MYC up-regulation confers resistance to everolimus and establishes vulnerability to cyclin dependent kinase inhibitors in pancreatic neuroendocrine neoplasms cells
This study aimed at identifying mechanisms involved in acquisition of resistance to everolimus.
Methods
BON-1 and everolimus-resistant (ER) BON-1 cells were used as in vitro system of sensitivity and acquired resistance. Transcriptome changes occurring in BON-1 and ER-BON-1 were investigated by RNA sequencing and validated by quantitative PCR analysis. RNA extracted from patients ’ biopsies was used to validate MYC up-regulation. Drug screening and functional assays were performed using ER-BON-1 cells. Cell cycle progression was evaluated by FACS analysis.
Results
Our results show that MYC overexpression is a key eve...
Source: Neuroendocrinology - July 1, 2020 Category: Endocrinology Source Type: research
Models of gastroenteropancreatic neuroendocrine neoplasms – Current status and future directions
Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are a rare, heterogeneous group of tumors that originate from the endocrine system of the gastrointestinal tract and pancreas. GEP-NEN are subdivided according to their differentiation into well differentiated gastroenteropancreatic neuroendocrine tumors (NET) and poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (NEC). Since GEP-NEN represent rare diseases only limited data from large prospective, randomized clinical trials are available, and recommendations for treatment of GEP-NEN are in part based on data from retrospective analyses or cas...
Source: Neuroendocrinology - July 1, 2020 Category: Endocrinology Source Type: research
Prognostic role of examined and positive lymph nodes after distal pancreatectomy for non-functioning neuroendocrine neoplasms
Background
The most appropriate nodal staging system for non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) remains unclear. Despite some evidence are available for pancreaticoduodenectomy (PD), the adequate nodal staging is still unknown for distal pancreatectomy (DP). Aim of the present study was to evaluate the prognostic impact of the number of positive lymph nodes after DP for NF-PanNENs and to define the minimal number of lymph nodes to be harvested for an appropriate nodal staging.
Methods
Data were retrospectively collected from patients who underwent DP with curative intent (R0-R1) for sporadic well...
Source: Neuroendocrinology - June 24, 2020 Category: Endocrinology Source Type: research
Diagnosis, Background, and Treatment of Hypothalamic Damage in Craniopharyngioma
Craniopharyngiomas (CP) are rare brain tumors managed primarily with surgery and radiotherapy. There are 2 phenotypes of CP, i.e., one with a rather good outcome without hypothalamic damage and another with hypothalamic damage. With hypothalamic damage, progressive disease with recurrent operations and additional cranial radiotherapy often result in hypothalamic obesity, an affected psychosocial life, and cognitive dysfunction. The morbidity and mortality are increased for particularly cerebrovascular diseases. Preoperative hypothalamic involvement to predict hypothalamic damage is important for decision making for hypotha...
Source: Neuroendocrinology - June 23, 2020 Category: Endocrinology Source Type: research
Pancreatic Neuroendocrine Tumors in patients with Multiple Endocrine Neoplasia Type 1: Diagnostic Value of Different MRI Sequences
Background: Magnetic Resonance Imaging (MRI) is a useful imaging modality to assess the presence of Pancreatic Neuroendocrine Tumors (PNETs), allowing repeat monitoring examinations in MEN-1 patients. Objectives: We aimed to compare the diagnostic accuracy of conventional MRI sequences identifying which better depict the presence of PNETs in MEN-1 patients. Method: We performed a retrospective analysis of consecutive MEN-1 patients who underwent a conventional MRI protocol to monitor previously proven PNETs. MRI sequences T1-w Chemical-Shift (CS), T2-w HASTE, fat-suppressed (FS) T2-w HASTE, Diffusion Weighted Imaging (DWI)...
Source: Neuroendocrinology - June 23, 2020 Category: Endocrinology Source Type: research
Diagnosis, background and treatment of hypothalamic damage in craniopharyngioma
Craniopharyngiomas (CPs) are rare brain tumours managed primarily with surgery and radiotherapy. There are two phenotypes of CPs, one with a rather good outcome without hypothalamic damage and the other with hypothalamic damage. With hypothalamic damage progressive disease with recurrent operations and additional cranial radiotherapy often result in hypothalamic obesity, affected psychosocial life and cognitive dysfunction. The morbidity and mortality is increased for particularly cerebrovascular diseases. Preoperative hypothalamic involvement to predict hypothalamic damage is important for decision making for hypothalamic...
Source: Neuroendocrinology - June 23, 2020 Category: Endocrinology Source Type: research
Bisphenol A induces Agrp gene expression in hypothalamic neurons through a mechanism involving ATF3.
Conclusions: Overall, these results indicate hypothalamic Agrp is susceptible to dysregulation by BPA and implicate ATF3 as a common mediator of the orexigenic effects of BPA in hypothalamic neurons. (Source: Neuroendocrinology)
Source: Neuroendocrinology - June 22, 2020 Category: Endocrinology Source Type: research
G protein-coupled estrogen receptor immunoreactivity in the rat hypothalamus is widely distributed in neurons, astrocytes and oligodendrocytes, fluctuates during the estrous cycle and is sexually dimorphic
Conclusions
These findings suggest that estrogenic regulation of hypothalamic function through GPER may be different in males and in females and may fluctuate during the estrous cycle in females. (Source: Neuroendocrinology)
Source: Neuroendocrinology - June 21, 2020 Category: Endocrinology Source Type: research
Skull base chordomas and chondrosarcomas
Skull base chordomas account for less than 0.2% and chondrosarcomas for less than 0.15% of all intracranial tumors. Although their clinical and imaging presentation is similar, they derive from different origins. Chordomas arise from embryonic remnants of the primitive notochord and chondrosarcomas from primitive mesenchymal cells or from the embryonic rest of the cranial cartilaginous matrix. Both entities are characterized by infiltration and destruction of surrounding bone and soft tissue and a high locoregional recurrence rate. Chondrosarcomas, when treated with similar complex strategies, display a much better prognos...
