1.The experimental study on anti-tumor effect of 131Ⅰ-Tyr-octreotide in nude mice bearing human non-small cell lung cancer
Yan, SU ; Feng, WANG ; Le-le, ZHANG ; Yu-ming, ZHENG ; Qing-le, MENG ; E, JING ; Shao-hua, LI ; Zi-zheng, WANG
Chinese Journal of Nuclear Medicine 2009;29(1):34-38
Objective Radionuclide-labeled low molecular weight polypeptide is reeently advocated for the diagnosis and treatment of malignant tumor. The purpose of this study was to evaluate the anti-tumor effect of 131Ⅰ-Tyr-octreotide in nude mice bearing human non-small cell lung cancer (NSCLC). Methods 131Ⅰ-Tyr-octreotide was prepared by Ch-T method. The radiochemical purity was measured and biodistribution was evaluated. The nude mice models bearing human NSCLC were studied and divided into four groups: group A injected 131Ⅰ-Tyr-octreotide through tail vein, group B injected normal saline, group C injected 131Ⅰ-Tyroctreotide through stroma and group D injected 131Ⅰ through stroma. The radioactivity ratio of tumor to normal tissue (T/NT) was calculated over region of interest (ROI). The tumor cell cycle and cell apoptosis were analyzed by flow cytometry (FCM), terminal deoxynucleotidyl transferase mediated dUTP-biotion nick end labeling (TUNEL) and histopathological analysis. Statistical analysis was performed with SPSS 11.0, and the comparison for difference between groups performed with one-way ANOVA analysis. Results The labeled radiochemical purity was (95.23±1.67)% and specific activity of 3.5×106Bq/ug. The biodistributiou showed high uptake in kidney, and low uptake in liver and spleen. The radioactive uptake in group C was higher than the other groups, and the retention time was longer. The T/NT was 52.74±0.13 after 24 h, which was much higher than that the other groups (group D: 8.90±0.23, group A: 6.42±0.02, q=628.81 and 664.33, all P<0.05). The resuits of tmnor cell cycle determined by FCM showed that the G1 phase was blocked mast remarkably in group C than the other groups [group C: (83.17±6.86)%, group A: (57.02±18.81)%, group D: (49.29±7.80)%, group B: (45.88±5.13)%, q=5.29, 6.86, 7.55, 1.56, 2.26, 0.69, all P<0.05]. Apeptotic cells were observed by TUNEL, and apoptotic body was detected by immuno-histochemical examination. Conclusions 131Ⅰ-Tyr-octreotide was easily labeled by Ch-T. 131Ⅰ-Tyr-octreotide could induce tumor cell apoptosis and inhibit the tumor cell of NSCLC. It might be a potential target-directed agent in NSCLC.
2.The effects of ulinastatin-containing autologous cold blood cardioplegic solution on the cardiac function of infants after open heart surgery
Baoying MENG ; Qing ZHANG ; Dingrong SHEN ; Yunxing TI ; Xiaolan PAN ; Chao MA ; Le PENG ; Yuanxiang WANG
Clinical Medicine of China 2012;28(3):228-231
Objective To investigate the effects of ulinastatin-containing autologous cold blood cardioplegic solution on the cardiac function of infants after cardiopulmonary bypass surgery.Methods Sixty infants younger than 10 months old,who underwent ventricular septal defect repair under cardiopulmonary bypass,were randomized into autologous cold blood cardioplegia group (30 patients,Group A)and ulinastatincontaining cold blood cardioplegia group (30 patients,Group B).CI,SI and LCWI were monitored 1 and 6 hours after opening the aorta.The time and rate of cardiac resuscitation,as well as the dependence on the inotropic drugs,were intraoperatively monitored.Results The automatic resuscitation rate in two groups was not siynificantly ( P > 0.05).The time for automatic resuscitation were (34.2 ± 4.7) s and (52.1 ± 6.5 ) s for Group B and Group A,respectively ( P < 0.05 ).The rate of dependence on inotropic drug were 40.0% (12/30) and 66.7% (20/30)for Group B and Gro~p A,respectively (P < 0.05).Mter the operation,the CI,SI and LCWI of group B were higher than that of group A ( P <0.05 ).Conclusion Ulinastatin-containing autologous cold blood cardioplegic solution is beneficial to the functional cardiac recovery of the infants after heart bypass surgery by protecting the immature myocardium.
