In recent years, the progress of science and medicine greatly has influenced human life span and health. However, lifestyle habits, like physical activity, smoking cessation, moderate alcohol ...consumption, diet, and maintaining a normal body weight represent measures that greatly reduce the risk of various diseases. The type of diet is very important for disease development. Numerous epidemiological clinical data confirm that longevity is linked to predominantly plant-based diets and it is related to a long life; whereas the western diet, rich in red meat and fats, increases the risk of oxidative stress and thus the risk of developing various diseases and pre-aging. This review is focused on the bioavailability of polyphenols and the use of polyphenols for the prevention of prostate diseases. Special focus in this paper is placed on the isoflavonoids and flavan-3-ols, subgroups of polyphenols, and their protective effects against the development of prostate diseases.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The aim of this study was to evaluate specific glutathione S-transferase (GST) gene variants as determinants of risk in patients with clear cell renal cell carcinoma (cRCC), independently or ...simultaneously with established RCC risk factors, as well as to discern whether phenotype changes reflect genotype-associated risk. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 cRCC patients and 274 matched controls. Benzo(a)pyrene diolepoxide (BPDE)-DNA adducts were determined in DNA samples obtained from cRCC patients by ELISA method. Significant association between GST genotype and risk of cRCC development was found for the GSTM1-null and GSTP1-variant genotype (p = 0.02 and p<0.001, respectively). Furthermore, 22% of all recruited cRCC patients were carriers of combined GSTM1-null, GSTT1-active, GSTA1-low activity and GSTP1-variant genotype, exhibiting 9.32-fold elevated cRCC risk compared to the reference genotype combination (p = 0.04). Significant association between GST genotype and cRCC risk in smokers was found only for the GSTP1 genotype, while GSTM1-null/GSTP1-variant/GSTA1 low-activity genotype combination was present in 94% of smokers with cRCC, increasing the risk of cRCC up to 7.57 (p = 0.02). Furthermore, cRCC smokers with GSTM1-null genotype had significantly higher concentration of BPDE-DNA adducts in comparison with GSTM1-active cRCC smokers (p = 0.05). GSTM1, GSTT1, GSTA1 and GSTP1 polymorphisms might be associated with the risk of cRCC, with special emphasis on GSTM1-null and GSTP1-variant genotypes. Combined GSTM1-null, GSTT1-active, GSTA1 low activity and GSTP1-variant genotypes might be considered as "risk-carrying genotype combination" in cRCC.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The emerging new standard of care for metastatic clear cell renal carcinoma (mRCC) becomes a challenge when access to new drugs is limited. In Serbia, sunitinib and pazopanib are the only ...available first-line therapies. The second-line treatment for mRCC has never been and is still not available. We aimed to assess overall survival (OS) in patients with mRCC who received first-line sunitinib or pazopanib when access to second-line treatment was not available.
Methods
This retrospective observational study analyzed data from a nationally representative cohort of 759 patients who started on first-line sunitinib or pazopanib between 1 January 2012 and 30 June 2019, in 4 centers in Serbia. The data cut-off date was 31 December 2019. Key eligibility criteria were clear cell RCC histology, measurable metastatic disease, performance status 0 or 1, and the Memorial Sloan Kettering Cancer Center favorable or intermediate prognosis. The primary outcome was OS from the start of first-line treatment to death or data cut-off date.
Results
The study population included 759 patients with mRCC who started with first-line sunitinib (n = 673; 88.7%) or pazopanib (n = 86; 11.3%). Overall, the mean age was 61.0 ± 9.7 years at treatment baseline, and 547 (72%) were men. mRCC was primarily diagnosed in 230 (30%) patients, and most of them underwent cytoreductive nephrectomy prior to systemic therapy (n = 181 79%). Additional treatment of metastases prior to and/or during treatment was used in 169 patients (22.3%). Grade 3 and 4 adverse events occurred in 168 (22.1%) and 47 patients (6.2%), respectively, and treatment was permanently stopped because of toxicity in 41 (6.9%). The OS was calculated from the start of first-line treatment, and the median follow-up was 14 months (range, 0–97). The median OS in the entire cohort was 17 months (95% CI, 14.6–19.4).
Conclusions
With only available sunitinib and pazopanib in first-line treatment, modest improvements are seen in the overall survival of patients with mRCC in real world clinical practice. In circumstances of limited availability of cancer medicines, our results can contribute to accelerating patient access to novel cancer therapies that have been shown to prolong survival in mRCC.
