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BACKGROUND: Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula, which has been reported to exert effective protection against cardiovascular diseases, including hypertension and myocarditis. METHODS: Cultured human umbilical vascular endothelial cells (HUVECs) were treated with angiotensin II (Ang II) and different concentrations of aqueous layer extracts (AqE). Subsequently nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) expression levels were detected. In addition, fifty Kunming mice were randomized into control, Nω-nitro-L-arginine methyl ester (L-NAME), L-NAME+AqE, L-NAME+XJEK and L-NAME+fosinopril treatment groups. Following 8 weeks of treatment, the cardiac hemodynamic index was measured, relaxation of the aorta was examined and pathological changes were observed. Colorimetric analysis and enzyme linked immunosorbent assay (ELISA) were applied to determine the relevant indicators in plasma and cardiac tissues. RESULTS: The in vitro study results demonstrated that AqE could preserve endothelial function (NO, 21.05 ± 2.03 vs. 8.64 ± 0.59; eNOS, 1.08 ± 0.17 vs.0.73 ± 0.06). In addition, the in vivo results demonstrated that compared with the control group, treatment with AqE could enhance a high hemodynamic state (left ventricular systolic pressure, 116.76 ± 9.96 vs.114.5 ± 15.16), improve endothelial function (NO, 7.98 ± 9.64 vs. 1.66 ± 3.11; eNOS, 19.78 ± 3.18 vs.19.38 ± 3.85), suppress oxidative stress (OS) (superoxide dismutase, 178.17 ± 13.78 vs. 159.38 ± 18.86; malondialdehyde, 0.77 ± 0.13 vs.1.25 ± 0.36) and reverse cardiovascular remodeling. CONCLUSION: Polysaccharide from XJEK exerts protective effects against Ang II-induced injury in HUVECs and L-NAME-induced hypertension in mice and the underlying mechanism may be attributed to improving endothelial dysfunction, OS and the inflammation status in mice.
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Medicamentos Herbarios Chinos/uso terapéutico , Células Endoteliales/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Remodelación Vascular/efectos de los fármacos , Angiotensina II , Animales , Aorta/efectos de los fármacos , Arginina/análogos & derivados , Arginina/sangre , Presión Sanguínea/efectos de los fármacos , Citocinas/metabolismo , Evaluación Preclínica de Medicamentos , Medicamentos Herbarios Chinos/farmacología , Células Endoteliales/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Hipertensión/inducido químicamente , Inflamación/tratamiento farmacológico , Masculino , Malondialdehído/sangre , Ratones , Miocardio/metabolismo , NG-Nitroarginina Metil Éster , Óxido Nítrico/sangre , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Superóxido Dismutasa/sangreRESUMEN
An ideal positron emission tomography (PET) tracer should be highly extractable by the tumor tissue or organ that contains low toxicity and can provide high-resolution images in vivo. In this work, the aim was to evaluate the application of Al18 F-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid containing sulfonamide group (18 F-Al-NOTA-SN) as a potential tumor-targeting signal-enhanced radioactive tracer in PET. SN as a tumor-targeting group was incorporated to NOTA to make a ligand. Subsequently, this ligand reacted with Na18 F and AlCl3 to produce a compound 18 F-Al-NOTA-SN. This compound was further characterized and its property in regard to cell cytotoxicity assay, microPET imaging, biodistribution, cell uptake assay, and tumor selectivity in vitro and in vivo, was also investigated. 18 F-Al-NOTA-SN possessed low cell cytotoxicity and uptake to COS-7 and 293T healthy cells and high cell cytotoxicity and uptake to MDA-MB-231, HepG2, and HeLa tumor cells in vitro. Moreover, 18 F-Al-NOTA-SN showed good tumor-targeting property and high PET signal enhancement of HeLa tumors, liver, and kidneys in mice, as well as the uptake ratios of tumor to blood and tumor to muscle, were 4.98 and 3.87, respectively. 18 F-Al-NOTA-SN can be accepted to be kidney and liver eliminated earlier and show a potential tumor-targeting signal-enhanced radioactive tracer in PET.
