Association of the cytochrome P450 and arylamine N-acetyltransferase gene polymorphisms with the incidence of head and neck cancer in Polish population.

OBJECTIVES: Head and neck cancer (HNC) is one of the most common cancers. Most exogenous HNC is head and neck squamous cell carcinomas. Scientists are striving to develop diagnostic tests that will allow the prognosis of HNC. The aim of the study was to determine the risk of HNC. The research concerned changes caused by polymorphisms in genes encoding proteins responsible for the metabolism of xenobiotics. MATERIAL AND METHODS: In group of 280 patients with HNC, the occurrence of polymorphic variants in NAT1(rs72554606), NAT2(rs1799930), CYP1A(rs1799814), CYP2D(rs3892097) were studied with TaqMan technique. The control group consisted of 260 cancer free people. The TNM scale was analyzed. Gene interactions of genotyped polymorphisms were investigated. The effects of smoking and alcohol consumption on HNC were assessed. RESULTS: The results indicated an increased risk of HNC in NAT1 polymorphisms in the GC genotype (OR = 1.772, 95% CI: 1.184-2.651, p = 0.005) and NAT2 polymorphism in the GA genotype (OR = 1.506, 95% CI: 1.023-2.216, p = 0.037). The protective phenomenon in the CYP1A polymorphism the GT genotype (OR = 0.587, 95% CI: 0.381-0.903, p = 0.015) and the TT genotype (OR = 0.268, 95% CI: 0.159-0.452, p = 0.001). The coexistence of GA-GC polymorphisms (OR = 2.687, 95% CI: 1.387-5.205, p = 0.003) in NAT2-NAT1 genes increases the risk of HNC. Risk-reducing effect in the polymorphism GG-GT (OR = 0.340, 95% CI: 0.149-0.800, p = 0.011), GG-TT (OR = 0.077, 95% CI: 0.028-0.215, p < 0.0001), GA-TT (OR = 0.250, 95% CI: 0.100-0.622, p = 0.002), AA-GT (OR = 0.276, 95% CI: 0.112-0.676, p = 0.002) in NAT2-CYP1A genes. In the CYP2D-CYP1A genes in the polymorphisms CT-CC (OR = 0.338, 95% CI: 0.132-0.870, p = 0.020), TT-GG (OR = 0.100, 95% CI: 0.027-0.359, p = 0.001), TT-GC (OR = 0.190, 95% CI: 0.072-0.502, p = 0.0004), TT-CC (OR = 0.305, 95% CI: 0.107-0.868, p = 0.024). Correlation was noted between cigarette smoking and HNC (OR = 7.297, 95% CI: 4.989-10.674, p < 0.0001) and consuming alcohol (OR = 1.572, 95% CI: 1.003-2.464, p = 0.047). CONCLUSIONS: The CYP1A polymorphism shows a protective association with HNC. On the other hand, NAT2, NAT1 polymorphism influence the susceptibility to developing HNC. The coexistence of the NAT2-NAT1 genotypes increases the risk of HNC. In contrast, NAT1-CYP1A and CYP1A-CYP2D reduce this risk. Smoking and alcohol consumption increase the incidence of HNC. Int J Occup Med Environ Health. 2023;36(6):812-24.

RNA-Based Liquid Biopsy in Head and Neck Cancer.

Head and neck cancer (HNC) is a prevalent and diverse group of malignancies with substantial morbidity and mortality rates. Early detection and monitoring of HNC are crucial for improving patient outcomes. Liquid biopsy, a non-invasive diagnostic approach, has emerged as a promising tool for cancer detection and monitoring. In this article, we review the application of RNA-based liquid biopsy in HNC. Various types of RNA, including messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), circular RNA (circRNA) and PIWI-interacting RNA (piRNA), are explored as potential biomarkers in HNC liquid-based diagnostics. The roles of RNAs in HNC diagnosis, metastasis, tumor resistance to radio and chemotherapy, and overall prognosis are discussed. RNA-based liquid biopsy holds great promise for the early detection, prognosis, and personalized treatment of HNC. Further research and validation are necessary to translate these findings into clinical practice and improve patient outcomes.

