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Clinical Molecular Pathology and Treatment Developments in Advanced Uveal Melanoma:State of the Art
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作者 Stefano Dore Matteo Sacchi +2 位作者 Antonio Pinna Giuseppe Palmieri Panagiotis Paliogiannis 《Oncology Research》 2026年第2期190-205,共16页
Uveal melanoma(UM)is the most common intraocular cancer,with approximately 5.2 individuals per million affected annually in the United States.It represents approximately 3%of the global malignant melanoma cases,accoun... Uveal melanoma(UM)is the most common intraocular cancer,with approximately 5.2 individuals per million affected annually in the United States.It represents approximately 3%of the global malignant melanoma cases,accounting for 80%of the overall noncutaneous melanomas.Clinically,it remains silent in about 30%of the cases;when symptomatic,it generally causes metamorphopsia(painless loss or distortion of vision)and/or photopsia(flashing or flickering of light in the visual field).Discoloration of the iris,astigmatism,glaucoma,and even blindness are other,less common clinical manifestations.Several pathophysiological mechanisms underlie the development of UM.Genetic mutations,involving especially the G protein subunit alpha q(GNAQ),guanine nucleotide-binding protein subunit alpha-11(GNA11),BRCA1 associated deubiquitinase 1(BAP1),splicing factor 3b subunit 1(SF3B1),and eukaryotic translation initiation factor 1A,X-linked(EIF1AX)genes as well as the MAPK/ERK signaling pathway genes,have been largely associated with the development of UM.Chromosomal aberrations,inflammatory and immunological alterations are often concurrent factors for the development and progression of UM.Therapies targeting specific genetic alterations and immunotherapy agents have been recently developed and introduced in clinical practice for the management of advanced-stage UMs.This review aims to present the latest advances in the clinical molecular pathology of UM,along with the resulting targeted,immunological,and other therapies that have been introduced or are currently under investigation. 展开更多
关键词 Eye uveal melanoma(UM) molecular pathology targeted therapy IMMUNOTHERAPY
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MATRIX METALLOPROTEINASE INHIBI-TION: A NEW APPROACH TO THE RE-DUCTION OF POST -OPERATIVE SCAR-RING FOLLOWING EXPERIMENTAL GLAUCOMA FILTRATION SURGERY 被引量:10
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作者 T.T.L.Wong A.L.Mead P.T.Khaw 《国际眼科杂志》 CAS 2003年第1期24-24,共1页
Purpose: In this study, the effect of the application of a broad-spectrum matrix metalloproteinase (MMP) inhibitor, GM6001 (Ilomastat) on the development of post-operative scarring following glaucoma filtration surger... Purpose: In this study, the effect of the application of a broad-spectrum matrix metalloproteinase (MMP) inhibitor, GM6001 (Ilomastat) on the development of post-operative scarring following glaucoma filtration surgery was investigated Methods: In a randomised, prospective, masked-observer study, 40 New Zealand white rabbits underwent modified glaucoma fil- 展开更多
关键词 青光眼滤过术 术后 瘢痕形成 基质金属蛋白酸抑制剂 调节作用
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Effect of Apigenin on Gap Junctional Intercellular Communication in Human Tenon's Capsule Fibroblasts 被引量:2
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作者 Shanshan Liu Jibing Wang +1 位作者 Huihui Zou Xudong Huang 《眼科学报(英文版)》 CAS 2013年第2期62-67,共6页
Purpose:To investigate the effect of apigenin on gap junctional intercellular communication (GJIC) in human Tenon's capsule fibroblasts (HTFs) and its underlying mechanism. Methods:After a 48 h treatment of cultur... Purpose:To investigate the effect of apigenin on gap junctional intercellular communication (GJIC) in human Tenon's capsule fibroblasts (HTFs) and its underlying mechanism. Methods:After a 48 h treatment of cultured HTFs with apigenin.