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Radioisótopos de Galio/química , Compuestos Heterocíclicos con 1 Anillo/farmacología , Tomografía de Emisión de Positrones/métodos , Sulfonamidas/química , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/tratamiento farmacológico , Animales , Células COS , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Femenino , Células HEK293 , Células HeLa , Células Hep G2 , Compuestos Heterocíclicos con 1 Anillo/síntesis química , Compuestos Heterocíclicos con 1 Anillo/farmacocinética , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Distribución Tisular , Neoplasias Uterinas/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Right heart catheterization is commonly used to measure right ventricle hemodynamic parameters and is the gold standard for pulmonary arterial hypertension diagnosis; however, it is not suitable for patients' long-term follow-up. Non-invasive echocardiography and nuclear medicine have been applied to measure right ventricle anatomy and function, but the guidelines for the usefulness of clinical parameters remain to be established. The goal of this study is to identify reliable clinical parameters of right ventricle function in pulmonary arterial hypertension patients and analyze the relationship of these clinical parameters with the disease severity of pulmonary arterial hypertension. In this study, 23 normal subjects and 23 pulmonary arterial hypertension patients were recruited from January 2015 to March 2016. Pulmonary arterial hypertension patients were classified into moderate and severe pulmonary arterial hypertension groups according to their mean pulmonary arterial pressure levels. All the subjects were subjected to physical examination, chest X-ray, 12-lead electrocardiogram, right heart catheterization, two-dimensional echocardiography, and technetium 99m (99mTc) myocardial perfusion imaging. Compared to normal subjects, the right heart catheterization indexes including right ventricle systolic pressure, right ventricle end diastolic pressure, pulmonary artery systolic pressure, pulmonary artery diastolic pressure, pulmonary vascular resistance, and right ventricle end systolic pressure increased in pulmonary arterial hypertension patients and were correlated with mean pulmonary arterial pressure levels. Echocardiography parameters, including tricuspid regurgitation peak velocity, tricuspid regurgitation pressure gradient, tricuspid annular plane systolic excursion and fractional area, right ventricle-myocardial performance index, were significantly associated with the mean pulmonary arterial pressure levels in pulmonary arterial hypertension patients. Furthermore, myocardial perfusion imaging was not observed in the normal subjects but in pulmonary arterial hypertension patients, especially severe pulmonary arterial hypertension subgroup, and showed potential diagnostic properties for pulmonary arterial hypertension. In conclusion, mean pulmonary arterial pressure levels are correlated with several right heart catheterization and echocardiography markers in pulmonary arterial hypertension patients; echocardiography and 99mTc myocardial perfusion can be used to evaluate right ventricle performance in pulmonary arterial hypertension patients. Impact statement In this study, we analyzed the clinical parameters for evaluating RV function, including right ventricle catheterization (RHC), echocardiography, and technetium 99m (99mTc) myocardial perfusion imaging (MPI) in normal Asian subjects and PAH patients ( n = 23 for each group). Our results demonstrated that six RHC indexes, four echocardiography indexes and MPI index were significantly altered in PAH patients and correlated with the levels of mean pulmonary arterial pressure. Importantly, we evaluated the diagnostic performance of MPI and found that MPI has a strong diagnostic accuracy in PAH patients. The findings from this study will be of interest to clinical investigators who make diagnosis and therapeutic strategies for PAH patients.
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Presión Sanguínea , Electrocardiografía , Ventrículos Cardíacos/fisiopatología , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/fisiopatología , Imagen de Perfusión Miocárdica , Función Ventricular Derecha , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tecnecio/administración & dosificaciónRESUMEN
BACKGROUND: Xin-Ji-Er-Kang (XJEK) shows protective effects on the myocardial ischemic diseases in our previous reports. We hypothesized that XJEK may exert preventing effects on L-NAME induced hypertensive mice by ameliorating oxidative stress (OS) and endothelial dysfunction (ED). METHODS: After treatment with XJEK for four weeks, cardiac function and cardiovascular pathology changes were evaluated. Then, endothelial-dependent vascular relaxation and serum NO, eNOS, AMDA, SOD, MDA content, and cardiac tissue eNOS expression were detected. RESULTS: The hypertensive mice displayed distinct cardiovascular remodeling including increased HW/BW index (4.7 ± 0.33 versus 5.2 ± 0.34), cross-section area, and collagen deposition. In addition, ED was found manifested by decreased serum NO (20.54 ± 8.05 versus 6.29 ± 2.33), eNOS (28.34 ± 2.36 versus 20.37 ± 2.30), content, and decreased eNOS expression in cardiac tissue and damaged endothelium-dependent diastolic function. Moreover, OS was detected confirmed by decreased SOD activity and increased MDA content in serum. However, treatment with XJEK for 4 wk could reverse cardiovascular remodeling (HW/BW index normalized from 5.2 ± 0.34 to 4.59 ± 0.25), ameliorate and preserve endothelial function (NO: 16.67 ± 7.24 versus 6.29 ± 2.33; eNOS: 16.67 ± 7.24 versus 6.29 ± 2.33), and suppress OS. CONCLUSION: XJEK has protective effects against cardiovascular remodeling in L-NAME induced hypertensive mice.
