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1.
Urol Case Rep ; 52: 102640, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38205041

ABSTRACT

Extragonadal germ cell tumors originating in the prostate are extremely rare. Thus far, less than 20 cases were described in the literature. To our knowledge, there are no published cases of primary embryonal carcinoma of the prostate. The present study presents a case of a 24-year-old male with primary prostate embryonal carcinoma. The patient received cisplatin-based chemotherapy. The patient refused a surgical treatment, which resulted in relapse of the disease and death in a short follow-up period. The present case shows that primary embryonal carcinoma may also be found in prostate and indicates the potential importance of timely surgical resection.

2.
Curr Oncol ; 30(10): 8841-8852, 2023 09 27.
Article in English | MEDLINE | ID: mdl-37887538

ABSTRACT

Considering the divergent biological behaviors of certain histological subtypes of urothelial carcinoma, it would be of great importance to examine the impact of variant histology and to predict its presence in patients with bladder cancer. A single-center cohort study included 459 patients who underwent radical cystectomy for urothelial carcinoma between 2017 and 2021. Patients were followed up with until July 2022. We compared clinical, laboratory, and histopathologic characteristics and the overall survival between patients with pure urothelial carcinoma and variant histologies. Our results showed that the patients with variant histology were older and preoperatively more frequently had hydronephrosis and higher values of leukocytes and neutrophils. Also, we found a significant association between variant histology and an advanced stage of tumor disease, the presence of lymphovascular invasion, positive surgical margins, and metastases in surgically resected lymph nodes. The number of neutrophils was identified as an independent preoperative predictor of the presence of variant histology after a radical cystectomy. The overall survival of the patients with variant histology was significantly lower compared to the patients with pure urothelial carcinoma. According to our results, the presence of variant histology represents a more aggressive form of the disease. Preoperative neutrophil counts may indicate the presence of variant histology of urothelial carcinoma in patients with bladder cancer.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/surgery , Carcinoma, Transitional Cell/surgery , Carcinoma, Transitional Cell/pathology , Cystectomy/methods , Cohort Studies , Retrospective Studies
3.
Urol Ann ; 15(2): 186-190, 2023.
Article in English | MEDLINE | ID: mdl-37304521

ABSTRACT

Objective: Mutation of p53 is detected in more than 50% of human cancers, expression of p53 has a potential prognostic value in patients with renal cell carcinoma (RCC). Survivin is a member of the inhibitor of apoptosis protein family, its overexpression is observed in many malignancies, including RCC. The aim of the study was to estimate a correlation between survivin and p53 expression in tumor samples and the histologic type of a tumor, tumor stage, tumor grade, and survival of patients. Materials and Methods: Tumor samples were collected from surgical specimens of 90 patients who underwent radical or partial nephrectomy for RCC between November 2017 and July 2020. Tumors were staged according to the UICC (The Union for International Cancer Control) TNM classification system and histopathologically graded according to Fuhrman nuclear grade system. Histopathological diagnosis was confirmed with standard light microscopic evaluation, using hematoxylin and eosin staining and standard p53 and survivin antibodies. Results: Positive p53 staining was observed in 36.7% of tumor specimens and 24.4% were survivin positive. There was a statistically significant correlation between p53 or survivin expression and histologic subtype of clear cell RCC as well as Type I and II of papillary RCC. There was a statistically significant correlation between p53 expression and tumor size, stage, and grade. The p53 or survivin expression was related to lower overall survival. Conclusion: The results of this study suggest that p53 overexpression and survivin positivity in RCC patients could be associated with poor prognosis. Thus, these proteins could be used as prognostic markers in RCC.

4.
Vaccines (Basel) ; 11(5)2023 Apr 28.
Article in English | MEDLINE | ID: mdl-37243015

ABSTRACT

At the time when mass COVID-19 vaccination began, providing appropriate vaccination advice to uro-oncology patients became a challenge. This was a single-center cross-sectional observational study aimed to investigate the rate of COVID-19 vaccination among uro-oncology patients receiving systemic therapy for metastatic renal cell carcinoma and metastatic castration-resistant prostate cancer. Furthermore, we aimed to assess patients' attitudes and identify factors influencing their decision to vaccinate against COVID-19. Data on patients' sociodemographic characteristics, vaccination status, and awareness and attitudes about COVID-19 vaccination were collected from questionnaires completed by the patients. A total of 173 patients were enrolled in this study, and 124 (71.7%) of them completed the COVID-19 vaccination. Significantly higher vaccination rates were found in male patients, and also in older patients, highly educated patients, and those who lived with one household member. Furthermore, we found significantly higher vaccination rates in patients who had consulted with doctors involved in their treatment, particularly with urologists. A significant association was observed between COVID-19 vaccination and doctor's advice, family member influence, and personal beliefs toward the vaccination. Our study showed multiple associations of patients' sociodemographic characteristics with vaccination rates. Furthermore, consultation with doctors who are particularly involved in oncology treatment and advice received from them were associated with significantly higher vaccination rates among uro-oncology patients.