3.Lung protection effect of intra-aortic protamine injection in infants underwent opening heart operation by cardiopulmonary bypass surgery
Baoying MENG ; Qing ZHANG ; Tao WANG ; Dingrong SHEN ; Le PENG ; Chao MA ; Xiaolan PAN ; Yuanxiang WANG
Clinical Medicine of China 2011;27(3):235-238
Objective To study the protective effect of intraaortic protamine injection on lung in infants undergwent opening heart operation by cardiopulmonary bypass surgery. Methods Sixty infants (age ≤ 1 year,weight ≤ 10 kg)who accepted opening heart operation by cardiopulmonary bypass surgery were randomly assigned into 2 groups ( n = 30 in each group) reciving intra-aortic and intra-venous protamine injection respectively. P-peak, P-plate, CL, Oxygenation Index, the number of WBC and neutrophil segregated in lungs were compared between two groups before injecting protamine and 10 minutes, 1 hour, 3 hours after injecting protamine. The time of mechanical ventilation were compared as well. Results P-peak, P-plate, the number of WBC and neutrophil segregated in lungs of intra-aortic injection group significantly decreased than intra-venous injection group at 1 hour, 3 hours after injecting protamine (t =2.743, 3.512; 3.218, 3.469; 3.716, 5.243; 3.853,4. 783 respectively, Ps < 0. 05 ), while the CL and Oxygenation Index increased significantly ( t = 3. 976,4. 267; 4. 557,4. 265 respectively, P < 0. 05 ). The duration of mechanical ventilation follow operation in intraaortic injection group ( [8. 03 ± 5. 14] h ) was shorter compared with intra-venous injection group ( [10. 56 ±6.95]h) (t =2.599,P<0.05). Conclusion By intra-aortic protamine injection the lung injury decreased significantly. It shows good protective effect on lung in infants underwent opening heart operation by cardiopulmonary bypass surgery.
4.The influence of autoblood cardioplegia on ATPase in neonatus
Qing ZHANG ; Le PENG ; Tao WANG ; Chao MA ; Baoying MENG ; Gong XU ; Chunyu ZHAO
Clinical Medicine of China 2009;25(4):354-356
Objective To study the influence of autoblood cardioplegia on ATPase in neonatus myocardium with congenital heart disease and approach the mechanism of self-blood cardioplegia in protecting the myocardium in neonatus.Methods There were 30 cases of neonatus with congenital heart disease with body weight less than 8 kg,including 2 cases of ventricular septal defect(VSD),11 of VSD with severe pulmonary hypertension(PH),9 cases of USD with ASD,2 cases of atrial septal defect (ASD),6 of VSD and FPO.30 neonatus were divided into autoblood cardioplegic solution group(group A,n=10),allograft blood cardioplegic solution group (group B,n=10)and crystalloid cardioplegic solution group(group C,n=10).The biopsies were taken from right atrium just before arrested and after heart self-recovery to measure ATPase.Results Comparing with preoperative one,Na+-K+-ATPase creased obviously after operation in group A,B ,C (P<0.05 ).There had no significant difference among the three groups before operation (P>0.05).After operation,myocardial cell's Na+-K+-ATPase,Ca2+-ATPase and Ca2+Mg2+-ATPase in group A were decreased obviously as compared with that in group B and C (P<0.05).Conclusion There is slight influence of autobloed cardioplegia on ATPase in neonatus with congenital heart disease,which can give a good protection to the myocardium in neonatus.
5.Periopeiative manngement of congenital esophageal atresia with severe pneumonia
Qing ZHANG ; Tao WANG ; Suyi LI ; Xiaopeng MA ; Chao MA ; Baoying MENG ; Le PENG
Chinese Journal of Primary Medicine and Pharmacy 2009;16(3):395-396
Objective To study the effect of the Periopeiative manngement on successful surgical treatment of congenital esophageal atresia with severe pneumonia.Method To review the Periopeiative manngement in congenital esophageal atresia with severe pneumonia.Result 33 cases were healed and one csse had anastomotic stoma leak and 2 cases died.Conclusion The key of one stage successful surgical treatment of congenital esophageal atresia with severe pneumonia is the good Pefiopeiative manngement.
6.Effect of Cold Self-blood Cardioplegia With Ulinastatin on Immature Myocardial Cell Apoptosis in Infant Patients
Baoying MENG ; Qing ZHANG ; Xiaolan PAN ; Yuanxiang WANG ; Dingrong SHEN ; Yunxing TI ; Chao MA ; Le PENG
Chinese Circulation Journal 2014;(12):1011-1014
Objective: To investigate the effect of cold self-blood cardioplegia with ulinastatin on immature myocardial cell apoptosis and protein expressions of Bcl-2, Bax in ventricular septal defect (VSD) infants.
