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We recently showed that lovastatin attenuates cyclosporin A (CsA)-induced damage of cortical collecting duct (CCD) principal cells by reducing intracellular cholesterol. Previous studies showed that, in cell expression models or artificial membranes, exogenous cholesterol directly inhibits inward rectifier potassium channels, including Kir1.1 (Kcnj1; the gene locus for renal outer medullary K(+) [ROMK1] channels). Therefore, we hypothesized that lovastatin might stimulate ROMK1 by reducing cholesterol in CCD cells. Western blots showed that mpkCCDc14 cells express ROMK1 channels with molecular masses that approximate the molecular masses of ROMK1 in renal tubules detected before and after treatment with DTT. Confocal microscopy showed that ROMK1 channels were not in the microvilli, where cholesterol-rich lipid rafts are located, but rather, the planar regions of the apical membrane of mpkCCDc14 cells. Furthermore, phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2], an activator of ROMK channels, was detected mainly in the microvilli under resting conditions along with the kinase responsible for PI(4,5)P2 synthesis, phosphatidylinositol-4-phosphate 5-kinase, type I γ [PI(4)P5K I γ], which may explain the low basal open probability and increased sensitivity to tetraethylammonium observed here for this channel. Notably, lovastatin induced PI(4)P5K I γ diffusion into planar regions and elevated PI(4,5)P2 and ROMK1 open probability in these regions through a cholesterol-associated mechanism. However, exogenous cholesterol alone did not induce these effects. These results suggest that lovastatin stimulates ROMK1 channels, at least in part, by inducing PI(4,5)P2 synthesis in planar regions of the renal CCD cell apical membrane, suggesting that lovastatin could reduce cyclosporin-induced nephropathy and associated hyperkalemia.
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Colesterol/metabolismo , Túbulos Renales Colectores/metabolismo , Lovastatina/farmacología , Microvellosidades/metabolismo , Canales de Potasio de Rectificación Interna/metabolismo , Análisis de Varianza , Animales , Western Blotting , Membrana Celular/metabolismo , Células Cultivadas , Ciclosporinas/metabolismo , Regulación de la Expresión Génica , Túbulos Renales Colectores/efectos de los fármacos , Ratones , Microscopía Confocal , Microvellosidades/efectos de los fármacos , Microvellosidades/ultraestructura , Modelos Animales , Canales de Potasio de Rectificación Interna/efectos de los fármacos , Canales de Potasio de Rectificación Interna/genética , ARN Interferente Pequeño/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Valores de Referencia , Sensibilidad y Especificidad , Transducción de SeñalRESUMEN
Clinical evidence suggests that statins reduce cancer incidence and mortality. However, there is lack of in vitro data to show the mechanism by which statins can reduce the malignancies of cancer cells. We used a human B lymphoma Daudi cells as a model and found that lovastatin inhibited, whereas exogenous cholesterol (Cho) stimulated, proliferation cell cycle progression in control Daudi cells, but not in the cells when transient receptor potential canonical 6 (TRPC6) channel was knocked down. Lovastatin decreased, whereas Cho increased, the levels of intracellular reactive oxygen species (ROS) respectively by decreasing or increasing the expression of p47-phox and gp91-phox (NOX2). Reducing intracellular ROS with either a mimetic superoxide dismutase (TEMPOL) or an NADPH oxidase inhibitor (apocynin) inhibited cell proliferation, particularly in Cho-treated cells. The effects of TEMPOL or apocynin were mimicked by inhibition of TRPC6 with SKF-96365. Lovastatin decreased TRPC6 expression and activity via a Cho-dependent mechanism, whereas Cho increased TRPC6 expression and activity via an ROS-dependent mechanism. Consistent with the fact that TRPC6 is a Ca(2+)-permeable channel, lovastatin decreased, but Cho increased, intracellular Ca(2+) also via ROS. These data suggest that lovastatin inhibits malignant B cell proliferation by reducing membrane Cho, intracellular ROS, TRPC6 expression and activity, and intracellular Ca(2+).
