Treatment of Neuroendocrine GEP Tumours with Somatostatin Analogues

Arnold, R.; Simon, Babette; Wied, M.

doi:10.1159/000051861

Cited by 146 publications

(88 citation statements)

References 24 publications

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“…SSTRs have been subdivided based on sequence homology into two subgroups: SSTR1 and SSTR4; and SSTR2, SSTR3, and SSTR5. The major functions of the latter group are well known because they have higher affinities for most commonly available SST analogs, including octreotide, which is widely used in a number of clinical settings (29,30). The functions of SSTR1 and SSTR4 remain unclear because, until recently (31)(32)(33), there were no receptor-specific analogs for members of this subgroup.…”

Section: Discussionmentioning

confidence: 99%

Somatostatin, Acting at Receptor Subtype 1, Inhibits Rho Activity, the Assembly of Actin Stress Fibers, and Cell Migration

Buchan

Lin

Choi

et al. 2002

Journal of Biological Chemistry

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Somatostatin regulates multiple biological functions by acting through a family of five G protein-coupled receptors, somatostatin receptors (SSTRs) 1-5. Although all five receptor subtypes inhibit adenylate cyclase activity and decrease intracellular cAMP levels, specific receptor subtypes also couple to additional signaling pathways. In CCL39 fibroblasts expressing either human SSTR1 or SSTR2, we demonstrate that activation of SSTR1 (but not SSTR2) attenuated both thrombin-and integrin-stimulated Rho-GTP complex formation. The reduction in Rho-GTP formation in the presence of somatostatin was associated with decreased translocation of Rho and LIM kinase to the plasma membrane and fewer focal contacts. Activation of Rho resulted in the formation of intracellular actin stress fibers and cell migration. In CCL39-R1 cells, somatostatin treatment prevented actin stress fiber assembly and attenuated thrombin-stimulated cell migration through Transwell membranes to basal levels. To show that native SSTR1 shares the ability to inhibit Rho activation, we demonstrated that somatostatin treatment of human umbilical vein endothelial cells attenuated thrombin-stimulated Rho-GTP accumulation. These data show for the first time that a G protein-coupled receptor, SSTR1, inhibits the activation of Rho, the assembly of focal adhesions and actin stress fibers, and cell migration.The low molecular mass GTPase Rho plays a central role in regulating organization of the actin-based cytoskeleton in mammalian cells. Activated, GTP-bound Rho promotes the formation of contractile actin filaments into stress fibers and the assembly of cell adhesion complexes (1, 2). Through its coordinate regulation of actin filaments, contractility, and cell adhesion, Rho also plays a critical role in cell migration (3, 4) and in tumor invasion (5, 6). Rho is activated by transmembrane receptors, including the integrin family of adhesion receptors (7) and a subset of heptahelical G protein-coupled receptors (GPCRs) 1 (8). Although the signaling pathway linking integrin receptors to Rho has not been determined, GPCRs, including those for lysophosphatidic acid (9 -11) and thrombin (11-13), activate Rho through the heterotrimeric GTPases G 12 and G 13 . However, GPCRs linked to the inhibition of Rho and downstream cytoskeletal reorganization have not been identified. We now report that somatostatin (SST), acting at the GPCR subtype SSTR1, inhibits Rho activity, attenuates the assembly of actin stress fibers and focal adhesions, and inhibits cell migration. Five distinct SSTR subtypes that are activated by SST have been identified, and these receptors generally have potent inhibitory effects on diverse cell functions such as hormone secretion, neurotransmitter release, smooth muscle contractility, and cell proliferation (14, 15). Effector pathways regulated by SSTRs, including inhibition of adenylate cyclase and Ca 2ϩ channel activity and stimulation of K ϩ channel and phosphatase activity, are mediated by pertussis toxin (PTX)-sensitive mechanisms, most lik...

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Section: Discussionmentioning

confidence: 99%

Somatostatin, Acting at Receptor Subtype 1, Inhibits Rho Activity, the Assembly of Actin Stress Fibers, and Cell Migration

Buchan

Lin

Choi

et al. 2002

Journal of Biological Chemistry

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“…Tumour shrinkage has been rarely observed but somatostatin analogs have been reported to induce tumour volume stabilization in 1045% of patients. (Arnold et al, 2000;Oberg 2004). In a group of patients with advanced midgut carcinoid tumours and progressive disease, high-dose formula of octreotide has been recently reported to stabilize hormone production and tumour growth in 75% of the patients (Welin et al, 2004).…”

Section: Antitumor Actions Of Somatostatin Analogsmentioning

confidence: 99%

Antitumor effects of somatostatin

Pyronnet

Bousquet

Najib

et al. 2008

Molecular and Cellular Endocrinology

160

118

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SummarySince its discovery three decades ago as an inhibitor of GH release from the pituitary gland, somatostatin has attracted much attention because of its functional role in the regulation of a wide variety of physiological functions in the brain, pituitary, pancreas, gastrointestinal tract, adrenals, thyroid, kidney and immune system. In addition to its negative role in the control of endocrine and exocrine secretions, somatostatin and analogs also exert inhibitory effects on the proliferation and survival of normal and tumor cells. Over the past 15 years, studies have begun to reveal some of the molecular mechanisms underlying the antitumor activity of somatostatin. This review covers the present knowledge in the antitumor effect of somatostatin and analogs and discusses the perspectives of novel clinical strategies based on somatostatin receptor sst2 gene transfer therapy.

