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Activation of the MAPK pathway in thyroid cancer. Most of the rearrangements identified in post-Chernobyl childhood thyroid cancers impair the physiological function of receptor tyrosine kinase activity, which results in constitutive activation of the MAPK pathway.
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After the Tokyo electric power company (TEPCO) Fukushima Daiichi nuclear power plant accident, cancer risk from low-dose radiation exposure has been deeply concerned. While the linear no-threshold (LNT) model is applied for the purpose of radiation protection, it is a model based upon the concept, in which ionizing radiation induces stochastic onco...
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... step for activation of tyrosine kinase activity. (31,32) The fusion partner proteins are commonly expressed in thyroid follicular cells and possess coiled-coil domains that enable homodimerization of the fusion RET ⁄ PTC proteins ( Fig. 1). As a result, RET ⁄ PTC proteins constitutively activate the MAPK pathway without any ligand binding (Fig. 2). (28,(33)(34)(35)(36) Other types of rearrangements identified in childhood thyroid cancer related to the Chernobyl accident include juxtaposition of the A kinase anchor protein 9 (AKAP9) gene and v-raf viral oncogene homolog B1 (BRAF), designated AKAP9- BRAF, (37,38) rearrangement between translocated protein region (TPR) and the ...
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Introduction:
The US government regulates allowable radiation exposures relying, in large part, on the seventh report from the committee to estimate the Biological Effect of Ionizing Radiation (BEIR VII), which estimated that most contemporary exposures- protracted or low-dose, carry 1.5 fold less risk of carcinogenesis and mortality per Gy than a...
Citations
... It is capable of inducing aging and subsequent death of thyroid follicular cells. Cell death stimulates the release of inflammatory cytokines, thereby establishing an inflammatory environment and creating conditions conducive to the initial carcinogenesis of the thyroid[59]. Two ecological studies conducted in Belgium analyzed the incidence of TC in the vicinity offour nuclear power plants. ...
In recent years, there has been a rapid increase in the prevalence of benign and malignant tumours of the thyroid gland worldwide, positioning it as one of the most prevalent neoplasms within the endocrine system. While the pathogenesis of thyroid tumours is still unclear, an increasing number of studies have found that certain lifestyle and residence environments are associated with their occurrence and development. This article endeavours to elucidate the correlation between lifestyle, residential environment, and the increased prevalence of thyroid cancer in recent years. It specifies the frequency of the lifestyle and outlines the scope of the residential environment. It also endeavours to summarise the main mechanistic pathways of various modifiable risk factors that cause thyroid cancer. Factors that prevent thyroid cancer include smoking and alcohol consumption, quality and regular sleep, consumption of cruciferous vegetables and dairy products, and consistent long-term exercise. Conversely, individuals with specific genetic mutations have an elevated risk of thyroid cancer from prolonged and frequent use of mobile phones. In addition, individuals who work in high-pressure jobs, work night shifts, and live near volcanoes or in environments associated with pesticides have an elevated risk of developing thyroid cancer. The impact of living near a nuclear power plant on thyroid cancer remains inconclusive. Raising awareness of modifiable risk factors for thyroid cancer will help to accurately prevent and control thyroid cancer. It will provide a scientific basis for future research on lifestyles and living environments suitable for people at high risk of thyroid cancer.
... сравнить объемные выборки семей, которые были подвержены вредоносному излучению с теми, кто не был облучен. Японские ученые во главе с K. Suzuki [18] изучили взаимосвязь воздействия больших доз радиации и частоту обнаружения рака щитовидной железы у детей, переживших аварию на Чернобыльской АЭС. Было показано, что онкологическое заболевание начало проявляться только через 4-5 лет после катастрофы. ...
