Metastatic melanoma is also a challenge for surgeons. Recently, it has been reported that aggressive surgery combined with supportive therapy may be potential benefit for the condition. Therefore, we report a case of ...Metastatic melanoma is also a challenge for surgeons. Recently, it has been reported that aggressive surgery combined with supportive therapy may be potential benefit for the condition. Therefore, we report a case of ocular melanoma metastatic to multiple visceral sites treated by cytoreductive surgery after initial intra-,arterial hepatic chemoembolization展开更多
Our population-based epidemiological studies demonstrated that the epidemiological aspects of ocular melanomas are different from those in cutaneous melanoma.The incidences of conjunctival melanoma increased in the pa...Our population-based epidemiological studies demonstrated that the epidemiological aspects of ocular melanomas are different from those in cutaneous melanoma.The incidences of conjunctival melanoma increased in the past decades and was higher in the South(greater sun exposure),which is consistent with the occurrence of cutaneous melanoma.On the contrary,incidences of uveal melanoma are in the opposite direction of cutaneous melanomas.This indicates that solar radiation does not cause an increase of incidences of melanoma in ocular tissues (uveal melanoma) that are not exposed to solar radiation.Solar radiation increases the incidence of melanoma only in tissues exposed to said radiation,such as in conjunctival and eyelid melanomas.Uveal melanoma incidences in lightpigmented individuals are much greater than in dark-pigmented individuals.This result cannot be attributed to a melanin photo-screening effect,and is possibly related to melanin's biophysical and biochemical effects.The difference in incidences between light-and dark-pigmented individuals in conjunctival melanomas,as well as in vulvar and vaginal melanomas,are much lower than that in the uveal and cutaneous melanomas.This difference may be related to the different histological structures in these melanomas;.conjunctival and vaginal melanomas occur in the mucous membrane,whereas cutaneous melanomas occur in the skin.Recent molecular biological studies indicate that each type of melanoma has its own molecular changes which are different from the others.Therefore,independent studies are required for each type of melanoma to discover their own etiology and pathogenesis,and to develop relevant novel prevention and treatment procedures.展开更多
Introduction: Ocular melanoma develops at the expense of eyes’ melanocytes which give to the eyes their color. It is the first primitive intraocular tumor in the White race. It is rare, as that of the skin in black p...Introduction: Ocular melanoma develops at the expense of eyes’ melanocytes which give to the eyes their color. It is the first primitive intraocular tumor in the White race. It is rare, as that of the skin in black people. The bilateral cases are exceptional even in the white race, estimated at 0.2%. We present the case of bilateral ocular melanoma with bad prognosis in a black patient. Patient and observation: A 56-year-old black male patient, who had benefited 4 years earlier from an enucleation of the right eye for ocular melanoma, and admitted for bilateral exophthalmos which evolved for three months in a context of bilateral blindness. The cerebral Scanning had allowed to objectify a bilateral lateral-conical mass which evoked an inflammatory pseudo tumor. The failure of the medical treatment led to the exeresis of a conical, juxta-orbital and mid-muscular blackish mass, to the later apex respecting the surrounding structures. The histological examination ends again in a melanoma. No additional therapy was undertaken. The evolution 2 years later was marked by a local recurrence, multiple hepatic metastases and patient death. Conclusion: Bilateral ocular melanoma is exceptional in Black people. The etiologic factors as well as bilateralism mechanisms are still hypothetic. Its most effective treatment is local and the prognosis, bad in case of metastases due to the absence of an effective chemotherapy.展开更多