(80 μmol/L),the GJIC was detected by a scrape-loading/dye transfer technique with Lucifer yellow dye and rhodamine (Rh) dextran. The coupling index represents a quantification of GJIC where a high coupling index is associated with a greater number of cells demonstrating cell-cell communication through gap junction channels.The changes in connexin 43 (Cx43) distribution and the expression of Cx43 at the protein and mRNA levels were statistically compared between the two groups by means of immunocytochemistry, western blotting,and real-time polymerase chain reaction (PCR). Results:The functioning of GJIC in the HTFs was significantly enhanced after 48 hours by apigenin treatment when compared with the control cells. In the apigenin group, the intercellular dye transfer grade was above 9, while this value was only grade 3-4 in the control group. The coupling index was significantly increased up to 9.205±0.3621 in the apigenin group,compared with 5.1775 ±0.3177 in the control group (F=279.581, P=0.000). The expression of Cx43 at the protein and mRNA levels was significantly up-regulated in the apigenin group compared with the control group. Conclusion:Apigenin can significantly enhance the function of GJIC in HTFs by up-regulating the expression of Cx43 at both the protein and mRNA levels,suggesting that the enhancement of GJIC in HTFs by apigenin probably acts as an important mechanism underlying the inhibitory effect of apigenin on HTF proliferation. 展开更多
关键词 细胞间隙连接通讯 成纤维细胞 芹菜素 MRNA水平 Cx43 连接蛋白 免疫细胞化学 聚合酶链反应
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On implications of somatostatin in diabetic retinopathy 被引量:1
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作者 Yanhong Fang Qionghua Wang +3 位作者 Youjian Li Li Zeng Jian Liu Kepeng Ou 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第9期1984-1990,共7页
Somatostatin,a naturally produced neuroprotective peptide,depresses excitatory neurotransmission and exerts anti-proliferative and anti-inflammatory effects on the retina.In this review,we summarize the progress of so... Somatostatin,a naturally produced neuroprotective peptide,depresses excitatory neurotransmission and exerts anti-proliferative and anti-inflammatory effects on the retina.In this review,we summarize the progress of somatostatin treatment of diabetic retinopathy through analysis of relevant studies published from February 2019 to February 2023 extracted from the PubMed and Google Scholar databases.Insufficient neuroprotection,which occurs as a consequence of declined expression or dysregulation of retinal somatostatin in the very early stages of diabetic retinopathy,triggers retinal neurovascular unit impairment and microvascular damage.Somatostatin replacement is a promising treatment for retinal neurodegeneration in diabetic retinopathy.Numerous pre-clinical and clinical trials of somatostatin analog treatment for early diabetic retinopathy have been initiated.In one such trial(EUROCONDOR),topical administration of somatostatin was found to exert neuroprotective effects in patients with pre-existing retinal neurodysfunction,but had no impact on the onset of diabetic retinopathy.Overall,we concluded that somatostatin restoration may be especially beneficial for the growing population of patients with early-stage retinopathy.In order to achieve early prevention of diabetic retinopathy initiation,and thereby salvage visual function before the appearance of moderate non-proliferative diabetic retinopathy,several issues need to be addressed.These include the needs to:a)update and standardize the retinal screening scheme to incorporate the detection of early neurodegeneration,b)identify patient subgroups who would benefit from somatostatin analog supplementation,c)elucidate the interactions of somatostatin,particularly exogenously-delivered somatostatin analogs,with other retinal peptides in the context of hyperglycemia,and d)design safe,feasible,low cost,and effective administration routes. 展开更多
关键词 diabetes retinopathy EXCITOTOXICITY growth hormone insulin like growth factor irisin NEURODEGENERATION NEUROINFLAMMATION neuroprotection neurovascular unit OCTREOTIDE oxidative stress SOMATOSTATIN
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Stem cell therapy for retinal pigment epithelium disorders
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作者 Francesco Saverio Sorrentino Francesco Parmeggiani +4 位作者 Lorenzo Gardini Luigi Fontana Mutali Musa Caterina Gagliano Marco Zeppieri 《World Journal of Stem Cells》 2025年第5期26-41,共16页
Retinal pigment epithelium(RPE)dysfunction is involved in the advancement of numerous degenerative retinal illnesses,such as age-related macular degeneration and hereditary retinal abnormalities.Transplantation of RPE... Retinal pigment epithelium(RPE)dysfunction is involved in the advancement of numerous degenerative retinal illnesses,such as age-related macular degeneration and hereditary retinal abnormalities.Transplantation of RPE produced from stem cells has emerged as a promising therapeutic strategy to restore retinal function and prevent vision loss.However,other obstacles impede its clinical application,including immunological rejection,cell viability,functional integration,and the necessity for consistent differentiation techniques.This review offers a thorough examination of the molecular processes regulating RPE integrity,investigates recent progress in stem cell-derived RPE therapeutics,and addresses significant challenges to their broad implementation.Furthermore,we emphasize prospective avenues intended to enhance the safety,efficacy,and enduring success of RPE transplantation in clinical environments. 展开更多
