Hedgehog信号通路与肿瘤的研究新进展

Hedgehog（Hh）信号通路在果蝇中被首次发现。该信号通路能有效调控哺乳动物的胚胎发育过程,此外,在调控细胞的分化、增殖、血管形成及肿瘤形成方面起重要作用。Hh信号通路是一个Hh-Ptch-Smo-Gli的级联反应过程。该通路的配体包括:Hedgehog配体［Sonic Hh（SHh）、Indian Hh（IHh）和Desert Hh（DHh）］,Ptch受体（Ptch1、Ptch2）,Smoothened受体（Smo）,融合同源物（Sufu）的抑制因子,驱动蛋白Kif7,蛋白激酶A（PKA）和环腺苷一磷酸（cAMP）。该级联反应中的终末转录因子Gli调控的下游基因过度表达可能是导致肿瘤产生的关键因素。许多研究者已经发现,Hegehog信号通路与一系列人类实体瘤的形成关系密切。本文就近年来Hedgehog信号通路及其与肿瘤关系的研究进行综述。     

多囊蛋白在肿瘤研究中的新进展

多囊蛋白（polycystin，PC）作为一个细胞表面的膜受体，是一种位于细胞表面的多功能跨膜蛋白，在多种上皮细胞中表达。作为一种新型的机械敏感分子，参与常染色体显性多囊肾病、多囊肝等疾病中囊肿形成扩张、骨骼生长发育及创伤愈合等多种生理病理过程。近年来研究发现多囊蛋白与肿瘤的发生发展密切相关,通过cAMP/PKA、Wnt/β-catenin、mTOR、GSK3β等多个信号传导通路，参与肿瘤细胞的增殖、黏附、凋亡及迁移过程，并与肿瘤治疗及预后相关。现总结近年来PC在肿瘤中的生物学作用及研究进展作一综述。     

胰腺肿瘤干细胞研究新进展

胰腺肿瘤尤其是胰腺导管腺癌的恶性程度高,转移性强,预后差。以往研究表明肿瘤干细胞(cancer stem cells,CSC)在胰腺肿瘤的发生、发展过程中起重要作用,深入了解胰腺肿瘤的发病机制将有助于针对性治疗。在胰腺发育过程中,复杂的信号通路和转录因子决定了其前体细胞分化方向,在胰腺发生恶变过程中,这些因素又参与其中,因而往往可以作为追溯CSC的标志。一些研究也应用特定蛋白来筛选胰腺CSC。现就胰腺CSC的来源、鉴定和靶向治疗进行综述。     

转录因子HOXB7在肿瘤及相关信号通路中的作用

转录因子HOXB7在多种肿瘤组织中高表达,且与肿瘤分期、预后密切相关。研究表明,HOXB7不仅参与调控细胞增殖和凋亡,在肿瘤转移过程中也发挥重要作用。多个信号转导通路可以调控HOXB7的表达与活化,同时HOXB7也可影响通路中多个重因子,其在肿瘤发生发展中发挥重要作用,可成为肿瘤治疗的潜在靶点。     

调控肿瘤EMT的转录因子及其相关信号通路

上皮细胞-间充质细胞转换(epithelial-mesenchymal transition,EMT)是指通过某种因素刺激,使上皮细胞表型发生改变,表现出间质表型的特定生物学变化,具体表现为上皮细胞标志蛋白减少,如E-钙黏素等,而间充质细胞标志蛋白上调,如N-钙黏素,波形蛋白等.研究表明,EMT在肿瘤的侵袭转移过程中发挥着关键调控作用,EMT是肿瘤细胞侵袭转移的第一步和最重要的影响因素,大约90％的肿瘤患者死亡都源于肿瘤的转移,因此对EMT机制的研究仍是肿瘤研究的热点,了解调控肿瘤EMT的具体分子机制对于肿瘤的防治意义重大.     

