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[A morphometric study of the lymphoid cell population in biopsy material from patients with different thyroid pathologies]

https://arctichealth.org/en/permalink/ahliterature22920
Source
Tsitologiia. 1996;38(1):89-94
Publication Type
Article
Date
1996
Author
V A Kirillov
Iu P Iushchenko
E P Demidchik
Source
Tsitologiia. 1996;38(1):89-94
Date
1996
Language
Russian
Publication Type
Article
Keywords
Accidents, Radiation
Adolescent
Adult
Biopsy
Byelarus
Child
Child, Preschool
Comparative Study
English Abstract
Female
Humans
Karyometry
Lymphocytes - pathology - radiation effects
Male
Middle Aged
Neoplasms, Radiation-Induced - pathology
Power Plants
Thyroid Diseases - pathology
Thyroid Gland - pathology - radiation effects
Thyroid Neoplasms - pathology
Ukraine
Abstract
Using cytometry of lymphocytes, prolymphocytes and lymphoblasts in touch smears of biopsy and autopsy samples of thyroid, it was revealed that in cancer the small lymphocytes, in the total population of these lymphoid cells, comprise 0-2%, and on distributional histograms of lymphoid cells, according to the average diameter, the maximum was in the range of 9.6-11.7 microns. In benign malformations, goiters and autoimmune thyroiditis, and in the norm the percentage of small lymphocytes varied in the range of 10-44, with the maximum in the range of 7.5-9.6 microns. Histograms, built according to the space occupied by lymphoid cells, evidenced that in malignant thyroid disease a cupola-shaped character of distribution was peculiar, whereas in other pathologies and in norm the exponential relationship was revealed.
PubMed ID
8768554 View in PubMed
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Childhood exposure due to the Chernobyl accident and thyroid cancer risk in contaminated areas of Belarus and Russia.

https://arctichealth.org/en/permalink/ahliterature20917
Source
Br J Cancer. 1999 Jul;80(9):1461-9
Publication Type
Article
Date
Jul-1999
Author
P. Jacob
Y. Kenigsberg
I. Zvonova
G. Goulko
E. Buglova
W F Heidenreich
A. Golovneva
A A Bratilova
V. Drozdovitch
J. Kruk
G T Pochtennaja
M. Balonov
E P Demidchik
H G Paretzke
Author Affiliation
GSF-Institute of Radiation Protection, Neuherberg, Germany.
Source
Br J Cancer. 1999 Jul;80(9):1461-9
Date
Jul-1999
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Byelarus
Child
Humans
Incidence
Iodine Radioisotopes - adverse effects
Monte Carlo Method
Neoplasms, Radiation-Induced - epidemiology - etiology
Poisson Distribution
Power Plants
Radiation Dosage
Research Support, Non-U.S. Gov't
Risk
Russia
Thyroid Neoplasms - epidemiology - etiology
Ukraine
Abstract
The thyroid dose due to 131I releases during the Chernobyl accident was reconstructed for children and adolescents in two cities and 2122 settlements in Belarus, and in one city and 607 settlements in the Bryansk district of the Russian Federation. In this area, which covers the two high contamination spots in the two countries following the accident, data on thyroid cancer incidence during the period 1991-1995 were analysed in the light of possible increased thyroid surveillance. Two methods of risk analysis were applied: Poisson regression with results for the single settlements and Monte Carlo (MC) calculations for results in larger areas or sub-populations. Best estimates of both methods agreed well. Poisson regression estimates of 95% confidence intervals (CIs) were considerably smaller than the MC results, which allow for extra-Poisson uncertainties due to reconstructed doses and the background thyroid cancer incidence. The excess absolute risk per unit thyroid dose (EARPD) for the birth cohort 1971-1985 by the MC analysis was 2.1 (95% CI 1.0-4.5) cases per 10(4) person-year Gy. The point estimate is lower by a factor of two than that observed in a pooled study of thyroid cancer risk after external exposures. The excess relative risk per unit thyroid dose was 23 (95% CI 8.6-82) Gy(-1). No significant differences between countries or cities and rural areas were found. In the lowest dose group of the settlements with an average thyroid dose of 0.05 Gy the risk was statistically significantly elevated. Dependencies of risks on age-at-exposure and on gender are consistent with findings after external exposures.
PubMed ID
10424752 View in PubMed
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Comparison of the breakpoint regions of ELE1 and RET genes involved in the generation of RET/PTC3 oncogene in sporadic and in radiation-associated papillary thyroid carcinomas.

