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Plasminogen activator inhibitor 1 (PAI-1) 1334G/A genetic polymorphism in colorectal cancer.

100%
Smolarz B., Romanowicz-Makowska H., Kulig A.
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2003
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vol. 50
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issue 2
489-495
EN
Plasminogen activator inhibitor 1 (PAI-1) content in colorectal cancer tissue extracts may be of strong prognostic value: high levels of PAI-1 in tumours predict poor prognosis. The gene encoding PAI-1 is highly polymorphic and PAI-1 gene variability could contribute to the level of PAI-1 biosynthesis. In the present work the distribution of genotypes and frequency of alleles of the 1334G/A polymorphism in 92 subjects with colorectal cancer in samples of cancer tissue and distant mucosa samples as well as in blood were investigated. Blood samples age matched healthy individuals (n = 110) served as control. The 1334G/A polymorphism was determined by PCR amplification using allele specific primers. No differences in the genotype distributions and allele frequencies between blood, distant mucosa samples and cancer tissue were detected. However, the distribution of the genotypes of the 1334G/A polymorphism in patients differed significantly (P <0.05) from those predicted by the Hardy-Weinberg equilibrium. There were significant differences in the frequencies of alleles between the colorectal cancer subjects and controls (P <0.05). The results support the hypothesis that the 1334G/A polymorphism may be associated with the incidence of colorectal cancer.
2
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Celecoxib - A Selective Cyclooxygenase-2 Inhibitor Exhibits Dose - Dependent Chemopreventive Activity on an Animal Model of Colorectal Cancer*

76%
Spychalski M., Dziki Ł., Buczyński J., Kulig A., Sporny S., Dziki A.
Polish Journal of Surgery
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2008
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vol. 80
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issue 5
248-255
EN
Colorectal cancer (CRC) is still one of the unresolved issues in medicine. Despite constant improvements in diagnosis and treatment, the prognosis for CRC is unsatisfactory. In recent years, much attention has been paid to experiments concerning chemoprevention of CRC.The aim of the study was evaluation of the effectiveness of celecoxib, a selective Cyclooxygenase-2 (COX-2) inhibitor of chemically-induced CRC carcinogenesis in Fisher F344 rats.Material and methods. Forty-five four-week old male F344 rats were randomized into four groups. In Groups 1, 2, and 3, we induced the CRC carcinogenesis through two subcutaneous injections of Azoxymethane in doses of 20 mg/kg. Rats from groups 1 and 2 were treated with celecoxib in doses of 10 and 30 mg/kg from the start of the experiment. Group 4 was a negative control. The experiment ended in the 26th week. We assessed the following parameters: the number of Aberrant Crypt Foci (premalignant lesions in colons) and the immunoexpression indexes: COX-2, Vascular Endothelial Growth Factor (VEGF), and c-myc.Results. Celecoxib reduced the ACF number. The ACF reduction was dose-dependent. The median ACF number per field of vision was as follows for each of the groups: 1.7, 0.75, 3.2, and 0.2. Celecoxib, irrespective of the dose, reduced the VEGF immunoexpression index. We did not observe a reduction of COX-2 or c-myc immunoexpression in the celecoxib groups.Conclusions. In this experiment, we proved that celecoxib possessed chemopreventive activity. Carcinogenesis inhibition by selective COX-2 inhibitor was dose-dependent. We demonstrated that celecoxib hidners angiogenesis, expressed as VEGF immunoexpression. We indirectly confirmed the hypothesis of a celecoxib COX-2 independent pathway mechanism of action.
3
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Antigen levels of urokinase-type plasminogen activator receptor and its gene polymorphism related to microvessel density in colorectal cancer

76%
Przybylowska K., Szemraj J., Kulig A., Dziki A., Ulanska J., Blasiak J.
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2008
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vol. 55
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issue 2
357-363
EN
We determined the distribution of genotypes and frequencies of alleles of the (CA)n repeat polymorphism in intron 3 of the urokinase plasminogen activator receptor (uPAR) gene, uPAR antigen levels and microvessel density (MVD) in tumour and distant mucosa samples from 52 patients with colorectal cancer. The uPAR level was higher for patients with high MVD comparing to patients with lower MVD which may suggest that uPAR can be correlated with progression of colorectal cancer. The significant relationship between the high MVD and uPAR antigen level appeared to be independent of the (CA)n repeat polymorphism because no differences in the level of uPAR antigen between carriers of alleles were found. The received results, indicate that uPAR might be considered as a target in colorectal cancer patients' therapy.
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