肿瘤相关异常脂质代谢研究进展

肿瘤细胞具有较强的适应周围环境的能力,而这种能力主要通过肿瘤细胞能量重排来实现,如糖酵解过度活跃、谷氨酰胺代谢活跃和脂肪酸氧化异常等。多项研究证实脂质代谢异常与肿瘤细胞恶性生物学行为密切相关,如增殖、侵袭转移、抗凋亡等。本文对不同肿瘤脂质代谢特点,不同脂质类型对肿瘤细胞的影响,肿瘤治疗过程对脂质代谢的影响,肿瘤脂质代谢相关信号通路等作一综述,希望对靶向肿瘤脂质代谢的临床治疗提供依据。     

核心蛋白聚糖与肿瘤信号通路

核心蛋白聚糖(decorin)是富含亮氨酸的小分子蛋白聚糖家族成员之一.decorin通过调节细胞内多种信号通路影响肿瘤的增殖、分化及迁移.decorin在调节细胞因子、免疫抑制及抑制肿瘤细胞生长和转移上的作用,必将成为肿瘤治疗的一个新靶点.     

miRNA - 338 与肿瘤相关研究新进展

MicroRNA（miRNA）是一类具有调控功能的小分子非编码RNA,在转录后水平调节多个靶基因的表达,对个体发育、细胞凋亡、增殖及分化等生命过程都有重要作用。近来研究发现miRNA一338在很多疾病中发生了异常表达,尤其与肿瘤的发生发展存在密切的联系。本文就miRNA一338与疾病关系的研究进展进行综述。     

胃肠道肿瘤与干细胞相关研究新进展

胃肠道肿瘤是人类最常见的恶性肿瘤之一,近年来其发病率与死亡率呈上升趋势,随着肿瘤发病机制研究的深入,大量证据表明肿瘤实际上是一种干细胞疾病,干细胞与肿瘤的发生、增殖、侵袭、转移、复发密切相关.     

星形细胞上调基因-1与肿瘤的关系

星形细胞上调基因-1(AEG-1)是经人类免疫缺陷病毒-1(HⅣ-1)感染、肿瘤坏死因子-α(TNF-α)或糖蛋白肽gp-120处理人胚胎初级星形胶质细胞后诱导表达的分子,其在多种肿瘤细胞中高表达,与肿瘤细胞增殖、侵袭和转移关系密切,能促进肿瘤血管生成,相关分子机制涉及PI3K-AKT、NF-κB及Wnt等重要信号通路...     

miRNA-21 as High Potential Prostate Cancer Biomarker in Prostate Cancer Patients in Indonesia

Objective: This study aimed to explore the diagnostic performance of miRNA-21 to differentiate between Prostate Cancer (PCa) and Benign Prostatic Hyperplasia (BPH) patients in Indonesia. Methods: Urine samples were collected from each PCa and BPH patient. miRNA-21 relative expression against the reference gene was analyzed and compared between the two. miRNA expression was then analyzed using the comparative quantification method to find the fold change. miR-21 validity in identifying PCa patients was performed by quantifying the sensitivity and specificity using samples in this study. Result: The results of this study indicated that miRNA-21 relative expression against miRNA-16 in PCa and BPH showed 12.95 differences in fold change. Moreover, using prostate biopsy as the gold standard to differentiate PCa and BPH, miRNA-21 Cq expression has 100% sensitivity and 75% specificity in differentiating the two. Conclusion: miRNA-21 relative expression can be used to discriminate PCa from BPH by using a urine sample. Furthermore, the expression of miR-21 has higher sensitivity than PSA; therefore, miR-21 has a high potential to be analyzed and developed further for clinical diagnosis of prostate cancer.     

