A post-irradiation-induced replication stress promotes RET proto-oncogene breakage.

Objective: Ionizing radiation generates genomic instability by promoting the accumulation of chromosomal rearrangements. The oncogenic translocation RET/PTC1 is present in more than 70% of radiation-induced thyroid cancers. Both RET and CCDC6, the genes implicated in RET/PTC1, are found within common fragile sites - chromosomal regions prone to DNA breakage during slight replication stress.

Methods for detection of mitochondrial reactive oxygen species in senescent cells.

Cellular senescence is a pathophysiological process with multifaceted effects. It is involved in wound healing, aging and age-related diseases as well as cancer. On the one hand, senescence is considered as barrier against tumorigenesis by inducing an irreversible/prolonged cell cycle arrest.

A Comparative Analysis of NOX4 Protein Expression in Malignant and Non-Malignant Thyroid Tumors.

The comparative analysis of the expression of the reactive oxygen species-generating NADPH oxidase NOX4 from TCGA data shows that the NOX4 transcript is upregulated in papillary thyroid carcinomas (PTC)-BRAF tumors compared to PTC-BRAF tumors. However, a comparative analysis of NOX4 at the protein level in malignant and non-malignant tumors is missing. We explored NOX4 protein expression by immunohistochemistry staining in malignant tumors (28 classical forms of PTC (C-PTC), 17 follicular variants of PTC (F-PTC), and three anaplastic thyroid carcinomas (ATCs)) and in non-malignant tumors (six lymphocytic thyroiditis, four Graves' disease, ten goiters, and 20 hyperplasias).

Caspase Inhibition Modulates Monocyte-Derived Macrophage Polarization in Damaged Tissues.

Circulating monocytes are recruited in damaged tissues to generate macrophages that modulate disease progression. Colony-stimulating factor-1 (CSF-1) promotes the generation of monocyte-derived macrophages, which involves caspase activation. Here, we demonstrate that activated caspase-3 and caspase-7 are located to the vicinity of the mitochondria in CSF1-treated human monocytes.

New insights in the molecular regulation of the NADPH oxidase 2 activity: Negative modulation by Poldip2.

Poldip2 was shown to be involved in oxidative signaling to ensure certain biological functions. It was proposed that, in VSMC, by interaction with the Nox4-associated membrane protein p22, Poldip2 stimulates the level of reactive oxygen species (ROS) production. In vitro, with fractionated membranes from HEK393 cells over-expressing Nox4, we confirmed the up-regulation of NADPH oxidase 4 activity by the recombinant and purified Poldip2.

Strategies for Radioiodine Treatment: What's New.

Radioiodine treatment (RAI) represents the most widespread and effective therapy for differentiated thyroid cancer (DTC). RAI goals encompass ablative (destruction of thyroid remnants, to enhance thyroglobulin predictive value), adjuvant (destruction of microscopic disease to reduce recurrences), and therapeutic (in case of macroscopic iodine avid lesions) purposes, but its use has evolved over time. Randomized trial results have enabled the refinement of RAI indications, moving from a standardized practice to a tailored approach.

Redox Homeostasis in Thyroid Cancer: Implications in Na/I Symporter (NIS) Regulation.

Radioiodine therapy (RAI) is a standard and effective therapeutic approach for differentiated thyroid cancers (DTCs) based on the unique capacity for iodide uptake and accumulation of the thyroid gland through the Na/I symporter (NIS). However, around 5-15% of DTC patients may become refractory to radioiodine, which is associated with a worse prognosis. The loss of RAI avidity due to thyroid cancers is attributed to cell dedifferentiation, resulting in NIS repression by transcriptional and post-transcriptional mechanisms.

Anaplastic Thyroid Carcinoma: An Update.

Anaplastic thyroid carcinoma (ATC) is a rare and undifferentiated form of thyroid cancer. Its prognosis is poor: the median overall survival (OS) of patients varies from 4 to 10 months after diagnosis. However, a doubling of the OS time may be possible owing to a more systematic use of molecular tests for targeted therapies and integration of fast-track dedicated care pathways for these patients in tertiary centers.

BRAF hot spot mutation in thyroid carcinomas: first Moroccan experience from a single-institution retrospective study.

Background: The incidence of thyroid cancer is increasing worldwide at an alarming rate. BRAF mutation is described to be associated with a worse prognostic of thyroid carcinomas, as well as extrathyroidal invasion and increased mortality.

Objective: To our knowledge, there are no reported studies neither from Morocco nor from other Maghreb countries regarding the prevalence of BRAF mutation in thyroid carcinomas.

Exercise-Stimulated ROS Sensitive Signaling Pathways in Skeletal Muscle.

Physical exercise represents a major challenge to whole-body homeostasis, provoking acute and adaptative responses at the cellular and systemic levels. Different sources of reactive oxygen species (ROS) have been described in skeletal muscle (e.g.

Redifferentiation-facilitated radioiodine therapy in thyroid cancer.

