Is gadoxetic acid-enhanced MRI limited in tumor characterization for patients with chronic liver disease?

Purpose

There are pros and cons to the use of gadoxetic acid in hepatocellular carcinoma (HCC) workup due to the potential for high false positive diagnosis. This study was conducted to investigate the preoperative diagnostic performance of gadoxetic acid-enhanced MRI protocol including diffusion-weighted imaging (DWI) with emphasis on tumor characterization developed in high risk HCC patients.

Materials and methods

We included 144 patients (102 men, 42 women; age range 33–74 years) with chronic viral hepatitis or cirrhosis and 183 focal hepatic tumors (size range, 0.4–11.0 cm; mean, 3.2 cm), including 148 HCCs, 13 cholangiocarcinomas, 12 hemangiomas, three hepatocellular adenomas, two focal nodular hyperplasias, and five other tumors. All patients underwent gadoxetic acid-enhanced MRI protocol with DWI. MRIs were independently interpreted by three observers for the detection and characterization of hepatic tumors.

Results

Sensitivities for detecting all 183 liver tumors were 98.4%, 97.8%, and 96.2% for each observer, respectively, with a 97.5% for pooled data. Among 183 hepatic tumors, 91.3% (n = 167), 87.4% (n = 160), and 86.9% (n = 159) were correctly characterized according to their reference standard by each observer, respectively. In 13 cholangiocarcinomas, one to three were misinterpreted as HCC, and the remaining tumors were correctly characterized by each observer. The accuracies (Az) of MRI for HCC diagnosis were 0.952 for observer 1, 0.906 for observer 2, and 0.910 for observer 3, with 0.922 for pooled data. There was good inter-observer agreement.

Conclusion

The gadoxetic acid-enhanced MRI including DWI showed a reasonable performance for tumor characterization with high sensitivity for tumor detection in patients with chronic liver disease, despite concerns of high false positive diagnosis of hypervascular tumors.     

Hepatoprotective Effect of Millettia dielsiana: In Vitro and In Silico Study

In silico docking studies of 50 selected compounds from Millettia dielsiana Harms ex Diels (family Leguminosae) were docked into the binding pocket of the PI3K/mTOR protein. In there, compounds trans−3−O-p-hydroxycinnamoyl ursolic acid (1) and 5,7,4′−trihydroxyisoflavone 7−O−β−D−apiofuranosyl−(1→6)−β−D−glucopyranoside (2) are predicted to be very promising inhibitors against PI3K/mTOR. They direct their cytotoxic activity against Hepatocellular carcinoma with binding affinity (BA) values, the pulling work spent to the co-crystallized ligand from the binding site of PI3K/mTOR (W and F_max), and the non-equilibrium binding free energy (∆G_neq^Jar) as BA values = −9.237 and −9.083 kcal/mol, W = 83.5 ± 10.6 kcal/mol with F_max = 336.2 ± 45.3 pN and 126.6 ± 21.7 kcal/mol with F_max = 430.3 ± 84.0 pN, and ∆G_neq^Jar = −69.86074 and −101.2317 kcal/mol, respectively. In molecular dynamic simulation, the RMSD value of the PI3K/mTOR complex with compounds (1 and 2) was in the range of 0.3 nm to the end of the simulation. Therefore, the compounds (1 and 2) are predicted to be very promising inhibitors against PI3K/mTOR. The crude extract, ethyl acetate fraction and compounds (1 and 2) from Millettia dielsiana exhibited moderate to potent in vitro cytotoxicity on Hepatocellular carcinoma cell line with IC₅₀ values of 81.2 µg/mL, 60.4 µg/mL, 23.1 μM, and 16.3 μM, respectively, and showed relatively potent to potent in vitro antioxidant activity on mouse hepatocytes with ED₅₀ values of 24.4 µg/mL, 19.3 µg/mL, 30.7 μM, and 20.5 μM, respectively. In conclusion, Millettia dielsiana and compounds (1 and 2) are predicted to have very promising cytotoxic activity against Hepatocellular carcinoma and have a hepatoprotective effect.     