Giant uterine myoma in a 15-year-old girl with thyroid cancer and hereditary diseases
© N.A. SHCHUKINA, I.V. BARINOVA, I.N. VOLOSHCHUK, S.N. BUYANOVA, E.L. BABUNASHVILI, N.YU. ZEMSKOVA, D.Y. SON, I.V. ZAV’YALOVA, M.A. BEKOVA
Moscow Regional Research Institute of Obstetrics and Gynecology, Moscow, Russia
Uterine myoma is one of the most common diseases of the female genital system, it is diagnosed in 70% of patients of reproduc- tive age. Studies demonstrate that this disease tends to rejuvenate, and in 15.3% of cases there is a connection between uterine myoma and hereditary diseases. Numerous scientific publications also convincingly testify to the contribution of genetic aberra- tions in the development of uterine myoma.
Objective. To present a clinical observation of giant uterine myoma in a fifteen-year-old female patient with genetic diseases and endocrine system pathology in anamnesis.
Material and methods. This publication describes the clinical observation of a 15-year-old female patient with giant uterine myoma who underwent thyroidectomy for thyroid cancer and who had Charcot-Marie-Tooth neural amyotrophy.
Results. An organ-sparing operation (myomectomy) was performed in a 15-year-old patient with a giant uterine myoma who under- went thyroidectomy for thyroid cancer and a genetic disease (Charcot-Marie-Tooth neural amyotrophy).
Conclusion. The presented observation is a confirmation of the fact that unfavorable environmental conditions may increase the risk of genetically determined combined severe extragenital and gynecological diseases. Undoubtedly, the development of molecular
INFORMATION ABOUT THE AUTHORS:
Schukina N.A. — https://orcid.org/0000-0003-2274-4070 Barinova I.V. — https://orcid.org/0000-0003-0447-1734 Voloshchuk I.N. — https://orcid.org/0000-0002-7059-5105 Buyanova S.N. — https://orcid.org/0000-0002-1358-6640 Babunashvili E.L. — https://orcid.org/0000-0002-3580-7221 Zemskova N.Yu. — https://orcid.org/0000-0001-5460-0122
Son D.Yu. — https://orcid.org/0000-0002-8570-1070
Zav’yalova I.V. — https://orcid.org/0000-0002-0893-476X Bekova M.A. — https://orcid.org/0000-0002-2362-433X
TO CITE THIS ARTICLE:
Shchukina NA, Barinova IV, Voloshchuk IN, Buyanova SN, Babunashvili EL, Zemskova NYu, Son DYu, Zav’yalova IV, Bekova MA. Giant uterine myoma in a 15-year-old girl with thyroid cancer and hereditary diseases. Russian Bulletin of Obstetrician-Gynecologist = Rossiiskii vestnik akushera-ginekologa. 2023;23(6-2):179–182. (In Russ.). https://doi.org/10.17116/rosakush202323062179
... Indeed, because sporadic childhood thyroid cancers found in the affected areas were quite rare, most of the cancer cases diagnosed after the Chernobyl accident could be attributable to radiation exposure. Therefore, molecular analyses were performed to understand the radiation signatures associated with malignant conversion of normal thyroid follicular cells (89). ...
... The data collected seem to show that the frequency of rearrangements, particularly that of the RET/PTC1 rearrangement, was comparable between the two groups of patients with radiation-induced and sporadic tumors (97,(101)(102)(103). This suggests that RET/PTC rearrangements in radiation-related cases might not be the signature of radiation, but rather, radiation exposure might unveil RET/PTC rearrangements that occurred spontaneously (89). In fact, considering that thyroid cancers in children started to occur 4-5 years after the Chernobyl accident, it would be reasonable to assume that thyroid follicular cells with RET/PTC rearrangements already existed, and radiation exposure could provide a chance for cells with such tumor signatures to proliferate (89). ...
... This suggests that RET/PTC rearrangements in radiation-related cases might not be the signature of radiation, but rather, radiation exposure might unveil RET/PTC rearrangements that occurred spontaneously (89). In fact, considering that thyroid cancers in children started to occur 4-5 years after the Chernobyl accident, it would be reasonable to assume that thyroid follicular cells with RET/PTC rearrangements already existed, and radiation exposure could provide a chance for cells with such tumor signatures to proliferate (89). ...
