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Lack of Association Between the 135G/CRad51Gene Polymorphism and the Risk of Colorectal Cancer Among Polish Population

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Mucha B., Przybyłowska-Sygut K., Dziki Ł., Dziki A., Sygut A., Majsterek I.
Polish Journal of Surgery
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2012
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vol. 84
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issue 7
358-362
EN
One of the major causes of carcinogenesis is loss of genome stability. RAD51 in process of homologous recombination (HR) played crucial role in maintenance integrity of genome through initiate of DNA double strand breaks repair. Presence of single nucleotide polymorphism (SNP) in RAD51 gene could change the capacity of DNA repair and altered the response to damaging agents. Research on potential impact of genetic variability on development and progression CRC may contribute to setting new genetic markers or/and determined individual susceptibility to CRC.The aim of the study. This study was designed to evaluate the effect of 135 G/C (rs1801320) RAD51 polymorphism located in the 5' untraslated region on the risk and progression of CRC.Material and methods. The subjects consisted of histologically confirmed colorectal cancer (n = 200) and controls (n = 200) with lack of previous history of cancer. The distribution of genotypes was determined by restriction fragment length polymorphism PCR (RFLP - PCR). Statistical analysis was based on multivariate regression model.Results and conclusion. Our study reveal no significance association of 135 G/C RAD51 polymorphism with occurrence and progression of colorectal cancer.
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The Antioxidative Barier in Patients with Colorectal Cancer

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Murlikiewicz Ł., Trzciński R., Sygut A., Rutkowski M., Grzegorczyk K., Dziki A.
Polish Journal of Surgery
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2010
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vol. 82
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issue 6
341-346
EN
Colorectal cancer is still a major medical, economical and public health problem. Pathogenesis of colorectal cancer remains unknown. It is thought both genetic and environmental factors contribute to the etiology and progression of the disease. Reactive oxygen species are known to play a dual role in biological systems they can be either harmful or beneficial. Oxygen-free radicals are important mediators of damage to cell structures, including lipids, proteins and nucleic acids. Radical-related damage to cell structures has been proposed to play a key role in the development of many diseases including cancer.Humans have evolved complex antioxidant strategies to protect cells from oxidation.Total antioxidant capacity (TAC) considers the cumulative action of all the antioxidants present in plasma or other body fluids.The aim of the study was to investigate antioxidant status in patients with colorectal cancer measuring plasma TAC as a tool.Material and methods. The study group comprised 102 patients in different clinical stages operated on for colorectal cancer. To evaluate plasma total antioxidant capacity we used "Total Antioxidant Status Kit" - RandoxResults. Statistical evaluation of results demonstrated significantly lower serum total antioxidant capacity in patients with colorectal cancer, as compared to the healthy control group. We observed increase mean plasma total antioxidant capacity correlating with decrease of clinical disease stage.Conclusions. Colorectal patient have impairment antioxidant barrier. The deterioration of its functioning corresponds with the stage of the disease.
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A/G Polymorphism of the MMP-7 Gene Promoter Region in Colorectal Cancer

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Dziki Ł., Przybyłowska K., Majsterek I., Trzciński R., Mik M., Sygut A.
Polish Journal of Surgery
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2011
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vol. 83
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issue 11
622-626
EN
In gastrointestinal malignancies increased expression of matrilysin - MMP-7 - is often observed. Its high level positively correlates with clinical stage of malignancy and is a negative prognostic factor. This suggests a possible relationship between functional polymorphisms of the MMP-7 gene and susceptibility to development of colorectal cancer and an aggressive course of the disease.The aim of the study was to assess the effects of A/G functional polymorphism at -181 site of the MMP-7 gene promoter region on development and progression of colorectal cancer.Material and methods. In total, 184 patients treated surgically for colorectal cancer at the Department of General and Colorectal Surgery of the Medical University in Łódź in the years 2006-2009 and a control group of 205 cancer-free individuals with a negative family history for malignancy have been investigated. Polymorphic variants of the MMP-7 gene promoter region have been analysed using the RFLP-PCR method.Results. A statistically significant difference in distribution of genotypes has been found between the investigated group and the control group, and the OR analysis confirmed a relationship between the A/G [1.67 (1.03-2.72); p= 0.038] and G/G [2.12 (1.34-3.38); p = 0.018] genotypes and an increased risk of colorectal cancer. The risk of lymph node involvement was more than twice higher for the G/G genotype (OR = 2.83 (1.18-6.79); P = 0.017). In addition, the analysis of genotype distribution in patients divided into groups according to the T parameter of the TNM classification revealed a relationship between the G/G genotype and advanced tumour infiltration. No relationship between the investigated A/G polymorphism and the presence of distant metastases has been found.Conclusions. Obtained results indicate a possible relationship between -181 A/G polymorphism of the MMP-7 gene and malignant transformation of colorectal epithelial cells and progression of colorectal cancer. This suggests applicability of this polymorphism as a predisposing factor for the disease and a prognostic factor, which in the future may be useful in the management algorithm for colorectal cancer.
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Contribution of the -173 G/C Polymorphism of Macrophage Migration Inhibitory Factor Gene to the Risk of Inflammatory Bowel Diseases

