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Anti-tumor effect of thalidomide and paclitaxel on hepatocellular carcinoma in nudemice

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Chinese Medical Journal 2005年第20期118卷 1688-1694页

作者： ZHANG Zhong-lin LIU Zhi-su SUN Quan Department of General Surgery Zhongnan Hospital WuhanUniversity Wuhan 430071 China

Background Thalidomide is reviving for its antiangiogenic effect on corneal neovascularization models. Recently, it has been employed in tumor research in several types of solid carcinomas. However, its effect on hepatocellular carcinoma （HCC） has not yet been clarified.Methods A total of 48 nude mice bearing human HCC with a high metastatic potential were randomly divided into 4 groups. Thalidomide （200 mg/kg）, paclitaxe] （ 13 mg/kg）, or their combination, which was dissolved in O. 5% sodium carboxy] methyl cellulose （CMC） suspension, was intraperitoneally injected in each group since the second day of the establishment of animal model. The group simply administered with O. 5 % CMC was set as placebo-controL The mice were sacrificed on the 30th day, for the measurement of tumor size, weight and metastasis in the lungs. The levels of CD34 and endothelial growth factor （VEGF） mRNA in tumor tissues were detected by immunohistochemistry and semiquantitative RT-PCR, respectively, and microvessel density （MVD） was evaluated.Results No statistical difference was found in tumor weight and volume between the thalidomide group and control （P〉0. 05 ）. Paclitaxel showed a growth-inhibiting effect on tumors （P〈0. 05 ）. The value of MVD and VEGF mRNA and metastases to the lungs in each group were lower than those in the placebo-control group （P〈0. 05 ） ; such difference in the combination group was statistically significant （P〈0. 05 ）. Conclusions Paclitaxel, but not thalidomide, has significant growth inhibitory effect on tumors, but both significantly inhibit angiogenesis and metastasis of human HCC in nude mice, such effects of paclitaxel can be amplified by thalidomide.

关键词： neovascularization pathologic · carcinoma hepatocellular · thalidomide · paclitaxel

Decreased numbers of circulating endothelial progenitor cells are associated with hyperglycemia in patients with traumatic brain injury

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Neural Regeneration Research 2019年第6期14卷 984-990页

作者： Hui-Jie Wei Li Liu Fang-Lian Chen Dong Wang Liang Wang Zeng-Guang Wang Rong-Cai Jiang Jing-Fei Dong Jie-Li Chen Jian-Ning Zhang Department of Neurosurgery Tianjin Medical University General HospitalTianjin Neurological InstituteKey Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous SystemMinistry of EducationTianjin Key Laboratory of InjuriesVariations and Regeneration of Nervous System Department of Neurosurgery Peking University International Hospital Thrombosis Research Section Department of MedicineBaylor College of Medicine Department of Neurology Henry Ford Health System

Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their function.However, the relationship between blood glucose levels and endothelial progenitor cells in peripheral blood of patients with traumatic brain injury is unclear. In this study, 101 traumatic brain injury patients admitted to the Department of Neurosurgery, Tianjin Medical University General Hospital or the Department of Neurosurgery, Tianjin Huanhu Hospital, China, were enrolled from April 2005 to March 2007. The number of circulating endothelial progenitor cells and blood glucose levels were measured at 1, 4, 7, 14 and 21 days after traumatic brain injury by flow cytometry and automatic biochemical analysis, respectively. The number of circulating endothelial progenitor cells and blood sugar levels in 37 healthy control subjects were also examined. Compared with controls, the number of circulating endothelial progenitor cells in traumatic brain injury patients was decreased at 1 day after injury, and then increased at 4 days after injury,and reached a peak at 7 days after injury. Compared with controls, blood glucose levels in traumatic brain injury patients peaked at 1 day and then decreased until 7 days and then remained stable. At 1, 4, and 7 days after injury, the number of circulating endothelial progenitor cells was negatively correlated with blood sugar levels(r =-0.147, P < 0.05). Our results verify that hyperglycemia in patients with traumatic brain injury is associated with decreased numbers of circulating endothelial progenitor cells. This study was approved by the Ethical Committee of Tianjin Medical University General Hospital, China(approval No. 200501) in January 2015.

