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.     

葡萄膜黑色素瘤的放射敷贴治疗现状

葡萄膜黑色素瘤是成人最常见的原发眼内恶性肿瘤[1] ,可发生于虹膜、睫状体及脉络膜 ,多数葡萄膜黑色素瘤位于后部葡萄膜[2 ] 。放射敷贴疗法是一种近距离放射治疗 ,是多年来治疗葡萄膜黑色素瘤最常用的方法之一[3] 。早在 1930年 ,Ｍｏｏｒｅ[4 ] 曾用镭针治疗脉络膜黑色素瘤。 196 6年Ｓｔａｌｌａｒｄ[5] 首先报道使用60 Ｃｏ放射敷贴器治疗脉络膜黑色素瘤。自 2 0世纪 70年代至今 ,12 5Ｉ、10 6Ｒｕ、192 Ｉｒ及10 3Ｐａ相继用于放射敷贴法治疗葡萄膜黑色素瘤。一、用于放射敷贴治疗的放射性元素的物理特点用于放射敷贴治疗的放射性元素…     

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.     

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。     

葡萄膜黑色素瘤细胞相关差异表达蛋白的研究进展

葡萄膜黑色素瘤是成年人最常见的眼内恶性肿瘤,尚缺少有效的治疗方法.葡萄膜黑色素瘤细胞相关差异表达蛋白包括黑色素小体特异性蛋白MART-1、gp100、TYR系列,以及其他与正常组织差异表达蛋白如S100、NSE、NDP kinase、MITF等.这些差异表达的蛋白在葡萄膜黑色素瘤发生发展中具有不同的功能,并逐渐被应用于肿瘤的鉴别诊断和治疗中.     

葡萄膜黑色素瘤细胞相关差异表达蛋白的研究进展

葡萄膜黑色素瘤是成年人最常见的眼内恶性肿瘤,尚缺少有效的治疗方法.葡萄膜黑色素瘤细胞相关差异表达蛋白包括黑色素小体特异性蛋白MART-1、gp100、TYR系列,以及其他与正常组织差异表达蛋白如S100、NSE、NDP kinase、MITF等.这些差异表达的蛋白在葡萄膜黑色素瘤发生发展中具有不同的功能,并逐渐被应用于肿瘤的鉴别诊断和治疗中.     

葡萄膜恶性黑色素瘤的敷贴放疗

敷贴放疗在许多国家已成为治疗葡萄膜恶性黑色素瘤最常采用的方法，本文通过对葡萄膜恶性黑色素瘤的敷贴放疗的历史，现状，适应证，疗效，并发症，与其它疗法的比较等介绍，显示了敷贴放疗用于治疗葡萄膜恶性黑色素瘤的优越性。     

葡萄膜黑色素瘤治疗方案的选择对预后的影响

葡萄膜黑色素瘤是成年人跟内最常见的恶性肿瘤.目前研究认为,各种治疗方法在改善葡萄膜黑色素瘤患者的生存率方面无明显差异,但对患者生活质量的影响不同.本文就各种方法的处理原理,治疗方案的选择原则作一简要介绍,着重介绍各种方法对患者预后的影响.     

葡萄膜黑色素瘤致病基因突变及其细胞遗传学进展

葡萄膜黑色素瘤是成人最常见的原发性眼内恶性肿瘤。近年的研究证明,一些分子途径与葡萄膜黑色素瘤的进展有关。其中GNAQ基因、GNA11基因、干细胞因子受体(c-Kit)、肝细胞生长因子(c-Met)以及微小RNA(miR-34a)都通过调节特定的分子途径影响肿瘤的进展,靶向分子治疗成为新的研究热点。分子遗传学研究表明,大...     

脉络膜黑色素瘤的研究进展

脉络膜黑色素瘤(choroidal melanoma,CM)是葡萄膜恶性肿瘤中的最多的一种,也是成年人较常见的眼内恶性肿瘤,其患病率在我国居眼内恶性肿瘤的第二位,仅次于视网膜母细胞瘤.本文就近年来脉络膜黑色素瘤的病理特征、发病机制、影像检查及治疗研究进展予以综述.     

Boron neutron capture therapy of anterior chamber melanoma with p-boronophenylalanine.