Glutathione S-transferases (GSTs), a superfamily of multifunctional enzymes, play an important role in the onset and progression of renal cell carcinoma (RCC). However, novel GST omega class (GSTO), ...consisting of GSTO1-1 and GSTO2-2 isoenzymes, has not been studied in RCC yet. Two coding single nucleotide polymorphisms (SNPs) supposedly affect their functions: GSTO1*C419A (rs4925) causing alanine to aspartate substitution (*A140D) and GSTO2*A424G (rs156697) causing asparagine to aspartate substitution (*N142D), and have been associated with several neurodegenerative diseases and cancers. Functional relevance of yet another GSTO2 polymorphism, identified at the 5′ untranslated (5′UTR) gene region (GSTO2*A183G, rs2297235), has not been clearly discerned so far. Therefore, we aimed to assess the effect of specific GSTO1 and GSTO2 gene variants, independently and in interaction with established risk factors (smoking, obesity and hypertension) on the risk for the most aggressive RCC subtype, the clear cell RCC (ccRCC). Genotyping was performed in 239 ccRCC patients and 350 matched controls, while plasma levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, were determined by ELISA. As a result, combined effect of all three variant genotypes exhibited almost 3-fold risk of RCC development. Additionally, this association was confirmed at the haplotype level variant GSTO1*A/GSTO2*G (rs156697)/GSTO2*G (rs2297235) haplotype, suggesting a potential role of those variants in propensity to RCC. Regarding the gene-environment interactions, variant GSTO2*G (rs156697) homozygous smokers are at higher ccRCC risk. Association in terms of oxidative DNA damage was found for GSTO2 polymorphism in 5′UTR and 8-OHdG. In conclusion, the concomitance of GSTO polymorphisms may influence ccRCC risk.
Background
There is still no consensus regarding intraprostatic androgen levels and the accumulation of androgens in the hyperplastic prostatic tissue. The current opinion is that intraprostatic ...dihydrotestosterone (DHT) concentrations are maintained but not elevated in benign prostatic hyperplasia (BPH), while there is no similar data concerning intraprostatic testosterone (T).
Methods
Tissue T (tT) and tissue DHT (tDHT) concentration were determined in 93 patients scheduled for initial prostate biopsy. The criteria for biopsy were abnormal DRE and/or PSA > 4 ng/mL. Total prostate volume (TPV) was determined by transrectal ultrasound (TRUS). During TRUS‐ guided prostate biopsy, 10‐12 samples were collected from the peripheral zone (PZ) and two additional samples were collected from the transition zone (TZ). The samples from the TZ were immediately frozen in liquid nitrogen at −70°C, and transported for tissue androgen determination, using liquid chromatography mass spectrometry (LC‐MS).
Results
Pathological analysis revealed that prostate cancer (PCa) was present in 45 and absent in 48 patients. In the whole group, there were 42 men with small prostate (TPV < 30 mL) and 51 with enlarged prostate (TPV ≥ 31 mL). The overall average tT level was 0.79 ± 0.66 ng/g, while the average tDHT level was 10.27 ± 7.15 ng/g. There were no differences in tT and tDHT level in prostates with and without PCa. However, tT and tDHT levels were significantly higher in larger, than in smaller prostates (tT: 1.05 ± 0.75 and 0.46 ± 0.29 ng/g, and tDHT: 15.0 ± 6.09 and 4.51 ± 2.75 ng/g, respectively). There were strong correlations between tT and TPV (r = 0.71), and tDHT and TPV (r = 0.74).
Conclusions
The present study confirmed that both T and DHT accumulated in the stroma of enlarged prostates; the degree of accumulation correlated with prostate volume.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
: One of the most frequent genetic alterations reported to date in prostate cancer (PC) is aberrant methylation of glutathione transferase P1 (
). Taking into consideration the involvement of ...oxidative stress in PC pathogenesis and recent advances in scientific understanding of the role of
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
IIe105Val rs1695 or
and
deletion polymorphisms.
: 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.
: We found that carriers of either
*Val (rs1138272) or
*Val (rs1695) variant alleles had a PC risk compared to individuals with both referent alleles (OR = 4.93, 95%CI: 2.89-8.40,
< 0.001 and OR = 1.8, 95%CI: 1.19-2.73,
= 0.006, respectively). Additionally, in a haplotype analysis we found that individuals with
haplotype, represented by both variant alleles
, had a 5.46 times higher risk of PC development compared to individuals with the most frequent haplotype (95%CI = 2.56-11.65,
< 0.001), suggesting a potential role of those variants in PC susceptibility. A regression analysis on the number of risk-associated alleles per individual (
and
) 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,
= 0.003) to an approximately 12-fold increase in carriers of all four risk alleles (95%CI = 3.05-44.93,
< 0.001).