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Proliferación Celular/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Lovastatina/farmacología , Linfoma de Células B/patología , Especies Reactivas de Oxígeno/metabolismo , Canales Catiónicos TRPC/antagonistas & inhibidores , Humanos , Técnicas de Placa-Clamp , Canal Catiónico TRPC6RESUMEN
Mutated epidermal growth factor receptor (EGFR) is an important biomarker for cancer diagnosis and molecular target for many anticancer drugs. Localizing EGFR and evaluating EGFR mutational status can help to identify patients who are potentially the most suitable ones for targeted treatments. Hence, we developed a novel EGFR tyrosine kinase inhibitor labeled with (99m)Tc ((99m)Tc-HYNIC-MPG) and evaluated its EGFR binding capacity in vitro and in vivo. This molecular probe was synthesized by one-step method that is simple and highly efficient. Importantly, the uptake rate for (99m)Tc-HYNIC-MPG in the liver was as low as 28.44 ± 0.15% (mean ± SD, n=3). This finding presents for the first time that (99m)Tc-HYNIC-MPG can bind to mutated EGFR efficiently and thus provides a novel molecular tool to detect mutated EGFR and suppress tumorigenesis.
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Receptores ErbB/antagonistas & inhibidores , Sondas Moleculares/farmacología , Compuestos de Organotecnecio/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Quinazolinas/farmacología , Radiofármacos/farmacología , Tomografía Computarizada de Emisión de Fotón Único , Animales , Línea Celular , Receptores ErbB/genética , Femenino , Humanos , Ratones , Ratones Endogámicos , Imagen Molecular , Sondas Moleculares/síntesis química , Sondas Moleculares/química , Mutación , Compuestos de Organotecnecio/síntesis química , Compuestos de Organotecnecio/química , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Quinazolinas/síntesis química , Quinazolinas/química , Radiofármacos/síntesis química , Radiofármacos/química , Relación Estructura-ActividadRESUMEN
OBJECTIVE: To investigate the image quality and radiation dose of combined coronary and carotid/cerebrovascular angiography with ECG gating and iterative reconstruction using 256-slice CT compared with the findings with the two examinations performed separately. PATIENTS AND METHODS: One hundred sixty-five consecutive patients underwent a single-injection single-pass combination of coronary and carotid/cerebrovascular CT angiography (group A), coronary CT angiography alone (group B), or carotid/cerebrovascular CT angiography alone (group C). We assessed the image quality of the combined and separate examinations and calculated the respective effective radiation doses. We evaluated the differences in the proportions of image quality grade between the combination and single-examination groups. Diagnostic performance of the combined scanning for detecting significant vascular stenosis has been compared with reference digital subtraction angiography (DSA) in the patient subgroup of group A. RESULTS: There was no significant difference in age, body mass index (BMI), or gender distribution among the 3 groups (all P > 0.05). But there was significant difference in scan length, DLP, and effective dose among the 3 groups (all P < 0.05). There were no significant differences in the effective radiation dose of coronary scanning between groups A and B (P > 0.05), while the effective radiation dose of carotid/cerebrovascular scanning in group A was significantly lower than that in group C (P < 0.05), and the total effective radiation dose in group A were relatively low (2.21 ± 1.38 mSv). The differences of the proportion of carotid/cerebrovascular image quality grades between groups A and C were not significant (P > 0.05). In a subgroup of group A of 30 patients with DSA, combined computed tomographic angiography successfully detected 56 coronary stenosis on per-segment basis, and 62 stenosis on carotid and cerebral artery. The sensitivity, specificity, positive and negative predictive value (NPV) of coronary stenosis were 91.80%, 95.60%, 87.50% and 97.21%, respectively. The sensitivity, specificity, positive and NPV of carotid/cerebrovascular stenosis were 93.55%, 94.68%, 92.06% and 95.70%, respectively. CONCLUSION: Combination of coronary and carotid/cerebrovascular angiography with 256-slice CT scanner with prospective ECG gating and iterative reconstruction produces diagnostic-quality images of the coronary, carotid, and cerebrovascular systems in a single examination, using less contrast medium and a lower radiation dose than when the two examinations are performed separately. This novel technique has high accuracy in detecting significant stenosis in one image setting.
