5 research outputs found
Polymorphisms and expression of glutathione transferase omega in development and progression of urinary bladder transitional cell carcinoma
Π¦ΠΈΡ: Π¦ΠΈΡ ΠΎΠ²Π΅ ΡΡΡΠ΄ΠΈΡΠ΅ ΡΠ΅ Π±ΠΈΠΎ Π΄Π° ΡΠ΅ ΡΠ°Π·ΡΠ°ΡΠ½ΠΈ ΡΠ»ΠΎΠ³Π° Π³Π΅Π½ΡΠΊΠΎΠ³ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·ΠΌΠ° GSTO1
(rs4925) ΠΈ GSTO2 (rs156697) Ρ ΠΈΠ½Π΄ΠΈΠ²ΠΈΠ΄ΡΠ°Π»Π½ΠΎΡ ΠΏΠΎΠ΄Π»ΠΎΠΆΠ½ΠΎΡΡΠΈ Π·Π° Π½Π°ΡΡΠ°Π½Π°ΠΊ ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΠ°
ΠΏΡΠ΅Π»Π°Π·Π½ΠΎΠ³ Π΅ΠΏΠΈΡΠ΅Π»Π° ΠΌΠΎΠΊΡΠ°ΡΠ½Π΅ Π±Π΅ΡΠΈΠΊΠ΅, Π·Π°ΡΠ΅Π΄Π½ΠΎ ΡΠ° ΡΠΈΡ
ΠΎΠ²ΠΈΠΌ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΡΡΡΡΠΈΠΌ Π΅ΡΠ΅ΠΊΡΠΎΠΌ Π½Π°
ΡΠΊΡΠΏΠ½ΠΎ ΠΏΡΠ΅ΠΆΠΈΠ²ΡΠ°Π²Π°ΡΠ΅ ΠΈ/ΠΈΠ»ΠΈ Ρ
Π΅ΠΌΠΎΡΠ΅ΡΠ°ΠΏΠΈΡΡ ΠΊΠΎΠ΄ ΠΎΠ²ΠΈΡ
Π±ΠΎΠ»Π΅ΡΠ½ΠΈΠΊΠ°. Π’Π°ΠΊΠΎΡΠ΅ ΡΠ΅ ΠΈΡΠΏΠΈΡΠΈΠ²Π°Π½Π°
ΠΈ Π΅ΠΊΡΠΏΡΠ΅ΡΠΈΡΠ° GSTO1-1 Ρ ΡΡΠΌΠΎΡΡΠΊΠΎΠΌ ΠΈ ΠΎΠΊΠΎΠ»Π½ΠΎΠΌ ΠΌΠΎΡΡΠΎΠ»ΠΎΡΠΊΠΈ Π½Π΅ΠΈΠ·ΠΌΠ΅ΡΠ΅Π½ΠΎΠΌ Π΅ΠΏΠΈΡΠ΅Π»Ρ
Π±ΠΎΠ»Π΅ΡΠ½ΠΈΠΊΠ° ΡΠ° ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΠΎΠΌ ΠΏΡΠ΅Π»Π°Π·Π½ΠΎΠ³ Π΅ΠΏΠΈΡΠ΅Π»Π° ΠΌΠΎΠΊΡΠ°ΡΠ½Π΅ Π±Π΅ΡΠΈΠΊΠ΅.