Iodine is an essential element for the production of thyroid hormones (THs). Both deficient and excess iodine intakes may precipitate in adverse thyroidal events. Radioactive iodine (RI) is a common byproduct of nuclear fission processes. During nuclear emergencies RI may be released in a plume, or cloud, contaminating the environment. If inhaled or ingested, it may lead to internal radiation exposure and the uptake of RI mainly by the thyroid gland that absorbs stable iodine (SI) and RI in the same way. A dose of radiation delivered to the thyroid gland is a main risk factor for the thyroid cancer development. The SI prophylaxis helps prevent childhood thyroid cancer. The thyroid gland saturation with prophylactic SI ingestion, reduces the internal exposure of the thyroid by blocking the uptake of RI and inhibiting iodide organification. However, negative impact of inadequate SI intake must be considered. We provide an overview on the recommended iodine intake and the impact of SI and RI on thyroid in children and adolescents, discussing the benefits and adverse effects of the prophylactic SI for thyroid blocking during a nuclear accident. The use of SI for protection against RI may be recommended in cases of radiological or nuclear emergencies, moreover the administration of iodine for prophylactic purposes should be cautious. Benefits and risks should also be considered according to age. Adverse effects from iodine administration cannot be excluded. Precise indications are mandatory to use the iodine for thyroid blocking. Due to this natural adaption mechanism it’s possible to tolerate large doses of iodine without clinical effects, however, a prolonged assumption of the iodine when not needed can be dangerous and may precipitate in severe thyroidal and non-thyroidal negative effects.
... accident. RNA microarray analyses of PTC tumours from primarily children exposed to radioactive fallout from the Chernobyl accident resulted in a plethora of suggested biomarkers, potentially due to the difficulty of using a representative control group (regarding age, dietary, geographical area, gender, etc.) [9][10][11][12][13][14][15][48][49][50][51][52][53][54][55][56][57][58] . Furthermore, CLIP2 and TG were the only previously suggested biomarkers that were also identified in the present study 11,12,16,53,54 . ...
131I is used clinically for therapy, and may be released during nuclear accidents. After the Chernobyl accident papillary thyroid carcinoma incidence increased in children, but not adults. The aims of this study were to compare 131I irradiation-dependent differences in RNA and protein expression in the thyroid and plasma of young and adult rats, and identify potential age-dependent biomarkers for 131I exposure. Twelve young (5 weeks) and twelve adult Sprague Dawley rats (17 weeks) were i.v. injected with 50 kBq 131I (absorbed dose to thyroid = 0.1 Gy), and sixteen unexposed age-matched rats were used as controls. The rats were killed 3-9 months after administration. Microarray analysis was performed using RNA from thyroid samples, while LC-MS/MS analysis was performed on proteins extracted from thyroid tissue and plasma. Canonical pathways, biological functions and upstream regulators were analysed for the identified transcripts and proteins. Distinct age-dependent differences in gene and protein expression were observed. Novel biomarkers for thyroid 131I exposure were identified: (PTH), age-dependent dose response (CA1, FTL1, PVALB (youngsters) and HSPB6 (adults)), thyroid function (Vegfb (adults)). Further validation using clinical samples are needed to explore the role of the identified biomarkers.
... Childhood thyroid carcinoma was of great concern in Fukushima Prefecture, and anxiety regarding thyroid carcinoma was noteworthy, especially in the residents of Fukushima as previous studies had reported that one of the main adverse health effects of radiation fallout from nuclear power plant (NPP) accidents, specifically the Chernobyl NPP accident, had been a substantial rise in thyroid cancer among young people exposed to radiation (13)(14)(15). Even though the radiation exposure levels of Fukushima residents were considered to be much lower than those of Chernobyl residents (16), surveys had to be conducted to fulfill both scientific and social concerns (17). ...
