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Biological characteristics and clinical management of uveal and conjunctival melanoma
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作者 SNJEŽANA KAŠTELAN ANA DIDOVIĆPAVIČIĆ +4 位作者 DARIA PAŠALIĆ TAMARA NIKUŠEVA-MARTIĆ SAMIRČANOVIĆ PETRA KOVAČEVIĆ SUZANA KONJEVODA 《Oncology Research》 SCIE 2024年第8期1265-1285,共21页
Uveal and conjunctival melanomas are relatively rare tumors;nonetheless,they pose a significant risk of mortality for a large number of affected individuals.The pathogenesis of melanoma at different sites is very simil... Uveal and conjunctival melanomas are relatively rare tumors;nonetheless,they pose a significant risk of mortality for a large number of affected individuals.The pathogenesis of melanoma at different sites is very similar,however,the prognosis for patients with ocular melanoma remains unfavourable,primarily due to its distinctive genetic profile and tumor microenvironment.Regardless of considerable advances in understanding the genetic characteristics and biological behaviour,the treatment of uveal and conjunctival melanoma remains a formidable challenge.To enhance the prospect of success,collaborative efforts involving medical professionals and researchers in thefields of ocular biology and oncology are essential.Current data show a lack of well-designed randomized clinical trials and limited benefits in current forms of treatment for these tumors.Despite advancements in the development of effective melanoma therapeutic strategies,all current treatments for uveal melanoma(UM)and conjunctival melanoma(CoM)remain unsatisfactory,resulting in a poor long-term prognosis.Ongoing trials offer hope for positive outcomes in advanced and metastatic tumors.A more comprehensive understanding of the genetic and molecular abnormalities involved in the development and progression of ocular melanomas opens the way for the development of personalized therapy,with various potential therapeutic targets currently under consideration.Increased comprehension of the molecular pathogenesis of UM and CoM and their specificities may aid in the development of new and more effective systemic therapeutic agents,with the hope of improving the prognosis for patients with metastatic disease. 展开更多
关键词 Uveal melanoma conjunctival melanoma Genetic characteristics Immune checkpoint inhibitors Target molecular inhibitors
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Cucurbitacin B-induced G2/M cell cycle arrest of conjunctival melanoma cells mediated by GRP78-FOXM1-KIF20A pathway 被引量:1
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作者 Jinlian Wei Xin Chen +11 位作者 Yongyun Li Ruoxi Li Keting Bao Liang Liao Yuqing Xie Tiannuo Yang Jin Zhu Fei Mao Shuaishuai Ni Renbing Jia Xiaofang Xu Jian Li 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2022年第10期3861-3876,共16页
Conjunctival melanoma(CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B(CuB). We found that CuB remarkably in... Conjunctival melanoma(CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B(CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16,CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also induce CM cells G2/M cell cycle arrest. RNA-seq screening identified KIF20A, a key downstream effector of FOXM1 pathway, was abolished by CuB treatment. Further target identification by activity-based protein profiling chemoproteomic approach revealed that GRP78 is a potential target of CuB. Several lines of evidence demonstrated that CuB interacted with GRP78 and bound with a Kdvalue of0.11 μmol/L. Furthermore, ATPase activity evaluation showed that CuB suppressed GRP78 both in human recombinant GRP78 protein and cellular lysates. Knockdown of the GRP78 gene significantly induced the downregulation of FOXM1 and related pathway proteins including KIF20A, underlying an interesting therapeutic perspective. Finally, CuB significantly inhibited tumor progression in NCG mice without causing obvious side effects in vivo. Taken together, our current work proved that GRP78-FOXM1-KIF20A as a promising pathway for CM therapy, and the traditional medicine CuB as a candidate drug to hinder this pathway. 展开更多
关键词 conjunctival melanoma Cucurbitacin B Activity-based protein profiling G2/M cell cycle GRP78 FOXM1 KIF20A Rare tumor
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Treatment of Conjunctival Malignant Melanoma with Topical Interferon Alpha-2a