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Przybyłowska K., Mrowicki J., Sygut A., Narbutt P., Dziki Ł., Dziki A., Majsterek I.
Polish Journal of Surgery
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2011
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vol. 83
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issue 2
76-80
EN
Inflammatory bowel disease (IBD) represents a heterogeneous group of chronic disorders characterized by inflammation of gastrointestinal tract, typically with a relapsing and remitting clinical course of unknown etiology. Presumably, IBD develops with response exogenous environmental factors only in persons with genetic predisposition. This predisposition was suggested to be associated with polymorphism and mutations in genes encoding proinflammatory immune system proteins. Enhanced production of macrophage migration inhibitory factor (MIF) was found in patients with inflammatory bowel disease (IBD) and mice with experimental colitis. These results suggest that MIF plays a critical role in etiology of the colitis.The aim of the study was determine whether the MIF -173 G/C gene polymorphism is associated with the susceptibility to inflammatory bowel disease (IBD).Material and methods. A total of 99 IBD patients, including 58 patients with ulcerative colitis (UC) and 41 with Crohn's disease (CD) and 436 healthy controls recruited from the Polish population, were genotyped for MIF polymorphisms. Genotyping of MIF gene polymorphism was performed by a RFLP-PCR.Results. We found an increased risk of UC for the C allele of the MIF-173 G/C polymorphism. The distribution of the genotypes was not significantly different in the CD group compared with the controls.Conclusions. We demonstrated that the C allele is associated with an increased risk for development of UC. This suggests that the G/C polymorphism in the MIF gene promoter may be a potential risk factor for UC in Polish population.
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Association of Polymorphism of Lys589glu Exo1 Gene with the Risk of Colorectal Cancer in the Polish Population

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Kabziński J., Przybylowska K., Mik M., Sygut A., Dziki Ł., Dziki A., Majsterek I.
Polish Journal of Surgery
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2015
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vol. 86
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issue 8
370-373
EN
The incidence of colorectal cancer (CRC) is increasing from year to year. Despite intensive research CRC etiology remains unknown. Studies suggest that at the basis of the process of carcinogenesis can lie reduced efficiency of DNA repair mechanisms, often caused by polymorphisms in DNA repair genes. The aim of the study was to determine the relationship between gene polymorphism Lys589Glu of EXO1 gene and modulation of the risk of colorectal cancer in the Polish population. Determination of the molecular basis of carcinogenesis process and predicting increased risk will allow qualifying patients to increased risk group and including them in preventive program. Material and methods. The material used in study was blood collected from 130 patients diagnosed with colorectal cancer. The control group consisted of 135 healthy people. Genotyping was performed by TaqMan method. Results. The results obtained indicate that the genotype Lys/Glu is associated with an increased risk of colorectal cancer (OR 1.811, 95% Cl 1.031-3.181, p = 0.038). Conclusion. On the basis of these results, we conclude that Exo1 gene polymorphism Lys589Glu may be associated with an increased risk of colorectal cancer.
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An Association of ARG399GLN Polymorphism ofXRCC1Gene with a Risk of Colorectal Cancer

