RESUMEN
We present a patient with a history of end-stage renal disease, who developed skin lesions in the bilateral calves a month after the initiation of hemodialysis. The lesions were biopsied, and the histological findings were consistent with a diagnosis of calciphylaxis. The patient had a baseline pretreatment bone scan that showed extensive systemic disease. The patient died 20 days after the imaging study. A review of the literature on bone scans and calciphylaxis is presented.
Asunto(s)
Huesos/patología , Calcifilaxia/diagnóstico por imagen , Calcifilaxia/diagnóstico , Fallo Renal Crónico/complicaciones , Cintigrafía/métodos , Biopsia , Resultado Fatal , Femenino , Gangrena/etiología , Humanos , Fallo Renal Crónico/mortalidad , Persona de Mediana Edad , RadiografíaRESUMEN
The prognosis for patients diagnosed with mesothelioma is generally poor, and currently available treatments are usually ineffective. Therapies that specifically target tumor cells hold much promise for the treatment of cancers that are resistant to current approaches. We have previously selected phage antibody display libraries on mesothelioma cell lines to identify a panel of internalizing human single chain (scFv) antibodies that target mesothelioma-associated, clinically represented cell surface antigens and further exploited the internalizing function of these scFvs to specifically deliver lethal doses of liposome-encapsulated small molecule drugs to both epithelioid and sarcomatous subtypes of mesothelioma cells. Here, we report the identification of MCAM/MUC18/CD146 as the surface antigen bound by one of the mesothelioma-targeting scFvs using a novel cloning strategy based on yeast surface human proteome display. Immunohistochemical analysis of mesothelioma tissue microarrays confirmed that MCAM is widely expressed by both epithelioid and sarcomatous types of mesothelioma tumor cells in situ but not by normal mesothelial cells. In addition, quantum dot-labeled anti-MCAM scFv targets primary meosthelioma cells in tumor fragment spheroids cultured ex vivo. As the first step in evaluating the therapeutic potential of MCAM-targeting antibodies, we performed single-photon emission computed tomography studies using the anti-MCAM scFv and found that it recognizes mesothelioma organotypic xenografts in vivo. The combination of phage antibody library selection on tumor cells and rapid target antigen identification by screening the yeast surface-displayed human proteome could be a powerful method for mapping the targetable tumor cell surface epitope space.