Source: Neuroendocrinology - June 14, 2020 Category: Endocrinology Source Type: research
Emerging Roles of Anti-M üllerian Hormone in Hypothalamic-Pituitary Function
Since its initial discovery in the 1940s, research into the physiological actions of anti-M üllerian hormone (AMH), from its eponymous role in male developmental biology to its routine clinical use in female reproductive health, has undergone a paradigm shifting change. With several exciting studies recently reporting hitherto unforeseen AMH actions at all levels in the hypogonadal-pituit ary-gonadal axis, the importance of this hormone for both hypothalamic and pituitary reproductive control is finding increasing support and significance. In this review, we will briefly summarize what is known about the traditional roles...
Source: Neuroendocrinology - July 5, 2019 Category: Endocrinology Source Type: research
An Assessment of Circulating Chromogranin A as a Biomarker of Bronchopulmonary Neuroendocrine Neoplasia: A Systematic Review and Meta-Analysis
Conclusion: The available data are scarce. An assessment of all published data showed that CgA exhibits major limitations as an effective and accurate biomarker for either PC or SCLC. Its utility especially for localized PC/limited SCLC (when surgery is potentially curative), is limited. The clinical value of CgA remains to be determined. This requires validated, well-constructed, multicenter, prospective, randomized studies. An assessment of all published data indicates that CgA does not exhibit the minimum required metrics to function as a clinically useful biomarker for lung NENs.Neuroendocrinology (Source: Neuroendocrinology)
Source: Neuroendocrinology - July 5, 2019 Category: Endocrinology Source Type: research
Intracranial germinoma masquerading as secondary granulomatous hypophysitis: A case report and review of literature
Germinomas are highly immunogenic tumors eliciting a strong peri-tumoral immune response that can spillover into the surrounding healthy tissues. This phenomenon can also occur in intracranial germinomas, manifesting as secondary hypophysitis. Herein, we report a case of 12-year-old-girl presenting with polyuria and polydispsia. She had central diabetes insipidus (CDI) and panhypopituitarism. Imaging revealed a sellar-suprasellar mass with infundibular stalk thickening. Transphenoidal biopsy revealed epitheloid granulomas with immunostaining negative for germinomatous cells. Other causes of hypophysitis were ruled out. Acc...
Source: Neuroendocrinology - July 3, 2019 Category: Endocrinology Source Type: research
Targeting the Enteric Nervous System to Treat Metabolic Disorders? “Enterosynes” as Therapeutic Gut Factors
The gut-brain axis is of crucial importance for controlling glucose homeostasis. Alteration of this axis promotes the type 2 diabetes (T2D) phenotype (hyperglycaemia, insulin resistance). Recently, a new concept has emerged to demonstrate the crucial role of the enteric nervous system in the control of glycaemia via the hypothalamus. In diabetic patients and mice, modification of enteric neurons activity in the proximal part of the intestine generates a duodenal hyper-contractility that generates an aberrant message from the gut to the brain. In turn, the hypothalamus sends an aberrant efferent message that provokes a stat...
Source: Neuroendocrinology - July 2, 2019 Category: Endocrinology Source Type: research
STK33 promotes the growth and progression of human pancreatic neuroendocrine tumour via activation of the PI3K/AKT/mTOR pathway
Background: Serine/threonine kinase 33 (STK33) has been reported to play an important role in cancer cell proliferation. We investigated the role of STK33 in pancreatic neuroendocrine tumour (PNET) and the underlying mechanisms.
Methods: PNET specimens and adjacent non-tumorous pancreatic tissues from 84 patients who underwent curative surgery for PNET were stained by immunochemistry for STK33. The relationships among STK33 expression, clinicopathological parameters and clinical prognosis were statistically analysed. MTT, scratching, transwell and apoptosis assays were employed to detect the effects of STK33 knockdown (si...
Source: Neuroendocrinology - July 1, 2019 Category: Endocrinology Source Type: research
Preweaning paternal deprivation impacts parental responses to pups and alters the serum OT and CORT levels and OTR, V1AR, ER, D1R, D2R levels in relevant brain regions in adult mandarin voles
Although maternal separation and neonatal paternal deprivation have been found to exert a profound and persistent effects on the physiological and behavioural development of offspring, whether preweaning paternal deprivation (PPD) (from PND 10 to 21) affects maternal and parental responses to pups and the underlying neuroendocrine mechanism are under-investigated. Using monogamous mandarin voles (Microtus mandarinus), the present study found that PPD increased the latency to approach a pup-containing ball, decreased the total durations of sniffing and contacting a pup-containing ball and walking, and increased the total du...
Source: Neuroendocrinology - June 30, 2019 Category: Endocrinology Source Type: research