关键词： nerve regeneration endothelial progenitor cells vascular repair vascular remodeling angiogenesis neovascularization blood glucose hyperglycemia traumatic brain injury mobilization suppression senescence alternative therapy brain damage neural regeneration

Transplantation of autologous adipose-derived stem cells ameliorates cardiac function in rabbits with myocardial infarction

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Chinese Medical Journal 2007年第4期120卷 300-307页

作者： ZHANG Duan-zhen GAI Lu-yue LIU Hong-wei JIN Qin-hua HUANG Jian-hua ZHU Xian-yang Department of Cardiology General Hospital of Shenyang MilitaryRegion Shenyang 110016 China Department of Cardiology Chinese PLA General Hospital Beijing 100853 China. Department of Basic Medical Research Chinese PLA ~eneral Hospital Beijing 100853 China.

Background Adipose-derived stem cells （ADSCs） are capable of differentiating into cardiomyogenic and endothelial cells in vitro. We tested the hypothesis that transplantation of ADSCs into myocardial scar may regenerate infracted myocardium and restore cardiac function. Methods ADSCs were isolated from the fatty tissue of New Zealand white rabbits and cultured in Iscove＇s modified dulbecco＇s medium. Three weeks after ligation of left anterior descending coronary artery of rabbits, either a graft of untreated ADSCs （UASCs, n=14）, 5-azacytidine-pretreated ADSCs （AASCs, n=13）, or phosphate buffer saline （n=13） were injected into the infarct region. Transmural scar size, cardiac function, and immunohistochemistry were performed 5 weeks after cell transplantation. Results ADSCs in culture demonstrated a fibroblast-like appearance and expressed CD29, CD44 and CD105. Five weeks after cell transplantation, transmural scar size in AASC-implanted hearts was smaller than that of the other hearts. Many ADSCs were differentiated into cardiomyocytes. The AASCs in the prescar appeared more myotube-like. AASCs in the middle of the scar and UASCs, in contrast, were poorly differentiated. Some ADSCs were differentiated into endothelial cells and participate in vessel-like structures formation. All the ADSC-implanted hearts had a greater capillary density in the infarct region than did the control hearts. Statistical analyses revealed significant improvement in left ventricular ejection fraction, myocardial performance index, end-diastolic pressure, and peak ＋dP/dt, in two groups of ADSC-implanted hearts relative to the control hearts. AASC-implanted hearts had higher peak -dP/dt values than did control, higher ejection fraction and peak ＋dP/dt values than did UASC-implanted hearts. Conclusions ADSCs transplanted into the myocardial scar tissue formed cardiac islands and vessel-like structures, induced angiogenesis and improved cardiac function. 5-Azacytidine pretreatment before implantation is desirable for augmenting myogen

关键词： adipose stem cells transplantation myocardial infarction neovascularization

Molecular mechanism of limbs＇ postischemic revascularization improved by perindopril in diabetic rats

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Chinese Medical Journal 2008年第21期121卷 2129-2133页

作者： GAO Lu YU De-min Key Lab of Hormones and Development Ministry of Health Hospital of Metabolic Diseases Tianjin Medical University Tianjin 300070 China

Background Currently, there are still divergent opinions about the mechanisms of the impaired neovascularization in diabetic subjects. Due to the remarkable therapeutic effect of angiotensin-converting enzyme inhibititors （ACEIs） on the reduction of blood pressure and the protection of target organs, the clinical application of this kind of drugs is very widespread. However, it is still not clear about the role and related molecular pathway of this kind of drugs in the limbs＇ postischemic revascularization. It is of major therapeutic importance to resolve these questions. This study aimed to investigate the reasons of the impaired angiogenesis in the hind limbs of rats with diabetic ischemia, the role and related molecular mechanisms of ACEI in postischemic revascularization. Methods Hind limbs ischemia was induced in diabetic rats by right femoral artery excision. Diabetic rats were randomly allocated to one of the following treatments for 4 weeks： ACEI by perindopril; perindopril in combination with a nitric oxide synthase （NOS） inhibitor; perindopril in combination with bradykinin （BK）-B1 receptor （BIR） antagonist or saline. The differences of angiogenesis, the mRNA and protein expression of endothelial nitric oxide synthase （eNOS）, vascular endothelial growth factor （VEGF） and basic fibroblast （bFGF）, constitutive nitric oxide synthase （cNOS） activity and nitric oxide （NO） content were observed after treatment. Results In non-ischemic hind limbs, no significant changes in capillary density, or the mRNA and protein expression of eNOS, VEGF and bFGF, or the NO content and the cNOS activity were observed among all groups. On the contrary, in ischemic hind limbs, the capillary density in diabetic rats decreased by 27% when compared with the control rats, so did the mRNA and protein expression of eNOS, VEGF and bFGF, or the NO content and the cNOS activity （P 〈0.05）. The capillary density was increased by 1.65-fold in the perindopril treatment group in reference to untreared diabetic rats. Moreover, administra