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作者 Naser Salihu Belinda Pustina Brigita Drnovsek-Olup 《Open Journal of Ophthalmology》 2015年第3期91-93,共3页
Conjunctival malignant melanoma (CMM) is a potentially lethal neoplasm with a high rate of recurrence. The modality of treatment includes a wide surgical excision, cryotherapy, topical mitomycin C and Interferon alpha... Conjunctival malignant melanoma (CMM) is a potentially lethal neoplasm with a high rate of recurrence. The modality of treatment includes a wide surgical excision, cryotherapy, topical mitomycin C and Interferon alpha 2b (INF α 2b). The aim of the study is to present the treatment of a case with CMM using topical Interferon alpha 2a. We present a 38-year-old female with diffuse bulbar dark pigmentation of the conjunctiva that arises from previously primary acquired melanosis (PAM). Biopsy resulted positive for CMM and further investigations were negative for any metastasis. Treatment with topical interferon alpha 2a was started immediately and after three months melanoma disappeared. One year after follow-up there was no sign of recurrence in regional lymph nodes or distant metastasis. 展开更多
关键词 conjunctival Malignant melanoma Interferon Alpha 2a
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Targeted therapy for malignant ocular melanomas 被引量:1
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作者 Rahul Arvo Jonas Alexander C.Rokohl Ludwig M.Heindl 《Annals of Eye Science》 2021年第1期46-52,共7页
In a comprehensive literature review,PubMed,Embasem and Web of Science were searched for studies examining targeted therapy of ocular malignant melanomas to present and discuss targeted therapy treatment options of oc... In a comprehensive literature review,PubMed,Embasem and Web of Science were searched for studies examining targeted therapy of ocular malignant melanomas to present and discuss targeted therapy treatment options of ocular tumors,mainly conjunctival and uveal melanoma(UM).Conjunctival malignant melanomas showed similarities in clinical and genetic aspects with cutaneous melanomas.Many therapies with checkpoint inhibitors already established for cutaneous melanomas may be a treatment option for conjunctival malignant melanomas with shared traits.Existing targeted therapies are for example checkpoint inhibitors like pembrolizumab or nivolumab.As a corollary,due to marked differences in clinics and genetics between UMs and conjunctival melanomas(CMs)or cutaneous melanomas,it has remained elusive whether the available possibilities of molecular targeted therapy will be an option for the therapy of metastasizing UMs.Possible novel ways of treating UM are being explored.Fotemustine or the inoculation of dendritic cells with tumorous RNA or sunitinib in combination with cisplatin and or tamoxifen may be used in future to treat UM.While CM are treatable using targeted therapies,UM have not been researched enough to find working targeted therapy options.Further research has to be done in order to find acceptable treatment options. 展开更多
关键词 conjunctival melanoma(CM) uveal melanoma(UM) RETINOBLASTOMA ocular tumor targeted therapies
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Preclinical models in ophthalmic oncology-a narrative review
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作者 Daria Lehrmann Nasrin Refaian +2 位作者 Michael Simon Alexander C.Rokohl Ludwig M.Heindl 《Annals of Eye Science》 2022年第2期59-73,共15页
Objective:This review serves as a comprehensive description and summary of currently available preclinical models of three tumors in ophthalmic oncology:conjunctival melanoma(CM),uveal melanoma(UM),and retinoblastoma.... Objective:This review serves as a comprehensive description and summary of currently available preclinical models of three tumors in ophthalmic oncology:conjunctival melanoma(CM),uveal melanoma(UM),and retinoblastoma.Background:Malignant melanomas are the most common tumors of the eye in adults,most often localized in the uvea and conjunctiva.Although the primary tumor can be successfully eliminated in many cases,nearly one in two UMs-and one in three CMs-are fatal to the patient due to metastasis.Effective therapies for metastatic uveal and CMs are unfortunately still not available,so there is an urgent need for new therapeutic strategies to improve prognosis quoad vitam and prolong the survival of melanoma patients.Another widely known tumor of