... These guidelines for the FNAC criteria were based on the ultrasound diagnostic criteria for thyroid nodule published by the Japan Society of Ultrasonics in Medicine ( JSUM), in which the primary findings indicating malignancy were irregular shape, the presence of an ill-defined nodule with a jagged border, and a low and heterogeneous internal echo level. The secondary findings indicating malignancy were fine strong echoes and a heterogeneous marginal hypoechoic zone (14). With respect to blood examinations, thyroid function tests were performed to evaluate the feasibility of FNAC, and FNAC was not performed in cases with overt thyrotoxicosis. ...
Background: The thyroid ultrasound examination (TUE) program was initiated among the residents of Fukushima Prefecture aged ≤18 years at the time of the Fukushima Dai-ichi Nuclear Power Plant accident. In this program, fine needle aspiration cytology (FNAC) was performed only in cases that conformed to the Japanese guidelines for the management of thyroid nodules. To analyze the suitability of the protocol in the TUE, we analyzed the implementation rate of FNAC and the detection rate of thyroid malignancy. Methods: There were 299,939 and 269,659 voluntary participants in the Preliminarily Baseline Survey (PLBS), first-round survey, and the first Full-scale Survey (FSS), second-round survey, of the TUE, respectively. FNAC is recommended for nodules with diameters 5.1-10.0 mm showing sonographic characteristics that are strongly suspicious for thyroid carcinoma; diameters 10.1-20.0 mm with characteristics that are suspicious for carcinoma; and all nodules with diameters >20 mm. Results: In the PLBS and the first FSS, 1362 and 1382 cases with thyroid nodules sized ≥5.1 mm in diameter were found, respectively. The implementation rates of FNAC in the PLBS were 20.1%, 63.2%, and 87.7% of subjects with nodules sized 5.1-10.0, 10.1-20.0, and ≥20.1 mm in diameter, respectively. In the first FSS, the FNAC implementation rates were 7.3%, 26.0%, and 50.0% in the subjects with nodules with diameters 5.1-10.0, 10.1-20.0, and ≥20.1 mm, respectively. In the subjects who underwent FNAC, the detection rates of malignant and suspected malignant nodules were 21.4% and 34.1% in the PLBS and first FSS, respectively. In the first FSS, malignant or suspected malignant nodules were found in 0.63% and 0.40% of subjects who had nodules of diameters ≤5.0 mm and 5.1-10.0 mm in the PLBS, respectively. In contrast, in the subjects with nodules measuring ≥10.0 mm in diameter in the PLBS, no malignancies were detected. Conclusions: The use of a protocol that conformed to the Japanese guidelines led to a reduction in the FNAC implementation rate and an increase in the malignancy detection rate in smaller nodules. In addition, the use of this strategy enabled us to avoid detection failure of thyroid carcinomas >10.0 mm.
... In Ukraine, there are recorded cases of tumors in the fetus and attempts of intrauterine resection of such tumors [9]. The Chernobyl accident in 1986 may provoke an environmental disaster in Ukraine with the gradual growth of cancer pathology of various locations [10][11][12][13]. In 2013, WHO adopted the Global Plan of Action on the prevention of non-communicable diseases and fight against them during 2013-2020, which provides for a series of actions aimed at reducing by 25% premature deaths from oncology and cardiovascular disease, diabetes, and acute respiratory diseases [14]. ...
... The sad outcome of the twenty-five-year history of the dynamics of morbidity after the Chernobyl disaster confirmed the dominance and progression of severe forms of vegetative-vascular dystonia in the first years after the Chernobyl disaster (which were veiled by radiophobia, psychosomatic disorders) and parallel progressive increase of oncopathology rate [10][11][12][13]. The discussed result of the visualization of PathoNeoAngioOncogenesis at the microcirculatory level due to vascular screening technology. ...