: Prostate cancer may be influenced by multiple glutathione transferase (GST) polymorphic genes, especially
, highlighting the role of gene-gene interactions in human susceptibility to this cancer.
Abstract Purpose Owing to dual functionality of cytosolic glutathione S-transferases (GSTs), they might affect both the development and the progression of renal cell carcinoma (RCC). However, the ...data on the prognostic value of GST polymorphism in patients with RCC are scarce. Hence, we evaluated the effect of GST gene variants on both the risk of RCC development and the postoperative prognosis in patients with clear cell RCC (ccRCC). Methods GST genotypes were determined in 305 patients with RCC and 326 matched controls, whereas the overall survival was evaluated in patients with ccRCC only. The presence of GSTM1:ASK1 protein-protein interaction in ccRCC tissue samples was analyzed by methods of immunoprecipitation and immunoblot. Results We noted an increased risk of RCC development in carriers of GSTM1-null and GSTP1-variant genotype ( P <0.05). On the contrary, survival analysis indicated shorter overall survival for patients with ccRCC with GSTM1-active genotype ( P = 0.026). Furthermore, patients with ccRCC with GSTM1-active genotype had significantly higher hazard ratio ( P <0.05), in analyzed regression models, compared with the carriers of GSTM1-null genotype. Finally, the presence of GSTM1:ASK1 protein-protein interaction was found in all RCC tissue samples studied. Conclusions Carriers of GSTM1-null and GSTP1-variant genotypes are in increased risk of RCC development. On the contrary, GSTM1-null genotype is associated with favorable postoperative prognosis in ccRCC. The possible molecular mechanism underlying the role of GSTM1 protein in RCC progression might be the presence of GSTM1:ASK1 protein-protein interaction. Hence, determination of GSTM1 -genotype might serve as a valuable indicator in both RCC risk assessment and postoperative prognosis.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background: Bladder neck preservation (BNP) has been adopted in open (ORP), laparoscopic (LRP), and robot-assisted radical prostatectomy (RARP). However, there are concerns that this technique can ...compromise oncological outcome and increase positive surgical margins (PSM). The aim was to evaluate the outcome of BNP, focusing on surgical and pathological outcomes, as well as biochemical recurrence (BCR). Methods: We prospectively collected demographic and clinical data from 170 consecutive patients who underwent ORP and LRP between 2014 and 2020. ORP was performed in 63 patients, and the rest underwent LRP. BNP was performed in 85 patients. Results: PSM were found in 24.7% of patients. Of patients with BNP, 22.4% had PSM. There was no significant statistical difference between patients with or without BNP in the form of PSM. Base-positive margins were detected in 9.4% of patients with BNP and in 5.9% of patients without BNP with no statistical significance. Bioptic Gleason score, clinical stage, and preoperative PSA were statistically significantly correlated with PSM. BCR was more common in patients without BNP (23.5%) vs. non-BNP (21.2%). The only statistically significant predictor of BCR was PSM. Conclusion: This study suggests that BNP in RP is not associated with an increased level of PSM. Preoperative PSA, bioptic Gleason score, and clinical T stage of disease were identified as predictors of PSM occurrence.
Acute renal failure (ARF) represents a severe complication of malignancies, that causes significant morbidity and mortality. ARF is a common part of multiple organ dysfunction in critically ill ...patients with cancer with reported mortality rates from 72% to 85% in patients who need renal replacement therapy. The pathways leading to ARF in cancer patients are common to the development of ARF in other conditions. However, certain factors leading to the development of ARF may be associated to the tumor or to the tumor therapy. The purpose of this review is to give specific aspects of renal disease in critically ill cancer patients (CICPs), to overview the causes of ARF in CICPs and to describe recent progress in the management of these complications, including treatment toxicity and bone marrow transplantation (BMT). The prevention of ARF is obligatory and therefore the possible treatments of ARF in CICPs are also discussed.
Objective Injuries of the ureter or bladder or development of vesicovaginal and ureterovaginal fistulas are the most serious complications in gynecological surgery. Study Design This study included ...536 women who underwent radical hysterectomy because of invasive cancer of the cervix uteri. Results During the surgery the ureter was injured in 1.32% of cases, whereas the percentage of bladder injuries was 1.49. In the early postoperative period vesicovaginal or ureterovaginal fistulas appeared in 2.61% and 2.43% of cases, respectively. Conclusion The stage of the disease, obesity, diabetes, and postoperative surgical infection acted as predisposing factors of the urinary tract complications.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
PDF
