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During the 25-year period subsequent to the Chernobyl accident, the morbidity of malignant renal tumors in Ukraine has increased from 4.7 to 10.7 per 100,000 of the total population. Recent studies of our group have shown that increases in morbidity, aggressiveness, and proliferative activity of renal cell carcinomas (RCCs), especially clear-cell renal cell carcinoma (CCRCC), in Ukrainian patients continuously inhabiting the radio-contaminated areas could be explained by specific molecular changes influenced by the so-called "chronic persistent low-dose ionizing radiation" (CPLDIR) exposure. This study aimed to examine the role of angiogenesis in CCRCC carcinogenesis associated with CPLDIR in patients living more than 20 years in cesium 137 ((137)Cs) contaminated areas after the Chernobyl accident in Ukraine. Paraffin-embedded specimens of 106 CCRCs were studied: Control cases were 18 tumors from Spanish patients (group 1), 25 tumors from Ukrainian patients from so-called clean areas without known radio-contamination (group 2), and 63 tumors from Ukrainian patients from radio-contaminated areas (group 3). For intratumoral microvessel density (MVD) determination, anti-CD31 antibody was used. A computerized image analysis program was used to quantitatively calculate the vascular density. Seventy-three percent of group 3 and 72 % of group 2 CCRCCs displayed the highest MVD. A striking increase in MVD was seen in group 3 CCRCCs, in comparison with groups 1 and 2 (p < 0.001). The majority of the hot spot vessels in group 3 was poorly differentiated. Moreover, MVD values for total vessels as well as for capillaries and tumor grade were strongly correlated. When we compared only tumor-node-metastasis tumor stages I and II, the differences remained statistically significant (p < 0.1). The ratio of the average total vessels and capillaries in the Ukrainian groups combined was 1.65:1 in comparison to the Spanish group. Our results provide evidence that CPLDIR exposure increases MVD (particularly capillary) in CCRCCs and is associated with a higher histological grade.

The leucine rich repeat containing 3B (LRRC3B) gene is a putative tumor suppressor located on human chromosome 3 in the 3p24 region. LRRC3B is frequently altered in colon and gastric cancers and also in leukaemias. In this study we investigated the promoter region methylation as a possible mechanism of LRRC3B gene inactivation in clear cell renal cell carcinomas. We found that the LRRC3B gene promoter was methylated in 43% of clear cell renal carcinoma samples. However, no correlation between DNA methylation and LRRC3B expression was found.

We determined whether ubiquitylation and sumoylation processes are involved in conventional renal cell carcinogenesis associated with chronic, long-term, persistent low doses of ionizing radiation (IR) in patients living for more than 20 years in cesium-137 ((137)Cs)-contaminated areas after the Chernobyl accident in Ukraine. To this end, we assessed the immunohistochemical expression of ubiquitin (Ub), SUMO1, SUMO E2 conjugating enzyme Ubc9, and the cell cycle regulators p53, mdm2, and p14(ARF) in 38 conventional renal cell carcinomas from Ukrainian patients with different degrees of radiation exposure after the Chernobyl accident. As control cases, 18 conventional renal carcinoma (cRCC) tissues from a Spanish cohort were analyzed. No significant differences between the Ukrainian and Spanish groups were found regarding Ub overexpression, although being higher in the Ukrainian cases. Furthermore, this expression was inversely associated with SUMO1 and Ubc9, with no correlation with tumor nuclear grade. There was also a direct relationship between Ubc9 and inflammatory response. These findings do not allow us to consider the immunohistochemical expression of ubiquitylation and sumoylation as valuable markers for discriminating the effects of long-term, low-dose IR exposure in cRCC carcinogenesis.

Two main ways playing a cardinal role in the pathogenesis of metastatic renal cell carcinoma (mRCC) have been identified in recent years, they are following: 1) a way of the mutation of a gene suppressor VHL (Van-Hippel-Lindau), stimulating various types of tyrosine-kinases participating in the development of tumors; 2) mTOR way, where ramapycyn plays a leading role, which effect proliferation and angiogenesis of mRCC. This discovery enabled the development of a new generation of highly effective medications for target-therapy of mRCCC--tyrosine-kinases inhibitors (VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-alpha/PDGFR-beta, Raf-kinases, etc.) sunitimab, sorafenib, pazopanib, axitinib, etc. and mTOR inhibitors--everolimus and temsirolimus as well as monoclonal neutralising antibody VEGF (bevasizumab). The review is devoted to the analysis of antitumor activity, patient tolerance and side effect of these preparations in the system therapy of patients with mRCC.