... 10. Individual approach in the diagnosis of circulatory disorders enables to optimize the further tactics of treating cancer patients with adequate selection of doses and treatment regimens on the basis of evidence-based medicine under the control of modern diagnostic equipment and vascular innovative technologies with the ability to obtain analytical data and clinical interpretation of the changes made at the expert conclusion level. 11. Pathological angiogenesis requires effective tools for controlling the process of reverse sanogeneous angiotransformation on the micro-and macrocirculatory levels in both the arterial and venous links. ...
The monograph is devoted to the current problem of visualization and assessment of the severity of pathological vascular transformations in cardiovascular and cancer diseases. The signs of pathological neoangiooncogenesis at the micro- and macroangiological levels are analyzed in detail.
... However, molecular and epidemiological studies so far have provided no apparent evidence of radiation signatures, indicating that the role of radiation exposure in radiation-induced cancer might not be the induction of driver oncogenic mutations. A good example supporting this idea has been seen in childhood thyroid cancer cases after the Chernobyl nuclear power plant (CNPP) accident [37][38][39]. According to a recent UNSCEAR report, a total of 19 233 thyroid cancer cases were documented in 1991-2015 among those who were <18 years of age at the time of the Chernobyl accident [40]. ...
... In other words, the frequency of thyroid cancer with gene fusions was increased dependent upon thyroid doses. However, we should be cautious in concluding that radiation exposure is a primary cause of the gene fusions, since oncogenic gene fusion is also a predominant driver mutation in sporadic pediatric cases [38,39,42]. If radiation exposure is the primary cause of gene fusions, the ratio of the cases with gene fusions vs point mutations should not be like that observed in pediatric sporadic cases. ...
DNA double-strand breaks (DSBs) induced by ionizing radiation are the major cause of cell death, leading to tissue/organ injuries, which is a fundamental mechanism underlying the development of tissue reaction. Since unscheduled senescence, predominantly induced among epithelial tissues/organs, is one of the major modes of cell death in response to radiation exposure, its role in tissue reaction has been extensively studied, and it has become clear that senescence-mediated secretion of soluble factors is an indispensable component of the manifestation of tissue reaction. Recently, an unexpected link between cytoplasmic DSBs and innate immunity was discovered. The activation of cyclic GMP-AMP (cGAMP) synthase (cGAS) results in the stimulation of the cGAS–stimulator of interferon genes (STING) pathway, which has been shown to regulate the transactivation of a variety of secretory factors that are the same as those secreted from senescent cells. Furthermore, it has been proven that cGAS–STING pathway also mediates execution of the senescence process by itself. Hence, an autocrine/paracrine feedback loop has been discussed in previous literature in relation to its effect on the tissue microenvironment. As the tissue microenvironment plays a crucial role in cancer development, tissue reaction could be involved in the late health effects caused by radiation exposure. In this paper, the novel findings in radiation biology, which should provide a better understanding of the mechanisms underlying radiation-induced carcinogenesis, are overviewed.
... Therefore, we need better knowledge of the effects of ionizing radiation on thyroid tissue, especially in young individuals. It is important to study both the short-and long-term radiobiological effects on thyroid tissue, since tumour initiation occurs early after exposure, while cancer diagnosis occurs years after exposure [10]. Exposure to ionizing radiation results in the activation/inhibition of several different cellular processes, where a number of the activated genes may have altered expression patterns [11,12]. ...
Background
Radioiodide (131I) is commonly used to treat thyroid cancer and hyperthyroidis.131I released during nuclear accidents, have resulted in increased incidence of thyroid cancer in children. Therefore, a better understanding of underlying cellular mechanisms behind 131I exposure is of great clinical and radiation protection interest. The aim of this work was to study the long-term dose-related effects of 131I exposure in thyroid tissue and plasma in young rats and identify potential biomarkers.