https://arctichealth.org/en/permalink/ahliterature22057
Source
Genomics. 1997 Jun 1;42(2):252-9
Publication Type
Article
Date
Jun-1-1997
Author
I. Bongarzone
M G Butti
L. Fugazzola
F. Pacini
A. Pinchera
T V Vorontsova
E P Demidchik
M A Pierotti
Author Affiliation
Division of Experimental Oncology A, Istituto Nazionale Tumori, Milan, Italy.
Source
Genomics. 1997 Jun 1;42(2):252-9
Date
Jun-1-1997
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Base Sequence
Carcinoma, Papillary - genetics
Cloning, Molecular
Comparative Study
DNA Primers - genetics
DNA, Neoplasm - genetics
Exons
Gene Rearrangement - radiation effects
Humans
Introns
Molecular Sequence Data
Neoplasms, Radiation-Induced - genetics
Oncogenes - radiation effects
Polymerase Chain Reaction
Recombination, Genetic - radiation effects
Research Support, Non-U.S. Gov't
Thyroid Neoplasms - genetics
Ukraine
Abstract
The RET/PTC3 oncogene is an activated form of the RET protooncogene, which is frequently rearranged in papillary thyroid carcinoma. RET/PTC3 results from a structural rearrangement between the ELE1 and the RET genes, and it has been observed in both sporadic and radiation-associated post-Chernobyl tumors. To understand the molecular basis that predisposes RET and ELE1 genes to be recurrent targets of "illegitimate" recombination, we examined the genomic regions containing the ELE1/RET breakpoints of six sporadic and three post-Chernobyl tumors in two papillary carcinomas of different origins. Our data indicated, in both genes, a clustering of the breakpoints in regions designated ELE1-bcr (1.8 kb) and RET-bcr (1.9 kb). Notably, in all sporadic tumors and in one post-Chernobyl tumor the ELE1/RET recombination corresponded with short sequences of homology (3-7 nt) between the two rearranging genes. In addition, we observed an interesting distribution of the post-Chernobyl breakpoints in ELE1-bcr located within an Alu element, or in between two close Alu elements, and always in A+T-rich regions.
PubMed ID
9192845 View in PubMed
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Cytogenetic changes in radiation-induced tumors of the thyroid.