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Aterosclerosis/diagnóstico por imagen , Técnicas de Imagen Sincronizada Cardíacas/métodos , Angiografía Cerebral/métodos , Angiografía Coronaria/métodos , Tomografía Computarizada Multidetector/métodos , Exposición a la Radiación/análisis , Arterias Carótidas/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal/métodos , Dosis de Radiación , Protección Radiológica/métodos , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
STUDY DESIGN: A cross-sectional study in a general health examination. OBJECTIVE: To investigate the relationship between brachial-ankle pulse wave velocity (baPWV) and lumbar disk herniation (LDH). SUMMARY OF BACKGROUND DATA: Lumbar disk herniation (LDH) is a major cause of low back pain and sciatica. Various vascular risk factors such as obesity, diabetes mellitus, and smoking have been reported to be associated with LDH. BaPWV is an early indicator of subclinical atherosclerosis. METHODS: A total of 490 participants with LDH and 490 participants without LDH were selected for the evaluation of baPWV. BaPWV was measured using an automatic device. The prevalence of LDH was calculated by the quartiles of baPWV levels. Multiple linear regression analysis was performed to evaluate the risk factors for baPWV. RESULTS: LDH patients had significantly higher readings of baPWV compared with non-LDH subjects (P<0.001). The prevalence rate of LDH gradually increased according to baPWV quartiles. In addition, the levels of baPWV tended to increase as the frequency of physical activity reduced. Multiple linear regression analysis showed that body mass index, low-density lipoprotein cholesterol, physical activity, and systolic blood pressure contributed to increased baPWV. CONCLUSIONS: The findings showed that LDH patients had higher baPWV levels. In addition, reduced physical activity was a risk factor contributing to increased baPWV. Further studies are warranted to determine the role of baPWV in LDH.
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Desplazamiento del Disco Intervertebral/fisiopatología , Vértebras Lumbares/fisiopatología , Actividad Motora , Rigidez Vascular/fisiología , Adulto , Anciano , Índice Tobillo Braquial , Estudios Transversales , Femenino , Humanos , Desplazamiento del Disco Intervertebral/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Análisis de la Onda del Pulso , Análisis de RegresiónRESUMEN
Podocyte number is significantly reduced in diabetic patients and animal models, but the mechanism remains unclear. In the present study, we found that high glucose induced apoptosis in control podocytes which express transient receptor potential canonical 6 (TRPC6) channels, but not in TRPC6 knockdown podocytes in which TRPC6 was knocked down by TRPC6 silencing short hairpin RNA (shRNA). This effect was reproduced by treatment of podocytes with the reactive oxygen species (ROS), hydrogen peroxide (H2O2). Single-channel data from cell-attached, patch-clamp experiments showed that both high glucose and H2O2 activated the TRPC6 channel in control podocytes, but not in TRPC6 knockdown podocytes. Confocal microscopy showed that high glucose elevated ROS in podocytes and that H2O2 reduced the membrane potential of podocytes and elevated intracellular Ca(2+) via activation of TRPC6. Since intracellular Ca(2+) overload induces apoptosis, H2O2-induced apoptosis may result from TRPC6-mediated elevation of intracellular Ca(2+). These data together suggest that high glucose induces apoptosis in podocytes by stimulating TRPC6 via elevation of ROS.
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Apoptosis/efectos de los fármacos , Calcio/metabolismo , Glucosa/farmacología , Podocitos/patología , Especies Reactivas de Oxígeno/metabolismo , Edulcorantes/farmacología , Canales Catiónicos TRPC/metabolismo , Western Blotting , Células Cultivadas , Humanos , Peróxido de Hidrógeno/farmacología , Potenciales de la Membrana/efectos de los fármacos , Oxidantes/farmacología , Técnicas de Placa-Clamp , Podocitos/efectos de los fármacos , Podocitos/metabolismo , Canal Catiónico TRPC6RESUMEN
We used mouse cortical collecting duct principal cells (mpkCCDc14 cell line) as a model to determine whether statins reduce the harmful effects of cyclosporine A (CsA) on the distal nephron. The data showed that treatment of cells with CsA increased transepithelial resistance and that the effect of CsA was abolished by lovastatin. Scanning ion conductance microscopy showed that CsA significantly increased the height of cellular protrusions near tight junctions. In contrast, lovastatin eliminated the protrusions and even caused a modest depression between cells. Western blot analysis and confocal microscopy showed that lovastatin also abolished CsA-induced elevation of both zonula occludens-1 and cholesterol in tight junctions. In contrast, a high concentration of CsA induced apoptosis, which was also attenuated by lovastatin, elevated intracellular ROS via activation of NADPH oxidase, and increased the expression of p47phox. Sustained treatment of cells with lovastatin also induced significant apoptosis, which was attenuated by CsA, but did not elevate intracellular ROS. These results indicate that both CsA and lovastatin are harmful to principal cells of the distal tubule, but via ROS-dependent and ROS-independent apoptotic pathways, respectively, and that they counteract probably via mobilization of cellular cholesterol levels.
