WANG ; Xue ZHANG ; Wei LIU
Chinese Journal of Clinical Oncology 2015;(2):120-124
The adenocarcinoma of the esophagogastric junction (EGJA) is located in a unique anatomical position and at the junction of the squamous epithelium and the columnar epithelium. The biological characteristics of this disease are different from those of esophageal or gastric cancer. The diagnostic classification of EGJA has been subject to controversies, and no gold standard therapeu-tic regimens have been established, especially in the choice of treatment of locally advanced EGJA. Results from large-scale clinical tri-als and imaging technology development showed that the treatment of EGJA has been individualized. Furthermore, this problem high-lights the importance of multidisciplinary collaboration. This article focuses on current progress in studies on EGJA.
5.Screening for selective TGF-βⅠinhibitors and structure-activity relationship analysis
Long LONG ; Feifei LI ; Xingzhou LI ; Wei CHEN ; Wei LI ; Lili WANG
Journal of International Pharmaceutical Research 2017;44(6):544-550
Objective To screen for selective transforming growth factor β(TGF-β)inhibitors from the compound library, and analyze their structure-activity relationship. Methods The inhibiting activities of 170 compounds to TGF-βpathway were evaluat-ed by the SMAD3 luciferase reporter system;the positive hits were examined for their selectivity towards activin receptor like kinase (ALK)4、ALK5 or ALK7 by a molecule based screening system composed of SMAD3,ATP and the purified kinase domain for ALK4, ALK5 or ALK7;the EGFP-SMAD2 fusion protein redistribution assay was used to confirm the inhibiting effects of positive hits. The structure-activity relationship was analyzed by comparing the docking module of SB431542 with ALK5 kinase domain. Results Fif-teen compounds were found capable of inhibiting luciferase expression downstream of SMAD3 with≥25%inhibitory rate;several of them showed different selectivity towards ALK4,ALK5 and ALK7. Compound 63 selectively inhibited the activity of ALK4 and ALK7 with IC500.234 and 0.370μmol/L,respectively,while compound 64 showed inhibiting activity towards all three kinases with the IC50 values 10,6 and 85 nmol/L for ALK4、ALK5 and ALK7,respectively. In addition,compounds 63 and 64 further inhibited the TGF-β1 induced EGFP-SMAD2 nuclear translocation,with the IC50 values of 0.45 and 6.30μmol/L,respectively. The MTT anti-proliferative assay indicated that compounds 63 and 64 exerted these activities at non-toxic concentrations. The analysis of structure-activity rela-tionship indicated that the compounds sharing a core structure,the 1,2,4-triarylimizazole or 1,3,5-triarylpyrazoline,with the 3,4 methyoenedioxyphenyl,6-methylpyridine and 4-aminocarboxyl substitution groups tended to exhibit better activities. Conclusion The two potent TGF-βpathway inhibitors,63 and 64 are identified through this screening project,of which,63 selectively inhibited the ALK4 and ALK7 activity,while 64 showed inhibiting activity towards all three tested types of ALKs.
6.Effects and Mechanisms of Xuebijing on Early Sepsis Induced Acute Lung Injury in Rats
Wei WANG ; Yuxiang ZHANG ; Hongshan LI ; Long YANG ; Zheng WANG
Progress in Modern Biomedicine 2017;17(25):4820-4823
Objective:To investigate the effects and mechanisms of Xuebijing injection on early sepsis induced acute lung injury and explore a new therapy.Methods:Thirty healthy male Sprague-Dawley rats were randomly divided into 3 groups:Sham group(n=10),NS group (NS 4mL/kg n=10),Xuebijing Group(Xuebijing 4mL/kg n=10).Cecal ligation and puncture (CLP) was used to duplicate severe sepsis model.At 6h after CLP,the rats were sacrificed,the lungs were resected and histopathological characteristic was observed by transmission electron microscopy technique.The change of the lung wet/dry (W/D) weight ratio were studied.Meanwhile,the lungs were resected for detection of ET-1,iNOS,MMP-9,TIMP-1 mRNA with reverse transcription-polymerase chain raction (RT-PCR).Results:The changes of pulmonary alveoli and the interstitial edema as well as lung tissue in Xuebijing group were better than those of NS group.The change of lung wet/dry (W/D) weight ratio in septic rats showed was significantly increased at 6 h after CLP (vs Sham group:5.37± 0.12 vs 4.33± 0.06,P<0.01).The lung W/D was significantly decreased in XBJ group (vs NS group:4.67± 0.09 vs 5.37± 0.12,P<0.05).The expressions in XBJ group lung tissue of ET-1 (0.511 ± 0.111 vs 0.705± 0.122,P<0.01),iNOS(0.45610.075 vs 0.548± 0.098,P<0.05)、MMP-9 (0.617± 0.079 vs 0.732± 0.131,P<0.05),TIMP-1 (0.438± 0.043 vs 0.515± 0.049,P <0.01) mRNA were significantly decreased than those in NS group.And the expressions of ET-1 (0.705± 0.122vs 0.400± 0.033,P<0.01),iNOS (0.548± 0.098 vs 0.334± 0.027,P<0.01),MMP-9(0.732± 0.131 vs 0.352± 0.061,P<0.01),TIMP-1(0.515± 0.049 vs 0.365± 0.068,P<0.01) mRNA in NS group were significantly increased compared with those in the sham group.Conclusions:Xuebijing could protect against sepsis induced acute lung injury,which might be related with the decrease ofET-1,iNOS,MMP-9 and TIMP-1 mRNA expressions.
