Search

Background: The incidence of thyroid cancer is increasing worldwide at an alarming rate. BRAFV600E 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 re- garding the prevalence of BRAFV600E mutation in thyroid carcinomas. Here we aim to evaluate the frequency of BRAFV600E oncogene in Moroccan thyroid carcinomas. Methods: In this Single-Institution retrospective study realized in the Anatomic Pathology and Histology Service in the Mil- itary Hospital of Instruction Mohammed V ‘HMIMV’ in Rabat, we report, using direct genomic sequencing, the assessment of BRAFV600E in 37 thyroid tumors. Results: We detected BRAFV600E mutation exclusively in Papillary Thyroid Carcinomas ‘PTC’ with a prevalence of 28% (8 PTC out 29 PTC). Like international trends, Papillary Thyroid Carcinomas ’PTC’ is more frequent than Follicular Thyroid Carcinomas ‘FTC’ and Anaplastic Thyroid Carcinomas ‘ATC’ (29 PTC, 7 FTC and 1 ATC). Conclusion: Our finding gives to the international community the first estimated incidence of this oncogene in Morocco showing that this prevalence falls within the range of international trends (30% to 90%) reported in distinct worldwide ge- ographic regions. Keywords: Biomarker; BRAFV600E; Thyroid cancer; Morocco.

216 Background: Morocco has the highest cancer mortality rate in MENA Countries. Colorectal cancer (CRC) is classified as the first digestive cancer and remains a burden in Morocco. According to the data on GLOBOCAN 2020, there were 4324 new CRC patients and 2374 deaths, accounting for 7.3% and 2.8% of all cancers, respectively. Our study aimed to investigate the frequency of the full RAS ( KRAS, NRAS) and BRAF genes in CRC patients from Morocco and their possible associations with clinico-pathological features. Methods: Archived FFPE of 169 CRC patients were screened for KRAS, NRAS and BRAF mutations by Idylla technology. Results: Full RAS mutations were identified in 46.1% (42% in KRAS, 4.1% in NRAS). In KRAS gene, exon 2 mutations accounted for 84.5% (69% in codon 12, 15.5 % in codon 13). Within codon 12, KRAS G12D and G12C were more frequently detected (29.5% and 16.9%, respectively). Detection of KRAS mutations, and particularly G12D and G12C subtypes, are of large significance for CRC patients, have possible therapeutic implications. Within codon 13, the most frequently observed mutation was G13D (15.5 %). Outside exon 2, the mutation rate was 35.1% (8.4% in exon 3 and 26.7% in exon 4). Concurrent KRAS mutations were identified in 8 cases, which suggests that multiple mutations can occur in the same or different codons. In NRAS gene, the mutation rates of exon 2 and 3 were 71.4% and 57.1% respectively. G13V and Q61K were the most common mutations, accounting for 28.6 % of each. Concurrent KRAS mutations were identified in 2 cases. Of the 169 samples, mutations in the BRAF gene at V600E were detected in 3.5%. Combined mutational analysis of KRAS, NRAS and BRAF was able to identify 49.6% of patients with CRC as likely non-responders to anti-EGFR therapy. There was an association between KRAS mutations and age, which were higher in the age group>50 years old (p=0.022). Tumors in the left colon (36.61%) are more likely to harbor mutations in KRAS than the rectum (19.7%) in both sexes. The adenocarcinoma well-differentiated was the most frequent for patients with KRAS mutations (54.9%). No significant clinicopathologic correlations with NRAS and BRAF mutations were identified. Conclusions: Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology in Morocco. This approach may be able to significantly reduce the burden of disease in the country. Moreover, the Moroccan government should develop policy on CRC prevention and public health programs which may serve as a feasible setting to increase public awareness on lifestyle risk factors.

Background The incidence of thyroid cancer is increasing worldwide at an alarming rate. BRAFV600E 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 BRAFV600E mutation in thyroid carcinomas. Here we aim to evaluate the frequency of BRAFV600E oncogene in Moroccan thyroid carcinomas. Methods In this Single-Institution retrospective study realized in the Anatomic Pathology and Histology Service in the Military Hospital of Instruction Mohammed V ‘HMIMV’ in Rabat, we report, using direct genomic sequencing, the assessment of BRAFV600E in 37 thyroid tumors. Results We detected BRAFV600E mutation exclusively in Papillary Thyroid Carcinomas ‘PTC’ with a prevalence of 28% (8 PTC out 29 PTC). Like international trends, Papillary Thyroid Carcinomas ‘PTC’ is more frequent than Follicular Thyroid Carcinomas ‘FTC’ and Anaplastic Thyroid Carcinomas ‘ATC’ (29 PTC, 7 FTC and 1 ATC). Conclusion Our finding gives to the international community the first estimated incidence of this oncogene in Morocco showing that this prevalence falls within the range of international trends (30% to 90%) reported in distinct worldwide geographic regions.