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Apoptosis/efectos de los fármacos , Ciclosporina/antagonistas & inhibidores , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inmunosupresores/antagonistas & inhibidores , Túbulos Renales Colectores/citología , Túbulos Renales Colectores/efectos de los fármacos , Lovastatina/farmacología , Uniones Estrechas/efectos de los fármacos , Análisis de Varianza , Animales , Western Blotting , Células Cultivadas , Colesterol/biosíntesis , Colorantes , Ciclosporina/farmacología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/ultraestructura , Inmunosupresores/farmacología , Túbulos Renales Colectores/ultraestructura , Ratones , Microscopía Confocal , Microscopía Electrónica de Rastreo , NADPH Oxidasas/metabolismo , Permeabilidad , Especies Reactivas de Oxígeno/metabolismo , Uniones Estrechas/metabolismo , Uniones Estrechas/ultraestructura , Proteína de la Zonula Occludens-1/biosíntesisRESUMEN
OBJECTIVE: to study the biochemistry of blood and feature of pathology of an animal model in rabbits with the early primary hyperparathyroidism(PHPT). METHODS: 60 rabbits were divided into six groups of 10 each and fed a control diet (Ca:P, 1:0.7) or a high-phosphate diet (Ca:P, 1:7) for 1-, 2- or 3-month intervals. Compared with the control animals, serum PTH levels, serum calcium levels and serum phosphorus levels were determined. The parathyroid and kidneys of all animals were performed by the histologic examination. RESULTS: compared with the control animals, serum parathyroid hormone (PTH) levels were elevated at 1-, 2-, 3-month intervals in experimental group (t = -7.665, t = -16.033, t = 12.877 respective, P < 0.05), whereas serum calcium levels were decreased at all three time intervals (t = 6.184, t = 9.329, t = 13.842, respective, P < 0.05), but serum phosphorus levels did not change (t = 0.611, t = 1.041, t = 1.941, respective, P > 0.05). Parathyroid histopathologic studies demonstrated no change at 1 month whereas six of ten experimental animals showed mild hyperplasia at 2 months and nine of ten showed mild to moderate hyperplasia with gland enlargement at 3 months compared with control animals. Histopathologic examination of the kidneys showed no change at 1 month but focal parenchymal inflammation with calcium deposition at 2- and 3-month in the experimental groups. CONCLUSION: the high-phosphate diet successfully induced an animal model in rabbits with the early primary hyperparathyroidism, which has a better stability and reproducibility.
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Modelos Animales de Enfermedad , Hiperparatiroidismo Primario/sangre , Hiperparatiroidismo Primario/patología , Animales , Calcio/sangre , Dieta , Riñón/patología , Glándulas Paratiroides/patología , Hormona Paratiroidea/sangre , Fosfatos/administración & dosificación , Fósforo/sangre , ConejosRESUMEN
BACKGROUND: Tumor angiogenesis is essential for primary and metastatic tumor growth. Computed tomography perfusion (CTP) is a new imaging method, made possible by the recent development of fast CT scanners and improved data analysis techniques, which allows measurement of the physiologic and hemodynamic properties of tissue vasculature. This study aimed to evaluate CTP in the quantification of angiogenesis and to assess the relationship between tissue perfusion parameters and microvascular density (MVD) and vascular endothelial growth factor (VEGF), attempting to detect the physiologic properties of angiogenesis. METHODS: Sixteen rabbits with VX2 liver tumors underwent multi-slice CT perfusion (MSCTP) on day 14 after tumor inoculation. CTP parameters included hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic artery index (HAI), hepatic artery perfusion (HAP), and hepatic portal perfusion (HPP). The border of the tumor was stained with CD34 and VEGF immunohistochemical stains, and MVD was measured by anti-CD34. Then, CTP parameters were determined whether they were correlated with MVD and VEGF using Pearsonos correlation coefficient. RESULTS: The positive expression of MVD was different in the center and border of the tumor (P<0.01). There was a positive correlation between MVD and VEGF in the border (P<0.05). As more VEGF was expressed, the number of microvessels increased. Correlation analyses were also made between the perfusion parameters and MVD and VEGF in the border of the tumor. HBF, PS, HAI, and HAP values were positively correlated with MVD and VEGF (P<0.05), HPP was negatively correlated with MVD and VEGF (P<0.01), and HBV and MTT values were not correlated with MVD and VEGF (P>0.05). CONCLUSIONS: Significant correlations were found between perfusion parameters and MVD and VEGF. Therefore, MSCTP can be used to evaluate tumor angiogenesis in vivo.