p53蛋白与肝细胞癌临床病理特征及预后的关系

目的 探讨p53蛋白表达与肝细胞癌的临床病理特征及预后的关系,为术后综合治疗及判断预后提供依据。方法 采用免疫组织化学方法检测88例肝细胞癌组织中p53蛋白的表达,比较阳性患者和阴性患者的临床病理因素和术后累积复发率、术后累积生存率的差异。结果 p53蛋白表达阳性组1、2、3累积生存率分别为75．0％、54.4%、24．2％,阴性组相应的分别为84．3％、77．8％、56．1％。与阴性组相比,p53蛋白阳性组有较高的术前AFP浓度（P=0．005）、有较大的肿瘤最大直径（P=0．042）、肿瘤包膜不完整或无包膜者多见（P=0．023）。结论 p53蛋白是评价肝细胞癌恶性程度及预后的一个有价值的生物学指标。     

树突状细胞瘤内注射联合放疗对小鼠肾癌细胞因子的影响

目的研究树突状细胞(Dendritic cell,DC)瘤内注射联合放疗对小鼠肾癌治疗后脾细胞分泌细胞因子水平的变化。方法用Renca肾癌细胞(2.5×106/只)制作小鼠皮下移植瘤模型,接受肿瘤局部放射治疗,7Gy 6脉伏电子线/次,并在肿瘤部位直接注射未负载肿瘤抗原的DC,1×106/次,第28 d处死小鼠。检测肿瘤生长速度和瘤体重量。ELISA检测小鼠脾细胞IL-2I、FN-γI、L-4、IL-10和TNF-α分泌水平。结果与肿瘤组比较,DC联合放疗组小鼠的肿瘤生长速度明显缓慢,肿瘤体积明显减小,脾细胞分泌IL-2、IFN-γ和IL-4的能力显著提高。结论瘤内树突状细胞注射联合放疗能够有效地抑制BALB/c小鼠肾癌的生长。     

Isotretinoin and Thalidomide Down-Regulate c-MYC Gene Expression and Modify Proteins Associated with Cancer in Hepatic Cells

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. The number of cases is increasing and the trend for the next few years is not encouraging. HCC is usually detected in the advanced stages of the disease, and pharmacological therapies are not entirely effective. For this reason, it is necessary to search for new therapeutic options. The objective of this work was to evaluate the effect of the drugs isotretinoin and thalidomide on c-MYC expression and cancer-related proteins in an HCC cellular model. The expression of c-MYC was measured using RT-qPCR and western blot assays. In addition, luciferase activity assays were performed for the c-MYC promoters P1 and P2 using recombinant plasmids. Dose-response-time analyses were performed for isotretinoin or thalidomide in cells transfected with the c-MYC promoters. Finally, a proteome profile analysis of cells exposed to these two drugs was performed and the results were validated by western blot. We demonstrated that in HepG2 cells, isotretinoin and thalidomide reduced c-MYC mRNA expression levels, but this decrease in expression was linked to the regulation of P1 and P1-P2 c-MYC promoter activity in isotretinoin only. Thalidomide did not exert any effect on c-MYC promoters. Also, isotretinoin and thalidomide were capable of inducing and repressing proteins associated with cancer. In conclusion, isotretinoin and thalidomide down-regulate c-MYC mRNA expression and this is partially due to P1 or P2 promoter activity, suggesting that these drugs could be promising options for modulating the expression of oncogenes and tumor suppressor genes in HCC.     