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Kabziński J., Przybyłowska K., Mik M., Sygut A., Dziki Ł., Dziki A., Majsterek I.
Polish Journal of Surgery
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2010
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vol. 82
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issue 12
677-680
EN
Colorectal cancer is one of the most commonly diagnosed cancer and a leading cause of death from cancer. DNA repair defects have been associated with an individual susceptibility to cancer. Therefore, polymorphisms of DNA repair genes, including XRCC1 gene, are suspected to may increase the risk of colorectal cancer.The aim of the study was to examine the association between Arg399Gln polymorphisms of XRCC1 gene and the occurrence of colorectal cancer. Research and understanding of the molecular basis of the formation of colorectal cancer will allow for typing of genetically loaded persons and qualifying them to a high-risk group.Material and methods. In case-control study we genotyped 150 colorectal cancer patients and 170 healthy subjects from Polish population. Analysis was performed by PCR-restriction fragment length polymorphism (PCR-RFLP).Results. We found that Gln/Gln genotype is associated with increased risk of colorectal cancer (OR 1.984; Cl 95% 1.070-3.677; p=0.029). We also found that Arg/Gln genotype is a risk factor for progression of tumor growth (OR 3.52; Cl 95% 1.157-10.707; p=0.023).Conclusions. The current state of research suggests a link between Arg399Gln XRCC1 polymorphism and increased risk of colorectal cancer. Therefore, we conclude that the Arg399Gln polymorphism of XRCC1 gene may underlie at the molecular basis of the causes of colorectal cancer.
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Association of -1112 C/T Promoter Region Polymorphism of the Interleukin 13 Gene with Occurrence of Colorectal Cancer

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Walczak A., Przybyłowska K., Trzciński R., Sygut A., Dziki Ł., Dziki A., Majsterek I.
Polish Journal of Surgery
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2011
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vol. 83
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issue 1
27-31
EN
Colorectal carcinoma is one of the leading causes of death from cancer amongst adults. Considering its molecular background, cytokines are the key component of the inflammatory microenvironment of these tumors. Investigations that enable better understanding of colorectal cancer concerning the molecular level, may provide important tools for genetic screening of disease high-risk groups, as well as molecular diagnostics for the non-invasive detection of cancer in its early stages.The aim of the study was to evaluate the association between colorectal cancer and the -1112 C/T single nucleotide polymorphism (SNP) of the interleukin-13 gene.Material and methods. The study group comprised 150 cancer patients and 170 healthy subject genotypes from the Polish population. Analysis was performed by PCR-restriction fragment length polymorphism (PCR-RFLP).Results. We showed that the CT genotype is connected with a higher risk of colon cancer occurrence (OR 2.51; 95% CI 1.57-4.02; p < 0.0001). We also correlated the polymorphic variants of the IL-13 gene with the clinical characteristics of colorectal cancer patients. We observed no association between the investigated polymorphism and colorectal cancer progression, evaluated by tumor stage, as well as lymph node metastasis.Conclusions. The presented study suggested the possibility of a connection between the IL-13 gene polymorphism (-1112 C/T) and colorectal cancer risk in the Polish population.
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Oxidative protein damage in patients with colorectal cancer

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Murlikiewicz Ł., Sygut A., Trzciński R., Grzegorczyk K., Rutkowski M., Dziki A.
Polish Journal of Surgery
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2010
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vol. 82
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issue 8
454-458
EN
Colorectal cancer is a major public health concern particularly in developed countries. Despite decades of advances in the treatment and prevention of colorectal cancer, it remains the second most common cause of cancer death. There now exists convincing evidence that reactive oxygen species play an important role in the etiology and progression of a number of human diseases including colorectal cancer. Reactive oxygen species may damage all types of biological molecules. However, proteins are possibly the most immediate vehicle for inflicting oxidative damage on cells since they are often catalysts rather than stoichiometric mediators, hence, the effect of damage to one molecule is greater than stoi-chiometric.The aim of the study was to investigate oxidative protein damage in patients with colorectal cancer and its correlation with the clinical stage of the disease.Material and methods. The study group comprised 102 patients operated on for colorectal cancer in different clinical stages of the disease. Plasma carbonyl levels were determined using Levin's method.Results. Patients in all tumor groups showed significantly higher levels of plasma carbonyls when compared to healthy people. We observed an increase in mean plasma carbonyl levels correlating with an increase in the degree of disease advancement.Conclusions. This study demonstrates that reactive oxygen species may have a role in pathogenesis of colorectal cancer. The outcomes of this research seem to confirm that antioxidants may play a role in chemoprevention of colorectal cancer.
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Genetic Variations of the CTNNA1 And The CTNNB1 Genes in Sporadic Colorectal Cancer in Polish Population

