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Maria Cecilia Mengoli, Giulio Rossi, Alberto Cavazza, Renato Franco, Federica Zito Marino, Mario Migaldi, Letizia Gnetti, Enrico Maria Silini, Luca Ampollini, Marcello Tiseo, Filippo Lococo, Ludovic Fournel, Paolo Spagnolo, Vincent Cottin, Thomas V Colby
The diagnostic criteria of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) are not well defined, and DIPNECH can be mistaken for carcinoids associated with neuroendocrine cell hyperplasia (NECH). In this study, we compared clinical, radiologic, histologic, immunohistochemical, and molecular features of DIPNECH and isolated carcinoids with/without NECH. The study population included 151 cases (77 female patients and 74 male patients), 19 with DIPNECH and 132 with carcinoids with/without NECH...
February 12, 2018: American Journal of Surgical Pathology
Christos Liolios, Benjamin Buchmuler, Ulrike Bauder-Wüst, Martin Schaefer, Karin Leotta, Uwe Haberkorn, Matthias Eder, Klaus Kopka
The GRPr, highly expressed in prostate PCa and breast cancer BCa, is a promising target for the development of new PET radiotracers. The chelator HBED-CC (N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid) was coupled to the bombesin peptides: HBED-C-BN(2-14) 1, HBED-CC-PEG 2 -[D-Tyr 6 ,β-Ala 11 ,Thi 13 ,Nle 14 ]-BN(6-14) 2, HBED-CC-Y-[D-Phe 6 ,Sta 13 ,Leu 14 ]-BN(6-14), (Y = 4-amino-1-carboxymethyl-piperidine) 3 and HBED-CC-{PEG 2 -Y-[D-Phe 6 ,Sta 13 ,Leu 14 ]-BN(6-14)} 2 4 (homodimer)...
February 12, 2018: Journal of Medicinal Chemistry
Paola Moreno, Samuel A Mantey, Suk H Lee, Irene Ramos-Álvarez, Terry W Moody, Robert T Jensen
Human bombesin receptors, GRPR and NMBR, are two of the most frequently overexpressed G-protein-coupled-receptors by lung-cancers. Recently, GRPR/NMBR are receiving considerable attention because they act as growth factor receptors often in an autocrine manner in different lung-cancers, affect tumor angiogenesis, their inhibition increases the cytotoxic potency of tyrosine-kinase inhibitors reducing lung-cancer cellular resistance/survival and their overexpression can be used for sensitive tumor localization as well as to target cytotoxic agents to the cancer...
February 2, 2018: Peptides
Zaida Moreno-Villegas, Antonio Martín-Duce, César Aparicio, Sergio Portal-Núñez, Raúl Sanz, Samuel A Mantey, Robert T Jensen, Oscar Lorenzo, Jesús Egido, Nieves González
BRS-3 has an important role in glucose homeostasis. Its expression was reduced in skeletal muscle from obese and/or diabetic patients, and BRS-3 KO-mice developed obesity. In this work, focused on rat/human adipose tissue, BRS-3 gene-expression was lower than normal-levels in hyperlipidemic, type-2-diabetic (T2D), and type-1-diabetic rats and also in obese (OB) and T2D patients. Moreover, BRS-3 protein levels were decreased in diabetic rat and in obese and diabetic human fat pieces; but neither mutation nor even polymorphism in the BRS-3-gene was found in OB or T2D patients...
January 31, 2018: Molecular and Cellular Endocrinology
Yan Zhang, Yanfang Liu, Lehao Wu, Chao Fan, Zhiwei Wang, Xiuli Zhang, Amal Alachkar, Xinmiao Liang, Olivier Civelli
Bombesin receptor subtype 3 (BRS-3) is a GPCR that is expressed in the CNS, peripheral tissues, and tumors. Our understanding of BRS-3's role in physiology and pathophysiology is limited because its natural ligand is unknown. In an attempt to identify this ligand, we screened toad skin ( Bufo bufo gargarizans Cantor) extracts and identified prostaglandins as putative ligands. In BRS-3-transfected human embryonic kidney (HEK) cells, we found that prostaglandins, with prostaglandin E2 (PGE2) being the most potent, fulfill the pharmacologic criteria of affinity, selectivity, and specificity to be considered as agonists to the BRS-3 receptor...
January 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Huijun Liu, Lihua Peng, Chi Liu, Yurong Tan, Yang Xiang, Xiangping Qu, H Christian Weber, Minhui Dai, Xiaoqun Qin
BACKGROUND: Bombesin receptor subtype-3 (BRS-3) is a member of the bombesin-like peptide receptor family. Our previous studies demonstrated that activation of the human BRS-3 plays a protective role in oxidation-injured human bronchial epithelial cells (HBEC). The present study was designed to determine the role of BRS-3 activation in the antigen-presenting action of HBEC and the corresponding proliferation and differentiation of T cells. MATERIALS AND METHODS: In vivo, an asthma animal model was established and the expression and distribution of BRS-3 were analyzed by immunocytochemistry...