https://arctichealth.org/en/permalink/ahliterature21285
Source
Cancer Res. 1999 Jan 1;59(1):135-40
Publication Type
Article
Date
Jan-1-1999
Author
H. Zitzelsberger
L. Lehmann
L. Hieber
H U Weier
C. Janish
J. Fung
T. Negele
F. Spelsberg
E. Lengfelder
E P Demidchik
K. Salassidis
A M Kellerer
M. Werner
M. Bauchinger
Author Affiliation
Institute of Radiobiology, GSF-Forschungszentrum für Umwelt und Gesundheit GmbH, Neuherberg, Germany. zitzelsberger@gsf.de
Source
Cancer Res. 1999 Jan 1;59(1):135-40
Date
Jan-1-1999
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adolescent
Adult
Byelarus
Child
Child, Preschool
Chromosome Aberrations
Female
Humans
Infant
Karyotyping
Male
Power Plants
Research Support, Non-U.S. Gov't
Thyroid Neoplasms - etiology - genetics
Ukraine
Abstract
Thyroid carcinoma incidence is increased significantly after ionizing irradiation; however, the possible mechanisms have not yet been identified. To provide clues for an understanding of the radiation-induced transformation of thyroid epithelium, we analyzed the karyotypes of 56 childhood thyroid tumors that appeared in Belarus after the Chernobyl nuclear accident in 1986. We also studied eight secondary thyroid tumors that developed after radiotherapy. Metaphase preparations obtained from primary cultures were analyzed by G-banding. Clonal structural aberrations were found in 13 of 56 Belarussian cases and in 6 of 8 secondary tumors that developed after radiotherapy. Furthermore, we detected multiple chromosomal aberrations as well as complex rearrangements in some of these tumors and performed a detailed analysis of marker chromosomes from a single case using spectral karyotyping and comparative genomic hybridization in a childhood tumor from Belarus with a near-triploid karyotype. Both comparative genomic hybridization and spectral karyotyping analysis revealed structural alterations affecting identical chromosomes 1, 2, 9, and 13, among others. In addition to the known hot spots of alterations in papillary thyroid carcinomas on chromosomes 1q and 10q, a comprehensive breakpoint analysis in the pooled data set revealed novel breakpoints on chromosomes 4q, 5q, 6p, 12q, 13q, and 14q. The chromosomal aberrations in these tumors may provide suitable starting points for the positional cloning of genes involved in radiation-induced tumorigenesis.
PubMed ID
9892198 View in PubMed
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Detection of a novel type of RET rearrangement (PTC5) in thyroid carcinomas after Chernobyl and analysis of the involved RET-fused gene RFG5.

https://arctichealth.org/en/permalink/ahliterature21835
Source
Cancer Res. 1998 Jan 15;58(2):198-203
Publication Type
Article
Date
Jan-15-1998
Author
S. Klugbauer
E P Demidchik
E. Lengfelder
H M Rabes
Author Affiliation
Institute of Pathology, Ludwig Maximilians University of Munich, Germany.
Source
Cancer Res. 1998 Jan 15;58(2):198-203
Date
Jan-15-1998
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adult
Amino Acid Sequence
Artificial Gene Fusion
Base Sequence
Blotting, Northern
Carcinoma, Papillary - genetics - metabolism - pathology
Child
DNA Probes - chemistry
DNA, Neoplasm - genetics
Drosophila Proteins
Female
Gene Expression Regulation, Neoplastic - genetics
Gene Rearrangement - radiation effects
Humans
Immunoenzyme Techniques
Male
Molecular Sequence Data
Neoplasm Proteins - genetics
Neoplasms, Radiation-Induced - genetics - metabolism - pathology
Oncogene Proteins, Fusion - genetics - metabolism
Proto-Oncogene Proteins - genetics - metabolism
Proto-Oncogene Proteins c-ret
RNA, Messenger - biosynthesis
Receptor Protein-Tyrosine Kinases - genetics - metabolism
Research Support, Non-U.S. Gov't
Thyroid Neoplasms - genetics - metabolism - pathology
Ukraine
Abstract
A novel type of RET rearrangement, PTC5, was detected in papillary thyroid carcinomas of two patients exposed to radioactive fallout after Chernobyl. Reverse transcription-PCR and rapid amplification of 5'-cDNA ends revealed a fusion of the ret tyrosine kinase (TK) domain with a sequence identical to that described previously as ret-II. Ret-II is a transfection artifact in NIH3T3 cells and has not yet been detected in any human tumor. Overlapping sequences found in the expressed sequence tag databases enabled us to sequence the COOH terminus of the ret-fused gene 5 (RFG5). The combined data made it possible to assemble a full-length rfg5 protein sequence. Computer-assisted analysis of this sequence reveals four putative coiled-coil structures, possibly involved in dimerization, but no membrane-binding sequences. Northern blots show a ubiquitous RFG5 expression in various normal tissues, including the thyroid gland. In addition to the RFG5/RET, we also detected the reciprocal RET/RFG5 transcript in both tumor samples, suggesting that the rearrangement is based on a balanced reciprocal translocation. In agreement with other rearranged TKs, it is concluded that the transforming action of the new fusion protein rfg5/ret in thyroid tumors may be due to an activation of the ret TK by constitutive expression and dimerization potential of the 5'-fused rfg5 protein. Ret immunohistochemistry indicates that the fusion protein is expressed in all cells of PTC5 tumors, suggesting that RFG5/RET rearrangement is an early event in thyroid carcinogenesis.
PubMed ID
9443391 View in PubMed
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Distinct frequency of ret rearrangements in papillary thyroid carcinomas of children and adults from Belarus.