MΠ°ΡΠ΅ΡΠΈΡΠ°Π» ΠΈ ΠΌΠ΅ΡΠΎΠ΄Π΅: ΠΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·Π°ΠΌ GSTO1 ΠΈ GSTO2 ΡΠ΅ ΠΎΠ΄ΡΠ΅ΡΠΈΠ²Π°Π½ Π°Π½Π°Π»ΠΈΠ·ΠΎΠΌ
ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π° ΡΠ΅ΡΡΡΠΈΠΊΡΠΈΠΎΠ½Π΅ Π΄ΠΈΠ³Π΅ΡΡΠΈΡΠ΅ ΠΠΠ ΡΡΠ°Π³ΠΌΠ΅Π½Π°ΡΠ° Π½Π°ΡΡΠ°Π»ΠΈΡ
ΡΠ΅Π°ΠΊΡΠΈΡΠΎΠΌ Π»Π°Π½ΡΠ°Π½ΠΎΠ³
ΡΠΌΠ½ΠΎΠΆΠ°Π²Π°ΡΠ° (PCR-RFLP). ΠΡΠ΅Π΄ΠΈΠΊΡΠΈΠ²Π½Π° Π²ΡΠ΅Π΄Π½ΠΎΡΡ ΡΠ°Π·Π»ΠΈΡΠΈΡΠΈΡ
GSTO Π³Π΅Π½ΠΎΡΠΈΠΏΠΎΠ²Π° ΡΠ΅
ΠΏΡΠΎΡΠ΅ΡΠΈΠ²Π°Π½Π° ΠΠΎΠΊΡΠΎΠ²ΠΈΠΌ ΡΠ΅Π³ΡΠ΅ΡΠΈΠΎΠ½ΠΈΠΌ Ρ
Π°Π·Π°ΡΠ΄Π½ΠΈΠΌ ΠΌΠΎΠ΄Π΅Π»ΠΈΠΌΠ°, Π΄ΠΎΠΊ ΡΡ ΠΠ°ΠΏΠ»Π°Π½-ΠΠ°ΡΠ΅ΡΠΎΠ²Π΅
ΠΊΡΠΈΠ²Π΅ ΠΊΠΎΡΠΈΡΡΠ΅Π½Π΅ Π·Π° Π·Π° ΠΏΡΠΈΠΊΠ°Π·ΠΈΠ²Π°ΡΠ΅ Π²Π΅ΡΠΎΠ²Π°ΡΠ½ΠΎΡΠ΅ ΠΈΡΠΏΠΈΡΠΈΠ²Π°Π½ΠΈΡ
Π΄ΠΎΠ³Π°ΡΠ°ΡΠ°, Π° Π»ΠΎΠ³-ΡΠ°Π½ΠΊ ΡΠ΅ΡΡ
Π·Π° ΡΡΠ²ΡΡΠΈΠ²Π°ΡΠ΅ ΡΠ°Π·Π»ΠΈΠΊΠ° Ρ Π²Π΅ΡΠΎΠ²Π°ΡΠ½ΠΎΡΠΈ ΠΏΡΠ΅ΠΆΠΈΠ²ΡΠ°Π²Π°ΡΠ°. GSTO1-1 Π΅ΠΊΡΠΏΡΠ΅ΡΠΈΡΠ° ΡΠ΅
ΠΎΠ΄ΡΠ΅ΡΠΈΠ²Π°Π½Π° ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΠ΅ΡΡΠ΅ΡΠ½ Π±Π»ΠΎΡΠ° ΠΈ ΡΠ΅Π°ΠΊΡΠΈΡΠΎΠΌ Π»Π°Π½ΡΠ°Π½ΠΎΠ³ ΡΠΌΠ½ΠΎΠΆΠ°Π²Π°ΡΠ° Ρ ΡΠ΅Π°Π»Π½ΠΎΠΌ
Π²ΡΠ΅ΠΌΠ΅Π½Ρ (RT-PCR), Π΄ΠΎΠΊ ΡΠ΅ Π·Π° ΠΈΡΠΏΠΈΡΠΈΠ²Π°ΡΠ΅ ΡΠΊΡΠΏΠ½Π΅ S-Π³Π»ΡΡΠ°ΡΠΈΠΎΠ½ΠΈΠ»Π°ΡΠΈΡΠ΅ ΠΈΠ·Π²Π΅Π΄Π΅Π½Π°
Π΅Π»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π·Π° ΠΏΠΎΠ΄ Π½Π΅ΡΠ΅Π΄ΡΠΊΡΡΡΡΠΈΠΌ ΡΡΠ»ΠΎΠ²ΠΈΠΌΠ°. ΠΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΠ° ΡΠΊΡΠΏΠ½ΠΎΠ³ ΠΈ ΠΎΠΊΡΠΈΠ΄ΠΎΠ²Π°Π½ΠΎΠ³
Π³Π»ΡΡΠ°ΡΠΈΠΎΠ½Π° ΡΠ΅ ΠΎΠ΄ΡΠ΅ΡΠ΅Π½Π° ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΎΡΠΎΠΌΠ΅ΡΡΠΈΡΡΠΊΠΈ. ΠΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΠ° ΠΈΠ½ΡΠ΅ΡΠ»Π΅ΡΠΊΠΈΠ½Π°-8 (IL-8)
Ρ ΡΠΈΡΠΎΡΠΎΠ»Ρ ΠΈ ΡΡΠΈΠ½Π°ΡΠ½ΠΈ 8-Ρ
ΠΈΠ΄ΡΠΎΠΊΡΠΈ-2β²-Π΄Π΅ΠΎΠΊΡΠΈΠ³ΡΠ°Π½ΠΎΠ·ΠΈΠ½ (8-OHdG) ΡΡ ΠΎΠ΄ΡΠ΅ΡΠ΅Π½ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ
Π΅Π½Π·ΠΈΠΌΡΠΊΠΎΠ³ ΠΈΠΌΡΠ½ΠΎΠ΅ΡΠ΅ΡΠ°.