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“…La citorreducció n con escleroterapia percutá nea, radiofrecuencia y embolizació n hepá tica son tratamientos alternativos 2,7 . Recientemente, el uso de aná logos de la somatostatina con estabilizació n del tumor en al menos 2/3 de los pacientes ha surgido como la terapia alternativa de la enfermedad avanzada 6,8 Empiema del muñ ó n ureteral. A propó sito de un caso y revisió n de la literatura Ureteral stump empyema.…”

Section: B I B L I O G Runclassified

Tumor neuroendocrino primario del riñón

Ribeiro

Santos

2010

Actas Urológicas Españolas

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Varias modalidades terapéuticas han sido propuestas en la literatura para solucionar la obstrucció n y el fracaso renal. Posicionar a la paciente en decú bito lateral puede mejorar la descompresió n del uréter afectado; asimismo, una amniotomía podría hacerse para aliviar la obstrucció n y mejorar la funció n renal, sobre todo en caso de polihidramnios. Pero actualmente, la colocació n de nefrostomías percutá neas o catéteres ureterales (si el reimplante lo permite) con control ecográ fico se ha convertido en el tratamiento de elecció n en estos casos. Sin embargo, la resolució n definitiva del cuadro se obtiene con la finalizació n del embarazo que debe realizarse en cuanto el feto sea suficientemente maduro [1][2][3][4][5] .Para evitar la obstrucció n en embarazos posteriores puede realizarse un nuevo reimplante ureteral, con una disecció n meticulosa del uré ter distal que se reinsertará a travé s de una tunelizació n submucosa má s caudal a nivel de la base de la vejiga 5 .Por tanto aquellas mujeres con una historia previa de reimplantació n ureteral bilateral segú n té cnica de PolitanoLeadbetter tienen incrementado el riesgo de obstrucció n ureteral, a nivel de la unió n uré tero-vesical y deterioro de la funció n renal secundario durante el embarazo. Por ello deben ser vigiladas desde el punto de vista uroló gico durante el embarazo, particularmente si presentan dolor lumbar, disminució n de la diuresis y/o hipertensió n. La detecció n precoz de esta entidad es esencial para proporcionar una adecuada derivació n urinaria provisional, evitando posteriores complicaciones mayores tanto para la madre como para el feto. Tumor neuroendocrino primario del riñ ó n Primary neuroendocrine tumor of the kidney Sr. Director: B I B L I O G RPresentamos el caso de un paciente con pé rdida de peso y una masa en el flanco izquierdo con varios meses de evolució n. En la TAC abdominal se podía ver un quiste complejo del riñ ó n de 16 cm y un nó dulo hepá tico solitario ( fig. 1). Los aná lisis de sangre y los marcadores tumorales estaban dentro de la normalidad. La nefrectomía radical izquierda reveló una neoplasia de 16 cm con necrosis y hemorragia central, delimitada por un tejido de 2 cm de aspecto blanquecino. La histología reveló un carcinoma de patró n cordonal sin atipias celulares o pleomorfismo celular y el índice mitó tico mínimo. La neoplasia, confinada por la cá psula renal, tenía infiltració n venosa microscó pica y un nó dulo linfá tico hilar metastatizado, pero ninguna invasió n vascular mayor. La marcació n inmunohistoquímica fue positiva para CD57/Leu7, NSE, sinaptofisina y cromogranina, demostrando que se trataba de un tumor neuroendocrino bien diferenciado ( fig. 2).En el postoperatorio se realizaron examen endoscó pico gastrointestinal, TAC torá cica y marcadores neuroendocrinos (5-HIAA y gastrina), que resultaron normales. En la A C TA S U R O L E S P. 2 0 1 0 ; 3 4 ( 1 0 ) : 8 9 8 -9 2 8 907 Documento descargado de http://www.elsevier.es el 18/06/2013. Copia para uso personal, se prohíbe la transmisión...

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Treatment of Neuroendocrine GEP Tumours with Somatostatin Analogues

Cited by 146 publications

References 24 publications

Somatostatin, Acting at Receptor Subtype 1, Inhibits Rho Activity, the Assembly of Actin Stress Fibers, and Cell Migration

Somatostatin, Acting at Receptor Subtype 1, Inhibits Rho Activity, the Assembly of Actin Stress Fibers, and Cell Migration

Antitumor effects of somatostatin

Tumor neuroendocrino primario del riñón

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