关键词 Retinal pigment epithelium Stem cell therapy Retinal degeneration Cell transplantation Molecular stem cell mechanisms
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Uveal melanoma:Recent advances in immunotherapy 被引量:2
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作者 Francesco Saverio Sorrentino Francesco De Rosa +6 位作者 Patrick Di Terlizzi Giacomo Toneatto Andrea Gabai Lucia Finocchio Carlo Salati Leopoldo Spadea Marco Zeppieri 《World Journal of Clinical Oncology》 2024年第1期23-31,共9页
Uveal melanoma(UM)is the most common primary intraocular cancer in adults.The incidence in Europe and the United States is 6-7 per million population per year.Although most primary UMs can be successfully treated and ... Uveal melanoma(UM)is the most common primary intraocular cancer in adults.The incidence in Europe and the United States is 6-7 per million population per year.Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection,up to 50%of UM patients develop metastases that usually involve the liver and are fatal within 1 year.To date,chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM,which is still characterized by poor prognosis.No standard therapeutic approaches for its prevention or treatment have been established.The application of immunotherapy agents,such as immune checkpoint inhibitors that are effective in cutaneous melanoma,has shown limited effects in the treatment of ocular disease.This is due to UM’s distinct genetics,natural history,and complex interaction with the immune system.Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations,UMs are usually triggered by a mutation in GNAQ or GNA11.As a result,more effective immunotherapeutic approaches,such as cancer vaccines,adoptive cell transfer,and other new molecules are currently being studied.In this review,we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM. 展开更多
关键词 Uveal melanoma IMMUNOTHERAPY Ocular oncology TUMOR Metastatic disease Genetic mutations
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Eyelid Kaposi Sarcoma in HIV-Negative Patient
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作者 Malalaniaina Andrianarison Malala Razakanaivo +7 位作者 Rindra Rafanomezantsoa Mendrika Fifaliana Rakotoarisaona Odilon Laza Fandresena Arilala Sendrasoa Irina Mamisoa Ranaivo Léa Raobela Lala Soavina Ramarozatovo Fahafahantsoa Rapelanoro Rabenja 《Journal of Cancer Therapy》 2024年第3期92-97,共6页
Introduction: Kaposi sarcoma disease is a proliferative and multifocal disorder with dual components, vascular and fibroblastic cellular, cutaneous and visceral expression. Kaposi Sarcoma can affect the ocular surface... Introduction: Kaposi sarcoma disease is a proliferative and multifocal disorder with dual components, vascular and fibroblastic cellular, cutaneous and visceral expression. Kaposi Sarcoma can affect the ocular surface and adnexa and can masquerade as other entities, delaying prompt diagnosis can lead to diagnostic wandering delaying treatment. Our aim is to describe a case of KS of the eyelid in an HIV seronegative patient. Case Presentation: A seventy-year-old man developed a bilateral growing tumoral reddish purple vascular mass on both the lower and upper eyelid involving rapidly for 6 months. Both feet and the two shanks show the presence of a brown-violet tumor-shaped formation. The patient was negative for HIV. Histology examination showed a nodular tumor-like mass with a fibro hemangioma-epitheliomatous. Polymerase chain reaction was positive for human herpes virus 8. Initial chemotherapy followed by surgery was proposed to the patient. Unfortunately, the patient rejected treatment and was lost to follow-up. Conclusion: This case reports the difficulty of managing KS in developing countries. 展开更多
关键词 EYELID HHV-8 INTERFERON Kaposi Sarcoma
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New frontiers in retinal transplantation
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作者 Francesco Saverio Sorrentino Patrick Di Terlizzi +5 位作者 Francesco De Rosa Carlo Salati Leopoldo Spadea Caterina Gagliano Mutali Musa Marco Zeppieri 《World Journal of Transplantation》 2024年第4期67-77,共11页
