RNA干扰技术在葡萄膜黑色素瘤治疗中的展望

葡萄膜黑色素瘤是成年人中最多见的一种恶性肿瘤。该肿瘤恶性程度高，预后较差，易行血流转移，主要通过眼球摘除术及相应的放疗、化疗治疗，但效果均不理想和确切。RNA干扰技术的出现已成为生命科学研究和临床治疗的又一次革命。利用RNA干扰技术，体外合成葡萄膜黑色素瘤中的相关的小片段核苷酸（19核苷酸），通过基因工程方法构建质粒，转染人葡萄膜黑色素瘤细胞，对葡萄膜黑色素瘤基因表达产生抑制作用，将会成为治疗葡萄膜黑色素瘤的一条新途径。     

非编码RNA对葡萄膜黑色素瘤发生机制影响研究新进展

葡萄膜黑色素瘤是成人最常见的一种眼内原发性肿瘤,恶性程度高,患者长期存活率低,易于肝转移。MicroRNA(miRNA)是一种单链非编码微小RNA,参与调节信使RNA的转录后翻译。长链非编码RNA(lncRNA)是一种长链(长度大于200 nt)核糖核酸,不具有蛋白质编码的功能。有研究表明,miRNAs和lncRNAs在葡萄膜黑色素瘤的发生发展过程中均起到调控作用。本文总结了近五年关于miRNAs和lncRNAs对葡萄膜黑色素瘤发生机制影响研究新进展,以期发现更多的可用于该病诊疗的新靶点。     

后部葡萄膜恶性黑色素瘤

本文报告我院１１年期间经病理证实的３５例后部葡萄膜恶性黑色素瘤。病理学分型：棱形细胞Ａ型８例，梭形细胞Ｂ型１４例，混合细胞型８例，上皮细胞型３例，气球细胞型及坏死型各１例。     

MicroRNA在葡萄膜恶性黑色素瘤中的研究进展

恶性黑色素瘤恶性程度高,易经血流转移,是成年人中最多见的一种恶性眼内肿瘤,其发生发展涉及到多步骤的分子生物学机制,包括原癌基因和抑癌基因的遗传和表观遗传学改变。因此研究参与此过程的分子机制能为肿瘤的有效治疗提供有益的见解。微小核糖核酸（ｍｉｃｒｏＲＮＡ,ｍｉＲＮＡ）是一类长约２２个核苷酸的非编码单链小分子ＲＮＡ,在各种生理病理过程中发挥了重要作用,最新的研究发现,异常表达的ｍｉｃｒｏＲＮＡ参与了葡萄膜恶性黑色素瘤众多的病理过程。本文综述了ｍｉｃｒｏＲＮＡ的发现、形成及作用机制,葡萄膜恶性黑色素瘤中ｍｉｃｒｏＲＮＡ的异常表达及其可能机制,ｍｉｃｒｏＲＮＡ与葡萄膜恶性黑色素瘤的发生与增殖、侵袭和转移以及ｍｉｃｒｏＲＮＡ在葡萄膜恶性黑色素瘤中的临床应用价值。     

端粒酶在葡萄膜恶性黑色素瘤中的表达及意义

目的 检测端粒酶在人眼葡萄膜黑色素瘤中的表达,探讨其在葡萄膜黑色素瘤发病机制中的作用,为其临床治疗提供新的思路.方法 选取16例因患葡萄膜黑色素瘤而行眼球摘除术的患者,取其葡萄膜黑色素瘤组织,采用PCR-ELISA及PCR-PAGE检测其端粒酶的含量及表达.结果 16例患者中15例的端粒酶检测呈阳性表达,占93.8%.PCR-ELISA结果显示其活性绝大多数呈中度、高度表达,仅1例△A值＜0.15.电泳结果显示为多少不等的梯形条带,其中15例显示为4条以上.结论 葡萄膜黑色素瘤患者端粒酶活性明显增高,可能是肿瘤发生、发展的重要原因之一,抑制端粒酶活性有可能成为葡萄膜黑色素瘤的新型疗法之一.     