Animal models are crucial for the study of tumorigenesis and therapies in oncology research.Though rare,uveal melanoma(UM)is the most common intraocular tumor and remains one of the most lethal cancers.Given the limit...Animal models are crucial for the study of tumorigenesis and therapies in oncology research.Though rare,uveal melanoma(UM)is the most common intraocular tumor and remains one of the most lethal cancers.Given the limitations of studying human UM cells in vitro,animal models have emerged as excellent platforms to investigate disease onset,progression,and metastasis.Since Greene’s initial studies on hamster UM,researchers have dramatically improved the array of animal models.Animals with spontaneous tumors have largely been replaced by engrafted and genetically engineered models.Inoculation techniques continue to be refined and expanded.Newer methods for directed mutagenesis have formed transgenic models to reliably study primary tumorigenesis.Human UM cell lines have been used to generate rapidly growing xenografts.Most recently,patient-derived xenografts have emerged as models that closely mimic the behavior of human UM.Separate animal models to study metastatic UM have also been established.Despite the advancements,the prognosis has only recently improved for UM patients,especially in patients with metastases.There is a need to identify and evaluate new preclinical models.To accomplish this goal,it is important to understand the origin,methods,advantages,and disadvantages of current animal models.In this review,the authors present current and historic animal models for the experimental study of UM.The strengths and shortcomings of each model are discussed and potential future directions are explored.展开更多
·AIM: To assess main indications, postoperative complications and clinicopathological correlation of ocular enucleation-evisceration.·METHODS: A total of 107 subjects who underwent enucleation and/or eviscer...·AIM: To assess main indications, postoperative complications and clinicopathological correlation of ocular enucleation-evisceration.·METHODS: A total of 107 subjects who underwent enucleation and/or evisceration and received hydroxyapatite implants(Scleral wrap or mesh) were assessed. For each patient clinicopathological data was collected which included demographic information,clinical history, primary clinical diagnosis, main cause of ophthalmic surgery(traumatic, non-traumatic), type of surgical procedure(enucleation, evisceration) and pathological report. Patients’ postoperative clinical visits were checked for procedure-related complications during first year after surgery.·RESULTS: One hundred and seven patients(male:65.4%; mean age: 26y) underwent enucleation(n=100) or evisceration(n =7) due to traumatic(n =41) and non-traumatic(n =66) causes. Disfiguring painful blind eye was the most common indication of surgery(66.4%),followed by leukocoria(19.6%) and endophthalmitis(4.7%). The main types of injury included firecracker,traffic and work accidents, and sharp object perforating injury. In 53(80.3%) subjects in non-traumatic group the initial clinical diagnosis matched the histopathologicalresults. Malignant tumors(retinoblastoma: 47.5%,malignant melanoma: 27.3%) were the most common pathological diagnoses followed by phthisis bulbi(25.8%).The most common procedure-related complications were major eye discharge(39.6%), and implant exposure and discharge(20.8%).·CONCLUSION: Trauma and malignant tumors are the leading causes of enucleation-evisceration. Despite developing new techniques and materials, enucleation is still associated with considerable postoperative complications.展开更多
目的·研究F-box蛋白38(F-box only protein 38,FBXO38)对眼部黑色素瘤增殖的作用以及潜在的调控通路。方法·使用FBXO38短发夹RNA(short hairpin RNA,shRNA)和FBXO38过表达质粒构建FBXO38敲低以及过表达的人皮肤黑色素瘤A375...目的·研究F-box蛋白38(F-box only protein 38,FBXO38)对眼部黑色素瘤增殖的作用以及潜在的调控通路。方法·使用FBXO38短发夹RNA(short hairpin RNA,shRNA)和FBXO38过表达质粒构建FBXO38敲低以及过表达的人皮肤黑色素瘤A375和葡萄膜黑色素瘤OMM2.3细胞系,并通过实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)和Western blotting在转录和蛋白水平验证FBXO38的敲低和过表达效率。通过克隆形成实验、BrdU免疫荧光染色和CCK8细胞增殖实验,探究FBXO38对黑色素瘤细胞增殖的影响。使用肿瘤基因组图谱计划数据库(The Cancer Genome Atlas,TCGA),分析FBXO38高表达和低表达组中的差异表达基因,并进行京都基因与基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集,揭示与FBXO38相关的信号通路。进一步通过CCK8细胞增殖实验检测信号通路抑制剂对不同FBXO38表达量细胞的抑制率。同时通过qRT-PCR和Western blotting,验证在敲低FBXO38之后该通路是否激活。结果·qRT-PCR和Western blotting验证A375和OMM2.3细胞系中的FBXO38的mRNA及蛋白质表达水平,发现与对照组相比敲低组的FBXO38表达水平下降,与野生型相比过表达组的FBXO38的表达水平提高(P<0.05)。克隆形成实验、BrdU免疫荧光染色和CCK8细胞增殖实验显示,敲低FBXO38显著增强A375和OMM2.3细胞的增殖能力(P<0.05),反之过表达FBXO38抑制A375和OMM2.3细胞增殖(P<0.05)。KEGG通路富集分析显示,在皮肤黑色素瘤和葡萄膜黑色素瘤中,FBXO38的表达影响磷脂酰肌醇3激酶/蛋白激酶B(phosphoinositide 3-kinase/protein kinase B,PI3K-Akt)通路激活。与对照组相比,PI3K抑制剂LY294002和mTOR1抑制剂Everolimus对FBXO38敲低组的抑制率显著提升(P<0.05),对FBXO38过表达组的抑制率则显著下降(P<0.05)。Western blotting结果显示,敲低FBXO38之后,与PI3K-Akt通路相关的PTEN、P21和P53蛋白水平下降,而MDM2蛋白水平上升。qRT-PCR结果显示在FBXO38敲低细胞中P53转录水平显著下降(P<0.05),而MDM2转录水平显著上升(P<0.05)。结论·FBXO38通过PI3K-Akt信号通路参与调控眼部黑色素瘤细胞的增殖。展开更多
文摘Metastatic melanoma is also a challenge for surgeons. Recently, it has been reported that aggressive surgery combined with supportive therapy may be potential benefit for the condition. Therefore, we report a case of ocular melanoma metastatic to multiple visceral sites treated by cytoreductive surgery after initial intra-,arterial hepatic chemoembolization
