不典型原发性肝癌的CT特征分析

目的分析不典型原发性肝癌(PLC)CT动态强化方式。方法回顾性分析临床及病理证实的29例原发性肝癌中4例多期动态增强CT不典型表现。结果 29例病灶平扫均呈低密度,22例肝细胞癌(hepatocellular carcinoma,HCC)增强扫描呈典型改变(动脉期强化,门脉期及平衡期造影剂廓出或门脉期强化,平衡期造影剂廓出)。1例HCC呈渐进性强化呈等密度,再延时扫描出现低密度环;1例肿块出现坏死、囊变并出血,周边持续明显强化并见增粗血管;2例胆管细胞癌(cholangiocarcinoma,CC)呈分叶或不规则,渐进性强化不达等密度,无胆管扩张。结论少部分原发性肝癌因病灶内组织成分不同致影像表现不典型,需结合多相期表现进行分析,必要时应行穿刺取活检,以减少误诊。     

5例腹膜后异位嗜铬细胞瘤的CT表现并文献复习

目的：分析腹膜后异位嗜铬细胞瘤的CT影像学结果,探讨其特异性的CT表现。方法：回顾性分析5例经病理证实为腹膜后异位嗜铬细胞瘤患者的临床、手术及CT资料。结果：5例均为单发肿块,位于腹主动脉周围,CT平扫表现为境界清楚的圆形或椭圆形肿块,肿块直径3CM-7CM,平均4．5CM,瘤体密度较均匀,无囊变和坏死,增强后呈明显较均匀强化。结论：腹膜后异住嗜铬细胞瘤常位于腹主动脉旁,CT增强显示腹主动脉旁类圆形富血供软组织肿块,若t临床合并高血压,应高度警惕嗜铬细胞瘤的可能。     

肝内胆管细胞癌的CT诊断

目的:研究肝内胆管细胞癌的CT表现,提高对肝内胆管细胞癌的认识。方法:回顾性分析经手术及病理证实的26例肝内胆管细胞癌的CT表现,并与手术结果对比分析。结果:肝内胆管细胞癌的CT表现为低密度不规则肿块,边界欠清,增强扫描肿瘤边缘实质部分轻中度强化。增强扫描:动脉期无强化11例,轻度强化15例。延迟扫描26例均有不同程度延迟强化。结论:肝内胆管细胞癌的CT表现有一定的特征性,对于与肝内其他常见痛变的鉴别诊断有重要价值。     

多层螺旋CT动态增强扫描对不同类型小肾癌的诊断价值研究

目的:探讨多层螺旋CT动态增强扫描对不同类型小肾癌的诊断价值。方法:回顾性分析2013年4月至2016年4月间我院收治的经病理证实的小肾癌患者62例的CT平扫及三期动态增强扫描征象进行分析与比较。结果:肾透明细胞癌患者、肾乳头状细胞癌患者及肾嫌色细胞癌患者一般资料无统计学差异(P0.05)。62例患者共检出低密度14例,等密度38例以及高密度10例。透明细胞癌以等密度居多(60.00%),乳头状细胞癌以等密度居多(70.43%),嫌色细胞癌以低密度居多(66.67%)。不同类型小肾癌患者CT平扫结果之间差异显著(P0.05)。透明细胞癌以明显强化居多(77.14%),乳头状细胞癌以轻度强化居多(90.48%),嫌色细胞癌以中等强化居多(66.67%),不同类型间强化程度比较有统计学差异(P0.05)。不同类型间强化模式以均匀强化及典型强化居多,三组差异不显著(P0.05)。透明细胞癌三期CT值均显著高于乳头状细胞癌及嫌色细胞癌,差异有统计学意义(P0.05),而乳头状细胞癌及嫌色细胞癌各期差异不显著(P0.05)。三种类型小肾癌实质期CT值均显著高于其他两期,三期比较差异显著(P0.05)。结论:多层螺旋CT动态增强扫描对于不同类型小肾癌的鉴别诊断具有积极的意义。     

