1.Activation of MAPK signaling is associated with migration and invasion of triple-negative breast cancer cells
Han XU ; Genhong DI ; Gong YANG
China Oncology 2013;(11):874-879
Background and purpose:Triple-negative breast cancer (TNBC) possesses high risk of relapse and metastasis. Clinically, there are no speciifc targeted-therapies to TNBC except chemotherapy. Therefore, studying the mechanism of relapse and metastasis has signiifcance to improve the patients’ survival rate. This experiment aimed to study the effect of MAPK activation on migration and invasion of triple-negative breast cancer cells. Methods:Difference of migration and invasion between lung-high metastasis breast cancer cell line 231-HM and its parental cell line 231-p were first examined by cell scratch and transwell;Then, metastasis-associated proteins and MAPK-associated molecules were detected by Western blot; Last, 231-p cells were treated with P38/MAPK inhibitor and used to determine cell migration, invasion, and metastasis-associated proteins thereafter. Results:Compared with the parental cell line 231-p, 231-HM cells displayed obviously higher ability of migration and invasion. With the increased expression of Caveolin-1and β-catenin, the phosphorylation of MAPK-associated molecules including P38, Erk1/2, and MEK was highly decreased. Treatment of 231-p cells with low concentration (10 μmol/L) of the P38/MAPK inhibitor SB202190 increased the migration and invasion of 231-p cells, and the expression of Caveolin-1 andβ-catenin. Conclusion:Activation of MAPK signaling inhibits the migration and invasion of triple-negative breast cancer.
2.Expression of CD14 in Kupffer′s cells induced by Lipopolysaccharide
Jianping GONG ; Mingqing XU ; Kun LI ; Jin ZHU ; Benli HAN
Journal of Third Military Medical University 2001;23(4):425-428
Objective To investigate the expression of LPS receptor-CD14(CD14) on the membrane of Kupffer′s cells (KCs) induced by Lipopolysaccharide (LPS )and its role in activation of KCs and production of cytokines. Methods KCs were isolated by collagenase perfused Wistar rats and routinely cultured in 24-well dishes for 12 h. Cells were harvested and adjusted to a concentration of 1×106/ml/well and were devided into two groups. Group of LPS: KCs were induced with different concentration of LPS (0, 100 ng/ml, 1 μg/ml and 100 μg/ml). Group of PI-PLC: KCs were pre-incubated for 30 min with one unit of phophatidy linositol specific phospholipase C (PI-PLC) before different concentrations of LPS were added. KCs were cultured for 30 and 60 min respectively. Supernatants were then collected for measuring the level of TNFα and IL-6. Cells were stained by indirect immunofluorescent method ( rabbit anti-CD14 antibody and goat anti-rabbit IgG conjugated with FITC ) and analyzed with flow cytometer (FCM). The percentage and mean fluorescence intensity (FI) of CD14-positive cells were taken as the indexes. Results In LPS group, after incubation of cells with increasing concentration of LPS, a significant increase in the percentage of CD14 positive KCs were found and the mean FI was stronger when compared with the control points or the group of PI-PLC. The levels of TNFα and IL-6 in supernatant also increased (P<0.01). In group of PI-PLC, decreased percentage of CD14 positive KCs and weakened mean FI were found when compared with group of LPS. The increasing production of TNFα and IL-6 slowed down in the group of PI-PLC. Conclusion CD14 expression of KCs might be up-regulated by LPS with increase of some cytokines. The production of cytokines in KCs induced by LPS is partially inhibited by PI-PLC.
3.Clinical and genetic evaluation of a family with isolated oligodontia
Han QIN ; Lifang MA ; Hongzhi XU ; Yongqing GONG ; Kun XUAN
The Journal of Practical Medicine 2015;(7):1117-1120
Objectives To investigate the mutational characteristics of MSX1 and PAX9 genes in a family affected by non-syndromic oligodonti so as to study the pathogenesis of oligodontia from a molecular prospective. Methods A family with oligodontia, but of different descent and unrelated healthy controls were enrolled in our study. Genomic DNA was isolated from the blood samples. Mutation analyses were performed by amplifying MSX1 and PAX9 exons and sequencing the products. Results DNA sequencing revealed a novel missense mutation c.348C>T in a highly conserved homeobox sequence of MSX1 and a known polymorphisms c. 469+35- c.469+45del in exon 1 and in intron in the two patients and in two unrelated healthy controls. But we did not detect any mutation in PAX9. Conclusion Our finding suggests the samesense mutation (c.348C>T) and the polymorphisms (c.469+35- c.469+45del) may be responsible for oligodontia phenotype in this Chinese family.