VEGF及其受体与鼻咽癌的关系

VEGF是新生血管形成的主要促进因子,鼻咽癌细胞的生长及转移与VEGF的产生及VEGFR的特异性激活密切相关。现综述近年来有关VEGF、VEGFR与鼻咽癌关系,以及VEGF、VEGFR抑制剂在鼻咽癌治疗中应用的研究进展。     

鼻咽癌旁原位癌的病理学研究

作者采用组织学、显微镜光度计和免疫组织化学的方法,描述了鼻咽癌旁原位癌的组织病理学特征及其在肿瘤组织发生和演进中的作用. 作者将鼻咽癌旁原位癌分为柱状和鳞状两型,比较了它们各自的组织学和细胞学特点. 本文认为:在浸润性鼻咽癌出现之前已经发生了一系列的改变,而原位癌则是癌症的组织发生和肿瘤演进过程中关键性的一步.已呈异型性改变的储备细胞或未分化中间细胞恶变为原位癌细胞;然后在未知因素的影响下,原位癌细胞呈侵袭性而形成浸润性鼻咽癌.     

性激素受体在大肠癌中的表达及临床意义

为研究性激素 (SR)在大肠癌及正常大肠组织中的表达情况及临床意义 ,采用免疫组化ABC法对 80例大肠癌、10例正常大肠粘膜进行雌激素受体 (ER)、孕激素受体 (PR)及雄激素受体 (AR)指标的检测 .80例大肠癌中ER、PR、AR的阳性率分别为 80 %、75 %、40 % ,正常大肠粘膜中三项指标表达很低 ,甚至无表达 .二者间有显著差异 (P <0 0 1) ,大肠癌中SR的高度表达说明其生理学行为与性激素有关 .因此对SR阳性大肠癌病人进行内分泌治疗可能是除手术、化疗及免疫治疗外一种新的治疗方法 ,并为早期诊断大肠癌及判定预后、指导临床治疗提供依据     

探讨MSCT对肝细胞癌合并动静脉分流的诊断价值

目的探讨肝细胞癌合并AVS(包括HAPVS和HAHVS)的MSCT影像学表现,评价MSCT在AVS诊断中的价值.方法回顾性分析298例HCC患者中的68例合并AVS患者的MSCT表现.所有患者采用SiemensSensation16层螺旋CT行动态增强扫描,动脉期延迟20~25 s,静脉期延迟55~60 s,将采集的薄层图像传到Wizard工作站进行血管重建,部分病例采用SSD,VRT,MIP技术,部分采用MPR技术.结果门静脉主干和/或1级分支提早显影,或显影密度大于肠系膜上动脉/脾动脉者,属于中央型(n=15);门静脉2级和/或以下分支提早显影,或显影密度大于上1级分支者,属于周围型-Ⅰ型(n=18);一过性肝实质强化者,属于周围型-Ⅱ型(n=32);4例HAHVS HCC病灶内粗大迂曲引流静脉汇集至肝静脉,肝静脉提早增强、浓密显影.SSD,VRT和MIP对中央型AVS显示率达100%,在显示能力上无统计学意义;在周围型-Ⅰ型上,SSD的显示能力不及VRT和MIP,VRT和MIP在统计学上无差异;对于周围型-Ⅱ型,3种技术显示均较低,无法用来评估,补充采用MPR,MPR对THPE的显示能力达100%.结论HCC合并AVS具有多种复杂的表现形式,CTA可以弥补CT横轴位的不足,二者结合,明显提高了AVS的诊断和鉴别诊断能力.     

Anti-HepG-2 Cell Properties of Rare Earth Tungstosilicic Polyoxometalates Containing 5-Fluorouracil

Two novel rare earth tungstosilicic polyoxometalate containing 5-fluorouracil,K26(C4H4FN2O2)8Pr(SiW11O39)4·10H2O(FPSW) and K26(C4H4FN2O2)8Sm(SiW11O39)4·9H2O(FSSW),were synthesized and their structure were characterized by using elemental analysis,FTIR spectra,X-ray powder diffraction and TG.The antitumor activity tests of the compounds FPSW and FSSW were carried out by the methyl thiazolyl tetrazolium method in hepatocellular carcinoma cell HepG-2.The results showed that FPSW and FSSW could inhibit the HepG-2 cells in vitro significantly.The EC50 of FPSW and FSSW is 1.94×10-5 and 1.32×10-5 mol·L-1 respectively.The therapeutic index of FPSW and FSSW is 0.76 and 1.58 respectively.