c-Met靶向成像在肿瘤诊断中的应用

肝细胞生长因子受体(c-Met)是一种酪氨酸激酶型受体，对于肿瘤的发生发展至关重要，c-Met靶向治疗已初步应用于临床，其对于癌症患者的治疗具有显著的益处。目前，由于无法对c-Met表达阳性的肿瘤患者进行有效的早期筛选，使得c-Met靶向治疗在肿瘤治疗中总体有效率偏低。c-Met靶向分子成像借助靶向分子成像探针能够实现肿瘤c-Met表达水平及活化状态的定量检测和直观揭示，对于肿瘤的早期诊断、治疗和预后具有重要意义和巨大的潜在价值。结合近年来c-Met靶向分子成像的研究，本文将深入分析、探讨c-Met靶向分子成像探针的构建及其在肿瘤诊断中的应用。     

分子成像与肿瘤靶向治疗*

肿瘤关键分子靶点的异常表达（表达水平和表达状态）与分子靶向治疗反应、治疗效果及预后密切相关。因此,精准评价肿瘤关键分子表达水平和表达状态,无论在肿瘤分子靶向治疗开展前、过程中以及治疗后均显得尤为关键。分子成像可以无创、实时而全面地对肿瘤关键靶点的表达水平及表达状态进行定性、定量研究,对筛选优势人群、指导治疗、判断预后具有重大意义。本文简述基于不同分子探针的分子成像技术在肿瘤靶向治疗过程中的应用,对比分析分子成像在靶向治疗中的价值,以期有益于新型治疗策略的开发。      

分子诊断技术在卵巢癌个体化诊治中应用的现状与进展

肿瘤患者的个体化治疗与疗效和预后的关系日益受到重视,而完善的分子诊断技术是实现个体化治疗的基础和前提。在恶性肿瘤的风险评估、早期诊断、分子分型、肿瘤生物学行为预测、预后评估、药物筛选、疗效监测等研究和临床应用方面,分子诊断技术已体现出巨大的优势。但目前分子诊断技术在寻找卵巢癌新的治疗靶点、指导卵巢癌的靶向治疗、预测卵巢癌患者的预后及指导复发性卵巢癌的个体化治疗方面的应用研究较少,还需要进一步积累数据。     

超顺磁性氧化铁纳米粒子诊断与治疗乳腺癌的研究进展

在乳腺癌的诊疗过程中，常规药物存在靶向性较差和严重的不良反应等缺陷。近年来，具有高选择性及优异成像性能的超顺磁性氧化铁纳米粒子（SPION）已成为影像学领域的研究热点。SPION 是一种具有磁性的纳米材料，其以氧化铁为核心，置于较弱的外磁场中就可产生较强的磁性。新型SPION 具有尺寸小、生物相容性好、制备流程简单和生产成本低等优点，且具有较好的磁响应能力，有望作为医学成像探针和药物靶向递送系统的载体，在提高肿瘤影像学特异性诊断和实现更精确给药等方面都具有良好的医学应用前景。在乳腺癌影像学诊断和治疗中，SPION 可作为分子靶向造影剂用于磁粒子成像观察，还可应用于化疗药物递送、基因传递、免疫治疗和光动力治疗等。随着以SPION为核心的临床试验进一步开展，SPION在乳腺癌诊疗中的应用将进一步拓展。     

