1.Recombinant human endostatin improves tumor vasculature and alleviates hypoxia in Lewis lung carcinoma
Fang PENG ; Jin WANG ; Yi ZOU ; Yong BAO ; Wenlin HUANG ; Guangming CHEN ; Xianrong LUO ; Ming CHEN
Chinese Journal of Radiation Oncology 2011;20(1):69-72
Objective To investigate whether recombinant human endostatin can create a time window of vascular normalization prior to vascular pruning to alleviate hypoxia in Lewis lung carcinoma in mice. Methods Kinetic changes in morphology of tumor vasculature in response to recombinant human endostatin were detected under a confocal microscope with immunofluorescent staining in Lewis lung carcinomas in mice. The hypoxic cell fraction of different time was assessed with immunohistochemical staining . Effects on tumor growth were monitored as indicated in the growth curve of tumors . Results Compared with the control group vascularity of the tumors was reduced over time by recombinant human endostatin treatment and significantly regressed for 9 days. During the treatment, pericyte coverage increased at day 3, increased markedly at day 5, and fell again at day 7. The vascular basement membrane was thin and closely associated with endothelial cells after recombinant human endostatin treatment, but appeared thickened, loosely associated with endothelial cells in control tumors. The decrease in hypoxic cell fraction at day 5 after treatment was also found. Tumor growth was not accelerated 5 days after recombinant human endostatin treatment. Conclusions Recombinant human endostatin can normalize tumor vasculature within day 3 to 7, leading to improved tumor oxygenation. The results provide important experimental basis for combining recombinant human endostatin with radiation therapy in human tumors.
2.The diagnosis and therapy of intractable upper gastrointestinal hemorrhage caused by hepatic arterioportal vein fistulas in hepatocellular carcinoma
Peng-Fei LUO ; Xiao-Ming CHEN ; Li-Gong LU ; Bao-Shan HU ; Yong LI ;
Chinese Journal of Radiology 2001;0(04):-
Objective To investigate the hemodynamics of increasing portal venous pressure(PVP) in hepatocellular carcinoma patients complicated with hepatic arterioportal vein fistulas (HAPVF)and the diagnosis and therapy of intractable upper gastrointestinal hemorrhage caused by HAPVF.Methods One hundred and fifteen cases of hepatocellular carcinoma with upper gastrointestinal hemorrhage were checked by hepatic arteriography and were treated through orifices embolization in cases with severe HAPCF by coils and/or ethanol. Results Twenty-six out of 31 patients suffering intractable upper gastrointestinal hemorrhage have severe HAPVF(the main stem of portal veins are visible).However,there are only 15 patients with light HAPVF among the 84 patients who have mild upper gastrointestinal hemorrhage (the main stem of portal veins are invisible).After the embolization,all of the 26 patients who have severe HAPVF stopped bleeding.Among them,the main stem of hepatic arteries are occluded in 2 patients. Conclusion The existence of severe HAPVF should be taken into consideration when intractable upper gastrointestinal hemorrhage occurs in hepatocellular carcinoma patients,and it can be diagnosed through hepatic artery DSA.Orifice embolization is the most effective method for such kind of hemorrhage.
3.ERK1/2 pathway involved in the expression of ETB receptors of the culturing smooth muscle cells of rat mesenteric artery.
Guo-gang LUO ; Yong-xiao CAO ; Cang-bao XU ; Ai-qun MA ; Lars EDVINSSON
Acta Pharmaceutica Sinica 2006;41(3):257-262
AIMTo determine the involvement of extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in the expression of endothelin receptor type B (ETB) during culture.
METHODSSB386023, a specific inhibitor for ERK1/2 pathway, was used to define the intracellular signaling pathway for the upregulation of ETB receptors and sarafotoxin 6c (S6c), a selective agonist for ETB receptors, induced contraction in isolated rat superior mesenteric arteries. The contraction was recorded by a sensitive in vitro myograph and the receptor mRNA was quantified by a real-time PCR. The phosphorylated ERK1/2 proteins were analyzed by phosphoELISA assay.