Urinary bladder urothelium as well as cells in the microenvironment of lamina propria (endothelial elements, fibroblasts and lymphocytes) demonstrate a number of responses to chronic persistent long-term, low-dose ionizing radiation (IR). Thus, oxidative stress occurs, accompanied by up-regulation of at least two signaling pathways (p38 mitogen-activated protein kinase and nuclear factor-kappaB cascades) and activation of growth factor receptors, in the bladder urothelium of people living in Cesium 137-contaminated areas of Ukraine, resulting in chronic inflammation and the development of proliferative atypical cystitis, so-called Chernobyl cystitis, which is considered a possible pre-neoplastic condition in humans. Furthermore, significant alterations in regulation of cell cycle transitions are associated with increased cell proliferation, along with up-regulated ubiquitination and sumoylation processes as well as inefficient DNA repair (base and nucleotide excision repair pathways) in the affected urothelium. The microenvironmental changes induced by chronic long-term, low-dose IR also appear to promote angiogenesis and remodeling of the extracellular matrix that could facilitate invasion as well as progression of pre-existing initiated cells to malignancy. Based on the available findings, new strategies have been developed for predicting and treatment of Chernobyl cystitis-a first step in urinary bladder carcinogenesis in humans.

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/beta-catenin complexes and p53 tumor suppressor gene protein, and transforming growth factor beta 1 (TGF-beta1) 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/beta-catenin complexes accompanied by elevated levels of p53 and TGF-beta1 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.

Compared to the 19-year period subsequent to the Chernobyl accident, the morbidity of malignant renal tumors in the Ukraine has increased from 4.7 to 9.0 per 100,000 of the total population. Cesium 137 ( 137 Cs), which accounts for 90% of the internal radioactivity in the Ukrainian population exposed to long-term low-dose radiation and 90% of the more labile pool of 137 Cs, is excreted via the kidneys. Our present study aimed to evaluate the status of pro- and anti-apoptotic regulatory molecules in conventional renal cell carcinomas (cRCCs) in Ukrainian patients. To achieve this objective, Bcl-2, Bcl-x, BAX, death receptor (DR5) and transcriptional nuclear factor kappa B (NF-κB, with p50 and p65 subunits) were immunohistochemically investigated using a tissue microarray technique in cRCCs from a group of 56 Ukrainian patients, comprising 18 patients living in non-contaminated areas and 41 patients from 137 Cs-contaminated areas. As a comparison, 19 Spanish patients with analogous tumors were also investigated. It was shown that BAX and DR5-positive cRCCs tended to increase among the Ukrainian patients living in the radio-contaminated areas, along with the suppression of anti-apoptotic molecules (Bcl-2 and Bcl-x) and with p65 and p50 overexpression in the same tumors. This study suggested that chronic long-term, low-dose radiation exposure might result in the alteration of the apoptotic regulatory mechanisms, which, in turn, could lead to enhanced tumor progression and resistance to apoptosis., (Copyright© 2006 International Institute of Anticaner Research (Dr. John G. Delinassios), All rights reserved.)