生物素-链霉亲和素介导受体靶向卵巢癌SKOV3细胞量子点体外成像的研究

  目的  研制一种生物素-亲和素系统（BAS）介导叶酸受体（FR）靶向量子点（QD）荧光探针,初步验证其靶向性及信号放大效应。   方法  采用活泼酯法,将链霉亲和素（SA）与QD共价偶联制备QD-SA并对其物理特性进行验证;采用活泼酯法以牛血清蛋白为载体合成生物素化叶酸（FA）。通过生物素化FA与QD-SA结合制备BAS介导叶酸受体（FR）靶向QD探针,比较该探针对卵巢癌SKOV3细胞及FR表达阴性的肺癌A549细胞的识别情况,并验证其靶向特异性;对比该探针在生物素化FA孵育1、4 h时成像的效果;比较该探针与未经BAS介导的QD-FA探针在不同孵育时间对卵巢癌SKOV3细胞成像的差异。   结果  BAS介导FR靶向QD探针可特异性识别FR表达阳性的卵巢癌SKOV3细胞,且孵育4 h较1 h荧光信号明显增强,同等条件下其产生的荧光强度较未经BAS介导的QD-FA探针明显增强。   结论  制备了一种特异性好、灵敏度高的BAS介导FR靶向QD探针,该探针在卵巢癌早期诊断方面具有潜在应用价值。      

先进诊疗技术下小细胞肺癌脑预防照射临床价值与研究进展

小细胞肺癌（SCLC）恶性程度高,侵袭性强,易发生颅脑转移。现有指南均推荐脑预防照射（PCI）作为初始系统性治疗后达到完全缓解的SCLC患者的标准治疗方案。但在MRI广泛应用于颅脑转移诊断的今天,放疗同时免疫治疗及分子靶向治疗的联合治疗方案广泛应用于肺癌,PCI在SCLC治疗中的价值受到质疑并面临挑战。而应用海马保护技术及相关药物减少PCI后神经认知功能损伤成为研究热点。本文将近期文献报道的PCI相关研究结果进行综述,为SCLC患者选择最适合的PCI个体化治疗方案提供参考。     

先进诊疗技术下小细胞肺癌脑预防照射临床价值与研究进展

小细胞肺癌（SCLC）恶性程度高,侵袭性强,易发生颅脑转移。现有指南均推荐脑预防照射（PCI）作为初始系统性治疗后达到完全缓解的SCLC患者的标准治疗方案。但在MRI广泛应用于颅脑转移诊断的今天,放疗同时免疫治疗及分子靶向治疗的联合治疗方案广泛应用于肺癌,PCI在SCLC治疗中的价值受到质疑并面临挑战。而应用海马保护技术及相关药物减少PCI后神经认知功能损伤成为研究热点。本文将近期文献报道的PCI相关研究结果进行综述,为SCLC患者选择最适合的PCI个体化治疗方案提供参考。     

含贝伐珠单抗联合方案治疗晚期卵巢癌的研究进展

卵巢癌是常见的女性生殖器官恶性肿瘤之一,严重威胁女性健康。传统一线化疗方案治疗晚期卵巢癌的获益有限且复发率高,探讨新方案以改善晚期卵巢癌患者的生存和预后成为临床和基础研究的热点。贝伐珠单抗是首个应用于卵巢癌的分子靶向药物,含贝伐珠单抗方案一线治疗已成为晚期卵巢癌患者的标准治疗方案,并得到指南推荐。为了探讨这一抗血管生成药物在晚期卵巢癌中更为广泛的应用,包括新的联合方案和应用范围的扩大,近年来,开展了一系列的研究。本文对含贝伐珠单抗联合方案治疗晚期卵巢癌的研究进展进行综述,旨在为开展相关临床研究提供思路。     

卵巢癌抗血管靶向治疗临床研究最新进展

靶向治疗是针对肿瘤组织有别于正常组织的特征,给予有针对性的治疗,从而达到较好的治疗效果和较小的副作用.目前抗肿瘤靶向治疗研究中最多的是抗血管治疗,许多新的药物不断被研发,并已广泛地应用于临床试验.本文对近年来卵巢癌抗血管靶向治疗的临床研究加以综述,以了解这一新的治疗方法在卵巢癌中的治疗现状、面临的问题和治疗前景.     