葡萄膜恶性黑色素瘤的现代处理

葡萄腆恶性黑色素瘤Uveal Melanoma(简称U.M.)是成年人最常见的一种恶性眼内肿瘤,恶性度较高,易经血液转移,一经确诊,早期手术摘除患眼是过去最主要的治疗措施。近年来随着诊断和处理技术的不断改进,使得眼球摘出率大大降低。传统上做为主要治疗措施的跟球摘出巳受到了不同意见的挑战,成为当前争论的课题。很久以前人们就认识到U.M.病人眼球摘出后会加速瘤的全身转移。也许术前病人就已经有了亚临床转移,只是被宿主防预功能所抑制,处于暂停活动状态。在外伤、手术、肝炎等情况下被激活。大约有40％的     

葡萄膜黑色素瘤的肿瘤免疫研究进展

葡萄膜黑色素瘤是成年人眼内原发性恶性肿瘤中最常见的一种，具有高度的侵袭性和转移性。多数肿瘤由T细胞介导的特异性免疫应答起主要的抗肿瘤免疫作用，而葡萄膜黑色素瘤具有特殊的免疫学特性，在其发生、发展过程中由NK细胞发挥主要的免疫监视作用，且MHC-Ⅰ类分子的下降与预后改善呈正相关。该肿瘤细胞可通过多种方式如MHC-Ⅰ类分子表达异常和分泌免疫抑制因子如TGF-8、IL-10、MIF等逃避NK细胞的杀伤。对其进行免疫治疗时，应侧重于激活NK细胞的活性以提高患者的免疫应答，杀伤肿瘤细胞及阻止肿瘤转移。目前常用的免疫疗法有：将细胞因子基因注射到肿瘤局部，建立抗肿瘤免疫反应的微环境；促进黑色素瘤细胞的凋亡，加强外周血单核细胞对肿瘤细胞淋巴因子的激活杀伤效应。     

不同病理类型的葡萄膜黑色素瘤中微小RNA差异表达谱分析

背景 目前研究证实微小RNA(miRNA)参与大多数人类肿瘤疾病的发生和发展,其作用类似于抑癌基因或癌基因.葡萄膜黑色素瘤(UM)是成人常见的眼部恶性肿瘤,其发生和转移机制仍未完全阐明.探讨UM组织中miRNA的差异表达情况有望为UM的靶向治疗提供依据. 目的 筛选不同病理类型的UM组织中特异性miRNA表达谱. 方法 收集于2013年3月至2015年10月在北京同仁医院手术局部切除并经常规组织病理学和免疫组织化学检测证实为梭型细胞型UM的标本4例和上皮细胞型UM标本4例,采用miRNA芯片分别检测2种UM组织中miRNA的表达,收集同期死于非肿瘤疾病的8个供体眼的正常葡萄膜组织作为对照,利用组间差异倍数筛选出差异≥2倍差异表达的miRNA;用在线软件预测差异表达miRNA的靶基因,采用生物信息学方法分析靶基因参与的信号功能通路.采用实时定量PCR法验证芯片检测结果.结果 收集的梭形细胞型和上皮细胞型UM标本经组织病理学检查均得到确诊,免疫组织化学检测梭形细胞型及上皮细胞型UM组织中HMB45、黑色素-A和S-100均呈阳性反应.与正常葡萄膜组织比较,在梭形细胞型UM组织中差异表达的miRNA有109个,其中29个上调,80个下调,上调的miRNA包括miR-146a-5p、miR-25-3p和miR-29b-1-5p,下调的miRNA包括miR-126-5 p、miR-183-5p和miR-96-5p;上皮细胞型UM中差异表达的miRNA有50个,其中23个上调,27个下调,上调的miRNA包括miR-155-5p、miR-210和miR-378 a-5p;下调的miRNA包括miR-199a-5p、miR-143-3p和miR-143-5p.在梭形细胞型和上皮细胞型UM组织中共同上调的miRNA为miR-132-3p、miR-21-5p、miR-34a-5p和miR-34b-5p,共同下调的miRNA为miR-125b-2-3p、miR-126-3p、miR-199a-3p和miR-214-3p.梭形细胞型和上皮细胞型UM组织中差异表达的miRNA所预测的靶基因分别参与癌症通路、丝裂原活化蛋白激酶(MAPK)信号通路、Wnt信号通路、细胞间黏附、胞吞作用、前列腺癌通路、结直肠癌通路和细胞黏附通路.结论 与正常葡萄膜组织相比,梭形细胞型UM和上皮细胞型UM组织中存在多种miRNA的差异表达,梭形细胞型UM和上皮细胞型UM组织之间也存在明显的miRNA差异表达,这些差异表达的miRNA可通过不同的信号转导通路参与调控UM的生物学行为.     