This study examines the molecular pathways of cell-cell communication in chronic inflammatory processes associated with long-term low-dose urinary bladder exposure to ionizing radiation in people without major disease living more than 19 years in radio-contaminated areas of Ukraine after the Chernobyl accident. Patterns of components of the E-cadherin/beta-catenin complex, and transforming growth factor-beta1 (TGF-beta1) and inducible nitric oxide synthase (iNOS) expression were immunohistochemically evaluated in urinary bladder biopsies from 52 males with benign prostate hyperplasia and 8 females with chronic cystitis (group 1). For comparison, 25 males and 6 females living in non-contaminated areas of Ukraine were also investigated (group 2). Fourteen patients with primary urothelial carcinomas, which were operated on before the Chernobyl accident, were included as a carcinoma group. Chronic proliferative atypical cystitis ('Chernobyl cystitis') was observed in group 1 patients. Foci of dysplasia and carcinoma in situ were found in 51 (85%) and 34 (57%) of the 60 cases, respectively. Chronic cystitis with areas of dysplasia was detected in only 4 (13%) cases of 31 group 2 patients. Statistically significant differences in immunohistochemical scores for TGF-beta1 in the urothelium and lamina propria, iNOS in the urothelium and both beta-catenin and E-cadherin in the cytoplasm were observed between groups 1 and 2 with marked expression in group 1. Furthermore, TGF-beta1 overexpression and alteration in E-cadherin/beta-catenin complexes in bladder urothelium might play a crucial role in urinary bladder carcinogenesis in humans exposed to long-term low-dose ionizing radiation., ((Cancer Sci 2005).)

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 ((137)Cs) 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.

After the Chernobyl accident in 1986, the incidence of urinary bladder cancers in the Ukraine increased gradually from 26.2 to 43.3 per 100,000 people between 1986 and 2001. In the areas of low level but persistent cesium-137 (137Cs) radio-contamination, a unique atypical radiation-related urinary bladder cystitis named 'Chernobyl cystitis', a possible pre-neoplastic condition in humans, has been detected. We have previously documented high incidences of bladder lesions, including severe dysplasias and/or carcinoma in situ, in association with this cystitis and correlating with oxidative DNA damage. To further investigate the molecular mechanisms underlying bladder carcinogenesis with this specific etiology, mutation analysis of p53 gene (exon 5-8) was performed for 11 and 18 paraffin-embedded bladder cancers in Ukrainians, respectively collected before and after the Chernobyl disaster. DNAs were extracted and subjected to nested PCR-single-strand conformational polymorphism analysis followed by direct DNA sequencing, as well as p53 immunohistochemistry (IHC). The incidences of p53 gene mutation were 54.5 and 16.7% for before and after the Chernobyl disaster, respectively, the difference being statistically significant. Also a tendency for higher p53 IHC score was apparent in the earlier group of lesions. No significant difference was noted for the proportions of historical types. These results point to possible distinct molecular carcinogenic pathways of bladder cancer formation, before and after the Chernobyl disaster, on the basis of variation in p53 gene alteration.

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 ((137)Cs) 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-activated protein kinase (MAPK), as well as the p50 and p65 subunits of nuclear factor kappa B (NF-kappa B). 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 (137)Cs 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 (137)Cs radiation. Alterations in the p38 MAPK cascade and accumulation of NF-kappa B subunits could be crucial early molecular events in the pathogenesis of Chernobyl cystitis.

Purpose: 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 Cs contaminated areas after the Chernobyl accident in Ukraine., Materials and Methods: Bladder urothelial biopsies from 204 patients were subjected to histological examination and biopsies from 35 were subjected to immunohistochemical study of 8-hydroxy-2'deoxyguanosine, 8-oxoguanine-DNA-glycosylase, apurinic/apyrimidinic endonuclease and xeroderma pigmentosum A endonuclease., Results: Chronic proliferative atypical cystitis with multiple foci of dysplasia and carcinoma in situ were observed in 139 (89%) and in 91 (58%) of 156 group 1 patients from radio contaminated areas, respectively, as well as 10 small transitional cell carcinomas. Chronic cystitis with areas of dysplasia was detected in 9 of 48 patients (19%) in control group 2 from clean (without radio contamination) areas of Ukraine. Greatly elevated levels of 8-hydroxy-2'deoxyguanosine, 8-oxoguanine-DNA-glycosylase, apurinic/apyrimidinic endonuclease and xeroderma pigmentosum A were evident in the urothelium in group 1, accompanied by increased Cs in the urine., Conclusions: These findings support the hypothesis that significant activation of DNA damage repair (base and nucleotide excision repair) is induced by the oxidative stress generated by long-term low doses of ionizing radiation. The levels of DNA oxidative adducts pointing to mutagenic and carcinogenic potential were in line with the histopathologically diagnosed urothelial lesions.