RESULTSS6c induced strong contractile responses of the artery after culture for 24 h, while there was no response to S6c in fresh vessel segments. The enhanced contractile response to S6c paralleled with an increase of mRNA for ETB receptors. The phosphorylated ERK1/2 proteins significantly increased after culture for 3 h. After co-culture with SB386023 for 24 h, S6c-induced contractions significantly decreased with reduction of Emax from (217 +/- 14) % to (127 +/- 23) % (P <0.01). This response paralleled with a decreased level of ETB receptor mRNA.
CONCLUSIONERK1/2 pathway was involved in the up-regulation of ETB receptors on smooth muscle cells isolated from rat mesenteric arteries during culture.
Animals ; Cells, Cultured ; Male ; Mesenteric Arteries ; cytology ; Mitogen-Activated Protein Kinase 1 ; antagonists & inhibitors ; metabolism ; Mitogen-Activated Protein Kinase 3 ; antagonists & inhibitors ; metabolism ; Muscle Contraction ; drug effects ; Muscle, Smooth, Vascular ; cytology ; metabolism ; Organ Culture Techniques ; Phosphorylation ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptor, Endothelin B ; biosynthesis ; genetics ; Signal Transduction ; Up-Regulation ; Vasoconstrictor Agents ; pharmacology ; Viper Venoms ; pharmacology
4.Role of erythrocyte on brain edema development after traumatic intracerebral hemorrhage in rats
Bao-Zhong SHI ; Yong-Gang ZHAO ; Dong-Hui LUO ; Jing-Fang LIU ; Li-Xin XU ; Yun-Sheng LIU
Chinese Journal of Trauma 2003;0(12):-
Objective To study the effects of erythrecyte on brain edema after traumatic intrace- rebral hemorrhage(TICH)and explore the mechanisms of erythrocyte in brain edema development follow- ing TICH.Methods Firstly,the brain injury model of SD rat was established by applying a free-fall- ing device,then whole blood(WB),lysed RBC(LRBC)or parked RBC(PRBC)were infused with ste- reotactic guidance into injured cortex to produce the model of TICH.All rats were killed at 1,3,and 5 days after injury.The brain water content was measured,immunohistochomistry(SABC)was applied to test HO-1 and TNF-?expressions.Results 1.In WB group,PRBC group and TBI group,the brain water content was the highest on the third day.The brain water content of LRBC group was markedly higher on the first day than on the third and fifth days.Comparison among the four groups showed the wa- ter content was the highest on the 1st day in LRBC group,and on the 3rd day in WB and PRBC groups; there was no significant difference among the four groups on 5th day.2.The positive expression of HO-1 and TNF-?coincided with the change of the water content in groups of WB,PRBC and LRBC.Conclu- sions In rat model of TICH,RBC plays an important role in delayed brain edema formation(3 days after injury),but has no influence at early stage(1 day after injury).The mechanisms of delayed brain edema involves RBC breakdown and inflammation reaction.
5.The effect and mechanism of neutralizing heat shock protein B6 antibody on tube formation of human choroidal endothelial cell
Hui-kang, CHEN ; Ji-ming, ZHANG ; Long-biao, LI ; Yi-yong, QIAN ; Gao-qin, LIU ; Bao-gen, LUO ; Mei, FEI
Chinese Journal of Experimental Ophthalmology 2013;32(11):1031-1036
Background The proliferation and migration of vascular endothelial cells is a primary link during angiogenesis.Studies showed that heat shock protein B6 (HspB6) promotes the secretion of multiple angiogenesis-related factors and therefore leads to neovascularization.Understanding the effects of neutralizing HspB6 antibody on the biological behavior of human choroidal vascular endothelial cells has an important significance in the target treatment of choroidal neovacularization diseases.Objective This study was to address the role and mechanism of neutralizing HspB6 antibody in tube formation of human choroidal vascular endothelial cells.Methods Human choroidal vascular endothelial cell line was normally cultured and harvested for total RNA extraction.Expressions of HspB6 mRNA and protein in human choroidal vascular endothelial cells were detected by reverse transcription PCR (RT-PCR) and flow cytometry (FCM).The cells were seeded on 96-well plate covered with matrigel at the density of 2×104/hole.Then the neutralizing