5 research outputs found

    Polymorphisms and expression of glutathione transferase omega in development and progression of urinary bladder transitional cell carcinoma

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    Π¦ΠΈΡ™: Π¦ΠΈΡ™ ΠΎΠ²Π΅ ΡΡ‚ΡƒΠ΄ΠΈΡ˜Π΅ јС Π±ΠΈΠΎ Π΄Π° сС Ρ€Π°Π·Ρ˜Π°ΡΠ½ΠΈ ΡƒΠ»ΠΎΠ³Π° гСнског ΠΏΠΎΠ»ΠΈΠΌΠΎΡ€Ρ„ΠΈΠ·ΠΌΠ° GSTO1 (rs4925) ΠΈ GSTO2 (rs156697) Ρƒ ΠΈΠ½Π΄ΠΈΠ²ΠΈΠ΄ΡƒΠ°Π»Π½ΠΎΡ˜ подлоТности Π·Π° настанак ΠΊΠ°Ρ€Ρ†ΠΈΠ½ΠΎΠΌΠ° ΠΏΡ€Π΅Π»Π°Π·Π½ΠΎΠ³ Π΅ΠΏΠΈΡ‚Π΅Π»Π° ΠΌΠΎΠΊΡ€Π°Ρ›Π½Π΅ бСшикС, зајСдно са ΡšΠΈΡ…ΠΎΠ²ΠΈΠΌ ΠΌΠΎΠ΄ΠΈΡ„ΠΈΠΊΡƒΡ˜ΡƒΡ›ΠΈΠΌ Π΅Ρ„Π΅ΠΊΡ‚ΠΎΠΌ Π½Π° ΡƒΠΊΡƒΠΏΠ½ΠΎ ΠΏΡ€Π΅ΠΆΠΈΠ²Ρ™Π°Π²Π°ΡšΠ΅ ΠΈ/ΠΈΠ»ΠΈ Ρ…Π΅ΠΌΠΎΡ‚Π΅Ρ€Π°ΠΏΠΈΡ˜Ρƒ ΠΊΠΎΠ΄ ΠΎΠ²ΠΈΡ… болСсника. Π’Π°ΠΊΠΎΡ’Π΅ јС испитивана ΠΈ Π΅ΠΊΡΠΏΡ€Π΅ΡΠΈΡ˜Π° GSTO1-1 Ρƒ туморском ΠΈ ΠΎΠΊΠΎΠ»Π½ΠΎΠΌ ΠΌΠΎΡ€Ρ„ΠΎΠ»ΠΎΡˆΠΊΠΈ нСизмСњСном Π΅ΠΏΠΈΡ‚Π΅Π»Ρƒ болСсника са ΠΊΠ°Ρ€Ρ†ΠΈΠ½ΠΎΠΌΠΎΠΌ ΠΏΡ€Π΅Π»Π°Π·Π½ΠΎΠ³ Π΅ΠΏΠΈΡ‚Π΅Π»Π° ΠΌΠΎΠΊΡ€Π°Ρ›Π½Π΅ бСшикС. MΠ°Ρ‚Π΅Ρ€ΠΈΡ˜Π°Π» ΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Π΅: ΠŸΠΎΠ»ΠΈΠΌΠΎΡ€Ρ„ΠΈΠ·Π°ΠΌ GSTO1 ΠΈ GSTO2 јС ΠΎΠ΄Ρ€Π΅Ρ’ΠΈΠ²Π°Π½ Π°Π½Π°Π»ΠΈΠ·ΠΎΠΌ ΠΏΡ€ΠΎΠΈΠ·Π²ΠΎΠ΄Π° рСстрикционС Π΄ΠΈΠ³Π΅ΡΡ‚ΠΈΡ˜Π΅ Π”ΠΠš Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Π°Ρ‚Π° насталих Ρ€Π΅Π°ΠΊΡ†ΠΈΡ˜ΠΎΠΌ Π»Π°Π½Ρ‡Π°Π½ΠΎΠ³ ΡƒΠΌΠ½ΠΎΠΆΠ°Π²Π°ΡšΠ° (PCR-RFLP). ΠŸΡ€Π΅Π΄ΠΈΠΊΡ‚ΠΈΠ²Π½Π° врСдност Ρ€Π°Π·Π»ΠΈΡ‡ΠΈΡ‚ΠΈΡ… GSTO Π³Π΅Π½ΠΎΡ‚ΠΈΠΏΠΎΠ²Π° јС ΠΏΡ€ΠΎΡ†Π΅ΡšΠΈΠ²Π°Π½Π° Коксовим рСгрСсионим Ρ…Π°Π·Π°Ρ€Π΄Π½ΠΈΠΌ ΠΌΠΎΠ΄Π΅Π»ΠΈΠΌΠ°, Π΄ΠΎΠΊ су Каплан-ΠœΠ°Ρ˜Π΅Ρ€ΠΎΠ²Π΅ ΠΊΡ€ΠΈΠ²Π΅ ΠΊΠΎΡ€ΠΈΡˆΡ›Π΅Π½Π΅ Π·Π° Π·Π° ΠΏΡ€ΠΈΠΊΠ°Π·ΠΈΠ²Π°ΡšΠ΅ Π²Π΅Ρ€ΠΎΠ²Π°Ρ‚Π½ΠΎΡ›Π΅ испитиваних Π΄ΠΎΠ³Π°Ρ’Π°Ρ˜Π°, Π° Π»ΠΎΠ³-Ρ€Π°Π½ΠΊ тСст Π·Π° ΡƒΡ‚Π²Ρ€Ρ’ΠΈΠ²Π°ΡšΠ΅ Ρ€Π°Π·Π»ΠΈΠΊΠ° Ρƒ Π²Π΅Ρ€ΠΎΠ²Π°Ρ‚Π½ΠΎΡ›ΠΈ ΠΏΡ€Π΅ΠΆΠΈΠ²Ρ™Π°Π²Π°ΡšΠ°. GSTO1-1 Π΅ΠΊΡΠΏΡ€Π΅ΡΠΈΡ˜Π° јС ΠΎΠ΄Ρ€Π΅Ρ’ΠΈΠ²Π°Π½Π° ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠΌ ВСстСрн Π±Π»ΠΎΡ‚Π° ΠΈ Ρ€Π΅Π°ΠΊΡ†ΠΈΡ˜ΠΎΠΌ Π»Π°Π½Ρ‡Π°Π½ΠΎΠ³ ΡƒΠΌΠ½ΠΎΠΆΠ°Π²Π°ΡšΠ° Ρƒ Ρ€Π΅Π°Π»Π½ΠΎΠΌ Π²Ρ€Π΅ΠΌΠ΅Π½Ρƒ (RT-PCR), Π΄ΠΎΠΊ јС Π·Π° ΠΈΡΠΏΠΈΡ‚ΠΈΠ²Π°ΡšΠ΅ ΡƒΠΊΡƒΠΏΠ½Π΅ S-Π³Π»ΡƒΡ‚Π°Ρ‚ΠΈΠΎΠ½ΠΈΠ»Π°Ρ†ΠΈΡ˜Π΅ ΠΈΠ·Π²Π΅Π΄Π΅Π½Π° Π΅Π»Π΅ΠΊΡ‚Ρ€ΠΎΡ„ΠΎΡ€Π΅Π·Π° ΠΏΠΎΠ΄ Π½Π΅Ρ€Π΅Π΄ΡƒΠΊΡƒΡ˜ΡƒΡ›ΠΈΠΌ условима. ΠšΠΎΠ½Ρ†Π΅Π½Ρ‚Ρ€Π°Ρ†ΠΈΡ˜Π° ΡƒΠΊΡƒΠΏΠ½ΠΎΠ³ ΠΈ оксидованог Π³Π»ΡƒΡ‚Π°Ρ‚ΠΈΠΎΠ½Π° јС ΠΎΠ΄Ρ€Π΅Ρ’Π΅Π½Π° ΡΠΏΠ΅ΠΊΡ‚Ρ€ΠΎΡ„ΠΎΡ‚ΠΎΠΌΠ΅Ρ‚Ρ€ΠΈΡ˜ΡΠΊΠΈ. ΠšΠΎΠ½Ρ†Π΅Π½Ρ‚Ρ€Π°Ρ†ΠΈΡ˜Π° ΠΈΠ½Ρ‚Π΅Ρ€Π»Π΅ΡƒΠΊΠΈΠ½Π°-8 (IL-8) Ρƒ цитосолу ΠΈ ΡƒΡ€ΠΈΠ½Π°Ρ€Π½ΠΈ 8-хидрокси-2β€²-дСоксигуанозин (8-OHdG) су ΠΎΠ΄Ρ€Π΅Ρ’Π΅Π½ΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠΌ Снзимског ΠΈΠΌΡƒΠ½ΠΎΠ΅ΡΠ΅Ρ˜Π°. Π Π΅Π·ΡƒΠ»Ρ‚Π°Ρ‚ΠΈ: Носиоци Π²Π°Ρ€ΠΈΡ˜Π°Π½Ρ‚Π½ΠΎΠ³ GSTO2*G/G Π³Π΅Π½ΠΎΡ‚ΠΈΠΏΠ° су Π±ΠΈΠ»ΠΈ ΠΏΠΎΠ΄ ΠΏΠΎΠ²Π΅Ρ›Π°Π½ΠΈΠΌ Ρ€ΠΈΠ·ΠΈΠΊΠΎΠΌ Π·Π° настанак ΠΊΠ°Ρ€Ρ†ΠΈΠ½ΠΎΠΌΠ° ΠΏΡ€Π΅Π»Π°Π·Π½ΠΎΠ³ Π΅ΠΏΠΈΡ‚Π΅Π»Π° ΠΌΠΎΠΊΡ€Π°Ρ›Π½Π΅ бСшикС (OR=2,6, 95% CI=1,2-5,8, p=0,041), који јС Π±ΠΈΠΎ још ΠΈΠ·Ρ€Π°ΠΆΠ΅Π½ΠΈΡ˜ΠΈ ΠΊΠ°Π΄Π° јС овај Π³Π΅Π½ΠΎΡ‚ΠΈΠΏ Π±ΠΈΠΎ ΡƒΠ΄Ρ€ΡƒΠΆΠ΅Π½ са ΠΏΡƒΡˆΠ΅ΡšΠ΅ΠΌ (OR-odds ratio =4,3, 95%CI-confidence interval =1,6-11,2, p=0,003). Π”Π°Ρ™Π΅, добијСни Ρ€Π΅Π·ΡƒΠ»Ρ‚Π°Ρ‚ΠΈ ΡƒΠΊΠ°Π·ΡƒΡ˜Ρƒ Π΄Π° су носиоци Ρ…Π°ΠΏΠ»ΠΎΡ‚ΠΈΠΏΠ° GSTO1*C/GSTO2*G (GSTO1 Ρ€Π΅Ρ„Π΅Ρ€Π΅Π½Ρ‚Π½ΠΈ Π°Π»Π΅Π»/GSTO2 Π²Π°Ρ€ΠΈΡ˜Π°Π½Ρ‚Π½ΠΈ Π°Π»Π΅Π») ΠΏΠΎΠ΄ Π½Π°Ρ˜Π²Π΅Ρ›ΠΈΠΌ Ρ€ΠΈΠ·ΠΈΠΊΠΎΠΌ Π·Π° настанак ΠΊΠ°Ρ€Ρ†ΠΈΠ½ΠΎΠΌΠ° ΠΌΠΎΠΊΡ€Π°Ρ›Π½Π΅ бСшикС (OR=2,8, 95%CI=1,5-5,2, p=0,002)...Purpose: The aim of the study was to clarify the role of GSTO1 (rs4925) and GSTO2 (rs156697) genetic polymorphisms in individual susceptibility to transitional cell carcinoma (TCC) of urinary bladder, together with their modifying effect on the overall survival and/or chemotherapy