Materials and methods
Male Sprague Dawley rats (5-week-old) were i.v. injected with 0.5, 5.0, 50 or 500 kBq 131I (Dthyroid ca 1–1000 mGy), and killed after nine months at which time the thyroid and blood samples were collected. Gene expression microarray analysis (thyroid samples) and LC-MS/MS analysis (thyroid and plasma samples) were performed to assess differential gene and protein expression profiles in treated and corresponding untreated control samples. Bioinformatics analyses were performed using the DAVID functional annotation tool and Ingenuity Pathway Analysis (IPA). The gene expression microarray data and LC-MS/MS data were validated using qRT-PCR and ELISA, respectively.
Results
Nine 131I exposure-related candidate biomarkers (transcripts: Afp and RT1-Bb, and proteins: ARF3, DLD, IKBKB, NONO, RAB6A, RPN2, and SLC25A5) were identified in thyroid tissue. Two dose-related protein candidate biomarkers were identified in thyroid (APRT and LDHA) and two in plasma (DSG4 and TGM3). Candidate biomarkers for thyroid function included the ACADL and SORBS2 (all activities), TPO and TG proteins (low activities). 131I exposure was shown to have a profound effect on metabolism, immune system, apoptosis and cell death. Furthermore, several signalling pathways essential for normal cellular function (actin cytoskeleton signalling, HGF signalling, NRF2-mediated oxidative stress, integrin signalling, calcium signalling) were also significantly regulated.
Conclusion
Exposure-related and dose-related effects on gene and protein expression generated few expression patterns useful as biomarkers for thyroid function and cancer.
... Ймовірна відповідь на це питання міститься в роботах, результати яких свідчать про можливість заміни Akt у сигнальному ланцюгу РІ3К іншими ферменту може попереджати таку стимуляцію чи навіть гальмувати загибель протеїнкіназами, зокрема Sgk3 (serum/glucocorticoid regulated kinase) [102]. [448]. Отже, внесок радіаційного впливу в індукцію онкогенних перебудов у пацієнтів потребує подальшого з'ясування [450]. ...
... In particular, the fallout of radioactive iodine resulted in significant internal exposures in children mainly through the ingestion of contaminated Since sporadic childhood thyroid cancers in the affected areas was quite rare, most cancer cases diagnosed after the Chernobyl accident could be attributable to the radiation exposure. Therefore, thyroid cancers diagnosed in children were expected to provide unique opportunities to scrutinize molecular radiation signatures associated with malignant conversion of the normal thyroid follicular cells [24]. ...
... The inter-chromosomal translocation is also involved in the formation of other types of rearrangements, such as ETV6-NTRK3 (Figure 1). Theoretically, rearrangements need at least two DNA double-strand breaks, so that exposure to the radiation, which is a well-known inducer for DNA double-strand breaks, has been assumed to cause such rearrangements through an illegitimate recombination of the broken DNA ends [24]. Furthermore, it has been proposed that the folding of the chromosomal 10q11.2-21 ...
... Although the experiments have proven that the RET/PTC rearrangements are induced by the Theoretically, rearrangements need at least two DNA double-strand breaks, so that exposure to the radiation, which is a well-known inducer for DNA double-strand breaks, has been assumed to cause such rearrangements through an illegitimate recombination of the broken DNA ends [24]. Furthermore, it has been proposed that the folding of the chromosomal 10q11.2-21 ...
Enormous amounts of childhood thyroid cancers, mostly childhood papillary thyroid carcinomas (PTCs), after the Chernobyl nuclear power plant accident have revealed a mutual relationship between the radiation exposure and thyroid cancer development. While the internal exposure to radioactive 131I is involved in the childhood thyroid cancers after the Chernobyl accident, people exposed to the external radiation, such as atomic-bomb (A-bomb) survivors, and the patients who received radiation therapy, have also been epidemiologically demonstrated to develop thyroid cancers. In order to elucidate the mechanisms of radiation-induced carcinogenesis, studies have aimed at defining the molecular changes associated with the thyroid cancer development. Here, we overview the literatures towards the identification of oncogenic alterations, particularly gene rearrangements, and discuss the existence of radiation signatures associated with radiation-induced thyroid cancers.