HspB6 antibody at the concentration of 100 μg/Land 500 μg/L was added into the medium respectively,and the control cells were set without the addition of HspB6 antibody.The number of capillary tubes was calculated 12 hours after culture by three-dimensional matrigel assay.In addition,0,50,100,500 μg/L of neutralizing HspB6 antibody were added into the cell medium separately for 24hours,cell counting kit-8 (CCK-8) method was employed to assay the inhibitory rate(IR) of the cells.Transwell test was used to count the cell number across chamber membrane for the evaluation of migration ability of the cells.The apoptosis of the cells was assayed by FCM.Results Both HspB6 mRNA and protein were expressed on human choroidal vascular endothelial cells.The number of capillary tube formation of human choroidal vascular endothelial cells was (67.25±5.75),(60.39±6.41) and (39.76±10.73) /field in the 0,100 and 500 μg/L neutralizing HspB6 antibody groups,with significant difference among them (F =10.210,P =0.012),and the tube number was significantly less in the 500 μg/L neutralizing HspB6 antibody group compared with 0 μg/L neutralizing HspB6 group (P =0.005).The IR of neutralizing HspB6 antibody to the cellular proliferation and migration was enhanced with the increases of concentration and time lapse(Fconcentration =7.485,P =0.002 ; Ftime =16.684,P =0.001).The number of the cells through Transwell chamber membrane was 14.0 ± 2.5,11.1 ± 0.8,6.6 ± 0.1,6.7 ± 0.2 in the 0,50,100,500 μg/L neutralizing HspB6 antibody group respectively,and that in the 100 μg/L and 500 μg/L neutralizing HspB6 antibody group was lessened in comparison with the 0 μg/L neutralizing HspB6 antibody group(both at P=0.000).The apoptosis rate of the cells was (22.73 ± 2.53)% in the neutralizing HspB6 antibody group,which was significantly lower than (13.33±2.08) % of the control group (t=4.967,P=0.008).Conclusions Neutralizing HspB6 antibody inhibits capillary tube formation of human choroidal endothelial cells in vitro in dose-and timedependent manner,probably through suppressing the proliferation and migration and promoting the apoptosis of choroidal endothelial cells.
6.Effect of heat exposure in the second trimester of pregnancy on intrauterine growth of fatal rat and the expression of HSP70, Bax and Bcl-2 of placenta.
Yong-Bao PENG ; Shu-Hui HUANG ; Jun-Ming ZHANG ; Yong LUO ; Qun ZHOU ; Huai LIU
Journal of Southern Medical University 2017;37(1):89-92
OBJECTIVETo investigate the effect of heat exposure during the second week of pregnancy on placental development and intrauterine growth of fetal rats.
METHODS24 pregnant rats were either exposed or not to a temperature of 35∓1 degrees celsius; during the second week of pregnancy. The body weight gain of the pregnant rats was measured regularly, and in late pregnancy, the pregnant rats were dissected and the number, weight, length, tail length, appearance of the offspring rats, number of live and still births, and the placental weight were recorded. The expressions of HSP70, Bax and Bcl-2 in the placenta were determined.
RESULTSCompared with the control group, the pregnant rats in heat exposure group had significantly lower body weight at the end of pregnancy and gestational weight gain, and the body weight, body length and tail length of the offspring rats were also significantly lower or smaller (P<0.05). The placental weight was comparable between the two groups. The placental expressions of HSP70,Bax,and Bcl-2 were significantly higher in the heat exposure group than in the control group (P<0.05).
CONCLUSIONHeat exposure during the second trimester of pregnancy has adverse effects on placental development and intrauterine growth of the fetal rats by inducing heat shock response of placental tissue and apoptosis of the placental cells.
7.Prognostic value of PSA kinetics in locally advanced prostate cancer treated by maximal androgen blockade combined with brachytherapy.
Yong LUO ; Neng-Bao WEI ; Jia-Hui ZHAO ; Xin-Hao CUI ; Ming-Chuan LI ; Yun-Hua LIN ; Zhu HOU ; Yi-Li HAN ; Yong-Guang JIANG
National Journal of Andrology 2014;20(3):229-233
OBJECTIVETo evaluate the effect of post-treatment PSA kinetics on the prognosis of prostate cancer (PCa).
