Immunotherapy for urothelial carcinoma: Metastatic disease and beyond

For advanced and metastatic urothelial carcinomas (UCs), platinum (preferably cisplatin)‐based chemotherapy has been the standard treatment for many years. However, many patients are ineligible for cisplatin‐based chemotherapy because of poor performance status and/or other age‐related conditions. At the other end of the spectrum, patients with localized non‐muscle–invasive bladder cancer who are unresponsive to intravesical Bacillus Calmette‐Guérin (BCG) treatment often face radical cystectomy as the only option. In recent years, the application of immunotherapy in the form of immune‐checkpoint inhibitors has provided viable alternatives in the second‐line postplatinum and first‐line cisplatin‐ineligible settings. Recent and ongoing clinical trials are also assessing the safety and efficacy of immunotherapy for neoadjuvant and adjuvant uses before/after cystectomy, for BCG‐unresponsive cases, and for combination treatments that include the newer indoleamine 2,3‐dioxygenase‐1 inhibitors and/or BCG. This review summarizes recent developments in immunotherapy for UCs.     

Rosmarinus plants: Key farm concepts towards food applications

Rosmarinus species are aromatic plants that mainly grow in the Mediterranean region. They are widely used in folk medicine, food, and flavor industries and represent a valuable source of biologically active compounds (e.g., terpenoids, flavonoids, and phenolic acids). The extraction of rosemary essential oil is being done using three main methods: carbon dioxide supercritical extraction, steam distillation, and hydrodistillation. Furthermore, interesting antioxidant, antibacterial, antifungal, antileishmanial, anthelmintic, anticancer, anti‐inflammatory, antidepressant, and antiamnesic effects have also been broadly recognized for rosemary plant extracts. Thus the present review summarized data on economically important Rosmarinus officinalis species, including isolation, extraction techniques, chemical composition, pharmaceutical, and food applications.     

The effect of nettle (Urtica dioica) supplementation on the glycemic control of patients with type 2 diabetes mellitus: A systematic review and meta‐analysis

Type 2 diabetes mellitus (T2DM) is a major health problem, worldwide, that is associated with increased morbidity and mortality. Several randomized controlled clinical trials (RCTs) have investigated the effect of nettle (Urtica dioica) supplementation on markers of glycemic status in patients with T2DM, with conflicting results. Therefore, the present study assessed the effect of nettle on some glycemic parameters in patients with T2DM. A comprehensive search was conducted in PubMed, Scopus, Cochrane Library, and Web of Science, from database inception up to June 2019, to identify RCTs investigating the effect of nettle supplementation on glycemic markers, including fasting blood sugar (FBS) concentrations, insulin levels, homeostasis model assessment‐estimated insulin resistance index, and glycosylated hemoglobin percentage in adults with T2DM. The Cochrane Collaboration tool was used to assess the methodological quality of the included studies. Results of this meta‐analysis were reported based on the random effects model. Eight RCTs, comprising 401 participants, were included in the present systematic review and meta‐analysis. Based on the Cochrane Collaboration risk of bias tool, five studies were considered as good quality, one was fair, and two studies were poor, respectively. The results of the meta‐analysis revealed a significant reduction in FBS concentrations (weighted mean difference [WMD]: ?18.01 mg/dl, 95% confidence interval [CI]: ?30.04 to ?5.97, p < .001, I² = 94.6%) following nettle supplementation. However, no significant reduction was observed in insulin levels (WMD: 0.83 Hedges' g, 95% CI: ?0.26 to 1.92, p = .13, I² = 89.4%), homeostasis model assessment‐estimated insulin resistance index (WMD: ?0.22, 95% CI: ?0.83 to 0.40, p = .49, I² = 69.2%), or glycosylated hemoglobin percentage (WMD: ?0.77%, 95% CI: ?1.77 to 0.22, p = .12, I² = 83.0%). The findings of the present study suggest that nettle supplementation may be effective in controlling FBS for T2DM patients. However, further studies are needed to confirm the veracity of these results.     

CDC25B and CDC25C overexpression in nonmelanoma skin cancer suppresses cell death

Non‐melanoma skin cancer frequently results from chronic exposure to ultraviolet (UV) irradiation. UV‐induced DNA damage activates cell cycle arrest checkpoints through degradation of the cyclin‐dependent kinase activators, the cell division cycle 25 (CDC25) phosphatases. We previously reported increased CDC25A in nonmelanoma skin cancer, but CDC25B and CDC25C had not been previously examined. Consequently, we hypothesized that increased expression of CDC25B and CDC25C increases tumor cell proliferation and skin tumor growth. We found that CDC25B and CDC25C were increased in mouse and human skin cancers. CDC25B was primarily cytoplasmic in skin and skin tumors and was significantly increased in the squamous cell carcinoma (SCC), while CDC25C was mostly nuclear in the skin, with an increased cytoplasmic signal in the premalignant and malignant tumors. Surprisingly, forced expression of CDC25B or CDC25C in cultured SCC cells did not affect proliferation, but instead suppressed apoptosis, while CDC25C silencing increased apoptosis without impacting proliferation. Targeting CDC25C to the nucleus via mutation of its nuclear export sequence, however, increased proliferation in SCC cells. Overexpression of CDC25C in the nuclear compartment did not hinder the ability of CDC25C to suppress apoptosis, neither did mutation of sites necessary for its interaction with 14‐3‐3 proteins. Analysis of apoptotic signaling pathways revealed that CDC25C increased activating phosphorylation of Akt on Ser⁴⁷³, increased inhibitory phosphorylation of proapoptotic BAD on Ser¹³⁶, and increased the survival protein Survivin. Silencing of CDC25C significantly reduced Survivin levels. Taken together, these data suggest that increased expression of CDC25B or CDC25C are mechanisms by which skin cancers evade apoptotic cell death.