Relevance of somatostatin receptors and other peptide receptors in pathology

Receptors for regulatory peptides can be overexpressed by several diseases, in particular by neoplasms. This review summarizes the current status of knowledge in this field, on the basis of in vitro receptor studies and with emphasis on receptors for somatostatin as well as for substance P (SP), vasoactive intestinal polypeptide (VIP), and cholecystokinin. It evaluates the existing and potential clinical implications of the findings for diagnosis and therapy and discusses the role of the pathologist in this contex

Peptide receptor expression in GEP-NET

Numerous peptide receptors have recently been reported to be expressed or overexpressed in various human cancers. For instance, somatostatin receptors are particularly frequently expressed in gastroenteropancreatic neuroendocrine tumors (GEP-NET), including both primaries and metastases. The density is often high, and the distribution is usually homogenous. While various somatostatin receptor subtypes can be expressed in these tumors, the sst2 is clearly predominant. These receptors represent the molecular basis for a number of clinical applications, including symptomatic therapy with octreotide in hormone-secreting GEP-NET, in vivo diagnostic with radiolabeled diethylene triamine pentaacetic acid octreotide (Octreoscan) to evaluate the extend of the disease, and 90Y- or 177Lu-[90Y-DOTA]-d-Phe1-Tyr3 octreotide radiotherapy. GEP-NET can, however, express peptide receptors other than somatostatin receptor: Insulinomas have more glucagon-like peptide 1 receptors than somatostatin receptors; gastrinomas express very high levels of secretin receptors. GEP-NET may also express cholecystokinin 2, bombesin, neuropeptide Y, or vasoactive intestinal peptide receptors. Often, several of these peptide receptors are expressed simultaneously in GEP-NET, providing a molecular basis for in vivo multireceptor targeting of those tumor

The Internationalisation of Tobacco Control, 1950-2010.

This article explores the internationalisation of tobacco control as a case study in the history of international health regulation. Contrary to the existing literature on the topic, it argues that the history of international anti-smoking efforts is longer and richer than the making of the World Health Organisation's Framework Convention on Tobacco Control in the early twenty-first century. It thereby echoes the point made by other scholars about the importance of history when making sense of contemporary global health. Specifically, the article shows how the internationalisation of tobacco control started in the 1950s through informal contacts between scientists working on cancer research and how these initial interactions were followed by a growing number of more formal initiatives, from the World Conferences on Tobacco or Health to the Bloomberg Initiative to Reduce Tobacco Use. Rather than arranging these efforts in a linear narrative of progress culminating with the Framework Convention on Tobacco Control, we take anthropological claims about global health's uneven terrain seriously and portray a history of international tobacco control marked by ruptures and discontinuities. Specifically, we identify three successive periods, with each of them characterised by specific understandings of international action, tobacco control expertise, advocacy networks and funding strategies

Value of the radiolabelled GLP-1 receptor antagonist exendin(9-39) for targeting of GLP-1 receptor-expressing pancreatic tissues in mice and humans

Purpose: Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. Moreover, it was recently reported that antagonist tracers were superior to agonist tracers for somatostatin and gastrin-releasing peptide receptor targeting of tumours. The present preclinical study determines therefore the value of an established GLP-1 receptor antagonist for the in vitro visualization of GLP-1 receptor-expressing tissues in mice and humans. Methods: Receptor autoradiography studies with 125I-GLP-1(7-36)amide agonist or 125I-Bolton-Hunter-exendin(9-39) antagonist radioligands were performed in mice pancreas and insulinomas as well as in human insulinomas; competition experiments were performed in the presence of increasing concentration of GLP-1(7-36)amide or exendin(9-39). Results: The antagonist 125I-Bolton-Hunter-exendin(9-39) labels mouse pancreatic β-cells and mouse insulinomas, but it does not label human pancreatic β-cells and insulinomas. High affinity displacement (IC50 approximately 2nM) is observed in mouse β-cells and insulinomas with either the exendin(9-39) antagonist or GLP-1(7-36)amide agonist. For comparison, the agonist 125I-GLP-1(7-36)amide intensively labels mouse pancreatic β-cells, mouse insulinoma and human insulinomas; high affinity displacement is observed for the GLP-1(7-36)amide in all tissues; however, a 5 and 20 times lower affinity is found for exendin(9-39) in the mouse and human tissues, respectively. Conclusion: This study reports a species-dependent behaviour of the GLP-1 receptor antagonist exendin(9-39) that can optimally target GLP-1 receptors in mice but not in human tissue. Due to its overly low binding affinity, this antagonist is an inadequate targeting agent for human GLP-1 receptor-expressing tissues, as opposed to the GLP-1 receptor agonist, GLP-1(7-36)amid

