Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease due to the absence of effective therapies. A more comprehensive understanding of molecular events, encompassing the dysregulation of microRNAs (miRs) and metabolic reprogramming, holds the potential to unveil precise mechanisms underlying mCRPC. This study aims to assess the expression of selected serum exosomal miRs (miR-15a, miR-16, miR-19a-3p, miR-21, and miR-141a-3p) alongside serum metabolomic profiling and their correlation in patients with mCRPC and benign prostate hyperplasia (BPH).
View Article and Find Full Text PDFIn recent decades, we have seen significant technical progress in the modern world, leading to the widespread use of telecommunications systems, electrical appliances, and wireless technologies. These devices generate electromagnetic radiation (EMR) and electromagnetic fields (EMF) most often in the extremely low frequency or radio-frequency range. Therefore, they were included in the group of environmental risk factors that affect the human body and health on a daily basis.
View Article and Find Full Text PDFBackground/aim: Our aim was to investigate possible influences of genetic variants in genes involved in the G/S transition [cyclin-dependent kinase-2 (CDK2), cyclin E1 (CCNE1) and cyclin-dependent kinase inhibitor 1B (p27)] on the expression/activity of their corresponding proteins and to assess the functional impact of these variants on the risk of prostate cancer.
Materials And Methods: We genotyped 530 cases and 562 healthy controls for two relevant single nucleotide polymorphisms (CDK2 rs2069408 and CCNE1 rs997669) by TaqMan genotyping assay. p27 rs2066827 polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism assay.
Sex steroid hormones have important roles in the function of the prostate; however, they may also serve as factors in the initiation and progression of carcinogenesis. Estrogens, acting through estrogen receptors, may significantly affect prostate cancer development and progression. The main aim of the present study was to analyze the association between the rs3020449, rs4986938 and rs1256049 polymorphisms in the promoter region of the estrogen receptor β () gene and prostate cancer risk in the Slovak population.
View Article and Find Full Text PDFBackground/aim: The aim of this study was to evaluate the relationship between MDM2 T309G polymorphism and prostate cancer risk in the Slovak population and the association of this polymorphism with MDM2 expression and clinicopathological features.
Materials And Methods: The MDM2 T309G polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 506 prostate cancer patients and 592 controls. Quantitative real-time (RT)-PCR and western blot analysis were applied to examine MDM2 expression in 47 prostate cancer tissues and 43 benign prostatic hyperplasia (BPH) tissues.
Elevated concentration of homocysteine (Hcy) in the blood plasma, hyperhomocysteinemia (HHcy), has been implicated in various disorders, including cardiovascular and neurodegenerative diseases. Accumulating evidence indicates that pathophysiology of these diseases is linked with mitochondrial dysfunction. In this review, we discuss the current knowledge concerning the effects of HHcy on mitochondrial homeostasis, including energy metabolism, mitochondrial apoptotic pathway, and mitochondrial dynamics.
View Article and Find Full Text PDFBackground/aim: The aim of this study was to evaluate the association between selected polymorphisms of the vascular endothelial growth factor gene (rs699947, rs144854329, rs833061, rs2010963, rs3025039) and the risk of prostate cancer development and progression.
Materials And Methods: The present study included 446 patients with prostate cancer and 241 healthy men. Genotyping was performed by polymerase-chain reaction-restriction fragment length polymorphism analysis.
Myocardial ischemia reperfusion is associated with mitochondrial dysfunction and increased formation of reactive oxygen/nitrogen species. The main purpose of this study was to assess the role of tyrosine nitration of mitochondrial proteins in postischemic contractile dysfunction known as myocardial stunning. Isolated Langendorff-perfused rat hearts were subjected to 20-min global ischemia followed by 30-min reperfusion.
View Article and Find Full Text PDFAndrogens and androgen receptor (AR) play a critical role not only in normal prostate development, but also in prostate cancer. For that reason, androgen deprivation therapy (ADT) is the primary treatment for prostate cancer. However, the majority of patients develop castration-resistant prostate cancer, which eventually leads to mortality.
View Article and Find Full Text PDFBackground/aim: Interleukin-6 is an important modulator of inflammation, which is one of the factors involved in prostate cancer. The aim of the study was to evaluate the possible association of the IL-6 -174 polymorphism (rs1800795) with the risk of prostate cancer development and progression.
Materials And Methods: The study population consisted of 446 prostate cancer patients, 377 benign prostatic hyperplasia (BHP) patients and 276 healthy men.
Cell cycle deregulation is common in human cancer. Alterations of the tumor-suppressor gene and its downstream effector p21 have been indicated in the development of numerous human malignancies. Therefore, we hypothesize that the codon 72 polymorphism, either on its own or in combination with ( and ) polymorphisms, modifies the risk of prostate cancer within the Slovak population, and no previous studies have investigated these gene-gene interactions in the pathogenesis of prostate cancer in the Slovak population.
View Article and Find Full Text PDFGene expression profile‑based taxonomy of breast cancer (BC) has been described as a significant breakthrough in comprehending the differences in the origin and behavior of cancer to allow individually tailored therapeutic approaches. In line with this, we hypothesized that the gene expression profile of histologically normal epithelium (HNEpi) could harbor certain genetic abnormalities predisposing breast tissue cells to develop human epidermal growth factor receptor 2 (HER2)‑positive BC. Thus, the aim of the present study was to assess gene expression in normal and BC tissue (BCTis) from patients with BC in order to establish its value as a potential diagnostic marker for cancer development.
