2.The anti-tumor activity and molecular mechanisms of an Aurora kinase inhibitor ZLJ213 in suppressing colon cancer growth.
Wan-qi ZHOU ; Li-jing ZHANG ; Han-ze YANG ; Zhi-qiang FENG ; Yan LI
Acta Pharmaceutica Sinica 2015;50(7):854-860
The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.
Animals
;
Apoptosis
;
Aurora Kinase A
;
antagonists & inhibitors
;
Cell Cycle Checkpoints
;
Cell Line, Tumor
;
drug effects
;
Cell Proliferation
;
Colonic Neoplasms
;
pathology
;
Humans
;
Protein Kinase Inhibitors
;
pharmacology
;
Receptors, Vascular Endothelial Growth Factor
;
metabolism
;
Xenograft Model Antitumor Assays
3.Synthesis and in vitro cytotoxic activities of sorafenib derivatives.
Ke WANG ; Yan LI ; Li-Jing ZHANG ; Han-Ze YANG ; Xiao-Guang CHEN ; Zhi-Qiang FENG
Acta Pharmaceutica Sinica 2014;49(5):639-643
A series of novel sorafenib analogues were designed and synthesized. The cytotoxic activities of these compounds were tested in four tumor cell lines. Some of the compounds showed potent antiproliferative activity against the tested cell lines with IC50 = 4-20 micromol x L(-1). Some compounds demonstrated competitive antiproliferative activities to sorafenib against tested cancer cell lines. Among them, compound 7c demonstrated significant inhibitory activities on ACHN, HCT116 and MDA-MB-231 cell lines with IC50 values of 9.01, 4.97, 6.61 micromol x L(-1), respectively.
Antineoplastic Agents
;
chemical synthesis
;
chemistry
;
pharmacology
;
Cell Line, Tumor
;
Cell Proliferation
;
drug effects
;
Humans
;
Inhibitory Concentration 50
;
Molecular Structure
;
Niacinamide
;
analogs & derivatives
;
chemical synthesis
;
chemistry
;
pharmacology
;
Phenylurea Compounds
;
chemical synthesis
;
chemistry
;
pharmacology
;
Structure-Activity Relationship
4.Mini-open anterior corrective surgery with assistance of thoracoscopy for thoracic idiopathic scoliosis
Yong QIU ; Bin WANG ; Feng ZHU ; Yang YU ; Ze-Zhang ZHU ; Bang-Ping QIAN ;
Chinese Journal of Microsurgery 2006;0(06):-
Objective To introduce the mini-open anterior correction under video assisted thoracosco- py for thoracic idiopathic scoliosis and report its clinical results.Methods From July 2001 to 2006,37 ca- ses of right thoracic idiopathic seoliosis were surgically corrected with mini-open anterior instrumentation. There were 4 males and 33 females with average age of 14.1 years and average Cobb angle of 56?.Fourteen cases with Lenke I A 14 cases,IB ++-++++ 14 cases,IC 9 cases.The Risser sign was ++-++++. The operative time,blood loss,instrumented levels,correction rate and loss of correction were analyzed. Results The operative time averaged 220 miu.The intraoperative blood loss averaged 320 ml.The average number of instrumented levels was 7.8.The postoperative Cobb angle was 16.8?on average with correction rate of 70%.With a follow-up of 18-36 months,the loss of correction averaged 4.6%,but no hardware complications.Conclusion The clinical results of mini-open anterior correction under thoracoscopy for tho- racic idiopathic scoliosis were satisfactory.It may minimize the complications of classical thoracotomic anterior correcion and mav reduce the high requirement for anesthesia,long operative time and high cost of thoraco- scopic anterior instrumentation.
5.Synthesis of novel curcumin mimics and preliminary evaluation for their antitumor activity.
Yong-Cheng WANG ; Yu-Shan LI ; Han-Ze YANG ; Yan LI ; Xiao-Guang CHEN ; Zhi-Qiang FENG
Acta Pharmaceutica Sinica 2014;49(7):1022-1028
Curcumin has been reported to possess antitumor activity with low toxicity. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. In order to overcome these limitations and discover novel small molecules with potential antitumor activity, 29 curcumin mimics were synthesized, which were confirmed by 1H NMR and HR-MS, and their cytotoxic property was evaluated against five human cancer cell lines in vitro. Compounds 16, 18 and 19 exhibited good cytotoxic property, their IC50 value were even below 5 micromol x L(-1) to some cancer cell lines, 5-9 times better than curcumin.
Antineoplastic Agents
;
chemical synthesis
;
pharmacology
;
Cell Line, Tumor
;
Curcumin
;
analogs & derivatives
;
chemical synthesis
;
pharmacology
;
Drug Screening Assays, Antitumor
;
Humans
;
Inhibitory Concentration 50
6.Influence of peritoneal dialysate on nitric oxide production and viability of macrophage
Ze-Ran YANG ; Ji-Cheng LI ; Kai ZHANG ; Xu-Feng MI
Journal of Zhejiang University. Medical sciences 2002;31(1):23-25
OBJECTIVE: To investigate the influence of commercial peritoneal dialysate (CDS) on function of macrophage. METHODS: Cultured peritoneal macrophages were divided into two experimental groups and their controls.(1) Macrophages were cultured in conditioned culture medium containing 50%CDS (0.139 mol/L glucose) for 24 h. (2)Macrophage were exposed to CDS containing 0.139mol/L glucose for 10, 30 and 60 min respectively, and then cultured in CDS-free medium for 24 h. The nitric oxide (NO) production and MTT in two groups were measured. In each control group, CDS was replaced by same amount of culture medium. RESULTS: NO production and MTT reduction ability (related to cell viability) of experimental groups were remarkably lower than those of controls and the NO production and MTT reduction in 60min CDS-exposed group were lower than that of 10 min and 30 min CDS-exposed group. CONCLUSION: Dialysate may have detrimental effects on viability and other function of macrophage and these effects may related to time length of CDS exposure.