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BACKGROUND: Myocardial infarction (MI) is a major risk factor responsible for morbidity and mortality. Xinji'erkang (XJEK) has been clinically used as an effective medication in the treatment of coronary heart disease and myocarditis. The purpose of this study was to investigate the cardioprotective effect of Xinji'erkang on MI mice. METHODS: Forty male mice were randomly assigned into four groups as follows (n = 10): sham, model, MI with administration of XJEK and fosinopril for four weeks. At the end of studies, hemodynamic parameters and electrocardiography (ECG) were recorded. Heart and body mass were measured and heart weight/body weight (HW/BW) ratio was calculated as index of hypertrophy. The hypertrophy of heart and aorta was examined using the hematoxylin and eosin (HE) staining, and the collagen deposition was evaluated using Van Gieson (VG) staining. Serum nitric oxide level (NO), superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration were assayed by colorimetric analysis. The expressions of endothelial NO synthetase (eNOS) expression in serum and cardiac tissues were determined using ELISA assay and immunohistochemistry. Angiotensin II (Ang II) in serum and cardiac tissues was measured using ELISA assay. Besides, tumor necrosis factor-α (TNF-α), interleukin1ß (IL-1ß) and interleukin10 (IL-10) were observed in cardiac tissues with ELISA assay as well. RESULTS: The administration of XJEK significantly improved cardiac dysfunction and abnormal ECG with reduced HW/BW ratio and ameliorated cardiomyocyte hypertrophy and collagen deposition compared to MI, which was partly due to the decreased SOD and increased MDA in serum. Moreover, XJEK treatment also improved endothelial dysfunction (ED) with not only enhanced eNOS activities in serum and cardiac tissues and elevated NO levels in serum, but also decreased Ang II content in serum and cardiac tissues. Finally, protein expressions of pro-inflammation cytokines, TNF-α and IL-1ß in the cardiac tissues with XJEK treatment were significantly decreased compared to model. On the contrary, IL-10, an anti-inflammatory cytokine concentrated in cardiac tissues was significantly enhanced compared to model. CONCLUSION: Xinji'erkang exerts cardioprotective effect on myocardial infarction in mice, which may be due to the improvement of endothelial dysfunction and the reduction of oxidative stress and inflammation response.
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Medicamentos Herbarios Chinos/administración & dosificación , Infarto del Miocardio/prevención & control , Animales , Corazón/efectos de los fármacos , Lesiones Cardíacas/complicaciones , Humanos , Interleucina-10/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , Infarto del Miocardio/etiología , Infarto del Miocardio/metabolismo , Miocardio/metabolismo , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacosRESUMEN
Increased uptake of Tc-99m-methylene diphosphonate in the area of jaw is a common finding on the whole body bone scan. To study its incidence, causes and clinical significance, we performed static anterior and bilateral head views on 52 consecutive patients, followed by a dental examination and a panoramic radiograph. We demonstrated that increased uptake of bone tracer in the area of jaw was observed at a high incidence, as well as its characteristic distribution. The mainly causes are some common dental diseases. These findings would better guide the diagnosis and treatment for patients.
