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1
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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.
3
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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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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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Analysis of the G/C polymorphism in the 5'-untranslated region of the RAD51 gene in breast cancer.

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Blasiak J., Przybyłowska K., Czechowska A., Zadrożny M., Pertyński T., Rykała J., Kołacińska A., Morawiec Z., Drzewoski J.
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2003
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vol. 50
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issue 1
249-253
EN
The breast cancer suppressor proteins BRCA1 and BRCA2 interact with RAD51, a protein essential for maintaining genomic stability by playing a central role in homology-dependent recombinational repair of the DNA double-strand breaks. Therefore, genetic variability in the RAD51 gene may contribute to the appearance and/or progression of breast cancer. A single nucleotide polymorphism in the 5'- untranslated region of RAD51 (a G to C substitution at position 135, the G/C polymorphism) is reported to modulate breast cancer risk. We investigated the distribution of genotypes and frequency of alleles of the G/C polymorphism in breast cancer. Tumor tissues were obtained from postmenopausal women with node-negative and node-positive breast carcinoma with uniform tumor size. Blood samples from age matched healthy women served as control. The G/C polymorphism was determined by PCR-based MvaI restriction fragment length polymorphism. The distribution of the genotypes of the G/C polymorphism did not differ significantly (P >0.05) from those predicted by the Hardy-Weinberg distribution. There were no differences in the genotype distribution and allele frequencies between node-positive and node-negative patients. There were no significant differences between distributions of the genotypes in subgroups assigned to histological grades according to Scarf-Bloom-Richardson criteria and the distribution predicted by Hardy-Weinberg equilibrium (P >0.05). Our study implies that the G/C polymorphism of the RAD51 gene may not be directly involved in the development and/or progression of breast cancer and so it may not be useful as an independent marker in this disease.
7
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Association of the-801G/A Polymorphism ofCXCL12Gene with the Risk of Inflammatory Bowel Diseases Development in a Polish Population

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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.
8
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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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