Methods: A total of 60 infants received VSD repairing operation with cardiopulmonary bypass (CPB) in our hospital were summarized. The patients were randomly divided into 2 groups:Test group, the infants received cold self-blood cardioplegia with ulinastatin when aortic cross-clamp was closed. Control group, the infants received cold self-blood cardioplegia when aortic cross-clamp was closed. n=30 in each group. The right atrium tissue was collected before CPB and 10 min after releasing aortic cross-clamp. The index of myocardial cell apoptosis was observed by TUNEL method, and the protein expressions of Bcl-2, Bax were examined by immunohistological method.
Results: Both groups showed the higher index of myocardial cell apoptosis at 10 min after releasing aortic cross-clamp than 5 min before CPB, and the apoptosis index in Test group was lower than that in Control group, all P<0.05. The protein expressions of Bcl-2 and Bax were obviously increased at 10 min after releasing aortic cross-clamp than 5 min before CPB in both groups. Compared with Control group, Test group presented the higher Bcl-2 protein expression and lower Bax protein expression, all P<0.05.
Conclusion: Cold self-blood cardioplegia with ulinastatin could protect immature myocardum from ischemia-reperfusion injury in VSD infants during CPB operation in clinical practice.
7.The effect of physical training on insulin resistance in patients with chronic heart failure
Zhao-Qiang DONG ; Yi-Meng DU ; Wan-Cai CAO ; Wei-Dong JIANG ; Qun WANG ; Qing-Hua LU ; Le JIANG ;
Chinese Journal of Physical Medicine and Rehabilitation 2003;0(10):-
Objective To investigate insulin resistance and the effect of physical training on it in the pa- tients with chronic heart failure (CHF). Methods One hundred and twenty NYHAⅡ-ⅢCHF patients were ran- domly divided into a training group( n = 65 ) and a routine therapy group (n = 55 ). Another 35 healthy subjects were recruited as control group. All the patients were treated with routine anti-CHF drugs, and the training group patients had received physical training twice a day in addition. The HOMA-IR, insulin sensitivity index (ISI) , left ventricu- lar ejection fraction (LEVF), left ventricular fractional shortening( LVFS), 6-minute walking distance, heart rate and mean blood pressure were compared between the training and routine therapy groups before and after physical ex- ercise in both groups, and a comparison was made between the patients and the controls before the intervention with regard to HOMA-IR and ISI. Results Comparing with control group, ISI was reduced while the HOMA-IR in- creased (P
8.A preliminary study of imaging paclitaxel-induced tumor apoptosis with (99)Tc(m)-His10-Annexin V.
Yu-min ZHENG ; Feng WANG ; Wei FANG ; Zi-chun HUA ; Zi-zheng WANG ; Qing-le MENG ; Jue YAN
Chinese Medical Journal 2013;126(15):2928-2933
BACKGROUNDIn tumors the process of apoptosis occurs over an interval of time after chemotherapy. It is important to determine the best time for detecting apoptosis by in vivo imaging. In this study, we evaluated the dynamics and feasibility of imaging non-small cell lung cancer (NSCLC) apoptosis induced by paclitaxel treatment using a (99)Tc(m)-labeled Annexin V recombinant with ten consecutive histidines (His10-Annexin V) in a mouse model.
METHODS(99)Tc(m)-His10-Annexin V was prepared by one step direct labeling; radio-chemical purity (RCP) and radio-stability was tested. The binding of (99)Tc(m)-His10-Annexin V to apoptotic cells was validated in vitro using camptothecin-induced Jurkat cells. In vivo bio-distribution was determined in mice by dissection. The human H460 NSCLC tumor cell line (H460) tumor-bearing mice were treated with intravenous paclitaxel 24, 48 and 72 hours later. (99)Tc(m)-His10-Annexin V was injected intravenously, and planar images were acquired at 2, 4 and 6 hours post-injection on a dual-head gamma camera fitted with a pinhole collimator. Tumor-to-normal tissue ratios (T/NT) were calculated by ROI analysis and they reflected specific binding of (99)Tc(m)-His10-Annexin V. Mice were sacrificed after imaging. Caspase-3, as the apoptosis detector, was determined by flow cytometry, and DNA fragmentation was analyzed by the terminal deoxynucleotidytransferase mediated dUTP nick-end labeling (TUNEL) assay. Nonspecific accumulation of protein was estimated using bovine serum albumin (BSA). The imaging data were correlated with TUNEL-positive nuclei and caspase-3 activity.