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Neoplasias Hepáticas/irrigación sanguínea , Neovascularización Patológica/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Animales , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Conejos , Factor A de Crecimiento Endotelial Vascular/análisisRESUMEN
BACKGROUND: Previous reports have confirmed that edaravone has protective effects against ischemia-reperfusion (IR) injury of many organs. In this study, we investigated the effect of edaravone on preventing IR injury of the lung in a canine lung transplantation model. METHODS: Twelve weight-matched pairs of random-bred dogs were randomized into two groups. Within each pair, one dog served as donor and the other as recipient. In the study group, prostaglandin E1(PGE1)(8 microg/kg) was injected into the donor pulmonary artery (PA) before occlusion and the donor lungs were flushed with 1.0 L of LPD solution containing edaravone (10 mg/kg) and stored in the same LPD solution at a temperature of 1 degrees C for 8 hours. The left single lung transplantation was then performed and recipients received intravenous injection with edaravone (10 mg/kg) at the onset of reperfusion. In the control group, edaravone was substituted by the same volume of sterile saline solution. Another six dogs were obtained as normal control group in which left lungs were dissected after thoracotomy without an IR injury. One hour after reperfusion, or after dissection of the left lung, the right lung was excluded from perfusion and ventilation after which, cardiopulmonary parameters were measured. Wet/dry ratios, malondialdehyde (MDA) and myeloperoxidase (MPO) levels were assessed and histological analysis of lung tissue performed at the same time. RESULTS: All animals survived until the end of the experiment. The study group showed significantly decreased wet/dry ratios (treated: (74.1 +/- 4.2)% vs control: (86.8 +/- 5.2)%, P < 0.01), MDA levels (treated: 0.50 +/- 0.08 vs. control: 0.88 +/- 0.15, P < 0.01) and MPO activity (treated: 0.23 +/- 0.05 vs. control: 0.43 +/- 0.07, P < 0.01) compared to the control group two hours after occlusion of the right side. In the control group, pulmonary vascular resistance (PVR) was increased markedly and arterial oxygen partial pressure deteriorated significantly after exclusion of the right side compared to those in the treatment group. CONCLUSIONS: Edaravone attenuates IR-induced lung injury and preserves lung function by inhibiting oxidative stress and decreasing leukocyte extravasation in a canine lung transplantation model.
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Antipirina/análogos & derivados , Trasplante de Pulmón/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Daño por Reperfusión/prevención & control , Animales , Antipirina/farmacología , Antipirina/uso terapéutico , Modelos Animales de Enfermedad , Perros , Edaravona , Peroxidación de Lípido , Pulmón/metabolismo , Pulmón/patología , Óxido Nítrico/biosíntesis , Peroxidasa/metabolismoRESUMEN
BACKGROUND: CT perfusion has been reported to have great advantages in detecting hepatic diseases. However, currently there are no studies showing the potential value of multi-slice CT perfusion with the deconvolution model method in diagnosing early hemodynamic changes caused by liver tumors. This study was undertaken to determine if early hemodynamic changes caused by liver tumors can be depicted with the perfusion imaging of multi-slice CT. METHODS: Ten New Zealand white rabbits before and after VX2 liver tumor inoculation served as the experimental animals. Ten normal rabbits served as controls. All underwent multi-slice CT perfusion for the measurement of hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS) and hepatic artery index (HAI). RESULTS: With the exception of MTT, which decreased significantly at the tumor periphery, HBF, HBV, PS and HAI increased significantly compared with the surrounding normal tissue. All these changes occurred at days 5-9 after tumor inoculation. Statistically significant changes in these values were detected with tumor growth. CONCLUSIONS: The hemodynamic changes in the liver caused by rabbit VX2 liver tumor can be detected after tumor inoculation, and functional CT can evaluate the physiological characteristics of early tumor angiogenesis.