肾嗜酸细胞腺瘤的诊疗分析（附47 例报告）

目的:分析肾嗜酸细胞腺瘤的临床特征,指导并提升诊疗水平。方法:回顾性分析47例肾嗜酸细胞腺瘤的临床资料,包括临床特点、影像表现、病理特征、治疗方法及预后等方面。结果:47例患者中43例因查体偶然发现,仅4例表现为患侧腰痛症状。术前影像诊断中1例考虑嗜酸细胞腺瘤,1例考虑腺瘤,2例CT与MRI报告不一致(CT与MRI各有1例诊断良性,具体类型不确定),其余43例均诊断为肾细胞癌(1例囊性肾癌)。27例行肾癌根治性切除术,16例行肾部分切除术,4例行微波或射频消融术。所有患者术后病理均诊断为肾嗜酸细胞腺瘤,随访4～179月,均无转移或复发。结论:肾嗜酸细胞腺瘤作为一种与肾细胞癌难相鉴别的良性肿瘤,因缺乏特异性表现,极易误诊为肾细胞癌,因此对肾肿瘤患者应尽可能选择保肾治疗方案。     

囊性肾细胞癌5例超声特征及诊断体会

目的：提高对囊性肾细胞癌的认识。方法：回顾我院5例经病理诊断为囊性肾细胞癌病例的超声图像、临床症状和预后随访。结果：肿瘤声像图在肾囊肿的基础上,分为(1)单房囊肿型(2例),囊壁见光斑,不均匀增厚,或乳突状突起。(2)多房囊肿型(2例)。(3)低回声实体型(1例)。CDFI、CDF在肿瘤的周围、内部及囊壁均无明显异常血流信号。5例患者均无明显临床症状,特别是血尿,全部为透明细胞癌,均行根治性切除术,无淋巴转移,均无复发和转移。结论：囊性肾细胞癌是一种罕见的肾细胞癌,是少血管性肿瘤,一般为早期,临床上一般无症状,预后较好。超声显示复杂性囊肿在临床上要引起重视。     

7例肺类癌的CT影像报道及文献复习

目的:分析肺类癌的CT影像表现,结合文献复习以提高对该病的认识。方法:回顾性分析7例经病理证实的肺类癌的CT表现,其中3例行胸部CT平扫检查,4例行胸部CT平扫及增强扫描。结果:7例患者中有6例为典型类癌,1例为非典型类癌。6例典型类癌中:1例为微瘤型类癌,表现为右侧肺门旁支气管扩张、结石及条片状影;1例为硬化性血管瘤合并类癌,表现为右侧肺门旁肿块,边缘较光整,伴晕征;2例为右侧肺门旁肿块,边缘光整,明显强化,伴有邻近支气管扩张或支气管粘液嵌塞、远端伴阻塞性肺不张或肺炎改变;2例表现为肺内孤立小结节,边缘光整,无强化。1例非典型类癌表现为不均匀强化的右肺门旁肿块,伴右肺门、纵隔淋巴结转移。结论:肺类癌的CT影像表现多样,典型病例的CT表现具有一定的特征性。     

孤立性纤维性肿瘤15例CT影像病理特征分析

对比研究孤立性纤维性肿瘤(SFTs)的CT影像学特征及其与病理学的关系,评估CT在SFTs诊断中的应用价值。方法:收集15例孤立性纤维性肿瘤,回顾分析CT表现以及病理形态学和免疫表型变化。结果:15例中6例发生于胸腔内(3例发生于肺,3例位于壁层胸膜);此外鼻腔2例,上颌窦、腹腔、咽旁、腮腺、肾脏、眼眶、髂窝各1例。临床主要表现为局部肿块及其引起的压迫症状,CT扫描显示肿块边界清楚,增强扫描早期呈明显均质性强化。病理学改变显示瘤细胞呈梭形细胞为主,具有细胞密集区与细胞疏松区特征,间质可见瘢痕样的胶原和鹿角样厚壁血管,瘤细胞排列方式多样,免疫组化染色CD34阳性(91．67%), CD99(88．88%),Bcl-2(87．5%)和Vim(100%)。结论:SFT因有完整的包膜,故多为境界清楚的软组织密度肿瘤,如境界不清多提示侵袭性生长。因病理学上肿瘤细胞分布以及有无变性坏死而呈现不同的密度特征,因富血管表现而在增强CT扫描时有较为明显的强化;最终诊断需要免疫组织化学染色证实。     

颅内血管外皮细胞瘤MRI诊断价值

目的:评价MRI对颅内血管外皮细胞瘤(intracranial hemangiopericytoma,HPC)的诊断价值.方法:回顾性分析手术、病理证实6例颅内血管外皮细胞瘤患者的MRI影像资料,研究病变基本特征、信号特点及强化方式.结果:6例均位于颅内脑外,多为不规则分叶状软组织肿物,病灶大小平均为5.3cm,占位效应明显,瘤周水肿较轻,肿瘤内均可见迂曲流空血管.病灶以等高TW2、等低TW1信号为主,4例出现囊变、坏死及出血信号.增强扫描病灶呈明显均匀强化,囊变部分无强化.结论:颅内血管外皮细胞瘤MRI表现具有一定特征性:肿瘤体积较大、多呈分叶状软组织肿块,以等TW1、等TW2信号为主,其内可见丰富血管流空、坏死及囊性变,有占位效应,但瘤周水肿不明显;增强扫描实体呈明显均匀强化,可出现“脑膜尾征”.     