5.
Medicina (Kaunas) ; 59(4)2023 Apr 19.
Article in English | MEDLINE | ID: mdl-37109749

ABSTRACT

Inflammatory myofibroblastic tumour (IMT) is a rare tumour with an intermediate biological behaviour. It usually occurs in children and adolescents, primarily in the abdomen or lungs. Histopathologically, IMT consists of spindle cells, i.e., myofibroblasts, and a variable inflammatory component. Localization in the urinary bladder is rare. We are presenting a rare case of IMT in the bladder in a middle-aged man treated by partial cystectomy. A 62-year-old man consulted a urologist because of haematuria and dysuric disturbances. A tumorous mass was detected by an ultrasound in the urinary bladder. CT urography described the tumorous mass at the dome of the urinary bladder measuring 2 × 5 cm. A smooth tumorous mass was cystoscopically observed at the dome of the urinary bladder. Transurethral resection of the bladder tumour was performed. Histopathological analysis of the specimen identified spindle cells with a mixed inflammatory infiltrate; immunohistochemical findings showed positivity for anaplastic lymphoma kinase (ALK), smooth muscle actin (SMA) and vimentin. A histopathological diagnosis of IMT was established. It was decided that the patient would undergo a partial cystectomy. A complete excision of the tumour from the dome of the urinary bladder with surrounding healthy tissue was performed. Histopathological and immunohistochemical findings of the sample confirmed the diagnosis of IMT, without the presence of the tumour at the surgical margins. The postoperative course went smoothly. IMT is a rare tumour in adults, especially localised in the urinary bladder. IMT of the urinary bladder is difficult to distinguish from urinary bladder malignancy both clinically and radiologically, as well as histopathologically. If the location and size of the tumour allow it, bladder-preserving surgeries such as partial cystectomy represent a reasonable modality of operative treatment.


Subject(s)
Urinary Bladder Neoplasms , Urinary Bladder , Adult , Male , Middle Aged , Child , Adolescent , Humans , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/surgery , Pelvis/pathology , Myofibroblasts , Biomarkers, Tumor/analysis
6.
Curr Oncol ; 30(3): 2582-2597, 2023 02 21.
Article in English | MEDLINE | ID: mdl-36975410

ABSTRACT

In recent years, the focus of numerous studies has been the predictive value of inflammatory and nutritional parameters in oncology patients. The aim of our study was to examine the relationship between the inflammatory and nutritional parameters and the histopathological characteristics of patients with bladder cancer. A retrospective study included 491 patients who underwent radical cystectomy for bladder cancer between 2017 and 2021. We calculated the preoperative values of the neutrophil-to-lymphocyte ratio (NLR), the derived neutrophil-to-lymphocyte ratio (dNLR), the systemic immune-inflammation index (SII), the systemic inflammatory response index (SIRI), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the prognostic nutritional index (PNI), and the geriatric nutritional risk index (GNRI). Statistically significant positive correlations were observed between NLR, dNLR, SII, SIRI, and PLR and the pathological stage of the tumor. We observed statistically significant inverse correlations for LMR, PNI, and GNRI with the tumor stage. SIRI was identified as an independent predictor of the presence of LVI. dNLR was identified as an independent predictor of positive surgical margins. GNRI was identified as an independent predictor of the presence of metastases in the lymph nodes. We noticed the predictive value of SIRI, dNLR, and GNRI in the pathology of bladder cancer patients.