METHODSWe retrospectively reviewed the clinical data of 114 cases of locally advanced PCa treated by maximal androgen blockade (MAB) combined with brachytherapy, and analyzed the association of the changes in PSA kinetics with the prognosis of the patients.
RESULTSThe median survival time of the patients was 81 (15 - 144) months, with 1-, 3- and 5-year survival rates of 91. 23%, 78.07% and 68.42% , respectively. Univariate analysis indicated that the baseline PSA level, PSA nadir, the time of PSA decreasing to nadir, PSA doubling time, and the extent of PSA declining were all predictive factors for the survival time of the PCa patients. Multivariate analysis demonstrated that PSA nadir, the time of PSA decreasing to nadir, and the extent of PSA declining were three independent prognostic factors, which prolonged the long-term survival of the patients by 1.7, 3.2 and 6.8 times, respectively.
CONCLUSIONFor locally advanced PCa treated by MAB combined with brachytherapy, PSA nadir <1 micro g/L, the time to nadir <3 months, and the extent of PSA declining >96% are independent prognostic factors.
Aged ; Aged, 80 and over ; Androgens ; administration & dosage ; therapeutic use ; Brachytherapy ; Humans ; Male ; Middle Aged ; Prognosis ; Prostate-Specific Antigen ; metabolism ; Prostatic Neoplasms ; metabolism ; therapy ; Retrospective Studies
8.Diagnostic value of electrocardiogram on anomalous origin of the left coronary artery from the pulmonary artery in infants.
Bao-jing GUO ; Ling HAN ; Mei JIN ; Gui-zhen ZHANG ; Lei WANG ; Bang-jun WU ; Yi LUO ; Yong-qing LI ; Xiao-fang WANG ; Ke ZHENG ; Ping LU
Chinese Journal of Pediatrics 2004;42(11):863-864
9.Nimesulide, a selective cyclooxygenase-2 inhibitor inhibits telomerase activity by blocking activation of PKB in gastric cancer cell line.
Guo-yong HU ; Bao-ping YU ; Jie-ping YU ; Zong-xue RAN ; He-sheng LUO
Chinese Journal of Oncology 2004;26(4):209-212
OBJECTIVETo study the effects of nimesulide, a selective COX-2 inhibitor, on cell viability, telomerase and PKB activities in human gastric cancer cell line SGC7901 and to explore its molecular mechanism of selective growth inhibition.
METHODSMTT assay was used to determine cell viability after incubation for 0, 12, 24, and 48 h in different concentrations (0, 25, 50, 100, 200 micro mol/L) of nimesulide and/or okadaic acid (300 nmol/L). Telomerase and protein kinase B (PKB) activities were detected using TRAP PCR-ELISA and nonradioactive IP-kinase assay.
RESULTSNimsulide caused a time and dose-dependent reduction of cell numbers of SGC7901. The telomerase and PKB activities were significantly inhibited, and the inhibition of telomerase activity was partly associated with decrease in PKB activity.
CONCLUSIONSelective COX-2 inhibitor nimesulide inhibits telomerase activity of gastric cancer cells by partly blocking the activation of protein kinase B. The results suggest an additional signaling pathway underlying the anti-cancer effect of COX-2 inhibitor.
Adenocarcinoma ; enzymology ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclooxygenase Inhibitors ; pharmacology ; Dose-Response Relationship, Drug ; Enzyme Activation ; drug effects ; Humans ; Protein-Serine-Threonine Kinases ; metabolism ; Proto-Oncogene Proteins ; metabolism ; Proto-Oncogene Proteins c-akt ; Stomach Neoplasms ; enzymology ; pathology ; Sulfonamides ; pharmacology ; Telomerase ; metabolism ; Time Factors
10.Effect of mycobacteriophage to intracellular mycobacteria in vitro.
Li PENG ; Bao-wen CHEN ; Yong-ai LUO ; Guo-zhi WANG
Chinese Medical Journal 2006;119(8):692-695