treatment in these patients. We also examined the GSTO1 expression pattern in tumor and non-tumor tissue of TCC patients. Methods: GSTO1 and GSTO2 genotyping was performed by polymerase chain reaction– restriction fragment length polymorphism (PCR-RFLP). The effect of GSTOs polymorphisms on predicting mortality was analyzed by the Cox proportional hazard models, while Kaplan-Meier curves with log-rank tests were used to assess differences in survival probability. GSTO1-1 expression was determined by Western blot and real time-PCR, while for the total S-glutathionylation electrophoresis under non-reducing conditions was performed. The total and oxidized glutathione content was measured by an enzymatic recycling method. Tumor cytosolic interleukin-8 (IL-8) and urine 8-hydroxy-2β€²- deoxyguanosine (8-OHdG) concentrations were estimated by enzyme-linked immunosorbent assay (ELISA). Results: Carriers of the variant GSTO2*G/G genotype were at increased risk of TCC development (OR-odds ratio =2.6, 95% CI-confidence interval =1.2-5.8, p=0.041), which was more pronounced, when associated with smoking (OR=4.3, 95%CI=1.6-11.2, p=0.003). Furthermore, these results indicate that GSTO1*C/GSTO2*G (GSTO1 wild type/GSTO2 variant) haplotype carriers were at the highest risk for the TCC development (OR=2.8, 95%CI=1.5-5.2, p=0.002). Although urinary 8-OHdG in TCC patients was significantly higher than in controls, the effect of combined GSTO1/GSTO2 genotype on the extent of oxidative damage was not found. GSTO1*A/A or GSTO2*G/G variant genotypes were independent predictors of the higher risk of death among TCC patients (HR-hazard ratio =2.9, p=0.022; HR=3.9, p=0.001; respectively) and significantly influenced the overall survival..

