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https://www.readbyqxmd.com/read/29350062/telotristat-ethyl-a-novel-agent-for-the-therapy-of-carcinoid-syndrome-diarrhea
#1
Joseph S Dillon, Chandrikha Chandrasekharan
Carcinoid syndrome (CS), characterized by diarrhea and flushing, is present in 20% of patients with neuroendocrine tumors at diagnosis and becomes more frequent with progression. The diarrhea of CS is caused mainly by tumoral secretion of serotonin. It may not be fully controlled by somatostatin analogs, the currently indicated drugs for symptomatic relief. Telotristat ethyl is a novel inhibitor of tryptophan hydroxylase, the rate-limiting enzyme in serotonin biosynthesis. Administration of the drug decreases diarrhea in patients with CS...
January 19, 2018: Future Oncology
https://www.readbyqxmd.com/read/29346766/cell-type-specificity-of-callosally-evoked-excitation-and-feedforward-inhibition-in-the-prefrontal-cortex
#2
Paul G Anastasiades, Joseph J Marlin, Adam G Carter
Excitation and inhibition are highly specific in the cortex, with distinct synaptic connections made onto subtypes of projection neurons. The functional consequences of this selective connectivity depend on both synaptic strength and the intrinsic properties of targeted neurons but remain poorly understood. Here, we examine responses to callosal inputs at cortico-cortical (CC) and cortico-thalamic (CT) neurons in layer 5 of mouse prelimbic prefrontal cortex (PFC). We find callosally evoked excitation and feedforward inhibition are much stronger at CT neurons compared to neighboring CC neurons...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346754/input-specific-nmdar-dependent-potentiation-of-dendritic-gabaergic-inhibition
#3
Chiayu Q Chiu, James S Martenson, Maya Yamazaki, Rie Natsume, Kenji Sakimura, Susumu Tomita, Steven J Tavalin, Michael J Higley
Preservation of a balance between synaptic excitation and inhibition is critical for normal brain function. A number of homeostatic cellular mechanisms have been suggested to play a role in maintaining this balance, including long-term plasticity of GABAergic inhibitory synapses. Many previous studies have demonstrated a coupling of postsynaptic spiking with modification of perisomatic inhibition. Here, we demonstrate that activation of NMDA-type glutamate receptors leads to input-specific long-term potentiation of dendritic inhibition mediated by somatostatin-expressing interneurons...
January 17, 2018: Neuron
https://www.readbyqxmd.com/read/29344905/management-of-nfas-medical-treatment
#4
REVIEW
Naomi Even-Zohar, Yona Greenman
INTRODUCTION: Non-functioning pituitary adenomas (NFPAs) are in general large tumors that present with symptoms secondary to local pressure on adjacent structures. Transsphenoidal surgery is the first line of treatment but residual tumor mass is often detected post-operatively. Medical therapy, in any stage of tumor management, is not well established. METHODS: A literature search was performed to review the available data on medical treatment of NFPAs. RESULTS: Medications investigated for the treatment of NFPAs include dopamine receptor agonists (DA) and somatostatin receptor ligands...
January 17, 2018: Pituitary
https://www.readbyqxmd.com/read/29344308/-albumin-hitchhiking-with-an-evans-blue-analog-for-cancer-theranostics
#5
EDITORIAL
Emily B Ehlerding, Xiaoli Lan, Weibo Cai
Although 177Lu-DOTA-TATE was recently approved in Europe for the treatment of certain neuroendocrine tumors, continued development and optimization has been ongoing to further improve the therapeutic efficacy of somatostatin receptor 2 targeted peptide receptor radionuclide therapy, as well as reducing the renal toxicity. In this work, the use of an Evans blue analog for "albumin hitchhiking" resulted in significant improvement in both the imaging performance and therapeutic efficacy of radiolabeled octreotate, as well as reducing the toxicity since much less radioactivity was used for therapy...
