Neurone-specific enolase is a molecular marker for peripheral and central neuroendocrine cells.
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Endocrine-paracrine cells of the prostate (also known as APUD or neuroendocrine cells) constitute, in addition to the basal and exocrine secretory cells, a third population of highly specialized epithelial cells in the prostate gland. These endocrine-paracrine cells contain, and most likely secrete, serotonin and calcitonin, as well as variety of other peptides. Little is known of the functional role of these cells, but they probably subserve a paracrine or local regulatory role. They may also regulate via endocrine, lumencrine, or neurocrine mechanisms. These endocrine-paracrine cells probably play a significant role during prostatic growth and differentiation as well as regulating the secretory process of the mature gland. Neuroendocrine differentiation in prostatic carcinoma occurs in the form of the relatively rare small cell carcinoma and carcinoid or carcinoid-like tumor, but most commonly as focal neuroendocrine differentiation in a conventional prostatic adenocarcinoma that is a very frequent, if not ubiquitous phenomenon, and reflects tumor cell heterogeneity mimicking the normal differentiation process. The world's literature on neuroendocrine differentiation in prostatic carcinoma is reviewed. Neuroendocrine differentiation in all types of prostatic carcinoma appears to correlate with a poor prognosis. This correlation is probably multifactorial and may relate to a positive correlation with grade, a direct resistance to hormonal manipulation, and/or autocrine/paracrine growth factor activity due to the secretion of neuroendocrine products. Neuron-specific enolase and chromogranin, as well as other neuroendocrine products, may be useful as serum markers in patients with prostatic carcinoma with neuroendocrine differentiation. New therapeutic strategies need to be developed to treat these tumors. This includes the use of specialized protocols that have been effective against neuroendocrine carcinomas arising in other organ systems.
The tumor-forming endocrine cells of the pancreas belong to the APUD system. These cells are of neuroectodermal origin. The tumor can be diagnosed in most cases by a distinct clinical picture, and the diagnosis can be veryfied by direct hormone determination or/and by the biochemical disorders caused by the hormones. For localisation angiography, szintigrams, endoscopic pancreatography, and sonograms were used up to now without convincing results in many cases; computerized tomography promises to be the decisive examination in the future. Three hormones can, up to now, not yet be correlated with a distinct clinical picture specific for a pancreatic tumor. On the other hand, four tumors are responsible for a very typical clinical entity, the insulinoma, the glucagonoma, the gastrinoma, and the vipoma, as illustrated by our own cases. The surgical therapy consists mainly in enucleation of an adenoma or in partial pancreatic resection. Total pancreatectomy is indicated only in few cases. The Zollinger-Ellison syndrome is treated best by total gastrectomy. Malignant tumors are sensible to streptozotozin.
To determine whether or not any pancreatic islet cell type arises from rhombencephalic levels of neurectoderm, lengths of presumptive rhombencephalon (containing potential neural crest) of Black Australorp chick embryos at 6- to 9-somite stages were replaced isotopically and isochronically by neural tube of Japanese quail embryos. Some transplants included mesencephalic regions. In some cases various levels of the rhombencephalon were deleted and not replaced. The quail nuclear marker was detected in cranial ganglia in operated embryos sacrificed at 3 3/4 days of incubation and in enteric ganglia and cells accompanying some pancreatic nerves, in embryos killed at 7 days of incubation. This provided evidence of normal migration of crest cells from the grafts. Dopa was administered to the younger embryos, which were submitted to the formaldehyde-induced fluorescence procedure to demonstrate APUD (Amine Precursor Uptake and Decarboxylation) cells. No pancreatic APUD cells exhibited the quail nuclear marker. In 9- to 11-day embryos, A and B cells were identified by specific light and electron microscopic features. None showed the quail marker. The marker was also absent from those D cells seen and from cells of an as yet unidentified type, but not enough of these were found to warrant a conclusion. All islet cell types were found in embryos from which various levels of the rhombencephalon had been deleted. It is concluded that at least A and B islet cells are not derived from the rhombencephalic neurectoderm and probably not from mesencephalic levels. Their most likely origin remains the endoderm, which was the accepted source until recently.
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A case of stomach carcinoma was examined in a 45-year-old male by using histochemical and electron microscopic techniques. The carcinoma had arisen from chronic gastric ulcer accompanied with fundic gland hyperplasia and located in the body of the stomach. Histologically, it was a nondifferentiated scirrhous carcinoma involving signet ring and minor polymorphic cells with eosinophilic cytoplasm. Electron microscopically, the tumors had cells containing a large body of mucoidal granules, great quantities of cells having various endocrine granules, and cells showing mixed endocrine-exocrine secretion. It was suggested that there might be a pathogenetic relationship of fundal cell hyperplasia and signet ring cell carcinoma development, on the one hand, and the existence of tumor endocrine cells, on the other.