7.Relationship between nitric oxide in cervical microenvironment and different HPV types and effect on cervical cancer cells
Xuemin WEI ; Qing WANG ; Shujun GAO ; Long SUI
Chinese Journal of Obstetrics and Gynecology 2011;46(4):260-265
Objective To study the relationship between nitric oxide within cervical microenvironment and different HPV types as well as the effect of sodium nitroprusside( SNP), a nitric oxide donor, on the proliferation and apoptosis of cervical cancer cell lines. Methods HPV typing test was assessed from 115 women by using high-risk HPV (HR-HPV) 21 typing test and the release of cervical nitric oxide(NO) was assessed as nitrate, nitrite in cervical fluid. Cervical NO was then compared between women showing different HPV types. Proliferation of Caski and HeLa cervical cells was determined by methyl thiazolyl tetrazolium (MTT) assay, cell apoptosis was detected by flow cytometry after 24 hours treated by different final concentration of SNP (0. 125,0. 25,0. 5,1.0 and 2. 0 mmol/L, respectively). The expressions of HPV E6,E7 gene mRNA and p53 protein were detected by SYBR Green Ⅰ quantitative real-time PCR and western blot. Results ( 1 ) The cervical NO release of women with HR-HPV was higher compared to that in HPV negative women [ (47. 6 ± 1.4) μmol/L vs ( 22. 8 ± 0. 3 ) μmol/L; P < 0. 05 ]; but there was no statistical difference between low-risk HPV (LR-HPV) group [ (24. 1 ± 1.2 ) μmol/L] and control group (P >0. 05 ). (2)After 24 hours treated by different final concentration of SNP, the results shown that SNP could inhibited the proliferation and increased apoptosis rate in Caski and HeLa cells, in which the concentration of SNP ≥ 1.0 mmol/L , there were significantly different ( P < 0. 05 ), while when SNP ≥2. 0mmol/L, the proliferation of cells inhibited seriously. Treated by SNP ( 1.0 mmol/L ) 24 hours, the expressions of HPV18 E6, E7 mRNA in HeLa cells were reduced from 27. 362 ±0. 191,22. 962 ±0. 053 to19. 181 ±0. 360, 17. 571 ±0. 010 and the protein expression of p53 increased from 1. 17 ±0. 03 to 0. 23 ±0. 05, there were statistically significant differences between adding SNP group and the control group ( P <0. 05); but there were no statistically significant differences in HPV16 E6, E7 mRNA and that of p53 in Caski cells( P > 0. 05 ). Conclusions The presence of HR-HPV is associated with an increased release of NO in the human uterine cervix; NO could inhibit the growth and proliferation and enhance the apoptosis of cervical cancer cells, inhibit the expression of HPV18 E6, E7 mRNA in HeLa cells and activate the expression of p53 protein, the mechanism may be due to higher sensitivity of HeLa cells (cervical adenocarcinoma cell) to SNP. The increasing release of NO may play a role in regulating the elimination of HPV in cervical microenvironment, which is a part of mucous membrane immunity.
8.Operation and essence of Toutianliang manipulation by professor ZHANG Jin.
Wei ZOU ; Long WANG ; Xueping YU ; Xiaowei SUN ; Jinrui LIU
Chinese Acupuncture & Moxibustion 2016;36(1):53-55
Toutianliang manipulation is the most representative compound needling technique of traditional reinforcing and reducing and has the remarkable efficacy on heat syndrome with muscle and bone involved for example. Professor ZHANG Jin is one of the famous acupuncture master in China and has contributed his lifelong to the research of acupuncture manipulation techniques. He has summarized 24 single-type manipulations and has given the comprehensive explanation of the manipulations for meridian conduction, reinforcing or reducing techniques for the excess or deficiency. In the paper, Toutianliang manipulation was introduced briefly and the key operation steps had been discussed.
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9.Coronary sinus drainage into left atrium: 2 cases report.
Hong-Wei ZHAO ; Yun-Long XIA ; Zhao-Qian WANG
Chinese Journal of Cardiology 2008;36(3):273-274
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10.Study on inhibition of lymphangiogenesis in gastric cancer by NM-3
Wei DA ; Jinshui ZHU ; Weixiong CHEN ; Long WANG ; Qun SUN
Chinese Journal of Digestion 2010;30(6):394-397
Objective To evaluate the inhibitory effect of 2-(8-hydroxy-6-methoxy-1-oxo-1-H-2-benzopyran-3-Y1) propionic acid (NM-3) on lymphangiogenesis in gastric cancer using orthotopic implantated tumor models of BALB/C nude mice. Methods A BALB/C nude mouse model of transplanted in situ human gastric cancer was established. Twenty-eight nude mice were divided into four groups with 7 each: control group, NM-3 treated group, carboplatin (10 mg/kg) treated group,and NM-3 combiantion group injected with normal saline, 5 mg/kg of NM-3, 10 mg/kg of carboplatin or 5 mg/kg of NM-3, + 10 mg/kg carboplatin, respectively, twice a week for 8 weeks. At the end of the 8th week, all mice were sacrificed for detection of lymphatic microvessel density (LMVD),lymphatic vessel endothelial hyaluranic acid receptor 1 (LYVE-1), podoplanin and Prox-1 byimmunohistochemistry with staining. Results In comparison with control group, the LYVE-1 level in other three groups was decreased with no significant difference (P> 0.05). The concentrations of podoplanin and Prox-1 in NM-3 group and combination group decreased significantly than those in control group and carboplatin group (P < 0.05). The number of LMVD in NM-3 group and combination group was 4.72±0.50 and 4.78± 0.38, respectively, which was significantly lower than that in control group (7.35±0.55)and carboplatin group (6.98i0.35, P<0.05). Conclusion The NM-3 can inhibit the growth of gastric cancer by interfering lymphangiogenesis of gastric cancer.