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Rosalba Mansi, Ryogo Minamimoto, Helmut Mäcke, Andrei H Iagaru
Imaging plays an important role in prostate cancer (PC), including accurate evaluation of the extent of disease, assessment of sites of recurrent disease, and monitoring of response to treatment. Molecular imaging techniques are among the novel developments related to the imaging of PC, and various SPECT and PET radiopharmaceuticals are now available in clinical trials or commercially. Here we describe the preclinical and clinical use of gastrin-releasing peptide receptors as targets for the imaging of PC, with a focus on the development of PET tracers for the imaging of gastrin-releasing peptide receptor-positive tumors...
October 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
David M Schuster, Cristina Nanni, Stefano Fanti
Conventional imaging of prostate cancer has limitations related to the frequently indolent biology of the disease. PET is a functional imaging method that can exploit various aspects of tumor biology to enable greater detection of prostate cancer than can be provided by morphologic imaging alone. Radiotracers that are in use or under investigation for targeting salient features of prostate cancer include those directed to glucose, choline, acetate, prostate-specific membrane antigen, bombesin, and amino acids...
October 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Karine Blais, Jasmine Sethi, Iustin V Tabarean
Bombesin, a pan agonist of the bombesin-like peptide receptor family, elicits potent hypothermia when applied centrally. The signaling mechanisms involved are not known. Here we report that GABAergic preoptic neurons express gastrin-releasing peptide (GRP) receptors and are directly excited by GRP or bombesin. This effect was abolished by a GRP receptor antagonist. A partially overlapping group of preoptic GABAergic neurons express bombesin-like receptor 3 (BRS3), however their activation results in a decrease in firing rate...
September 28, 2016: Neuroscience Letters
Anjuman Ara Begum, Peter M Moyle, Istvan Toth
Gastrin releasing peptide (GRP) receptor (GRPR), a bombesin family receptor, is overexpressed in many cancers including breast, prostate, pancreatic and lung. The targeting of therapeutics to GRPR can be achieved using the full-length (14 amino acid) GRP analogue Bombesin (BBN) or the truncated BBN(6-14) sequence, both of which bind GRPR with high affinity and specificity. In this study, we have investigated the level of GRPR expression in various cancerous (Caco-2, HeLa, LNCap, MDA-MB-231, and PC-3) and non-cancerous (WPMY-1) cell lines using a western blotting approach...
September 16, 2016: Bioorganic & Medicinal Chemistry
Agnieszka Tąta, Aleksandra Szkudlarek, Younkyoo Kim, Edyta Proniewicz
This work demonstrates the application of commercially available stable surface composed of gold nanograins with diameters ranging from 70 to 226nm deposited onto silicon wafer for surface-enhanced Raman scattering investigations of biologically active compounds, such as bombesin (BN) and its fragments. BN is an important neurotransmitter involved in a complex signaling pathways and biological responses; for instance, hypertensive action, contractive on uterus, colon or ileum, locomotor activity, stimulation of gastric and insulin secretion as well as growth promotion of various tumor cell lines, including: lung, prostate, stomach, colon, and breast...
September 20, 2016: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Mana Taweevisit, Boochit Theerasantipong, Kanlaya Taothong, Paul Scott Thorner
The pulmonary neuroendocrine system includes pulmonary neuroendocrine cells (PNECs) and neuroepithelial bodies (NEBs) that are distributed throughout respiratory epithelium, and regulate lung growth and maturation antenatally. Abnormalities in this system have been linked to many hypoxia-associated pediatric pulmonary disorders. Hemoglobin (Hb) Bart disease is a severe form of α-thalassemia resulting in marked intrauterine hypoxia with hydrops fetalis (HF) and usually death in utero. Affected fetuses can serve as a naturally occurring human model for the effects of intrauterine hypoxia and we postulated these effects should include changes in the pulmonary neuroendocrine system...
September 6, 2016: Pediatric and Developmental Pathology
Inge van der Kroon, Lieke Joosten, Berthold A Nock, Theodosia Maina, Otto C Boerman, Maarten Brom, Martin Gotthardt
OBJECTIVE: Accurate assessment of the (111)In-exendin-3 uptake within the pancreas requires exact delineation of the pancreas, which is highly challenging by MRI and CT in rodents. In this study, the pancreatic tracer (99m)Tc-demobesin-4 was evaluated for accurate delineation of the pancreas to be able to accurately quantify (111)In-exendin-3 uptake within the pancreas. METHODS: Healthy and alloxan-induced diabetic Brown Norway rats were injected with the pancreatic tracer (99m)Tc-demobesin-4 ([(99m)Tc-N4-Pro(1),Tyr(4),Nle(14)]bombesin) and the beta cell tracer (111)In-exendin-3 ([(111)In-DTPA-Lys(40)]exendin-3)...