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Cineangiografía , Hemodinámica , Circulación Hepática , Neoplasias Hepáticas Experimentales/irrigación sanguínea , Neoplasias Hepáticas Experimentales/diagnóstico por imagen , Neovascularización Patológica/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Animales , Velocidad del Flujo Sanguíneo , Volumen Sanguíneo , Permeabilidad Capilar , Medios de Contraste , Arteria Hepática/diagnóstico por imagen , Arteria Hepática/fisiopatología , Yohexol , Modelos Cardiovasculares , Trasplante de Neoplasias , Neovascularización Patológica/fisiopatología , Valor Predictivo de las Pruebas , Conejos , Factores de TiempoRESUMEN
Piwi-interacting RNAs (piRNAs/piRs) are small non-coding RNAs that can serve important roles in genome stability by silencing transposable genetic elements. piR651, one of these novel piRNAs, regulates a number of biological functions, as well as carcinogenesis. Previous studies have reported that piR651 is overexpressed in human gastric cancer tissues and in several cancer cell lines, including non-small cell lung cancer (NSCLC) cell lines. However, the role of piRNAs in carcinogenesis has not been clearly defined. In the present study, a small interfering RNA inhibitor of piR651 was transfected into the NSCLC A549 and HCC827 cell lines to evaluate the effect of piR651 on cell growth. The association between piR651 expression and apoptosis was evaluated by flow cytometry and western blot analysis. Wound-healing and Transwell migration and invasion assays were used to determine the effect of piR651 on the migration and invasion of NSCLC cell lines. The results revealed that inhibition of piR651 inhibited cell proliferation and significantly increased the apoptotic rate compared with the negative control (NC), as well as altering the expression of apoptosis-associated proteins. There were fewer migrating and invading cells in the piR651-inhibited group than in the NC group in the Transwell assays. Furthermore, in the wound-healing assay, the wound remained wider in the piR651 inhibitor group, suggesting decreased cell migration compared with that in the NC group. The results of the present study demonstrate that piR651 potentially regulates NSCLC tumorigenic behavior by inhibiting cell proliferation, migration and invasion and by inducing apoptosis. Therefore, piR651 is a potential cancer diagnosis marker.
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OBJECTIVE: To investigate the value of multi-slice computed tomography in diagnosis of different types of coronary atherosclerotic plaques. METHODS: Twenty-eight patients undergoing CT angiography (CTA) with normal coronary arteries were randomly selected to measure the CT values of different sections of the 4 main branches of coronary artery. Twenty-five specimens of human heart from the bodies of the patients who died of non-cardiogenic diseases were scanned by 16-slice CT scanner and 64-slice CT scanner: a mixture of CT contrast media and normal saline was injected into the coronary arteries to achieve in-vivo-like contrast enhancement within the coronary artery lumen to detect atherosclerotic plaques. The CT values of plaques were measured in several regions of interest (ROI) selected in each plaque. The CT images thus obtained were evaluated by 2 experienced radiologists. There are nine specimens with coronary atherosclerotic plaques among them. Then the atherosclerotic lesions in the coronary were made into tissue specimens to undergo pathological examination. RESULTS: 7560 CT values were obtained from the 28 patients. Thirty-eight atherosclerotic plaques were found by CAT in 9 heart specimens and confirmed by pathology. When the CT value of coronary lumen was 370 HU, the predominant lipid-rich plaque showed a mean CT value of 53 +/- 12 HU; the fibrous-rich plaque showed a mean CT value of 106 +/- 17 HU; and the calcified plaque showed a mean CT value of 429 +/- 94 HU measured by 16-slice CT; and the predominant lipid-rich plaque showed a mean CT value of 51 +/- 13 HU; the fibrous-rich plaque showed a mean CT value of 110 +/- 19 HU; and the calcified plaque showed a mean CT value of 435 +/- 87 HU measured by 64-slice CT. The CT value of the fibrous-rich plaque was significantly higher than that of the lipid-rich plaque (P = 0.008), and lower than that of the calcified plaque (P < 0.01). There was no significant difference between the results obtained by the two kinds of CT scanners. CONCLUSION: CTA can non-invasively assess the atherosclerotic plaques.
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Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico , Tomografía Computarizada Espiral/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Considering the general application of dedicated small-animal positron emission tomography/computed tomography is limited, an acceptable alternative in many situations might be clinical PET/CT. To estimate the feasibility of using clinical PET/CT with [F-18]-fluoro-2-deoxy-D-glucose for high-resolution dynamic imaging and quantitative analysis of cancer xenografts in nude mice. Dynamic clinical PET/CT scans were performed on xenografts for 60 min after injection with [F-18]-fluoro-2-deoxy-D-glucose. Scans were reconstructed with or without SharpIR method in two phases. And mice were sacrificed to extracting major organs and tumors, using ex vivo γ-counting as a reference. Strikingly, we observed that the image quality and the correlation between the all quantitive data from clinical PET/CT and the ex vivo counting was better with the SharpIR reconstructions than without. Our data demonstrate that clinical PET/CT scanner with SharpIR reconstruction is a valuable tool for imaging small animals in preclinical cancer research, offering dynamic imaging parameters, good image quality and accurate data quatification.