4.Preliminary study of the optic radiation in healthy adults by MR diffusion tensor imaging
Jing SUN ; Jing GUO ; Han XU ; Tao LIU ; Zhen JIANG ; Xiaoqiu XU ; Zhigang GONG ; Junkang SHEN
Chinese Journal of Radiology 2009;43(8):789-792
the incidence of the complication.
5.Phosphorylcholine coating enhances biocompatibility of expanded polytetrafluoroethylene used in polymeric prosthetic heart valves
Ben ZHANG ; Dejun GONG ; Xiwu ZHANG ; Tongyi XU ; Lin HAN ; Hao TANG ; Fanglin LU ; Zhiyun XU
Chinese Journal of Tissue Engineering Research 2014;(34):5509-5514
BACKGROUND:Our preliminary study found that the monocusp valves made of ultramicropore expanded
polytetrafluoroethylene (ePTFE) revealed no significant thrombus, calcification, or degradation 20 weeks after implanted into the descending aorta and the left pulmonary artery in sheep, which verified the good property of ePTFE. However, the surface of ePTFE in the left pulmonary artery was covered with obvious neointima.
OBJECTIVE: To assess the biocompatibility of phosphorylcholine-coated ePTFE.
METHODS:ePTFE surface was modified by phosphorylcholine derivative. Then the changes of surface shape, tensile stress at yield and elasticity modulus, water contact angle, and protein absorption capacity of ePTFE after surface modification were observed. (1) Hemolytic test: the leaching solution of phosphorylcholine-coated ePTFE, leaching solution of uncoated ePTFE, normal saline, and distiled water were added to the diluted human blood, respectively. (2) Platelet count test: the phosphorylcholine-coated ePTFE, uncoated ePTFE, high density
polyethylene, and Zymosan A were added to the whole blood samples from healthy volunteers, respectively.
(3) Platelet activation test: the phosphorylcholine-coated ePTFE, uncoated ePTFE, γ-Globulins, and Zymosan A
were added to the whole blood samples from healthy volunteers, respectively.
RESULTS AND CONCLUSION: The mean micropore diameter of ePTFE was significantly decreased after
phosphorylcholine coating (P < 0.001). The hydrophilicity and the ability of suppressing protein adsorption were
significantly strengthened after phosphorylcholine coating (P < 0.001). Phosphorylcholine coating did not influence
ePTFE in biomechanical properties and hemolytic test. The platelet count test and platelet activation test demonstrated that phosphorylcholine coating significantly improved anti-thrombus function of ePTFE. So, phosphorylcholine coating can enhance anti-thrombus function, suppress protein adsorption, and improve biocompatibility of ePTFE.