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Sygut A., Przybyłowska K., Ferenc T., Dziki Ł., Spychalski M., Mik M., Dziki A.
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EN
Experimental as well as clinical observations have demonstrated that the E-cadherin/catenin complex is a powerful inhibitor of invasion. Abrogation of this pathway is implicated in the carcinogenesis of several malignancies, especially colorectal cancer. The aim of the study was to determine the CTNNA1 and the CTNNB1 mutations and its relationship to clinical and pathological features of sporadic colorectal cancer (CRC) in Polish patients. Material and methods. Paired tumor and normal tissue samples from 110 sporadic CRC patients undergoing resective surgery were prospectively studied for the alpha catenin (CTNNA1) gene and beta catenin (CTNNB1)gene mutations by PCR/single strand conformation polymorphism (SSCP). Results. The CTNNA1 gene alteration in exon 7 were detected in 4 samples and in exon 3 of CTNNB1 gene were found in 3 samples. There was a trend at the limit of statistical significance associating younger age at diagnosis (<50) with CTNNA1 and the CTNNB1 mutations. The mutation of CTNNB1 seemed to occur more frequently in the proximal colon than distal. The CRC patients with CTNNA1 mutation had a significantly increased lymph node metastasis. On the other hand, there was no correlation between mutations and the other clinical variables (e.g. sex, grade and depth of invasion). Conclusion. Although we found a low frequency of mutations in the CTNNA1 and the CTNNB1 genes, but the analysis the relationship with clinical and pathological features of CRC patients may indicated an association of these mutations with the risk and progression of CRC.
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Association of the-801G/A Polymorphism ofCXCL12Gene with the Risk of Inflammatory Bowel Diseases Development in a Polish Population

84%
Mrowicki J., Przybyłowska K., Dziki Ł., Sygut A., Wiśniewska-Jarosińska M., Chojnacki J., Dziki A., Majsterek I.
Polish Journal of Surgery
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2011
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vol. 83
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issue 6
334-338
EN
Inflammatory bowel diseases (IBDs), mainly ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic and idiopathic inflammatory conditions of gastrointestinal tract that are immunologically mediated. Stromal cell-derived factor 1 (CXCL12) has been demonstrated to be involved in the pathophysiology of IBD.The aim of the study was to investigate whether the CXCL12 -G/A polymorphism (rs1801157) is associated to IBD in a sample of Polish population.Material and methods. A total of 188 patients with IBD including 103 patients with CU and 72 patients with CD and 184 controls were enrolled in the study. Both groups came from the Polish population. The G/A polymorphism of CXCL12 was determined by PCR-RFLP analysis.Results. There was no association between G/A polymorphism at position -801 promoter region of CXCL12 gene and increased risk of IBD. The study population was not found a difference in genotype distribution between the control group and with both CD and CU patients.Conclusions. These results suggest that G/A polymorphism at position -801 promoter region of CXCL12 gene relates neither to the risk of the development of inflammatory bowel disease nor to the clinical subtypes of IBD in the Polish population. Whether this polymorphism truly contributes to disease susceptibility needs to be further addressed, and should stimulate additional studies in other populations.
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Large Colorectal Polyps - Endoscopic Polypectomy as an Alternative to Surgery

