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Immune parameters may be altered in urolithiasis (UL) patients after coronavirus infection (COVID-19).

The present study was carried out in order to examine molecular alterations of extracellular matrix (ECM), associated with cell–cell communication in conventional (clear-cell) renal cell carcinomas (cRCCs) influenced by persistent long-term, low-dose ionizing radiation (IR) exposure to patients living more than 19 years after the Chernobyl accident in Cesium 137 (137Cs)-contaminated areas of Ukraine. The ECM major components such as fibronectin, laminin, E-cadherin/β-catenin complexes and p53 tumor suppressor gene protein, and transforming growth factor beta 1 (TGF-β1) were immunohistochemically (IHC) evaluated in cRCCs from 59 Ukrainian patients, which represented 18 patients living in non-contaminated areas and 41 patients from 137Cs-contaminated areas. In contrast, a control group of 19 Spanish patients with analogue tumors were also investigated. For IHC evaluation, a tissue microarray technique was used. Decrease or loss and abnormal distribution of fibronectin, laminin, E-cadherin/β-catenin complexes accompanied by elevated levels of p53 and TGF-β1 were detected in the Ukrainian cRCCs from 137Cs-contaminated areas with statistically significant differences. Thus, our study suggests that chronic long-term, low-dose IR exposure might result in global remodeling of ECM components of the cRCCs with disruption in peri-epithelial stroma and epithelial basement membranes.The present study was carried out in order to examine molecular alterations of extracellular matrix (ECM), associated with cell–cell communication in conventional (clear-cell) renal cell carcinomas (cRCCs) influenced by persistent long-term, low-dose ionizing radiation (IR) exposure to patients living more than 19 years after the Chernobyl accident in Cesium 137 (137Cs)-contaminated areas of Ukraine. The ECM major components such as fibronectin, laminin, E-cadherin/β-catenin complexes and p53 tumor suppressor gene protein, and transforming growth factor beta 1 (TGF-β1) were immunohistochemically (IHC) evaluated in cRCCs from 59 Ukrainian patients, which represented 18 patients living in non-contaminated areas and 41 patients from 137Cs-contaminated areas. In contrast, a control group of 19 Spanish patients with analogue tumors were also investigated. For IHC evaluation, a tissue microarray technique was used. Decrease or loss and abnormal distribution of fibronectin, laminin, E-cadherin/β-catenin complexes accompanied by elevated levels of p53 and TGF-β1 were detected in the Ukrainian cRCCs from 137Cs-contaminated areas with statistically significant differences. Thus, our study suggests that chronic long-term, low-dose IR exposure might result in global remodeling of ECM components of the cRCCs with disruption in peri-epithelial stroma and epithelial basement membranes.

Previous studies have shown that during the period subsequent to the Chernobyl accident, increases in morbidity, aggressivity and proliferative activity of renal-cell carcinomas (RCCs) in Ukrainian patients were recognized. The present paper describes the molecular alterations of those tumor suppressor genes located on chromosome 9p21 ( INK4a/ARF locus and p15 INK4B) in 26 primary renal-cell epithelial tumors from patients with different degrees of radiation exposure after the Chernobyl accident in Ukraine. Radiometric measurement of Cesium 137 ( 137Cs) was conducted with 1-day urine from all patients before surgery. Our results demonstrate that RCCs from patients living in the radio-contaminated areas showed aberrant hypermethylation of p14 ARF and p16 INK4A genes, associated with increased p38MAPK, p14 ARF, mdm2, cyclinD1 and Ki67 protein expression levels. Present findings show the possibility that chronic long-term low-dose radiation activates the INK4a/ARF locus, targeted by activation of the p38MAPK cascade. These actions could lead to disruptions and loss of cell cycle checkpoints and, thereby, to cellular transformation.