October 3, 2016: Molecular Pharmaceutics
Christos C Liolios, Stavros Xanthopoulos, George Loudos, Alexandra D Varvarigou, Gregory B Sivolapenko
The bombesin analogue, [(99m)Tc-GGC]-(Ornithine)3-BN(2-14), (99m)Tc-BN-O, targeting gastrin releasing peptide receptors (GRPrs) on the surface of tumors, was pre-clinically investigated as potential imaging agent for single photon emission computed tomography (SPECT). In addition, the improvement of its pharmacokinetic profile (PK) was investigated through the co-administration of a succinylated gelatin plasma expander (Gelofusine), aiming to reduce its kidney accumulation and enhance its tumor-to-normal tissue contrast ratios...
October 2016: Nuclear Medicine and Biology
Jingjing Zhang, Gang Niu, Lixin Lang, Fang Li, Xinrong Fan, Xuefeng Yan, Shaobo Yao, Weigang Yan, Li Huo, Libo Chen, Zhiyuan Li, Zhaohui Zhu, Xiaoyuan Chen
: This study aims to document the first-in-human application of a (68)Ga-labeled heterodimeric peptide BBN-RGD (bombesin-RGD) that targets both integrin αvβ3 and gastrin releasing peptide receptor (GRPR). We evaluated the safety and assessed the clinical diagnosis value of (68)Ga- BBN-RGD positron emission tomography (PET)/x-ray computed tomography (CT) in prostate cancer patients in comparison with (68)Ga-BBN. METHODS: Five healthy volunteers (M 4, F 1, 28-53 y) were enrolled to validate the safety of (68)Ga-BBN-RGD...
August 4, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Yohei Kiyotsuka, Kousei Shimada, Shozo Kobayashi, Masanori Suzuki, Mayuko Akiu, Masayoshi Asano, Yoshitaka Sogawa, Takashi Hara, Masahiro Konishi, Rie Abe-Ohya, Masanori Izumi, Yoko Nagai, Kazuhiro Yoshida, Yasuyuki Abe, Hideo Takamori, Hisashi Takahashi
Novel compounds based on 1a were synthesized with the focus of obtaining agonists acting upon peripheral BRS-3. To identify potent anti-obesity compounds without adverse effects on the central nervous system (CNS), a carboxylic acid moiety and a labile carboxylic ester with an antedrug functionality were introduced. Through the extensive synthetic exploration and the pharmacokinetic studies of intravenous administration in mice, the ester 2b was selected owing to its most suitable pharmacological profile. In the evaluation of food intake suppression in C57BL/6N mice, 2b showed significant in vivo efficacy and no clear adverse effects on blood pressure change in dogs administered the compound by intravenous infusion...
September 1, 2016: Bioorganic & Medicinal Chemistry Letters
Mercedes Salido, Jose Vilches
The acquisition of neuroendocrine (NE) characteristics by prostate cancer (PC) cells relates to tumor progression and hormone resistance. PC cells may survive and function in androgen-deprived environments, where they could establish paracrine signaling networks, providing stimuli for the propagation of local carcinoma cells. We previously demonstrated, using electron probe X-ray microanalysis (EPXMA), in LNCaP, PC-3, and Du 145 cell lines that apoptosis is associated with intracellular elemental changes, and that the NE secretory products, bombesin and calcitonin, inhibit etoposide-induced apoptosis, as well as some of these elemental changes...
August 2016: Microscopy and Microanalysis
Xiaole Chen, He Wang, Lei Wang, Mei Zhou, Tianbao Chen, Chris Shaw
The chemical compounds synthesised and secreted from the dermal glands of amphibian have diverse bioactivities that play key roles in the hosts' innate immune system and in causing diverse pharmacological effects in predators that may ingest the defensive skin secretions. As new biotechnological methods have developed, increasing numbers of novel peptides with novel activities have been discovered from this source of natural compounds. In this study, a number of defensive skin secretion peptide sequences were obtained from the European edible frog, P...
August 2016: Protein Journal
Yao Sun, Xiaowei Ma, Zhe Zhang, Ziyan Sun, Mathias Loft, Bingbing Ding, Changhao Liu, Liying Xu, Meng Yang, Yuxin Jiang, Jianfeng Liu, Yuling Xiao, Zhen Cheng, Xuechuan Hong
Gastrin-releasing peptide receptor (GRPR) targeted positron emission tomography (PET) is a highly promising approach for imaging of prostate cancer (PCa) in small animal models and patients. Developing a GRPR-targeted PET probe with excellent in vivo performance such as high tumor uptake, high contrast, and optimal pharmacokinetics is still very challenging. Herein, a novel bombesin (BBN) analogue (named SCH1) based on JMV594 peptide modified with an 8-amino octanoic acid spacer (AOC) was thus designed and conjugated with the metal chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA)...
August 17, 2016: Bioconjugate Chemistry
Kim-Marie Engster, Arthur L Kroczek, Matthias Rose, Andreas Stengel, Peter Kobelt
As anorexigenic hormones bombesin and nucleobindin2 (NUCB2)/nesfatin-1 decrease food intake in rodents. Both hormones have been described in brain nuclei that play a role in the modulation of hunger and satiety, like the paraventricular nucleus of the hypothalamus (PVN) and the nucleus of the solitary tract (NTS). However, the direct interaction of the two hormones is unknown so far. The aim of study was to elucidate whether bombesin directly interacts with NUCB2/nesfatin-1 neurons in the PVN and NTS. Therefore, we injected bombesin intraperitoneally (ip) at two doses (26 and 32nmol/kg body weight) and assessed c-Fos activation in the PVN, arcuate nucleus (ARC) and NTS compared to vehicle treated rats (0...