Subject(s)
Nutrition Assessment , Urinary Bladder Neoplasms , Humans , Aged , Prognosis , Retrospective Studies , Cystectomy , Urinary Bladder Neoplasms/surgery , Inflammation
7.
BMC Womens Health ; 22(1): 458, 2022 11 18.
Article in English | MEDLINE | ID: mdl-36401287

ABSTRACT

BACKGROUND: Cervical cancer is often associated with malignant ureteral obstruction and consequent hydronephrosis. Hydronephrosis caused in this way can be resolved by placing ureteral stents or performing a percutaneous nephrostomy. Complications that may occur during the retrograde ureteral stent placement are usually mild, but serious complications such as stent migration into the cardiovascular system are also possible. Here we present an unusual case where a ureteral stent entered the abdominal aorta during the cystoscopic ureteral stenting, which was resolved by a cystoscopic stent removal kept in check by endovascular catheters. CASE PRESENTATIONS: The 48-year-old female patient was treated in the regional secondary healthcare facility due to bilateral hydronephrosis caused by cervical cancer. The patient had bilateral percutaneous nephrostomies and ureteral stents. Due to the calcification of the left ureteral stent, an urethrorenoscopy with lithotripsy of the calculus in the left ureter was performed in the regional secondary healthcare facility, and the ureteral stent was cystoscopically replaced. The control radiography of the urinary tract showed a misplacement of the left ureteral stent, and a computed tomography showed that the stent was located in the abdominal aorta. The patient was referred to the University Clinical Center of Serbia, where a ureteral stent was cystoscopically removed from the abdominal aorta under the control of endovascular catheters. The patient was in good general condition at all times, with no signs of bleeding, and she was discharged from the hospital on the fourth postoperative day. CONCLUSIONS: The migration of a ureteral stent into the abdominal aorta and the cardiovascular system in general is a rare type of ureteral stenting complication whose treatment requires a multidisciplinary approach. In order to prevent such complications, it is necessary to strictly adhere to the indications for the ureteral stent placement in the case of malignant ureteral obstruction. Also, this procedure should be performed according to the current guidelines and controlled by an X-ray or ultrasound.


Subject(s)
Hydronephrosis , Ureter , Ureteral Obstruction , Uterine Cervical Neoplasms , Female , Humans , Middle Aged , Ureteral Obstruction/complications , Ureteral Obstruction/surgery , Aorta, Abdominal/diagnostic imaging , Uterine Cervical Neoplasms/complications , Hydronephrosis/complications , Hydronephrosis/surgery , Stents/adverse effects
8.
Medicina (Kaunas) ; 58(10)2022 Oct 09.
Article in English | MEDLINE | ID: mdl-36295574

ABSTRACT

Background and Objectives: Mounting evidence implicates oxidative damage in prostate carcinogenesis, contributing to modifications of macromolecules that drive cellular malignant transformation. Functional single-nucleotide polymorphisms (SNPs) of enzymes involved in redox homeostasis can disrupt pro-oxidant-antioxidant balance, leading to accumulation of reactive oxygen species and oxidative damage. We investigated the potential role of genetic polymorphisms of antioxidant enzymes glutathione peroxidase 1 (GPX1 rs1050450) and superoxide dismutase 2 (SOD2 rs4880) and regulatory antioxidant protein nuclear factor erythroid 2-related factor 2 (Nrf2 rs6721961) in the susceptibility to prostate cancer development (PC) and prognosis. Materials and Methods: We conducted a case-control study consisting of 235 patients with PC and 240 controls. Gene polymorphisms were determined by quantitative polymerase chain reaction (qPCR) and polymerase chain reaction with confronting two-pair primers (PCR-CTTP) methods. Multiple risk models were composed to inspect the separate and mutual effect of multiple genes and in combination with acquired contributory factors on the risk of PC development. Results: Independently, carriers of at least one SOD2*C allele had increased risk of PC development, which was significantly further amplified in advanced statistical models. When tested in combination, individuals with both SOD2*C allele and Nrf2*C/C genotype were also at increased risk of PC development, which was augmented when combined with acquired contributory factors. During the mean 75 ± 25 months of follow-up, investigated gene polymorphisms did not affect overall survival. Conclusion: Our results suggest that these gene polymorphisms could be used as risk biomarkers of PC evolution.