2018: Theranostics
https://www.readbyqxmd.com/read/29344302/evans-blue-attachment-enhances-somatostatin-receptor-subtype-2-imaging-and-radiotherapy
#6
Rui Tian, Orit Jacobson, Gang Niu, Dale O Kiesewetter, Zhantong Wang, Guizhi Zhu, Ying Ma, Gang Liu, Xiaoyuan Chen
Purpose: Radionuclide therapy directed against tumors that express somatostatin receptors (SSTRs) has proven effective for the treatment of advanced, low- to intermediate-grade neuroendocrine tumors in the clinic. In clinical usage, somatostatin peptide-based analogs, labeled with therapeutic radionuclides, provide an overall response rate of about 30%, despite the high cumulative activity injected per patient. We set out to improve the effectiveness of somatostatin radiotherapy by preparing a chemical analog that would clear more slowly through the urinary tract and, concomitantly, have increased blood circulation half-life and higher targeted accumulation in the tumors...
2018: Theranostics
https://www.readbyqxmd.com/read/29344295/peptide-receptor-radionuclide-therapy-as-a-new-tool-in-treatment-refractory-sarcoidosis-initial-experience-in-two-patients
#7
Constantin Lapa, Malte Kircher, Heribert Hänscheid, Andreas Schirbel, Götz Ulrich Grigoleit, Erdwine Klinker, Markus Böck, Samuel Samnick, Theo Pelzer, Andreas K Buck
Sarcoidosis is a multisystem granulomatous disorder of unknown etiology that can involve virtually all organ systems. Whereas most patients present without symptoms, progressive and disabling organ failure can occur in up to 10% of subjects. Somatostatin receptor (SSTR)-directed peptide receptor radionuclide therapy (PRRT) has recently received market authorization for treatment of SSTR-positive neuroendocrine tumors. Methods: We describe the first case series comprising two patients with refractory multi-organ involvement of sarcoidosis who received 4 cycles of PRRT...
2018: Theranostics
https://www.readbyqxmd.com/read/29343878/cxcl14-like-immunoreactivity-exists-in-somatostatin-containing-endocrine-cells-and-in-the-lamina-propria-and-submucosal-somatostatinergic-nervous-system-of-mouse-alimentary-tract
#8
Hirohumi Suzuki, Kentaro Yamada, Yasuhiro Matsuda, Minoru Onozuka, Toshiharu Yamamoto
In the present study, we investigated the distribution of CXCL14 immunoreactive endocrine cells and neurons in mouse alimentary tract by immunohistochemistry. CXCL14 immunoreactive endocrine cells were found as closed-type cells in the stomach and open-type cells in the small intestine. The immunostaining of these endocrine cells corresponded with that of the somatostatin-containing endocrine cells. Only a few CXCL14 immunoreactive endocrine cells were seen in the large intestine. CXCL14 immunoreactive fibers were observed in the muscular layer from the stomach to the rectum with most abundance in the rectum...
December 26, 2017: Acta Histochemica et Cytochemica
https://www.readbyqxmd.com/read/29343737/moderate-decline-in-select-synaptic-markers-in-the-prefrontal-cortex-ba9-of-patients-with-alzheimer-s-disease-at-various-cognitive-stages
#9
Odile Poirel, Sébastien Mella, Catherine Videau, Lauriane Ramet, Maria Antonietta Davoli, Etienne Herzog, Pavel Katsel, Naguib Mechawar, Vahram Haroutunian, Jacques Epelbaum, Stéphanie Daumas, Salah El Mestikawy
Synaptic loss, plaques and neurofibrillary tangles are viewed as hallmarks of Alzheimer's disease (AD). This study investigated synaptic markers in neocortical Brodmann area 9 (BA9) samples from 171 subjects with and without AD at different levels of cognitive impairment. The expression levels of vesicular glutamate transporters (VGLUT1&2), glutamate uptake site (EAAT2), post-synaptic density protein of 95 kD (PSD95), vesicular GABA/glycine transporter (VIAAT), somatostatin (som), synaptophysin and choline acetyl transferase (ChAT) were evaluated...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339530/management-of-endocrine-disease-personalized-medicine-in-the-treatment-of-acromegaly
#10
Leandro Kasuki, Luiz Eduardo Wildemberg, Monica R Gadelha
Acromegaly is associated with high morbidity and elevated mortality when not adequately treated. Surgery is the first-line treatment for most patients as it is the only one that can lead to immediate cure. In patients who are not cured by surgery, treatment is currently based on a trial-and-error approach. First-generation somatostatin receptor ligands (fg-SRL) are initiated for most patients, although approximately 25% of patients present resistance to this drug class. Some biomarkers of treatment outcome are described in the literature, with the aim of categorizing patients into different groups to individualize their treatments using a personalized approach...