New frontiers about retinal cell transplantation for retinal degenerative diseases start from the idea that acting on stem cells can help regenerate retinal layers and establish new synapses among retinal cells.Defici... New frontiers about retinal cell transplantation for retinal degenerative diseases start from the idea that acting on stem cells can help regenerate retinal layers and establish new synapses among retinal cells.Deficiency or alterations of synaptic input and neurotrophic factors result in trans-neuronal degeneration of the inner retinal cells.Thus,the disruption of photoreceptors takes place.However,even in advanced forms of retinal degeneration,a good percentage of the ganglion cells and the inner nuclear layer neurons remain intact.This phenomenon provides evidence for obtaining retinal circuitry through the transplantation of photoreceptors into the subretinal region.The eye is regarded as an optimal organ for cell transplantation because of its immunological privilege and the relatively small number of cells collaborating to carry out visual activities.The eyeball's immunological privilege,characterized by the suppression of delayed-type hypersensitivity responses in ocular tissues,is responsible for the low rate of graft rejection in transplant patients.The main discoveries highlight the capacity of embryonic stem cells(ESCs)and induced pluripotent stem cells to regenerate damaged retinal regions.Recent progress has shown significant enhancements in transplant procedures and results.The research also explores the ethical ramifications linked to the utilization of stem cells,emphasizing the ongoing issue surrounding ESCs.The analysis centers on recent breakthroughs,including the fabrication of three-dimensional retinal organoids and the innovation of scaffolding for cell transportation.Moreover,researchers are currently assessing the possibility of CRISPR and other advanced gene editing technologies to enhance the outcomes of retinal transplantation.The widespread use of universally recognized safe surgical and imaging methods enables retinal transplantation and monitoring of transplanted cell growth toward the correct location.Currently,most therapy approaches are in the first phases of development and necessitate further research,including both pre-clinical and clinical trials,to attain favorable visual results for individuals suffering from retinal degenerative illnesses. 展开更多
关键词 Retinal transplantation Retinal stem cell Human embryonic stem cells Pluripotent stem cells Retinal tissue transplant
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细胞因子基因多态性与英国特发性中间葡萄膜炎患者预后有无相关性
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作者 Stanford M.R. Vaughan R.W. +2 位作者 Kondeatis E. G.R. Wallace 韩静 《世界核心医学期刊文摘(眼科学分册)》 2005年第11期29-30,共2页
Background/aim: Competing levels of cytokines, either locally within the eye o r systemically, may influence the eventual out-come of ocular inflammation. Pol ymorphism in the promoter part of the genes controlling cy... Background/aim: Competing levels of cytokines, either locally within the eye o r systemically, may influence the eventual out-come of ocular inflammation. Pol ymorphism in the promoter part of the genes controlling cytokine production may result in either higher or lower production of the relevant cytokine to a given stimulus. The authors hypothesised that such polymorphisms may relate to visual outcome in patients with idiopathic intermediate uveitis. Methods: DNA was obtai ned from 125 patients with idiopathic intermediate uveitis and analysed for the interleukin 10 IL-10-1082G/Aand IL-10-819C/T, and interferon γIFNγ874T/A g ene polymorphisms. Associations with disease were calculated by both allelic fre quency and haplotype analysis, and associations between ocular disease outcomes and the presence of polymorphismswere identified. A bad outcome was defined as l oss of vision <6/12 Snellen in both eyes at 5 years from presentation when the e yes were quiet. Results: An initial screen showed that the 874T allele of the IF Nγgene was more prevalent in patients than controls (χ2=7.9; p=0.004 OR 1.7; 9 5%CI 1.2 to 2.6 (Pc=0.02), whereas the IL-10-1082/-819 AT haplotype of the i nterleukin 10 (IL-10) gene was not. Analysis of disease outcome showed an assoc iation between IL-10-1082 AA homozygosity and bad outcome (χ2 =13; p=0.0003). Moreover, the two cytokine polymorphisms taken together showed that up to 75%o f patients with a poor visual outcome had the combined IFNγ874TA or TT genotype together with the IL-10-1082AA genotype (χ2=13.2 p=0.0008 OR 6.4; 95%CI 1.8 5 to 23.6 Pc=0.1). Conclusion: These results show that disease outcome in interm ediate uveitis may be partly determined by a complex interplay between cytokine genes and these results may have implications for future treatment with biologic al agents that target these cytokines. 展开更多