Π Π΅Π·ΡΠ»ΡΠ°ΡΠΈ: ΠΠΎΡΠΈΠΎΡΠΈ Π²Π°ΡΠΈΡΠ°Π½ΡΠ½ΠΎΠ³ GSTO2*G/G Π³Π΅Π½ΠΎΡΠΈΠΏΠ° ΡΡ Π±ΠΈΠ»ΠΈ ΠΏΠΎΠ΄ ΠΏΠΎΠ²Π΅ΡΠ°Π½ΠΈΠΌ
ΡΠΈΠ·ΠΈΠΊΠΎΠΌ Π·Π° Π½Π°ΡΡΠ°Π½Π°ΠΊ ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΠ° ΠΏΡΠ΅Π»Π°Π·Π½ΠΎΠ³ Π΅ΠΏΠΈΡΠ΅Π»Π° ΠΌΠΎΠΊΡΠ°ΡΠ½Π΅ Π±Π΅ΡΠΈΠΊΠ΅ (OR=2,6, 95%
CI=1,2-5,8, p=0,041), ΠΊΠΎΡΠΈ ΡΠ΅ Π±ΠΈΠΎ ΡΠΎΡ ΠΈΠ·ΡΠ°ΠΆΠ΅Π½ΠΈΡΠΈ ΠΊΠ°Π΄Π° ΡΠ΅ ΠΎΠ²Π°Ρ Π³Π΅Π½ΠΎΡΠΈΠΏ Π±ΠΈΠΎ ΡΠ΄ΡΡΠΆΠ΅Π½ ΡΠ°
ΠΏΡΡΠ΅ΡΠ΅ΠΌ (OR-odds ratio =4,3, 95%CI-confidence interval =1,6-11,2, p=0,003). ΠΠ°ΡΠ΅,
Π΄ΠΎΠ±ΠΈΡΠ΅Π½ΠΈ ΡΠ΅Π·ΡΠ»ΡΠ°ΡΠΈ ΡΠΊΠ°Π·ΡΡΡ Π΄Π° ΡΡ Π½ΠΎΡΠΈΠΎΡΠΈ Ρ
Π°ΠΏΠ»ΠΎΡΠΈΠΏΠ° GSTO1*C/GSTO2*G (GSTO1
ΡΠ΅ΡΠ΅ΡΠ΅Π½ΡΠ½ΠΈ Π°Π»Π΅Π»/GSTO2 Π²Π°ΡΠΈΡΠ°Π½ΡΠ½ΠΈ Π°Π»Π΅Π») ΠΏΠΎΠ΄ Π½Π°ΡΠ²Π΅ΡΠΈΠΌ ΡΠΈΠ·ΠΈΠΊΠΎΠΌ Π·Π° Π½Π°ΡΡΠ°Π½Π°ΠΊ
ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΠ° ΠΌΠΎΠΊΡΠ°ΡΠ½Π΅ Π±Π΅ΡΠΈΠΊΠ΅ (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 reactionβ
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-2β²-
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
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-2β²-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.
