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https://www.readbyqxmd.com/read/28100630/a-multivariable-prediction-model-for-pegvisomant-dosing-monotherapy-and-in-combination-with-long-acting-somatostatin-analogues
#1
Sanne Elisabeth Franck, Tim Korevaar, Patrick Petrossians, Adrian F Daly, Philippe Chanson, Marielise Jaffrian-Rea, Thierry Brue, Günter K Stalla, Davide Carvalho, Annamaria Anita Livia Colao, Vasik Hana, Brigitte Delemer, Carmen Fajardo Montañana, A J Van der Lely, Albert Beckers, Sebastian J C M M Neggers
BACKGROUND: Effective treatment of acromegaly with pegvisomant (PEGV), a growth hormone receptor antagonist, requires an appropriate dose titration. PEGV doses vary widely among individual patients, and various covariates may affect its dosing and pharmacokinetics. OBJECTIVE: To identify predictors of the PEGV dose required to normalize insulin-like growth factor I (IGF-I) levels during PEGV monotherapy and in combination with long-acting somatostatin analogues (LA-SSAs)...
January 18, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28100033/relaxin-3-inputs-target-hippocampal-interneurons-and-deletion-of-hilar-relaxin-3-receptors-in-floxed-rxfp3-mice-impairs-spatial-memory
#2
M Haidar, G Guèvremont, C Zhang, Rad Bathgate, E Timofeeva, C M Smith, A L Gundlach
Hippocampus is innervated by γ-aminobutyric acid (GABA) 'projection' neurons of the nucleus incertus (NI), including a population expressing the neuropeptide, relaxin-3 (RLN3). In studies aimed at gaining an understanding of the role of RLN3 signaling in hippocampus via its Gi/o -protein-coupled receptor, RXFP3, we examined the distribution of RLN3-immunoreactive nerve fibres and RXFP3 mRNA-positive neurons in relation to hippocampal GABA neuron populations. RLN3-positive elements were detected in close-apposition with a substantial population of somatostatin (SST)- and GABA-immunoreactive neurons, and a smaller population of parvalbumin- and calretinin-immunoreactive neurons in different hippocampal areas, consistent with the relative distribution patterns of RXFP3 mRNA and these marker transcripts...
January 18, 2017: Hippocampus
https://www.readbyqxmd.com/read/28097640/priming-increases-the-anti-tumor-effect-and-therapeutic-window-of-177-lu-octreotate-in-nude-mice-bearing-human-small-intestine-neuroendocrine-tumor-got1
#3
Johanna Dalmo, Johan Spetz, Mikael Montelius, Britta Langen, Yvonne Arvidsson, Henrik Johansson, Toshima Z Parris, Khalil Helou, Bo Wängberg, Ola Nilsson, Maria Ljungberg, Eva Forssell-Aronsson
BACKGROUND: (177)Lu-[DOTA(0), Tyr(3)]-octreotate ((177)Lu-octreotate) is used for treatment of patients with somatostatin receptor (SSTR) expressing neuroendocrine tumors. However, complete tumor remission is rarely seen, and optimization of treatment protocols is needed. In vitro studies have shown that irradiation can up-regulate the expression of SSTR1, 2 and 5, and increase (177)Lu-octreotate uptake. The aim of the present study was to examine the anti-tumor effect of a (177)Lu-octreotate priming dose followed 24 h later by a second injection of (177)Lu-octreotate compared to a single administration of (177)Lu-octreotate, performed on the human small intestine neuroendocrine tumor cell line, GOT1, transplanted to nude mice...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28094316/somatostatin-receptor-expression-on-von-hippel-lindau-associated-hemangioblastomas-offers-novel-therapeutic-target
#4
Saman Sizdahkhani, Michael J Feldman, Martin G Piazza, Alexander Ksendzovsky, Nancy A Edwards, Abhik Ray-Chaudhury, Dragan Maric, Marsha J Merrill, Karel Pacak, Zhengping Zhuang, Prashant Chittiboina
Von Hippel-Lindau (VHL)-associated hemangioblastomas (VHL-HB) arise in the central nervous system (CNS), and are a leading cause of morbidity and mortality in VHL disease. Currently, surgical resection is the most effective way to manage symptomatic VHL-HBs. Surgically unresectable VHL-HBs or those in frail patients are challenging problems. Therapies targeting oncologic and vascular endothelial growth factor (VEGF) pathways have failed to demonstrate tumor control. Our experience and previous reports on VHL-HB avidity to somatostatin analogues suggested somatostatin receptor (SSTR) expression in VHL-HBs, offering an alternative therapeutic strategy...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28091879/new-medical-therapies-on-the-horizon-oral-octreotide
#5
REVIEW
Nienke R Biermasz
Somatostatin analog treatment is first line medical treatment in patients with acromegaly. This drug is currently mainly administered by monthly depot preparations of octreotide and lanreotide. With the innovative transient permeability enhancer, a technology enabling the absorption of drug molecules via transient opening of the tight junctions of the gut epithelium, it is possible to achieve therapeutic octreotide levels after oral ingestion. The present review summarized the preclinical work and the recently reported phase I and III study on oral octreotide capsules in patients with acromegaly...