宫颈及其他鳞癌SCC-Ag、Survivin研究现状

宫颈癌是目前全球女性第三大常见恶性肿瘤,有较高的发病率和死亡率,高危型HPV(HR-HPV)持续感染为其主要致病因素。鳞状细胞癌（squamous cell carcinoma,SCC）是宫颈癌最主要的病理类型,也常见于皮肤、头颈、食管、肺等,严重威胁人类健康及生命。作为一种新型手段,生物标记物及靶向治疗对于鳞癌的诊治具有十分重要的意义。血清SCC-Ag单独检测目前多用于鳞癌的辅助诊断,联合应用诸如HPV-DNA、磁共振技成像（magnetic resonance imaging,MRI）等检查手段,可提高鳞癌诊断的敏感性与特异性,并有助于其致病机制的研究;生存素在鳞癌中的作用近年来正被广泛研究,尤其于鳞癌发病早期凸显其在诊断中的独特应用价值,更进一步研究展示出了其在靶向治疗中的潜在应用前景。     

Noninvasive Imaging Reveals Inhibition of Ovarian Cancer by Targeting CXCL12-CXCR4

Patients with metastatic ovarian cancer continue to have a dismal prognosis, emphasizing the need for new strategies to identify and develop new molecular targets for therapy. Chemokine CXCL12 and its receptor CXCR4 are upregulated in metastatic ovarian cancer cells and the intraperitoneal tumor microenvironment. CXCL12-CXCR4 signaling promotes multiple steps in proliferation and dissemination of ovarian cancer cells, suggesting that targeted inhibition of this pathway will limit tumor progression. To investigate CXCL12-CXCR4 signaling in ovarian cancer and establish effects of inhibiting this pathway on tumor progression and survival, we designed a Gaussia luciferase complementation imaging reporter system to detect CXCL12 binding to CXCR4 in ovarian cancer cells. In cell-based assays, we established that the complementation imaging reporter could detect CXCL12 binding to CXCR4 and quantify specific inhibition of ligand-receptor interaction. We monitored CXCL12-CXCR4 binding and inhibition in a mouse xenograft model of metastatic human ovarian cancer by imaging Gaussia luciferase complementation and assessed tumor progression with firefly luciferase. Bioluminescence imaging studies in living mice showed that treatment with AMD3100, a clinically approved inhibitor of CXCL12-CXCR4, blocked ligand-receptor binding and reduced growth of ovarian cancer cells. Treatment with AMD3100 also modestly improved overall survival of mice with metastatic ovarian cancer. The Gaussia luciferase complementation imaging reporter system will facilitate further preclinical development and optimization of CXCL12-CXCR4 targeted compounds for treatment of ovarian cancer. Our research supports clinical translation of existing CXCR4 inhibitors for molecular therapy for ovarian cancer.     

基于MUC1为靶点的乳腺癌治疗研究进展北大核心

黏蛋白1(mucin 1,MUC1)是黏蛋白家族中最容易被识别的跨膜蛋白,在乳腺癌细胞中过度表达且糖基化水平明显降低,并在乳腺癌发生发展中起到至关重要的作用。作为乳腺癌的治疗靶点,MUC1多年来受到广泛的研究,并已经取得了显著成效。目前,以MUC1为靶点的乳腺癌的治疗研究主要包括基于配体靶向治疗、免疫疗法及一体化诊疗。本文对近年来基于MUC1基因为靶点的乳腺癌治疗研究进展情况进行综述。     

siRNA在卵巢癌靶向治疗中的研究进展

小干扰RNA(siRNA)可以以高度精确的方式诱导基因沉默，因此可用作研究体内和体外单基因功能的工具，也可成为潜在的新靶向治疗药物。卵巢癌是目前最致命的妇科恶性肿瘤，治疗选择有限，需要改进的靶向疗法来对抗卵巢癌。近些年来，siRNA在卵巢癌靶向治疗中的研究越来越受到关注，本文将对siRNA在卵巢癌靶向治疗中的研究进展展开综述。     

Fluorescence imaging agents in cancerology

BACKGROUND: One of the major challenges in cancer therapy is to improve early detection and prevention using novel targeted cancer diagnostics. Detection requests specific recognition. Tumor markers have to be ideally present on the surface of cancer cells. Their targeting with ligands coupled to imaging agents make them visible/detectable. CONCLUSIONS: Fluorescence imaging is a newly emerging technology which is becoming a complementary medical method for cancer diagnosis. It allows detection with a high spatio-temporal resolution of tumor markers in small animals and in clinical studies. In this review, we focus on the recent outcome of basic studies in the design of new approaches (probes and devices) used to detect tumor cells by fluorescence imaging.     