关键词 中间葡萄膜炎 细胞因子 基因多态性 眼部炎症 单体型分析 眼部疾病 眼部征象 等位基因频率 双眼视力 疾病预后
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青光眼多焦视诱发电位和SITA标准视野检查的测试-再测试变异性研究
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作者 Bjerre A. Grigg J.R. +2 位作者 Parry N.R.A. Henson D.B. 杨建刚 《世界核心医学期刊文摘(眼科学分册)》 2005年第4期42-43,共2页
PURPOSE. To investigate the test- retest variability of multifocal visual evoked potential (mfVEP) and threshold perimetry in glaucoma, and to examine the relationship between the two techniques. METHODS. Data were re... PURPOSE. To investigate the test- retest variability of multifocal visual evoked potential (mfVEP) and threshold perimetry in glaucoma, and to examine the relationship between the two techniques. METHODS. Data were recorded using the AccuMap mfVEP and SITA standard program of the Humphrey Field Analyzer. Data were obtained twice within a 4- week period from both eyes of 74 patients with varying amounts of glaucomatous visual field loss. The number of defective test locations (those falling beyond a given probability value of being normal) were calculated for mfVEP and SITA, using databases incorporated within the instruments software. Reliability measures and test times were recorded along with patient test preference. RESULTS. Both tests showed a large degree of test- retest variability in the number of defective test locations (95% limits of agreement for mfVEP and SITA being 13.39 and 9.88, respectively). A “ fair to moderate” degree of spatial agreement was found between mfVEP and SITA. The number of mfVEP defective locations was dependent on the signal amplitude. No relationship was found between test- retest variability and the reliability indices for either test. The mean time taken to perform mfVEP and SITA standard was 33 and 20 minutes, respectively, and 73 of the 74 patients preferred the mfVEP test. CONCLUSIONS. Test- retest variability was found to be slightly greater for mfVEP. The processing of mfVEP signals needs to be changed to remove the relationship between the number of defective locations and signal amplitude. The majority of patients preferred mfVEP to conventional perimetiy although mfVEP takes longer to perform. 展开更多
关键词 视野检查 SITA 多焦视诱发电位 视野分析仪 视野缺损 视野计 测试区域 概率值
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1组脉络膜恶性黑色素瘤病例的脉络膜新生血管
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作者 Guerin E. Hiscott P. +1 位作者 Damato B. 潘家鸿(译) 《世界核心医学期刊文摘(眼科学分册)》 2006年第9期50-50,共1页
Purpose:To examine a series of choroidal melanoma specimens to determine the frequency of overlying choroidal neovascularization(CNV)and to ascertain whether CNV over choroidal malignant melanoma is associated with an... Purpose:To examine a series of choroidal melanoma specimens to determine the frequency of overlying choroidal neovascularization(CNV)and to ascertain whether CNV over choroidal malignant melanoma is associated with any particular histological tumour characteristics.Methods:We carried out a retrospective histological analysis of globes containing choroidal melanomas for evidence of choroidal neovascular membranes.Results:Microscopic evidence of choroidal neovascular membranes was evident in 6% of cases.Choroidal neovascularization was not associated with any particular histological tumour characteristic.Conclusion:Choroidal neovascularization over choroidal malignant melanoma is not an infrequent occurrence and possibly appears as frequently as CNV over choroidal naevi.The presence of a choroidal neovascular membrane over a pigmented fundal lesion should not be taken as reassurance that the lesion is benign. 展开更多
关键词 脉络膜新生血管 脉络膜恶性黑色素瘤 脉络膜黑色素瘤 病例 新生血管形成 组织学证据 回顾性地分析 肿瘤特征
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初级医疗中关于非炎症性眼疼痛的评估
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作者 Lucia Kuffova John V Forrester +2 位作者 Andrew Dick 郝洁 李树宁 《英国医学杂志中文版》 2016年第3期160-163,共4页
眼部疼痛很普遍,大约2%~5%的综合门诊患者主诉涉及眼部及眼周边疼痛的情况(眼部、眼周边、眼眶周边的疼痛在文中统称为眼部疼痛)。在新西兰眼科急诊的患者中,大于50%的患者由综合门诊转诊而来。,绝大部分主诉都包含眼部疼痛。... 眼部疼痛很普遍,大约2%~5%的综合门诊患者主诉涉及眼部及眼周边疼痛的情况(眼部、眼周边、眼眶周边的疼痛在文中统称为眼部疼痛)。在新西兰眼科急诊的患者中,大于50%的患者由综合门诊转诊而来。,绝大部分主诉都包含眼部疼痛。笔者建议,这些人中,如果在初诊时可以得到较好的诊断,那么转诊人数将会下降。 展开更多
关键词 初级医疗 非炎症性 眼部疼痛 检查视力
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Double vision
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作者 Liying Low Waqaar Shah Caroline J MacEwen 《英国医学杂志中文版》 2016年第3期177-178,共2页
关键词 复视 定义 发病原因 病史
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