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Maxilares/efectos de los fármacos , Radiofármacos , Medronato de Tecnecio Tc 99m , Imagen de Cuerpo Entero , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: This study aims at evaluating the safety and efficacy of a porous stent system consisting of multiple overlapping uncovered stents in the treatment of complex aortic aneurysms with vital branches. METHODS: Data of all patients with aortic aneurysms treated in our center with multiple overlapping uncovered stents between February 2010 and December 2011 were retrospectively reviewed. Preoperative characteristics, intraoperative details, and follow-up outcomes were documented. Technical success was defined as successful deployment of the stents to target locations without procedure-related complications. Clinical success was characterized by complete shrinkage or stabilization of the aneurysm, preservation of vital branches, and absence of major complications. Patients were grouped, according to rapidity of aneurysm thrombosis, into fast-thrombosis group (complete thrombosis of aneurysmal sac was achieved in ≤6 months) and a delayed-thrombosis group (>6 months required for complete thrombosis). Possible factors affecting the speed of thrombosis were analyzed statistically with the Fisher exact test and the t-test. RESULTS: This porous stent system was used to treat 34 patients (23 men, 11 women; mean age, 65.7 years). Technical success was achieved in all patients (100%). Regular follow-up over 6 months was achieved in 29 patients (mean length of follow-up, 11.4 months). Complete thrombosis of the aneurysm sac within 12 months was observed in 24 patients (83%). Aneurysm shrinkage was documented in seven patients (24%) and stabilization in 21 (72%). All branch arteries covered by bare stents stayed patent during follow-up. The overall clinical success rate reached 97% in the follow-up group. Risk factors for delayed thrombosis included fewer stents implanted (P = .013), longer sac entrance (P = .043), and use of antiplatelet medication (P = .040). CONCLUSIONS: An alternative method of management of complicated aortic aneurysm appears to be feasible using overlapping bare stents, which may prevent aneurysm growth while preserving vital branches. The short-term outcome of our study seems encouraging but is not sufficient to draw a robust conclusion. Further hemodynamic and clinical studies are warranted to evaluate long-term efficacy.
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Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/instrumentación , Procedimientos Endovasculares/instrumentación , Stents , Anciano , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/fisiopatología , Aortografía/métodos , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Femenino , Hemodinámica , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Porosidad , Valor Predictivo de las Pruebas , Diseño de Prótesis , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To review the recent progress of multilayer stents in treating arterial aneurysms and to draw an initial conclusion about its paradigm. DATA SOURCES: PubMed database and ELSEVIER database were searched with the keywords "cardiatis" or "multilayer stent" for relevant articles from January 2008 to September 2012. Relevant websites (provided by Cardiatis) were also involved in the review process. STUDY SELECTION: Well-controlled, relatively large-scale, retrospective studies as well as meaningful individual cases were all selected as materials. RESULTS: A total of 23 articles were involved in this review. The newly introduced Cardiatis multilayer stent aims at creating an active flow-modulating barrier between normal blood flow and aneurismal sac, which can induce thrombosis within aneurismal sac and preserve collateral circulation at the same time. Currently, it has been applied for complicated aneurysms located in different segments of the arterial system. CONCLUSION: This new concept of multilayer uncovered stent offers a promising alterative in the treatment of arterial aneurysms. However, a further large-scale clinical and hemodynamic study is required to evaluate the long-term effects.
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Aneurisma/terapia , Stents , Aneurisma/fisiopatología , Bases de Datos Factuales , Hemodinámica/fisiología , Humanos , Estudios RetrospectivosRESUMEN
PURPOSE: To describe a new technique that combines traditional stent graft and multiple overlapping uncovered stents to form a sandwich-like structure in the management of a wide-necked saccular suprarenal aneurysm. CASE REPORT: An 83-year-old woman was admitted to the hospital with a large symptomatic aortic aneurysm that involved celiac trunk. Traditional stent graft and coiling were precluded due to the anatomical complexity of the aneurysm. A novel combination of multiple overlapping stents and grafted stents was utilized in this patient in order to maximally reduce the blood flow into the sac and to preserve visceral branches. At 3-month follow-up, patent celiac artery and superior mesenteric artery along with complete shrinkage of aneurismal sac were documented. CONCLUSION: The combination of grafted stents and uncovered stents can effectively reduce velocity and volume of blood flow into the aneurismal sac, which induces thrombosis within the sac, while all the branches could be preserved.