Clinical Significance of Circulatory miRNA-21 as an Efficient Non-Invasive Biomarker for the Screening of Lung Cancer Patients

Dysregulation in the miRNA-21 expression has been previously observed in a number of malignancies and not onlyin the tumor cell itself but also in the body fluids of the cancer patients. The present study aimed to find out the clinicalsignificance of cell-free circulating miRNA-21 as an efficient non-invasive biomarker for the screening of lung cancerpatients. The present case-control study included plasma samples from 80 lung cancer patients and 80 healthy controls.Magnetic bead technology was used for efficient miRNA isolation and advanced TaqMan miRNA assays were usedfor the quantification of miRNA-21 level in the plasma of the lung cancer patients and healthy individuals.The overallmean relative expression level of plasma miRNA-21 among lung cancer patients (2.32±1.7) was higher when comparedto healthy individuals (0.715 ± 0.48) and it showed a significant difference of pwas 0.8913 [95% confidence interval (CI): 0.8394 to 0.9431, p< 0.0001] and the sensitivity and specificity were both80.0% when the cut-off value was 1.207. In conclusion, plasma miRNA-21 can be efficiently extracted by the magneticbead technology and quantified by the advanced TaqMan miRNA assay. Plasma miRNA-21 showed a high ability todistinguish between lung cancer patients and healthy individuals, therefore can be used as an efficient non-invasivebiomarker for the screening of Lung cancer patients.     

Evaluation of miRNA-21 and miRNA Let-7 as Prognostic Markers in Patients With Breast Cancer

Background

Breast cancer remains one of the top threats to women’s health. The current lack of tumor markers with desirable sensitivity and specificity is a major obstacle toward the future management of breast cancer. Many studies are directed to reveal the diagnostic and prognostic potentials of circulating miRNAs in breast cancer. In this study, we attempt to evaluate the feasibility and clinical utility of circulating miRNA-21 and let-7 as prognostic biomarkers for breast cancer.

血清miRNA-21在胃癌中的诊断价值

目的:探讨血清miRNA-21在胃癌中的表达及其诊断价值.方法:收集2015年1月至2016年1月于上海交通大学医学院附属新华医院及新华医院崇明分院收治住院的50例胃镜病理确诊胃癌患者的血清及临床资料,同时收集25例胃癌癌前病变患者及25例胃黏膜基本正常患者的血清作为对照.用荧光定量PCR的方法检测miRNA-21的表达量,比较三者的表达差异,用ROC曲线确定其诊断价值.结果:胃癌患者血清中miRNA-21的表达水平显著高于癌前病变患者及胃黏膜正常患者,癌前病变患者及胃黏膜正常患者未见明显差异.此外,胃癌患者血清miRNA-21表达水平与年龄、性别、肿瘤大小无显著相关性,但因浸润深度、淋巴结转移、TNM分期不同而有显著差异.血清miRNA-21诊断胃癌的最佳灵敏度和特异度分别为0.78、0.98(P ＜0.05).结论:血清miRNA-21能区分胃癌患者与非胃癌患者,并且其表达水平与胃癌的TNM分期有关,有着较高诊断价值.     

唾液中miRNA-21对早期喉鳞状细胞癌的诊断价值

目的 初步探讨喉鳞状细胞癌患者唾液中miRNA-21对早期喉鳞状细胞癌（LSCC）的诊断价值。方法 收集20例喉鳞状细胞癌患者和15例喉息肉患者及15例健康对照组的唾液,采用RT-PCR定量检测比较miRNA-21的相对表达情况,监测比较6例LSCC患者手术前和手术后6月的miRNA-21的变化。结果 喉鳞状细胞癌患者的唾液中miRNA-21的表达水平较健康对照组显著上调（P=0.036）。ROC曲线分析miRNA-21对LSCC的诊断价值发现,唾液中miRNA-21在ROC曲线下面积 （AUC）为 0.792（95%CI: 0.5353~0.885, P=0.036）。手术后6月的miRNA-21相对表达水平较手术前明显下降（P=0.041）。结论 喉鳞状细胞癌患者唾液中的miRNA-21存在高表达,将来可能有望成为早期诊断喉鳞状细胞癌的指标。     

miRNA 和恶性肿瘤研究进展

microRNA（miRNA）是一类小RNA分子,在转录后水平对基因的表达进行调控。大量的证据显示绝大多数人类恶性肿瘤具有miRNA异常表型。miRNA与肿瘤中许多细胞过程如分化、增生和凋亡的改变有关。本文回顾了miRNA在肿瘤发生发展中的作用及其作为诊断、预后和治疗工具的可能性。      