January 16, 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29337050/impairments-in-social-novelty-recognition-and-spatial-memory-in-mice-with-conditional-deletion-of-scn1a-in-parvalbumin-expressing-cells
#11
Tetsuya Tatsukawa, Ikuo Ogiwara, Emi Mazaki, Atsushi Shimohata, Kazuhiro Yamakawa
Loss of function mutations in the SCN1A gene, which encodes the voltage-gated sodium channel Nav1.1, have been described in the majority of Dravet syndrome patients presenting with epileptic seizures, hyperactivity, autistic traits, and cognitive decline. We previously reported predominant Nav1.1 expression in parvalbumin-expressing (PV+) inhibitory neurons in juvenile mouse brain and observed epileptic seizures in mice with selective deletion of Scn1a in PV+ cells mediated by PV-Cre transgene expression (Scn1afl/+/PV-Cre-TG)...
January 11, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29333742/parvalbumin-fast-spiking-interneurons-are-selectively-altered-by-pediatric-traumatic-brain-injury
#12
Joshua Nichols, George Reed Bjorklund, Jason Newbern, Trent Anderson
Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in children. Traditionally, ongoing neurodevelopment and neuroplasticity have thought to confer children with an advantage following TBI. However, recent findings indicate that the pediatric brain may be more sensitive to brain injury. Inhibitory interneurons are essential for proper cortical function and implicated in the pathophysiology of TBI, yet few studies have directly examined for TBI induced changes to interneurons themselves...
January 15, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29333632/binding-of-cu-and-cu2-with-peptides-peptides-oxytocin-arg8-vasopressin-bradykinin-angiotensin-i-substance-p-somatostatin-and-neurotensin
#13
Thankan Jayasekharan, Shyam L Gupta, Vikas Dhiman
The intrinsic binding ability of seven natural peptides (oxytocin, arg8 -vasopressin, bradykinin, angiotensin-I, substance-P, somatostatin, and neurotensin) with copper in two different oxidation states (CuI/II ) derived from different Cu+/2+ precursor sources have been investigated for their charge dependent binding characteristics. The peptide-CuI/II complexes, [M - (n-1)H + nCuI ] and [M - (2n-1)H + nCuII ] are prepared/generated by the reaction of peptides with CuI solution/Cu-target and CuSO4 solution, and are analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS)...
January 15, 2018: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/29333565/manual-on-the-proper-use-of-lutetium-177-labeled-somatostatin-analogue-lu-177-dota-tate-injectable-in-radionuclide-therapy-2nd-ed
#14
Makoto Hosono, Hideharu Ikebuchi, Yoshihide Nakamura, Nobutaka Nakamura, Takahiro Yamada, Sachiko Yanagida, Asami Kitaoka, Kiyotaka Kojima, Hiroyasu Sugano, Seigo Kinuya, Tomio Inoue, Jun Hatazawa
Here we present the guideline for the treatment of neuroendocrine tumors using Lu-177-DOTA-TATE on the basis of radiation safety aspects in Japan. This guideline was prepared by a study supported by Ministry of Health, Labour, and Welfare, and approved by Japanese Society of Nuclear Medicine. Lu-177-DOTA-TATE treatment in Japan should be carried out according to this guideline. Although this guideline is applied in Japan, the issues for radiation protection shown in this guideline are considered internationally useful as well...
