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Aberrant expression of E-cadherin and beta-catenin in association with transforming growth factor-beta1 in urinary bladder lesions in humans after the Chernobyl accident.

https://arctichealth.org/en/permalink/ahliterature16573
Source
Cancer Sci. 2006 Jan;97(1):45-50
Publication Type
Article
Date
Jan-2006
Author
Alina Romanenko
Keiichirou Morimura
Anna Kinoshita
Hideki Wanibuchi
Alexander Vozianov
Shoji Fukushima
Author Affiliation
Department of Pathology, Institute of Urology, Academy of Medical Sciences of Ukraine, 9a, Yu. Kotzubinsky Street, 04053, Kiev, Ukraine.
Source
Cancer Sci. 2006 Jan;97(1):45-50
Date
Jan-2006
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adult
Aged
Aged, 80 and over
Bladder Neoplasms - metabolism - pathology
Cadherins - metabolism
Chernobyl Nuclear Accident
Female
Gene Expression Regulation
Humans
Immunohistochemistry
Male
Middle Aged
Research Support, Non-U.S. Gov't
Transforming Growth Factor beta - metabolism
beta Catenin - metabolism
Abstract
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.
PubMed ID
16367920 View in PubMed
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DNA damage repair in bladder urothelium after the Chernobyl accident in Ukraine.

https://arctichealth.org/en/permalink/ahliterature18935
Source
J Urol. 2002 Sep;168(3):973-7
Publication Type
Article
Date
Sep-2002
Author
Alina Romanenko
Keiichirou Morimura
Min Wei
Wadim Zaparin
Alexander Vozianov
Shoji Fukushima
Author Affiliation
Department of Pathology, Institute of Urology and Nephrology, Academy of Medical Sciences of Ukraine, Kiev, Ukraine.
Source
J Urol. 2002 Sep;168(3):973-7
Date
Sep-2002
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adult
Aged
Aged, 80 and over
Bladder - chemistry - radiation effects
Bladder Neoplasms - etiology - genetics
Carbon-Oxygen Lyases - analysis
Chronic Disease
Cystitis - pathology
DNA Damage - radiation effects
DNA Repair
DNA-(Apurinic or Apyrimidinic Site) Lyase
DNA-Formamidopyrimidine Glycosylase
Deoxyguanosine - analogs & derivatives - analysis
Endonucleases - analysis
Female
Humans
Immunohistochemistry
Male
Middle Aged
N-Glycosyl Hydrolases - analysis
Neoplasms, Radiation-Induced - genetics
Oxidative Stress
Prostatic Hyperplasia - pathology
Research Support, Non-U.S. Gov't
Ukraine
Urothelium - chemistry - radiation effects
Abstract
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.
PubMed ID
12187202 View in PubMed
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The INK4a /ARF locus: role in cell cycle control for renal cell epithelial tumor growth after the Chernobyl accident.

https://arctichealth.org/en/permalink/ahliterature17626
Source
Virchows Arch. 2004 Sep;445(3):298-304
Publication Type
Article
Date
Sep-2004
Author
Alina Romanenko
Luisa Morell-Quadreny
Jose Antonio Lopez-Guerrero
Antonio Pellin
Valentin Nepomnyaschy
Alexander Vozianov
Antonio Llombart-Bosch
Author Affiliation
Department of Pathology, Institute of Urology, Academy of Medical Sciences of Ukraine, 9(a) Yu. Kotzubinsky, 04053 Kiev, Ukraine.
Source
Virchows Arch. 2004 Sep;445(3):298-304
Date
Sep-2004
Language
English
Publication Type
Article
Keywords
Adult
Aged
Carcinoma, Renal Cell - genetics - metabolism - pathology
Cell Cycle - genetics - radiation effects
Cesium Isotopes - urine
Comparative Study
Cyclin-Dependent Kinase Inhibitor p16 - genetics - radiation effects
DNA Methylation
Female
Genes, p16 - radiation effects
Humans
Immunohistochemistry
Kidney Neoplasms - genetics - metabolism - pathology
Male
Middle Aged
Mutation
Neoplasms, Radiation-Induced - genetics - pathology
Polymerase Chain Reaction
Research Support, Non-U.S. Gov't
Tumor Suppressor Protein p14ARF - genetics - radiation effects
Ukraine
p38 Mitogen-Activated Protein Kinases - metabolism
Abstract
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.
PubMed ID
15232742 View in PubMed
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P16INK4A and p15INK4B gene alteration associated with oxidative stress in renal cell carcinomas after the chernobyl accident (pilot study).