Volatiles contents, degassing and crystallisation of intermediate magmas at Volcan de Colima, Mexico, inferred from melt inclusions

In volatile-saturated magmas, degassing and crystallisation are interrelated processes which influence the eruption style. Melt inclusions provide critical information on volatile and melt evolution, but this information can be compromised significantly by post-entrapment modification of the inclusions. We assess the reliability and significance of pyroxene-hosted melt inclusion analyses to document the volatile contents (particularly H2O) and evolution of intermediate arc magmas at Volcán de Colima, Mexico. The melt inclusions have maximal H2O contents (≤4wt%) consistent with petrological estimates and the constraint that the magmas crystallised outside the amphibole stability field, demonstrating that pyroxene-hosted melt inclusions can preserve H2O contents close to their entrapment values even in effusive eruptions with low effusion rates (0.6m3s−1). The absence of noticeable H2O loss in some of the inclusions requires post-entrapment diffusion coefficients (≤1×10−13m2s−1) at least several order of magnitude smaller than experimentally determined H+ diffusion coefficient in pyroxenes. The H2O content distribution is, however, not uniform, and several peaks in the data, interpreted to result from diffusive H2O reequilibration, are observed around 1 and 0.2wt%. H2O diffusive loss is also consistent with the manifest lack of correlations between H2O and CO2 or S contents. The absence of textural evidence supporting post-entrapment H2O loss suggests that diffusion most likely occurred via melt channels prior to sealing of the inclusions, rather than through the host crystals. Good correlation between the melt inclusion sealing and volcano-tectonic seismic swarm depths further indicate that, taken as a whole, the melt inclusion population accurately records the pre-eruptive conditions of the magmatic system. Our data demonstrate that H2O diffusive loss is a second-order process and that pyroxene-hosted melt inclusions can effectively record the volatile contents and decompression-induced crystallisation paths of vapour-saturated magma

Co-expressed peptide receptors in breast cancer as a molecular basis for in vivo multireceptor tumour targeting

Breast cancers can express different types of peptide receptors such as somatostatin, vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP) and NPY(Y1) receptors. The aim of this in vitro study was to evaluate which is the most appropriate peptide receptor or peptide receptor combination for in vivo diagnostic and therapeutic targeting of breast cancers. Seventy-seven primary breast cancers and 15 breast cancer lymph node metastases were investigated in vitro for their expression of somatostatin, VPAC1, GRP and NPY(Y1) receptors using in vitro receptor autoradiography on successive tissue sections with 125I-[Tyr3]-octreotide, 125I-VIP, 125I-[Tyr4]-bombesin and 125I-[Leu31,Pro34]-PYY respectively. This study identified two groups of tumours: a group of 68 tumours (88%) with at least one receptor expressed at high density (>2,000dpm/mg tissue) that may provide a strong predictive value for successful in vivo targeting, and a group of nine tumours (12%) with no receptors or only a low density of them (<2,000dpm/mg tissue). In the group with high receptor density, 50 of the 68 tumours (74%) expressed GRP receptors, 45 (66%) expressed NPY(Y1) receptors, 25 (37%) expressed VPAC1 receptors and 14 (21%) expressed somatostatin receptors. Mean density was 9,819±530dpm/mg tissue for GRP receptors, 9,135±579dpm/mg for NPY(Y1) receptors, 4,337±528dpm/mg for somatostatin receptors and 3,437±306dpm/mg for VPAC1 receptors. It is of note that tumours expressing NPY(Y1) or GRP receptors, or both, were found in 63/68 (93%) cases. Lymph node metastases showed a similar receptor profile to the corresponding primary tumour. This in vitro study strongly suggests that the combination of radiolabelled GRP and Y1 analogues should allow targeting of breast carcinomas and their lymph node metastases for in vivo peptide receptor scintigraphy and radiotherap