The Experts below are selected from a list of 2274 Experts worldwide ranked by ideXlab platform
Gilberto Schwartsmann - One of the best experts on this subject based on the ideXlab platform.
-
Gastrin-Releasing Peptide Receptor Expression in Cervical Cancer
Oncology, 2020Co-Authors: Daniela Baumann Cornelio, Luíse Meurer, Rafael Roesler, Gilberto SchwartsmannAbstract:Objectives: It was the aim of this study to evaluate whether cervical neoplasms and adjacent tissues express the Gastrin-Releasing Peptide Receptor (GRPR) and whether there is a sig
-
Histone deacetylase inhibition prevents the impairing effects of hippocampal Gastrin-Releasing Peptide Receptor antagonism on memory consolidation and extinction.
Behavioural Brain Research, 2016Co-Authors: Fernanda Dos Santos Petry, Gilberto Schwartsmann, Arethuza S. Dornelles, Caroline Brunetto De Farias, Martina Lichtenfels, Fernanda E. Valiati, Marise B. Parent, Rafael RoeslerAbstract:Abstract Hippocampal Gastrin-Releasing Peptide Receptors (GRPR) regulate memory formation and extinction, and disturbances in GRPR signaling may contribute to cognitive impairment associated with neurodevelopmental disorders. Histone acetylation is an important epigenetic mechanism that regulates gene expression involved in memory formation, and histone deacetylase inhibitors (HDACis) rescue memory deficits in several models. The present study determined whether inhibiting histone deacetylation would prevent memory impairments produced by GRPR blockade in the hippocampus. Male Wistar rats were given an intrahippocampal infusion of saline (SAL) or the HDACi sodium butyrate (NaB) shortly before inhibitory avoidance (IA) training, followed by an infusion of either SAL or the selective GRPR antagonist RC-3095 immediately after training. In a second experiment, the infusions were administered before and after a retention test trial that served as extinction training. As expected, RC-3095 significantly impaired consolidation and extinction of IA memory. More importantly, pretraining administration of NaB, at a dose that had no effect when given alone, prevented the effects of RC-3095. In addition, the combination of NaB and RC-3095 increased hippocampal levels of the brain-derived neurotrophic factor (BDNF). These findings indicate that HDAC inhibition can protect against memory impairment caused by GRPR blockade.
-
Gastrin-Releasing Peptide Receptor Knockdown Induces Senescence in Glioblastoma Cells.
Molecular Neurobiology, 2016Co-Authors: Pâmela Rossi Menegotto, Gilberto Schwartsmann, Guido Lenz, Patrícia Luciana Da Costa Lopez, Bárbara Kunzler Souza, Caroline Brunetto De Farias, Eduardo C. Filippi-chiela, Igor Araújo Vieira, Rafael RoeslerAbstract:Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor, characterized by excessive cell proliferation, resistance to apoptosis, and invasiveness. Due to resistance to currently available treatment options, the prognosis for patients with GBM is very dismal. The activation of Gastrin-Releasing Peptide Receptors (GRPR) stimulates GBM cell proliferation, whereas GRPR antagonists induce antiproliferative effects in in vitro and in vivo experimental models of GBM. However, the role of GRPR in regulating other aspects of GBM cell function related to tumor progression remains poorly understood, and previous studies have not used RNA interference techniques as tools to examine GRPR function in GBM. Here, we found that stable GRPR knockdown by a lentiviral vector using a short hairpin interfering RNA sequence in human A172 GBM cells resulted in increased cell size and altered cell cycle dynamics consistent with cell senescence. These changes were accompanied by increases in the content of p53, p21, and p16, activation of epidermal growth factor Receptors (EGFR), and a reduction in p38 content. These results increase our understanding of GRPR regulation of GBM cells and further support that GRPR may be a relevant therapeutic target in GBM.
-
Expression of Gastrin-Releasing Peptide Receptor in epidermoid carcinoma of the anal canal.