The incidence of urinary bladder cancer in the Ukraine increased from 26.2 to 43.3 per 100 000 population between 1986 and 2001 after the Chernobyl accident. The present study was conducted to evaluate the development of radiation‐dependent lesions in the urinary bladders of people living in cesium 137 (137Cs) radio‐contaminated areas of the Ukraine. Bladder urothelial biopsies from 159 male and 5 female patients were subjected to histological examination and immunohistochemical study of p38 mitogen‐acti‐vated protein kinase (MAPK), as well as the p50 and p65 subunits of nuclear factor kappa B (NF‐kB). A pattern of chronic proliferative atypical cystitis accompanied with large areas of sclerosis of connective tissue in the lamina propria was commonly observed in all cases. Interestingly, these lesions were associated with a dramatic increase in the incidences of dysplasia/carcinoma in situ, and, moreover, small urothelial carcinomas were incidentally detected. We defined the overall condition as “Chernobyl cystitis.'’Greatly elevated levels of p38, p65 and p50 expression in the urothelium were evident and the patients showed increased 137Cs in urine. The data support conclusions from our previous studies of a critical role for increased oxidative stress in generation of urinary bladder urothelial lesions in individuals chronically exposed to low‐dose 137Cs radiation. Alterations in the p38 MARK cascade and accumulation of NF‐kB subunits could be crucial early molecular events in the pathogenesis of Chernobyl cystitis. (Cancer Sci 2003; 94: 328–333)

Our study was undertaken to better understand the role of G1/S transition abnormalities in the malignant progression of renal cell carcinomas (RCCs), exposed to long-term low doses of ionizing radiation (IR), from patients living in radiocontaminated areas of the Ukraine after the Chernobyl accident. We studied p16INK4Aand p15INK4Bgene alteration in association with oxidative stress markers, including inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). We analyzed 88 samples collected from 22 patients with RCCs and with different exposure to IR. Homozygous deletion of the p16INK4Aand p15INK4Bgenes, as well as hypermethylation of the 5CpG island in the promoter region of the same genes, were analyzed by differential PCR and Methylation-Specific PCR respectively, in association with histopathology and immunohistochemical analysis of p16INK4Aand p15INK4Bproteins. COX2 and iNOS expression in the same tumors were likewise analyzed. Aberrant hypermethylation was observed in 7 (32) and 5 (23) cases accompanied, by immunohistochemical loss of expression for p16INK4Aand p15INK4Bgenes respectively, in both high stage and grade tumors from patients living in radiocontaminated areas, this being especially outstanding for the p16INK4Agene. An association with COX2 and less iNOS overexpression in the same tumors was observed. Our data suggest that inactivation of p16INK4Agene, but not p15INK4B, induced by increased oxidative stress generated by persistent chronic exposure to IR, could be one of the major pathways responsible for RCCs malignant progression.

We determined whether base and nucleotide excision repair is activated in bladder urothelium by chronic persistent low doses of ionizing radiation in male patients with benign prostate hyperplasia and females with chronic cystitis living more than 15 years in 137Cs contaminated areas after the Chernobyl accident in Ukraine.

After the Chernobyl accident, the morbidity of renal-cell carcinomas in Ukraine increased gradually from 4.7 to 7.5 per 100,000 of the total population. Cesium 137 (¹³⁷Cs) is responsible for 80-90% of the internal radioactivity in people living in radiocontaminated areas of Ukraine, and 90% of ¹³⁷Cs is eliminated through the kidneys. Histological and immunohistochemical study of proliferating cell nuclear antigen (PCNA) and K-ras protein was performed in peritumoral kidney tissues of 167 Ukrainian patients (groups I-III, according to varying degrees of internal exposure to radiation), and of 85 analog Spanish patients, as a control group. Our data showed in the majority of Ukrainian patients a radiation sclerosing proliferative atypical nephropathy (RSPAN) in association with an increase in the incidences of tubular epithelial nuclear atypia and carcinoma in situ (CIS). Areas of epithelial nuclear atypia and CIS of the cortex and medulla showed significant PCNA expression with means of extent as 12, 14, and 15% of stained nuclei in groups I, II, and III respectively. K-ras expression of the same areas occurred in 67, 87, and 85% of cases in groups I, II, and III respectively. The present study points to a strong relationship between the long term of low-dose radiation exposure of the Ukrainian population and the development of RSPAN as a possible precursor of malignancy. In addition, it confirms the possible initiator, promoter, or progressor role of chronic low-level radiation of renal human carcinogenesis in Ukraine.