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). Since DUOX enzymes, as extracellular hydrogen peroxide (H2O2­­)-generating systems, are involved in extracellular matrix formation and in wound healing in different experimental models, we hypothesised that DUOX-based NADPH oxidase plays a role in the pathophysiology of pulmonary fibrosis.Our in vivo data (idiopathic pulmonary fibrosis patients and mouse models of lung fibrosis) showed that the NADPH oxidase DUOX1 is induced in response to lung injury. DUOX1-deficient mice (DUOX1+/− and DUOX1−/−) had an attenuated fibrotic phenotype. In addition to being highly expressed at the epithelial surface of airways, DUOX1 appears to be well expressed in the fibroblastic foci of remodelled lungs. By using primary human and mouse lung fibroblasts, we showed that TGF-β1 upregulates DUOX1 and its maturation factor DUOXA1 and that DUOX1-derived H2O2 promoted the duration of TGF-β1-activated Smad3 phosphorylation by preventing phospho-Smad3 degradation. Analysis of the mechanism revealed that DUOX1 inhibited the interaction between phospho-Smad3 and the ubiquitin ligase NEDD4L, preventing NEDD4L-mediated ubiquitination of phospho-Smad3 and its targeting for degradation.These findings highlight a role for DUOX1-derived H2O2 in a positive feedback that amplifies the signalling output of the TGF-β1 pathway and identify DUOX1 as a new therapeutic target in pulmonary fibrosis.

Aims: The BRAFV600E oncogene, reported in 40%–60% of papillary thyroid cancer (PTC), has an important role in the pathogenesis of PTC. It is associated with the loss of thyroid iodide-metabolizing genes, such as sodium/iodide symporter (NIS), and therefore with radioiodine refractoriness. Inhibition of mitogen-activated protein kinase (MAPK) pathway, constitutively activated by BRAFV600E, is not always efficient in resistant tumors suggesting that other compensatory mechanisms contribute to a BRAFV600E adaptive resistance. Recent studies pointed to a key role of transforming growth factor β (TGF-β) in BRAFV600E-induced effects. The reactive oxygen species (ROS)-generating NADPH oxidase NOX4, which is increased in PTC, has been identified as a new key effector of TGF-β in cancer, suggestive of a potential role in BRAFV600E-induced thyroid tumors. Results: Here, using two human BRAFV600E-mutated thyroid cell lines and a rat thyroid cell line expressing BRAFV600E in a conditional manner, we show tha...

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. The thyroid gland represents a good model for studying the impact of oxidative stress on genomic instability. Indeed, one particularity of this organ is that follicular thyroid cells synthesise thyroid hormones through a complex mechanism that requires H2O2. Because of their detection in thyroid adenomas and in early cell transformation, both oxidative stress and DNA damage are believed to be neoplasia-preceding events in thyroid cells. Oxidative DNA damage is, in addition, detected in the advanced stages of thyroid cancer, suggesting that oxidative lesions of DNA also contribute to the maintenance of genomic instability during the subsequent phases of tumourigenesis. Finally, ionizing radiation and the mutation of oncogenes, such as RAS and BRAF, play a key role in thyroid carcinogenesis through separate and unique mechanisms: they upregulate the expression of two distinct ‘professional’ ROS-generating systems, the NADPH oxidases DUOX1 and NOX4, which cause DNA damage that may promote chromosomal instability, tumourigenesis and dedifferentiation.

Hydrogen peroxide (H2O2) is a crucial substrate for thyroid peroxidase, a key enzyme involved in thyroid hormone synthesis. However, as a potent oxidant, H2O2 might also be responsible for the high level of oxidative DNA damage observed in thyroid tissues, such as DNA base lesions and strand breakages, which promote chromosomal instability and contribute to the development of tumours. Although the role of H2O2 in thyroid hormone synthesis is well established, its precise mechanisms of action in pathological processes are still under investigation. The NADPH oxidase/dual oxidase family are the only oxidoreductases whose primary function is to produce reactive oxygen species. As such, the function and expression of these enzymes are tightly regulated. Thyrocytes express dual oxidase 2, which produces most of the H2O2 for thyroid hormone synthesis. Thyrocytes also express dual oxidase 1 and NADPH oxidase 4, but the roles of these enzymes are still unknown. Here, we review the structure, expression, localization and function of these enzymes. We focus on their potential role in thyroid cancer, which is characterized by increased expression of these enzymes.