Subject(s)
Antioxidants , Prostatic Neoplasms , Humans , Male , Biomarkers , Case-Control Studies , Genetic Predisposition to Disease , Genotype , NF-E2-Related Factor 2/genetics , Polymorphism, Single Nucleotide/genetics , Prostatic Neoplasms/genetics , Reactive Oxygen Species , Glutathione Peroxidase GPX1
9.
J Pers Med ; 12(5)2022 May 20.
Article in English | MEDLINE | ID: mdl-35629255

ABSTRACT

Sustained and dysregulated inflammation, concurrent tumor-induced immune suppression, and oxidative stress are profoundly involved in cancer initiation, presentation, and perpetuation. Within this prospective study, we simultaneously analyzed the preoperative indices of systemic inflammatory response and the representative byproducts of oxidative DNA, protein, and lipid damage with the aim of evaluating their clinical relevance among patients diagnosed with testicular germ-cell tumors (GCT). In the analytical cohort (n = 88, median age 34 years), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and C-reactive protein (CRP) were significantly altered in patients with a higher tumor stage (p < 0.05). Highly suggestive correlations were found between NLR, dNLR, and SII and modified nucleoside 8-OHdG. CRP and albumin-to-globulin ratio (AGR) significantly correlated with thiols group level and maximal tumor dimension (p < 0.05). Based on receiver operating characteristic (ROC) curve analyses, all the evaluated pre-orchiectomy inflammation markers demonstrated strong performance in predicting metastatic disease; optimal cut-off points were determined for each indicator. Although further large-scale studies are warranted, inflammatory and redox indices may both complement the established tumor markers and standard clinicopathological prognostic variables and contribute to enhanced personalized risk-assessment among testicular GCT patients.

10.
Front Mol Biosci ; 8: 620690, 2021.
Article in English | MEDLINE | ID: mdl-33937322

ABSTRACT

Considering the pleiotropic roles of glutathione transferase (GST) omega class members in redox homeostasis, we hypothesized that polymorphisms in GSTO1 and GSTO2 might contribute to prostate cancer (PC) development and progression. Therefore, we performed a comprehensive analysis of GSTO1 and GSTO2 SNPs' role in susceptibility to PC, as well as whether they might serve as prognostic biomarkers independently or in conjunction with other common GST polymorphisms (GSTM1, GSTT1, and GSTP1). Genotyping was performed in 237 PC cases and 236 age-matched controls by multiplex PCR for deletion of GST polymorphisms and quantitative PCR for SNPs. The results of this study, for the first time, demonstrated that homozygous carriers of both GSTO1*A/A and GSTO2*G/G variant genotypes are at increased risk of PC. This was further confirmed by haplotype analysis, which showed that H2 comprising both GSTO1*A and GSTO2*G variant alleles represented a high-risk combination. However, the prognostic relevance of polymorphisms in GST omega genes was not found in our cohort of PC patients. Analysis of the role of other investigated GST polymorphisms (GSTM1, GSTT1, and GSTP1) in terms of PC prognosis has shown shorter survival in carriers of GSTP1*T/T (rs1138272) genotype than in those carrying at least one referent allele. In addition, the presence of GSTP1*T/T genotype independently predicted a four-fold higher risk of overall mortality among PC patients. This study demonstrated a significant prognostic role of GST polymorphism in PC.

11.
Urol Oncol ; 39(11): 786.e9-786.e16, 2021 11.
Article in English | MEDLINE | ID: mdl-34006438

ABSTRACT

BACKGROUND: To identify the prognostic impact of residence in a BEN-endemic area and gender on upper tract urothelial carcinoma (UTUC) outcomes in Serbian patients treated with radical nephroureterectomy (RNU). METHODS: The study included 334 consecutive patients with UTUC. Patients with permanent residence in Balkan endemic nephropathy (BEN) or non-endemic areas from their birth to the end of follow-up were included in the analysis. Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates. RESULTS: Female patients were more likely to have preoperative pyuria (P = 0.01), tumor multifocality was significantly associated with the female gender (P = 0.003). Gender was not associated with pathologic stage and grade, lymph node metastasis, lymphovascular invasion, adjuvant chemotherapy, bladder cancer history, tumor size, distribution of tumor location, preoperative anemia and demographic characteristics. A total of 107 cases recurred, with a median time to bladder recurrence of 24.5 months. History of bladder tumor (HR, 1.98; P = 0.005), tumor multifocality (HR, 3.80; P < 0.001) and residence in a BEN-endemic area (HR, 1.81; P = 0.01) were independently associated with bladder cancer recurrence. The 5-year bladder cancer RFS for the patients from areas of BEN was 77.8 % and for the patients from non-BEN areas was 64.7 %. The 5-year CSS for the men was 66.2% when compared to 66.6% for the women (P = 0.55). CONCLUSIONS: Residence in a BEN-endemic area represents an independent predictor of bladder cancer recurrence in patients who underwent RNU. Gender cannot be used to predict outcomes in a single-centre series of consecutive patients who were treated with RNU for UTUC.


