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Eric Raymond, Matthew Kulke, Shu-Kui Qin, Xianjun Yu, Michael Schenker, Antonio Cubillo, Wenhui Lou, Jiri Tomasek, Espen Thiis-Evensen, Jian-Ming Xu, Adina Croitoru, Mustafa Khasraw, Eva Sedlackova, Ivan Borbath, Paul Ruff, Paul Oberstein, Tetsuhide Ito, Liqun Jia, Pascal Hammel, Lin Shen, Shailesh V Shrikhande, Yali Shen, Jozef Sufliarsky, Gazala Khan, Chigusa Morizane, Salvatore Galdy, Reza Khosravan, Kathrine Fernandez, Brad Rosbrook, Nicola Fazio
<br>Background: In a phase III study, sunitinib led to a significant increase in progression- free survival (PFS) vs. placebo in patients with pancreatic neuroendocrine tumours (panNETs). This study was a post-marketing commitment to support the phase III data. <br><br>Methods: In this ongoing, open-label, phase IV trial (NCT01525550), patients with progressive, advanced unresectable/metastatic, well-differentiated panNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to the phase III study...
July 10, 2018: Neuroendocrinology
Sophie Moog, Sophie Moog, Sébastien Houy, Elodie Chevalier, Stéphane Ory, Georges Weryha, Marion Rame, Marc Klein, Laurent Brunaud, Stéphane Gasman, Thomas Cuny
<br>Background: 18F-FDOPA positron emission tomography/computed tomography (PET/CT) is a sensitive nuclear imaging for the diagnosis of pheochromocytomas (PHEO). However, its utility as a predictive factor of the secretion of catecholamines remains poorly studied. METHODS: Thirty-nine histologically-confirmed PHEO were included in this retrospective monocentric study. Patients underwent 18F-FDOPA PET/CT before surgery with evaluation of several uptake parameters (SUVmax, SUVmean and the metabolic burden [MB] calculated as follows: MB = SUVmean x tumor volume) and measurement of plasma and/or urinary metanephrine (MN), normetanephrine (NM) and chromogranin A (CGA)...
June 27, 2018: Neuroendocrinology
Michaela Fredrich, Elmar Christ, Horst-Werner Korf
<br>Background/Aims: Zeitgeber time (ZT)-dependent changes in cell proliferation and apoptosis are regulated by melatonin receptor (MT)-mediated signaling in the adult hippocampus and hypothalamic-hypophyseal system. There are two G-protein-coupled MT-subtypes, MT1 and MT2. Therefore, the present study examined which MT-subtype is required for regulation of ZT-dependent changes in cell proliferation and/or apoptosis in the adult murine brain and pituitary. METHODS: Adult melatonin-proficient (C3H) mice with targeted deletion of MT1 (MT1 KO) or MT2 (MT2 KO) were adapted to a 12-hour light, 12-hour dark photoperiod and sacrificed at ZT00, ZT06, ZT12, and ZT18...
June 27, 2018: Neuroendocrinology
Helene Kvistgaard, Jane H Christensen, Jan-Ove Johansson, Niels Gregersen, Charlotte Rittig, Soeren Rittig, Thomas Juhl Corydon
<br>Objective: Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is characterized by severe polyuria and polydipsia and is caused by variations in the gene encoding the AVP prohormone. The study aimed to ascertain a correct diagnosis, to identify the underlying genetic cause of adFNDI in a Swedish kindred, and to test the hypothesis that the identified synonymous exonic variant in the AVP gene (c.324G>A), causes missplicing, and endoplasmic reticulum (ER) retention of the prohormone...
June 27, 2018: Neuroendocrinology
Michelle Bedenbaugh, Rick McCosh, Justin Lopez, John Connors, Robert L Goodman, Stan Hileman
<br> Background: Neuronal intermediates that communicate estrogen and progesterone feedback to gonadotropin-releasing hormone (GnRH) neurons are essential for modulating reproductive cyclicity. Individually, kisspeptin and nitric oxide (NO) influence GnRH secretion. However, it is possible these two neuronal intermediates interact with one another to affect reproductive cyclicity. METHODS: We investigated the neuroanatomical relationship of one isoform of the enzyme that synthesizes NO, neuronal nitric oxide synthase (nNOS), to kisspeptin and GnRH in adult female rhesus monkeys and sheep using dual-label immunofluorescence...
June 21, 2018: Neuroendocrinology
Sheng-Feng Tsai, Hung-Tsung Wu, Po See Chen, Pei-Chun Chen, Yun-Wen Chen, Megan Yu, Shun-Fen Tzeng, Pei-Hsuan Wu, Yu-Min Kuo
<br>Background: The notion that exposure to chronic stress predisposes individuals to develop Type 2 diabetes (T2D) has gained much attention in recent decades. Long-term stress induces neuroadaptation in the amygdala and increases corticosterone levels. Corticosterone, the major stress hormone in rodents, induces insulin resistance and obesity in mice. However, little is known whether the stress-induced amygdalar neuroadaptation could promote the risk of T2D. METHODS: We used an 11-week high-fat-diet (HFD) feeding paradigm to induce insulin dysfunction in mice, followed by implementing a 10-day social defeat (SD) stress protocol...
