The tumor microenvironment is abundant with exosomes that are secreted by the cancer cells themselves. Exosomes are nanosized, organelle-like membranous structures that are increasingly being recognized as major contributors in the progression of malignant neoplasms. A critical element in melanoma progression is its propensity to metastasize, but little is known about how melanoma cell-derived exosomes modulate the microenvironment to optimize conditions for tumor progression and metastasis. Here, we provide evidence that melanoma cell-derived exosomes promote phenotype switching in primary melanocytes through paracrine/autocrine signaling. We found that the mitogen-activated protein kinase (MAPK) signaling pathway was activated during the exosome-mediated epithelial-to-mesenchymal transition (EMT)-resembling process, which promotes metastasis. Let-7i, an miRNA modulator of EMT, was also involved in this process. We further defined two other miRNA modulators of EMT (miR-191 and let-7a) in serum exosomes for differentiating stage I melanoma patients from non-melanoma subjects. These results provide the first strong molecular evidence that melanoma cell-derived exosomes promote the EMT-resembling process in the tumor microenvironment. Thus, novel strategies targeting EMT and modulating the tumor microenvironment may emerge as important approaches for the treatment of metastatic melanoma.
One word can be used to best describe the theme of each day that has transpired since the onset of the COVID-19 pandemic: uncertainty. Urologic surgical residents around the nation are faced with the unknown when they walk through the doors of the hospital each day. While experience has taught us navigational strategies to handle these circumstances, the COVID-19 pandemic has undoubtedly brought new meaning to this concept. Priorities have quickly transitioned from closely following our previously developed academic curriculum and enhancing our surgical skills, to limiting physician-patient encounters and ensuring the safety and health of our team. Normalcy within our professional and personal lives is completely lost. Yet, as health care providers, we must and will forge on. We review the techniques and guidelines that our institution has implemented in order to allow us to do just that.We believe that our leadership, both at an enterprise and program level, has taken the necessary and early measures to prepare our residency cohort for the uncertain future and challenges posed by COVID-19. This plan emphasizes social and professional distancing, allows residents and faculty to stay current on academic topics, and provides reasonable opportunities for personal wellness, all while emphasizing safety and rationalization. Most importantly, however, we have continued to provide our patients with exceptional urologic care at 2 adult hospitals and 1 children's hospital in the Greater Akron, Ohio area. While we understand each residency program has a unique curriculum with a different number of residents that cover a range of different hospitals, we hope to provide insight into our personal experience. We believe that this method of organization allows a residency program to continue to grow professionally, socially, academically, and personally during the uncertainty that is COVID-19. This framework could serve as an immediate action plan for future pandemics and natural disasters, especially for residency programs that cover multiple hospitals and health care settings.
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