    The Polymorphisms of Genes Encoding Catalytic Antioxidant Proteins Modulate the Susceptibility and Progression of Testicular Germ Cell Tumor

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    The simultaneous analysis of redox biomarkers and polymorphisms encoding for regulatory and catalytic antioxidant proteins was performed in order to evaluate their potential role in the development of testicular germ cell tumor (GCT), as well as the progression of the disease. NRF2 (rs6721961), GSTM3 (rs1332018), SOD2 (rs4880) and GPX3 (rs8177412) polymorphisms were assessed in 88 patients with testicular GCT (52 with seminoma) and 88 age-matched controls. The plasma levels of 8-hydroxy-2β€²-deoxyguanosine (8-OHdG), thiol groups and the plasma activity of glutathione peroxidase were measured. A significant association between variant GPX3*TC+CC genotype and risk of overall testicular GCT, as well as seminoma development, was found. Moreover, carriers of variant SOD2*TT genotype were at almost 3-fold increased risk of seminoma development. Interestingly, combined SOD2*TT/GPX3*TC+CC genotype conferred a 7-fold higher risk for testicular GCT development. Finally, variant GSTM3*AC+CC genotype was associated with a higher risk for the development of advanced diseased. The presence of assessed genetic variants was not associated with significantly higher levels of redox biomarkers in both testicular GCT patients, as well as in those diagnosed with seminoma. In conclusion, the polymorphic expression of certain antioxidant enzymes might affect susceptibility toward testicular GCT development, as well as the progression of the disease

    Physiological and cell ultrastructure disturbances in wheat seedlings generated by Chenopodium murale hairy root exudate.

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    Chenopodium murale L. is an invasive weed species significantly interfering with wheat crop. However, the complete nature of its allelopathic influence on crops is not yet fully understood. In the present study, the focus is made on establishing the relation between plant morphophysiological changes and oxidative stress, induced by allelopathic extract. Phytotoxic medium