June 19, 2018: Neuroendocrinology
Lunpo Wu, Fei Chen, Shujie Chen, Liangjing Wang
<br>Background: The effectiveness of current Tumor, Lymph node, Metastases (TNM) staging system in small intestinal neuroendocrine tumors (SiNETs) is unsatisfactory. Current N classification only distinguishes between node-negative and node-positive status. We aim to refine the N classification for updated TNM stage. METHODS: Patients with non-metastatic SiNETs between 1988 and 2012 were enrolled in the Surveillance, Epidemiology, and End Results (SEER) database. Using the X-tile program, we calculated an optimal cut-off value for lymph node ratio (LNR) and proposed a novel Nr category...
June 19, 2018: Neuroendocrinology
David H Abbott, Sarah H Vepraskas, Teresa H Horton, Ei Terasawa, Jon E Levine
BACKGROUND/AIMS: Ovarian theca cell hyperandrogenism in women with PCOS is compounded by androgen receptor-mediated impairment of estradiol and progesterone negative feedback regulation of episodic LH release. The resultant LH hypersecretion, likely the product of accelerated episodic release of GnRH from the median eminence of the hypothalamus, hyperstimulates ovarian theca cell steroidogenesis, enabling testosterone (T) and androstenedione excess. Prenatally androgenized female monkeys (PA) exposed to fetal male levels of T during early-to-mid gestation, when adult, demonstrate PCOS-like traits, including high T and LH levels...
June 15, 2018: Neuroendocrinology
Alessandro Vanoli, Stefano La Rosa, Emanuela Miceli, Catherine Klersy, Roberta Maragliano, Francesca Capuano, Andrea Persichella, Michele Martino, Frediano Inzani, Ombretta Luinetti, Antonio Di Sabatino, Fausto Sessa, Marco Paulli, Gino Roberto Corazza, Guido Rindi, Cesare Bordi, Carlo Capella, Enrico Solcia
BACKGROUND: Gastric neuroendocrine neoplasms (NENs) are very heterogeneous, ranging from mostly indolent, atrophic gastritis-associated, type I neuroendocrine tumors (NETs), through highly malignant, poorly differentiated neuroendocrine carcinomas (pdNECs), to sporadic type III NETs with intermediate prognosis, and various rare tumor types. Histologic differentiation, proliferative grade, size, level of gastric wall invasion, and local or distant metastases are used as prognostic markers...
June 12, 2018: Neuroendocrinology
Delanie Macedo, Monica M França, Luciana Montenegro, Marina Cunha-Silva, Danielle S Bessa, Ana Paula Abreu, Ursula B Kaiser, Berenice B Mendonca, Alexander A L Jorge, Vinicius N Brito, Ana C Latronico
<br>Context: Loss-of-function mutations in the coding region of MKRN3, a maternally imprinted gene at chromosome 15q11.2, are a common cause of familial central precocious puberty (CPP). Whether MKRN3 alterations in regulatory regions can cause CPP has not been explored to date. We aimed to investigate potential pathogenic variants in the promoter region of MKRN3 in patients with idiopathic CPP. Patients/ Methods: A cohort of 110 patients with idiopathic CPP was studied. Family history of precocious sexual development was present in 25%...
May 15, 2018: Neuroendocrinology
Ali Abbara, Sophie A Clarke, Alexander Nesbitt, Sabreen Ali, Alexander N Comninos, Emma Hatfield, Niamh Martin, Amir Sam, Karim Meeran, Waljit S Dhillo
<br>Background/Aims: Hyperprolactinemia is a common cause of amenorrhea due to hypogonadotropic hypogonadism. Prolactin is hypothesized to impede the reproductive axis through an inhibitory action at the hypothalamus. However, limited data exists to aid the interpretation of serum gonadotropins in the context of hyperprolactinemia. METHODS: Serum gonadotropin values were reviewed in 243 patients with elevated serum monomeric prolactin due to discrete etiologies at a tertiary reproductive endocrine centre between 2012 and 2015...
April 16, 2018: Neuroendocrinology
Jan Maarten van der Zwan, Sabine Siesling, Loes van Velthuysen, Thera Links, Annemiek Walenkamp, Margot Tesselaar
BACKGROUND: Extra-pulmonary neuroendocrine carcinomas (EP-NEC) are rare tumours that require expertise for correct and timely diagnosis, which is essential for clinical decision making. The number of patients affected, treatment given, and the proportion surviving the disease is based on limited evidence. The aim of this study is to retrospectively analyse the incidence, treatment, and relative survival (RS) of EP-NEC patients in the Netherlands. METHODS: Patients diagnosed between 2008-2012 with EP-NEC or NEC with unknown primary site (UP-NEC) were selected from the Netherlands Cancer Registry based on combinations of tumour localisation and morphology code...