January 16, 2017: Pituitary
https://www.readbyqxmd.com/read/28089247/-mid-gut-neuroendocrine-tumors-news-on-medical-treatment
#6
Marie Dior, Johann Dreanic, Caroline Prieux-Klotz, Bertrand Brieau, Catherine Brezault, Romain Coriat
CONTEXT: Mid gut neuroendocrine tumors (NET) are rare tumors whose incidence is increasing. Curative surgery remains the gold standard for the treatment of NETs of the small intestine. Surgery should be considered as soon as possible even if a metastatic stage is diagnosed. The management of unresectable well-differentiated metastatic NETs of the small intestine recently changed with the publication of trials demonstrating the benefit of targeted therapies and metabolic radiotherapy, leading to a change of practices and update of French and international recommendations...
January 11, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28076709/phase-3-trial-of-177-lu-dotatate-for-midgut-neuroendocrine-tumors
#7
Jonathan Strosberg, Ghassan El-Haddad, Edward Wolin, Andrew Hendifar, James Yao, Beth Chasen, Erik Mittra, Pamela L Kunz, Matthew H Kulke, Heather Jacene, David Bushnell, Thomas M O'Dorisio, Richard P Baum, Harshad R Kulkarni, Martyn Caplin, Rachida Lebtahi, Timothy Hobday, Ebrahim Delpassand, Eric Van Cutsem, Al Benson, Rajaventhan Srirajaskanthan, Marianne Pavel, Jaime Mora, Jordan Berlin, Enrique Grande, Nicholas Reed, Ettore Seregni, Kjell Öberg, Maribel Lopera Sierra, Paola Santoro, Thomas Thevenet, Jack L Erion, Philippe Ruszniewski, Dik Kwekkeboom, Eric Krenning
Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 ((177)Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either (177)Lu-Dotatate (116 patients) at a dose of 7...
12, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28072620/fibrous-dysplasia-mimicking-malignancy-on-68ga-dotatate-pet-ct
#8
Georgios Z Papadakis, Corina Millo, Samira M Sadowski, Apostolos H Karantanas, Ulas Bagci, Nicholas J Patronas
Fibrous dysplasia of the bone is a developmental benign skeletal disorder characterized by replacement of normal bone and normal bone marrow with abnormal fibro-osseous tissue. We report on a case of a biopsy-proven fibrous dysplasia lesion in the left temporal bone, with intensely increased activity (SUVmax, 56.7) on Ga-DOTATATE PET/CT. The presented data indicate cell surface overexpression of somatostatin receptors by fibrous dysplastic cells and highlight the need of cautious management of Ga-DOTATATE-avid bone lesions, which could mimic malignancy especially in patients with history of neuroendocrine tumors...
January 9, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28070731/evaluation-of-two-intraoperative-gamma-detectors-for-assessment-of-177-lu-activity-concentration-in-vivo
#9
Viktor Sandblom, Ingun Ståhl, Roger Olofsson Bagge, Eva Forssell-Aronsson
BACKGROUND: Patients with somatostatin receptor-expressing neuroendocrine tumours can be treated with intravenously administered (177)Lu-octreotate. Few patients are cured with the present protocol due to the current dose limitation of normal organs at risk, such as the kidneys. By locally administering (177)Lu-octreotate to the liver for the purpose of treating liver metastases, a substantially reduced absorbed dose to organs at risk could be achieved. The development of such a technique requires the capability of measuring the (177)Lu activity concentration in tissues in vivo...
December 2017: EJNMMI Physics
https://www.readbyqxmd.com/read/28069397/influence-of-neuropeptide-y-and-pancreatic-polypeptide-on-islet-function-and-beta-cell-survival
#10
Dawood Khan, Srividya Vasu, R Charlotte Moffett, Nigel Irwin, Peter R Flatt
BACKGROUND: In the present study we assessed the impact of neuropeptide Y receptor (NPYR) modulators, neuropeptide Y (NPY) and pancreatic polypeptide (PP), on islet function and beta-cell survival. METHODS: The effects of NPY and PP on beta-cell function were examined in BRIN BD11 and 1.1B4 beta-cells, as well as isolated mouse islets. Involvement of both peptides in pancreatic islet adaptations to streptozotocin and hydrocortisone, as well as effects on beta-cell proliferation and apoptosis was also evaluated...
