Estrogens can stimulate the development, proliferation, migration, and survival of target cells. These biological effects are mediated through their action upon the plasma membrane estrogen receptors (ERs). ERs regulate transcriptional processes by nuclear translocation and binding to specific response elements, which leads to the regulation of gene expression. This effect is termed genomic or nuclear. However, estrogens may exert their biological activity also without direct binding to DNA and independently of gene transcription or protein synthesis. This action is called non-genomic or non-nuclear. Through non-genomic mechanisms, estrogens can modify regulatory cascades such as MAPK, P13K, and tyrosine cascade as well as membrane-associated molecules such as ion channels and G-protein-coupled receptors. The recent studies on the mechanisms of estrogen action provide an evidence that non-genomic and genomic effects converge. An example of such convergence is the potential possibility to modulate gene expression through these two independent pathways. The understanding of the plasma membrane estrogen receptors is crucial for the development of novel drugs and therapeutic protocols targeting specific receptor actions.

Sawicka E, Jurkowska K, Piwowar A. Chromium (III) and chromium (VI) as important players in the induction of genotoxicity-current view. Ann Agric Environ Med.

In recent years, bladder cancer (BC) has been reported as one of the most commonly occurring cancers among older people, and its detection is still difficult. Therefore, there is a need to search for additional useful markers of disease. Some studies indicate the important roles of inflammation and oxidative stress (OS) in bladder tumour pathogenesis. The aim of this study was to examine the levels of selected markers of OS, inflammation and angiogenesis in blood plasma/serum samples derived from patients with BC, and a healthy control group. Moreover the degrees of change and strength of correlation between values of the analysed markers and tumour stage or grade were estimated. Concentrations of: malondialdehyde (MDA) and advanced oxidation protein products (AOPP), and total antioxidant status (TAS) divided into slow (TAS-s) and fast (TAS-f) antioxidants (spectrophotometric measurement), angiogenin (ANG) (immunoenzymatic method) and C-reactive protein (CRP) (immunoturbidimetric method) were determined in both the studied groups. The majority of values of the examined parameters were significantly higher among patients, while subfractions of TAS were significantly lower in comparison to the control group. Moreover, different values and different strengths of correlation between the examined parameters and cancer stage or grade were noticed. The most significant changes for CRP were observed in T2 and for MDA in G3, while the lowest TAS-f activity was revealed in G1 patients. Increased values of OS parameters, angiogenesis and inflammation markers, in combination with reduced TAS subfractions activity in BC are important in its pathogenesis and will be helpful in estimation of patients' condition.

The epidemiological studies confirm that the overproduction of free radical is an important factor of cancer induction as well as development, and loss of antioxidant systems efficiency is associated with an increased risk of carcinogenesis. While bladder cancer is the fourth most common type of cancer all over the world, there is little evidence of the advancing changes in oxidative/nitrative stress during the progression of bladder cancer. Our study aimed to investigate the plasma levels of typical markers of oxidative/nitrative stress depending on the clinical classification of bladder cancer differentiation and infiltration degree. We examined 40 patients with newly diagnosed bladder cancer and 20 healthy volunteers as a control group. We analysed the plasma levels of protein carbonyls, thiol groups, 3-nitrotyrosine, lipid peroxidation, as well as non-enzymatic plasma antioxidant capacity using DPPH· and ABTS·+ radicals. We confirmed that all analysed biomarkers are higher in enrolled BC patients than in healthy subjects. Furthermore, our findings demonstrate a positive correlation between the degree of bladder cancer progression and the level of oxidative stress, but no correlation in the case of NT-3. Based on obtained results, we might conclude that during carcinogenesis of the bladder increased oxidative damage of biomolecules is manifested. This indicates the participation of oxidative stress in the development of bladder cancer, and it is important the ensure the proper antioxidant protection.

The review of the knowledge concerning the impact of oxidative and nitrosative stress on signaling pathways and transcription factors involved in the formation of bladder cancer was prepared. In the industrialized countries, bladder cancer is the fourth most frequently occurring malignant tumors. Recent studies indicate the involvement of oxidative and nitrosative stress in the formation and development of this disease. Red-ox disorders are characteristic for both, the initiation and progression of bladder cancer. There are observed changes in the activity of transcription factors, such as nuclear factor NF-kB; transcription factors: AP-1, Nrf2 and STAT3 and hypoxia-inducible factor HIF-1α. In addition, studies indicate a role for oxidative stress in the regulation of MAPK cascade and its involvement in carcinogenesis consisting bladder. Examples of kinases belonging to the MAPK family are ERK kinases, which expression is proportional to the severity and malignant of bladder cancer. Nitric oxide also plays an important role in tumor biology. Overproduction of NO can both inhibit and promote tumor growth, depending on its concentration, duration of action and tumor microenvironment. Numerous studies show that the bladder cancer is characterized by an intensified production of NO. Reactive forms of nitrogen, similar to oxygen free radicals, could cause oxidative and nitrosative damage to DNA and have capacity to post-translational modification of proteins. In contrast to the ROS, which overproduction result from exposure to carcinogenic xenobiotic, nitrogen oxide in high level is produced during inflammation. Sustained iNOS activity therefore plays an important role in carcinogenesis associated with the inflammatory response, characteristic also for bladder cancer.