Subject(s)
Balkan Nephropathy/etiology , Nephroureterectomy/adverse effects , Urinary Bladder Neoplasms/complications , Urinary Bladder Neoplasms/surgery , Aged , Balkan Nephropathy/physiopathology , Cohort Studies , Female , Humans , Male , Nephroureterectomy/methods , Prognosis , Urinary Bladder Neoplasms/pathology
12.
Curr Probl Cancer ; 45(6): 100747, 2021 12.
Article in English | MEDLINE | ID: mdl-33883080

ABSTRACT

To identify the prognostic impact of tumor multifocality on upper tract urothelial carcinoma (UTUC) outcomes in patients treated with radical nephroureterectomy (RNU). Study included 342 consecutive patients with UTUC. Tumor multifocality was defined as the synchronous presence of 2 or more pathologically confirmed tumors in any upper urinary tract location. Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates. Tumor multifocality was significantly associated with a history of previous non-muscle invasive bladder cancer (P < 0.001), tumor size (P < 0.001), gender (P = 0.009), tumor location (P = 0.005), and anemia (P = 0.01). The Kaplan-Meier method showed that tumor multifocality was significantly associated with worse recurrence-free survival (P < 0.001, log rank). Using multivariate analysis, tumor multifocality (HR, 2.86; 95% CI, 2.06 - 3.99; P < 0.001) was independently associated with recurrence free survival. During the follow-up, a total of 128 (37.4%) patients died, including 92 (28.2%) from UTUC. However, tumor multifocality was not associated with CSS (HR, 1.29; 95% CI, 0.89 - 1.96; P = 0.21) in univariate Cox regression analyses. Tumor stage (HR, 11.1; 95% CI, 3.64 - 33.8; P < 0.001), lymph node status (HR, 2.04, 95% CI, 1.05 - 3.94; P = 0.03) and preoperative anemia (HR, 3.50, 95% CI, 2.02 - 6.08; P < 0.001) were the only independent predictors associated with worse cancer-specific survival. Tumor multifocality is an independent prognostic factor of disease recurrence in patients treated with RNU for UTUC. Tumor multifocality is unable to predict cancer specific survival in a single-center series of consecutive patients who were treated with RNU.


Subject(s)
Urologic Neoplasms/mortality , Urologic Neoplasms/pathology , Adult , Aged , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Grading , Nephroureterectomy , Prognosis , Serbia/epidemiology , Survival Rate , Urologic Neoplasms/surgery
13.
Medicina (Kaunas) ; 56(3)2020 Mar 13.
Article in English | MEDLINE | ID: mdl-32183092

ABSTRACT

Background and Objectives: One of the most frequent genetic alterations reported to date in prostate cancer (PC) is aberrant methylation of glutathione transferase P1 (GSTP1). Taking into consideration the involvement of oxidative stress in PC pathogenesis and recent advances in scientific understanding of the role of GSTP1*Ala114Val rs1138272 polymorphism in carcinogenesis, we hypothesized that this single-nucleotide polymorphism (SNP) influences the risk of PC independently of, or in combination with, other GST polymorphisms, including GSTP1*IIe105Val rs1695 or GSTM1 and GSTT1 deletion polymorphisms. Materials and Methods: Genotyping was performed in 237 PC cases and in 236 age-matched controls by multiplex polymerase chain reaction (PCR) for deletion of GST polymorphisms and by quantitative PCR for SNPs. Results: We found that carriers of either GSTP1*Val (rs1138272) or GSTP1*Val (rs1695) variant alleles had a PC risk compared to individuals with both referent alleles (OR = 4.93, 95%CI: 2.89-8.40, p < 0.001 and OR = 1.8, 95%CI: 1.19-2.73, p = 0.006, respectively). Additionally, in a haplotype analysis we found that individuals with GSTP1*C haplotype, represented by both variant alleles (GSTP1*Val rs1695 + GSTP1*Val rs1138272), had a 5.46 times higher risk of PC development compared to individuals with the most frequent haplotype (95%CI = 2.56-11.65, p < 0.001), suggesting a potential role of those variants in PC susceptibility. A regression analysis on the number of risk-associated alleles per individual (GSTM1*active, GSTT1*null, GSTP1*Val rs1695 and GSTP1*Val rs1138272) showed a significant increase in the risk of developing PC, from 3.65-fold in carriers of two risk alleles (95%CI = 1.55-8.61, p = 0.003) to an approximately 12-fold increase in carriers of all four risk alleles (95%CI = 3.05-44.93, p < 0.001). Conclusion: Prostate cancer may be influenced by multiple glutathione transferase (GST) polymorphic genes, especially GSTP1, highlighting the role of gene-gene interactions in human susceptibility to this cancer.


