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皮肤恶性黑色素瘤与基质金属蛋白酶:通向高效治疗的有希望的关联。

Skin Malignant Melanoma and Matrix Metalloproteinases: Promising Links to Efficient Therapies.

机构信息

Faculty of General Medicine, University of Medicine and Pharmacy "Carol Davila", 050474 Bucharest, Romania.

General Surgery Clinic, Colentina Clinical Hospital, 020125 Bucharest, Romania.

出版信息

Int J Mol Sci. 2024 Jul 17;25(14):7804. doi: 10.3390/ijms25147804.

Abstract

Skin malignant melanoma (MM) is one of the most frequent and aggressive neoplasia worldwide. Its associated high mortality rates are mostly due to its metastases, while diagnosis and treatment of MM in its early stages is of favorable prognostic. Even skin superficial MMs at incipient local stages can already present with lymph node invasion and distant metastases. Therefore, knowledge of the controllable risk factors and pathogenic mechanisms of MM development, spreading, and metastatic pattern, as well as early diagnosis, are essential to decrease the high mortality rates associated with cutaneous malignant melanoma. Genetic factors are incriminated, although lifetime-acquired genetic mutations appear to be even more frequently involved in the development of MM. Skin melanocytes divide only twice per year and have time to accumulate genetic mutations as a consequence of environmental aggressive factors, such as UV exposure. In the search for more promising therapies, matrix metalloproteinases have become of significant interest, such as MMP-1, MMP-2, MMP-9, and MMP-13, which have been linked to more aggressive forms of cancer and earlier metastases. Therefore, the development of specific synthetic inhibitors of MMP secretion or activity could represent a more promising and effective approach to the personalized treatment of MM patients.

摘要

皮肤恶性黑色素瘤(MM)是全球最常见和侵袭性的肿瘤之一。其相关的高死亡率主要归因于转移,而早期诊断和治疗 MM 具有良好的预后。即使处于局部早期的皮肤浅表 MM 也可能已经存在淋巴结侵犯和远处转移。因此,了解 MM 发展、扩散和转移模式的可控风险因素和发病机制,以及早期诊断,对于降低与皮肤恶性黑色素瘤相关的高死亡率至关重要。遗传因素被归咎于其中,尽管一生中获得的遗传突变似乎更频繁地参与 MM 的发展。皮肤黑素细胞每年仅分裂两次,由于环境侵袭性因素(如紫外线暴露),它们有时间积累遗传突变。在寻找更有前途的治疗方法时,基质金属蛋白酶(matrix metalloproteinases,MMPs)引起了人们的极大兴趣,其中包括 MMP-1、MMP-2、MMP-9 和 MMP-13,它们与更具侵袭性的癌症形式和更早的转移有关。因此,开发针对 MMP 分泌或活性的特异性合成抑制剂可能是 MM 患者个体化治疗的更有前途和有效的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76a9/11277423/710c8a9ebbe4/ijms-25-07804-g001.jpg

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