关键词： angiotensin-converting enzyme inhibitor limb ischemia diabetes mellitus neovascularization

Relationship between intravascular ultrasound imaging features of coronary plaques and soluble CD105 level in patients with coronary heart disease

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Chinese Medical Journal 2007年第7期120卷 595-597页

作者： CUI Song LUe Shu-zheng CHEN Yun-dai HE Guo-xiang LIU Jian-ping SONG Zhi-yuan SHU Mao-qin HU Hou-yuan RAN Bo-li JING Tao Department of Cardiology Anzhen Hospital Affiliated to Capital Medical University Beijing 100029 China Department of Cardiology Southwest Hospital Third Military University Chongqing 400038 China

Plaque rupture with subsequent thrombus formation is the common pathophysiological substrate of acute coronary syndrome （ACS）. Moreno et al reported mat neovascularization as manifested by the localized appearance of microvessels is increased in ruptured plaques in the human aorta. Microvessel density is also increased in inflammatory lesions, with intraplaque hemorrhage and in thin-cap fibroatheromas. Microvessels at the base of the plaque are independently correlated with plaque rupture, suggesting a contributory role for neovascularization in the process of plaque rupture. Soluble CD105, a sensitive serum marker of neovascularization, is thought to be associated with cardiovascular disease. The purpose of this study was to assess the relationship between the level of soluble CD105 and the morphological plaques by intravascular ultrasound （IVUS） in patients with stable angina （SA） and those with unstable angina （UA） and whether soluble CD105 may serve as a non-invasive marker of coronary plaque destabilization.

关键词： intravascular ultrasound soluble CD105 neovascularization angina pectoris

Expression of Total Vascular Endothelial Growth Factor and the Anti-angiogenic VEGF165b Isoform in the Vitreous of Patients with Retinopathy of Prematurity

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Chinese Medical Journal 2015年第18期128卷 2505-2509页

作者： Min Zhao Department of Ophthalmology Peking University People's Hospital Beijing 100044 China Key Laboratory of Vision Loss and Restoration Ministry of Education Beijing 100044 China Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases Beijing 100044 China

Background： This study was to examine the expression of total vascular endothelial growth factor （VEGF） and the anti-angiogenic VEGF165b isoform in the vitreous body ofretinopathy of prematurity （ROP） patients, and to further study the role of the VEGF splicing in the development of ROP. Methods： This was a prospective clinical laboratory investigation study. All patients enrolled received standard ophthalmic examination with stage 4 ROP that required vitrectomy to collect the vitreous samples. The control samples were from congenital cataract patients. The expression of total VEGF and the anti-angiogenic VEGF165b were measured by enzyme-linked immunosorbent assay. Results were analyzed statistically using nonparametric tests. Results： The total VEGF level was markedly elevated in ROP samples while VEGF165b was markedly decreased compared to control group. The relative protein expression level ofVEGF165b isoform was significantly decreased in ROP patients which were correlated with the ischemia-induced neovascularization. Conclusions： There was a switch of VEGF splicing from anti-angiogenic to pro-angiogenic family in ROP patients. A specific inhibitor that more selectively targets VEGF165 and controls the VEGF splicing between pro- and anti-angiogenic families might be a more effective therapy for ROP.

关键词： neovascularization Retinopathy of Prematurity Vascular Endothelial Growth Factor VEGFxxx VEGFxxxb

Vascular surgery and diabetic foot revascularization

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Chinese Medical Journal 2010年第15期123卷 2116-2119页

作者： GU Yong-quan Vascular Surgery Department Xuan Wu Hospital Institute of Vascular Surgery Capital Medical University Beijing 100053 China

Patients with diabetes mellitus have an increased incidence of atherosclerotic vascular disease and infection involving the lower extremities.Lower limb arterial disease is more common among patients with diabetes, and lower limb atherosclerosis is the main cause of lower limb ischemia for these patients.Two types of vascular disease are seen in patients with diabetes.