During the 13-year period subsequent to the Chernobyl accident, the morbidity of malignant renal tumors in Ukraine has increased from 4.7 to 7.5 per 100,000 of total population. Cesium 137 (¹³⁷Cs) accounts for 90% of the incorporated radioactivity in the Ukrainian population, which has been exposed to long-term, low dose ionizing radiation and 90% of the more labile pool of (¹³⁷Cs) is excreted via kidneys. The present study was performed to evaluate the histopathological features and the immunohistochemical status of proliferating cell nuclear antigen (PCNA) and K-ras in renal cell carcinomas (RCCs) of 236 Ukrainian patients (groups I to V), which represents a varying degrees of internal exposure to radiation and were operated in 2 different periods of time after the Chernobyl accident. The control group VI of 112 analog patients with RCCs was selected in Spain. The strong significant differences between the Ukrainian and Spanish groups were found in tumoral nuclear grade, in the percentage of sarcomatoid changes, the level of the peritumoral inflammatory response as well as in the peritumoral lesions. The dramatic increase of aggressivity and proliferative activity supported by strong PCNA and K-ras expression of RCCs from Ukrainian groups, associated with chronic radiation nephropathy of peritumoral kidney tissue, showed good correlation with the duration of radiation exposure and confirmed the influence of chronic but regular and sustained low dose of ionizing radiation on renal carcinogenesis of the Ukrainian population. Int. J. Cancer 87:880–883, 2000. © 2000 Wiley-Liss, Inc.

We have previously shown that bladder urothelium of people living in the cesium-137 (¹³⁷Cs)–contaminated areas of Ukraine demonstrates accumulation of stable p53 and p53 mutational inactivation, preferentially through G:C to A:T transition mutations at CpG dinucleotides, with a codon 245 hot spot. In the present study, we analyzed immuno-histochemically the relationship between oxidative stress markers and over-expression of p53 and H-ras in urinary bladder urothelium from 42 men with benign prostatic hyperplasia. Bladder mapping biopsies were obtained from 15 patients from a highly radiocontaminated area (group I), 14 patients from the less contaminated city of Kiev (group II) and 13 patients as a control group from “clean” (without radiocontamination) areas of Ukraine (group III). Irradiation cystitis with multiple foci of severe dysplasia and carcinoma in situ were observed in 15 of 15 (100%, group I) and 9 of 14 (64%, group II) cases, with 4 small transitional-cell carcinomas incidentally detected in groups I and II. Markedly elevated levels of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and 8-hydroxy-2`-deoxyguanosine (8-OHdG) were noted in these bladder urothelial lesions from groups I and II, accompanied by strong over-expression of p53 and less H-ras expression. These findings support the hypothesis that iNOS, COX-2 and 8-OHdG in bladder urothelium are induced by long-term exposure to low-dose radiation with a close relationship to p53 over-expression that could predispose to bladder carcinogenesis. Int. J. Cancer 86:790–798, 2000. © 2000 Wiley-Liss, Inc.

During the 11‐year period subsequent to the Chernobyl accident, the incidence of urinary bladder cancer in Ukraine has increased from 26.2 to 36.1 per 100,000 population. Cesium‐137 (137Cs) accounts for 80–90% of the incorporated radioactivity in this population, which has been exposed to long‐term, low‐dose ionizing radiation, and 80% of the more labile pool of cesium is excreted via the urine. The present study was performed to evaluate the histopathological features and the immunohistochemical status of p53, p21WAF1/Cip1, cyclin D1 and PCNA (proliferating cell nuclear antigen) in urinary bladder mucos a of 55 males (49‐92 years old) with benign prostatic hyperplasia who underwent surgery in Kiev, Ukraine, in 1995 and 1996. Group I (28 patients) inhabiting radiocontaminated areas of the country, group II (17 patients) from Kiev city with less radiocontamination and a control group III (10 patients) living in so‐called “clean” areas of Ukraine were compared. In groups I and II, an increase in multiple areas of moderate or severe dysplasia or carcinoma in situwas seen in 42 (93%) of 45 cases. In addi tion, two small transitional cell carcinomas were found in one patient in each of groups I and II. Nuclear accumulation of p53, PCNA, cyclin D1, and to a lesser extent p21WAF1/Cip1, was significantly increased in both groups I and II as compared with the control group III, indicating possible transformation events or enhancement of repair activities, that may precede the defect in the regulatory pathway itself, at least in the G1 phase of the cell cycle. Our results suggest that early malignant transformation is taking place in the bladder urothelium of people in the radiocontaminated areas of Ukraine and that this could possibly lead sometime in the future to an increased incidence of urinary bladder cancer.