scholarly journals Single neonatal irradiation induces long-term gene expression changes in the thyroid gland, which may be involved in the tumorigenesis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nariaki Fujimoto ◽  
Mutsumi Matsuu-Matsuyama ◽  
Masahiro Nakashima

AbstractExposure to ionizing radiation in childhood has been recognized as a risk factor for thyroid cancer. We previously demonstrated that neonatal X-irradiation induced specific deformation of the thyroid follicles. Here, we further analyzed this model to understand the possible relationship with thyroid carcinogenesis. Wistar rats were subjected to cervical X-irradiation at different ages of 1–8 weeks old and at different doses of 1.5–12 Gy. For tumor promotion, rats were fed with an iodine-deficient diet (IDD). In cervically X-irradiated neonatal rats, the size of thyroid follicles decreased, accompanied by an increase in the number of TUNEL-positive cells. Fas and Lgals3 mRNA levels increased, while Mct8 and Lat4 expressions decreased. The co-administration of IDD induced the proliferation and the upregulation in Lgals3 expression, resulting in thyroid adenoma development at 28 weeks post-exposure. Our data demonstrated that single neonatal X-irradiation induced continuous apoptotic activity in the thyroid with the long-term alternation in Fas, Mct8, Lat4, and Lgals3 mRNA expressions. Some of these changes were similar to those induced by IDD, suggesting that neonatal X-irradiation may partially act as a thyroid tumor promoter. These radiation-induced thyroidal changes may be enhanced by the combined treatment with IDD, resulting in the early development of thyroid adenoma.

Neurosurgery ◽  
2012 ◽  
Vol 71 (6) ◽  
pp. 1139-1148 ◽  
Author(s):  
Lucia Schwyzer ◽  
Chun-Po Yen ◽  
Avery Evans ◽  
Sebastian Zavoian ◽  
Ladislau Steiner

ABSTRACT BACKGROUND: The effectiveness and risk of Gamma Knife surgery (GKS) in the management of partially embolized cerebral arteriovenous malformations (AVMs) remain to be elucidated. OBJECTIVE: To evaluate the long-term imaging and clinical outcomes of GKS in AVM patients who had undergone previous partial embolization and compare the results with patients treated with GKS alone. METHODS: A total of 215 embolized AVMs were analyzed. The mean patient age was 32.9 years. The mean volume of the nidus was 4.6 mL (range, 0.1-29.4 mL), and the mean prescription dose was 19.6 Gy (range, 4-28 Gy). This group was compared with 729 nonembolized AVMs. RESULTS: After embolization and GKS, angiographically confirmed total obliteration of the AVMs was significantly lower (33%) compared with patients in whom GKS was used alone (60.9%; P < .001). However, the mean nidus size was larger and the Spetzler-Martin grade was higher for the embolized AVMs compared with the nonembolized AVMs. Radiation-induced changes occurred more often in the embolized (43.4%) than the nonembolized (33.4%) AVMs (P = .028). Permanent neurological deficits associated with radiation-induced changes occurred in 2.7% of the embolized compared with 1.3% of the nonembolized patients (P = .14). CONCLUSION: In our retrospective and historical series, the long-term results suggest that the obliteration rate is significantly lower in embolized AVMs compared with nonembolized AVMs, also because of the fact that the combined treatment is applied to higher grade AVMs; the percentage of grade III-V AVMs was 58.6% and 48.8% for nonembolized AVMs.


Author(s):  
I.V. Vasilieva ◽  
◽  
V.V. Egorov ◽  
S.V. Kostenev ◽  
A.V. Vasiliev ◽  
...  

2001 ◽  
Vol 95 (2) ◽  
pp. 232-235 ◽  
Author(s):  
Andrew J. Martin ◽  
Christopher J. Hammond ◽  
H. Jane Dobbs ◽  
Safa Al-Sarraj ◽  
Nicholas W. M. Thomas

✓ Long-term survivors of Hodgkin disease may develop second primary tumors caused by the mutagenic effects of radio- and chemotherapy. The authors describe the case of a 35-year-old woman who presented with an unusual meningioma of the cervical spine 9 years after undergoing combined-modality treatment for Hodgkin disease. To the authors' knowledge, this is the first report of spinal meningioma as a complication of such therapy. Whereas radiation-induced intracranial meningiomas are well described in the literature, treatment-induced meningiomas of the spine have not been widely recognized.


2020 ◽  
Author(s):  
Xiang Yu ◽  
Minshu Li ◽  
Lin Zhu ◽  
Jingfei li ◽  
Guoli Zhang ◽  
...  

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Mayarling Francisca Troncoso ◽  
Mario Pavez ◽  
Carlos Wilson ◽  
Daniel Lagos ◽  
Javier Duran ◽  
...  

Abstract Background Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake—via AMP-activated protein kinase (AMPK)—after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). Methods Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of β-myosin heavy chain (β-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). Results Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated β-mhc, Hk2 and Pfk2 mRNA levels. Conclusion These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.