https://arctichealth.org/en/permalink/ahliterature21258
Source
Int J Cancer. 1999 Jan 5;80(1):32-8
Publication Type
Article
Date
Jan-5-1999
Author
J. Smida
K. Salassidis
L. Hieber
H. Zitzelsberger
A M Kellerer
E P Demidchik
T. Negele
F. Spelsberg
E. Lengfelder
M. Werner
M. Bauchinger
Author Affiliation
Radiobiological Institute, University of Munich, Germany.
Source
Int J Cancer. 1999 Jan 5;80(1):32-8
Date
Jan-5-1999
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adenocarcinoma, Follicular - genetics - pathology - surgery
Adolescent
Adult
Age Factors
Aged
Byelarus
Carcinoma, Papillary - genetics - pathology - surgery
Child
Comparative Study
Drosophila Proteins
Female
Gene Rearrangement
Germany
Humans
Male
Middle Aged
Neoplasm Staging
Neoplasms, Radiation-Induced - genetics - pathology - surgery
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-ret
Proto-Oncogenes
RNA, Messenger - analysis
Receptor Protein-Tyrosine Kinases - genetics
Research Support, Non-U.S. Gov't
Thyroid Neoplasms - genetics - pathology - surgery
Ukraine
Abstract
Rearrangements of the ret oncogene were investigated in papillary thyroid carcinomas (PTC) from 51 Belarussian children with a mean age of 3 years at the time of the Chernobyl radiation accident. For comparison, 16 PTC from exposed Belarussian adults and 16 PTC from German patients without radiation history were included in the study. ret rearrangements were detected and specified by RT-PCR and direct sequencing using specific primers for ret/PTC1, 2 and 3. Only ret/PTC1, and no ret/PTC3, was found in the adult patients, with a frequency of 69% for the Belarussian cases, but of only 19% in the German patients. In contrast, 13 ret/PTC3 (25.5%) and 12 ret/PTC1 (23.5%) rearrangements were present in PTC from Belarussian children. Thus, our study reveals about a 1:1 ratio of ret/PTC3 and ret/PTC1, in contrast to earlier studies with lower numbers of cases and exhibiting a high predominance of ret/PTC3 (ratio about 3:1). A ratio (2.5:1) similar to that in earlier investigations (diagnosed 1991-94) was obtained for cases included in our study that were diagnosed in 1993/94. The present data suggest that ret/PTC3 may be typical for radiation-associated childhood PTC with a short latency period, whereas ret/PTC1 may be a marker for later-occurring PTC of radiation-exposed adults and children.
PubMed ID
9935226 View in PubMed
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Gene rearrangement and Chernobyl related thyroid cancers.