6.Spermine inhibits expression of Fas/FasL in simulated ischemia-reperfusion-injured cardiomyocytes of neonatal rat
Liping HAN ; Hongzhu LI ; Chunming JIANG ; Changqing XU ; Yongsheng GONG ; Yimin GUO
Chinese Journal of Pathophysiology 2010;26(4):630-634
AIM: To explore the effects and possible mechanism of exogenous spermine on the apoptosis of primary cultured neonatal cardiomyocytes induced by simulated ischemia-reperfusion (I/R) injury. METHODS: To establish a model of simulated I/R, the primary cultured neonatal rat cardiomyocytes were incubated in ischemia-mimetic solution (under the conditions of hypoxia plus serum deprivation) for 2 h, and re-incubated the cells in normal culture medium for 24 h. The apoptotic cell death was assayed by flow cytometry. The morphological alterations of the cells were observed under transmission electron microscope. The transcription and expression of Fas and FasL were determined by the methods of RT-PCR, Western blotting and immunofluorescence. RESULTS: The cells exposed to I/R underwent significant apoptosis, and the percentage of apoptotic cells was 27.4%±1.8%, much higher than that in normal group (5.7%±0.3%). In I/R group the evident histopathological changes were observed and the myocardial transcription and expression of Fas and FasL were significantly upregulated. Compared to normal group, mRNA expression of Fas and FasL increased 2.2 folds and 2.4 folds, respectively, and their proteins increased 1.7 folds and 1.9 folds at 24 h of reperfusion respectively (P<0.01). Pretreatment with 10 μmol/L spermine significantly inhibited apoptosis of I/R injured cells, and the percentage of apoptotic cells was 21.7%±1.3% (P<0.01, as compared to I/P group). Spermine also suppressed the expression of Fas and FasL significantly (P<0.05 or P<0.01, as compared to I/P group). CONCLUSION: Spermine plays anti-apoptotic effect on the cultured neonatal myocardial cells under the condition of I/R injury by suppressing the expression of Fas/FasL.
7.Expression of HGF/Met mRNA and TGF-α/EGFR mRNA in the liver/hepatocyte after partial hepatectomy in noncirrhotic obstructive rats
Mingqing XU ; Benli HAN ; Lan XUE ; Jianping GONG ; Jiahong DONG ; Shuguang WANG
Journal of Third Military Medical University 2001;23(3):334-337
Objective To investigate the expression of HGF and TGF-α and their receptor, Met (HGF receptor) and EGFR (TGF-αreceptor) mRNA, in the regenerative liver/hepatocytes after 70% partial hepatectomy (70% PH) in noncirrhotic biliary obstruction rats. Methods Wistar rats were divided randomly into N-PH group, BDO-RBF-PH group and BDO-RBF group. The expression of HGF/Met mRNA and TGF-α/EGFR mRNA was measured by RT-PCR in the liver/hepatocytes at the time point of 0, 6, 12, 24, 48 and 72 h after 70% PH or RBF. Results In N-PH group, the expression of HGF/Met mRNA increased sharply and peaked at 6 h, and maintained at a high level until 24 h after 70% PH. In BDO-RBF-PH group however, the expression of HGF/Met mRNA increased slowly and peaked at 12 h after 70% PH. The peak level was lower in BDO-RBF-PH group than in N-PH one. The expression of TGF-α/EGFR mRNA increased sharply and peaked at 24 h after 70% PH in N-PH group. However, the expression of TGF-α/EGFR mRNA elevated slowly and peaked at 48 h after 70% PH in BDO-RBF-PH group with a lower peak level than that in N-PH group. Conclusion The expression of HGF/Met mRNA and TGF-α/EGFR mRNA in the regenerative liver/hepatocytes after 70% PH decreases significantly in noncirrhotic biliary duct obstruction rats. There is a tendency that the expression of HGF mRNA and TGF-α mRNA is less than Met mRNA and EGFR mRNA.