文摘Our population-based epidemiological studies demonstrated that the epidemiological aspects of ocular melanomas are different from those in cutaneous melanoma.The incidences of conjunctival melanoma increased in the past decades and was higher in the South(greater sun exposure),which is consistent with the occurrence of cutaneous melanoma.On the contrary,incidences of uveal melanoma are in the opposite direction of cutaneous melanomas.This indicates that solar radiation does not cause an increase of incidences of melanoma in ocular tissues (uveal melanoma) that are not exposed to solar radiation.Solar radiation increases the incidence of melanoma only in tissues exposed to said radiation,such as in conjunctival and eyelid melanomas.Uveal melanoma incidences in lightpigmented individuals are much greater than in dark-pigmented individuals.This result cannot be attributed to a melanin photo-screening effect,and is possibly related to melanin's biophysical and biochemical effects.The difference in incidences between light-and dark-pigmented individuals in conjunctival melanomas,as well as in vulvar and vaginal melanomas,are much lower than that in the uveal and cutaneous melanomas.This difference may be related to the different histological structures in these melanomas;.conjunctival and vaginal melanomas occur in the mucous membrane,whereas cutaneous melanomas occur in the skin.Recent molecular biological studies indicate that each type of melanoma has its own molecular changes which are different from the others.Therefore,independent studies are required for each type of melanoma to discover their own etiology and pathogenesis,and to develop relevant novel prevention and treatment procedures.
文摘Introduction: Ocular melanoma develops at the expense of eyes’ melanocytes which give to the eyes their color. It is the first primitive intraocular tumor in the White race. It is rare, as that of the skin in black people. The bilateral cases are exceptional even in the white race, estimated at 0.2%. We present the case of bilateral ocular melanoma with bad prognosis in a black patient. Patient and observation: A 56-year-old black male patient, who had benefited 4 years earlier from an enucleation of the right eye for ocular melanoma, and admitted for bilateral exophthalmos which evolved for three months in a context of bilateral blindness. The cerebral Scanning had allowed to objectify a bilateral lateral-conical mass which evoked an inflammatory pseudo tumor. The failure of the medical treatment led to the exeresis of a conical, juxta-orbital and mid-muscular blackish mass, to the later apex respecting the surrounding structures. The histological examination ends again in a melanoma. No additional therapy was undertaken. The evolution 2 years later was marked by a local recurrence, multiple hepatic metastases and patient death. Conclusion: Bilateral ocular melanoma is exceptional in Black people. The etiologic factors as well as bilateralism mechanisms are still hypothetic. Its most effective treatment is local and the prognosis, bad in case of metastases due to the absence of an effective chemotherapy.
基金supported by National Institutes of Health,National Eye Institute,NIH NEI P3006360 and by an unrestricted departmental grant to the Emory Eye Center from Research to Prevent Blindness(New York,NY).
文摘Animal models are crucial for the study of tumorigenesis and therapies in oncology research.Though rare,uveal melanoma(UM)is the most common intraocular tumor and remains one of the most lethal cancers.Given the limitations of studying human UM cells in vitro,animal models have emerged as excellent platforms to investigate disease onset,progression,and metastasis.Since Greene’s initial studies on hamster UM,researchers have dramatically improved the array of animal models.Animals with spontaneous tumors have largely been replaced by engrafted and genetically engineered models.Inoculation techniques continue to be refined and expanded.Newer methods for directed mutagenesis have formed transgenic models to reliably study primary tumorigenesis.Human UM cell lines have been used to generate rapidly growing xenografts.Most recently,patient-derived xenografts have emerged as models that closely mimic the behavior of human UM.Separate animal models to study metastatic UM have also been established.Despite the advancements,the prognosis has only recently improved for UM patients,especially in patients with metastases.There is a need to identify and evaluate new preclinical models.To accomplish this goal,it is important to understand the origin,methods,advantages,and disadvantages of current animal models.In this review,the authors present current and historic animal models for the experimental study of UM.The strengths and shortcomings of each model are discussed and potential future directions are explored.