乳腺导管内乳头状瘤、非典型乳头状瘤与导管内乳头状癌诊断与鉴别诊断

目的:探讨乳腺导管内乳头状癌和导管内乳头状瘤、非典型乳头状瘤的病理表现及诊断与鉴别诊断.方法:对20例乳腺导管内乳头状癌及23例导管内乳头状瘤、5例非典型导管内乳头状瘤进行大体及镜下病理学分析及免疫组化分析,并结合文献对其病理表现、病理形态特点及鉴别诊断进行探讨.结果:20例乳腺导管内乳头状癌HE染色表现为导管明显扩张,有真性乳头,乳头之轴心由纤维血管束组成,乳头覆盖细胞有多种形式,但真正的肌上皮是缺如的.免疫组化SMA/p63显示局部或完全的肌上皮细胞消失,CEA85%的乳头状癌阳性.23例导管内乳头状瘤乳头存在肌上皮层,免疫组化结果与导管内乳头状癌相反.5例非典型乳头状瘤局部(＜1/3的区域)显示有不典型上皮增生,局部有肌上皮缺失.结论:乳腺导管内乳头状癌是一种具有乳头状癌样结构基础上的原位恶性上皮增生,但无浸润的癌.预后好于其他型导管原位癌,免疫标记SMA、p63和CEA可以帮助该肿瘤的诊断及与乳腺导管内乳头状瘤、非典型导管内乳头状瘤鉴别诊断.     

Activity of a short course of interferon α for metastatic renal cell carcinoma — a phase-2 study

Twelve patients with metastatic renal cell carcinoma were entered into a phase-2 study of an 8-week course of interferon (INF) therapy. INF was given subcutaneously at a dose of 3 mu, three times per week. The patients were WHO performance status 0–2. A complete response was obtained in two patients (17% response rate), which has been maintained at 23 and 45 months. One of these patients presented with cranial and lung metastases and received cranial irradiation and decradron concurrent with INF. The toxicity of INF has been low. The optimal duration of INF therapy warrants further evaluation.     

MicroRNA-34a通过多向调控促癌基因抑制肾癌细胞生长

目的:探讨microRNA-34a(miR-34a)在肾癌细胞中的生物学作用及调控机制.方法:应用miR-34amimics在体外转染769P,786-O和Caki-1细胞;运用qRT-PCR检测miR-34a在三个细胞株的相对表达情况,以及转染后癌基因mRNA的表达情况;观察miR-34a对细胞生长的影响.结果:769P,786-O和Caki-1细胞中miR-34a在786-O中表达最低,769P次之,Caki-1表达最高;利用miR-34a mimics升高769P,786-O和Caki-1细胞miR-34a,发现三个细胞株多个癌基因mRNA表达不同程度的降低(P＜0.05)及生长和集聚能力的降低.结论:miR-34a可能通过调控多个癌基因表达在肾癌中起抑癌作用.miR-34a mimics可抑制肾癌细胞的生长,因此miR-34a有可能作为肾癌基因治疗的新靶点.     

Design,synthesis and biological evaluation of 4-aniline-thieno[2,3-d]pyrimidine derivatives as MNK1 inhibitors against renal cell carcinoma and nasopharyngeal carcinoma

MAP Kinase Interacting Serine/Threonine Kinase 1 (MNK1) play important roles in the signaling transduction of MAPK pathways. It is significantly overexpressed in renal clear cell carcinoma and head-neck squamous cell carcinoma tissues in both mRNA and protein levels. Based on the crystallographic structure of MNK1 protein and binding modes analysis of known MNK inhibitors, we have designed and synthesized a series of 4-aniline-thieno[2,3-d]pyrimidine derivatives as potential MNK1 inhibitors. These synthetic compounds are tested in biochemical and cell proliferation assays, and six of them display potent inhibitory capacity against MNK1 kinase and cancer cell lines. Compound 12dj with strongest inhibitory capacity is transferred to molecular mechanism studies, and the results indicated that 12dj remarkably suppresses the phosphorylation of EIF4E, a substrate of MNK1. And the expression levels of MNK1, ERK1/2 and pERK1/2 are not affected by compound 12dj incubation in SUNE-1 and 786-O cells. In summary, our works suggested that these novel 4-aniline-thieno[2,3-d]pyrimidine based MNK1 inhibitors might be attractive lead compounds for targeted therapy of renal cell carcinoma and nasopharyngeal carcinoma.     