View Article and Find Full Text PDFAndrogens are actively involved in the development of the prostate gland and appear to be essential for prostate carcinogenesis. The product of the SRD5A2 gene, membrane‑bound steroid 5‑α‑reductase, type II enzyme, is key in testosterone metabolism. The present study explored the association between the SRD5A2 V89L gene polymorphism and the risk of developing prostate cancer.
View Article and Find Full Text PDFN-acetyltransferase 2 (NAT2) is an enzyme involved in the biotransformation of xenobiotics, mainly aromatic and heterocyclic amines and hydrazines, all of which represent an important class of carcinogens found in tobacco smoke. Polymorphism in NAT2 gene is reported to be associated with susceptibility to various types of cancer. This study investigated the relationship between the NAT2 polymorphism and the risk of prostate cancer with reference to the link between cigarette smoking and the xenobiotic-metabolizing enzyme NAT2.
View Article and Find Full Text PDFThe aim of our study was to evaluate the effect of two polymorphisms in the estrogen receptor alpha, PvuII and XbaI, on the development of prostate cancer within Slovak population, as well as their correlation with selected clinical characteristics. The study was performed using 311 prostate cancer patients and 256 healthy male controls. Both polymorphisms were significantly associated with higher risk of prostate cancer development.
View Article and Find Full Text PDFThe cell cycle regulator p21 plays an important role in regulating critical cell activities including cell cycle control, DNA repair and apoptosis. Consequently, it may affect the efficacy of the response to DNA damage and tumor development. The aim of our study was to evaluate the frequencies of the p21 C70T polymorphism, the association between this genetic variant and smoking status, and the serum prostate-specific antigen (PSA) levels and Gleason score in 118 prostate cancer patients and 130 males routinely screened for prostate cancer in the Slovak population.
View Article and Find Full Text PDFCytochrome P-450c17α (CYP17) and prostate-specific antigen (PSA) genes, which are involved in the androgen metabolism cascade, have been studied as possible candidates for genetic influences on prostate cancer development. Contradictory results prompted us to evaluate the frequencies of polymorphisms in the CYP17 and PSA genes as well as the association between these genetic variants and serum PSA levels in prostate cancer patients and men routinely screened for prostate cancer with PSA in the Slovak male population. The CYP17 and PSA polymorphisms were determined by the PCR-RFLP analysis in 197 Caucasian prostate cancer patients and 256 Caucasian controls.
View Article and Find Full Text PDFPolymorphisms in tobacco carcinogen metabolizing enzymes may generate interindividual variations towards the risk of developing prostate cancer. One of these enzymes is microsomal epoxide hydrolase (EPHX1) which metabolizes polycyclic aromatic hydrocarbons, or PAH, carcinogens found in cigarette smoke. The activity of this enzyme is affected by two polymorphisms, a substitution of Tyr113 by His in exon 3 and a substitution of His139 by Arg in exon 4.
View Article and Find Full Text PDFObjective: The aim of present study was to present the results of a case-control study focused on genetic polymorphisms of selected Phase II metabolizing enzymes (GSTM1, T1, and P1) and to investigate the association of these polymorphisms with lung cancer risk in the Slovakian population.
Material And Methods: The study encompassed 160 lung cancer cases and 220 controls. DNA was extracted from peripheral blood leukocytes, and the polymorphisms of GSTM1, GSTT1 and GSTP1 enzymes were determined by PCR-based methods.
N-acetyltransferase 2 (NAT2) is phase II enzyme with major roles in catalyzing the detoxification of aromatic amines, which are known risk factors for bladder cancer, and are ubiquitously present in the environment. We assessed the association between common polymorphisms in NAT2 gene and the risk of bladder cancer in 90 Slovak patients and 274 ethnicity-matched healthy controls. Effect modifications by smoking, age and gender were also evaluated.
View Article and Find Full Text PDFThe aim of the paper is to determine whether IGF1, IGFBP3 and IGF1/IGFBP3 molar ratio in addition to PSA and one-nucleotide polymorphism in PSA and CYP17 gene might contribute to early diagnostics of prostate cancer (PCa). Serum level of PSA, IGF1 and IGFBP3 in the group of 158 individuals (92 PCa and 66 controls) was examined by RIA method and IGF1/IGFBP3 was calculated. PCR RLFP method was used to examine one- nucleotide polymorphism in PSA and CYP 17 gene.
View Article and Find Full Text PDFOxidative damage is considered to play an important role in the pathogenesis of several diseases, such as diabetes mellitus (DM), atherosclerosis, cardiovascular complications and chronic renal failure. DM is associated with the oxidative stress and formation of advanced glycation end products (AGEs). Different drugs inhibit oxidative stress and formation of advanced glycation end products.
View Article and Find Full Text PDFThe aim of present study was to summarize the results of a case-control study focused on genetic polymorphisms of selected Phase II metabolizing enzymes (GSTM1, T1, P1) and to investigate the association of these polymorphisms with the colorectal cancer risk among the Slovak population. A case-control study with 183 colorectal cancer cases and 422 controls was conducted. DNA was extracted from peripheral blood leukocytes, and the polymorphisms of GSTM1, GSTT1 and GSTP1 enzymes were determined by PCR-based methods.
View Article and Find Full Text PDFIschemic preconditioning (IPC) represents the phenomenon of CNC adaptation, which results in increased tolerance of CNS to lethal ischemia. Brain ischemia/reperfusion (IRI) initiates a catastrophic cascade in which many subcellular organelles play an important role. The Golgi apparatus, which is a part of secretory pathways (SP), represents the Ca(2+) store and regulates secretion of proteins for growth/reorganization of neuronal circuit by secretory Ca(2+)ATPases (SPCA1).
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