the eye is retinoblastoma,which is the most common pediatric ocular malignancy,occurring in approximately 1 in 15,000-18,000 live births.Overall,it is considered well treatable,with a survival rate of approximately 90%at 3 years,although fatal if untreated.For a long time,enucleation was also considered the treatment of choice,with bilateral cases having one eye irradiated and the eye with the more advanced tumor removed.Since the 1990s,however,systemic chemotherapy has been predominantly used to preserve the quality of life and vision of young patients,although the cellular activity of the retinoblastoma often remains after treatment with chemotherapeutic agents.Prognosis of the disease is immensely depending on the stage and time of diagnosis and is varying between countries due to different developmental status of health care systems.Methods:We review recent advances in the available literature on established preclinical models in CM,UM,and retinoblastoma.In addition,we discuss the advantages and limitations of these models and provide an overview of current alternatives to animal testing in preclinical studies.Conclusions:In the case of all three diseases,further research is needed for improved therapeutic options.Animal models in particular are indispensable for cancer research in order to mimic the extremely complex processes of human carcinogenesis,physiology and progression.Certainly,animal studies do not easily translate to human diseases due to biological differences and limitations.However,they continue to serve as the primary source and link between in vitro testing and clinical studies in patients.In order to minimize animal experiments and possibly even replace them in the future,alternatives such as 3D cell cultures and in silico predictions are useful and insightful additions and require further development.Still,no currently available preclinical model can be fully translated to some of here described diseases.Nevertheless,they all provide essential insights and knowledge that should be of use in the future for better understanding and pursuit of new therapeutic strategies. 展开更多
关键词 conjunctival melanoma(CM) uveal melanoma(UM) RETINOBLASTOMA ocular tumor preclinical models
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A UV-related risk analysis in ophthalmic malignancies:Increased UV exposure may cause ocular malignancies
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作者 Xiaojun Ju Alexander C.Rokohl +4 位作者 Xueting Li Yongwei Guo Ke Yao Wanlin Fan Ludwig M.Heindl 《Advances in Ophthalmology Practice and Research》 2024年第2期98-105,共8页
Purpose:To explore the role of ultraviolet radiation(UVR)in the occurrence and development of various ocular malignancies.Methods:In this article,we retrieved ocular malignancy data from the Global Cancer Observatory(... Purpose:To explore the role of ultraviolet radiation(UVR)in the occurrence and development of various ocular malignancies.Methods:In this article,we retrieved ocular malignancy data from the Global Cancer Observatory(GCO)and performed correlation analysis with the global UV index and sunshine duration.We searched for associated studies using the following databases:Embase,Pubmed,Cochrane Library,and Google Scholar.We conducted the literature by searching the Mesh terms denoting an exposure of interest("UV radiation","ultraviolet rays",and"ocular malignancies"),All studies included are published until December 30,2023 without language restrictions.Results:The mechanisms and epidemiological statistics of UVR on the onset and progression of eyelid malig-nancies are the most studied and clear.The role of UVR in conjunctival melanoma is similar to that in eyelid melanoma.The relationship between uveal melanoma and UVR is controversial,however,it may have at least a certain impact on its prognosis.UVR causes ocular surface squamous neoplasia by further activating HPV infection.Conclusions:UVR is a decisive risk factor for ocular malignancies,but the incidence of ultraviolet-induced tumors is also affected by many other factors.A correct and comprehensive understanding of the mechanisms of UVR in the pathogenesis of ocular malignant tumors can provide patients with more effective and selective immune regulation strategies. 展开更多
关键词 Ultraviolet radiation Eyelid malignancies conjunctival melanoma Uveal melanoma Ocular surface squamous neoplasia
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