关键词： diabetic foot revascularization arterial bypass intervention neovascularization

Relationship among soluble CD105, hypersensitive C-reactive protein and coronary plaque morphology： an intravascular ultrasound study

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Chinese Medical Journal 2008年第2期121卷 128-132页

作者： CUI Song Lü Shu-zheng CHEN Yun-dai HE Guo-xiang MENG Li-jun LIU Jian-ping SONG Zhi-yuan LIU Xian-liang SONG Xian-tao GE Chang-jiang LIU Hong Department of Cardiology Anzhen Hospital Affiliated to Capital Medical University Beijing 100029 China Department of Cardiology Southwest Hospital Third Military Medical University Chongqing 400038 China Department of Cardiology Binzhou Central Hospital Binzhou Shandong 251700 China

Background Rupture of unstable plaque with subsequent thrombus formation is the common pathophysiological substrate of acute coronary syndrome （ACS）. It is of potential significance to explore the blood indexes predicting plaque characteristics. We investigated the relationship among soluble CD105, hypersensitive C-reactive protein （hs-CRP）, and coronary plaque morphology.Methods A clinical study from April 2004 to December 2006 was conducted in 130 patients who were divided into 3 groups： 56 patients （43.1%） in stable angina （SA） group, 52 patients （40.0%） in unstable angina （UA） group and 22 patients （16.9%） in acute myocardial infarction group. The concentrations of soluble CD105 and hs-CRP were measured in all of the patients by cardioangiography （CAG）. Plasma samples of arterial blood were collected prior to the procedure. The levels of soluble CD105 and hs-CRP were measured by enzyme-linked immunosorbent assay （ELISA）.Results Unstable and ruptured plaque was found more frequently in patients with acute myocardial infarction and UA. External elastic membrane cross-sectional area （EEM CSA）, plaque area, lipid pool area and plaque burden were significantly larger in the ruptured and unstable plaque group. Positive remodeling, thinner fabric-cap, smaller minimal lumen cross-sectional area （MLA）, dissection and thrombus were significantly more frequent in the ruptured and unstable plaque group. Remodeling index （RI） was positively correlated with the levels of soluble CD105 in the UA group （r=0.628, P〈0.01） and the acute myocardial infarction group （r=0.639, P〈0.01）. The levels of soluble CD105 and hs-CRP were higher in the ruptured plaque group. Soluble CD105 〉4.3 ng/ml was used to predict ruptured plaque with a receiver operating characteristic （ROC） curve area of 0.77 （95% confidence interval （CI）, 66.8%-87.2%）, a sensitivity of 72.8%, a specificity of 78.0% and an accuracy of 70.2% （P〈0.01）, similarly for hs-CRP 〉 5.0 mg/ml with a ROC curve area of 0.70 （95% CI, 59.2%-80.2%）, a sensitivity of 70.2%, a sp

关键词： intravascular ultrasound soluble CD105 neovascularization hypersensitive C-reactive protein

Endothelial progenitor cells as factors in neovascularization and endothelial repair

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World Journal of Cardiology 2010年第12期2卷 411-420页

作者： Stefano Capobianco Venu Chennamaneni Mayank Mittal Department of Cardiology Gaetano Rummo Hospital Department of Internal Medicine University of Missouri-Columbia

Endothelial progenitor cells(EPCs)are a heterogeneous population of cells that are provided by the bone marrow and other adult tissue in both animals and humans.They express both hematopoietic and endothelial surface markers,which challenge the classic dogma that the presumed differentiation of cells into angioblasts and subsequent endothelial and vascular differentiation occurred exclusively in embryonic development.This breakthrough stimulated research to understand the mechanism(s)underlying their physiologic function to allow development of new therapeutic options.One focus has been on their ability to form new vessels in injured tissues,and another has been on their ability to repair endothelial damage and restore both monolayer integrity and endothelial function in denuded vessels.Moreover,measures of their density have been shown to be a better predictor of cardiovascular events,both in healthy and coronary artery disease populations than the classical tools used in the clinic to evaluate the risk stratification.In the present paper we review the effects of EPCs on revascularization and endothelial repair in animal models and human studies,in an attempt to better understand their function,which may lead to potential advancement in clinical management.

关键词： Atherosclerosis Bone marrow Endothelial dysfunction Endothelial progenitor cells neovascularization Stem cells