April 14, 2018: Neuroendocrinology
Anna Malczewska, Mark Kidd, Somer Matar, Beata Kos-Kudla, Irvin M Modlin
BACKGROUND/AIMS: A key issue in neuroendocrine neoplasia management is the identification of blood signatures that specifically define the activity of a cancer or local tumor microenvironment. MicroRNAs (miRNAs) may represent such a candidate. To evaluate their clinical utility as biomarkers in gastroenteropancreatic neuroendocrine tumors (GEP-NETs), we assessed their expression in tissue and blood. METHODS: A systematic review of PubMed was undertaken to identify studies investigating miRNAs in GEP-NETs and their utility as blood or tissue biomarkers...
March 22, 2018: Neuroendocrinology
Ron Basuroy, Cathy Bouvier, John Ramage, Maia Sissons, Alexandra Kent, Raj Srirajaskanthan
<br>Introduction The gastrointestinal tract and pancreas are common primary sites for neuroendocrine tumours (NETs). Patients often report long duration of non-specific symptoms in the year prior to diagnosis. The aims of this study were to establish pre-diagnosis patterns of symptoms. Secondly, to determine the time from onset of symptoms to NET diagnosis and understand the interaction with primary and secondary healthcare providers. Method A survey was designed on a web-based survey platform with the focus on patient symptoms prior to diagnosis and a screen for functional diarrhoea (Rome III criteria (C4))...
March 18, 2018: Neuroendocrinology
John Russell, Emily Lodge, Cynthia Andoniadou
<br>As a central regulator of major physiological processes, the pituitary gland is a highly dynamic organ, capable of responding to hormonal demand and hypothalamic influence, through adapting secretion as well as remodelling cell numbers among its seven populations of differentiated cells. Stem cells of the pituitary have been shown to actively generate new cells during postnatal development but remain mostly quiescent during adulthood, where they persist as a long-lived population. Despite a significant body of research characterising attributes of anterior pituitary stem cells, the regulation of this population is poorly understood...
March 14, 2018: Neuroendocrinology
David L Chan, Lesley Moody, Eva Segelov, David Metz, Jonathan Strosberg, Nick Pavlakis, Simron Singh
<br>Objectives: There is no consensus regarding optimal follow-up in resected GEP-NETS. We aimed to perform a practice survey to ascertain follow-up patterns by health care practitioners and highlight areas of variation that may benefit from further quantitative research. METHODS: A web-based survey targeted at NET health care providers in Australia, New Zealand, Canada and the United States was developed by a steering committee of medical oncologists and a research methodologist...
March 14, 2018: Neuroendocrinology
Anna Pellat, Chantal Dreyer, Camille Couffignal, Thomas Walter, Catherine Lombard-Bohas, Patricia Niccoli, Jean François Seitz, Olivia Hentic, Thierry André, Romain Coriat, Sandrine Faivre, Magaly Zappa, Philippe Ruszniewski, Nicolas Pote, Anne Couvelard, Eric Raymond
BACKGROUND/AIMS: Angiogenesis is extensively developed in well-differentiated pancreatic neuroendocrine tumours (PanNET) where sunitinib was shown to prolong progression-free survival, leading to nationwide approval. However, clinical experience in patients with grade 3 gastroenteropancreatic neuroendocrine neoplasms (GEPNEN-G3) remains limited. This prospective phase II trial evaluated potential predictive biomarkers of sunitinib activity in patients with advanced GEPNEN-G3. METHODS: Sunitinib was given at a dose of 37...
March 8, 2018: Neuroendocrinology
Sarah Robins, Maia Kokoeva
<br>There is increasing evidence that glia act not only as neuronal support cells, but that they can also influence physiological outcomes via effects on neural signalling. The role of NG2-glia in this regard is especially enigmatic, as they are known to interact with neural circuits but their precise functions other than as oligodendrocyte progenitor cells remain elusive. Here we summarise recent evidence suggesting that NG2-glia play a role in the maintenance of energy homeostasis, most notably via the support of leptin sensing neural circuits...
March 5, 2018: Neuroendocrinology
Christine Lu, Eleanor Hutchens, Leon Farhy, Heather Bonner, Paul Suratt, Christopher McCartney
<br>Objective: During the early follicular phase, sleep-related luteinizing hormone (LH) pulse initiation is positively associated with brief awakenings but negatively associated with random eye movement (REM) sleep. The relationship between sleep architecture and LH pulse initiation has not been assessed in other cycle stages or in women with polycystic ovary syndrome (PCOS). DESIGN AND METHODS: We performed concomitant frequent blood sampling (LH pulse analysis) and polysomnography in 8 normal women (cycle day 7-11) and 7 women with PCOS (at least cycle day 7)...
March 5, 2018: Neuroendocrinology
Maud Gratuze, Aurélie Joly-Amado, Didier Vieau, Luc Buée, David Blum
<br>Alzheimer's disease (AD) is a progressive neurodegenerative disorder mainly characterized by cognitive deficits and neuropathological changes such as Tau lesions and amyloid plaques, but also associated with non-cognitive symptomatology. Metabolic and neuroendocrine abnormalities, such as alterations in body weight, brain insulin impairments and lower brain glucose metabolism, that often precede clinical diagnosis, have been extensively reported in AD patients. However, the origin of these symptoms and their relation to pathology and cognitive impairments remain misunderstood...
February 13, 2018: Neuroendocrinology
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