Immune targeted therapy of nitric oxide (NO) synthases are being considered as a potential frontline therapeutic to treat patients diagnosed with locally advanced and metastatic prostate cancer. However, the role of NO in castration-resistant prostate cancer (CRPC) is controversial because NO can increase in nitrosative stress while simultaneously possessing antiinflammatory properties. Accordingly, we tested the hypothesis that increased NO will lead to tumor suppression of CRPC through tumor microenvironment. S-nitrosoglutathione (GSNO), an NO donor, decreased the tumor burden in murine model of CRPC by targeting tumors in a cell nonautonomous manner. GSNO inhibited both the abundance of antiinflammatory (M2) macrophages and expression of pERK, indicating that tumor-associated macrophages activity is influenced by NO. Additionally, GSNO decreased IL-34, indicating suppression of tumor-associated macrophage differentiation. Cytokine profiling of CRPC tumor grafts exposed to GSNO revealed a significant decrease in expression of G-CSF and M-CSF compared with grafts not exposed to GSNO. We verified the durability of NO on CRPC tumor suppression by using secondary xenograft murine models. This study validates the significance of NO on inhibition of CRPC tumors through tumor microenvironment (TME). These findings may facilitate the development of previously unidentified NO-based therapy for CRPC.
Objectives: Recent advancements in robotics have set forth a growing body of evidence for the clinical application of the robotic cochlear implantation (RCI), with many potential benefits. This review aims to summarize these efforts, provide the latest developments in this exciting field, and explore the challenges associated with the clinical implementation of RCI. Data Sources: MEDLINE, PubMed, and EMBASE databases. Study Selection: A search was conducted using the keywords ''robotics otolaryngology,'' ''robotic cochlear implant,'' ''minimally-invasive cochlear implantation,'' ''minimally-invasive mastoidectomy,'' and ''percutaneous cochlear implant'' with all of their synonyms. Literature selection criteria included articles published in English, and articles from 1970 to present. Results: The use of robotics in neurotology is a relatively new endeavor that continues to evolve. Robotics is being explored by various groups to facilitate in the various steps of cochlear implant surgery, including drilling a keyhole approach to the middle ear for implants, inner ear access, and electrode insertion into the cochlea. Initial clinical trials have successfully implanted selected subjects using robotics. Conclusions: The use of robotics in cochlear implants remains in its very early stages. It is hoped that robotics will improve clinical outcomes. Although successful implants with robots are reported in the literature, there are some challenges that need to be addressed before this approach can become an acceptable option for the conventional cochlear implant surgery, such as safety, time, efficiency, and cost. However, it is hoped that further advancements in robotic technology will help in overcoming these barriers leading to successful implementation for clinical utility.
Male infertility is an often overlooked component of a couple's inability to conceive. We outline many common and often overlooked sports and recreational exposures that have been associated with male infertility.
<b><i>Background:</i></b> Although meningiomas are the most common central nervous system neoplasms, extracranial metastases are exceedingly rare. There are even fewer reports of metastatic meningiomas to the neck. <b><i>Methods:</i></b> We described a patient with multiply recurrent orbital meningioma with metastasis to the neck found incidentally during neck exploration for composite resection and free tissue reconstruction. We performed a systematic review for all records pertaining to metastatic meningiomas to the cervical regions. <b><i>Results:</i></b> We found 9 previous reports of cervical metastatic meningiomas. Almost all cases underwent extensive local resection. There was no evidence of an association between the histological grade of the tumor and risk of metastasis to the neck. Cervical lymph node dissemination is more common in patients presenting after previous primary tumor resection. <b><i>Conclusions:</i></b> In the context of a neck mass, our findings suggest that metastatic meningioma should be included in the differential diagnosis, especially in patients with previous resections.
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