January 27, 2018: International Archives of Allergy and Immunology
Cuiying Xiao, Ramón A Piñol, Jesse Lea Carlin, Cuiling Li, Chuxia Deng, Oksana Gavrilova, Marc L Reitman
No abstract text is available yet for this article.
December 27, 2017: Molecular Metabolism
Fiona Haxho, Sabah Haq, Myron R Szewczuk
G protein-coupled receptors (GPCR) can participate in a number of signaling pathways, and this property led to the concept of biased GPCR agonism. Agonists, antagonists and allosteric modulators can bind to GPCRs in different ways, creating unique conformations that differentially modulate signaling through one or more G proteins. A unique neuromedin B (NMBR) GPCR-signaling platform controlling mammalian neuraminidase-1 (Neu1) and matrix metalloproteinase-9 (MMP9) crosstalk has been reported in the activation of the insulin receptor (IR) through the modification of the IR glycosylation...
December 24, 2017: Cellular Signalling
Gerardo J Ramírez-Nava, Clara L Santos-Cuevas, Isaac Chairez, Liliana Aranda-Lara
The aim of this study was to characterize the in vivo volumetric distribution of three folate-based biosensors by different imaging modalities (X-ray, fluorescence, Cerenkov luminescence, and radioisotopic imaging) through the development of a tridimensional image reconstruction algorithm. The preclinical and multimodal Xtreme imaging system, with a Multimodal Animal Rotation System (MARS), was used to acquire bidimensional images, which were processed to obtain the tridimensional reconstruction. Images of mice at different times (biosensor distribution) were simultaneously obtained from the four imaging modalities...
December 1, 2017: Medical & Biological Engineering & Computing
Nematallah Mansour, Michel Paquette, Samia Ait-Mohand, Véronique Dumulon-Perreault, Brigitte Guérin
INTRODUCTION: Gastrin releasing peptide receptors (GRPRs) are significantly over-expressed on a large proportion of prostate cancers making them prime candidates for receptor-mediated nuclear imaging by PET. Recently, we synthesized a novel bifunctional chelator (BFC) bearing hydroxamic acid arms (DOTHA2). Here we investigated the potential of a novel DOTHA2-conjugated, (64)Cu-radiolabeled GRPR peptide antagonist, [D-Phe(6)-Sta(13)-Leu(14)-NH2]bombesin(6-14) (DOTHA2-PEG-RM26) to visualize prostate tumors by PET imaging...
October 23, 2017: Nuclear Medicine and Biology
Li Wan, Hua Jin, Xian-Yu Liu, Joseph Jeffry, Devin M Barry, Kai-Feng Shen, Jia-Hang Peng, Xue-Ting Liu, Jin-Hua Jin, Yu Sun, Ray Kim, Qing-Tao Meng, Ping Mo, Jun Yin, Ailin Tao, Rita Bardoni, Zhou-Feng Chen
A key question in our understanding of itch coding mechanisms is whether itch is relayed by dedicated molecular and neuronal pathways. Previous studies suggested that gastrin-releasing peptide (GRP) is an itch-specific neurotransmitter. Neuromedin B (NMB) is a mammalian member of the bombesin family of peptides closely related to GRP, but its role in itch is unclear. Here, we show that itch deficits in mice lacking NMB or GRP are non-redundant and Nmb/Grp double KO (DKO) mice displayed additive deficits. Furthermore, both Nmb/Grp and Nmbr/Grpr DKO mice responded normally to a wide array of noxious stimuli...
November 13, 2017: Scientific Reports
Xiangping Qu, Hui Wang, Rujiao Liu
PURPOSE OF REVIEW: The current review highlights recent advances in physiological and pharmacological researches in biology of mammalian bombesin-like peptides (BLPs). RECENT FINDINGS: BLPs and their receptors were found to have regulatory roles in many biological processes in central nervous system. Two BLPs, neuromedin B and gastrin-releasing peptide (GRP), and their receptors are required for regulation of basal and induced sighing activity in rodents. This is the first study demonstrating central pathways involved in regulation of sighing activity...
February 2018: Current Opinion in Endocrinology, Diabetes, and Obesity
Cuiying Xiao, Ramón A Piñol, Jesse Lea Carlin, Cuiling Li, Chuxia Deng, Oksana Gavrilova, Marc L Reitman
OBJECTIVE: Bombesin-like receptor 3 (BRS-3) is an orphan G protein-coupled receptor. Brs3 null mice have reduced resting metabolic rate and body temperature, increased food intake, and obesity. Here we study the role of Brs3 in different neuron types. METHODS: Mice able to undergo Cre recombinase-dependent inactivation or re-expression of Brs3 were generated, respectively Brs3(fl/y) and Brs3(loxTB/y). We then studied four groups of mice with Brs3 selectively inactivated or re-expressed in cells expressing Vglut2-Cre or Vgat-Cre...