January 15, 2018: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/29330294/establishment-of-the-first-well-differentiated-human-pancreatic-neuroendocrine-tumor-model
#15
Daniel Benten, Yasmin Behrang, Ludmilla Unrau, Victoria Weissmann, Gerrit Wolters-Eisfeld, Susanne Burdak-Rothkamm, Felix R Stahl, Martin Anlauf, Patricia Grabowski, Markus Möbs, Jan Dieckhoff, Bence Sipos, Martina Fahl, Corinna Eggers, Daniel Perez, Maximilian Bockhorn, Jakob R Izbicki, Ansgar W Lohse, Joerg Schrader
Clinical options for systemic therapy of neuroendocrine tumors (NET) are limited. Development of new drugs requires suitable representative in vitro and in vivo model systems. So far, the unavailability of a human model with a well-differentiated phenotype and typical growth characteristics has impaired pre-clinical research in NET. Herein, we establish and characterize a lymph node-derived cell line (NT-3) from a male patient with well-differentiated pancreatic NET. Neuroendocrine differentiation and tumor biology was compared to existing NET cell lines BON and QGP-1...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330194/telotristat-ethyl-in-carcinoid-syndrome-safety-and-efficacy-in-the-telecast-phase-3-trial
#16
Marianne E Pavel, David J Gross, Marta Benavent, Petros Perros, Raj Srirajaskanthan, Richard R P Warner, Matthew H Kulke, Lowell Anthony, Pamela Kunz, Dieter Hörsch, Martin O Weickert, Pablo Lapuerta, Wenjun Jiang, Kenneth Kassler-Taub, Suman Wason, Rosanna Fleming, Douglas Fleming, Rocio García-Carbonero
Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the Phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a Phase 3 companion study, assessed safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea, or elevated urinary 5-hydroxyindoleacetic acid [u5-HIAA]) with <4 BMs/day on SSAs (or ≥1 symptom or ≥4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE)...
January 12, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29329401/morphological-and-functional-characterization-of-non-fast-spiking-gabaergic-interneurons-in-layer-4-microcircuitry-of-rat-barrel-cortex
#17
Vishalini Emmenegger, Guanxiao Qi, Haijun Wang, Dirk Feldmeyer
GABAergic interneurons are notorious for their heterogeneity, despite constituting a small fraction of the neuronal population in the neocortex. Classification of interneurons is crucial for understanding their widespread cortical functions as they provide a complex and dynamic network, balancing excitation and inhibition. Here, we investigated different types of non-fast-spiking (nFS) interneurons in Layer 4 (L4) of rat barrel cortex using whole-cell patch-clamp recordings with biocytin-filling. Based on a quantitative analysis on a combination of morphological and electrophysiological parameters, we identified 5 distinct types of L4 nFS interneurons: 1) trans-columnar projecting interneurons,2) locally projecting non-Martinotti-like interneurons, 3) supra-granular projecting Martinotti-like interneurons,4) intra-columnar projecting VIP-like interneurons,and5) locally projecting neurogliaform-like interneurons...
January 10, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29326366/highly-proliferative-alpha-cell-related-islet-endocrine-cells-in-human-pancreata
#18
Carol J Lam, Aaron R Cox, Daniel R Jacobson, Matthew M Rankin, Jake A Kushner
The proliferative response of non-β islet endocrine cells in response to type 1 diabetes (T1D) remains undefined. We quantified islet endocrine cell proliferation in a large collection of non-diabetic control and T1D human pancreata across a wide range of ages. Surprisingly, islet endocrine cells with abundant proliferation were present in many adolescent and young adult T1D pancreata. But, the proliferative islet endocrine cells were also present in similar abundance within control samples. We queried the proliferating islet cells with antisera against various islet hormones...
January 11, 2018: Diabetes
https://www.readbyqxmd.com/read/29326172/diversity-and-connectivity-of-layer-5-somatostatin-expressing-interneurons-in-the-mouse-barrel-cortex
#19
Nigro Maximiliano José, Yoshiko Hashikawa, Bernardo Rudy
Inhibitory interneurons represent 10-15% of the neurons in the somatosensory cortex, and their activity powerfully shapes sensory processing. Three major groups of GABAergic interneurons have been defined according to developmental, molecular, morphological, electrophysiological, and synaptic features. Dendritic-targeting somatostatin-expressing interneurons (SST-INs) have been shown to display diverse morphological, electrophysiological and molecular properties and activity patterns in vivo. However, the correlation between these properties and SST-IN subtype is unclear...
January 11, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29324681/ppoma-review-epidemiology-aetiopathogenesis-prognosis-and-treatment
#20
REVIEW
Thais Ligiero Braga, Ralph Santos-Oliveira
Generally, pancreatic polypeptide-secreting tumor of the distal pancreas (PPoma) is classified as a rare tumor, and may occur sporadically or be associated in families or with multiple endocrine neoplasia type 1 (NEM 1). It grows slowly, reaching large dimensions at the time of diagnosis and the symptomatology is fundamentally due to the mass effect, causing either non-specific abdominal pain or symptoms suggestive of obstruction of the pancreatic or biliary duct. Therefore, when detected, they are usually malignant, with metastases mainly in the liver...
January 11, 2018: Diseases (Basel)
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