Here, using two human BRAF-mutated thyroid cell lines and a rat thyroid cell line expressing BRAF in a conditional manner, we show that NOX4 upregulation is controlled at the transcriptional level by the oncogene via the TGF-β/Smad3 signaling pathway. Importantly, treatment of cells with NOX4-targeted siRNA downregulates BRAF-induced NIS repression. Innovation and Conclusion: Our results establish a link between BRAF and NOX4, which is confirmed by a comparative analysis of NOX4 expression in human (TCGA) and mouse thyroid cancers. Remarkably, analysis of human and murine BRAF-mutated thyroid tumors highlights that the level of NOX4 expression is inversely correlated to thyroid differentiation suggesting that other genes involved in thyroid differentiation in addition to NIS might be silenced by a mechanism controlled by NOX4-derived ROS. This study opens a new opportunity to optimize thyroid cancer therapy. Antioxid. Redox Signal. 26, 864-877.
Background. The contribution of BRCA1 mutations to both hereditary and sporadic breast and ovarian cancer (HBOC) has not yet been thoroughly investigated in MENA. Methods. To establish the knowledge about BRCA1 mutations and their correlation with the clinical aspect in diagnosed cases of HBOC in MENA populations. A systematic review of studies examining BRCA1 in BC women in Cyprus, Jordan, Egypt, Lebanon, Morocco, Algeria, and Tunisia was conducted. Results. Thirteen relevant references were identified, including ten studies which performed DNA sequencing of all BRCA1 exons. For the latter, 31 mutations were detected in 57 of the 547 patients ascertained. Familial history of BC was present in 388 (71%) patients, of whom 50 were mutation carriers. c.798_799delTT was identified in 11 North African families, accounting for 22% of total identified BRCA1 mutations, suggesting a founder allele. A broad spectrum of other mutations including c.68_69delAG, c.181T>G, c.5095C>T, and c.5266dupC, as well as sequence of unclassified variants and polymorphisms, was also detected. Conclusion. The knowledge of genetic structure of BRCA1 in MENA should contribute to the assessment of the necessity of preventive programs for mutation carriers and clinical management. The high prevalence of BC and the presence of frequent mutations of the BRCA1 gene emphasize the need for improving screening programs and individual testing/counseling.
BackgroundUrothelial bladder carcinoma (UBC) is one of the most prevalent cancers in men worldwide. Human epidermal growth factor receptor 2 (HER2) expression has been detected in a wide range of urothelial carcinoma. Despite many reports in the literature, the prognostic significance of this overexpression remains unclear. The aim of this study was to assess the expression of HER2 in urothelial bladder carcinomas and its association with clinical and pathological parameters.Methods103 cases of UBC were diagnosed in our department between January 2014 and December 2015. The tumor specimens obtained by transurethral resection or cystectomy were evaluated by immunohistochemistry using HER2 antibody.ResultsHER2 protein overexpression was present in 11.7% of cases and associated with tumor grade (p = 0.003) and pathological stage (p = 0.015). In multivariate analysis, HER2 overexpression was associated only with tumor grade (P = 0.04).ConclusionHER2 protein overexpression is noted in patients with high grade cancer. This expression may select patients for anti HER2 targeted therapy. Future larger and prospective studies will verify the frequency of HER2 alteration and the role of HER2 in the aggressive behavior.Electronic supplementary materialThe online version of this article (doi:10.1186/s12907-017-0046-z) contains supplementary material, which is available to authorized users.
BackgroundPrimary thyroid lymphoma is an uncommon pathological entity that accounts for only 1 to 5 % of all thyroid malignancies. Primary Burkitt lymphoma of the thyroid gland is very rare. This article presents the first Moroccan case of a primary BL of the thyroid to be reported in the literature to date.Case presentationWe describe here a case of a 70-year-old male who developed a rapidly enlarging thyroid gland with progressive symptoms of compression. Core biopsy confirmed the diagnosis of Burkitt lymphoma. The patient died of septic shock, 2 weeks after the first cycle of appropriate therapeutic chemotherapy.ConclusionsThis presentation emphasizes the importance of considering lymphoma when dealing with a thyroid mass, as its management is different from that of other thyroid pathologies, and affords an opportunity to review a very rare type of primary thyroid lymphoma.
Introduction Glioblastomas are aggressive primary intracranial tumours of the central nervous system causing significant mortality and morbidity worldwide. Objective This study aims to evaluate the prognostic value of tissue expression by immunostaining of hypoxia-inducible factor (HIF-1α), isocitrate dehydrogenase 1 (IDH1), and tumour protein p53 in glioblastoma in Moroccan patients. The association of HIF-1α, IDH1, and p53 expression with the clinicopathological data and overall patient survival (OS) was also evaluated. Materials and methods Confirmed glioblastomas were included in this study. Twenty-two tissue samples were obtained by neurosurgical intervention resulting from total resection, and subtotal resection or biopsy. Karnofsky index, histological type of tumour, and the status of IDH1, p53 protein, and HIF-1α expression by immunostaining were reported. Results The majority of the patients were males (64%) with a sex ratio of 1.75. The average age was 54 ± 13. Median follow-up was 10.10 months and median overall survival was 10 months. The expression of HIF-1α was high in 10 samples (45%) and low in 12 (55%). There was a statistically significant difference in OS of 85% at 12 months for the subgroup of patients “HIF-1α negative IDH1 positive” p = 0.038, the unadjusted analysis showed that the group “HIF-1α positive, IDH1 positive” was a poor prognostic factor, the HR was 0.08 (95% CI: 0.009–0.756, p = 0.027). Conclusion Patients with negative HIF-1α expression and positive IDH1 expression have a better prognosis, suggesting that these two biomarkers may be useful in the search for new approaches for targeted therapy in glioblastoma.
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