Moroccan flora is rich in medicinal plants that are widely used in traditional medicine for the treatment of various diseases including cancer. These plants have several bioactive molecules, which belong to secondary metabolites such as polyphenols, flavonoids, and alkaloids. This review presents an overview of all published works, including our publications, on the anticancer efficacy of Moroccan medicinal plants with a focus on their cellular and molecular insights. Moreover, the worldwide place of the phytotherapy in the management of cancer will be discussed. Results revealed that numerous Moroccan medicinal plants belonging to several botanical families, such as Lamiaceae, Asteraceae, Fabaceae, Solanaceae, Verbenaceae, and Berberidaceae, show important anticancer activities. These plants have remarkable cytotoxic effects on different types of tumor-derived cell lines. Indeed, the antitumor mechanisms of these plants is not well-understood. However, the anti-cancer activities of certain molecules isolated from Moroccan medicinal plants such as thymol, carvacrol, limonene, tomentosin, and artemisinin are now better understood. Indeed, these compounds induce the cytotoxicity of tumor cells via activation of the intrinsic and/or extrinsic pathway of apoptosis, telomerase inhibition, and limit cell proliferation by inducing an array of signaling pathways that inhibit cell proliferation. These molecules can be applied as alternative compounds in chemotherapy, as well as in cancer target therapy.

Background: Dual oxidases (DUOX1 and DUOX2) were initially identified as H2O2 sources involved in thyroid hormone synthesis. Congenital hypothyroidism (CH) resulting from inactivating mutations in ...

Dual oxidases (DUOX1 and DUOX2) were initially identified as HTo analyze the role of these cysteine residues in both the targeting and function of dual oxidase, different human DUOX1 mutants were constructed, where the cysteine residues were replaced with glycine. The effect of these mutations on cell surface expression and HMutations of two cysteine residues (C118 and C1165), involved in the formation of the intramolecular disulfide bridge between the N-terminal ectodomain and one of the extracellular loops, mildly altered the function and the targeting of DUOX1, while this bridge is crucial for DUOX2 function. Unlike DUOXA2, with respect to DUOX2, the stability of the maturation factor DUOXA1 is not dependent on the oxidative folding of DUOX1. Only mutation of C579 induced a strong alteration of both targeting and function of the oxidase by preventing the covalent interaction between DUOX1 and DUOXA1.An intermolecular disulfide bridge rather than an intramolecular disulfide bridge is important for both the trafficking and H

Reactive oxygen species (ROS) derive from molecular oxygen and present higher reactivity. ROS designation comprehends free radicals such as superoxide radical (O

Aims: The BRAFV600E oncogene, reported in 40%–60% of papillary thyroid cancer (PTC), has an important role in the pathogenesis of PTC. It is associated with the loss of thyroid iodide-metabolizing genes, such as sodium/iodide symporter (NIS), and therefore with radioiodine refractoriness. Inhibition of mitogen-activated protein kinase (MAPK) pathway, constitutively activated by BRAFV600E, is not always efficient in resistant tumors suggesting that other compensatory mechanisms contribute to a BRAFV600E adaptive resistance. Recent studies pointed to a key role of transforming growth factor β (TGF-β) in BRAFV600E-induced effects. The reactive oxygen species (ROS)-generating NADPH oxidase NOX4, which is increased in PTC, has been identified as a new key effector of TGF-β in cancer, suggestive of a potential role in BRAFV600E-induced thyroid tumors.

Context: Thyroperoxidase (TPO) and dual oxidase (DUOX) are present at the apical membrane of thyrocytes, where TPO catalyzes thyroid hormone biosynthesis in the presence of H2O2 produced by DUOX. Both enzymes are colocalized and associated, but the consequences of this interaction remain obscure.Objective: The objective of this study was to evaluate the functional consequences of TPO-DUOX interaction at the plasma membrane.Design: The functional consequences of DUOX-TPO interaction were studied by measuring extracellular H2O2 concentration and TPO activity in a heterologous system. For this purpose, HEK293 cells were transiently transfected with a combination of human TPO with human DUOX1 or DUOX2 in the presence of their respective maturation factors, DUOXA1 or DUOXA2. The effect of human DUOX2 mutants in which cysteine residues in the N-terminal domain were replaced by glycines was also analyzed.Results: We observed that production of H2O2 decreases both TPO and DUOX activities. We show that TPO presents a catalase-like effect that protects DUOX from inhibition by H2O2. This catalase-like effect depends on the association between both enzymes, which probably occurs through the DUOX peroxidase-like domain because this effect was not observed with human DUOX2 mutants.Conclusion: The DUOX-TPO association at the plasma membrane is relevant for normal enzyme properties. Normally, TPO consumes H2O2 produced by DUOX, decreasing the availability of this substance at the apical membrane of thyrocytes and, in turn, probably decreasing the oxidative damage of macromolecules.

