Endocrine Abstracts

Objectives: BRAFV600E- anaplastic thyroid cancers (ATCs) show remarkable responses to dabrafenib and trametinib (dab/tram) an effect that may be in part immune-mediated. Murine BRAFV600E-ATCs regress upon BRAF inhibition. We find that recurrences are frequent and associated with loss of Mhc class II (MhcII) expression. Our goal was to investigate the mechanisms of loss of antigen presentation by tumor cells and whether this contributes to disease recurren...

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from simple intrahepatic lipid accumulation to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). 5β-reductase (AKR1D1) is a liver enzyme that catalyses a fundamental step in bile acid (BA) synthesis. Both BAs and BA intermediates are established as potent regulators of metabolic and proliferative phenotype. We have hypothesised that AKR1D1 plays a crucial role in NAFLD and HCC. Human liver b...

Obesity is associated with an increased risk of hormone receptor positive breast cancer after menopause. The aromatase enzyme catalyzes the conversion of androgens into oestrogens and the breast adipose-specific expression of aromatase is hypothesized to be a major driver of breast cancer growth when ovarian oestrogen biosynthesis has ceased. We have found that aromatase is elevated in breast adipose stromal cells in relation to obesity and menopausal status. Furthermore, obes...

Background: Genetic alterations underlying the pathogenesis of autonomous cortisol secretion and early adrenocortical tumorigenesis have been identified in 40% of adrenocortical tumors (ACT). Nonetheless, the molecular events leading to development of ACT and steroid secretion remain obscure for a large proportion of patients.Aim: Aims of our study were to investigate the relationship between transcriptome profile and genetic background in a large series...

Background: Since the last decade, the disease pattern has significantly changed around the world. Non-communicable diseases, most commonly diabetes mellitus, have become the main threat to global health. The incidence of diabetes mellitus type 2 (DM2) is rising steadily, accounting for about two-thirds of deaths in Germany. Based on a prevalence of 9 million diabetic patients per year, DM2 constitutes a considerable medical and economic burden in Germany. However, the healthc...

Undifferentiated thyroid carcinomas are extremely aggressive and currently lack effective treatment. Aberrant RAS-ERK signaling, triggered mainly by BRAF and RAS mutations, is responsible for the occurrence and progression of most thyroid carcinomas, which led to the clinical use of small kinase inhibitors targeting kinases of the pathway. The results were disappointing, because of the emergence of resistance and high-associated toxicity. A more specific approach, targeting si...

Clinical interactions with patients are fulfilling and rewarding. We can make a difference to patients’ health and lives by tuning care and attention to their individual needs on a 1:1 basis. Frustrations sometimes emerge from clinicians due to perceived restrictions and limitations in the healthcare system that appear to perversely impact patient care. Those frustrations are often exacerba...

We studies the correlation between levels of educational attainment and the prevalence of obesity, as well as the effectiveness of its treatment surveying 200 patients of the Khorezm endocrinology dispensary in Urgench, Uzbekistan in March-October 2022. Lowest prevalence of obesity is, unsurprisingly, observed among the group with the highest educational attainment – in this group pre-obesity and 1st degree obesity prevail. Noteworthy, however, is a trend towards higher o...

Oestrogens promote breast cancer development and progression by binding to the oestrogen receptors. Oestrogen receptor-alpha (ER) is a transcription regulatory protein that is activated upon binding oestrogen and acts by controlling gene expression in breast cancer cells and is the target for endocrine therapies that inhibit its activity by competing with oestrogen for binding to ER (anti-oestrogens) or by inhibiting oestrogen biosynthesis (aromatase inhibitors). These therapi...

CYP17A1 inhibition with abiraterone is an effective treatment for castration-resistance prostate cancer (CRPC), with significant improvements in survival, radiological progression free survival, pain, skeletal related events and other secondary end-points. However, resistance invariably develops. Due to mineralocorticoid excess, abiraterone is administered with glucocorticoids. Next-generation sequencing of circulating plasma DNA from CRPC offers an opportunity to monitor tumo...