文摘·AIM: To assess main indications, postoperative complications and clinicopathological correlation of ocular enucleation-evisceration.·METHODS: A total of 107 subjects who underwent enucleation and/or evisceration and received hydroxyapatite implants(Scleral wrap or mesh) were assessed. For each patient clinicopathological data was collected which included demographic information,clinical history, primary clinical diagnosis, main cause of ophthalmic surgery(traumatic, non-traumatic), type of surgical procedure(enucleation, evisceration) and pathological report. Patients’ postoperative clinical visits were checked for procedure-related complications during first year after surgery.·RESULTS: One hundred and seven patients(male:65.4%; mean age: 26y) underwent enucleation(n=100) or evisceration(n =7) due to traumatic(n =41) and non-traumatic(n =66) causes. Disfiguring painful blind eye was the most common indication of surgery(66.4%),followed by leukocoria(19.6%) and endophthalmitis(4.7%). The main types of injury included firecracker,traffic and work accidents, and sharp object perforating injury. In 53(80.3%) subjects in non-traumatic group the initial clinical diagnosis matched the histopathologicalresults. Malignant tumors(retinoblastoma: 47.5%,malignant melanoma: 27.3%) were the most common pathological diagnoses followed by phthisis bulbi(25.8%).The most common procedure-related complications were major eye discharge(39.6%), and implant exposure and discharge(20.8%).·CONCLUSION: Trauma and malignant tumors are the leading causes of enucleation-evisceration. Despite developing new techniques and materials, enucleation is still associated with considerable postoperative complications.
文摘目的·研究F-box蛋白38(F-box only protein 38,FBXO38)对眼部黑色素瘤增殖的作用以及潜在的调控通路。方法·使用FBXO38短发夹RNA(short hairpin RNA,shRNA)和FBXO38过表达质粒构建FBXO38敲低以及过表达的人皮肤黑色素瘤A375和葡萄膜黑色素瘤OMM2.3细胞系,并通过实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)和Western blotting在转录和蛋白水平验证FBXO38的敲低和过表达效率。通过克隆形成实验、BrdU免疫荧光染色和CCK8细胞增殖实验,探究FBXO38对黑色素瘤细胞增殖的影响。使用肿瘤基因组图谱计划数据库(The Cancer Genome Atlas,TCGA),分析FBXO38高表达和低表达组中的差异表达基因,并进行京都基因与基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集,揭示与FBXO38相关的信号通路。进一步通过CCK8细胞增殖实验检测信号通路抑制剂对不同FBXO38表达量细胞的抑制率。同时通过qRT-PCR和Western blotting,验证在敲低FBXO38之后该通路是否激活。结果·qRT-PCR和Western blotting验证A375和OMM2.3细胞系中的FBXO38的mRNA及蛋白质表达水平,发现与对照组相比敲低组的FBXO38表达水平下降,与野生型相比过表达组的FBXO38的表达水平提高(P<0.05)。克隆形成实验、BrdU免疫荧光染色和CCK8细胞增殖实验显示,敲低FBXO38显著增强A375和OMM2.3细胞的增殖能力(P<0.05),反之过表达FBXO38抑制A375和OMM2.3细胞增殖(P<0.05)。KEGG通路富集分析显示,在皮肤黑色素瘤和葡萄膜黑色素瘤中,FBXO38的表达影响磷脂酰肌醇3激酶/蛋白激酶B(phosphoinositide 3-kinase/protein kinase B,PI3K-Akt)通路激活。与对照组相比,PI3K抑制剂LY294002和mTOR1抑制剂Everolimus对FBXO38敲低组的抑制率显著提升(P<0.05),对FBXO38过表达组的抑制率则显著下降(P<0.05)。Western blotting结果显示,敲低FBXO38之后,与PI3K-Akt通路相关的PTEN、P21和P53蛋白水平下降,而MDM2蛋白水平上升。qRT-PCR结果显示在FBXO38敲低细胞中P53转录水平显著下降(P<0.05),而MDM2转录水平显著上升(P<0.05)。结论·FBXO38通过PI3K-Akt信号通路参与调控眼部黑色素瘤细胞的增殖。