Quantitative proteomic analysis to discover potential diagnostic markers and therapeutic targets in human renal cell carcinoma

Renal cell carcinoma (RCC) is relatively resistant to chemotherapy and radiotherapy. Recent advances in drug development are providing novel agents for the treatment of RCC, but the effects are still minimal. In addition, there is an urgent need to identify diagnostic markers for RCC. In this report, to discover potential diagnostic markers and therapeutic targets, we subjected RCC samples to a quantitative proteomic analysis utilizing 2-nitrobenzenesulfenyl (NBS) reagent. Proteins were extracted from RCC and adjacent normal tissue, obtained surgically from patients, and labeled with NBS reagent containing six (12)C or (13)C. This was followed by trypsin digestion and the enrichment of labeled peptides. Samples were then subjected to analysis by MALDI-TOF MS. NBS-labeled peptides with a 6 Da difference were identified by MS/MS. Thirty-four proteins were upregulated in more than 60% of the patients of which some were previously known, and some were novel. The identity of a few proteins was confirmed by Western blotting and quantitative real time RT-PCR. The results suggest that NBS-based quantitative proteomic analysis is useful for discovering diagnostic markers and therapeutic targets for RCC.     

Inhibition of human renal cancer by monoclonal-anti-body-linked methotrexate in an ascites tumor model

Summary The monoclonal antibody DAL K29 against a cell-surface antigen associated with a human renal cell carcinoma was covalently linked to the antifolate methotrexate with full retention of antibody activity and partial retention of drug activity. Using an ascites tumor model, developed after intraperitoneal (i.p.) inoculation of 5 × 10⁶ cells of the human kidney cancer line Caki-1 per pristane-primed nude mouse, we showed that the methotrexate-Dal-K29 conjugate was a more potent tumor inhibitor (P <0.0005) of human renal cell carcinoma (which is resistant to currently available modalities including chemotherapy) than the drug or mAb alone, the drug linked to an isotype-matched nontumor-specific IgG or a mixture of the drug and the mAb. Only the conjugate could produce tumor-free survival in a proportion of the mice during the period of observation (i.e. 150 days after tumor inoculation).     

Synthesis and biological evaluation of some novel thiobenzimidazole derivatives as anti-renal cancer agents through inhibition of c-MET kinase

Benzimidazole is an interesting scaffold constituting a main core in many anticancer agents against variable cell lines as Carbendazim (I) and Nocodazole (II). Accordingly, eighteen compounds of 2-((1H-benzoimidazol-2-yl)thio)-1-(aryl/heteroaryl)ethan-1-ones, in their sulfate salt and free forms, were designed and investigated as anticancer agents. In vitro preliminary screening of selected compounds by the National Cancer Institute (NCI) on a panel of 60 cell lines revealed renal cancer cell line (A498) as the most vulnerable cell line; accordingly, IC₅₀ values against A498 cell line were determined for compounds with the best results. The best inhibitory activity was for compound 4a with (IC₅₀ = 6.97 µM) compared to sunitinib as a reference drug (IC₅₀ = 6.99 µM). Compound 4a was further subjected to cell cycle analysis that indicated the decrease in cell population in the G2/M phase when compared to the untreated control cells. In addition, it showed significant increase in the late apoptosis in Annexin-V FTIC study compared to the control cells. An enzymatic inhibitory study on compound 4a against c-Met and MAP kinases revealed its better activity against c-Met kinase with (IC₅₀ = 0.27 µM) compared to sunitinib (IC₅₀ = 0.18 µM). Molecular docking study was conducted to reveal the interactions of compound 4a in the active site of c-Met kinase. Computational ADME study was performed to insure that compound 4a has proper pharmacokinetic and drug-likeness properties.     