Boron neutron capture therapy (BNCT) is a form of radiation therapy that requires selective uptake of boron by the tumor and irradiation with thermal neutrons. Phenylalanine is an amino acid precursor of melanin and when boronated (p-boronophenylalanine [BPA]) was found to be selectively taken up by Greene melanoma cells in the anterior chamber of rabbits. This tumor model was irradiated 24 hr after oral administration of BPA and was used for biodistribution studies that compared BPA and sodium pentaborate. Three groups were irradiated: group 1 (11 rabbits) received BPA followed by thermal neutron irradiation, group 2 (9 rabbits) received thermal neutron irradiation only, and group 3 (9 rabbits) served as unirradiated, undrugged control animals. Eight of the 11 tumors in group 1 were treated successfully; all tumors in groups 2 and 3 grew. Histopathologic examination did not reveal vascular or retina damage in group 1. These preliminary experiments confirm that newer boronated compounds, such as BPA, used in BNCT and improved neutron beams can provide selective irradiation of ocular melanomas.     

Photodynamic therapy for recurrent hyphema after proton beam radiotherapy of iris melanoma

Background Recurrent hemorrhage with secondary glaucoma is a rare but serious complication following proton beam irradiation (PBI) of iris melanoma. We report a case in which photodynamic therapy (PDT) was successfully used to treat this complication. Methods The history, clinical features and management of a patient with iris melanoma who was treated with PBI and later developed recurrent hyphema and increased intraocular pressure are presented. PDT was used to treat the abnormal intralesional blood vessels which caused the recurrent intraocular haemorrhage. Results The intralesional blood vessels regressed following PDT. The patient did not experience any further episodes of hyphema or elevated intraocular pressure. Conclusions Our case demonstrates that the vascular abnormalities following irradiation of iris melanoma may respond favorably to PDT in selected cases. To our knowledge, this is the first reported case in which PDT was used to treat recurrent hyphema caused by abnormal intralesional blood vessels after proton beam irradiation of iris melanoma. The authors have full control of all primary data, and agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review their data upon request.     

Treatment of metastatic uveal melanoma: Review and recommendations

This article reviews the published clinical responses of metastatic uveal melanoma and metastatic cutaneous melanoma with visceral involvement to current therapeutic protocols. Despite isolated patient responses to systemic treatment, no effective treatment currently exists for metastatic uveal melanoma. However, several new approaches involving interferons and interleukin and combination chemotherapy have shown some activity against metastatic cutaneous melanoma. The effectiveness against metastatic uveal melanomas has not been determined. A new approach to intrahepatic administration of chemotherapy also warrants further evaluation because of the high incidence of hepatic involvement with metastatic uveal melanoma. When an effective systemic treatment is found, early administration as an adjuvant to primary treatment may provide the best strategy for control of systemic spread.     

Non-contiguous recurrence or secondary choroidal melanoma following plaque radiotherapy

Non-contiguous local recurrence of posterior uveal melanoma occurs rarely after plaque therapy. A 50-year-old white first presented with choroidal melanoma. He underwent therapy with episcleral iodine-125 radioactive plaque therapy. Nine years later fundus evaluation revealed a new pigmented lesion in the inferotemporal equatorial area. Patient was considered to have a non-contiguous recurrent melanoma and the eye was enucleated. Histologic microscopic examination disclosed a 3 x 1.8 mm densely pigmented tumour internal to the choroid at the equator. The tumour was composed of large round cells with round nuclei, prominent nucleoli, abundant cytoplasm and spindle-shaped cells with spindle-shaped nuclei and prominent nucleoli. The tumour extended through the retina. The superior nasal area of plaque therapy had extensive chorioretinal atrophy with loss of retinal pigment epithelium, thinning of the retina and thinning and depigmentation of the choroids. Within this area of atrophy, there was a pigmented lesion composed by densely packed, spindle-shaped cells with spindle-shaped nuclei. Our patient illustrated non-contiguous recurrence of choroidal melanoma, such finding raises concerns about physiopathology and treatment of choroidal melanoma.     