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Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/métodos , Arteria Celíaca , Procedimientos Endovasculares/métodos , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/fisiopatología , Aortografía/métodos , Prótesis Vascular , Implantación de Prótesis Vascular/instrumentación , Arteria Celíaca/diagnóstico por imagen , Arteria Celíaca/fisiopatología , Procedimientos Endovasculares/instrumentación , Femenino , Humanos , Stents , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
We report a highly enantioselective Morita-Baylis-Hillman (MBH) reaction of isatins and acrolein to provide enantiomerically enriched 3-substituted 3-hydroxyoxindoles, which could serve as valuable synthetic building blocks. This is also the first time that a ketone has been used as the electrophile and acrolein as the nucleophile in a highly enantioselective catalytic asymmetric MBH reaction. Hatakeyama's catalyst, ß-isocupreidine (1), turned out to be a powerful catalyst for this transformation.
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OBJECTIVE: To investigate the infective efficiency of Ad5/EGFP versus AdF35/EGFP to rat bone marrow mesenchymal stem cells (rBMSC) and understand its mechanism. METHODS: rBMSC were isolated from rat bone marrow by density gradient method. The expressions of CD90, CD29, CD44, CD34, CD11b and CD45 on the surface of rBMSC were measured by flow cytometry. The EGFP-carrying Ad5 and AdF35 were infected into rBMSC respectively. The effect of Ad5/EGFP and AdF35/EGFP with different MOIs to rBMSC was tested by MTT. Infected rBMSC were observed by fluorescence microscopy. The infective efficiency and mean fluorescence intensity were determined by flow cytometry after a cellular infection for 1 - 9 days. The expressions of CAR and CD46 on rBMSC were measured by real-time PCR. RESULTS: The expressions of CD90, CD29 and CD44 on rBMSC were positive while those of CD34, CD11b and CD45 were negative. When MOI
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Adenoviridae/genética , Células de la Médula Ósea , Células Madre Hematopoyéticas , Receptores Virales/genética , Transfección , Animales , Línea Celular , Citometría de Flujo , Vectores Genéticos , Ratas , Ratas Sprague-Dawley , Transducción GenéticaRESUMEN
OBJECTIVE: To explore the mechanism of ginsenoside Rh2 in reversing the resistance of lung adenocarcinoma cells to cisplatin. METHODS: In the Rh2, DDP and DDP + Rh2 group A549DDP cells were treated with Rh2, cisplatin, cisplatin + Rh2 respectively for 48 hours. In the control group the A549DDP cells were not treated with any kind of drugs. The state of mitochondrial permeability transition pore (PTP) was evaluated by ultra violate spectrofluorometer. Concentration of calcium in cells, membrane potential of mitochondrion and apoptosis cells were determined by flow cytometry. The expression of cyt-c and Caspase-3 was estimated by Western blots. Cellular shapes were observed by fluorescent microscopy. RESULTS: The concentrations of calcium were similar among the former three groups, but was obviously increased in the Rh2 + DDP group (t = 22.47, P < 0.01). A(540) of mitochondrion among the former three groups were not different, but decreased significantly in the Rh2 + DDP group (t = 8.21, P < 0.01). The membrane potentials of mitochondrion showed no difference in the former groups, that was remarkably lower in the Rh2 + DDP group than in the control group (chi(2) = 46.01, P < 0.01). There was little expression of cty-c and Caspase-3 in the former groups, but high expression of those in the Rh2 + DDP group. Fluorescence was distributed equally on the cells nucleus in the former groups. In the Rh2 + DDP group many cell nucleus shrank or were distorted. The apoptosis rate of the cells was 6.32%, 7.24%, 7.41% and 21.96% in the four groups respectively. Which in Rh2 + DDP group was higher than that in the control group (t = 10.92, P < 0.05). CONCLUSIONS: The effect of ginsenoside Rh2 reversing resistance of lung adenocarcinoma A549DDP cells to cisplatin can be performed by apoptotic mitochondria pathway.