New cyclopentaquinoline and 3,5-dichlorobenzoic acid hybrids with neuroprotection against oxidative stress for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative brain disease. Thus, drugs including donepezil, rivastigmine, and galantamine are not entirely effective in the treatment of this multifactorial disease. The present study evaluates eight derivatives (3a-3h) as candidates with stronger anti-AD potential but with less side effects. Reactive oxygen species (ROS) assays were used to assess oxidative stress which involve in the neurodegeneration. The neuroprotective properties of 3e against oxidative stress were done in three experiments using MTT test. The anti-AD potential was determined based on their anticholinesterase inhibition ability, determined using Ellman's method, Aß aggregation potential according to thioflavin (Th) fluorescence assay, and their antioxidative and anti-inflammatory activities. Compound 3e exhibited moderate cholinesterase inhibition activity (AChE, IC50 = 0.131 µM; BuChE, IC50 = 0.116 µM; SI = 1.13), significant inhibition of Aß(1-42) aggregation (55.7%, at 5 µM) and acceptable neuroprotective activity. Extensive analysis of in vitro and in vivo assays indicates that new cyclopentaquinoline derivatives offer promise as candidates for new anti-AD drugs.

Association of base excision repair pathway genes OGG1, XRCC1 and MUTYH polymorphisms and the level of 8-oxo-guanine with increased risk of colorectal cancer occurrence.

OBJECTIVES: Reduced efficiency of DNA repair systems has long been a suspected factor in increasing the risk of cancer. In this work authors investigate influence of selected polymorphisms of DNA repair genes (XRCC1, OGG1 and MUTYH) and level of oxidative damage (measured as level of 8-oxo-guanine, 8-oG) on modulation of the risk of colorectal cancer. MATERIAL AND METHODS: In group of 324 patients with colorectal cancer the occurrence of polymorphic variants in Ser326Cys of OGG1, Arg399Gln of XRCC1 and Gln324His of MUTYH were studied with TaqMan technique. In addition level of 8-oG in isolated DNA was determined. RESULTS: Studied polymorphisms of OGG1, XRCC1 and MUTYH genes influence the risk of CRC: OGG1 Ser326Cys (OR = 1.259, 95% CI: 1.058-1.499, p = 0.007), XRCC1 Arg399Gln (OR = 2.481, 95% CI: 1.745-3.529, p < 0.0001) and MUTYH Gln324His (OR = 1.421, 95% CI: 1.017-1.984, p = 0.039) increase the risk. At the same time, studies examined level of 8-oG for each of the genotypes in both the patient and control group, and have shown that OGG1 Ser326Cys and XRCC1 Arg399Gln are associated with elevated 8-oG level, while MUTYH Gln324His is not, suggesting, that in case of OGG1 Ser326Cys and XRCC1 Arg399Gln CRC risk modulation is connected to mechanisms associated with 8-oG levels. CONCLUSIONS: This work shows that patients with CRC not only have an increased level of 8-oG and that the studied polymorphisms modulate risk of cancer, but also indicate a relationship between these 2 phenomena, which may contribute to a better understanding of the mechanism of neoplastic process in case of reduced effectiveness of DNA repair mechanisms. Int J Occup Med Environ Health. 2022;35(5):625-33.

Polymorphism association of NIL1, NIL2, CYP1A1 xenobiotic metabolism genes and their expression with the risk of colorectal cancer in the Polish population.

<b>Introduction:</b> Colorectal cancer (CRC), despite intensive research on the improvement of diagnosis and treatment, is still the second most deadly cancer in Poland in terms of mortality. One of the factors predisposing to a higher risk of CRC may be the individual differences in the effectiveness of proteins responsible for the metabolism of xenobiotics - it seems that the removal of potentially harmful exogenous substances significantly reduces the risk of carcinogenesis. </br></br> <b>Aim:</b> In this work, we analyzed the effect of polymorphisms of genes responsible for metabolizing xenobiotics on the risk of CRC - rs72554606 polymorphism of N AT 1 gene, rs1799930 polymorphism of N AT 2 gene and rs1799814 polymorphism of CYP1A1 gene, as well as the level of expression of these genes. </br></br> <b> Conclusions:</b> The results indicate that the GC genotype for N AT 1 and the GA genotype for CYP1A1 may increase the risk of CRC, and in those already diagnosed with colorectal cancer, the expression level of NAT1 is significantly lower than in the control. We believe that these factors may have potential prognostic and diagnostic significance in the treatment of CRC.