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 p16 and p15 gene 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 p16 and p15 genes, 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 p16 and p15 proteins. 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 p16 and p15 genes respectively, in both high stage and grade tumors from patients living in radiocontaminated areas, this being especially outstanding for the p16 gene. An association with COX2 and less iNOS overexpression in the same tumors was observed. Our data suggest that inactivation of p16 gene, but not p15, induced by increased oxidative stress generated by persistent chronic exposure to IR, could be one of the major pathways responsible for RCCs malignant progression.

The authors present the results of a six-year clinicoimmunological study of a therapeutic effect of cytkins combined with 5-fluoruracyl in metastatic renal-cell carcinoma. Two therapeutic regiments have been used: rhIFN-a + 5-FU and rhIL-2 + RHifn-A + 5-FU. In cytokin-sensitive patients, both therapy protocols vrs conventional therapeutic alternatives (cytostatics, hormones, irradiation) have been shown to increase the frequency of achievement of remission by objective scoring and life span of the patients. There was an improvement in patients on having received the complex with IL-2 but a higher therapeutic effect appeared to be accompanied by substantial side effects. Recommendatory measures well-targeted to those patients with metastatic renal-cell carcinoma who are to be placed on cytokinotherapy are presented together with immunological indices to monitor the treatments administered and prognosis.

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 ((137)Cs) 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 ((137)Cs) 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., (Copyright 2000 Wiley-Liss, Inc.)

We have previously shown that bladder urothelium of people living in the cesium-137 ((137)Cs)-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., (Copyright 2000 Wiley-Liss, Inc.)

Human biological liquids comprise various surfactants, which adsorb at liquid interfaces and lead to a variation in surface tension. The adsorption processes involving low molecular weight surfactants, proteins and phospholipids play a vital role in the physiological functions of the human organism, especially if large surfaces are involved (e.g., gas exchange in lungs, metabolism of kidneys, liver and brain). Dynamic surface tensiometric studies of biological liquids like serum and cerebrospinal fluid provide surrogate parameters that reflect surface tension phenomena. We provide dynamic surface tension data of serum and cerebrospinal fluid that were collected from healthy volunteers and patients with rheumatic, neurological or oncological diseases. Our studies indicate that dynamic surface tension data are helpful for diagnostic purposes and for monitoring of therapeutic interventions.

After the Chernobyl accident, the incidence of urinary bladder cancers in the Ukraine population increased gradually from 26.2 to 36.1 per 100,000 between 1986 and 1996. Urinary bladder epithelium biopsied from 45 male patients with benign prostatic hyperplasia living in radiocontaminated areas of Ukraine demonstrated frequent severe urothelial dysplasia, carcinoma in situ, and a single invasive transitional cell carcinoma, combined with irradiation cystitis in 42 cases (93%). No neoplastic changes (carcinoma in situ or transitional cell carcinoma) were found in 10 patients from clean areas (areas without radiocontamination). DNA was extracted from the altered urothelium of selected paraffin-embedded specimens that showed obviously abnormal histology (3 cases) or intense p53 immunoreactivity (15 cases), and mutational analysis of exons 5-8 of the p53 gene was performed by PCR-single-strand conformational polymorphism analysis followed by DNA sequencing. Nine of 17 patients (53%) had one or more mutations in the altered urothelium. Urine sediment samples were also collected from the patients at 4-27 months after biopsy and analyzed by PCR-single-strand conformational polymorphism analysis or yeast functional assay, and identical or additional p53 mutations were found in four of five cases. Interestingly, a relative hot spot at codon 245 was found in five of nine (56%) cases with mutations, and 11 of the 13 mutations determined (73%) were G:C to A:T transitions at CpG dinucleotides, reported to be relatively infrequent (approximately 18%) in human urinary bladder cancers. Therefore, the frequent and specific p53 mutations found in these male patients may alert us to a future elevated occurrence of urinary bladder cancers in the radiocontaminated areas.

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 mucosa 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 situ was seen in 42 (93%) of 45 cases. In addition, 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.

