Small extracellular vesicles: Roles and clinical application in prostate cancer.

Prostate cancer is a significant health problem in the United States. It is remarkably heterogenous, ranging from slow growing disease amenable to active surveillance to highly aggressive forms requiring active treatments. Therefore, being able to precisely determine the nature of disease and appropriately match patients to available and/or novel therapeutics is crucial to improve patients' overall outcome and quality of life. Recently small extracellular vesicles (sEVs), a subset of nanoscale membranous vesicles secreted by various cells, have emerged as important analytes for liquid biopsy and promising vehicles for drug delivery. sEVs contain various biomolecules such as genetic material, proteins, and lipids that recapitulate the characteristics and state of their donor cells. The application of existing and newly developed technologies has resulted in an increased depth of knowledge about biophysical structures, biogenesis, and functions of sEVs. In prostate cancer patients, tumor-derived sEVs can be isolated from biofluids, commonly urine and blood. They mediate intercellular signaling within the tumor microenvironment and distal organ-specific sites, supporting cancer initiation, progression, and metastasis. A mounting body of evidence suggests that sEV components can be potent biomarkers for prostate cancer diagnosis, prognosis, and prediction of disease progression and treatment response. Due to enhanced circulation stability and bio-barrier permeability, sEVs can be also used as effective drug delivery carriers to improve the efficacy and specificity of anti-tumor therapies. This review discusses recent studies on sEVs in prostate cancer and is focused on their role as biomarkers and drug delivery vehicles in the clinical management of prostate cancer.

A Patient With Minimally Conscious Syndrome Due to Cerebrovascular Accident Whose Symptoms Resolved With Zolpidem.

OBJECTIVE: In this report, we discuss the case of a patient with minimally conscious state (MCS) whose clinical condition significantly improved after Zolpidem therapy. We aim to provide supportive evidence for inclusion of zolpidem trials in patients with MCS. METHODS: Our team used electronic medical records, direct patient care experiences, and literature review to obtain information for this case report. RESULTS: Twice daily zolpidem therapy led to significant clinical improvement in our patient with MCS. In addition, this improvement was maintained throughout an increasingly arduous medical course. CONCLUSIONS: Minimally conscious state is a disorder with limited proven therapeutic options. Zolpidem administration has demonstrated immense benefit in a select population of patients, including ours. Given the potential for great improvement with limited downside, zolpidem trial presents an intriguing treatment option. Further clarification of prognostic features to stratify responders and nonresponders to therapy is needed.

Tumor Treating Fields: At the Crossroads Between Physics and Biology for Cancer Treatment.

Despite extraordinary advances that have been achieved in the last few decades, cancer continues to represent a leading cause of mortality worldwide. Lethal cancer types ultimately become refractory to standard of care approaches; thus, novel effective treatment options are desperately needed. Tumor Treating Fields (TTFields) are an innovative non-invasive regional anti-mitotic treatment modality with minimal systemic toxicity. TTFields are low intensity (1-3 V/cm), intermediate frequency (100-300 kHz) alternating electric fields delivered to cancer cells. In patients, TTFields are applied using FDA-approved transducer arrays, orthogonally positioned on the area surrounding the tumor region, with side effects mostly limited to the skin. The precise molecular mechanism of the anti-tumor effects of TTFields is not well-understood, but preclinical research on TTFields suggests it may act during two phases of mitosis: at metaphase, by disrupting the formation of the mitotic spindle, and at cytokinesis, by dielectrophoretic dislocation of intracellular organelles leading to cell death. This review describes the mechanism of action of TTFields and provides an overview of the most important in vitro studies that investigate the disruptive effects of TTFields in different cancer cells, focusing mainly on anti-mitotic roles. Lastly, we summarize completed and ongoing TTFields clinical trials on a variety of solid tumors.