More Than Skin Deep - the Effects of Ultraviolet Radiation on Cathepsin K and Progerin Expression in Cultured Dermal Fibroblasts.

INTRODUCTION: Photoaging is a premature skin aging developing secondarily to the excessive exposure to ultraviolet radiation. Due to its complexity, an exact mechanism of photoaging has not been found yet; however, recent research has shown two new emerging players in this process - cathepsin K and progerin. AIM: To evaluate how different wavelengths of ultraviolet radiation (UVA, narrowband UVB and broadband UVB) influence cathepsin K and progerin protein and mRNA expression in dermal cultured fibroblasts. MATERIALS AND METHODS: Primary human dermal fibroblasts (Detroit 551, ATCC CCL-110) were cultured and irradiated with UVA, narrowband UVB (UVBnb) and broadband UVB (UVBwb). Fibroblasts were irradiated with 2 protocols: single high-dose exposure to UVR with protein/mRNA extraction immediately after exposure, 24 h after exposure and 48 h after exposure, and repeated (0 h, 24 h and 48 h) low-dose exposure to UVR with protein/mRNA extraction 48 h after first exposure. RESULTS: Single high doses of UVA, UVBwb and UVBnb resulted in decreased expression of cathepsin K and progerin protein/mRNA in all subsequent time points. Repeated exposure to low doses of UVA results in significant increase of progerin mRNA and significant decrease of progerin protein after 48 h, but repeated exposure to UVBwb and UVBnb resulted in decreased progerin mRNA and protein expression. Repeated exposure to UVA, UVBwb and UVBnb resulted in decreased cathepsin K protein and mRNA expression. CONCLUSION: The results suggest that there could be another progerin/cathepsin K regulatory pathway, which has not been described yet. Being contradictory with previous research, the influence of ultraviolet radiation on progerin and cathepsin K needs to be further elucidated.

MicroRNA as a Novel Biomarker in the Diagnosis of Head and Neck Cancer.

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide, with 890,000 new cases and 450,000 deaths in 2018, and although the survival statistics for some patient groups are improving, there is still an urgent need to find a fast and reliable biomarker that allows early diagnosis. This niche can be filled by microRNA, small single-stranded non-coding RNA molecules, which are expressed in response to specific events in the body. This article presents the potential use of microRNAs in the diagnosis of HNSCC, compares the advances in this field to other diseases, especially other cancers, and discusses the detailed use of miRNA as a biomarker in profiling and predicting the treatment outcome with radiotherapy and immunotherapy. Potential problems and difficulties related to the development of this promising technology, and areas on which future research should be focused in order to overcome these difficulties, were also indicated.

Influence of Arg399Gln, Arg280His and Arg194Trp XRCC1 gene polymorphisms of Base Excision Repair pathway on the level of 8-oxo-guanine and risk of head and neck cancer in the Polish population.