siRNA下调EZH2基因对肾癌细胞系769-P增殖的影响

目的：运用小干扰RNA下调果蝇zeste基因增强子人类同源物（enhancer ofzeste homolog 2,EZH2）在肾癌细胞系769-P中的表达,明确其对肾癌细胞增殖的影响。方法：将处于对数生长期769-P细胞分为实验组（experiment group）、阴性对照组（negative group）、空白对照组（blank group）,合成靶向EZH2基因的小干扰RNA片段（EZH2-siRNA）和无效序列片段后,通过脂质体介导分别转染至实理组和阴性对照组,空白对照组未做任何处理。以qRealtime-PCR检测EZH2基因mRNA水平的变化情况,以MTT法检测各组细胞增殖变化;流式细胞术（FCM）检测转染后细胞周期变化情况。结果：实理组中EZH2在mRNA表达水平明显受抑制;MTT实验中第4天始,实验组中769-P细胞的增殖能力开始受抑制,第5天时实验组细胞抑制更明显,与阴性对照组和空白组比较差异有统计学意义（P〈0.05）。siRNA转染后实验组中G0/G1期细胞比例明显增多（81.32±3.14）%,与阴性对照组（44.13±1.52）%和空白对照组（45.71±2.32）%差异有统计学意义。结论：EZH2-siRNA可有效下调并抑制肾癌细胞769-P的增殖,EZH2在肾癌的发生、发展中发挥了重要作用,为下一步研究肾癌基因治疗提供了理论支持。     

RNA干扰Ezrin体外对肾癌细胞株786-0增殖、凋亡的影响

目的：构建膜- 细胞骨架联接蛋白Ezrin 基因特异性短发卡RAN 表达载体（small hairpin RNA,shRNA）,探讨其对肾癌细胞株786-0 细胞凋亡、增殖的影响。方法：以Ezrin 为靶基因,以Pgenesil-1 质粒为载体,设计和构建重组体,设计2 条发夹式RNA（shRNA）,合成后克隆入载体Pgenesil-1,扩增并中量提取质粒,应用脂质体Lipofectamine 2000 转染进786-0 细胞,重组质粒转染786-0 肾癌细胞株,用运实时荧光定量PCR 进行筛选鉴定,筛选出抑制率较高的重组质粒载体shRNA-Ezrin1,用shRNA-Ezrin1转染786-0 细胞,采用MTT、流式细胞仪、电镜检测,观察RNA干扰Ezrin 后肾癌细胞株786-0 细胞增殖能力的改变。结果：shRNA干扰后786-0 细胞增殖活性减弱,G0/G1时段明显延长（P〈0.01）,PI缩短（P〈0.01）,细胞凋亡率增加（P〈0.01）。结论：Ezrin与肾癌细胞凋亡、增殖有关,有望成为肾癌基因治疗的一个新靶点。     

siRNA下调EZH2 基因对肾癌细胞系769-P增殖的影响

目的：运用小干扰RNA下调果蝇zeste 基因增强子人类同源物（enhancer of zeste homolog 2,EZH2）在肾癌细胞系769-P 中 的表达,明确其对肾癌细胞增殖的影响。方法：将处于对数生长期769-P 细胞分为实验组（experiment group）、阴性对照组(negative group)、空白对照组（blank group）,合成靶向EZH2 基因的小干扰RNA片段（EZH2-siRNA）和无效序列片段后,通过脂质体介导分 别转染至实理组和阴性对照组,空白对照组未做任何处理。以qRealtime-PCR 检测EZH2 基因mRNA 水平的变化情况,以MTT 法检测各组细胞增殖变化;流式细胞术（FCM）检测转染后细胞周期变化情况。结果：实理组中EZH2 在mRNA 表达水平明显受 抑制;MTT实验中第4 天始,实验组中769-P 细胞的增殖能力开始受抑制,第5 天时实验组细胞抑制更明显,与阴性对照组和空 白组比较差异有统计学意义（P < 0.05）。siRNA 转染后实验组中G0/G1 期细胞比例明显增多(81.32± 3.14)%,与阴性对照组 (44.13± 1.52)%和空白对照组(45.71± 2.32)%差异有统计学意义。结论：EZH2-siRNA 可有效下调并抑制肾癌细胞769-P的增殖, EZH2在肾癌的发生、发展中发挥了重要作用,为下一步研究肾癌基因治疗提供了理论支持。     

肾癌预后分子生物标记物研究进展

肾癌发病率约占全身恶性肿瘤的3%。肾癌组织学行为多变,预后有不确定性。外科手术可以治疗局限性肾癌,但有将近20%的局限性肾癌患者原发肿瘤切除后出现转移,而且肾癌对化疗及放疗均不敏感。基于此临床上开展了许多辅助试验的研究,并建立了许多模型来研究肾癌术后的预后,而模型的精准度一般都需要依据肾癌的生物标记物监测。有很多分子生物标记物已经证实和肾癌预后相关,如VHL、P53、Ki-67等,本文综述了肾癌预后的分子生物标记物的最新进展。