Applied Immunohistochemistry & Molecular Morphology, 2014Co-Authors: Fabiola Fernandes Martins, Luíse Meurer, Gilberto Schwartsmann, Paulo De Carvalho Contu, Daniel C. DaminAbstract:: Gastrin-Releasing Peptide is a neuroendocrine homolog of bombesin that demonstrated important growth-stimulatory effects in various types of cancer. High levels of expression of Gastrin-Releasing Peptide Receptors (GRPR) has been found in different malignancies, and the studies exploring the therapeutic use of GRPR antagonists have shown promising results. Our aim was to determine the GRPR expression in epidermoid carcinoma of the anal canal and discuss its potential clinical applications. We performed immunohistochemical analysis for GRPR on formalin-fixed and paraffin-embedded tumor samples obtained from 35 patients with anal cancer. As a control group, we analyzed 24 samples of nonmalignant anal tissues (hemorrhoidectomy specimens). GRPR expression was evaluated using a semiquantitative approach according to the intensity and distribution of staining. All analyzed tissues, except 1 control sample, showed positive GRPR immunoexpression. GRPR was strongly expressed in 54% of cancer specimens as compared with only 12% of the control specimens (P
-
The Gastrin-Releasing Peptide Receptor as a Marker of Dysplastic Alterations in Cervical Epithelial Cells
Oncology, 2012Co-Authors: Daniela Baumann Cornelio, Luíse Meurer, Gilberto Schwartsmann, Rafael RoeslerAbstract:Background: Cervical cancer is a leading cancer in women worldwide. The Papanicolaou test (Pap test) remains the main screening tool; however, it produces high rates of false-negative and false-positive results. Gastrin-Releasing Peptide is a growth factor that has been implicated in many cancers, and its main Receptor, the Gastrin-Releasing Peptide Receptor (GRPR), is nearly always expressed in cervical dysplasias and invasive carcinomas. The aim of this study was to evaluate the diagnostic potential of GRPR immunocytochemistry in detecting cervical dysplasia and invasive cancer. Methods: Cervical smears were collected from 66 women in Brazil and subjected to GRPR immunocytochemistry and the Pap test. GRPR and p16 immunohistochemistry were performed in biopsies if abnormalities were detected. Results: GRPR immunostaining sensitivity in detecting cervical lesions was 87.5% and its specificity was 76.7%. GRPR immunostaining showed 80% accuracy in identifying atypical squamous cells of undetermined significance (ASCUS), with 88% sensitivity and 71% specificity. Conclusion: This is the first immunocytochemical evaluation of GRPR expression in cervical epithelial cells. This biomarker was strongly associated with cervical dysplasia and invasive cancers. GRPR immunosignaling showed high accuracy in detecting dysplasias in cells classified as ASCUS by Pap tests. Based on these results, immunocytochemistry for GRPR may be regarded as a valuable method for early detection of cervical intraepithelial neoplasia.
Rafael Roesler - One of the best experts on this subject based on the ideXlab platform.
-
Gastrin-Releasing Peptide Receptor Expression in Lung Cancer
Archives of Pathology & Laboratory Medicine, 2020Co-Authors: Jane Mattei, Luíse Meurer, Rafael Roesler, Rosane R.d. Achcar, Carlos C.h. Cano, Bruno B.r. Macedo, Brenda B.s. Batlle, Steve D. Groshong, Jane J.m. Kulczynski, Lissandra Dal LagoAbstract:Context.—Gastrin-Releasing Peptide Receptors (GRPRs) activate mitogen-activated protein kinase signaling pathway primarily through epidermal growth factor Receptor activation and are under investigation as a molecular target because they are overexpressed in several solid tumors. Objective.—To determine GRPR expression in both non–small cell lung carcinoma and small cell lung carcinoma, comparing results with clinical stages and demographic data. Design.—We analyzed the immunohistochemical expression of GRPR in 200 non–small cell lung carcinoma and 38 small cell lung carcinoma archival cases from 2004 to 2008. Results.—Non–small cell lung carcinoma cases tended to be higher GRPR expressers at a rate of 62.5% (weak, moderate, and strong expression in 41.5%, 13.5%, and 7.5%, respectively), compared with 52.62% in small cell lung carcinoma cases (weak, moderate, and strong expression in 34.21%, 15.78%, and 2.63%, respectively; P = .30). In non–small cell lung carcinoma there was a trend for higher percentage...