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Recent studies indicate that the transient receptor potential canonical 6 (TRPC6) channel is highly expressed in several types of cancer cells. However, it remains unclear whether TRPC6 contributes to the malignancy of human non-small cell lung cancer (NSCLC). We used a human NSCLC A549 cell line as a model and found that pharmacological blockade or molecular knockdown of TRPC6 channel inhibited A549 cell proliferation by arresting cell cycle at the S-G2M phase and caused a significant portion of cells detached and rounded-up, but did not induce any types of cell death. Western blot and cell cycle analysis show that the detached round cells at the S-G2M phase expressed more TRPC6 than the still attached polygon cells at the G1 phase. Patch-clamp data also show that TRPC whole-cell currents in the detached cells were significantly higher than in the still attached cells. Inhibition of Ca2+-permeable TRPC6 channels significantly reduced intracellular Ca2+ in A549 cells. Interestingly, either blockade or knockdown of TRPC6 strongly reduced the invasion of this NSCLC cell line and decreased the expression of an adherent protein, fibronectin, and a tight junction protein, zonula occluden protein-1 (ZO-1). These data suggest that TRPC6-mediated elevation of intracellular Ca2+ stimulates NSCLC cell proliferation by promoting cell cycle progression and that inhibition of TRPC6 attenuates cell proliferation and invasion. Therefore, further in vivo studies may lead to a consideration of using a specific TRPC6 blocker as a complement to treat NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Imidazoles/farmacología , Neoplasias Pulmonares/metabolismo , ARN Interferente Pequeño/farmacología , Canal Catiónico TRPC6/antagonistas & inhibidores , Células A549 , Calcio/metabolismo , Ciclo Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Fibronectinas/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/genética , Invasividad Neoplásica , Proteína de la Zonula Occludens-1/metabolismoRESUMEN
BACKGROUND: Hyperparathyroidism (HPT) occurs at an early age and has a high disability rate. Unfortunately, confirmed diagnosis in most patients is done at a very late stage, when the patients have shown typical symptoms and signs, and when treatment does not produce any desirable effect. It has become urgent to find a method that would detect early bone diseases in HPT to obtain time for the ideal treatment. This study evaluated the accuracy of high field magnetic resonance imaging (MRI) combined with spiral computed tomography (SCT) scan in detecting early bone diseases in HPT, through imaging techniques and histopathological examinations on an animal model of HPT. METHODS: Eighty adult rabbits were randomly divided into two groups with forty in each. The control group was fed normal diet (Ca:P = 1:0.7); the experimental group was fed high phosphate diet (Ca:P = 1:7) for 3, 4, 5, or 6-month intervals to establish the animal model of HPT. The staging and imaging findings of the early bone diseases in HPT were determined by high field MRI and SCT scan at the 3rd, 4th, 5th and 6th month. Each rabbit was sacrificed after high field MRI and SCT scan, and the parathyroid and bones were removed for pathological examination to evaluate the accuracy of imaging diagnosis. RESULTS: Parathyroid histopathological studies revealed hyperplasia, osteoporosis and early cortical bone resorption. The bone diseases in HPT displayed different levels of low signal intensity on T(1)WI and low to intermediate signal intensity on T(2)WI in bone of stage 0, I, II or III, but showed correspondingly absent, probable, osteoporotic and subperiosteal cortical resorption on SCT scan. CONCLUSION: High field MRI combined with SCT scan not only detects early bone diseases in HPT, but also indicates staging, and might be a reliable method of studying early bone diseases in HPT.
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Enfermedades Óseas/diagnóstico , Hiperparatiroidismo/complicaciones , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada Espiral/métodos , Animales , Enfermedades Óseas/patología , Calcio/sangre , Femenino , Masculino , Osteoporosis/diagnóstico , Fósforo/sangre , ConejosRESUMEN
AIM: To identify a small, clinically applicable immunohistochemistry (IHC) panel that could be combined with magnetic resonance imaging (MRI)-detected extramural vascular invasion (EMVI) for assessment of prognosis concerning the non-advanced rectal cancer patients prior to operation. METHODS: About 329 patients with pathologically confirmed rectal carcinoma (RC) were screened in this research, all of whom had been examined via an MRI and were treatment-naïve from July 2011 to July 2014. The candidate proteins that were reported to be altered by RC were examined in tissues by IHC. All chosen samples were adopted from the fundamental cores of histopathologically confirmed carcinomas during the initial surgeries. RESULTS: Of the three proteins that were tested, c-MYC, PCNA and TIMP1 were detected with relatively significant expression in tumors, 35.9%, 23.7% and 58.7% respectively. The expression of the three proteins were closely connected with prognosis (P = 0.032, 0.003, 0.021). The patients could be classified into different outcome groups according to an IHC panel (P < 0.01) via these three proteins. Taking into consideration known survival covariates, especially EMVI, the IHC panel served as an independent prognostic factor. The EMVI combined with the IHC panel could categorize patients into different prognostic groups with distinction (P < 0.01). CONCLUSION: These studies argue that this three-protein panel of c-MYC, PCNA, coupled with TIMP1 combined with MRI-detected EMVI could offer extra prognostic details for preoperative treatment of RC.