https://arctichealth.org/en/permalink/ahliterature20628
Source
Br J Cancer. 2000 Jan;82(2):315-22
Publication Type
Article
Date
Jan-2000
Author
M. Santoro
G A Thomas
G. Vecchio
G H Williams
A. Fusco
G. Chiappetta
V. Pozcharskaya
T I Bogdanova
E P Demidchik
E D Cherstvoy
L. Voscoboinik
N D Tronko
A. Carss
H. Bunnell
M. Tonnachera
J. Parma
J E Dumont
G. Keller
H. Höfler
E D Williams
Author Affiliation
Centro di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Moleculare, Universita di Napoli, Italy.
Source
Br J Cancer. 2000 Jan;82(2):315-22
Date
Jan-2000
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adolescent
Carcinoma, Papillary - etiology - genetics
Child
Child, Preschool
Chromosomes, Human, Pair 10 - genetics
Disasters
Female
Humans
Infant
Infant, Newborn
Male
Neoplasms, Radiation-Induced - genetics
Power Plants
Proto-Oncogenes - genetics
Research Support, Non-U.S. Gov't
Thyroid Neoplasms - etiology - genetics
Ukraine
Abstract
The increase in thyroid carcinoma post-Chernobyl has been largely confined to a specific subtype of papillary carcinoma (solid/follicular). This subtype is observed predominantly in children under 10 in unirradiated populations, but maintains a high frequency in those aged 10-15 from those areas exposed to fallout from the Chernobyl accident. The aim of this study was to link morphology with molecular biology. We examined 106 papillary carcinomas from children under the age of 15 at operation. All were examined for rearrangements of the RET oncogene by reverse transcription polymerase chain reaction (RT-PCR); a subset of these cases were also examined for mutations of the three ras oncogenes, exon 10 of the thyroid stimulating hormone receptor, associated more usually with a follicular rather than papillary morphology, and exons 5, 6, 7 and 8 of the p53 gene, commonly involved in undifferentiated thyroid carcinoma. Rearrangements of the REToncogene were found in 44% of papillary carcinomas in which we studied fresh material; none of the tumours examined showed mutation in any of the other genes. The two rearrangements resulting from inversion of part of chromosome 10 (PTC1 and PTC3) accounted for the majority of RET rearrangements identified, with PTC1 being associated with papillary carcinomas of the classic and diffuse sclerosing variants and PTC3 with the solid/follicular variant.
PubMed ID
10646883 View in PubMed
Less detail

High prevalence of RET rearrangement in thyroid tumors of children from Belarus after the Chernobyl reactor accident.

https://arctichealth.org/en/permalink/ahliterature22965
Source
Oncogene. 1995 Dec 21;11(12):2459-67
Publication Type
Article
Date
Dec-21-1995
Author
S. Klugbauer
E. Lengfelder
E P Demidchik
H M Rabes
Author Affiliation
Institute of Pathology, Ludwig Maximillyians University of Munich, Germany.
Source
Oncogene. 1995 Dec 21;11(12):2459-67
Date
Dec-21-1995
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adult
Base Sequence
Carcinoma, Papillary - genetics
Child
Child, Preschool
Drosophila Proteins
Female
Gene Rearrangement
Humans
Infant
Male
Middle Aged
Molecular Sequence Data
Neoplasms, Radiation-Induced - genetics
Nuclear Reactors
Polymerase Chain Reaction
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-ret
Proto-Oncogenes
Receptor Protein-Tyrosine Kinases - genetics
Research Support, Non-U.S. Gov't
Thyroid Neoplasms - etiology - genetics
Ukraine
Abstract
RET rearrangement was studied in papillary thyroid carcinomas (PTC) of children exposed to radioactive fallout in Belarus after the Chernobyl accident. To detect RET rearrangement in small tissue samples from thyroidectomy specimen (12 PTC of children; 2 PTC and 1 follicular carcinoma of adults; non-tumorous thyroid tissue of 4 children and 4 adults as controls), a RT-multiplex PCR was developed using primers suited to amplify fragments in different quantities depending on the presence or absence of RET rearrangements in the tissues. The type of rearrangement was determined by RT-PCR and direct sequencing using primers for ret/PTC1, 2 and 3. Two-thirds of the papillary thyroid carcinomas of the children revealed a RET rearrangement, with ret/PTC3 being more frequent by a factor of 3 than ret/PTC1. ret/PTC2 was not detected. All RET rearrangement-positive tumors had lymph node metastasis while half of the tumors with wild-type cRET had not. More than half of the cases with ret/PTC3 expressed not only the ELE/RET transcript as expected, but also the RET/ELE transcript. Intrachromosomal rearrangement involving RET and the adjacent H4 or ELE gene on chromosome no. 10 is a very frequent event in thyroid cancer of children of the Chernobyl-contaminated zone of Belarus.
PubMed ID
8545102 View in PubMed
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27 records – page 1 of 3.