BACKGROUND: Reduced efficiency of DNA repair systems has long been a suspected factor in increasing the risk of cancer. OBJECTIVE: In this work we investigate influence of three selected polymorphisms of DNA repair gene XRCC1 and level of oxidative damage (measured as level of 8-oxo-guanine) on modulation of the risk of HNSCC. METHODS: In group of 359 patients with HNSCC (diagnosed with OSCC) the occurrence of polymorphic variants in Arg399Gln, Arg280His and Arg194Trp of XRCC1 were studied with TaqMan technique. In addition we determined level of 8-oxo-guanine with ELISA. RESULTS: Arg399Gln polymorphism and Arg194Trp polymorphism of XRCC1 gene increases the risk of HNSCC. The coexistence of Arg399Gln and Arg194Trp simultaneously enhances this effect. At the same time, their coexistence with His280His raises the risk to a level higher than in the absence of such coexistence, although the His280His itself is not associated with an increased risk of HNSCC. Patients have higher levels of 8-oxo-guanine than control group, and His280His is polymorphism with highest mean value of 8-oxoG level among studied. CONCLUSION: Patients with HNSCC not only have an increased level of 8-oxoguanine and the Arg399Gln and Arg/Trp of XRCC1 modulate risk of cancer, but there is also a relationship between these two phenomena, and it can be explained using intragenic combinations revealing that a high level of 8-oxoG could be a potential mechanism behind the modulation of HNSCC risk by the polymorphisms studied.

New Tetrahydroacridine Hybrids with Dichlorobenzoic Acid Moiety Demonstrating Multifunctional Potential for the Treatment of Alzheimer's Disease.

A series of new tetrahydroacridine and 3,5-dichlorobenzoic acid hybrids with different spacers were designed, synthesized, and evaluated for their ability to inhibit both cholinesterase enzymes. Compounds 3a, 3b, 3f, and 3g exhibited selective butyrylcholinesterase (EqBuChE) inhibition with IC50 values ranging from 24 to 607 nM. Among them, compound 3b was the most active (IC50 = 24 nM). Additionally, 3c (IC50 for EeAChE = 25 nM and IC50 for EqBuChE = 123 nM) displayed dual cholinesterase inhibitory activity and was the most active compound against acetylcholinesterase (AChE). Active compound 3c was also tested for the ability to inhibit Aß aggregation. Theoretical physicochemical properties of the compounds were calculated using ACD Labs Percepta and Chemaxon. A Lineweaver-Burk plot and docking study showed that 3c targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Moreover, 3c appears to possess neuroprotective activity and could be considered a free-radical scavenger. In addition, 3c did not cause DNA damage and was found to be less toxic than tacrine after oral administration; it also demonstrated little inhibitory activity towards hyaluronidase (HYAL), which may indicate that it possesses anti-inflammatory properties. The screening for new in vivo interactions between 3c and known receptors was realized by yeast three-hybrid technology (Y3H).

Association of XRCC6 C1310G and LIG4 T9I polymorphisms of NHEJ DNA repair pathway with risk of colorectal cancer in the Polish population.

INTRODUCTION: Colorectal cancer is the second most common cancer worldwide. DNA double strand breaks (DSBs) are the most dangerous lesions which can lead to carcinogenesis. Nonhomologous end joining (NHEJ) is an important pathway, that allows for recovering DNA by direct end joining. The XRCC6 and LIG4 genes encode respectively Ku70 protein and human ATP-dependent DNA ligase, which are the components of the NHEJ repair pathway. The aim of our study was to evaluate the influence of XRCC6 C1310G and LIG4 T9I genes polymorphisms on colorectal cancer risk among Polish population. MATERIALS AND METHOD: Genotyping was performed using TaqMan probes based on analysis of PCR products amplified in Real Time PCR. The research has been carried out on the material obtained from 100 patients with colorectal cancer and 100 cancer-free individuals who were age and sex-matched as a control group. The results were developed using the chi - squer test and odds ratio (OR). RESULTS: Odd ratio analysis indicates reduced risk of colorectal cancer for LIG4 T9I polymorphism in heterozygotus model C/T (OR= 0.2717 95% CI= 0.1247-0,5918) and homozygous model T/T (OR= 0.3593 95% CI= 0.1394-0.9266). Similar situation we observed for XRCC6 C1310G gene polymorphism, which indicated on heterozygotus variant C/G (OR= 0.1181 95% CI= 0.0145-0.964) and homozygotus variant G/G (OR= 0.0972 95% CI= 0.0097-0.9713) to decrease the risk of colorectal cancer. Conslusions: Our research revealed XRCC6 C1310G and LIG4 T9I polymorphisms are associated with diminished risk of colorectal cancer. However, to confirm obtained results, a further investigations should be carried out.