A many as 20 patients with acute purulent pyelonephritis were studied for clinical and immunological effects of leukinferone. The above patients were convalescent earlier than control subjects. There were instances where clinical status was not accompanied by shifts in immunity. However, on an average in the group, such parameters as level of lymphocytes, amounts of B-cells, Igs G, A, T-helpers, and Tx/Tc ratio were found to be increased as was activity of EK-cells. Stimulating effects of leukinferone were particularly pronounced in those patients with decreased values for immunological status. A conclusion is reached to the effect that patients with acute pyelonephritis may benefit from those treatments involving the use of the above drug preparation.

Results were studied of use of T-activin in those clinical settings related to acute inflammatory diseases of the kidneys. There was a positive clinical effect from this preparation in all twenty-eight patients with acute purulent pyelonephritis, accompanied by readjustments in the patients' immune system. A rise to the norm was found to occur in T-helper counts, and accordingly, immunoregulatory index, NK-cell activity, blood microbocydic activity. The in vitro investigations done suggested the need for individual testing of immunocompetent cells of the patient to optimize the therapy.

Patients with adenoma of the prostate appear to benefit from application of the unit "Prostatron" in one session without anesthesiologic maintenance and under outpatient conditions in the absolute majority of cases, as evidenced by reports from abroad and our own experience gained in the treatment of patients with adenoma of the prostate. This permits it to be recommended for widespread use in urological settings. Clinical, uroflowmetric and ultrasonic monitoring of the urogenital system status in patients with adenoma of the prostate, which is to be delivered in all such patients,--if used in combination with TUMWT,--becomes a means of really active assessment of treatment effectiveness rather than a passive recording of the moment of worsening of the patient' state.

Conventional routine renography and dynamic renoscintigraphy fail to yield sufficient diagnostic criteria in vasorenal hypertension, being associated with 21.5% false negative and 33.3% false positive results. Capoten induces statistically significant functional changes manifested by worsening of time-associated indicators of secretory-excretory function of the kidney, glomerular filtration rate and effective renal plasma flow on the side of the unilateral renal artery stenosis; relative hypotension in this situation leads to a statistically insignificant improvement of functional activity of the contralateral kidney parenchyma.

With the purpose of improving a differential diagnosis between stress and urgent forms of UI (urinary incontinence), functional condition was studied of lower urinary tract in 62 women suffering from the above pathologies, using general clinical, urologic and neuroelectromyographic methods. In women suffering from urinary incontinence, a decrease is noted of contractile activity of all the anatomical formations responsible for the continence of urine, and the pattern of the electromyograms recorded permits identification of the form of the pathology. The authors hold the view that the onset of an UI symptom in the majority of the examinees is associated with the degenerative dystrophic lesion of the lumbosacral portion of the spine.

The effect of leukinferon (LKF) administration to 20 patients with acute renal inflammation was evaluated versus the effect of basic therapy given to 19 matched patients. A short course of LKF (3 injections) promoted more rapid discontinuation of the fever, recovery of satisfactory general condition, healing of postoperative wounds. Immunologically, the test subjects exhibited a rise in the previously low levels of lymphocytes, B-cells, T-helpers, IgA and IgG. The proportion of T-lymphocyte subpopulations improved and the activity of EC-cells enhanced. It is thought valid to use LKF in acute renal inflammation and surgical urological affections.

Of 507 patients with renal tumours 36 (7.1%) presented with primary epithelial neoplasms of the renal pelvis. Histological investigation revealed benign papillomas in 3 (8.3%) cases. These patients underwent resection of the renal pelvis along with the tumour. Nephro-ureterectomy was performed in 33 patients, of whom 27 (75%) had it for transitional cell carcinoma, 5 (14%) for squamous cell carcinoma and 1 (2.7%) patient for solid carcinoma of the pelvis. Results of surgical treatment vary with the process stage so that the more advanced the stage, the poorer is the prognosis. High efficiency was shown of nephro-ureterectomy. At 5 years 9 of 13 operated on are alive without signs of metastatic disease.

