Endocrine Abstracts

The way to maleness is a long process starting with fertilization when sperm delivers the testis-determining Y chromosome to the oocyte and ending with puberty and the action of testicular hormones. Since Sertoli cells are at the crossroads of the entire process, the analysis of the factors driving their differentiation and function is essential to the global understanding of male sexual development. By using mouse functional genetics, we will show that growth factors of the i...

Integrative genomics studies of paragangliomas (PGL) have shown that PGL susceptibility genes are the main drivers of tumorigenesis. Comprehensive genetic analyses have identified germline SDHB and, to a lesser extent, FH gene mutations, as predominant causes of metastatic PGL. However, some suspicious cases remain unexplained. We performed whole-exome sequencing of a paraganglioma exhibiting an SDHx-like molecular profile in the absence of SDHx<...

The androgen receptor (AR) functions as a master transcriptional regulator of prostate tissue homeostasis. This master transcriptional regulator function is maintained in prostate cancer. Therefore, prostate cancer is an androgen-dependent disease and suppression of AR transcriptional activity with androgen deprivation therapy (ADT) is an effective systemic therapy. However, development of therapy resistance and transition to castration resistant prostate cancer (CRPC) represe...

Adrenocortical carcinoma (ACC) is a rare malignancy with an incidence of 0.7–2.0 per million per year. Prognosis of ACC is generally poor but variable and therapeutic approaches are scarce. While surgical resection presents the best option for definitive cure, mitotane remains the only approved drug for adjuvant therapy in ACC to date. Advancements regarding novel treatment strategies as well as fostered understanding of potential drivers of adrenocortical carcinogenesis ...

Background: International consensus supports interval biochemical and imaging surveillance for all asymptomatic carriers of succinate dehydrogenase (SDHx) gene mutations and patients with a history of SDH deficient tumours. There is growing awareness that the life time penetrance of the SDHx genes is much lower than that originally estimated and that long term radiological surveillance carries a significant risk including ionizing radiation exposure and incidental findings. Th...

Metabolic dysfunction in skeletal muscle disturbs both the critical vascular network and fundamental muscle fibre architecture. However, the molecular drivers during metabolic stress responsible for transmitting these events remain poorly defined. To reveal these we mapped changes in the spatial proteome occurring as a result of impaired metabolic health. We exposed male and female mice (C57/BL6J) to high fat diets and conducted digital spatial profiling (NanoString GEOMX) on ...

Background: Patients with advanced pheochromocytoma/paraganglioma (PPGL) or pancreatic neuroendocrine tumor (panNET) are in need of novel targeted therapies. Hypoxia-inducible factor 2α (HIF-2α) is one of the key oncogenic drivers in neuroendocrine tumors. Hypoxia signaling pathway alterations or other mechanisms that stabilize HIFs are common in some PPGLs and panNETs. Belzutifan (MK-6482), a HIF-2α inhibitor, has shown antitumor activity in advanced renal cell...

Introduction: Diabetes is a chronic metabolic disease that can have a significant impact on fitness for work. The aim of our study was to study the impact of diabetes on work activity in diabetics.Methods: It was a descriptive and analytical study. It was conducted in 200 diabetic patients at the National Institute of Nutrition in Tunis. Patients received a clinical examination and standard biological assessment.Results: We include...

Estrogen receptors (ER) are expressed in the majority of breast cancers, are key drivers of breast cancer development and progression and hence therapies to inhibit their activities are a mainstay of treatment for breast cancer. A large proportion of patients develop resistance to these therapies, so determining the mechanisms of ER action is important for improving patient management and for identifying new therapies. In defining the mechanisms by which ER regulates gene expr...

Background: Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid cancer and has no effective therapy. Due to its dismal prognosis, it is vital to understand the genetic alterations of ATC and identify effective molecular targets. We performed targeted next-generation sequencing to investigate the mutational profile of ATC using a massive parallel sequencing approach.Methods: DNA from formalin-fixed, paraffin-embedded archival samples...