January 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28068959/pancreatic-neuroendocrine-tumor-with-metastasis-to-the-spleen-a-case-report
#11
Yasunaru Sakuma, Yoshikazu Yasuda, Naohiro Sata, Yoshinori Hosoya, Atsushi Shimizu, Hirofumi Fujii, Daisuke Matsubara, Noriyuki Fukushima, Atsushi Miki, Misato Maeno, Alan Kawarai Lefor
BACKGROUND: Long-term term survival in patients with pancreatic neuroendocrine tumors has been reported, even in patients with metastatic disease. Metastases to the spleen are extremely rare, but have been reported from a number of primary malignancies, such as breast cancer, lung cancer, melanoma and ovarian cancer. This is the first report of a splenic metastasis from a primary pancreatic neuroendocrine tumor. CASE PRESENTATION: The patient presented as a 53 years old white male with anemia and fatigue...
January 9, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28062624/plasma-n-terminal-prosomatostatin-and-risk-of-incident-cardiovascular-disease-and-all-cause-mortality-in-a-prospective-observational-cohort-the-prevend-study
#12
Ali Abbasi, Lyanne M Kieneker, Eva Corpeleijn, Ron T Gansevoort, Rijk O B Gans, Joachim Struck, Rudolf A de Boer, Hans L Hillege, Ronald P Stolk, Gerjan Navis, Stephan J L Bakker
BACKGROUND: Somatostatin is a component of the well-known insulin-like growth factor-1/growth hormone (GH) longevity axis. There is observational evidence that increased GH is associated with an increased risk of cardiovascular disease (CVD). We aimed to investigate the potential association of plasma N-terminal fragment prosomatostatin (NT-proSST) with incident CVD and all-cause mortality in apparently healthy adults. METHODS: We studied 8134 participants without history of CVD (aged 28-75 years; women, 52...
January 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28059098/somatostatin-receptor-expression-related-to-tp53-and-rb1-alterations-in-pancreatic-and-extrapancreatic-neuroendocrine-neoplasms-with-a-ki67-index-above-20
#13
Björn Konukiewitz, Anna Melissa Schlitter, Moritz Jesinghaus, Dominik Pfister, Katja Steiger, Angela Segler, Abbas Agaimy, Bence Sipos, Giuseppe Zamboni, Wilko Weichert, Irene Esposito, Nicole Pfarr, Günter Klöppel
Somatostatin receptor 2A expression is a feature of well-differentiated neuroendocrine neoplasms and is important for their diagnosis and therapy. Little is known about somatostatin receptor 2A expression in poorly differentiated neuroendocrine neoplasms in relation to TP53 and RB1 status and how these features may contribute to the separation of well from poorly differentiated neuroendocrine neoplasms with a proliferation index above 20%. This study investigates the expression of somatostatin receptors, p53 and Rb1, and TP53 alterations in pancreatic and extrapancreatic well and poorly differentiated neuroendocrine neoplasms (Ki67-index >20%)...
January 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28058079/zollinger-ellison-syndrome-a-rare-case-of-chronic-diarrhea
#14
Ali Aamar, Kamraan Madhani, Hafeezulhassan Virk, Zeeshan Butt
Zollinger-Ellison syndrome (ZES) is caused by hypersecretion of gastrin from duodenal or pancreatic gastrinomas. We report a case of a 57-year-old female who presented with chronic diarrhea. CT abdomen showed multiple liver masses. Liver biopsy suggested metastatic well-differentiated neuroendocrine tumor. Serum gastrin level was markedly elevated. MRI abdomen, somatostatin receptor scintigraphy and endoscopic ultrasound failed to reveal primary site of the tumor. Upper gastrointestinal endoscopy showed hyperplastic gastric folds and multiple duodenal ulcers consistent with ZES...
December 2016: Gastroenterology Research
https://www.readbyqxmd.com/read/28057099/-the-surgery-of-thyrotropin-secreting-pituitary-adenomas-and-the-significance-of-thyroid-stimulating-hormone-level-in-follow-up
#15
Y Y Yang, H Liu, A Hu, Y Zou, B Xing, Y Yao, R Z Wang, W Lian
Objective: To explore the clinical characteristics of thyrotropin-secreting pituitary adenomas and the effect of the transsphenoidal approach of procedure with/without drug treatment for thyrotropin-secreting pituitary adenomas, and to investigate the correlation between the prognosis of thyrotropin-secreting pituitary adenomas and the postoperative level of thyroid stimulating hormone (TSH). Methods: A total of 45 patients with thyrotropin-secreting pituitary adenoma who hospitalized in Peking Union Medical College Hospital from 2000 to 2015 were enrolled in the study...