The Role of the ER-Induced UPR Pathway and the Efficacy of Its Inhibitors and Inducers in the Inhibition of Tumor Progression.

Cancer is the second most frequent cause of death worldwide. It is considered to be one of the most dangerous diseases, and there is still no effective treatment for many types of cancer. Since cancerous cells have a high proliferation rate, it is pivotal for their proper functioning to have the well-functioning protein machinery. Correct protein processing and folding are crucial to maintain tumor homeostasis. Endoplasmic reticulum (ER) stress is one of the leading factors that cause disturbances in these processes. It is induced by impaired function of the ER and accumulation of unfolded proteins. Induction of ER stress affects many molecular pathways that cause the unfolded protein response (UPR). This is the way in which cells can adapt to the new conditions, but when ER stress cannot be resolved, the UPR induces cell death. The molecular mechanisms of this double-edged sword process are involved in the transition of the UPR either in a cell protection mechanism or in apoptosis. However, this process remains poorly understood but seems to be crucial in the treatment of many diseases that are related to ER stress. Hence, understanding the ER stress response, especially in the aspect of pathological consequences of UPR, has the potential to allow us to develop novel therapies and new diagnostic and prognostic markers for cancer.

Discovery of New Cyclopentaquinoline Analogues as Multifunctional Agents for the Treatment of Alzheimer's Disease.

Here we report the two-step synthesis of 8 new cyclopentaquinoline derivatives as modifications of the tetrahydroacridine structure. Next, the biological assessment of each of them was performed. Based on the obtained results we identified 6-chloro-N-[2-(2,3-dihydro-1H-cyclopenta[b]quinolin-9-ylamino)-hexyl]]-nicotinamide hydrochloride (3e) as the most promising compound with inhibitory potencies against EeAChE and EqBuChE in the low nanomolar level 67 and 153 nM, respectively. Moreover, 3e compound is non-hepatotoxic, able to inhibit amyloid beta aggregation, and shows a mix-type of cholinesterase's inhibition. The mixed type of inhibition of the compound was confirmed by molecular modeling. Then, yeast three-hybrid (Y3H) technology was used to confirm the known ligand-receptor interactions. New derivatives do not show antioxidant activity (confirmed by the use of two different tests). A pKa assay method was developed to identify the basic physicochemical properties of 3e compound. A LogP assay confirmed that 3e compound fulfills Lipinsky's rule of five.

Sirt3 regulates the level of mitochondrial DNA repair activity through deacetylation of NEIL1, NEIL2, OGG1, MUTYH, APE1 and LIG3 in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors. One of the factors increasing the risk of its occurrence may be the reduced efficiency of repairing DNA damage, both nuclear and mitochondrial. The main mechanism for repairing oxidative damage is the BER system (in mitochondria mtBER), whose key proteins NEIL1, NEIL2, OGG1, MUTYH, APE1 and LIG3 obtain full efficiency only at the appropriate level of acetylation. Sirtuin 3 is a key protein for mitochondrial homeostasis, regulating a number of metabolic processes related mainly to the control of the level of reactive oxygen species. Because Sirt3 possesses acetylase activity, it can modulate the level of activity of mtBER proteins by their deacetylation. The conducted study showed that the tested proteins NEIL1, NEIL2, OGG1, MUTYH, APE1 and LIG3 are the substrate for the enzymatic deacetylation activity of Sirt3, which may lead to modulation of the risk of CRC, and in cancer cells may be a potential therapeutic target enhancing the action of cytostatic drugs.

Impact of the Ser326Cys polymorphism of the OGG1 gene on the level of oxidative DNA damage in patients with colorectal cancer.