AL cells of the oxyntic stomach area were studied in rats using ultrastructurometric technique. High-threshold, short-term direct electrical vagostimulation (5 V, 4 msec, 30 Hz, 10 sec) was performed in experimental group of 12 animals. Animals were killed 1, 10 and 30 min after stimulation. High post-stimulation lipolytic activity of AL cells and intensification of "granule autophagy" phenomenon were noted. Our findings as well as the literature data suggest a hypothesis on possible prostaglandin production by AL cells. Direct evidence in favour of this hypothesis is difficult to obtain due to the lack of sufficiently reliable methods of their morphological detection in cells.
Electron microscopy of human gastric mucosa has demonstrated that the endocrine cells are closely and specifically related to the adjacent glandular cells and the basal membrane. Cytoplasmic strands of the adjacent cells surround the endocrine cells and their projections, probably, regulating their secretion. The above outlined relations are considered a structural basis for complex regulatory endocrine and paracrine functions of the gastric endocrine cells.
Horse radish peroxidase-labelled cholera toxin (choleragen) binds to the receptors of entero-endocrine cell (Ec-cells) plasmalemma. Unlike columnar epitheliocytes, the effect of choleragen on Ec-cells.
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Gastric apudoma (argyrophilic carcinoma) some cells of which are characterized by intensive production of intestinal mucosa is described. Endocrine granules were found in the cytoplasm of the tumor cells, including mucosa-producing ones, by means of diagnostic APUD-reactions (Grimelius method, staining with toluidine blue after acid hydrolysis, lead hematoxylin) and electron microscopy. In the opinion of the authors, mucosa production indicates the entodermal nature of the tumor which casts doubt on the conception of the common neuroectodermal origin of all apudomas.
Pancreatic endocrine tumors (PETs) are rare neoplasms originating from the amine precursor uptake and decarboxylation (APUD) stem cells. Although the majority of PETs are sporadic, they frequently occur in familial syndromes. PETs may cause a variety of functional syndromes or symptoms of local progression if they are non-functional. General neuroendocrine tumor markers are highly sensitive in the diagnostic assessment of a PET. Imaging studies for tumor localization and staging include computer tomography (CT) scan, magnetic resonance imaging (MRI), In(111)-octreotide scan, MIBG, and endoscopic ultrasonography (EUS). Treatment of PETs often requires a multi-modality approach; however, surgical resection remains the only curative therapy for localized (non-metastatic) disease. Treatment of metastatic disease includes biologic agents, cytotoxic chemotherapy, and liver-directed therapies.
A case of Cushing's syndrome in a patient with an ACTH-producing prostatic carcinoma is presented. Initial transurethral biopsy showed a moderately well-differentiated adenocarcinoma. The development of Cushing's syndrome was associated with a change in the morphology of the tumor; repeat transurethral prostatic biopsy and autopsy showed an admixture of moderately well-differentiated adenocarcinoma and anaplastic carcinoma. Immunoperoxidase studies revealed ACTH only within the anaplastic component of the tumor, which also showed strong argyrophilia. Electron microscopic studies revealed abundant dense-core granules within the anaplastic portion of the tumor with only very scanty granules in the differentiated portion. This case strongly supports the contention that cells with APUD characteristics can differentiate within epithelial tissues of multiple embryologic origins, and that the possession of APUD features does not necessarily imply origin from any specific neuroendocrine progenitor cell.
A novel endocrine cell type has been identified in the guinea-pig gastric mucosa which preferentially occurs in the oxyntic area. Cells of this type exhibit immunoreactivities for bovine adrenal medulla dodecapeptide (BAM-12P) and in many cases for Met-enkephalin and are thus presumed to contain a pro-enkephalin-like precursor protein. Systematic immunohistochemical investigations show that these cells do not contain immunoreactivities for various enteric hormones, neuropeptides and biogenic amines (serotonin, histamine). However, they do contain immunoreactivity for chromogranin A, an acidic glycoprotein which is common to the majority of entero-endocrine cells. Using silver impregnation techniques BAM-12P immunoreactive cells prove to be argyrophil, but fail to react argentaffin. On the electron microscopical level, these cells contain a well-developed endoplasmic reticulum and Golgi apparatus and numerous polymorphous secretion granules which measure about 290 nm in diameter. The secretion granules are ovoid or pear-shaped but largely plump compared to those of enterochromaffin cells. Light and electron microscopical findings indicate that BAM-12P immunoreactive cells constitute an endocrine cell population of the gastric epithelium in addition to the "established" endocrine cells hitherto known in this location.
Thyroid glands of young rats were incubated for 3 h in Eagle's solution supplemented with 5-hydroxy-l-tryptophan (5-HTP) or with serotonin. Following control incubations or incubations with serotonin, no serotonin could be demonstrated in C cells using immunocytochemical techniques. However, serotonin was demonstrated in the secretory granules of all C cells following incubation with 5-HTP. The secretory function of C cells was evaluated by ultrastructural and immunocytochemical studies, and by calcitonin radioimmunoassays of the incubation medium. Following incubation with 5-HTP, the secretory function of the majority of C cells was inhibited, and calcitonin levels in the media were decreased. Incubation with serotonin produced an increased secretory function of C cells and higher calcitonin levels in the media. The results indicate that serotonin and its direct precursor, 5-HTP, affect calcitonin secretion by rat thyroid C cells by distinct mechanisms.
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