Abstract:In recent years, the role of zinc in biological systems has been a subject of intense research. Despite wide increase in our knowledge and understanding of zinc homeostasis, numerous questions remain to be answered, encouraging further research. In particular, the quantification of intracellular zinc ions and fluctuation, as well as the function of zinc in signaling processes are being intensely investigated. The determination of free intracellular zinc ions is difficult and error-prone, as concentrations are extremely low (in the pico-to nanomolar range), but techniques exist involving fluorescent probes and sensors. In spite of zinc deficiency being accepted as a global problem, causing death and disease worldwide, to date there are no markers to reliably assess a person's zinc status. This review summarizes the difficulties and major pitfalls when working with zinc in in vitro and in vivo research. Additionally, it specifies important aspects for zinc substitution and supplementation, including the bioavailability of zinc and its intestinal absorption. In particular, it is intended to help researchers with yet minor experience working with zinc efficiently set up experiments and avoid commonly occurring mistakes, starting with the choice and preparation of reagents and instrumentation, and concluding with possibilities for measuring the status of zinc in humans.
Zinc ions serve as second messengers in major cellular pathways, including the regulation pathways of proliferation and their proper regulation is necessary for homeostasis and a healthy organism. Accordingly, expression of zinc transporters can be altered in various cancer cell lines and is often involved in producing elevated intracellular zinc levels. In this study, human B cells were infected with Epstein–Barr virus (EBV) to generate immortalized cells, which revealed traits of tumor cells, such as high proliferation rates and an extended lifespan. These cells showed differentially altered zinc transporter expression with ZIP7 RNA and protein expression being especially increased as well as a corresponding increased phosphorylation of ZIP7 in EBV-transformed B cells. Accordingly, free zinc levels were elevated within these cells. To prove whether the observed changes resulted from immortalization or rather high proliferation, free zinc levels in in vitro activated B cells and in freshly isolated B cells expressing the activation marker CD69 were determined. Here, comparatively increased zinc levels were found, suggesting that activation and proliferation, but not immortalization, act as crucial factors for the elevation of intracellular free zinc.
Purpose: To evaluate the impact of adjuvant intravesical bacillus Calmette-Guérin (BCG) treatment in patients with high-grade transitional cell carcinoma of bladder. Patients and Methods: A total of 207 consecutive patients who underwent transurethral resection for high-grade T1 transitional cell carcinoma of bladder at our institution between January 1, 2005 and December 31, 2012. Of those patients, 77 underwent early cystectomy without BCG instillation and were excluded from the analysis. The overall survival and cancer-specific mortality were compared in 2 different therapy options groups (group of patients who received adjuvant BCG instillation vs. the group of patients who did not receive BCG therapy). Overall mortality was estimated by the Kaplan-Meier method, univariate comparisons were made with the log rank test. The cumulative incidence of deaths from bladder cancer (BC) was determined by univariate and multivariate competing risk analysis. Cox proportional hazard models for competing risks were used to study the combined effects of the variables on BC-specific mortality. Results: The 5-year overall survival in patients with BCG instillation vs. patients who did not receive BCG therapy was 74 vs. 28% (p = 0.0016). In the univariate analysis, the adjuvant intravesical BCG treatment was associated with decreased cancer-specific mortality (p = 0.0062). In the multivariable analysis, the age and the BCG instillation were independent factors of overall survival (hazard ratio 0.26, 95% CI 0.15-0.46, p < 0.0001) and cancer-specific mortality (hazard ratio 0.29, 95% CI 0.12-0.71, p = 0.0067). Conclusion: Dispensing from adjuvant intravesical BCG treatment is associated with increased overall- and disease-specific mortality in patients with T1 high-grade transitional cell carcinoma of bladder. This observation confirms that adjuvant BCG instillation is a crucial part of treatment in this patient population.
Exosomes are extracellular vesicles that are formed by two invaginations of the plasma membrane and can be released by all eukaryotic cells. Because of their bioactive contents, including nucleic acids and proteins, exosomes can activate a variety of functions in their recipient cells. Due to the plethora of physiological and pathophysiological functions, exosomes have received a lot of attention from researchers over the past few years. However, there is still no consensus regarding isolation and characterization protocols of exosomes and their subtypes. This heterogeneity poses a lot of methodical challenges but also offers new clinical opportunities simultaneously. So far, exosome-based research is still mostly limited to preclinical experiments and early-stage clinical trials since the translation of experimental findings remains difficult. Exosomes could potentially play an important role as future diagnostic and prognostic agents and might also be part of the development of new treatment strategies. Therefore, they have previously been investigated in a variety of nephrological and urological conditions such as acute kidney injury or prostate cancer.
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