Informative value of ultrasonography potential in the diagnosis of nephrotuberculosis was studied by comparison with conventional x-ray and intraoperative findings in 78 relevant patients. Three patterns of renal ultrasonic architectonics changes in nephrotuberculosis were revealed: 1) focal heterogeneity of renal parenchyma, 2) pseudocystic type, 3) hydronephrotic transformation. It is concluded that ultrasonography is superior to routine diagnostic methods, but is recommended for use in combination with standard methods of phthisiourological diagnosis.

In 22 and 19 patients with vasorenal hypertension the influence of exercise loading and capoten action on renal function accordingly were analyzed using the data obtained with the help of radionuclide renography. In 10 (45.4%) of 22 patients after the bicycle ergometry application the changes in hippuran transport occurred, in 12 (54.6%) the significant changes of renal function was not determined. In patients of these groups the arterial pressure after operation was accordingly 24.0/14.7 kPa (180/110 mm Hg) and 18.7/10.7 kPa (140/80 mm Hg). According to the data obtained with the help of radionuclide renography the curve height lowering was noted in 7 (36.9%) of 19 patients, and after capoten injection--in 18 (94.7%).

42 patients underwent conservative surgery for renal cancer. Conservative surgery was applied in 6 patients with only kidney, in 17--with unilateral cancer and contralateral kidney damaged by urological disease, in 17--with simultaneous tumorous process and in 8 patients with unilateral renal cancer and sound contralateral organ. Terms of postoperative follow-up ranged from 9 to 121 months, 14 patients have died for this period, exacerbation of cancer or metastasis being the cause of death in 9 of them. 5-year survival rate made up 64.4% although with regard to deaths related to cancer it equaled 81%. In 5 patients operated kidneys demonstrated complete functional failure due to nephrosclerosis. 5-year survival rate correlated inversely with advance of the process and was higher in unilateral lesions as compared to that of patients with bilateral tumors.

Recombinant interferon treatment of donors' and bladder cancer patients' lymphocytes results in activation of natural killer cells which is in correlation with enhanced activity of 2,5-oligoadenylate synthetase in them. The study of sensitivity of bladder cancer cell primary cultures showed that the cells are sensitive to various interferons virtually in all the cases observed as indicated by high synthetase activity. The baseline level of 2,5-oligoadenylate synthetase in tumor cells surpassed that in natural killers from healthy donors which may be related to elevated levels of serum gamma-interferon in the above patients.

The role of echo scanning in the diagnosis of acute pyelonephritis was evaluated in 123 patients. It was established that ultrasonography in acute pyelonephritis is a highly informative diagnostic method. The importance is high in acute obstructive pyelonephritis and less informative in acute non-obstructive pyelonephritis. The method has no equal counterparts in the most difficult cases for diagnosis. Association of renal echo scanning with traditional method significantly increases the diagnosis quality.

Enterosgel was used in 89 patients with different stages of renal failure treated surgically and medically. It is concluded that isolated or complex detoxication using enterosgel is a perspective approach in the treatment of patients with surgical renal diseases complicated by chronic renal failure. The use of enterosorption in the preoperative period allows to perform operative intervention in situations when infusion treatment by traditional methods was not sufficient.

The organ-preserving surgical intervention for renal cancer was performed in 42 patients. Five-year survival was 64.4%.

A clinical and immunological study is presented of 1030 practically healthy persons inhabiting Kiev from the moment of the Chernobyl accident. It was established clinically that during the last 5 years more frequent became acute respiratory viral infections, exacerbation of existing infection foci, appearance of complaints of reduced working capacity, somnolence apathy, increased fatiguability, worsening of memory, periodic subfebrility and oth. This symptom complex was determined as the "increased fatiguability syndrome". It was characterized immunologically by different changes showing most frequently a reduction of the functional activity of natural killers. The authors analyze different variants of immunological disorders in this group of subjects and give practical recommendations on using immunotropic drugs. They emphasize the importance of a service of clinical immunology in Ukraine able to organize special services to the population.