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
Π¦ΠΈΡ: Π¦ΠΈΡ ΠΎΠ²Π΅ ΡΡΡΠ΄ΠΈΡΠ΅ ΡΠ΅ Π±ΠΈΠΎ Π΄Π° ΡΠ΅ ΡΠ°Π·ΡΠ°ΡΠ½ΠΈ ΡΠ»ΠΎΠ³Π° Π³Π΅Π½ΡΠΊΠΎΠ³ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·ΠΌΠ° GSTO1
(rs4925) ΠΈ GSTO2 (rs156697) Ρ ΠΈΠ½Π΄ΠΈΠ²ΠΈΠ΄ΡΠ°Π»Π½ΠΎΡ ΠΏΠΎΠ΄Π»ΠΎΠΆΠ½ΠΎΡΡΠΈ Π·Π° Π½Π°ΡΡΠ°Π½Π°ΠΊ ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΠ°
ΠΏΡΠ΅Π»Π°Π·Π½ΠΎΠ³ Π΅ΠΏΠΈΡΠ΅Π»Π° ΠΌΠΎΠΊΡΠ°ΡΠ½Π΅ Π±Π΅ΡΠΈΠΊΠ΅, Π·Π°ΡΠ΅Π΄Π½ΠΎ ΡΠ° ΡΠΈΡ
ΠΎΠ²ΠΈΠΌ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΡΡΡΡΠΈΠΌ Π΅ΡΠ΅ΠΊΡΠΎΠΌ Π½Π°
ΡΠΊΡΠΏΠ½ΠΎ ΠΏΡΠ΅ΠΆΠΈΠ²ΡΠ°Π²Π°ΡΠ΅ ΠΈ/ΠΈΠ»ΠΈ Ρ
Π΅ΠΌΠΎΡΠ΅ΡΠ°ΠΏΠΈΡΡ ΠΊΠΎΠ΄ ΠΎΠ²ΠΈΡ
Π±ΠΎΠ»Π΅ΡΠ½ΠΈΠΊΠ°. Π’Π°ΠΊΠΎΡΠ΅ ΡΠ΅ ΠΈΡΠΏΠΈΡΠΈΠ²Π°Π½Π°
ΠΈ Π΅ΠΊΡΠΏΡΠ΅ΡΠΈΡΠ° GSTO1-1 Ρ ΡΡΠΌΠΎΡΡΠΊΠΎΠΌ ΠΈ ΠΎΠΊΠΎΠ»Π½ΠΎΠΌ ΠΌΠΎΡΡΠΎΠ»ΠΎΡΠΊΠΈ Π½Π΅ΠΈΠ·ΠΌΠ΅ΡΠ΅Π½ΠΎΠΌ Π΅ΠΏΠΈΡΠ΅Π»Ρ
Π±ΠΎΠ»Π΅ΡΠ½ΠΈΠΊΠ° ΡΠ° ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΠΎΠΌ ΠΏΡΠ΅Π»Π°Π·Π½ΠΎΠ³ Π΅ΠΏΠΈΡΠ΅Π»Π° ΠΌΠΎΠΊΡΠ°ΡΠ½Π΅ Π±Π΅ΡΠΈΠΊΠ΅.
