Glioblastoma multiforme (GBM) is the most common, malignant, poorly promising primary brain tumor. GBM is characterized by an infiltrating growth nature, abundant vascularization, and a rapid and aggressive clinical course. For many years, the standard treatment of gliomas has invariably been surgical treatment supported by radio- and chemotherapy. Due to the location and significant resistance of gliomas to conventional therapies, the prognosis of glioblastoma patients is very poor and the cure rate is low. The search for new therapy targets and effective therapeutic tools for cancer treatment is a current challenge for medicine and science. microRNAs (miRNAs) play a key role in many cellular processes, such as growth, differentiation, cell division, apoptosis, and cell signaling. Their discovery was a breakthrough in the diagnosis and prognosis of many diseases. Understanding the structure of miRNAs may contribute to the understanding of the mechanisms of cellular regulation dependent on miRNA and the pathogenesis of diseases underlying these short non-coding RNAs, including glial brain tumors. This paper provides a detailed review of the latest reports on the relationship between changes in the expression of individual microRNAs and the formation and development of gliomas. The use of miRNAs in the treatment of this cancer is also discussed.
The most lethal damage for the cell among all damage is double-strand breaks (DSB) of DNA. DSB cause development of cancer diseases including the triple-negative molecular subtype of breast cancer. The aim of this work was to evaluate the single nucleotide polymorphism -135G>C (rs1801320) of the RAD51 gene encoding DNA repair proteins by homologous recombination (HR) in triple-negative breast cancer (TNBC). We assessed the RAD51 -135G>C polymorphism in 50 women with triple-negative breast cancer and in 50 women from the control group. RAD51 polymorphism was analysed by the PCR-RFLP (restriction fragment length polymorphism) technique. Our results demonstrated a significant positive association between the RAD51 C/C genotype and TNBC, with an adjusted odds ratio (OR) of 5.95 (p = 0.002). The homozygous C/C genotype was found in 68% of breast cancer cases and 20% of controls. The variant 135C allele of RAD51 increased TNBC risk. This is the first study linking single nucleotide polymorphisms of the RAD51 gene with TNBC incidence in the population of Polish women. In conclusion, RAD51 polymorphisms may be regarded as predictive factors of triple-negative breast cancer in the female population. Large studies are needed to confirm our findings.
PurposeEpilepsy is a disease of neurological character. Approximately one third of epileptic patients demonstrate a drug-resistant phenotype, which is associated with the development of drug-resistant epilepsy. The multidrug resistance protein 1 and glycoprotein P, encoded by MDR1, play a significant role in the transmembrane transport of anti-epileptic agents. Single nucleotide polymorphism C3435T (rs1045642) within MDR1 gene may be associated with an increased expression of P-gp which affects the levels of antiepileptic drugs in plasma. The presented studies analysed the association between C3435T polymorphism of MDR1 gene and the incidence of drug-resistant epilepsy in the population of Polish children.MethodsC3435T polymorphism of MDR1 gene was analysed by the high resolution melting technique in a group of patients with drug-resistant (n = 106) and drug-responsive epilepsy (n = 67), as well as in non-epileptic children (n = 98) hospitalised at the Department of Neurology, Polish Mother’s Memorial Hospital in Lodz. Genotype and allele distributions were evaluated and their compatibility with the Hardy–Weinberg distribution was assessed by means of the χ2 test. Genotype and allele evaluation, regarding their relationship with a given feature, was supported by an analysis of odds ratio and 95 % confidence interval, calculated according to the logistic regression model.ResultsAn association was observed between the incidence rate of DRE and the presence of C allele in C3435T polymorphism of MDR1 gene, which may enhance the risk of the disease. The T allele may then play a protective role. No differences were found in the studied groups, regarding either genotype or allele distribution in reference to patient’s gender or concomitant diseases.ConclusionFollowing the obtained results, C3435T polymorphism of MDR1 gene may be connected with the incidence of drug-resistant epilepsy in the population of Polish children.ISRCTN ISRCTN73824458. Registered 28th September 2014.
XRCC2 and XRCC3 genes involved in homologous recombination repair (HRR) of DNA and in the maintenance of the genome integrity play a crucial role in protecting against mutations that lead to cancer. The aim of the present work was to evaluate associations between the risk of triple-negative breast cancer (TNBC) and polymorphisms in the genes, encoding for two key proteins of HRR: XRCC2 Arg188His (c. 563 G>A; rs3218536, Genbank Accession Number NT 007914) and XRCC3 Thr241Met (c. 722 C>T; rs861539, Genbank Accession Number NT 026437). The polymorphisms of the XRCC2 and XRCC3 were investigated by PCR–RFLP in 70 patients with TNBC and 70 age- and sex-matched non-cancer controls. In the present work, a relationship was identified between XRCC2 Arg188His polymorphism and the incidence of triple-negative breast cancer. The 188His allele and 188His/His homozygous variant increased cancer risk. An association was confirmed between XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms and TNBC progression, assessed by the degree of lymph node metastases and histological grades. In conclusion, XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms may be regarded as predictive factors of triple-negative breast cancer in female population.
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