-
Gastrin-Releasing Peptide Receptor Expression in Cervical Cancer
Oncology, 2020Co-Authors: Daniela Baumann Cornelio, Luíse Meurer, Rafael Roesler, Gilberto SchwartsmannAbstract:Objectives: It was the aim of this study to evaluate whether cervical neoplasms and adjacent tissues express the Gastrin-Releasing Peptide Receptor (GRPR) and whether there is a sig
-
Histone deacetylase inhibition prevents the impairing effects of hippocampal Gastrin-Releasing Peptide Receptor antagonism on memory consolidation and extinction.
Behavioural Brain Research, 2016Co-Authors: Fernanda Dos Santos Petry, Gilberto Schwartsmann, Arethuza S. Dornelles, Caroline Brunetto De Farias, Martina Lichtenfels, Fernanda E. Valiati, Marise B. Parent, Rafael RoeslerAbstract:Abstract Hippocampal Gastrin-Releasing Peptide Receptors (GRPR) regulate memory formation and extinction, and disturbances in GRPR signaling may contribute to cognitive impairment associated with neurodevelopmental disorders. Histone acetylation is an important epigenetic mechanism that regulates gene expression involved in memory formation, and histone deacetylase inhibitors (HDACis) rescue memory deficits in several models. The present study determined whether inhibiting histone deacetylation would prevent memory impairments produced by GRPR blockade in the hippocampus. Male Wistar rats were given an intrahippocampal infusion of saline (SAL) or the HDACi sodium butyrate (NaB) shortly before inhibitory avoidance (IA) training, followed by an infusion of either SAL or the selective GRPR antagonist RC-3095 immediately after training. In a second experiment, the infusions were administered before and after a retention test trial that served as extinction training. As expected, RC-3095 significantly impaired consolidation and extinction of IA memory. More importantly, pretraining administration of NaB, at a dose that had no effect when given alone, prevented the effects of RC-3095. In addition, the combination of NaB and RC-3095 increased hippocampal levels of the brain-derived neurotrophic factor (BDNF). These findings indicate that HDAC inhibition can protect against memory impairment caused by GRPR blockade.
-
Gastrin-Releasing Peptide Receptor Knockdown Induces Senescence in Glioblastoma Cells.
Molecular Neurobiology, 2016Co-Authors: Pâmela Rossi Menegotto, Gilberto Schwartsmann, Guido Lenz, Patrícia Luciana Da Costa Lopez, Bárbara Kunzler Souza, Caroline Brunetto De Farias, Eduardo C. Filippi-chiela, Igor Araújo Vieira, Rafael RoeslerAbstract:Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor, characterized by excessive cell proliferation, resistance to apoptosis, and invasiveness. Due to resistance to currently available treatment options, the prognosis for patients with GBM is very dismal. The activation of Gastrin-Releasing Peptide Receptors (GRPR) stimulates GBM cell proliferation, whereas GRPR antagonists induce antiproliferative effects in in vitro and in vivo experimental models of GBM. However, the role of GRPR in regulating other aspects of GBM cell function related to tumor progression remains poorly understood, and previous studies have not used RNA interference techniques as tools to examine GRPR function in GBM. Here, we found that stable GRPR knockdown by a lentiviral vector using a short hairpin interfering RNA sequence in human A172 GBM cells resulted in increased cell size and altered cell cycle dynamics consistent with cell senescence. These changes were accompanied by increases in the content of p53, p21, and p16, activation of epidermal growth factor Receptors (EGFR), and a reduction in p38 content. These results increase our understanding of GRPR regulation of GBM cells and further support that GRPR may be a relevant therapeutic target in GBM.
