RESUMO
Choroidal metastasis as an initial presenting feature of lung cancer with EML4-ALK translocation is exceedingly rare and greatly impacts patient quality of life (QOL). There are no recommended treatments for such patients, and palliative care remains limited. It is unclear whether surgical resection of primary pulmonary lesions, systemic antitumor therapy, targeted therapy, or localized ocular therapy are effective in treating choroidal metastases in EML4-ALK rearranged oligometastatic non-small cell lung cancer (NSCLC). Here, we present the case of choroidal metastases secondary to lung cancer and EML4-ALK translocation in a 57-year-old woman who firstly underwent resection of lung lesions followed by oral administration of crizotinib without local treatment or systemic chemotherapy. Since then she had a rapid and complete response to crizotinib with 27 months of progression-free survival.
RESUMO
The inflammatory cytokine interleukin (IL)1ß has been implicated in demyelinating diseases, such as multiple sclerosis and experimental autoimmune encephalomyelitis, and brain degenerative diseases, such as Alzheimer's disease. However, the cellular and molecular mechanisms underlying the damaging effects of IL1ß on myelination are poorly understood. Therefore, the present study was designed to investigate whether IL1ß modifies the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) through regulating the miR2023p/ßcatenin/gliomaassociated oncogene homolog 1 (Gli1) axis. It was observed that IL1ß significantly attenuated the proliferation and differentiation of OPCs, as evidenced by a decrease in bromodeoxyuridine incorporation and reduced percentage of myelin basic proteinpositive cells among the total number of oligodendrocyte transcription factor 2positive cells. In addition, IL1ß markedly decreased the expression of miR2023p and increased the protein expression of ßcatenin and Gli1, all of which were reversed by the IL1ß inhibitor, IL1Ra. Treatment with the ßcatenin inhibitor XAV939, Gli1 siRNA, or miR2023p mimic transfection, attenuated the IL1ßinduced suppression of OPC proliferation and differentiation. Treatment with XAV939 decreased the expression of Gli1. Transfection of miR2023p mimic attenuated the expression of ßcatenin and Gli1. As demonstrated by the findings of the present study, IL1ß suppressed the proliferation and differentiation of OPCs through regulation of the miR2023p/ßcatenin/Gli1 axis. Therefore, the miR2023p/ßcatenin/Gli1 axis may be of value as a therapeutic target in multiple sclerosis.