A clinical trial of polypeptide prostatic preparation prostatilen has been performed in 37 and 15 patients with chronic prostatitis and prostatic adenoma, respectively. The treatment resulted in attenuation of algetic and dysuria symptoms. Copulative function and spermatogenesis improved. The uroflowmetric index rose, while residual urine and leukocyte count in prostatic secretion reduced. The drug demonstrated antibacterial and immunomodulation effects in the absence of adverse reactions. Prostatilen is indicated in: chronic prostatitis, prostatic adenoma stage I, normospermatogenic and toxic sterility, interoceptive copulative dysfunction, dysuria. The drug in recommended for clinical application.

The paper presents evidence on dysfunction of natural killer cells and abnormal proliferative response of peripheral blood mononuclears to T- and B-cell mitogens (PHA, Phytolacca) in patients at varying stages of acute pyelonephritis. A number of immunomodulators (recombinant alpha 2-interferon, IL-2 and tactivin) produce different effects on natural killer activity and lymphocyte blast transformation in healthy donors and pyelonephritis patients. Immunotropic effects of immunopeptides depend on the drug dose, the response of various subpopulations of the immunocompetent cells being individual. It is suggested that immune system, natural killer activity in particular, plays an important part in pathogenesis of acute pyelonephritis. In vitro experiments demonstrate that there can be a positive clinical response to tactivin and recombinant alpha 2-interferon administered in doses activating the function of certain immunocompetent cells.

The diagnostic possibilities of intravenous digital subtraction angiography (DSA) were evaluated in 2393 patients. The diagnostic value was 97.2%. DSA is contraindicated via the subclavian vein in children, inadequate preparation of the patients, vein abnormalities. The informative value was 92% in vasorenal hypertension, 100% in renal abnormalities, 85% in renal tumours. Intravenous DSA may be a screening method in the diagnosis of hypertension of unclear etiology, abnormalities of the upper urinary tract, while in tumours, especially of small size, DSA is a supplementary method to ultrasound and CT. The method is of economic importance.

The quantitative and functional state of different populations of immunocompetent cells was studied in 45 patients with acute serous and 46 patients with acute purulent pyelonephritis. An imbalance has been found in the system of regulatory cells, activation of phagocytosis with reduction of its reserve capacities, disorders of IL-producing capacity of mononuclears and suppression of the functional activity of NK cells.

With the purpose of improving the results of treatment of chronic prostatitis the authors has reflexotherapy (corporal and auricular). It is shown that the used method has advantages over the existing traditional methods. A multiple-criteria mathematical analysis was carried out of the efficacy of laser reflexotherapy in chronic prostatitis and is was found to equal 89%.

The functional state of urethral neutrophil granulocytes in patients with chronic urethro-prostatitis, and possibility of miramistin use in complex treatment of the disease were investigated. The data revealed functional suppression of these granulocytes in the patients. Complex treatment with miramistin normalized indices of urethral phagocytic activity, on the contrary, after treatment of the patients without the agent there was no tendency to normalize urethral phagocytic function. The findings suggest that miramistin supplemented to routine antiinflammatory therapy improves curative results in patients with chronic urethro-prostatitis but the drug should be prescribed in accordance with the initial function of urethral neutrophil granulocytes.

It was found that addition of mirastimin to the traditional anti-inflammatory treatment results in stimulation of the absorptive capacity of the urethral phagocytes and improves the results of treatment of patients with chronic urethroprostatitis. The immunomodulator mirastimin should be given with consideration of the initial functional state of urethral neutrophilic granulocytes.

The results of treatment with homeopathic remedies in dilutions 10(-400), 10(-2000), 10(-20000) are represented. The informative energetic hologramic conception of homeopathy is proposed. The homeopathic drugs are considered as holograms and the human organic as a biohologram. The resonance is a mode of their interaction with a wide therapeutic effect as a result.

Treatment results were studied in 45 patients with vasorenal hypertension complicated by chronic renal in failure after surgical treatment. Transarterial endarterectomy, roentgen endovascular dilatation of the renal arteries, splenorenal arterial anastomosis, renal autotransplantation were used. A hypotensive effect followed in 21 (46.7%), function improvement in 29 (64.4%). Causes of failures: nephrosclerosis due to prolonged hypertension, concomitant diseases of the upper urinary tract, technical complications of the operation.