-
The Gastrin-Releasing Peptide Receptor as a Marker of Dysplastic Alterations in Cervical Epithelial Cells
Oncology, 2012Co-Authors: Daniela Baumann Cornelio, Luíse Meurer, Gilberto Schwartsmann, Rafael RoeslerAbstract:Background: Cervical cancer is a leading cancer in women worldwide. The Papanicolaou test (Pap test) remains the main screening tool; however, it produces high rates of false-negative and false-positive results. Gastrin-Releasing Peptide is a growth factor that has been implicated in many cancers, and its main Receptor, the Gastrin-Releasing Peptide Receptor (GRPR), is nearly always expressed in cervical dysplasias and invasive carcinomas. The aim of this study was to evaluate the diagnostic potential of GRPR immunocytochemistry in detecting cervical dysplasia and invasive cancer. Methods: Cervical smears were collected from 66 women in Brazil and subjected to GRPR immunocytochemistry and the Pap test. GRPR and p16 immunohistochemistry were performed in biopsies if abnormalities were detected. Results: GRPR immunostaining sensitivity in detecting cervical lesions was 87.5% and its specificity was 76.7%. GRPR immunostaining showed 80% accuracy in identifying atypical squamous cells of undetermined significance (ASCUS), with 88% sensitivity and 71% specificity. Conclusion: This is the first immunocytochemical evaluation of GRPR expression in cervical epithelial cells. This biomarker was strongly associated with cervical dysplasia and invasive cancers. GRPR immunosignaling showed high accuracy in detecting dysplasias in cells classified as ASCUS by Pap tests. Based on these results, immunocytochemistry for GRPR may be regarded as a valuable method for early detection of cervical intraepithelial neoplasia.
Fernando Albericio - One of the best experts on this subject based on the ideXlab platform.
-
multifunctionalized gold nanoparticles with Peptides targeted to gastrin releasing Peptide Receptor of a tumor cell line
Bioconjugate Chemistry, 2010Co-Authors: Leticia Hostarigau, Ivonne Olmedo, Jordi Arbiol, Luis J Cruz, Marcelo J Kogan, Fernando AlbericioAbstract:Functionalization of gold nanoparticles (AuNPs) with both a targeting Peptide (an analogue of the Peptide Bombesin) and a drug Peptide ligand (an analogue of the RAF Peptide) with the aim of improving selectivity in the delivery of the conjugates as well as the antitumor activity is described. Studies on the internalization mechanism of Peptide−AuNP conjugates and viability of cells were carried out. An enhancement of the activity and selectivity of the Peptide multifunctionalized conjugates was observed.
Zhoufeng Chen - One of the best experts on this subject based on the ideXlab platform.
-
Cross-talk between Human Spinal Cord μ-opioid Receptor 1Y Isoform and Gastrin-Releasing Peptide Receptor Mediates Opioid-induced Scratching Behavior.