As a result of reactive oxygen species operation, cell damage occurs in both cellular organelles and molecules, including DNA. Oxidative damage within the genetic material can lead to accumulation of mutations and consequently to cancer transformation. OGG1 glycosylase, a component of the Base Excision Repair (BER) system, is one of the enzymes that prevents excessive accumulation of 8-oxoguanine (8-oxG), the most common compound formed by oxidative DNA damage. In case of structural changes of OGG1 resulting from polymorphic variants, we can observe a significant increase in the concentration of 8-oxG. Linking individual polymorphisms to DNA repair systems with increased risk of colorectal cancer will allow patients to be classified as high risk and included in a prophylactic program. The aim of the study was to determine the level of oxidative DNA damage and to analyze the distribution of Ser326Cys polymorphism of the OGG1 gene in a group of patients with colorectal cancer and in a control group in the Polish population. MATERIAL AND METHODOLOGY: DNA was isolated from the blood of 174 patients with colorectal cancer. The control group consisted of 176 healthy individuals. The level of oxidative damage was determined by analyzing the amount of 8-oxguanine using the HT 8-oxo-dG ELISA II Kit. Genotyping was performed via the TaqMan method. RESULTS: The obtained results indicate that Ser326Cys polymorphism of the OGG1 gene increases the risk of RJG and is associated with significantly increased levels of 8-oxoguanine. CONCLUSIONS: Based on the results obtained, we conclude that Ser326Cys polymorphism of the OGG1 gene may modulate the risk of colorectal cancer by increasing the level of oxidative DNA damage.

Tetrahydroacridine derivatives with dichloronicotinic acid moiety as attractive, multipotent agents for Alzheimer's disease treatment.

A novel series of 9-amino-1,2,3,4-tetrahydroacridine and 5,6-dichloronicotinic acid moiety were conjugated with different linkers. Afterwards new derivatives were evaluated as potential multifunctional acetylcholinesterase inhibitors (AChEIs), anti-Alzheimer's disease (AD) drug candidates. All the compounds were synthesized and tested for capacity for the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. Specifically, the most promising derivative 3b (IC50 = 1.02 nM) had higher inhibitory potency compared to the reference drug, tacrine. Consequently, kinetic studies of 3b compound showed a mixed-type inhibition of both AChE and BuChE. Afterwards the best potent AChE inhibitor has been examined on amyloid ß (Aß) self-induced aggregation. Furthermore, 3b compound was tested in various concentrations and had moderate activity against Aß aggregation. Inhibition of Aß aggregation was 46.63% and 19.41% at 50 µM and 5  µM concentrations, respectively. Moreover, no cytotoxicity was observed for the mentioned concentrations. Therefore, 3b compound is a promising multipotent agent for the treatment of AD.

New cyclopentaquinoline hybrids with multifunctional capacities for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is the most common progressive form of brain neurodegeneration and the most prevailing cause of dementia. Unfortunately, the aetiology of AD is not completely studied but different factors are associated with the development of AD such as among others low level of acetylcholine, aggregation of ß-amyloid (Aß), hyperphosphorylated tau protein, oxidative stress, and inflammation. The study encompass organic syntheses of 2,3-dihydro-1H-cyclopenta[b]quinoline with 5,6-dichloronicotinic acid and suitable linkers derivatives as multifunctional agents for AD treatment. Afterwards self-induced amyloid beta aggregation, inhibition studies of acetylcholinesterase and butyrylcholinesterase and molecular docking studies were performed. The results showed that 3b compound exhibited the best acetylcholinesterase inhibitory activity, with IC50 value of 0.052 µM which is lower compared to references. Besides, all synthesised compounds showed good butyrylcholinesterase inhibitory activity with IC50 values from 0.071 to 0.797 µM. Compound 3b exhibited strong Aß1-42 aggregation inhibitory effect with 25.7% at 5 µM to 92.8% at 100 µM as well as good anti-inflammatory effect. Thus, new compounds could create new perspectives for further development as a multi-target-directed agent for AD treatment.

Tetrahydroacridine derivatives with fluorobenzoic acid moiety as multifunctional agents for Alzheimer's disease treatment.