November 2017: Molecular Metabolism
Bogdan Mitran, Helge Thisgaard, Ulrika Rosenström, Johan Hygum Dam, Mats Larhed, Vladimir Tolmachev, Anna Orlova
High gastrin releasing peptide receptor (GRPR) expression is associated with numerous cancers including prostate and breast cancer. The aim of the current study was to develop a (55)Co-labeled PET agent based on GRPR antagonist RM26 for visualization of GRPR-expressing tumors. Labeling with (57)Co and (55)Co, stability, binding specificity, and in vitro and in vivo characteristics of (57)Co-NOTA-PEG2-RM26 were studied. NOTA-PEG2-RM26 was successfully radiolabeled with (57)Co and (55)Co with high yields and demonstrated high stability...
2017: Contrast Media & Molecular Imaging
Xiaowei Zhou, Chengbang Ma, Mei Zhou, Yuning Zhang, Xinping Xi, Ruimin Zhong, Tianbao Chen, Chris Shaw, Lei Wang
Bombesin-like peptides, which were identified from a diversity of amphibian skin secretions, have been demonstrated to possess several biological functions such as stimulation of smooth muscle contraction and regulation of food intake. Here, we report two novel bombesin-like peptides, bombesin-OS and bombesin-PE, which were isolated from Odorrana schmackeri and Pelophylax kl. esculentus, respectively. The mature peptides were identified and structurally confirmed by high performance Scliquid chromatography (HPLC) and tandem mass spectrometry (MS/MS)...
October 23, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Danting Cui, Xiaodan Lu, Chenggong Yan, Xiang Liu, Meirong Hou, Qi Xia, Yikai Xu, Ruiyuan Liu
Bombesin (BBN), an analog of gastrin-releasing peptide (GRP), specifically binds to GRP receptors, which are overexpressed in human prostate cancer (PC). Here, we synthesized a BBN-modified gadolinium oxide (Gd2O3) nanoprobe containing fluorescein (Gd2O3-5(6)-carboxyfluorescein [FI]-polyethylene glycol [PEG]-BBN) for targeted magnetic resonance (MR)/optical dual-modality imaging of PC. The Gd2O3-FI-PEG-BBN nanoparticles exhibited a relatively uniform particle size with an average diameter of 52.3 nm and spherical morphology as depicted by transmission electron microscopy...
2017: International Journal of Nanomedicine
Zhiyu Ma, Ying Zhang, Juan Su, Xiang Li, Sheng Yang, Wenna Qiao, Chuan Suo, Zhihai Lei
Gastrin-releasing peptide (GRP) is a mammalian bombesin (BN)-like peptide which plays a role in a number of important physiological functions via its receptor (gastrin-releasing peptide receptor, GRPR) in most animals. However, little is known about the gene encoding GRPR and its functions (especially reproduction) in pigs. In this study, we first cloned and analyzed the pig GRPR cDNA. Then we systematically investigated the expression levels of GRPR mRNA by relative real-time PCR (RT-PCR), and analyzed the distribution of the GRPR protein in pig tissues via immunohistochemistry (IHC)...
September 28, 2017: Peptides
Jen-Chieh Tseng, Nara Narayanan, Guojie Ho, Kevin Groves, Jeannine Delaney, Bagna Bao, Jun Zhang, Jeffrey Morin, Sylvie Kossodo, Milind Rajopadhye, Jeffrey D Peterson
Physical measurement of tumor volume reduction is the most commonly used approach to assess tumor progression and treatment efficacy in mouse tumor models. However, it is relatively insensitive, and often requires long treatment courses to achieve gross physical tumor destruction. As alternatives, several non-invasive imaging methods such as bioluminescence imaging (BLI), fluorescence imaging (FLI) and positron emission tomography (PET) have been developed for more accurate measurement. As tumors have elevated glucose metabolism, 18F-fludeoxyglucose (18F-FDG) has become a sensitive PET imaging tracer for cancer detection, diagnosis, and efficacy assessment by measuring alterations in glucose metabolism...
2017: PloS One
Chae-Eun Yeo, Woo Youl Kang, Sook Jin Seong, Seungil Cho, Hae Won Lee, Young-Ran Yoon, Hyun-Ju Kim
Neuromedin B (NMB), a mammalian bombesin-like peptide, regulates diverse physiological processes, such as energy metabolism, memory and fear behavior, and cellular growth, through its cognate receptor, NMBR. In this study, we report that NMB expression was upregulated during osteoclast development and that silencing NMB or NMBR attenuated osteoclast generation mediated by macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). We found that knockdown of NMB or NMBR using a small hairpin RNA suppressed M-CSF-induced proliferation of osteoclast precursor cells without altering osteoclast differentiation...
October 1, 2017: Experimental Cell Research
Anna Lucia Tornesello, Luigi Buonaguro, Maria Lina Tornesello, Franco Maria Buonaguro
Many synthetic peptides have been developed for diagnosis and therapy of human cancers based on their ability to target specific receptors on cancer cell surface or to penetrate the cell membrane. Chemical modifications of amino acid chains have significantly improved the biological activity, the stability and efficacy of peptide analogues currently employed as anticancer drugs or as molecular imaging tracers. The stability of somatostatin, integrins and bombesin analogues in the human body have been significantly increased by cyclization and/or insertion of non-natural amino acids in the peptide sequences...
August 2, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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