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Adenocarcinoma/tratamiento farmacológico , Cisplatino/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Ginsenósidos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Calcio/análisis , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Potencial de la Membrana MitocondrialRESUMEN
OBJECTIVE: To explore the feasibility of single photon emission computed tomography (SPECT) detection of heart reporter gene expression and observed the optimal transfecting titer and imaging time by using herpes simplex virus 1-thymidine kinase (HSV1-tk) as reporter gene and 131I-2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil (131I-FIAU) as reporter probe in rabbit myocardium. METHODS: The recombinant Ad-tk carrying HSV1-tk gene and adenovirus (Ad) as vector was constructed and intramyocardially injected to rabbits at various concentrations (1 x 10(9) pfu, 5 x 10(8) pfu, 1 x 10(8) pfu, 5 x 10(7) pfu, 1 x 10(7) pfu). Two days later, rabbits were injected with 600 microCi 131I-FIAU in ear-margin vein and then underwent SPECT myocardium imaging for detection of HSV1-tk expression at 6 h, 24 h, 48 h and 72 h after injection, rabbits with 1 x 10(9) pfu Ad-tk injection were imaged at 96 h and 120 h. Rabbits were sacrificed after imaging and the total myocardial 131I-FIAU accumulation was quantified in percent of injected dose per gram myocardium (% ID/g). The myocardial Ad-tk expression was determined with RT-PCR. RESULTS: Reporter gene was detected by SPECT imaging in the injection site while not detected in the control myocardium and site remote from injection. RT-PCR results also evidenced HSV1-tk express in the injection site. The SPECT target/nontarget ratio was correlated with ex vivo gamma-counting (r2 = 0.933, P<0.01) and expression of HSV1-tk (r2 = 0.877, P<0.01). Myocardial accumulation could be identified at viral titers as low as 1 x 10(7) pfu by SPECT imaging. CONCLUSION: The cardiac SPECT reporter gene imaging with HSV1-tk as reporter gene and 131I-FIAU as reporter probe is feasible.
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Genes Reporteros , Corazón/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Animales , Femenino , Expresión Génica , Técnicas de Transferencia de Gen , Masculino , Miocardio/metabolismo , Conejos , Timidina Quinasa/genética , Transfección , Uracilo/análogos & derivadosRESUMEN
AIM: Somatostatin receptor subtype 2 (SSTR2) is the principal mediator of somatostatin's (SST) antiproliferative effects on normal and cancer cells. Therefore, we investigated whether the enhanced expression of SSTR2 could inhibit the proliferation of tumor cells, and, if so, the mechanisms that might be involved. METHODS: SSTR2 expression levels were determined by qRT-PCR in several tumor cell lines. Then, a plasmid pIRES2-EGFP-SSTR2 (pSIG) was constructed and stably transfected into MCF-7 cells (MCF-7/pSIG). After SSTR2 overexpression was identified by qRT-PCR, immunofluorescence staining and a receptor binding assay, the MCF-7/pSIG cells were analyzed by PI staining for apoptosis and cell cycle arrest was tested by flow cytometry for epidermal growth factor receptor (EGFR) expression. The EGF-stimulated proliferation of MCF-7 cells was assayed by MTT. RESULTS: The human breast cancer cell line MCF-7 expresses a lower level of SSTR2, thereby partly accounting for the decreased response to SST. The overexpression of SSTR2 in MCF-7 cells resulted in apoptosis, cytostasis and G(1)/S cell cycle arrest. Furthermore, the expression of EGFR, together with EGF-stimulated proliferation, was markedly decreased in the MCF-7/pSIG cells. CONCLUSION: Enhanced SSTR2 expression played an antiproliferative role in MCF-7 cells through inducing apoptosis and G(1)/S cell cycle arrest, and also by decreasing EGFR expression, thereby counteracting the growth-stimulating effect of EGF. Our data seem to indicate that developing a new therapeutic agent capable of upregulating SSTR expression could potentially be a way to block tumor progression.Acta Pharmacologica Sinica (2009) 30: 1053-1059; doi: 10.1038/aps.2009.59.