2020 ◽  
Vol 22 (1) ◽  
pp. 221
Author(s):  
Joanna Wójtowicz ◽  
Adam K. Jagielski ◽  
Agnieszka Mostowska ◽  
Katarzyna B. Gieczewska

The origin of chlorophyll b deficiency is a mutation (ch1) in chlorophyllide a oxygenase (CAO), the enzyme responsible for Chl b synthesis. Regulation of Chl b synthesis is essential for understanding the mechanism of plant acclimation to various conditions. Therefore, the main aim of this study was to find the strategy in plants for compensation of low chlorophyll content by characterizing and comparing the performance and spectral properties of the photosynthetic apparatus related to the lipid and protein composition in four selected Arabidopsis ch1 mutants and two Arabidopsis ecotypes. Mutation in different loci of the CAO gene, viz., NW41, ch1.1, ch1.2 and ch1.3, manifested itself in a distinct chlorina phenotype, pigment and photosynthetic protein composition. Changes in the CAO mRNA levels and chlorophyllide a (Chlide a) content in ecotypes and ch1 mutants indicated their significant role in the adjustment mechanism of the photosynthetic apparatus to low-light conditions. Exposure of mutants with a lower chlorophyll b content to short-term (1LL) and long-term low-light stress (10LL) enabled showing a shift in the structure of the PSI and PSII complexes via spectral analysis and the thylakoid composition studies. We demonstrated that both ecotypes, Col-1 and Ler-0, reacted to high-light (HL) conditions in a way remarkably resembling the response of ch1 mutants to normal (NL) conditions. We also presented possible ways of regulating the conversion of chlorophyll a to b depending on the type of light stress conditions.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.


2021 ◽  
Vol 22 (2) ◽  
pp. 599
Author(s):  
Lucia Carboni ◽  
Luisa Ponzoni ◽  
Daniela Braida ◽  
Mariaelvina Sala ◽  
Cecilia Gotti ◽  
...  

Nicotine addiction is a severe public health problem. The aim of this study was to investigate the alterations in key neurotransmissions after 60 days of withdrawal from seven weeks of intermittent cigarette smoke, e-cigarette vapours, or an e-cigarette vehicle. In the nicotine withdrawal groups, increased depressive and anxiety/obsessive–compulsive-like behaviours were demonstrated in the tail suspension, sucrose preference and marble burying tests. Cognitive impairments were detected in the spatial object recognition test. A significant increase in Corticotropin-releasing factor (Crf) and Crf1 mRNA levels was observed, specifically after cigarette withdrawal in the caudate-putamen nucleus (CPu). The nociceptin precursor levels were reduced by cigarette (80%) and e-cigarette (50%) withdrawal in the CPu. The delta opioid receptor showed a significant reduction in the hippocampus driven by the exposure to an e-cigarette solubilisation vehicle, while the mRNA levels doubled in the CPu of mice that had been exposed to e-cigarettes. Withdrawal after exposure to e-cigarette vapour induced a 35% Bdnf mRNA decrease in the hippocampus, whereas Bdnf was augmented by 118% by cigarette withdrawal in the CPu. This study shows that long-term withdrawal-induced affective and cognitive symptoms associated to lasting molecular alterations in peptidergic signalling may determine the impaired neuroplasticity in the hippocampal and striatal circuitry.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anne-Christine Plank ◽  
Stefan Frey ◽  
Lukas Andreas Basedow ◽  
Jalal Solati ◽  
Fabio Canneva ◽  
...  

AbstractIn our previous study, we found that prenatal trauma exposure leads to an anxiety phenotype in mouse pups, characterized by increased corticosterone levels and increased anxiety-like behavior. In order to understand the mechanisms by which aversive in utero experience leads to these long-lasting behavioral and neuroendocrine changes, we investigated stress reactivity of prenatally traumatized (PT) mice, as well as the expression and methylation levels of several key regulatory genes of the stress axis in the dorsal hippocampus (dHPC) of the PT embryo and adult mice. We detected increased corticotropin-releasing hormone receptor 1 (Crhr1) and decreased FK506 binding protein 5 (Fkbp5) mRNA levels in the left dHPC of adult PT mice. These alterations were accompanied by a decreased methylation status of the Crhr1 promoter and an increased methylation status of the Fkbp5 promoter, respectively. Interestingly, the changes in Fkbp5 and Crhr1 mRNA levels were not detected in the embryonic dHPC of PT mice. Together, our findings provide evidence that prenatal trauma has a long-term impact on stress axis function and anxiety phenotype associated with altered Crhr1 and Fkbp5 transcripts and promoter methylation.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhuoqun Fang ◽  
Penghong Chen ◽  
Shijie Tang ◽  
Aizhen Chen ◽  
Chaoyu Zhang ◽  
...  

AbstractRadiation-induced skin injury (RISI) is one of the common serious side effects of radiotherapy (RT) for patients with malignant tumors. Mesenchymal stem cells (MSCs) are applied to RISI repair in some clinical cases series except some traditional options. Though direct replacement of damaged cells may be achieved through differentiation capacity of MSCs, more recent data indicate that various cytokines and chemokines secreted by MSCs are involved in synergetic therapy of RISI by anti-inflammatory, immunomodulation, antioxidant, revascularization, and anti-apoptotic activity. In this paper, we not only discussed different sources of MSCs on the treatment of RISI both in preclinical studies and clinical trials, but also summarized the applications and mechanisms of MSCs in other related regenerative fields.


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