Ionizing radiation (IR) causes not only acute tissue damage, but also late effects in several cell generations after the initial exposure. The thyroid gland is one of the most sensitive organs to the carcinogenic effects of IR, and we have recently highlighted that an oxidative stress is responsible for the chromosomal rearrangements found in radio-induced papillary thyroid carcinoma. Using both a human thyroid cell line and primary thyrocytes, we investigated the mechanism by which IR induces the generation of reactive oxygen species (ROS) several days after irradiation. We focused on NADPH oxidases, which are specialized ROS-generating enzymes known as NOX/DUOX. Our results show that IR induces delayed NADPH oxidase DUOX1-dependent H2O2 production in a dose-dependent manner, which is sustained for several days. We report that p38 MAPK, activated after IR, increased DUOX1 via IL-13 expression, leading to persistent DNA damage and growth arrest. Pretreatment of cells with catalase, a scavenger of H2O2, or DUOX1 down-regulation by siRNA abrogated IR-induced DNA damage. Analysis of human thyroid tissues showed that DUOX1 is elevated not only in human radio-induced thyroid tumors, but also in sporadic thyroid tumors. Taken together, our data reveal a key role of DUOX1-dependent H2O2 production in long-term persistent radio-induced DNA damage. Our data also show that DUOX1-dependent H2O2 production, which induces DNA double-strand breaks, can cause genomic instability and promote the generation of neoplastic cells through its mutagenic effect.

Aims: The dual oxidase 2 (DUOX2) protein belongs to the NADPH oxidase (NOX) family. As H2O2 generator, it plays a key role in both thyroid hormone biosynthesis and innate immunity. DUOX2 forms with its maturation factor, DUOX activator 2 (DUOXA2), a stable complex at the cell surface that is crucial for the H2O2-generating activity, but the nature of their interaction is unknown. The contribution of some cysteine residues located in the N-terminal ectodomain of DUOX2 in a surface protein–protein interaction is suggested. We have investigated the involvement of different cysteine residues in the formation of covalent bonds that could be of critical importance for the function of the complex. Results: We report the identification and the characterization of an intramolecular disulfide bond between cys-124 of the N-terminal ectodomain and cys-1162 of an extracellular loop of DUOX2, which has important functional implications in both export and activity of DUOX2. This intramolecular bridge provides structural support for the formation of interdisulfide bridges between the N-terminal domain of DUOX2 and the two extracellular loops of its partner, DUOXA2. Innovation: Both stability and function of the maturation factor, DUOXA2, are dependent on the oxidative folding of DUOX2, indicating that DUOX2 displays a chaperone-like function with respect to its partner. Conclusions: The oxidative folding of DUOX2 that takes place in the endoplasmic reticulum (ER) appears to be a key event in the trafficking of the DUOX2/DUOXA2 complex as it promotes an appropriate conformation of the N-terminal region, which is propitious to subsequent covalent interactions with the maturation factor, DUOXA2. Antioxid. Redox Signal. 23, 724–733.

The dual oxidase (Duox)2 flavoprotein is strongly expressed in the thyroid gland, where it plays a critical role in the synthesis of thyroid hormones by providing thyroperoxidase with H2O2. DUOX2 mRNA was recently detected by RT-PCR and in-situ hybridization experiments in other tissues, such as rat colon and rat and human epithelial cells from the salivary excretory ducts and rectal glands. We examined Duox2 expression at the protein level throughout the porcine digestive tract and in human colon. Western blot analysis identified Duox2 as the same two molecular species ( Mr 165 and 175 kDa) as detected in the thyroid. It was expressed in all the tissues tested, but the highest levels were found in the cecum and sigmoidal colon. Immunohistochemical studies showed that Duox2 protein is mainly present in these parts of the gut and located at the apical membrane of the enterocytes in the brush border, indicating that it is expressed only in highly differentiated cells. A Ca2+/NADPH-dependent H2O2-generating system was associated with Duox2 protein expression, which had the same biochemical characteristics as the NADPH oxidase in the thyroid. Indeed, treatment of the thyroid and cecum particulate fractions with phenylarsine oxide resulted in complete calcium desensitization of both enzymes. A marked increase in DUOX2 expression was also found during spontaneous differentiation of postconfluent Caco-2 cells. The discovery of Duox2 as a novel source of H2O2 in the digestive tract, particularly in the cecum and colon, makes it a new candidate mediator of physiopathological processes.