噬菌体展示技术在乳腺癌靶向治疗中的应用(英文)

Phage display is a technology of gene expression and screening, it is widely used in the fields of defining antigen epitopes, signal transduction, genetic treatment, parasites research and tumor targeted therapy. Breast cancer is the most common cancer in women, we can obtain peptides specially associated with breast cancer by using phage display technology, and this method has great potential in early diagnosis of breast cancer and development new targeted drugs.     

Fibroblast recruitment as a tool for ovarian cancer detection and targeted therapy

Metastatic ovarian cancer, the most lethal of gynecologic malignancies, is typically managed by debulking surgery, followed by chemotherapy. However, despite significant efforts, survival rate remains low. We have previously demonstrated, in mouse models, a specific systemic homing of labeled fibroblasts to solid ovarian tumors. Here, we demonstrate the feasibility of utilizing this specific homing of genetically modified fibroblasts for detection and targeted therapy of orthotopic metastatic ovarian carcinoma model in immune‐deficient mice. Using an in vivo metastatic mouse model for ovarian cancer, we demonstrated that fibroblasts expressing fluorescent reporters injected intra‐peritoneally, were specifically recruited to peritoneal tumor nodules (resulting in 93‐100% co‐localization). We further used fibroblasts over expressing the soluble receptor variant of VEGFR1 (s‐Flt1). Mice bearing tumors were injected weekly with either control or s‐Flt1 expressing fibroblasts. Injection of s‐Flt1 expressing fibroblasts resulted in a significant reduction in the ascites volume, reduced vascularization of adherent metastases, and improved overall survival. Using fluorescently labeled fibroblasts for tumor detection with readily available intra‐operative fluorescence imaging tools may be useful for tumor staging and directing biopsies or surgical efforts during exploratory or debulking surgery. Fibroblasts may serve as a beacon pointing to the otherwise invisible metastases in the peritoneal cavity of ovarian cancer patients. Utilizing the recruited fibroblasts also for targeted delivery of anti angiogenic or antitumor molecules may aid in controlling tumor progression. Thus, these results suggest a novel approach for targeting ovarian tumor metastases for both tumor detection and therapy.     

IGF system targeted therapy: Therapeutic opportunities for ovarian cancer

The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential.     

FRα : une cible pour la thérapie photodynamique prophylactique des métastases péritonéales ovariennes ?

Partly due to delays in its diagnosis, ovarian cancer's prognosis remains dire after primary therapy. Treatment consists in complete cytoreductive surgery and platinum-based chemotherapy. Recurrence rates are disappointingly high, as 60 % of women with advanced epithelial ovarian cancer considered in remission will develop recurrent disease within five years. Special attention to undetected peritoneal metastasis and residual tumorous cells during surgery is necessary as they are the main predictors of recurrences. Targeted therapies aim to bring chemotherapy, radiotherapy and selective tumor photosensitizer (PS) agents to the targeted cell and its tumoral microenvironment. Folate receptor α (FRα) shows promising prospects in targeting ovarian cancerous cells. Indeed, with good specificity and frequent overexpression in ovarian cancer, FRα is a recurrent topic in recent publications. The aim of this review is to present FRα and the reasons that make it an ideal targeting ligand for ovarian carcinoma therapy. Prophylactic photodynamic therapy (PPDT) using new generation FRα-coupled agents combined with complete cytoreductive surgery could allow for a significant decrease in recurrence rates. Preclinical trials are being run in order to allow for human clinical applications.