of C. murale hairy root clone R5 reduced the germination rate (24% less than control value) of wheat cv. NataΕ‘a seeds, as well as seedling growth, diminishing shoot and root length significantly, decreased total chlorophyll content, and induced abnormal root gravitropism. The R5 treatment caused cellular structural abnormalities, reflecting on the root and leaf cell shape and organization. These abnormalities mostly included the increased number of mitochondria and reorganization of the vacuolar compartment, changes in nucleus shape, and chloroplast organization and distribution. The most significant structural changes were observed in cell wall in the form of amoeboid protrusions and folds leading to its irregular shape. These structural alterations were accompanied by an oxidative stress in tissues of treated wheat seedlings, reflected as increased level of H2O2 and other ROS molecules, an increase of radical scavenging capacity and total phenolic content. Accordingly, the retardation of wheat seedling growth by C. murale allelochemicals may represent a consequence of complex activity involving both cell structure alteration and physiological processes.This is a post-peer-review, pre-copyedit version of an article published in Protoplasma. The final authenticated version is available online at: [http://dx.doi.org/10.1007/s00709-018-1250-0

    Polymorphisms and expression of glutathione transferase omega in development and progression of urinary bladder transitional cell carcinoma

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    Π¦ΠΈΡ™: Π¦ΠΈΡ™ ΠΎΠ²Π΅ ΡΡ‚ΡƒΠ΄ΠΈΡ˜Π΅ јС Π±ΠΈΠΎ Π΄Π° сС Ρ€Π°Π·Ρ˜Π°ΡΠ½ΠΈ ΡƒΠ»ΠΎΠ³Π° гСнског ΠΏΠΎΠ»ΠΈΠΌΠΎΡ€Ρ„ΠΈΠ·ΠΌΠ° GSTO1 (rs4925) ΠΈ GSTO2 (rs156697) Ρƒ ΠΈΠ½Π΄ΠΈΠ²ΠΈΠ΄ΡƒΠ°Π»Π½ΠΎΡ˜ подлоТности Π·Π° настанак ΠΊΠ°Ρ€Ρ†ΠΈΠ½ΠΎΠΌΠ° ΠΏΡ€Π΅Π»Π°Π·Π½ΠΎΠ³ Π΅ΠΏΠΈΡ‚Π΅Π»Π° ΠΌΠΎΠΊΡ€Π°Ρ›Π½Π΅ бСшикС, зајСдно са ΡšΠΈΡ…ΠΎΠ²ΠΈΠΌ ΠΌΠΎΠ΄ΠΈΡ„ΠΈΠΊΡƒΡ˜ΡƒΡ›ΠΈΠΌ Π΅Ρ„Π΅ΠΊΡ‚ΠΎΠΌ Π½Π° ΡƒΠΊΡƒΠΏΠ½ΠΎ ΠΏΡ€Π΅ΠΆΠΈΠ²Ρ™Π°Π²Π°ΡšΠ΅ ΠΈ/ΠΈΠ»ΠΈ Ρ…Π΅ΠΌΠΎΡ‚Π΅Ρ€Π°ΠΏΠΈΡ˜Ρƒ ΠΊΠΎΠ΄ ΠΎΠ²ΠΈΡ… болСсника. Π’Π°ΠΊΠΎΡ’Π΅ јС испитивана ΠΈ Π΅ΠΊΡΠΏΡ€Π΅ΡΠΈΡ˜Π° GSTO1-1 Ρƒ туморском ΠΈ ΠΎΠΊΠΎΠ»Π½ΠΎΠΌ ΠΌΠΎΡ€Ρ„ΠΎΠ»ΠΎΡˆΠΊΠΈ нСизмСњСном Π΅ΠΏΠΈΡ‚Π΅Π»Ρƒ болСсника са ΠΊΠ°Ρ€Ρ†ΠΈΠ½ΠΎΠΌΠΎΠΌ ΠΏΡ€Π΅Π»Π°Π·Π½ΠΎΠ³ Π΅ΠΏΠΈΡ‚Π΅Π»Π° ΠΌΠΎΠΊΡ€Π°Ρ›Π½Π΅ бСшикС. MΠ°Ρ‚Π΅Ρ€ΠΈΡ˜Π°Π» ΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Π΅: ΠŸΠΎΠ»ΠΈΠΌΠΎΡ€Ρ„ΠΈΠ·Π°ΠΌ GSTO1 ΠΈ GSTO2 јС ΠΎΠ΄Ρ€Π΅Ρ’ΠΈΠ²Π°Π½ Π°Π½Π°Π»ΠΈΠ·ΠΎΠΌ ΠΏΡ€ΠΎΠΈΠ·Π²ΠΎΠ΄Π° рСстрикционС Π΄ΠΈΠ³Π΅ΡΡ‚ΠΈΡ˜Π΅ Π”ΠΠš Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Π°Ρ‚Π° насталих Ρ€Π΅Π°ΠΊΡ†ΠΈΡ˜ΠΎΠΌ Π»Π°Π½Ρ‡Π°Π½ΠΎΠ³ ΡƒΠΌΠ½ΠΎΠΆΠ°Π²Π°ΡšΠ° (PCR-RFLP). ΠŸΡ€Π΅Π΄ΠΈΠΊΡ‚ΠΈΠ²Π½Π° врСдност Ρ€Π°Π·Π»ΠΈΡ‡ΠΈΡ‚ΠΈΡ… GSTO Π³Π΅Π½ΠΎΡ‚ΠΈΠΏΠΎΠ²Π° јС ΠΏΡ€ΠΎΡ†Π΅ΡšΠΈΠ²Π°Π½Π° Коксовим рСгрСсионим Ρ…Π°Π·Π°Ρ€Π΄Π½ΠΈΠΌ ΠΌΠΎΠ΄Π΅Π»ΠΈΠΌΠ°, Π΄ΠΎΠΊ су Каплан-ΠœΠ°Ρ˜Π΅Ρ€ΠΎΠ²Π΅ ΠΊΡ€ΠΈΠ²Π΅ ΠΊΠΎΡ€ΠΈΡˆΡ›Π΅Π½Π΅ Π·Π° Π·Π° ΠΏΡ€ΠΈΠΊΠ°Π·ΠΈΠ²Π°ΡšΠ΅ Π²Π΅Ρ€ΠΎΠ²Π°Ρ‚Π½ΠΎΡ›Π΅ испитиваних Π΄ΠΎΠ³Π°Ρ’Π°Ρ˜Π°, Π° Π»ΠΎΠ³-Ρ€Π°Π½ΠΊ тСст Π·Π° ΡƒΡ‚Π²Ρ€Ρ’ΠΈΠ²Π°ΡšΠ΅ Ρ€Π°Π·Π»ΠΈΠΊΠ° Ρƒ Π²Π΅Ρ€ΠΎΠ²Π°Ρ‚Π½ΠΎΡ›ΠΈ ΠΏΡ€Π΅ΠΆΠΈΠ²Ρ™Π°Π²Π°ΡšΠ°. GSTO1-1 Π΅ΠΊΡΠΏΡ€Π΅ΡΠΈΡ˜Π° јС ΠΎΠ΄Ρ€Π΅Ρ’ΠΈΠ²Π°Π½Π° ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠΌ ВСстСрн Π±Π»ΠΎΡ‚Π° ΠΈ Ρ€Π΅Π°ΠΊΡ†ΠΈΡ˜ΠΎΠΌ Π»Π°Π½Ρ‡Π°Π½ΠΎΠ³ ΡƒΠΌΠ½ΠΎΠΆΠ°Π²Π°ΡšΠ° Ρƒ Ρ€Π΅Π°Π»Π½ΠΎΠΌ Π²Ρ€Π΅ΠΌΠ΅Π½Ρƒ (RT-PCR), Π΄ΠΎΠΊ јС Π·Π° ΠΈΡΠΏΠΈΡ‚ΠΈΠ²Π°ΡšΠ΅ ΡƒΠΊΡƒΠΏΠ½Π΅ S-Π³Π»ΡƒΡ‚Π°Ρ‚ΠΈΠΎΠ½ΠΈΠ»Π°Ρ†ΠΈΡ˜Π΅ ΠΈΠ·Π²Π΅Π΄Π΅Π½Π° Π΅Π»Π΅ΠΊΡ‚Ρ€ΠΎΡ„ΠΎΡ€Π΅Π·Π° ΠΏΠΎΠ΄ Π½Π΅Ρ€Π΅Π΄ΡƒΠΊΡƒΡ˜ΡƒΡ›ΠΈΠΌ условима. ΠšΠΎΠ½Ρ†Π΅Π½Ρ‚Ρ€Π°Ρ†ΠΈΡ˜Π° ΡƒΠΊΡƒΠΏΠ½ΠΎΠ³ ΠΈ оксидованог Π³Π»ΡƒΡ‚Π°Ρ‚ΠΈΠΎΠ½Π° јС ΠΎΠ΄Ρ€Π΅Ρ’Π΅Π½Π° ΡΠΏΠ΅ΠΊΡ‚Ρ€ΠΎΡ„ΠΎΡ‚ΠΎΠΌΠ΅Ρ‚Ρ€ΠΈΡ˜ΡΠΊΠΈ. ΠšΠΎΠ½Ρ†Π΅Π½Ρ‚Ρ€Π°Ρ†ΠΈΡ˜Π° ΠΈΠ½Ρ‚Π΅Ρ€Π»Π΅ΡƒΠΊΠΈΠ½Π°-8 (IL-8) Ρƒ цитосолу ΠΈ ΡƒΡ€ΠΈΠ½Π°Ρ€Π½ΠΈ 8-хидрокси-2β€²-дСоксигуанозин (8-OHdG) су ΠΎΠ΄Ρ€Π΅Ρ’Π΅Π½ΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠΌ Снзимског ΠΈΠΌΡƒΠ½ΠΎΠ΅ΡΠ΅Ρ˜Π°. Π Π΅Π·ΡƒΠ»Ρ‚Π°Ρ‚ΠΈ: Носиоци Π²Π°Ρ€ΠΈΡ˜Π°Π½Ρ‚Π½ΠΎΠ³ GSTO2*G/G Π³Π΅Π½ΠΎΡ‚ΠΈΠΏΠ° су Π±ΠΈΠ»ΠΈ ΠΏΠΎΠ΄ ΠΏΠΎΠ²Π΅Ρ›Π°Π½ΠΈΠΌ Ρ€ΠΈΠ·ΠΈΠΊΠΎΠΌ Π·Π° настанак ΠΊΠ°Ρ€Ρ†ΠΈΠ½ΠΎΠΌΠ° ΠΏΡ€Π΅Π»Π°Π·Π½ΠΎΠ³ Π΅ΠΏΠΈΡ‚Π΅Π»Π° ΠΌΠΎΠΊΡ€Π°Ρ›Π½Π΅ бСшикС (OR=2,6, 95% CI=1,2-5,8, p=0,041), који јС Π±ΠΈΠΎ још ΠΈΠ·Ρ€Π°ΠΆΠ΅Π½ΠΈΡ˜ΠΈ ΠΊΠ°Π΄Π° јС овај Π³Π΅Π½ΠΎΡ‚ΠΈΠΏ Π±ΠΈΠΎ ΡƒΠ΄Ρ€ΡƒΠΆΠ΅Π½ са ΠΏΡƒΡˆΠ΅ΡšΠ΅ΠΌ (OR-odds ratio =4,3, 95%CI-confidence interval =1,6-11,2, p=0,003). Π”Π°Ρ™Π΅, добијСни Ρ€Π΅Π·ΡƒΠ»Ρ‚Π°Ρ‚ΠΈ ΡƒΠΊΠ°Π·ΡƒΡ˜Ρƒ Π΄Π° су носиоци Ρ…Π°ΠΏΠ»ΠΎΡ‚ΠΈΠΏΠ° GSTO1*C/GSTO2*G (GSTO1 Ρ€Π΅Ρ„Π΅Ρ€Π΅Π½Ρ‚Π½ΠΈ Π°Π»Π΅Π»/GSTO2 Π²Π°Ρ€ΠΈΡ˜Π°Π½Ρ‚Π½ΠΈ Π°Π»Π΅Π») ΠΏΠΎΠ΄ Π½Π°Ρ˜Π²Π΅Ρ›ΠΈΠΌ Ρ€ΠΈΠ·ΠΈΠΊΠΎΠΌ Π·Π° настанак ΠΊΠ°Ρ€Ρ†ΠΈΠ½ΠΎΠΌΠ° ΠΌΠΎΠΊΡ€Π°Ρ›Π½Π΅ бСшикС (OR=2,8, 95%CI=1,5-5,2, p=0,002)...Purpose: The aim of the study was to clarify the role of GSTO1 (rs4925) and GSTO2 (rs156697) genetic polymorphisms in individual susceptibility to transitional cell carcinoma (TCC) of urinary bladder, together with their modifying effect on the overall survival and/or chemotherapy treatment in these patients. We also examined the GSTO1 expression pattern in tumor and non-tumor tissue of TCC patients. Methods: GSTO1 and GSTO2 genotyping was performed by polymerase chain reaction– restriction fragment length polymorphism (PCR-RFLP). The effect of GSTOs polymorphisms on predicting mortality was analyzed by the Cox proportional hazard models, while Kaplan-Meier curves with log-rank tests were used to assess differences in survival probability. GSTO1-1 expression was determined by Western blot and real time-PCR, while for the total S-glutathionylation electrophoresis under non-reducing conditions was performed. The total and oxidized glutathione content was measured by an enzymatic recycling method. Tumor cytosolic interleukin-8 (IL-8) and urine 8-hydroxy-2β€²- deoxyguanosine (8-OHdG) concentrations were estimated by enzyme-linked immunosorbent assay (ELISA). Results: Carriers of the variant GSTO2*G/G genotype were at increased risk of TCC development (OR-odds ratio =2.6, 95% CI-confidence interval =1.2-5.8, p=0.041), which was more pronounced, when associated with smoking (OR=4.3, 95%CI=1.6-11.2, p=0.003). Furthermore, these results indicate that GSTO1*C/GSTO2*G (GSTO1 wild type/GSTO2 variant) haplotype carriers were at the highest risk for the TCC development (OR=2.8, 95%CI=1.5-5.2, p=0.002). Although urinary 8-OHdG in TCC patients was significantly higher than in controls, the effect of combined GSTO1/GSTO2 genotype on the extent of oxidative damage was not found. GSTO1*A/A or GSTO2*G/G variant genotypes were independent predictors of the higher risk of death among TCC patients (HR-hazard ratio =2.9, p=0.022; HR=3.9, p=0.001; respectively) and significantly influenced the overall survival..
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