Single and repeated oral administration of the aqueous extract of Eucalyptus globulus leaves at the doses of 150 and 300 mg/kg body weight exhibited a significant, dose-dependent hypoglycemic effect in streptozotocin diabetic rats. In rats with a normal functioning pancreas, however, no significant changes in blood glucose levels were observed after a single or repeated oral administration of Eucalyptus globulus leaf extract. In diabetic rats, the repeated oral administration of Eucalyptus globulus aqueous leaf extract significantly increased the basal plasma insulin concentrations (P < 0.05). The oral acute toxicity study in mice demonstrated that the LD50 value for the Eucalyptus globulus leaf tissue was 4.5 g/kg. The results support the validity of empirical uses of EG in the treatment of diabetes mellitus.

Introduction: Human papillomavirus (HPV) is associated with more human cancers than any other virus. Many studies have investigated the association between bladder cancer and HPV but the results remain controversial. The aim of the present study is to evaluate whether HPV have an etiological role in bladder carcinogenesis among Moroccan patients. Methodology: Forty-eight fresh biopsies (43 bladder tumors and 5 non-tumor samples) were collected for this purpose. Nested PCR with the consensus MY09/MY11 and GP5+/GP6+ primers was performed to detect the presence of HPV L1 gene DNA. Results: The results showed that 52.4% of bladder cancer patients were positive for HPV. Subsequent DNA sequencing of positive cases of HPV revealed the presence of HPV16 in 95.5% of bladder tumor samples. The occurrence of HPV infection varies according to clinicopathological features, but there is no significant correlation between the viral infection and tumor stage or grade. In addition, statistical analysis demonstrated that there is no association between age or sex and HPV infection. Conclusion: Our data indicate for the first time that bladder tumors from Moroccan patients harbor HR-HPV genotypes, especially HPV16, and thereby suggest that this virus may play a causative role in bladder cancer.

During childhood, the thyroid gland is one of the most sensitive organs to the carcinogenetic effects of ionizing radiation that may lead to papillary thyroid carcinoma (PTC) associated with RET/PTC oncogene rearrangement. Exposure to ionizing radiation induces a transient “oxidative burst” through radiolysis of water, which can cause DNA damage and mediates part of the radiation effects. H2O2 is a potent DNA-damaging agent that induces DNA double-strand breaks, and consequently, chromosomal aberrations. Irradiation by 5 Gy X-ray increased extracellular H2O2. Therefore, we investigated the implication of H2O2 in the generation of RET/PTC1 rearrangement after X-ray exposure. We developed a highly specific and sensitive nested reverse transcription-PCR method. By using the human thyroid cell line HTori-3, previously found to produce RET/PTC1 after γ-irradiation, we showed that H2O2, generated during a 5 Gy X-ray irradiation, causes DNA double-strand breaks and contributes to RET/PTC1 formation. Pretreatment of cells with catalase, a scavenger of H2O2, significantly decreased RET/PTC1 rearrangement formation. Finally, RET/PTC chromosomal rearrangement was detected in HTori-3.1 cells after exposure of cells to H2O2 (25 μmol/L), at a dose that did not affect the cell viability. This study shows for the first time that H2O2 is able to cause RET/PTC1 rearrangement in thyroid cells and consequently highlights that oxidative stress could be responsible for the occurrence of RET/PTC1 rearrangement found in thyroid lesions even in the absence of radiation exposure. Cancer Res; 70(10); 4123–32. ©2010 AACR.