7.Epstein-Barr virus infection and p16INK4a overexpression in gastric adenocarcinoma
Ping WANG ; Qing ZHANG ; Jin-Feng YANG ; Ze-Nong CHENG ; Ke ZHANG ; Dong-Hong YU
Chinese Journal of Experimental and Clinical Virology 2008;22(4):244-246
Objective To study Epstein-Barr vires infection and p16 protein abnormal expresson in carcinogenesis and progression of gastric adenocarcinomas (GAC). Methods Immunohistochemical staining SP method was used to detect the expression of LMP-1 and p16 in 97 cases of GAC. Results EBV LMP-1 and p16 protein were detected in 30.9% (30/97) and in 63.91% (62/97) cases of gastric adenocarcinomas respectively.There was no significant difference between EBV-positive and EBV-negative gastric carcinomas in sex, histologic type, depth of tumor invision, lymph node metastasis and clinical stages (P>0.05);overexpression of p16 was associated with lymph node metastasis and clinical stages; no correlation was found between the expression of EBV LMP-1 and p16 protein. Conclusion ①EBV play a role in carcinogensis of GAC. ②P16 gene abnormality is frequently involved in GAC and might be one of the important prognostic factors. ③EBV infection and p16 alteration are two independent roles in GAC carcinogenesis.
8.Study on the risk of age-related diabetes mellitus among 8280 cases with metabolic syndrome patients and normal persons in Beijing
Jing MA ; Jig FENG ; Ze-Ping LV ; Hui HUANG ; Gang WAN ; Jin HUANG ; Jian-Yi ZHANG ; Shuang-Yu YANG ; Jian-Ling DU ; Li-Xin GUO ; Ze YANG
Chinese Journal of Epidemiology 2010;31(3):241-244
Objective To investigate the impact of age on patients with metabolic syndrome (MS) and normal persons. Methods Data was gathered from 8280 persons including 4873 males and 3407 females who were randomly selected. All subjects were devided into normal group and MS group. According to the interval of ten years, the subjects were devided into seven age groups, to calculate the difference of impaired fasting glycaemia (IFG) between patients with diabetes mellitus (DM) and normal people, as well as the related portions. Results (1) The risk of IFG and DM appeared to be different among age groups among the target subjects as well as in the normal and the MS groups (P<0.05). (2) Among the whole subjects, the overall prevalence of IFG was increasing with age. The prevalence of DM had an increasing trend with age augment in 20-79 years group, whereas a decreasing trend appeared in people over 80 years of age. (3) For normal persons, the prevalence of IFG and DM were all increasing with age augment in 20-79 years group, and then decreasing with age augment in the over-80-years group. (4)For MS patients, the prevalence of IFG had an increasing trend with age augment in 20-69 years group, whereas a decreasing trend appeared in people over 70 years of age. There was no tendency of variation with age augment in DM.Conclusions (1) For normal persons, high prevalence rates of IFG and DM were correlated to age augment, especially in senior persons. (2) For MS patients, high prevalence of IFG was also correlated to age augment, but no association between prevalence of DM and age augment was seen. (3)Age from 70 to 79 years appeared to be in high risk with MS.
9.Epidemic and control on tobacco in China.
Yuan JIANG ; Qiang LI ; Lin XIAO ; Guo-ze FENG ; Yan YANG ; Yan-na YANG
Chinese Journal of Epidemiology 2011;32(12):1181-1187
10.Acquired factor V inhibitor: 3 cases report and literature review.
Yan-hui YANG ; Hong-mei WANG ; Feng XUE ; Xiao-fan LIU ; Yong-ze LIU ; Lei ZHANG ; Ren-chi YANG
Chinese Journal of Hematology 2012;33(4):294-298
OBJECTIVETo better understand the acquired factor V (FV) inhibitors.
METHODSThe clinical features, laboratory manifestations, treatment options and prognosis of 3 cases were reported and related literature were reviewed.
RESULTSAll the 3 patients were older than 50 years without family history and related disease. Their clinical manifestations included spontaneously mucous bleeding, hematuria, epistaxis and encephalic bleeding. Laboratory test showed prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). The FV levels decreased and the presence of FV inhibitor was confirmed by Bethesda method. All patients were treated with glucocorticoid and immunosuppressive agents. The haemorrhages of two patients stopped but their coagulation test and FV level recovered slowly. One patient died from encephalic bleeding.
CONCLUSIONSAcquired FV inhibitor is a rare coagulation disorder with variable clinical symptoms. Immunosuppressive agents are effective to eliminate the inhibitors. The prognosis of acquired FV inhibitors seemed to be strictly related to the basic disease.
Coagulation Protein Disorders ; Factor V ; antagonists & inhibitors ; Female ; Humans ; Male ; Middle Aged