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Spychalski M., Buczyński J., Cywiński J., Dziki Ł., Langner E., Sygut A., Trzciński R., Dziki A.
Polish Journal of Surgery
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2011
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vol. 83
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issue 10
531-536
EN
Endoscopic polypectomy of colorectal polyps is a common procedure. However, endoscopic treatment of large polyps (those with a diameter exceeding 2 cm) remains questionable. There is a serious risk of colorectal carcinoma presence inside these lesions, which eventually would require surgical intervention. Apart from this fact endoscopic polypectomy of large polyps is connected with substantial risk of complications, such as perforation and bleeding. Many patients with large colorectal polyps are qualified for surgical intervention.The aim of the study was to determine the efficacy and safety of polypectomy of large colorectal polyps.Material and methods. The study presented results of endoscopic treatment in case of patients with large colorectal polyps at the Department of General and Colorectal Surgery, Medical University in Łódź. Patients were admitted to the hospital during the period between January, 2008 and January, 2010. The following parameters were analysed: location of polyps, percentage of high grade dysplasia, complete excision rate, and complications connected with polypectomy procedures.Results. During the analyzed period of time 488 endoscopic polypectomies were performed. Forty-three large colorectal polyps were removed (8.8%). Seven (16.3%) of them were classified as flat polyps. Out of 488 removed polyps, 39 were classified as adenomas with high grade dysplasia (7.9%), while 16 were large-exceeding 2 cm (37.2%). Considering the group of large polyps no invasive carcinoma case was detected. The radical excision rate for large pedunculated polyps was obtained in 88.8% (32/36) of cases. In case of flat adenomas the above-mentioned parameter was lower - 57.1% (4/7). During polypectomy of large colorectal polyps one perforation was observed during the excision of a flat cecal polyp. In two cases immediate bleeding occurred (2/43). In both cases endoscopic treatment of bleeding proved sufficient.Conclusions. Endoscopic polypectomy of large pedunculated polyps is a safe and efficient method, which makes it a rationale alternative for surgery. Polypectomy of flat adenomas is connected with a lower radical excision rate and higher risk of perforation.
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The -2518 A/GMCP-1Polymorphism as a Risk Factor of Inflammatory Bowel Disease

84%
Walczak A., Przybyłowska K., Sygut A., Dziki Ł., Chojnacki C., Chojnacki J., Dziki A., Majsterek I.
Polish Journal of Surgery
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2012
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vol. 84
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issue 5
238-241
EN
Inflammatory bowel diseases (IBD) are disorders originated from immune disturbances.The aim of the study was to evaluate the association between the -2518 A/G MCP-1 polymorphism and the risk of IBD development.Material and methods. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Study group consisted of 197 subjects with IBD (120 with ulcerative colitis and 77 with Crohn's disease) as well as 210 healthy controls.Results. The presence of the -2518 G/G MCP-1 genotype in the investigated groups seems to be connected with higher risk of inflammatory bowel disease as well as Crohn's disease only (OR 2.26; 95% CI 1.44-3.54 and OR 2.08; 95% CI 1.21-3.46, respectively).Conclusions. Our data showed that the -2518 A/G MCP-1 polymorphism might be associated with the IBD occurrence and might be used as predictive factor of these diseases in a Polish population.
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The - 801 G/A Polymorphism ofCXCL12Promoter Gene as Unfavorable Genetic Prognosis factor involved in Colorectal Cancer

84%
Langner E., Przybyłowska K., Sygut A., Mik M., Dziki Ł., Dziekiewicz M., Majsterek I., Dziki A.
Polish Journal of Surgery
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2010
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vol. 82
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issue 8
459-463
EN
CCXL12 also called stromal derived factor-1 (SDF-1), a protein related to angiogenesis and inflammation, has been correlated with the progression of a number of malignancies. Single nucleotide - 801G/A polymorphism of CXCL12 gene has been described and is regarded as a target for cis-acting factor that has the ability to up-regulate CXCL12 expression.The aim of the study. Based on the suggested role of CXCL12 in the pathogenesis of cancer we examined the association of the gene variant CXCL12-A with colorectal cancer.Material and methods. We genotyped - 801G/A polymorphism of CXCL12 gene in 164 colorectal patients and 184 age-matched healthy subjects. Genotyping was done with PCR-RFLP.Results. There were no significant differences in the frequencies of SDF1-3'A allele, between patients and controls. The frequency of CXCL12 G/A and G/A plus A/A genotype was significantly higher in a group of patients with lymph node metastasis compared with those without metastasis.Conclusions. The CXCL12 gene G/A polymorphism was not related to colorectal cancer risk but is associated with the induction of lymph-node metastasis of colorectal cancer disease in Polish.
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