MΠ°ΡΠ΅ΡΠΈΡΠ°Π» ΠΈ ΠΌΠ΅ΡΠΎΠ΄Π΅: ΠΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·Π°ΠΌ GSTO1 ΠΈ GSTO2 ΡΠ΅ ΠΎΠ΄ΡΠ΅ΡΠΈΠ²Π°Π½ Π°Π½Π°Π»ΠΈΠ·ΠΎΠΌ
ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π° ΡΠ΅ΡΡΡΠΈΠΊΡΠΈΠΎΠ½Π΅ Π΄ΠΈΠ³Π΅ΡΡΠΈΡΠ΅ ΠΠΠ ΡΡΠ°Π³ΠΌΠ΅Π½Π°ΡΠ° Π½Π°ΡΡΠ°Π»ΠΈΡ
ΡΠ΅Π°ΠΊΡΠΈΡΠΎΠΌ Π»Π°Π½ΡΠ°Π½ΠΎΠ³
ΡΠΌΠ½ΠΎΠΆΠ°Π²Π°ΡΠ° (PCR-RFLP). ΠΡΠ΅Π΄ΠΈΠΊΡΠΈΠ²Π½Π° Π²ΡΠ΅Π΄Π½ΠΎΡΡ ΡΠ°Π·Π»ΠΈΡΠΈΡΠΈΡ
GSTO Π³Π΅Π½ΠΎΡΠΈΠΏΠΎΠ²Π° ΡΠ΅
ΠΏΡΠΎΡΠ΅ΡΠΈΠ²Π°Π½Π° ΠΠΎΠΊΡΠΎΠ²ΠΈΠΌ ΡΠ΅Π³ΡΠ΅ΡΠΈΠΎΠ½ΠΈΠΌ Ρ
Π°Π·Π°ΡΠ΄Π½ΠΈΠΌ ΠΌΠΎΠ΄Π΅Π»ΠΈΠΌΠ°, Π΄ΠΎΠΊ ΡΡ ΠΠ°ΠΏΠ»Π°Π½-ΠΠ°ΡΠ΅ΡΠΎΠ²Π΅
ΠΊΡΠΈΠ²Π΅ ΠΊΠΎΡΠΈΡΡΠ΅Π½Π΅ Π·Π° Π·Π° ΠΏΡΠΈΠΊΠ°Π·ΠΈΠ²Π°ΡΠ΅ Π²Π΅ΡΠΎΠ²Π°ΡΠ½ΠΎΡΠ΅ ΠΈΡΠΏΠΈΡΠΈΠ²Π°Π½ΠΈΡ
Π΄ΠΎΠ³Π°ΡΠ°ΡΠ°, Π° Π»ΠΎΠ³-ΡΠ°Π½ΠΊ ΡΠ΅ΡΡ
Π·Π° ΡΡΠ²ΡΡΠΈΠ²Π°ΡΠ΅ ΡΠ°Π·Π»ΠΈΠΊΠ° Ρ Π²Π΅ΡΠΎΠ²Π°ΡΠ½ΠΎΡΠΈ ΠΏΡΠ΅ΠΆΠΈΠ²ΡΠ°Π²Π°ΡΠ°. GSTO1-1 Π΅ΠΊΡΠΏΡΠ΅ΡΠΈΡΠ° ΡΠ΅
ΠΎΠ΄ΡΠ΅ΡΠΈΠ²Π°Π½Π° ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΠ΅ΡΡΠ΅ΡΠ½ Π±Π»ΠΎΡΠ° ΠΈ ΡΠ΅Π°ΠΊΡΠΈΡΠΎΠΌ Π»Π°Π½ΡΠ°Π½ΠΎΠ³ ΡΠΌΠ½ΠΎΠΆΠ°Π²Π°ΡΠ° Ρ ΡΠ΅Π°Π»Π½ΠΎΠΌ
Π²ΡΠ΅ΠΌΠ΅Π½Ρ (RT-PCR), Π΄ΠΎΠΊ ΡΠ΅ Π·Π° ΠΈΡΠΏΠΈΡΠΈΠ²Π°ΡΠ΅ ΡΠΊΡΠΏΠ½Π΅ S-Π³Π»ΡΡΠ°ΡΠΈΠΎΠ½ΠΈΠ»Π°ΡΠΈΡΠ΅ ΠΈΠ·Π²Π΅Π΄Π΅Π½Π°
Π΅Π»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π·Π° ΠΏΠΎΠ΄ Π½Π΅ΡΠ΅Π΄ΡΠΊΡΡΡΡΠΈΠΌ ΡΡΠ»ΠΎΠ²ΠΈΠΌΠ°. ΠΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΠ° ΡΠΊΡΠΏΠ½ΠΎΠ³ ΠΈ ΠΎΠΊΡΠΈΠ΄ΠΎΠ²Π°Π½ΠΎΠ³
Π³Π»ΡΡΠ°ΡΠΈΠΎΠ½Π° ΡΠ΅ ΠΎΠ΄ΡΠ΅ΡΠ΅Π½Π° ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΎΡΠΎΠΌΠ΅ΡΡΠΈΡΡΠΊΠΈ. ΠΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΠ° ΠΈΠ½ΡΠ΅ΡΠ»Π΅ΡΠΊΠΈΠ½Π°-8 (IL-8)
Ρ ΡΠΈΡΠΎΡΠΎΠ»Ρ ΠΈ ΡΡΠΈΠ½Π°ΡΠ½ΠΈ 8-Ρ
ΠΈΠ΄ΡΠΎΠΊΡΠΈ-2β²-Π΄Π΅ΠΎΠΊΡΠΈΠ³ΡΠ°Π½ΠΎΠ·ΠΈΠ½ (8-OHdG) ΡΡ ΠΎΠ΄ΡΠ΅ΡΠ΅Π½ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ
Π΅Π½Π·ΠΈΠΌΡΠΊΠΎΠ³ ΠΈΠΌΡΠ½ΠΎΠ΅ΡΠ΅ΡΠ°.