葡萄膜黑色素瘤动物模型的建立

葡萄膜黑色素瘤是成年人最常见的原发性眼内恶性肿瘤,在过去的数十年里,研究葡萄膜黑色素瘤所面对的主要挑战是建立合适的动物模型.最常见的葡萄膜黑色素瘤动物模型可分为动物的自发性肿瘤、诱发肿瘤和移植性肿瘤.开始应用人葡萄膜黑色素瘤细胞系和肿瘤组织碎片建立模型是原发的和转移的实验性动物模型的一大进步.葡萄膜黑色素瘤动物模型常被用于原发和转移葡萄膜黑色素瘤的预后因素及治疗手段等方面的研究.尽管动物模型与人类的疾病有一定差异,但它们确实为研究人葡萄膜黑色素瘤的发生、发展、转移预后及治疗手段等方面提供了有力的工具.本文对近年来葡萄膜黑色素瘤动物模型研究做一综述.     

Metastatic uveal melanoma: diagnosis and treatment. A literature review

In the past three decades many efforts were done to improve the visual prognosis of patients with uveal melanoma. However, mortality has remained unchanged. The systemic prognosis depends on the size and other characteristics of the lesion. It is not affected by the choice of local treatment. This suggests dissemination at an early stage. The failure to improve survival is caused by difficulties in early detection of metastases and the limited susceptibility of these metastases to systemic therapies.     

Personalized treatment of uveal melanoma

Personalized treatment of uveal melanoma involves the tailoring of all aspects of care to the condition, needs, wishes, and fears of the patient, taking account of the individual''s circumstances. When selecting between radiotherapy, surgical resection, and phototherapy, or when deciding how best to combine these different therapeutic modalities, it is necessary to understand the patients utilities, with respect to tumour control, visual conservation, and preservation of the eye, so as to prioritize outcomes accordingly. For example, such considerations would influence the width of the safety margins when administering radiotherapy, according to whether the patient considers it more important to conserve vision or to guarantee tumour control. With ‘suspicious naevi'', the choice between observation, immediate treatment, and biopsy is complicated by the lack of adequate survival data on which to base rational decisions, making it necessary for both patient and doctor to accept uncertainty. Personalized care should involve close relatives, as appropriate. It must also adapt to changes in the patient''s needs over time. Such personalized care demands the ability to respond to such needs and the sensitivity to identify these requirements in the first place. Personalized treatment enhances not only the patient''s satisfaction but also the ‘job satisfaction'' of all members of the multidisciplinary team, improving quality of care.     

葡萄膜黑色素瘤的药物治疗研究现状

葡萄膜黑色素瘤（uveal melanoma,UM）是成人眼内最常见的恶性肿瘤,虽然近30 a来涌现出许多局部治疗方法,但患者的生存率一直无明显改善,主要原因是缺乏UM的治疗药物,尤其是抑制转移的药物。国外学者针对UM的药物治疗已经开展了大量的临床试验,我国目前仍然采用传统的眼球摘除术治疗UM,缺乏相应的临床药物研究。本文对国内外开展的UM临床药物试验展开综述,以期为眼科医师或肿瘤科医师提供治疗UM的新思路。     

葡萄膜恶性黑色素瘤治疗新进展

葡萄膜恶性黑色素瘤(uveal melanoma,UM)是成人最常见的原发性眼内恶性肿瘤。虽然目前治疗手段多种多样,眼球摘除术仍是本病的传统治疗,但手术摘除眼球并不能完全控制肿瘤的远处转移。对于伴全身转移的患者,据30a来的统计,生存率仍很低。近年来许多研究致力于靶向治疗、免疫治疗、放射治疗,并取得了可喜的效果,本文对相关研究进行综述。     

New treatment modalities for uveal melanoma

The management of uveal melanoma has evolved tremendously for the past century, and more recently there is a trend toward more focal conservative treatment. Enucleation is still performed for large uveal melanoma when there is no hope for useful vision with conservative treatment. Plaque radiotherapy is particularly recommended for medium- or small-sized uveal melanoma. Special custom-designed plaque radiotherapy can be used for iris, ciliary body, or juxtapapillary choroidal melanoma. Charged-particle irradiation constitutes an alternative treatment modality for posterior uveal melanoma. However, charged-particle therapy is limited by the availability of appropriate therapeutic facilities. Local tumor resection using lamellar sclerouvectomy is mainly suitable for selected iris, ciliary body, or anterior choroidal tumors with smaller basal dimension and greater thickness. Ablative laser photocoagulation is indicated for very selected cases of small posterior choroidal uveal melanoma. Combined plaque radiotherapy with indirect ophthalmoscope laser therapy appears to be a more effective local tumor treatment plan than plaque radiotherapy alone. Transpupillary thermotherapy is the newest modality used as primary treatment or as complementary method to brachytherapy for treatment of selected choroidal melanomas. Hyperthermia with infrared irradiation below photocoagulation level produces tumor necrosis with few ocular complications. Based on the published ophthalmic literature, it seems that enucleation carries the same survival prognosis as each of the conservative treatment modalities.     

Diagnosis and treatment of orbital invasion in uveal melanoma

The presence of extraocular extension of uveal melanoma is a known prognostic factor that significantly affects patient survival and the risk of orbital recurrence. Interest in this uncommon event in patients with uveal melanoma has been renewed owing to recent reports of extraocular growth after conservative treatment. Ultrasonography and magnetic resonance imaging seem to be the most sensitive imaging techniques to detect even small degrees of extraocular extension. However, some cases are identified at surgery during enucleation or brachytherapy. Although there is a lack of consensus as to the optimal therapeutic management of orbital invasion in uveal melanoma, the current treatment options include isolated resection and modified enucleation or exenteration combined with radiotherapy or other forms of adjuvant therapy.     

Analysis of melanoma cell type in uveal melanoma following treatment failure

PURPOSE: To determine whether an increase (or progression) in the degree of malignancy according to cytologic or histopathologic criteria corresponded with failure of intraocular melanoma control. DESIGN: Retrospective case control study from a single institution. METHODS: Uveal melanoma patients had either fine-needle aspiration biopsy followed by irradiation and later enucleation or an eyewall resection followed by enucleation. The observation procedures were serial histology or cytopathology and histology, reanalyzed in a masked manner. The main outcome measures were change in the predominant tumor cell type, local tumor control, and metastases. RESULTS: There was not a significant correlation between a change in melanoma cell type and failure to control intraocular melanoma. Similarly, the latency between treatment and enucleation was actually less (but not statistically so) in tumors that showed no increase in melanoma malignancy cell type compared with those that had a more malignant cell type on serial examination. CONCLUSIONS: There was no correlation between a change to more a malignant cell type and local control failure in patients treated either with radiation or eyewall resection for uveal melanoma.