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Antineoplásicos/metabolismo , Neoplasias de la Mama/metabolismo , Proliferación Celular , Receptores de Somatostatina/metabolismo , Apoptosis/fisiología , Ciclo Celular/fisiología , Línea Celular Tumoral , Receptores ErbB/metabolismo , Femenino , Humanos , ARN Mensajero/metabolismo , Receptores de Somatostatina/genéticaRESUMEN
OBJECTIVE: To investigate the post-operative complications of aortic endovascular grafting exclusion (EVGE) and its reasons and treatments. METHODS: Clinical data of 82 cases received aortic endovascular grafting exclusion from January 2002 to October 2008 were retrospectively analyzed. Seventy-one cases were male and 11 cases were female with the age of 33 to 78 years and the average age of 49.2 years. There were 66 cases of thoracic aortic dissecting aneurysms and 16 cases of abdominal aortic aneurysm. The effect, post-operational complications and its treatment were investigated. RESULTS: There were 90.1% patients had been followed up with the time of 3 to 78 months with technical success of 90.3%, clinical success of 94.1%, peri-operational mortality of 2.4%, total mortality of 6.1% and mortality associated with EVGE of 2.4%. Twenty-one cases underwent complications including type I endoleak (13 cases), abdominal aortoduodenal fistula (1 case), narrow true lumen (2 cases), reverse Stanford A dissection (2 cases), post EVGE syndrome (12 cases), delayed healing of inguinal incision (5 cases), constipation (3 cases), cerebral infarction (1 case). No paraplegia, left subclavian artery ischemia, contrast media associated nephrosis, ischemic colitis, ischemic neurologic injury, and artery embolism occurred. Post operation 4 cases had the second intervention including 2 type I endoleak and 2 narrow true lumen. CONCLUSIONS: The technique-related complications still hinder the long-term effect of EVGE. It needs to be further investigated on technique improvement and treatment standardization.
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Aneurisma de la Aorta/cirugía , Implantación de Prótesis Vascular/efectos adversos , Complicaciones Posoperatorias/terapia , Adulto , Anciano , Disección Aórtica/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios RetrospectivosRESUMEN
OBJECTIVE: Radionuclide imaging of reporter gene expression holds promise for noninvasive monitoring of gene therapy. Herpes simplex virus 1-thymidine kinase (HSV1-tk) has been successfully applied to the tumor tissue.We explored the feasibility of the expression imaging of HSV1-tk reporter gene in rat myocardium by using SPECT reporter probe (131)I-2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil ((131)I-FIAU) and autoradiography (ARG). METHODS: The recombinant Ad5-tk carrying HSV1-tk gene and adenovirus (Ad5-null) as vector were constructed and intramyocardially injected into SD rats. Experiment was grouped for different aims as follows: (1) Influence of time on the imaging after transfection reporter gene: rats were injected with (131)I-FIAU at day 1, 2, 3, 5 and 7 after transfection of 1 x 10(8)pfu Ad5-tk; (2) Influence of various titers on the imaging: rats underwent intramyocardial injection with various titers of Ad5-tk (5 x 10(8), 1 x 10(8), 5 x 10(7), 1 x 10(7)pfu). After 2 days, rats were injected with (131)I-FIAU in tail vein. Equal volume Ad-nulls was intramyocardially injected to control rats. Rats were killed 24 h after injection of (131)I-FIAU and the hearts were rapidly dissected for gamma counts measurement. The total myocardial (131)I-FIAU accumulation was quantified in percent of injected dose per gram myocardium (%ID/g). The myocardial reporter gene expression was semi-quantitatively determined by ARG and RT-PCR. RESULTS: ARG and RT-PCR showed that the local expression of reporter gene increased in proportion with increasing titer and decreased in proportion with time post injection. The semi-quantitative assay showed there were significant correlations among %ID/g, RT-PCR and ARG: r(2) = 0.963, P < 0.05 for RT-PCR and ARG; r(2) = 0.996, P < 0.01 for %ID/g and ARG in rats received various reporter gene titers at identical time point post injection; r(2) = 0.950, P < 0.05 for RT-PCR and ARG; r(2) = 0.980, P < 0.01 for %ID/g and ARG for rats received identical reporter gene titer on various time points post injection. CONCLUSIONS: The present study showed that cardiac reporter gene imaging with HSV1-tk as reporter gene and (131)I-FIAU as reporter probe was feasible in rats. The optimal Ad5-tk titer is 1 x 10(8) pfu and the optimal imaging time is 24 h to 48 h post gene transfer. HSV1-tk/FIAU may be used for the noninvasive monitoring of cardiac gene therapy.
