MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours.

BACKGROUND: MYC is amplified in approximately 15% of breast cancers (BCs) and is associated with poor outcome. c-MYC protein is multi-faceted and participates in many aspects of cellular function and is linked with therapeutic response in BCs. We hypothesised that the functional role of c-MYC differs between molecular subtypes of BCs. METHODS: We therefore investigated the correlation between c-MYC protein expression and other proteins involved in different cellular functions together with clinicopathological parameters, patients' outcome and treatments in a large early-stage molecularly characterised series of primary invasive BCs (n=1106) using immunohistochemistry. The METABRIC BC cohort (n=1980) was evaluated for MYC mRNA expression and a systems biology approach utilised to identify genes associated with MYC in the different BC molecular subtypes. RESULTS: High MYC and c-MYC expression was significantly associated with poor prognostic factors, including grade and basal-like BCs. In luminal A tumours, c-MYC was associated with ATM (P=0.005), Cyclin B1 (P=0.002), PIK3CA (P=0.009) and Ki67 (P<0.001). In contrast, in basal-like tumours, c-MYC showed positive association with Cyclin E (P=0.003) and p16 (P=0.042) expression only. c-MYC was an independent predictor of a shorter distant metastases-free survival in luminal A LN+ tumours treated with endocrine therapy (ET; P=0.013). In luminal tumours treated with ET, MYC mRNA expression was associated with BC-specific survival (P=0.001). In ER-positive tumours, MYC was associated with expression of translational genes while in ER-negative tumours it was associated with upregulation of glucose metabolism genes. CONCLUSIONS: c-MYC function is associated with specific molecular subtypes of BCs and its overexpression confers resistance to ET. The diverse mechanisms of c-MYC function in the different molecular classes of BCs warrants further investigation particularly as potential therapeutic targets

Marital status in patients with functional (psychogenic nonepileptic) seizures: An international study

Purpose: The study aimed to investigate the marital status in a cohort of patients with functional seizures from seven countries in four continents. Factors associated with marital status were also explored. Methods: Adult patients with functional seizures who were admitted to the epilepsy monitoring units at centers in Iran, Qatar, USA, France, Georgia, Egypt, and United Arab Emirates (UAE) were retrospectively identified. Marital status was assessed in the whole cohort. Results: Four hundred thirty-two patients were included (241 from Iran, 52 from France, 48 from Qatar, 41 from the USA, 19 from UAE, 18 from Egypt, and 13 from Georgia); 302 were women and 130 were men. One hundred fifty (35%) subjects were single, 245 (57%) were married, and 37 (8%) were separated (31 divorced, 7%; 6 widowed, 1%). Auras with functional seizures were less frequently reported by single people in comparison with that by married patients (54% vs. 61%) [odds ratio (OR) = 0.58]. Separated people compared with those who were married less often had auras with their functional seizures (27% vs. 61%; OR = 0.26) and more often reported a history of sexual abuse (49% vs. 12%; OR = 6.14). Conclusion: The marital status has significant associations with the semiology of functional seizures. A history of sexual abuse is significantly associated with being separated and should be inquired and tackled appropriately during the management process of patients with functional seizures

Gene and Protein Expressions Induced by 17β-estradiol and Parathion in Cultured Breast Epithelial Cells

Cancer of the breast is the most common form of malignant disease occurring among women of the western world and environmental substances seem to be involved in the etiology of this disease. Many studies have found an association between human cancer and exposure to agricultural pesticides and among them parathion, the organophosphorous pesticide used in agriculture to control mosquito plagues. The association between breast cancer and prolonged exposure to estrogens suggests that this hormone also may have a role in such process. However, the causative factors for breast carcinogenesis remain an enigma. The objective of this study was to determine the effects of 17β-estradiol (E2) and parathion on cell transformation of human breast epithelial cells in vitro. The results of this study showed that parathion alone and in combination with E2 induced malignant transformation of an immortalized human breast epithelial cell line, MCF-10F, and the malignant feature was confirmed by anchorage independency and invasive capabilities. Parathion alone efficiently elevated the expression of EGFR, c-Kit, Trio, Rac 3, Rho-A, and mutant p53 proteins. Analysis of gene expression using commercially available human cell cycle array revealed transcriptional alterations in 22 out of a total of 96 genes. Among them, nine genes involved in the regulation of cell cycle were altered. These included cyclins (A1, A2, C, G1, G2, and H), cyclin-dependent kinases (CDKs), and minichromosome maintenance deficient (MCM). Results suggest that parathion has the potency to cause malignant transformation of breast epithelial cells through modulation of expression of cell cycle regulated genes