Π Π΅Π·ΡΠ»ΡΠ°ΡΠΈ: ΠΠΎΡΠΈΠΎΡΠΈ Π²Π°ΡΠΈΡΠ°Π½ΡΠ½ΠΎΠ³ GSTO2*G/G Π³Π΅Π½ΠΎΡΠΈΠΏΠ° ΡΡ Π±ΠΈΠ»ΠΈ ΠΏΠΎΠ΄ ΠΏΠΎΠ²Π΅ΡΠ°Π½ΠΈΠΌ
ΡΠΈΠ·ΠΈΠΊΠΎΠΌ Π·Π° Π½Π°ΡΡΠ°Π½Π°ΠΊ ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΠ° ΠΏΡΠ΅Π»Π°Π·Π½ΠΎΠ³ Π΅ΠΏΠΈΡΠ΅Π»Π° ΠΌΠΎΠΊΡΠ°ΡΠ½Π΅ Π±Π΅ΡΠΈΠΊΠ΅ (OR=2,6, 95%
CI=1,2-5,8, p=0,041), ΠΊΠΎΡΠΈ ΡΠ΅ Π±ΠΈΠΎ ΡΠΎΡ ΠΈΠ·ΡΠ°ΠΆΠ΅Π½ΠΈΡΠΈ ΠΊΠ°Π΄Π° ΡΠ΅ ΠΎΠ²Π°Ρ Π³Π΅Π½ΠΎΡΠΈΠΏ Π±ΠΈΠΎ ΡΠ΄ΡΡΠΆΠ΅Π½ ΡΠ°
ΠΏΡΡΠ΅ΡΠ΅ΠΌ (OR-odds ratio =4,3, 95%CI-confidence interval =1,6-11,2, p=0,003). ΠΠ°ΡΠ΅,
Π΄ΠΎΠ±ΠΈΡΠ΅Π½ΠΈ ΡΠ΅Π·ΡΠ»ΡΠ°ΡΠΈ ΡΠΊΠ°Π·ΡΡΡ Π΄Π° ΡΡ Π½ΠΎΡΠΈΠΎΡΠΈ Ρ
Π°ΠΏΠ»ΠΎΡΠΈΠΏΠ° GSTO1*C/GSTO2*G (GSTO1
ΡΠ΅ΡΠ΅ΡΠ΅Π½ΡΠ½ΠΈ Π°Π»Π΅Π»/GSTO2 Π²Π°ΡΠΈΡΠ°Π½ΡΠ½ΠΈ Π°Π»Π΅Π») ΠΏΠΎΠ΄ Π½Π°ΡΠ²Π΅ΡΠΈΠΌ ΡΠΈΠ·ΠΈΠΊΠΎΠΌ Π·Π° Π½Π°ΡΡΠ°Π½Π°ΠΊ
ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΠ° ΠΌΠΎΠΊΡΠ°ΡΠ½Π΅ Π±Π΅ΡΠΈΠΊΠ΅ (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 reactionβ
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-2β²-
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..