NADPH oxidase 4 (NOX4) belongs to the NOX family that generates reactive oxygen species (ROS). Function and tissue distribution of NOX4 have not yet been entirely clarified. To date, in the thyroid gland, only DUOX1/2 NOX systems have been described. NOX4 mRNA expression, as shown by real-time PCR, was present in normal thyroid tissue, regulated by TSH and significantly increased in differentiated cancer tissues. TSH increased the protein level of NOX4 in human thyroid primary culture and NOX4-dependent ROS generation. NOX4 immunostaining was detected in normal and pathologic thyroid tissues. In normal thyroid tissue, staining was heterogeneous and mostly found in activated columnar thyrocytes but absent in quiescent flat cells. Papillary and follicular thyroid carcinomas displayed more homogeneous staining. The p22phox protein that forms a heterodimeric enzyme complex with NOX4 displayed an identical cellular expression pattern and was also positively regulated by TSH. ROS may have various biological effects, depending on the site of production. Intracellular NOX4–p22phox localization suggests a role in cytoplasmic redox signaling, in contrast to the DUOX localization at the apical membrane that corresponds to an extracellular H2O2 production. Increased NOX4–p22phox in cancer might be related to a higher proliferation rate and tumor progression but a role in the development of tumors has to be further studied and established in the future.

Duox2 (and probably Duox1) is a glycoflavoprotein involved in thyroid hormone biosynthesis, as the thyroid H2O2 generator functionally associated with Tpo (thyroperoxidase). So far, because of the impairment of maturation and of the targeting process, transfecting DUOX into nonthyroid cell lines has not led to the expression of a functional H2O2-generating system at the plasma membrane. For the first time, we investigated the H2O2-generating activity in the particulate fractions from DUOX2- and DUOX1-transfected HEK293 and Chinese hamster ovary cells. The particulate fractions of these cells stably or transiently transfected with human or porcine DUOX cDNA demonstrate a functional NADPH/Ca2+-dependent H2O2-generating activity. The immature Duox proteins had less activity than pig thyrocyte particulate fractions, and their activity depended on their primary structures. Human Duox2 seemed to be more active than human Duox1 but only half as active as its porcine counterpart. TPO co-transfection produced a slight increase in the enzymatic activity, whereas p22(phox), the 22-kDa subunit of the leukocyte NADPH oxidase, had no effect. In previous studies on the mechanism of H2O2 formation, it was shown that mature thyroid NADPH oxidase does not release O2*- but H2O2. Using a spin-trapping technique combined with electron paramagnetic resonance spectroscopy, we confirmed this result but also demonstrated that the partially glycosylated form of Duox2, located in the endoplasmic reticulum, generates superoxide in a calcium-dependent manner. These results suggest that post-translational modifications during the maturation process of Duox2 could be implicated in the mechanism of H2O2 formation by favoring intramolecular superoxide dismutation.

Thyroglobulin (Tg) is cleaved into several peptides during thyroid hormone synthesis, an oxidative process. P40, an iodinated C-terminal peptide from human Tg, has a molecular weight of about 40 kDa and contains two hormonogenic sites. P40 is the smallest peptide that is still recognized by monoclonal antibodies from mice immunized with human Tg directed against its immunodominant region. Since P40 also contains several T-cell epitopes, it is a good candidate for studying the primary events involved in the process of hormone synthesis leading to thyroid autoimmunity. The present results show that P40 is recognized by Tg antibodies from patients with thyroid disorders and induces Tg antibodies in CBA mice. P40 may therefore be involved in the autoimmune process, thus providing a useful tool for diagnostic and therapeutic purposes.

Background: The p53 codon 72 polymorphism has been investigated extensively for its association with various cancers around the world. Several studies have investigated the association between p53 polymorphism at codon 72 and risk of developing bladder cancer, but the results are still controversial. Aim: The aim of our study was to evaluate the association between the p53 polymorphism and the bladder cancer risk among Moroccan patients. Materials and Methods: This study was carried out on fresh biopsies from 41 patients with bladder cancer confirmed and 38 blood samples from control donors. Deoxyribonucleic acid was genotyped by Allele-specific polymerase chain reaction using specific primers to each polymorphic variant. Results: Frequencies of Arg/Arg, Arg/Pro and Pro/Pro genotypes among cases were 17%, 66%, and 17%, while in controls the frequencies of Arg/Arg, Arg/Pro and Pro/Pro were 15.8%, 63.2%, and 21%, respectively. The difference between cases and controls was not statistically significant. An increased risk of bladder cancer development was not clearly related to any polymorphic variant of the p53 Arg72Pro in our study group from Moroccan population. Moreover, the frequency of the Arg allele was higher (71.45%) than the Pro allele (28.55%) in high stage of bladder tumors, but this difference was statistically not significant. Conclusion: This study suggests that Arg allele could be more involved in developing bladder tumor in Moroccan population than the Pro allele. Therefore, enlarging the sampling will be necessary to confirm this association in Moroccan population.