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Genes Reporteros , Miocitos Cardíacos/citología , Miocitos Cardíacos/diagnóstico por imagen , Animales , Autorradiografía , Femenino , Expresión Génica , Herpesvirus Humano 1/genética , Miocitos Cardíacos/metabolismo , Ratas , Ratas Sprague-Dawley , Timidina Quinasa/genética , Tomografía Computarizada de Emisión de Fotón Único , TransfecciónRESUMEN
OBJECTIVE: To evaluate if 99mTc-HYNIC-annexin V may be used to detect the early chemotherapeutic effect and to determine the best timing for detecting apoptosis in vivo. METHODS: Annexin V was labeled with 99mTc using HYNIC as a bifunctional agent. Normal Kunming mice received inoculation of Ehrlich ascites cells into the right upper limb. After the tumor reached 1 cm in diameter, the mice were randomly divided into saline treatment group as control and cyclophosphamide (150 mg/kg injected intraperitoneally) treatment group. 99mTc-HYNIC-annexin V was injected intravenously at 1 h and 24 h after treatment. Region of interest technique (ROI) from the SPECT images taken at different time was used to get the ratio of tumor/limb in each group. TUNEL staining was used to detect apoptotic cells and the rates of positive stained cells were calculated. RESULTS: After treatment with saline, only little amount of the radiolabeled tracer could be seen in the tumor and showed weak image of the tumor. But after 24 h of treatment with cyclophosphamide, clear image on the tumor could be seen. 24 h after the treatment of cyclophosphamide, the ratio of tumor/limb was (6.27 +/- 0.24) which was much higher than that at 24 h after treatment with saline (2.36 +/- 0.18) and that at 1 h after cyclophosphamide treatment (4.00 +/- 0.38). At 24 h after cyclophosphamide treatment, TUNEL staining showed a significantly higher rate of apoptotic cells in the mice. CONCLUSION: 99mTc-HYNIC-annexin V can be used as an apoptosis-imaging agent to detect and evaluate the early curative effect after chemotherapy. The effective detection of apoptotic response in tumor with 99mTc-HYNIC-annexin V requires a 24 h interval after chemotherapy. SPECT images can be obtained at 60 min after injection of the imaging agent. It suggests that 99mTc-HYNIC-annexin V may become a promising agent for apoptosis-imaging in clinical application.
Asunto(s)
Anexina A5 , Apoptosis , Carcinoma de Ehrlich/diagnóstico por imagen , Ciclofosfamida/uso terapéutico , Compuestos de Organotecnecio , Animales , Anexina A5/farmacocinética , Antineoplásicos Alquilantes/uso terapéutico , Apoptosis/efectos de los fármacos , Carcinoma de Ehrlich/tratamiento farmacológico , Carcinoma de Ehrlich/patología , Masculino , Ratones , Trasplante de Neoplasias , Compuestos de Organotecnecio/farmacocinética , Radiofármacos/farmacocinética , Distribución Aleatoria , Distribución Tisular , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
OBJECTIVE: To assess the role of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in the management of unknown primary primary (CUP) with metastatic loci. METHODS: Thirty-four patients of CUP with metastatic loci who had undergone unsuccessful conventional diagnostic work-up underwent (18)F-FDG PET/CT. The images thus obtained were analyzed with visual and semi-quantitative methods. Histopathology, cytology, and/or follow-up were used to evaluate the PET/CT results. RESULTS: In 20 of the 34 patients (18)F-FDG PET/CT showed focal tracer accumulations corresponding to potential primary tumor sites located in the lung (n = 9), colon (n = 3), rectum (n = 2), pancreas (n = 1), right aryepiglottic wall (n = 1), esophagus (n = 1), breast (n = 1), and ovary (n = 2). The detection rate of primary tumor by (18)F-FDG PET/CT was 50.0% (17/34), the primary tumors were identified in the lung (n = 8), colon (n = 2), rectum (n = 1), pancreas (n = 1), right aryepiglottic wall (n = 1), esophagus (n = 1), ovary (n = 2), and breast (n = 1). The false positive rate was 8.8% (3/34) with the diagnosis of primary tumor in the lung (n = 1), colon (n = 1), and rectum (n = 1) to be identified as false. In 14 of the 34 patients, (18)F-FDG PET/CT did not reveal lesions suspected to be the primary tumor sites in 13 patients, and it was impossible to identify one lesion as the most likely primary tumor in one patient due to the presence of multiple hot spots in several organs. The (18)F-FDG PET/CT findings affected the medical management in 17 of the 34 (50.0%) patients due to the finding of primary sites and/or additional metastases. CONCLUSION: (18)F-FDG PET/CT has relevant impact on the therapeutic management of patients with unknown primary tumor. It is recommended that (18)F-FDG PET/CT be performed in the patient with unknown primary tumor after unsuccessful conventional diagnostic workup.