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Melanoma-Bearing Libechov Minipig (MeLiM): The Unique Swine Model of Hereditary Metastatic Melanoma

机译:携带黑色素瘤的Libechov Minipig(MeLiM):遗传性转移性黑色素瘤的独特猪模型

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摘要

National cancer databases document that melanoma is the most aggressive and deadly cutaneous malignancy with worldwide increasing incidence in the Caucasian population. Around 10% of melanomas occur in families. Several germline mutations were identified that might help to indicate individuals at risk for preventive interventions and early disease detection. More than 50% of sporadic melanomas carry mutations in Ras/Raf/mitogen-activated protein kinase (MAPK/MEK) pathway, which may represent aims of novel targeted therapies. Despite advances in targeted therapies and immunotherapies, the outcomes in metastatic tumor are still unsatisfactory. Here, we review animal models that help our understanding of melanoma development and treatment, including non-vertebrate, mouse, swine, and other mammal models, with an emphasis on those with spontaneously developing melanoma. Special attention is paid to the melanoma-bearing Libechov minipig (MeLiM). This original swine model of hereditary metastatic melanoma enables studying biological processes underlying melanoma progression, as well as spontaneous regression. Current histological, immunohistochemical, biochemical, genetic, hematological, immunological, and skin microbiome findings in the MeLiM model are summarized, together with development of new therapeutic approaches based on tumor devitalization. The ongoing study of molecular and immunological base of spontaneous regression in MeLiM model has potential to bring new knowledge of clinical importance.
机译:国家癌症数据库记录说,黑色素瘤是最具侵害性和致命性的皮肤恶性肿瘤,全世界白种人的发病率均在上升。黑色素瘤约有10%发生在家庭中。确定了几种种系突变,可能有助于表明个体处于预防干预和早期疾病检测的风险中。超过50%的散发性黑色素瘤在Ras / Raf /丝裂原激活的蛋白激酶(MAPK / MEK)途径中带有突变,这可能代表了新型靶向疗法的目标。尽管靶向疗法和免疫疗法取得了进展,但转移性肿瘤的治疗效果仍不令人满意。在这里,我们回顾了有助于我们了解黑色素瘤发展和治疗的动物模型,包括非脊椎动物,小鼠,猪和其他哺乳动物模型,重点是那些自发性发展的黑色素瘤模型。要特别注意带有黑素瘤的Libechov小型猪(MeLiM)。这种原始的猪遗传性转移性黑色素瘤模型能够研究潜在的黑色素瘤进展以及自发消退的生物学过程。总结了MeLiM模型中当前的组织学,免疫组化,生化,遗传,血液学,免疫学和皮肤微生物组研究结果,以及基于肿瘤灭活的新治疗方法的开发。正在进行的关于MeLiM模型中自发消退的分子和免疫学基础的研究有可能带来新的临床意义的知识。

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