A novel series of 9-amino-1,2,3,4-tetrahydroacridine derivatives with 2-fluorobenzoic acid or 3-fluorobenzoic acid moiety were designed, synthesized and evaluated as inhibitors of cholinesterases and aggregation of ß-amyloid. In the study target compounds were very potent inhibitors of AChE and BChE. The most promising agents had higher inhibitory potency than the reference drugs which was tacrine. Ultimately, the kinetic assay shows the most active target compound 3c against AChE. Almost all of them were more potent against BChE than AChE. Compound 3c in various concentrations was tested by aggregation experiment. Inhibition of ß-amyloid aggregation was 77.32% and 80.43% at 50µM and 100µM, respectively. Therefore, compound 3c is a promising agent for the treatment of AD.

Potential of redox therapies in neurodegenerative disorders.

Recently significant advances have been made to understand the pathophysiological mechanisms of neurodegenerative disorders to provide real therapeutic benefits. There is evidence that persistent inflammation and oxidative stress are the crucial factors of ongoing cell damage in neurodegenerative complex etiology. The variety of reactive oxygen and nitrogen species are the cause of both axonal and neuronal destruction, which is pathological hallmark of neurodegeneration. Therefore, the reduction of oxidative stress is currently one of the main neuroprotective strategies. The World Health Organization (WHO) estimates that, by 2040, neurodegenerative diseases will be the main cause of death in industrialized countries ahead of the cancers. The redox therapeutic approch can target: degnerative component, inflammatory/autoimmune component and neurodegenerative component. Redox therapy should not be applied uniformly, and must be develop to target specific mechanisms. This review focus on the main antitoxidative therapies that are used in many countries as a supplements or even as a standart treatment. Aditionally, clinical synmptoms of most common neurodegenerative disordes and centralnervous system structures involved in oxidative/nitrosative stress are showed.

Polymorphism within the distal RAD51 gene promoter is associated with colorectal cancer in a Polish population.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in developed countries. Annually, over one million of new cases in the world are recorded. Majority of CRCs occur sporadically with dominant phenotype of chromosomal instability (CIN). Permanent exposure to DNA damaging agents such as ionizing radiation result in DNA double-stranded breaks, which create favorable conditions for chromosomal aberration to arise. Homologous recombination repair (HRR) is the leading process engaged in maintaining of the genome integrity. RAD51 protein was recognized as crucial in HRR. Single nucleotide polymorphisms are the primary source of genetic variation which presence in the RAD51 promoter region can affect on its expression and consequently modulate HR efficiency. OBJECTIVES: The aim of this study was to analyze the distribution of genotypes and allele frequencies of -4791A/T and -4601A/G RAD51 gene polymorphisms, followed by an assessment of their relationship with the risk of CRC. MATERIAL AND METHODS: The study included 115 patients with confirmed CRC. Control group was consisted of 118 cancer-free individuals with a negative family history. The genotypes were identified by PCR-RFLP method. CONCLUSION: This study revealed statistically significant association between appearance of G/A genotype in position -4601 of RAD51 gene and CRC risk.

The Role of the XPF Gene Polymorphism (Xrcc4) Ser835ser in the Risk of Malignant Transformation of Cells in the Colorectal Cancer.

UNLABELLED: Participation of DNA repair systems in the pathogenesis of cancer has been a suspected phenomenon for a long time. Decreased efficiency in DNA repair translates to their ability to fix and consequently leads to mutations and the process of carcinogenesis. Linking individual polymorphisms of DNA repair systems with an increased risk of colorectal cancer will allow the classification of patients to high-risk groups and their placement under preventive program. The aim of the study was to determine the effect of XPF gene polymorphism Ser835Ser on increasing the risk of colorectal cancer in the Polish population. MATERIAL AND METHODS: as the material blood collected from 146 patients diagnosed with colon cancer was used. The control group consisted of 149 healthy subjects. Genotyping was performed by Taq- Man method. RESULTS: The results indicate that genotype TCC/TCT is associated with an decreased risk of colorectal cancer (OR 0.574; CI 95% 0.335-0.984; p=0.043). CONCLUSIONS: Based on these results, we conclude that the XPF gene polymorphism Ser835Ser may be associated with a decreased risk of colorectal cancer.