https://arctichealth.org/en/permalink/ahliterature18898
Source
Diagn Mol Pathol. 2002 Sep;11(3):163-9
Publication Type
Article
Date
Sep-2002
Author
Alina Romanenko
Luisa Morell-Quadreny
Jose Antonio Lopez-Guerrero
Antonio Pellin
Valentin Nepomnyaschy
Alexander Vozianov
Antonio Llombart-Bosch
Author Affiliation
Department of Pathology, Medical School, University of Valencia, Spain.
Source
Diagn Mol Pathol. 2002 Sep;11(3):163-9
Date
Sep-2002
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adolescent
Adult
Aged
Carcinoma, Renal Cell - genetics - metabolism - pathology
Cell Cycle Proteins - genetics - metabolism
Cyclin-Dependent Kinase Inhibitor p15
Cyclin-Dependent Kinase Inhibitor p16 - genetics - metabolism
DNA Methylation - radiation effects
DNA, Neoplasm - analysis
Female
Humans
Immunoenzyme Techniques
Kidney Neoplasms - genetics - metabolism - pathology
Male
Middle Aged
Neoplasm Staging
Oxidative Stress
Pilot Projects
Polymerase Chain Reaction
Power Plants
Research Support, Non-U.S. Gov't
Tumor Markers, Biological - metabolism
Tumor Suppressor Proteins
Ukraine
Abstract
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.
PubMed ID
12218456 View in PubMed
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Possible distinct molecular carcinogenic pathways for bladder cancer in Ukraine, before and after the Chernobyl disaster.

https://arctichealth.org/en/permalink/ahliterature17865
Source
Oncol Rep. 2004 Apr;11(4):881-6
Publication Type
Article
Date
Apr-2004
Author
Keiichirou Morimura
Alina Romanenko
Wei Min
Elsayed I Salim
Anna Kinoshita
Hideki Wanibuchi
Alexander Vozianov
Shoji Fukushima
Author Affiliation
Department of Pathology, Osaka City University Medical School, Osaka, Japan. fukuchan@med.osaka-cu.ac.jp
Source
Oncol Rep. 2004 Apr;11(4):881-6
Date
Apr-2004
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adult
Bladder Neoplasms - diagnosis - genetics - metabolism
Carcinoma - diagnosis - genetics - metabolism
DNA Mutational Analysis
Female
Genes, p53
Humans
Immunochemistry
Male
Research Support, Non-U.S. Gov't
Tumor Suppressor Protein p53 - metabolism
Ukraine
Abstract
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.
PubMed ID
15010889 View in PubMed
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Urinary bladder lesions induced by persistent chronic low-dose ionizing radiation.

https://arctichealth.org/en/permalink/ahliterature18349
Source
Cancer Sci. 2003 Apr;94(4):328-33
Publication Type
Article
Date
Apr-2003
Author
Alina Romanenko
Keiichirou Morimura
Hideki Wanibuchi
Min Wei
Wadim Zaparin
Wladimir Vinnichenko
Anna Kinoshita
Alexander Vozianov
Shoji Fukushima
Author Affiliation
Department of Pathology, Institute of Urology, Academy of Medical Sciences of Ukraine, Kiev, Ukraine. fukuchan@med.osaka-cu.ac.jp
Source
Cancer Sci. 2003 Apr;94(4):328-33
Date
Apr-2003
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adult
Aged
Aged, 80 and over
Bladder - metabolism - pathology - radiation effects
Bladder Neoplasms - etiology - metabolism - pathology
Cesium Radioisotopes - adverse effects - urine
Cystitis - etiology - metabolism - pathology
Female
Humans
Immunoenzyme Techniques
Male
Middle Aged
Mitogen-Activated Protein Kinases - metabolism
NF-kappa B - metabolism
Neoplasms, Radiation-Induced - etiology - metabolism - pathology
Oxidative Stress
Power Plants
Precancerous Conditions - etiology
Radiation Dosage
Radiation, Ionizing
Research Support, Non-U.S. Gov't
Ukraine
p38 Mitogen-Activated Protein Kinases
Abstract
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.
PubMed ID
12824899 View in PubMed
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6 records – page 1 of 1.