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OBJECTIVE: To investigate the anticancer efficacy and the hepatic and renal toxicity of As2O3-lipiodol emulsion via transarterial embolization in a rabbit VX2 liver tumor model. METHODS: VX2 tumors were implanted in rabbit livers successfully, followed by transarterial embolization with high-dose As2O3(5 mg/kg with 0.2 mL lipiodol, n=10), low-dose As2O3(1 mg/kg with 0.2 mL lipiodol, n=10), and control(0.2 mL lipiodol, n=10). The growth ratios and microvessel densities(MVDs) of the tumors were estimated by multi-row spiral CT and CD34 immunohistochemical staining, respectively. Hepatic and renal function was also evaluated by means of blood biochemical analysis. RESULTS: The growth ratios of the tumors differed significantly among three groups(P<0.01). The high-dose and low dose group showed significantly lower tumor growth ratios[44.05%(-36.40%~64.60%), 95.20%(-11.60%~159.40%)] than control group[145.55%(98.90%~250.30%), all P<0.05]. The MVDs of the tumors were significantly lower in the high-dose(21.4±10.6) and low-dose group(34.1±12.0) than those in control group(57.9±16.1,all P<0.05). The levels of blood ALT and AST obtained 28 days after transarterial embolization were significantly lower in the high-dose[(25.50±12.37)U/L,(24.25±10.89)U/L] and low-dose group[(45.00±14.04)U/L,(35.22±11.86)U/L] than in control group[(79.12±30.52)U/L,(75.25±25.89)U/L, all P<0.05]. CONCLUSION: As2O3-lipiodol emulsion via transarterial embolization has anticancer effect without significant hepatic and renal functional damage in rabbit VX2 liver tumors.
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Antineoplásicos/farmacología , Arsenicales/farmacología , Aceite Etiodizado/farmacología , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Óxidos/farmacología , Animales , Trióxido de Arsénico , Embolización Terapéutica , Emulsiones/farmacología , Conejos , Tomografía Computarizada EspiralRESUMEN
OBJECTIVE: To evaluate the diagnostic value of diffusion weighted imaging (DWI) combined with dynamic contrast-enhanced (DCE) MRI in monitoring the efficacy for hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). METHODS: MRI and CT scan were performed 4-6 weeks after TACE in 31 patients.With digital signature algorithm (DSA) examination as the reference standard, the value in detection of the residue and recurrence of HCC was compared between MRI and CT results. RESULTS: Seventy-three lesions were detected in 31 patients. Fourteen lesions confirmed by DSA had no tumor staining, and 59 lesions had tumor staining. Diagnostic sensitivity and specificity of DCE-CT were 78.0% and 85.7%, respectively; while those of DWI combined with DCE-MRI were 100% and 92.9% (P<0.001). CONCLUSION: DWI combined with DCE-MRI is more effective than DCE-CT in detecting the residue and recurrence of HCC after TACE.
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Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Adulto , Anciano , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: The purpose of this study was to evaluate the performance of magnetic resonance imaging (MRI) findings and texture parameters for prediction of the histopathologic grade of pancreatic neuroendocrine tumors (PNETs) with 3-T magnetic resonance. PATIENTS AND METHODS: PNETs are classified into Grade 1 (G1), Grade 2 (G2), and Grade 3 (G3) tumors based on the Ki-67 proliferation index and the mitotic activity. A total of 77 patients with pathologically confirmed PNETs met the inclusion criteria. Texture analysis (TA) was applied to T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) maps. Patient demographics, MRI findings, and texture parameters were compared among three different histopathologic subtypes by using Fisher's exact tests or Kruskal-Wallis test. Then, logistic regression analysis was adopted to predict tumor grades. ROC curves and AUCs were calculated to assess the diagnostic performance of MRI findings and texture parameters in prediction of tumor grades. RESULTS: There were 31 G1, 29 G2, and 17 G3 patients. Compared with G1, G2/G3 tumors showed higher frequencies of an ill-defined margin, a predominantly solid tumor type, local invasion or metastases, hypo-enhancement at the arterial phase, and restriction diffusion. Four T2-based (inverse difference moment, energy, correlation, and differenceEntropy) and five DWI-based (correlation, contrast, inverse difference moment, maxintensity, and entropy) TA parameters exhibited statistical significance among PNETs (P<0.001). The AUCs of six predicting models on T2WI and DWI ranged from 0.703-0.989. CONCLUSION: Our data indicate that MRI findings, including tumor margin, texture, local invasion or metastases, tumor enhancement, and diffusion restriction, as well as texture parameters can aid the prediction of PNETs grading.
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INTRODUCTION: Hepatocellular carcinoma is currently the second leading cause of cancer-related deaths worldwide with an increasing incidence. OBJECTIVE: The objective of this study is to investigate the effect of vascular endothelial growth factor small interfering RNA (VEGF-siRNA) on rabbit VX2 carcinoma cell viability in vitro and the effect of transarterial embolization (TAE)-mediated VEGF-siRNA delivery on the growth of rabbit VX2 liver-transplanted model in vivo. METHODS: Quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot technologies were used to detect the expression level of VEGF. TAE and computed tomography scan were used to deliver the VEGF-siRNA and detect the tumor volume in vivo, respectively. Microvessel density was detected by immunohistochemistry with CD34 antibody. A biochemical autoanalyzer was used to evaluate the hepatic and renal toxicity. RESULTS: The designed VEGF-siRNAs could effectively decrease the expression levels of VEGF mRNA and protein in vitro and in vivo. In vitro, the viability of rabbit VX2 carcinoma cells was reduced by 38.5%±7.3% (VEGF-siRNA no 1) and 30.0%±5.8% (VEGF-siRNA no 3) at 48 hours after transfection. Moreover, in rabbit VX2 liver-transplanted model, the growth ratios of tumors at 28 days after TAE-mediated siRNA delivery were 155.18%±19.42% in the control group, 79.67%±19.63% in the low-dose group, and 36.09%±15.73% in the high-dose group, with significant differences among these three groups. Microvessel density dropped to 34.22±4.01 and 22.63±4.07 in the low-dose group and high-dose group, respectively, compared with the control group (57.88±5.67), with significant differences among these three groups. Furthermore, inoculation of VX2 tumor into the liver itself at later stage induced significant increase in alanine aminotransferase and aspartate aminotransferase, indicating an obvious damage of liver functions, while treatment of VX2 tumor via TAE-mediated VEGF-siRNA had no toxicity to the livers and kidneys of rabbits, and VEGF-siRNA had the ability to protect liver damage induced by tumor growth. CONCLUSION: This is the first study to demonstrate that targeting VEGF via TAE-mediated siRNA delivery may become a powerful new option for effective treatment of hepatocellular carcinoma in the clinic.