December 20, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28054107/-evidence-based-supportive-measures-to-secure-pancreatic-anastomoses
#16
O Belyaev, W Uhl
BACKGROUND: Pancreatic anastomosis is the Achilles heel of pancreatic surgery. Despite substantial progress in surgical techniques the rate of postoperative pancreatic fistulas remains very high. For this reason various supportive measures to secure pancreatic anastomoses are of continuing interest. OBJECTIVE: This review presents the newest evidence-based data on supportive measures designed to secure a pancreatic anastomosis. MATERIAL AND METHODS: The most recent meta-analyses, randomized controlled trials and the largest retrospective studies on the role of pancreatic duct stenting, double loop reconstruction, autologous patches and drainage in pancreaticoduodenectomy were taken into account...
January 2017: Der Chirurg; Zeitschrift Für Alle Gebiete der Operativen Medizen
https://www.readbyqxmd.com/read/28050631/head-to-head-comparison-between-18-f-fdopa-pet-ct-and-mr-ct-angiography-in-clinically-recurrent-head-and-neck-paragangliomas
#17
Céline Heimburger, Francis Veillon, David Taïeb, Bernard Goichot, Sophie Riehm, Julie Petit-Thomas, Gerlinde Averous, Marcela Cavalcanti, Fabrice Hubelé, Gerard Chabrier, Izzie Jacques Namer, Anne Charpiot, Alessio Imperiale
PURPOSE: Head and neck paragangliomas (HNPGLs) can relapse after primary treatment. Optimal imaging protocols have not yet been established for posttreatment evaluation. The aim of the present study was to assess the diagnostic value of (18)F-FDOPA PET/CT and MR/CT angiography (MRA/CTA) in HNPGL patients with clinical relapse during their follow-up. METHODS: Sixteen consecutive patients presenting with local pain, tinnitus, dysphagia, hoarse voice, cranial nerve involvement, deafness, or retrotympanic mass appearing during follow-up after the initial treatment of HNPGLs were retrospectively evaluated...
January 3, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28045522/model-based-discovery-of-synthetic-agonists-for-the-zn-sup-2-sup-sensing-g-protein-coupled-receptor-39-gpr39-reveals-novel-biological-functions
#18
Thomas M Frimurer, Franziska Mende, Anne-Sofie Graae, Maja S Engelstoft, Kristoffer L Egerod, Rie Nygaard, Lars-Ole Gerlach, Jakob Bondo Hansen, Thue W Schwartz, Birgitte Holst
The G-protein coupled receptor 39 (GPR39) is a G protein-coupled receptor activated by Zn<sup>2+</sup>. We used a homology model-based approach to identify small-molecule pharmacological tool compounds for the receptor. The method focused on a putative binding site in GPR39 for synthetic ligands and knowledge of ligand binding to other receptors with similar binding pockets to select iterative series of mini-libraries. These libraries were cherry-picked from all commercially available synthetic compounds...
January 3, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28043006/synthesis-and-evaluation-of-a-99m-tc-tricarbonyl-labeled-somatostatin-receptor-targeting-antagonist-peptide-for-imaging-of-neuroendocrine-tumors
#19
Lauren Radford, Fabio Gallazzi, Lisa Watkinson, Terry Carmack, Ashley Berendzen, Michael R Lewis, Silvia S Jurisson, Dionysia Papagiannopoulou, Heather M Hennkens
INTRODUCTION: A somatostatin receptor (SSTR)-targeting antagonist peptide (sst2-ANT) was radiolabeled with (99m)Tc tricarbonyl via a tridentate [N,S,N]-type ligand (L) to develop a radiodiagnostic agent, (99m)TcL-sst2-ANT, for imaging of SSTR-expressing neuroendocrine tumors. METHODS: Receptor affinity was assessed in vitro with the nonradioactive analogue, ReL-sst2-ANT, via a challenge experiment in AR42J cells with (125)I-SS-14 as the competing radioligand. Preparation of (99m)TcL-sst2-ANT was achieved via reaction of [(99m)Tc(CO)3(H2O)3](+) with L-sst2-ANT...
December 9, 2016: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28041880/dynamic-cell-type-specific-roles-for-gabaergic-interneurons-in-a-mouse-model-of-optogenetically-inducible-seizures
#20
Sattar Khoshkhoo, Daniel Vogt, Vikaas S Sohal
GABAergic interneurons play critical roles in seizures, but it remains unknown whether these vary across interneuron subtypes or evolve during a seizure. This uncertainty stems from the unpredictable timing of seizures in most models, which limits neuronal imaging or manipulations around the seizure onset. Here, we describe a mouse model for optogenetic seizure induction. Combining this with calcium imaging, we find that seizure onset rapidly recruits parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptitde (VIP)-expressing interneurons, whereas excitatory neurons are recruited several seconds later...
January 18, 2017: Neuron
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