Subject(s)
Glutathione S-Transferase pi/analysis , Polymorphism, Genetic/genetics , Prostatic Neoplasms/genetics , Aged , Case-Control Studies , Genetic Predisposition to Disease , Glutathione S-Transferase pi/blood , Humans , Male , Middle Aged , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/physiopathology , Risk Adjustment/methods , Serbia
14.
Acta Chir Iugosl ; 61(1): 21-4, 2014.
Article in English | MEDLINE | ID: mdl-25782220

ABSTRACT

OBJECTIVE: Our objective is to evaluate the efficacy, safety and 12 month outcome of a 980 nm diode laser with Twister fiber in the treatment of benign prostatic enlargement. MATERIALS AND METHODS: Between February 2011 and January 2013, 73 patients with benign pros- tatic enlargement had undergone diode laser vaporization of prostate at our institution. The fol- lowing parameters were assessed at baseline, and after a follow-up period of 3 and 12 months: International Prostate Symptom Score, peak urinary flow rate, post-void residual urine volume, and quality of life score. RESULTS: The procedure was completed successfully in all patients with no intraoperative complications. At 12 months postoperatively the percentage improvements in IPSS was -69.09%, Qmax +197%, PVR -88.54%, and QoL -68.29%. CONCLUSION: Diode laser vaporization of prostate is safe and effective method for treatment of benign prostatic enlargement.


Subject(s)
Laser Therapy , Postoperative Complications , Prostatic Hyperplasia/surgery , Quality of Life , Aged , Follow-Up Studies , Humans , Laser Therapy/adverse effects , Laser Therapy/instrumentation , Laser Therapy/methods , Lasers, Semiconductor/therapeutic use , Male , Postoperative Complications/diagnosis , Postoperative Complications/physiopathology , Postoperative Complications/psychology , Prostate , Prostatic Hyperplasia/pathology , Serbia , Treatment Outcome , Urodynamics
15.
Redox Rep ; 18(1): 1-7, 2013.
Article in English | MEDLINE | ID: mdl-23394311

ABSTRACT

OBJECTIVES: To examine the association between gene variants of the detoxifying and antioxidant enzymes glutathione transferase M1 (GSTM1) and glutathione transferase A1 (GSTA1) and the extent of oxidative damage in patients with transitional cell carcinoma (TCC) of the urinary bladder. METHODS: GSTM1 deletion polymorphism was identified by polymerase chain reaction, and the restriction fragment length polymorphism method was used for the single nucleotide polymorphism of GSTA1. Enzyme immunoassay was used to determine markers of DNA (8-hydroxy-2'-deoxyguanosine, 8-OHdG) and lipid (8-epiprostaglandin F2α) oxidative damage in the urine of 80 TCC patients and 60 age-matched controls. RESULTS: Urinary 8-OHdG and 8-epi-prostaglandin F2α concentrations in TCC patients were significantly higher than in controls (P=0.043 and 0.001, respectively). GSTM1 and GSTA1 polymorphisms influence vulnerability to both DNA and lipid oxidation, with the GSTM1-null gene variant having a more pronounced effect. A significant effect of combined GSTM1 and GSTA1 genotypes on the extent of oxidative damage was found only for 8-OHdG (P=0.018). In addition, TCC patients with the most malignant tumors exhibited significantly higher frequencies of GSTM1-null or GSTA1-low activity genotypes, associated with a twofold increase in urinary 8-OHdG concentration (P=0.044). CONCLUSIONS: Our results suggest that absent GSTM1 or reduced GSTA1 antioxidant activity may increase the accumulation of oxidative DNA damage, thereby contributing to the malignant potential of TCC.


Subject(s)
Carcinoma, Transitional Cell/genetics , Glutathione Transferase/genetics , Oxidative Stress , Urinary Bladder Neoplasms/genetics , 8-Hydroxy-2'-Deoxyguanosine , Aged , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Carcinoma, Transitional Cell/metabolism , Case-Control Studies , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/urine , Dinoprost/analogs & derivatives , Dinoprost/urine , Female , Gene Frequency , Genetic Association Studies , Genotype , Heterozygote , Humans , Immunoenzyme Techniques , Lipid Peroxidation , Male , Middle Aged , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Urinary Bladder Neoplasms/metabolism
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