Based on experimental data, the inhibition of the MAPkinase pathway in patients with radioiodine-refractory thyroid cancer was capable of inducing a redifferentiation. Preliminary data obtained in a small series of patients were encouraging and this strategy might become an alternative treatment in those patients with a druggable mutation that induces a stimulation of the MAP kinase pathway. This is an active field of research to answer many still unresolved questions.

NADPH oxidase DUOX1 sustains TGF-β1 signalling and promotes lung fibrosis.

Interstitial lung fibroblast activation coupled with extracellular matrix production is a pathological signature of pulmonary fibrosis, and is governed by transforming growth factor (TGF)-β1/Smad signalling. TGF-β1 and oxidative stress cooperate to drive fibrosis. Cells can produce reactive oxygen species through activation and/or induction of NADPH oxidases, such as dual oxidase (DUOX1/2).

Dual oxidase 1 limits the IFNγ-associated antitumor effect of macrophages.

Background: Macrophages play pivotal roles in tumor progression and the response to anticancer therapies, including radiotherapy (RT). Dual oxidase (DUOX) 1 is a transmembrane enzyme that plays a critical role in oxidant generation.

Methods: Since we found DUOX1 expression in macrophages from human lung samples exposed to ionizing radiation, we aimed to assess the involvement of DUOX1 in macrophage activation and the role of these macrophages in tumor development.

Redifferentiation of radioiodine-refractory thyroid cancers.

The management of radioiodine refractory thyroid cancers (RAIR TC) is challenging for the clinician. Tyrosine kinase inhibitors classically prescribed in this setting can fail due to primary or acquired resistance or the necessity of drug withdrawal because of serious or moderate but chronic and deleterious adverse effects. Thus, the concept of redifferentiation strategy, which involves treating patients with one or more drugs capable of restoring radioiodine sensitivity for RAIR TC, has emerged.

Redox Signaling in Widespread Health Benefits of Exercise.

Exercise-induced reactive oxygen species (ROS) production activates multiple intracellular signaling pathways through genomic and nongenomic mechanisms that are responsible for the beneficial effects of exercise in muscle. Beyond the positive effect of exercise on skeletal muscle cells, other tissues such as white and brown adipose, liver, central nervous system, endothelial, heart, and endocrine organ tissues are also responsive to exercise. Crosstalk between different cells is essential to achieve homeostasis and to promote the benefits of exercise through paracrine or endocrine signaling.

Selective modification of a native protein in a patient tissue homogenate using palladium nanoparticles.

We have developed new benign palladium nanoparticles able to catalyze the Suzuki-Miyaura cross-coupling reaction on human thyroglobulin (Tg), a naturally iodinated protein produced by the thyroid gland, in homogenates from patients' tissues. This represents the first example of a chemoselective native protein modification using transition metal nanoobjects in near-organ medium.

Redox modifications of cysteine-containing proteins, cell cycle arrest and translation inhibition: Involvement in vitamin C-induced breast cancer cell death.

Vitamin C (VitC) possesses pro-oxidant properties at high pharmacologic concentrations which favor repurposing VitC as an anti-cancer therapeutic agent. However, redox-based anticancer properties of VitC are yet partially understood. We examined the difference between the reduced and oxidized forms of VitC, ascorbic acid (AA) and dehydroascorbic acid (DHA), in terms of cytotoxicity and redox mechanisms toward breast cancer cells.

Redifferentiation of a -Mutated Poorly Differentiated Thyroid Cancer Patient with Dabrafenib and Trametinib Treatment.

A 59-year-old woman with locally invasive poorly differentiated thyroid cancer with synchronous lung, mediastinal, and bone metastases and a somatic mutation with contraindication for antiangiogenic drugs was treated with dabrafenib and trametinib. During treatment, serum levels of thyroglobulin increased as early as day 7 up to 10-fold over baseline at week 4. Concurrently, clinical hyperthyroidism occurred, with free triiodothyronine and free thyroxine levels increasing to 6.

Oxidative stress in thyroid carcinomas: biological and clinical significance.

At physiological concentrations, reactive oxygen species (ROS), including superoxide anions and H2O2, are considered as second messengers that play key roles in cellular functions, such as proliferation, gene expression, host defence and hormone synthesis. However, when they are at supraphysiological levels, ROS are considered potent DNA-damaging agents. Their increase induces oxidative stress, which can initiate and maintain genomic instability.

Conformation of the N-Terminal Ectodomain Elicits Different Effects on DUOX Function: A Potential Impact on Congenital Hypothyroidism Caused by a HO Production Defect.

Background: Dual oxidases (DUOX1 and DUOX2) were initially identified as HO sources involved in thyroid hormone synthesis. Congenital hypothyroidism (CH) resulting from inactivating mutations in the DUOX2 gene highlighted that DUOX2 is the major HO provider to thyroperoxidase. The role of DUOX1 in the thyroid remains unknown.

HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via mitochondrial ROS production.

Human immunodeficiency virus (HIV) infection is associated with B-cell malignancies in patients though HIV-1 is not able to infect B-cells. The rate of B-cell lymphomas in HIV-infected individuals remains high even under the combined antiretroviral therapy (cART) that reconstitutes the immune function. Thus, the contribution of HIV-1 to B-cell oncogenesis remains enigmatic.