Fever of Unknown Origin, Wasting Syndrome and Bone Marrow Involvement: A Leprosy Case Report.

Mycobacterium leprae, the etiologic agent of leprosy, is an acid-fast-staining and slow-growing bacilli that infect macrophages and Schwann cells individually or through forming globi. The clinical presentation of leprosy is broad and depends on the host immune response. We report a case of a 42-year-old Brazilian man presenting with fever of unknown origin (FUO), anemia, wasting syndrome, and neuropathy. The diagnosis of lepromatous leprosy was made after an extensive investigation revealed the presence of M. leprae in the bone marrow. Bone marrow involvement in leprosy is rare and some authors believe the presence of M. leprae in the bone marrow can act as a reservoir of the disease facilitating future relapses. It is important to investigate bone marrow involvement in leprosy, especially when the patient presents with cytopenias and positive epidemiologic history.

Annexin A1 promotes the nuclear localization of the epidermal growth factor receptor in castration-resistant prostate cancer.

Epidermal growth factor receptor is a cancer driver whose nuclear localization has been associated with the progression of prostate cancer to the castration-resistant phenotype. Previous reports indicated a functional interaction between this receptor and the protein Annexin A1, which has also been associated with aggressive tumors. The molecular pathogenesis of castration-resistant prostate cancer remains largely unresolved, and herein we have demonstrated the correlation between the expression levels and localization of the epidermal growth factor receptor and Annexin A1 in prostate cancer samples and cell lines. Interestingly, a higher expression of both proteins was detected in castration-resistant prostate cancer cell lines and the strongest correlation was seen at the nuclear level. We verified that Annexin A1 interacts with the epidermal growth factor receptor, and by using prostate cancer cell lines knocked down for Annexin A1, we succeeded in demonstrating that Annexin A1 promotes the nuclear localization of epidermal growth factor receptor. Finally, we showed that Annexin A1 activates an autocrine signaling in castration-resistant prostate cells through the formyl peptide receptor 1. The inhibition of such signaling by Cyclosporin H inhibits the nuclear localization of epidermal growth factor receptor and its downstream signaling. The present work sheds light on the functional interaction between nuclear epidermal growth factor receptor and nuclear Annexin A1 in castration-resistant prostate cancer. Therefore, strategies to inhibit the nuclear localization of epidermal growth factor receptor through the suppression of the Annexin A1 autocrine loop could represent an important intervention strategy for castration-resistant prostate cancer.