miRNA-214在乳腺癌组织中的表达及其意义

[目的]探讨miRNA-214在乳腺癌组织中的表达及其与临床病理特征及预后的关系.[方法]应用实时定量qPCR检测45例乳腺癌及癌旁正常组织中miRNA-214的含量,分析其与临床病理特征、预后的关系.[结果]乳腺癌组织中miRNA-214的含量明显低于癌旁正常组织,差异有统计学意义(P＜0.01);miRNA-214在Ki-67阴性组的表达量明显高于Ki-67阳性组,差异具有统计学意义(P=0.01);miRNA-214水平与患者的年龄、月经状况、临床分期、肿瘤大小、淋巴结转移、ER、PR、Her-2及p53的表达均无关(P＞0.05).[结论]miRNA-214在乳腺癌组织中呈低表达,并与Ki-67表达相关,提示其可能与乳腺癌的发生、发展及预后有关.     

血清miRNA-21、IL-25表达水平与肾癌患者临床特征的关系

目的探讨血清微小RNA-21(miRNA-21)、白细胞介素-25(IL-25)表达水平与肾癌患者临床特征的关系。方法选取60例肾癌患者作为肾癌组,选取60例健康体检者作为对照组。采用酶联免疫吸附测定(ELISA)法检测两组受试者的血清IL-25表达水平,采用逆转录聚合酶链反应(RT-PCR)技术检测两组受试者的血清miRNA-21表达水平。分析不同Fuhrman分级、肿瘤直径、肿瘤分期、淋巴结转移情况的肾癌患者血清miRNA-21、IL-25表达水平的差异。结果肾癌组患者的血清miRNA-21、IL-25表达水平均明显高于对照组(P<0.01);不同Fuhrman分级、肿瘤直径、肿瘤分期、淋巴结转移情况肾癌患者的血清miRNA-21表达水平比较,差异均无统计学意义(P>0.05)。肿瘤分期为Ⅲ～Ⅳ期、有淋巴结转移肾癌患者的血清IL-25表达水平高于肿瘤分期为Ⅰ～Ⅱ期、无淋巴结转移的患者,差异均有统计学意义(P<0.05)。结论肾癌患者的血清miRNA-21、IL-25表达水平较健康人群明显升高,且血清IL-25水平升高可能与肾癌患者的病理学分期和淋巴结转移情况有关。     

Quantitative Assessment the Relationship between p21 rs1059234 Polymorphism and Cancer Risk

p21 is a cyclin-dependent kinase inhibitor, which can arrest cell proliferation and serve as a tumor suppressor.Though many studies were published to assess the relationship between p21 rs1059234 polymorphism andvarious cancer risks, there was no definite conclusion on this association. To derive a more precise quantitativeassessment of the relationship, a large scale meta-analysis of 5,963 cases and 8,405 controls from 16 eligiblepublished case–control studies was performed. Our analysis suggested that rs1059234 was not associated withthe integral cancer risk for both dominant model [(T/T+C/T) vs C/C, OR=1.00, 95% CI: 0.84-1.18] and recessivemodel [T/T vs (C/C+C/T), OR=1.03, 95% CI: 0.93-1.15)]. However, further stratified analysis showed rs1059234was greatly associated with the risk of squamous cell carcinoma of head and neck (SCCHN). Thus, larger scaleprimary studies are still required to further evaluate the interaction of p21 rs1059234 polymorphism and cancerrisk in specific cancer subtypes.     

LincRNA-p21在癌症机制中的研究进展CSCD

长链非编码RNA是一类不编码蛋白质的RNA,通过多种机制参与不同的生物学行为。lincRNA-p21是一种抑癌基因,并与p53密切相关。lincRNA-p21通过MDM2、ING1b和p21等多个靶标调节p53参与细胞周期、增殖、凋亡的调控,并通过HIF-1α协调Warburg效应参与细胞代谢等多种生物学作用。lincRNA-p21与肿瘤的预后和治疗密切相关。因此lincRNA-p21可作为癌症的诊断和预后的生物标志物。本文就lincRNA-p21生物学功能与在疾病中的作用机制作一简要综述。