Estimating prognosis for survival after treatment of choroidal melanoma

Choroidal melanoma is fatal in about 50% of patients. This is because of metastatic disease, which usually involves the liver. Kaplan–Meier survival curves based only on tumor size and extent do not give a true indication of prognosis. This is because the survival prognosis of choroidal melanoma correlates not only with clinical stage but also with histologic grade, genetic type, and competing causes of death. We have developed an online tool that predicts survival using all these data also taking normal life-expectancy into account. The estimated prognosis is accurate enough to be relevant to individual patients. Such personalized prognostication improves the well-being of patients having an excellent survival probability, not least because it spares them from unnecessary screening tests. Such screening can be targeted at high-risk patients, so that metastases are detected sooner, thereby enhancing any opportunities for treatment. Concerns about psychological harm have proved exaggerated. At least in Britain, patients want to know their prognosis, even if this is poor. The ability to select patients with a high risk of metastasis improves prospects for randomised studies evaluating systemic adjuvant therapy aimed at preventing or delaying metastatic disease. Furthermore, categorization of tissue samples according to survival prognosis enables laboratory studies to be undertaken without waiting many years for survival to be measured. As a result of advances in histologic and genetic studies, biopsy techniques and statistics, prognostication has become established as a routine procedure in our clinical practice, thereby enhancing the care of patients with uveal melanoma.     

Proton beam radiotherapy of uveal melanoma

Proton beam radiotherapy of uveal melanoma can be administered as primary treatment, as salvage therapy for recurrent tumor, and as neoadjuvant therapy prior to surgical resection. The physical properties of proton beams make it possible to deliver high-doses of radiation to the tumor with relative sparing of adjacent tissues. This form of therapy is effective for a wider range of uveal melanoma than any other modality, providing exceptionally-high rates of local tumor control. This is particularly the case with diffuse iris melanomas, many of which are unresectable. The chances of survival, ocular conservation, visual preservation and avoidance of iatrogenic morbidity depend greatly on the tumor size, location and extent. When treating any side-effects and/or complications, it is helpful to consider whether these are the result of collateral damage or persistence of the irradiated tumor (‘toxic tumor syndrome’).     

Current management of uveal melanoma: A review

Uveal melanoma is the most frequent primary intraocular cancer in adulthood and is mostly localised to the choroid. It can be treated using radiation therapy, laser therapy, local resection and enucleation, with the best results achieved by combining these procedures. However, up to half of patients develop metastatic disease. There are no efficacious treatment methods for patients in advanced stage or with metastasis. In recent years, several novel treatment modalities aimed at improving tumour control and reducing adverse events have emerged. This review summarises current clinical treatment methods and new therapeutic perspectives for uveal melanoma.     

眼部黑色素瘤的临床和病理学特点分析

目的：分析眼部黑色素瘤临床和病理学特点,以利于早期正确诊断和治疗。方法：回顾性系列病例研究。收集我院2001-08/2011-08门诊及住院眼部黑色素瘤24例,复习患者的临床和病理资料,所有病例采用常规石蜡切片、HE染色,部分病例常规诊断困难的加做S-100蛋白和HMB-45免疫组织化学染色。Excel建立数据库,应用SPSS17.0软件进行统计学分析。结果：患者24例均为单眼发病,男13例,女11例;左眼14例,右眼10例;3例眼睑恶性黑色素瘤,6例原发性结膜黑色素瘤;15例葡萄膜黑色素瘤。结论：黑色素瘤组织病理学变化多样,多数病例常规病理确诊,免疫组织化学对黑色素瘤诊断和鉴别诊断有重要价值。     

Conservative resection and adjuvant plaque brachytherapy for early-stage conjunctival melanoma

Background: To describe the outcome of patients treated by conservative surgical excision followed by adjuvant plaque brachytherapy for early‐stage primary or recurrent conjunctival melanoma. Design: Retrospective, non‐comparative, interventional case series. Participants: We reviewed 19 eyes in 19 consecutive patients presenting with biopsy proven conjunctival melanoma with pathologic stage pT1c or less. Methods: Patients with primary or recurrent early‐stage conjunctival melanoma were identified and treated using a conservative resection technique (tractional micro‐dissection) involving avoidance of deep dissection and modest lateral clearance followed by adjuvant plaque brachytherapy. Main Outcome Measure: Local recurrence and ocular complications. Results: Mean age was 55.2 years and male : female (8:11). Mean follow up was 43.1 months (range 30.1–54.3 months). All patients were treated by conservative resection followed by adjuvant Iodine‐125 plaque brachytherapy. The treatment dose was 100 Gy to a depth of 1.5–3.0 mm. Outcomes: median visual acuity and intraocular pressure were unchanged after surgery. Six patients experienced corneal ulceration in the immediate postoperative period. No patients experienced recurrence at the treatment site or metastases. Three patients experienced new lesions distant from the treatment site. Conclusions: Conservative resection and adjuvant plaque brachytherapy is an effective and well‐tolerated modality for the management of patients with early‐stage conjunctival melanoma.