RESULTS(99)Tc(m)-His10-Annexin V had a RCP > 98% and high stability 2 hours after radio-labeling, and it could bind to apoptotic cells with high affinity. Bio-distribution of (99)Tc(m)-His10-Annexin V showed predominant uptake in kidney, relatively low uptake in myocardium, liver and gastrointestinal tract, and rapid clearance from blood and kidney was observed. The T/NT was significantly increased after paclitaxel treatment, whereas it was low in untreated tumors (T/NT = 1.43 ± 0.18). The %ID/g activity in Group 2 (24 hours), Group 3 (48 hours) and Group 4 (72 hours) after treatment was 2.55 ± 0.73, 3.35 ± 1.10, and 3.4 ± 0.96, respectively. Whereas in the non-treated group, Group 1, %ID/g was 1.10 ± 0.18. The radiotracer uptake was positively correlated to the apoptotic index (r = 0.852, P < 0.01), as well as caspase-3 activity (r = 0.816, P < 0.01).
CONCLUSIONThis study addresses the dynamics and feasibility of imaging non-small cell lung tumor apoptosis using (99)Tc(m)- His10-Annexin V.
Animals ; Annexin A5 ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Apoptosis ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cell Line, Tumor ; Disease Models, Animal ; Histidine ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Mice ; Organotechnetium Compounds ; Paclitaxel ; therapeutic use ; Radiopharmaceuticals
9.Novel quantitative method for evaluating oxygen/glucose deprivation-induced injury of hippocampal slices
Le-Qin YAN ; Er-Qing WEI ; Hai-Tao HU ; Wei-Ping ZHANG ; Meng-Ling WANG ; Jian-Zong SHEN
Journal of Zhejiang University. Medical sciences 2002;31(2):81-85
OBJECTIVE: To establish a simple, sensitive in vitro method to evaluate oxygen/glucose deprivation (OGD)-induced injury of brain hippocampal slices in rats. METHODS: Rat hippocampal slices were incubated in 2% 2, 3, 5-triphenyltetrazolium chloride (TTC) solution after oxygen/glucose deprivation. They were then soaked in a measured volume of ethanol and dimethylsulfoxide (50:50) to extract the TTC formazan Product which was then measured by spectrophotometry. OGD induced LDH release was simultaneously measured. RESULTS: Progressive prolongation of OGD induced hippocampal injury resulted in decreased formazan coloration as determined by spectrophotometry. There was a parallel increase in LDH release, thus a negative correlation in these two products was noted. (r=-0.933,P <0.01). The injury was attenuated in the brain slices pre-treated with nimodipine, dexamethasone, and ketamine, but not ONO-1078. CONCLUSION: Solvent extraction and spectrophotometric quantification of formazan represents an objective measurement of OGD-induced injury of rat hippocampal slices.
10.Preparation and identification of polyclonal antiserum against angiotensinogen.
Qing-Jun MENG ; Jian LI ; Wen-Hong ZHANG ; Le-Ning ZHANG ; Li-Fan ZHANG
Acta Physiologica Sinica 2003;55(1):110-113
For studying the expression and distribution of angiotensinogen (AGT), the C-teminus of rat AGT gene was expressed in E.coli. Rabbits were immunized with expressed AGT protein and sera from different rabbits were raised. ELISA showed a high titre (1:25600) of the antiserum. With the antiserum, Western blotting recognized not only the prokaryotic expressed AGT, but also the endogenous AGT protein in liver tissue of both rats and humans. Using this antiserum, immunohistochemistry showed the expression of AGT protein in islet cells of human pancreas as well as in epithelium of human bile duct. These results suggest that the prokaryotic expressed AGT protein is an effective immunogen for the preparation of anti-AGT antiserum. Our present work provides an important tool for study of the pathophysiological role of AGT as well as local renin-angiotensin system.
Angiotensinogen
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genetics
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immunology
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Animals
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Antibodies, Monoclonal
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biosynthesis
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Escherichia coli
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genetics
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metabolism
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Humans
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Immune Sera
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biosynthesis
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immunology
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Immunization
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Rabbits
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Rats
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Recombinant Proteins
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biosynthesis
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genetics
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immunology
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Renin-Angiotensin System
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physiology