| 1. |
- Grönberg, Malin, 1980-, et al.
(författare)
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Distribution of obestatin and ghrelin in human tissues : immunoreactive cells in the gastrointestinal tract, pancreas, and mammary glands
- 2008
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Ingår i: Journal of Histochemistry and Cytochemistry. - : SAGE Publications. - 0022-1554 .- 1551-5044. ; 56:9, s. 793-801
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Tidskriftsartikel (refereegranskat)abstract
- Obestatin and ghrelin are two peptides derived from the same prohormone. It is well established that ghrelin is produced by endocrine cells in the gastric mucosa. However, the distribution of human obestatin immunoreactive cells is not thoroughly characterized. A polyclonal antibody that specifically recognizes human obestatin was produced. Using this antibody and a commercial antibody vs ghrelin, the distribution of obestatin and ghrelin immunoreactive cells was determined in a panel of human tissues using immunohistochemistry. The two peptides were detected in the mucosa of the gastrointestinal tract, from cardia to ileum, and in the pancreatic islets. Interestingly, epithelial cells in the ducts of mammary glands showed distinct immunoreactivity for both ghrelin and obestatin. By double immunofluorescence microscopy, it was shown that all detected cells were immunoreactive for both peptides. Furthermore, the subcellular localization of obestatin and ghrelin was essentially identical, indicating that obestatin and ghrelin are stored in the same secretory vesicles.
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| 2. |
- Grönberg, Malin, 1980-
(författare)
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Expression of Neuroendocrine Markers in Normal and Neoplastic Tissue with an Emphasis on Ghrelin and Obestatin
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to characterize the expression of the peptides ghrelin and obestatin, as well as other neuroendocrine markers in human normal tissues, in invasive breast cancer and a wide panel of neuroendocrine tumors (NETs). In normal tissues the expression of ghrelin and obestatin was mainly localized to the gastric mucosa, and in lesser extent in the remaining gastrointestinal tract, endocrine pancreas and mammary glands. Double immunofluorescence studies demonstrated that ghrelin and obestatin were co-localized in the same cells displaying the same cytoplasmic distribution. In normal breast tissue, ghrelin, obestatin, adrenomedullin, apelin and vesicular monoamine transporter 2 were specifically demonstrated in the luminal epithelial cells. Consecutive sections indicated that mammary epithelial cells could express several of these peptides. Secretogranin II and III were also detected in breast tissue, but their presence was restricted to the outer layer of myoepithelial cells, whereas chromogranin B immunoreactivity was found in both the epithelial and myoepithelial cells. Ghrelin and obestatin immunoreactivity was seen in invasive breast cancer, where the expression could be correlated to factors associated with prognosis. Furthermore, multivariate analysis indicated that ghrelin expression was a possible independent prognostic factor for prolonged recurrence-free and breast cancer-specific survival. In a panel of NETs and endocrine-related disorders it was revealed that ghrelin and obestatin immunoreactivity was primarily found in tumors originating from the respective normal tissues. The two proteins were detected in only a few cases and only occasional tumor cells were immunoreactive. In conclusion, ghrelin and obestatin are localized in the gastrointestinal tract, endocrine pancreas and mammary glands. This thesis has contributed to our understanding of the distribution of ghrelin and obestatin in both normal tissue and tumor cells. A potential role of ghrelin as a prognostic factor in invasive breast cancer has been identified and should be further explored.
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| 3. |
- Grönberg, Malin, 1980-, et al.
(författare)
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Neuroendocrine markers are expressed in human mammary glands
- 2010
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 160:1-3, s. 68-74
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRegulatory peptides have previously been detected in epithelial cells of human mammary glands. As these peptides are produced by scattered neuroendocrine cells in the epithelium of other tissues the aim of this study was to investigate whether the mammary glands express molecular markers for neuroendocrine cells.Material and methodsSpecimens from 28 human mammary glands were retrieved. The distribution of immunoreactive cells was determined using immunohistochemistry with antibodies versus a set of endocrine markers including peptide hormones, chromogranins/secretogranins, vesicular monoamine transporters, synaptophysin, serotonin and synaptic vesicle protein 2.ResultsCells of the luminal epithelium of ducts and lobules of human mammary glands expressed vesicular monoamine transporter 2 and chromogranin B, as well as the previously reported regulatory peptides obestatin, ghrelin, adrenomedullin and apelin. Using consecutive sections, it was revealed that the immunoreactivity patterns of the regulatory peptides and vesicular monoamine transporter 2 were similar. Interestingly, immunoreactivity for secretogranin II, secretogranin III and chromogranin B was identified in myoepithelial cells. No immunoreactivity was detected for chromogranin A or synaptophysin.ConclusionSpecific cells in the epithelium and myoepithelium of mammary glands express neuroendocrine markers suggesting that mammary glands may have neuroendocrine functions.
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| 4. |
- Saras, Jan, et al.
(författare)
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Somatostatin induces rapid contraction of neuroendocrine cells
- 2007
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Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 581:10, s. 1957-1962
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Tidskriftsartikel (refereegranskat)abstract
- The peptide hormone somatostatin, as well as the somatostatin analog octreotide, induces rapid morphological changes in neuroendocrine cells. The effect can be detected in less than 2min: retraction fibers are formed, cells round up and cell–cell contacts are broken. Somatostatin-dependent cell contraction is inhibited by Y-27632, indicating that this effect is dependent on Rho kinase. In BON1 cells, the somatostatin-induced inhibition of forskolin-induced secretion of chromogranin A is not blocked by Y-27632. It is therefore concluded that the inhibitory effect of somatostatin in forskolin-stimulated cells is not dependent on cell contraction.
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| 5. |
- Tsolakis, Apostolos V., et al.
(författare)
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Obestatin/ghrelin cells in normal mucosa and endocrine tumours of the stomach
- 2009
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 160:6, s. 941-949
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Tidskriftsartikel (refereegranskat)abstract
- Objective:Obestatin and ghrelin are derived from the same gene and co-expressed in the same endocrine cells. Vesicular monoamine transporter-2 (VMAT-2), a marker for enterochromaffin-like (ECL) cells, is considered to be expressed in ghrelin cells. The aim was to establish if the two peptides and the transporter are co-expressed, both in normal gastric mucosa and in gastric endocrine tumours.Design: An immunohistochemical study was performed on gastric biopsy material and on surgical specimens from 63 patients with gastric endocrine tumours and from individuals with normal gastric mucosa. Cells displaying obestatin immunoreactivity were examined regarding co-localization with ghrelin and VMAT-2. Both single- and double-immunostaining techniques were applied. Obestatin concentration in blood was measured in a subgroup of these patients. The results were correlated to various clinico-pathological parameters.Results:In the normal mucosa, obestatin/ghrelin-immunoreactive cells rarely co-expressed VMAT-2. In most tumour tissue specimens, only a fraction of neoplastic cells displayed immunoreactivity to obestatin, and these cells always co-expressed ghrelin. Neoplastic obestatin-/ ghrelin-IR cells invariably expressed VMAT-2, except for two ghrelinomas. The obestatin concentrations in blood were consistently low and did not correlate to clinico-pathological data.Conclusions:Obestatin and ghrelin immunoreactivity always occurred in the same endocrine cells in the gastric mucosa but these cells only occasionally co-expressed VMAT-2, opposite to the findings in tumours. These results indicate that endocrine cells expressing obestatin and ghrelin mainly differ from VMAT-2 expressing cells (ECL-cells) and can develop into pure ghrelinomas. Plasma concentrations of obestatin did not correlate to cellular expression.
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