8.Comparative study of the displacement of the selected clips in the cavity measured by orthogonal kilovoltage X-ray film in conditions of free breath and active breathing control for patients treated by external-beam partial breast irradiation
Jianbin LI ; Lei HAN ; Yingjie ZHANG ; Min XU ; Tingyong FAN ; Qian SHAO ; Guanzhong GONG
Chinese Journal of Radiation Oncology 2010;19(3):236-240
Objective To compare the displacements of the clips in the cavity measured with orthagonal kilovoltage (KV) X-my plain film in conditions of moderate deep inspiration breathing hold(mDIBH) and free breath (FB), and compare the margins from clinical target volume (CTV) to planning target volume (PTV) based on the displacements. Methods Before radiotherapy, 2 and 5 sets of orthogonal KV plain film were respectively collected in mDIBH and FB group, then the automatic registration of the reconstructed KV plain film and DRR derived from the planning OF images was finished. In conditions of mDIBH and FB, the displacements of the selected clip at the same location in the different directions and of the different selected clips in the same direction were compared. The margins in three dimensional directions were calculated and compared in conditions of mDIBH and FB . Results In FB hold group, the difference of displacement in left-right (LR), cranial-caudal (CC) and anterior-posterior (AP) directions were statistically significant between the clips at the cranial and caudal border of the cavity (9. 7 mm and 10. 6 nun (Z = -2. 12,P =0. 037) ,7. 3 mm and 8. 3 mm (Z = -2. 31 ,P=0. 041) ,15.5 mm and 16. 1 nun (Z = -2. 32,P = 0. 041)), but not statistically significant for the clips at the bottom and lateral P=0.814),15.7 mm and 16.5 mm (Z=-0.26,P=0.856)). The corresponding differences in the different directions were statistically significant (5.0 mm and 7. 8 mm(Z = -2. 31, P =0. 036), 5.0 mm and 9. 3 nun (Z= -2. 21,P=0. 021),7. 8 mm and9.3 mm (Z= -2. 11,P=0.041)). In FB group, the differences of the displacements of the four selected clips were statistically significant in CC and AP directions (7.3 mm and 8.4 mm (Z= -2.45,P=0.021), 15.5 mm and 16.5 mm (Z= -2.41,P= 0.043)), but not in LF direction (10.6 nun and 10.6 mm (Z= -0.24,P=0. 815)). In mDIBH group, the displacements in LF direction were statistically significant (4. 4 mm and 5.4 mm (Z = -2. 31, P = O. 031)), but not in CC and AP directions (8. 6 mm and 8.6 mm (Z =-0. 21, P = 0. 815), 10. 5 mm and 10. 8 mm (Z = -0. 27 ,P =0. 754)). There were statistically significant difference of the margins in LF and AP directions (9.7 mm and 5.0 mm (Z= -2.34,P=0.029),15.5 mm and 9.3 mm (Z= -2. 31,P= 0.021)), but not in CC direction (7.3 mm and 7. 8 mm (Z= -0.29,P =0.770)) between mDIBH and FB conditions. Conclusions The margins extended from CTV to PTV for EBPBI should be determined based on the respiratory status, border location and border direction.
9.Dosimetric comparison between RapidArc and fixed gantry dynamic IMRT for central-type lung cancer radiotherapy
Jian GONG ; Rong YU ; Hao WU ; Shukui HAN ; Bo XU ; Guangying ZHU ; Fan JIANG
Chinese Journal of Radiological Medicine and Protection 2010;30(4):448-451
Objective To compare the dosimetric difference between RapidArc and fixed gantry angle dynamic IMRT (dIMRT) for central-type lung cancer radiotherapy. Methods Therapy for 10 patients previously treated with dIMRT was replanned with RapidArc. Dose prescription was 66 Gy/33 fraction. Comparative endpoints were planning target volume (PTV) dose, doses to surrounding structures,number of monitor units, and treatment delivery time. Results There was no significant dosimetric difference between RapidArc and dIMRT. Compared with dIMRT, RapidArc slightly elevated target volume dose, lung V5, V10. The average values of lung V20, V30 and heart V30 were larger in dIMRT than those in RapidArc. The number of monitor units was reduced by 32% and the treatment time by 66% in RapidArc.Conclusions Both RapidArc and dIMRT plans could meet the clinical therapy needs. RapidArc could achieve similar target coverage and sparing of organs at risk, with fewer monitor units and shorter delivery time than dIMRT.
10.A Research Approach on the Quality Cognition and Quality Evaluation of Traditional Chinese Medicine (TCM) Based on the Concept of Precision Medicine
Tiejun ZHANG ; Gang BAI ; Jun XU ; Yanqi HAN ; Suxiao GONG ; Hongbing ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(1):35-43
Precision medicine pointed out the future direction for medicine,providing new opportunities for the development of TCM,putting forward higher requirements and encountering severe challenges of the quality research of TCM.In view of the core connotation of precision medicine and the characteristics of TCM,we presented the precision connotation of quality based on the basic attributes,the clinical application and function characteristics of TCM in accordance with the thinking mode and method of the transformation research.In this article,we indicated the research approach for the scientific evaluation and effective control of quality based on the precise cognition of TCM.