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Inmunohistoquímica/métodos , Imagen por Resonancia Magnética/métodos , Neoplasias del Recto/irrigación sanguínea , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/irrigación sanguínea , Carcinoma/diagnóstico por imagen , Carcinoma/patología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Antígeno Nuclear de Célula en Proliferación/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Estudios Retrospectivos , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Adulto JovenRESUMEN
AIM: To evaluate the therapeutic effect of radiotherapy for esophageal cancer after expandable metallic stent placement. METHODS: Ten cases of advanced esophageal cancer were evaluated, 7 having complete obstruction and 3 with digestive-respiratory fistula. Ten nitinol stents were placed at the site of stenosis. Patients were treated with a total dose of 1 200 cGy divided into 3 fractions of 400 cGy 4-7 d after stents placement. RESULTS: All the 10 stents were placed successfully at one time. After radiotherapy for advanced esophageal cancer, the survival period of the cases ranged from 14 to 22 mo, with a mean survival of 17 mo. No re-stenosis occurred among all the 10 cases. CONCLUSION: Stent placement combined with radiotherapy for esophageal cancer is helpful to prolong patients' survival and reduce occurrence of re-stenosis.
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Aleaciones , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/radioterapia , Estenosis Esofágica/etiología , Estenosis Esofágica/cirugía , Stents , Anciano , Anciano de 80 o más Años , Materiales Biocompatibles Revestidos , Femenino , Humanos , Masculino , Membranas Artificiales , Persona de Mediana Edad , Siliconas , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To study the effect of hepatic artery embolization on the microwave coagulated area, an in vivo animal experiment. METHODS: Twenty-four suitable hepatic lobes of ten dogs were divided into two groups: microwave coagulation alone 12 lobes (control group) and hepatic artery occlusion with iodized oil and gelatin sponge particles followed by microwave coagulation 12 (experiment group). Microwave coagulation was delivered with an output of 50 W for 300 or 400 seconds with thermal needles introduced parallel to and 5 approximately 20 mm from the puncture needle. After sacrifice of the dogs, their hepatic lobes were sectioned along the puncture line. Then, the appearance and size of the coagulated area were recorded. The tissue specimens were fixed in formalin for light microscopic evaluation. RESULTS: A decline in temperature gradient was detected from the center to the periphery of the affected tissue after the application of microwave coagulation, which was sharper in the control group than in the experimental group. Single polar microwave coagulation at 50 W for 300 seconds produced a necrotic volume of 25 approximately 33 mm in longitudinal diameter and 13 approximately 22 mm in transverse diameter in control group, 33 approximately 44 mm and 24 approximately 32 mm in the experimental group. The coagulation area was slightly bigger when the duration of coagulation was 400 seconds than 300 seconds, without significant difference. CONCLUSION: Hepatic artery occlusion, inhibiting the heat loss caused by hepatic arterial blood flow, is able to significantly enlarge the necrotic volume of microwave coagulation.
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Electrocoagulación , Embolización Terapéutica , Neoplasias Hepáticas/terapia , Hígado/patología , Microondas/uso terapéutico , Animales , Perros , Femenino , Arteria Hepática , MasculinoRESUMEN
AIM: To investigate the relationship between epicardial adipose tissue (EAT) volume and coronary plaque composition. METHODS: EAT volume (measured using coronary computed tomography angiography) and coronary plaque characteristics were assessed on a per-segment basis (modified 15-segment American College of Cardiology/American Heart Association classification) in patients with severe coronary artery stenosis. Coronary plaques were classified into four types: 1, calcified plaques; 2, mixed plaques (calcification dominant); 3, mixed plaques (non-calcification dominant); and 4, non-calcified plaques. The gold standard for luminal stenosis was conventional coronary angiography. RESULTS: In 365 patients (mean age 58.7 ± 8.0 years), EAT volume was 169.85 ± 29.94 ml. There were no significant between-group differences in patient characteristics. Statistically significant differences in EAT volume between non-calcified and calcified plaque groups were observed. EAT volume showed a positive correlation with total cholesterol and low-density-lipoprotein cholesterol, and a very weak correlation with age, triglyceride, body mass index and high-density-lipoprotein cholesterol. CONCLUSION: EAT volume was higher in the presence of non-calcified and mixed plaques in patients with ≥50% severe coronary artery stenosis.