Anesthesiology, 2019Co-Authors: Yehuda Ginosar, Joseph Yazdi, Alexander Hincker, Zhoufeng ChenAbstract:Editor’s PerspectiveWhat We Already Know about This TopicThe spinal administration of opioids can cause intense pruritisInteractions between specific μ-opioid Receptor isoforms and the gastrin releasing Peptide Receptor in spinal tissues likely mediate morphine-induced pruritusWhat This Article Tell
-
a gastrin releasing Peptide Receptor mediates the itch sensation in the spinal cord
Nature, 2007Co-Authors: Zhoufeng ChenAbstract:The unpleasant sense of itching, or pruritus, is well known, but its neurobiological basis has remained elusive. Now the first molecular player in the 'itch pathway' has been identified. Historically, itch has been regarded as a less intense variant of the pain sensation. But work with knockout mice shows that the 'Gastrin-Releasing Peptide Receptor' is important for communication of itchy, but not painful, stimuli to the central nervous system. This Receptor could therefore be a target for the development of antipruritic drugs that do not affect pain signalling. The neurobiological basis of unpleasant sense of itching, or pruritus has been elusive, but this study shows that the 'gastrin releasing Peptide Receptor' is important for communication of itchy, but not painful, stimuli to the central nervous system. This Receptor could therefore be a target for the development of antipruritic drugs that do not affect pain signalling. Itching, or pruritus, is defined as an unpleasant cutaneous sensation that serves as a physiological self-protective mechanism to prevent the body from being hurt by harmful external agents. Chronic itch represents a significant clinical problem resulting from renal diseases and liver diseases, as well as several serious skin diseases such as atopic dermatitis1,2,3. The identity of the itch-specific mediator in the central nervous system, however, remains elusive. Here we describe that the Gastrin-Releasing Peptide Receptor (GRPR) plays an important part in mediating itch sensation in the dorsal spinal cord. We found that Gastrin-Releasing Peptide is specifically expressed in a small subset of Peptidergic dorsal root ganglion neurons, whereas expression of its Receptor GRPR is restricted to lamina I of the dorsal spinal cord. GRPR mutant mice showed comparable thermal, mechanical, inflammatory and neuropathic pain responses relative to wild-type mice. In contrast, induction of scratching behaviour was significantly reduced in GRPR mutant mice in response to pruritogenic stimuli, whereas normal responses were evoked by painful stimuli. Moreover, direct spinal cerebrospinal fluid injection of a GRPR antagonist significantly inhibited scratching behaviour in three independent itch models. These data demonstrate that GRPR is required for mediating the itch sensation rather than pain, at the spinal level. Our results thus indicate that GRPR may represent the first molecule that is dedicated to mediating the itch sensation in the dorsal horn of the spinal cord, and thus may provide a central therapeutic target for antipruritic drug development.
Isabel Santos - One of the best experts on this subject based on the ideXlab platform.
-
Nuclear targeting with cell-specific multifunctional tricarbonyl M(I) (M is Re, ^99mTc) complexes: synthesis, characterization, and cell studies
JBIC Journal of Biological Inorganic Chemistry, 2011Co-Authors: Teresa Esteves, Fernanda Marques, António Paulo, José Rino, Prasant Nanda, C. Jeffrey Smith, Isabel SantosAbstract:Auger-emitting radionuclides such as ^99mTc have been the focus of recent studies aiming at finding more selective therapeutic approaches. To explore the potential usefulness of ^99mTc as an Auger emitter, we have synthesized and biologically evaluated novel multifunctional structures comprising (1) a pyrazolyl-diamine framework bearing a set of donor atoms to stabilize the [M(CO)_3]^+ (M is Re, ^99mTc) core; (2) a DNA intercalating moiety of the acridine orange type to ensure close proximity of the radionuclide to DNA and to follow the internalization and subcellular trafficking of the compounds by confocal fluorescence microscopy; and (3) a bombesin (BBN) analogue of the type X-BBN[7-14] (where X is SGS, GGG) to provide specificity towards cells expressing the gastrin releasing Peptide Receptor (GRPr). Of the evaluated ^99mTc complexes, Tc ^ 3 containing the GGG-BBN[7-14] Peptide showed the highest cellular internalization in GRPr-positive PC3 human prostate tumor cells, presenting a remarkably high nuclear uptake in the same cell line. Live-cell confocal imaging microscopy studies with the congener Re complex, Re ^ 3 , showed a considerable accumulation of fluorescence in the nucleus, with kinetics of uptake similar to that exhibited by Tc ^ 3 . Together, these data show that the acridine orange intercalator and the metal fragment are colocalized in the nucleus, which indicates that they remain connected despite the lysosomal degradation of Tc ^ 3 / Re ^ 3 . These compounds are the first examples of ^99mTc bioconjugates that combine specific cell targeting with nuclear internalization, a crucial issue to explore use of ^99mTc in Auger therapy. Graphical abstract Pyrazolyl-diamine Re/^99mTc tricarbonyl complexes bearing an acridine orange intercalator and bombesin Peptides internalize and target the nucleus of gastrin releasing Peptide Receptor positive PC3 human prostate tumor cells.