October 1, 2016: Brain Research
Taichi Nakamura, Irene Ramos-Álvarez, Tatiana Iordanskaia, Paola Moreno, Samuel A Mantey, R T Jensen
Bombesin-receptor-subtype-3 (BB3 receptor) is a G-protein-coupled-orphan-receptor classified in the mammalian Bombesin-family because of high homology to gastrin-releasing peptide (BB2 receptor)/neuromedin-B receptors (BB1 receptor). There is increased interest in BB3 receptor because studies primarily from knockout-mice suggest it plays roles in energy/glucose metabolism, insulin-secretion, as well as motility and tumor-growth. Investigations into its roles in physiological/pathophysiological processes are limited because of lack of selective ligands...
September 1, 2016: Biochemical Pharmacology
Jayshil J Patel, Martin D Rosenthal, Keith R Miller, Robert G Martindale
PURPOSE OF REVIEW: The purpose of this review is to describe established and emerging mechanisms of gut injury and dysfunction in trauma, describe emerging strategies to improve gut dysfunction, detail the effect of trauma on the gut microbiome, and describe the gut-brain connection in traumatic brain injury. RECENT FINDINGS: Newer data suggest intraluminal contents, pancreatic enzymes, and hepatobiliary factors disrupt the intestinal mucosal layer. These mechanisms serve to perpetuate the inflammatory response leading to multiple organ dysfunction syndrome (MODS)...
August 2016: Current Opinion in Critical Care
Izabella S Pinto, Aline A Mourão, Elaine F da Silva, Amanda S Camargo, Stefanne M Marques, Karina P Gomes, James O Fajemiroye, Angela A da Silva Reis, Ana C S Rebelo, Marcos L Ferreira-Neto, Daniel A Rosa, André H Freiria-Oliveira, Carlos H Castro, Eduardo Colombari, Diego B Colugnati, Gustavo R Pedrino
Intrathecal injection of bombesin (BBS) promoted hypertensive and sympathoexcitatory effects in normotensive (NT) rats. However, the involvement of rostral ventrolateral medulla (RVLM) in these responses is still unclear. In the present study, we investigated: (1) the effects of BBS injected bilaterally into RVLM on cardiorespiratory and sympathetic activity in NT and spontaneously hypertensive rats (SHR); (2) the contribution of RVLM BBS type 1 receptors (BB1) to the maintenance of hypertension in SHR. Urethane-anesthetized rats (1...
2016: Frontiers in Physiology
Amir Reza Jalilian, Davood Beiki, Arman Hassanzadeh-Rad, Arash Eftekhari, Parham Geramifar, Mohammad Eftekhari
During past 3 decades, nuclear medicine has flourished as vibrant and independent medical specialty in Iran. Since that time, more than 200 nuclear physicians have been trained and now practicing in nearly 158 centers throughout the country. In the same period, Tc-99m generators and variety of cold kits for conventional nuclear medicine were locally produced for the first time. Local production has continued to mature in robust manner while fulfilling international standards. To meet the ever-growing demand at the national level and with international achievements in mind, work for production of other Tc-99m-based peptides such as ubiquicidin, bombesin, octreotide, and more recently a kit formulation for Tc-99m TRODAT-1 for clinical use was introduced...
July 2016: Seminars in Nuclear Medicine
Shyam L Gupta, Vikas Dhiman, T Jayasekharan, N K Sahoo
RATIONALE: The increased use of silver nanoparticles (AgNPs) for various biological applications, and over-expression of various peptide receptors in different tumors/cancer cells, necessitate the need for dedicated investigations on the intrinsic binding ability of Ag with various biologically important peptides for better understanding of AgNPs-peptide interactions and for the future development of contrasting agents as well as drugs for imaging/biomedical applications. METHODS: The [M+(Ag)n ](+) complexes are prepared and characterized using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS)...
June 15, 2016: Rapid Communications in Mass Spectrometry: RCM
Samantha L White, Helene Volkoff, Robert H Devlin
Survival, competition, growth and reproductive success in fishes are highly dependent on food intake, food availability and feeding behavior and are all influenced by a complex set of metabolic and neuroendocrine mechanisms. Overexpression of growth hormone (GH) in transgenic fish can result in greatly enhanced growth rates, feed conversion, feeding motivation and food intake. The objectives of this study were to compare seasonal feeding behavior of non-transgenic wild-type (NT) and GH-transgenic (T) coho salmon (Oncorhynchus kisutch), and to examine the effects of intraperitoneal injections of the appetite-regulating peptides cholecystokinin (CCK-8), bombesin (BBS), glucagon-like peptide-1 (GLP-1), and alpha-melanocyte-stimulating hormone (α-MSH) on feeding behavior...
August 2016: Hormones and Behavior
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