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PubMed1994

The prostatic endocrine-paracrine (neuroendocrine) regulatory system and neuroendocrine differentiation in prostatic carcinoma: a review and future directions in basic research.

Endocrine-paracrine (neuroendocrine, amine precursor uptake and decarboxylation [APUD]) cells of the prostato-urethral region are serotonin and peptide containing regulatory cells, which are part of a dispersed neuroendocrine regulatory system also known as the APUD system. These cells most likely regulate growth and differentiation, as well as the secretory functions of the prostate. Prostatic carcinoma exhibits neuroendocrine differentiation in 3 forms: 1) small cell neuroendocrine carcinoma, 2) carcinoid-like tumors and 3) conventional prostatic adenocarcinoma with focal neuroendocrine differentiation. Small cell carcinoma and carcinoid-like tumors are rather rare (1 to 2% of all prostatic malignancies) and generally pursue an aggressive course. Focal neuroendocrine differentiation in adenocarcinoma is extensive in 10% of the cases and may be present in virtually all adenocarcinomas to a minor degree. There are conflicting studies on the prognostic significance of focal neuroendocrine differentiation in prostatic carcinoma, although several suggest a poor prognosis. The finding that serum neuroendocrine markers predict initial insensitivity to or the development of resistance to hormonal suppression therapy, coupled with the recent observation that androgen receptor is not expressed in neoplastic neuroendocrine cells suggests that neuroendocrine differentiation directly results in resistance to hormonal manipulation therapy. Neuroendocrine differentiation in prostatic carcinoma raises the possibility of innovative modes of treatment. Future directions of research should concentrate on the quantitative analysis of serotonin and various peptides in prostatic malignancy, since high levels of constitutive secretion may not be appreciated by immunocytochemistry, as well as analysis of tumors for receptors to neuroendocrine products, which are necessary for these products to have a functional role. Finally, specific subtypes of neoplastic cells with neuroendocrine differentiation based on serotonin and peptide profiles should be analyzed.

APUD Cells↗
PubMed1978

Polypoid nonchromaffin paraganglioma of the duodenum.

A polypoid tumor was surgically removed from the second part of the duodenum of a 56-year-old male. The main body consisted of large epithelioid cells arranged in an adenoma like pattern of strands and nests. These cells were argyrophil and had marked nonspecific esterase activity. Unmyelinated nerves with proliferated Schwann cells accompanied these epithelioid cells together with scattered gangliocyte like elements. Ultramicroscopically, the epithelioid cells were seen to contain round electron dense granules, 150 nm in diameter on average. The tumor is considered to be a nonchromaffin paraganglioma, as it probable developed from paraganglion cells associated with small arteries or branches of the vagus nerve, or from the undifferentiated pluripotent APUD cells of the duodenum.

APUD Cells↗
PubMed1982

Gastric carcinomas with argyrophil and argentaffin cells.

In series of 248 gastric carcinomas from surgical resections the occurence of argyrophil and argentaffin cells was studied. These cells were distinctly more frequent in diffuse than in tubular carcinomas. In all cases with both types of APUD-cells, argyrophil cells were more numerous than argentaffin cells. These tumors are considered to be a variant of current gastric carcinoma, with more pronounced APUD-differentiation of neoplastic cells. This variant stands apart from carcinoid tumors and also from those rare nasal adenocarcinomas with argentaffin cells.

APUD Cells↗
PubMed1997

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in thyroid C-cells and medullary thyroid carcinomas.

AIMS: Hyperplastic C-cells of the thyroid and medullary thyroid carcinomas (MTCs) were studied immunocytochemically for calcitonin, carcinoembryonic antigen (CEA), chromogranin A, matrix metalloproteinase (MMP)-2 and -9, and tissue inhibitor of metalloproteinase (TIMP)-1 and -2. METHODS AND RESULTS: Non-neoplastic C-cells were positive for all these substances whereas MTC tumour cells were relatively weaker stained, and thyroid follicular cells were negative for all the substances studied. We have recently reported that pancreatic islet cells and islet cell tumours were positive for MMPs and TIMPs, and, in addition, anterior pituitary cells and pituitary adenomas and parathyroid gland and its adenomas were also positively stained. The MMP- and TIMP-positive endocrine cells correspond to Pearse's APUD cells, derived from neural crest and endodermal cells. CONCLUSIONS: MMPs and TIMPs may well be added as newly recognized markers for neuroendocrine cells. The possible function of MMP-TIMP homeostasis in C-cells and MTCs is discussed.

Adult↗
PubMed1980

[Pancreatic apudoma].

Endocrine tumors of the pancreas apparently develop from a premature stem-cell, possibly originating from the ectodermal neural crest. These tumors belong to the APUD-cell system, which is identical with the "Helle-Zellen-system". Following a description of the various forms of appearance there is a discussion of the different syndromes. The present-day differentiated diagnostic procedures are described. Finally, details and problems of treatment, especially regarding surgical intervention, are discussed. Cases from the author's own clinic are considered.

APUD Cells↗
PubMed1982

Development of neuroepithelial bodies and solitary endocrine cells in fetal rabbit lungs. II. Nonspecific esterase as an indicator of early maturation.

Activity for nonspecific esterases has been demonstrated histochemically in fetal rabbit lungs using alpha-naphthyl acetate as substrate. Commencing with a homogeneous distribution in pseudoglandular lungs, activity gradually heightens in the epithelium, progresses centrifugally along the bronchial tree, and reaches full expression in postnatal lungs, when most cells in conducting airways are strongly reactive. Well before this general rise, small clusters become conspicuously reactive in the epithelium, first in the larger bronchi and later in the smaller bronchi. At 25 days' gestation most of these are neuroepithelial bodies, which are recognizable in frozen sections and occur selectively near bronchial bifurcations. Subsequently, while the bodies formed earlier continue active, other clusters and solitary cells become reactive in more recently formed airways, amounting in all to 1-2% of the epithelial cells present. Near term these and the more organized neuroepithelial bodies occur throughout the bronchial tree up to the primitive respiratory zone. The small clusters and single cells may include some mature elements; however, as they generally correspond in incidence and distribution to clear cells and clusters, identified as precursors of neuroepithelial bodies, many are incompletely differentiated. Esterase activity, a characteristic shared with APUD cells in other organs, evidently rises about the time pulmonary endocrine cells become functional. Using the histochemical method, a large population of these cells is therefore demonstrable in lungs until after birth, when the increasing activity of nonendocrine cells finally obscures it.

APUD Cells↗
PubMedDate not supplied

[Apudoma of the prostate].

Prostatic apudomas are represented by well-, moderately- and poorly differentiated variants. Histologic differentiation determines various functional properties of tumor cells. Tumor cells of well-differentiated apudomas produce serotonin, less frequently calcitonin, poorly differentiated ones produce only ACTH. Apud cells of moderately differentiated tumors, besides their main function to synthesize biogenic amines and hormones (serotonin, ACTH) possess immunoreactivity to epithelial membrane antigen, carcinoembryonal antigen and prostatic specific antigen.

APUD Cells↗
PubMed1987

[The disseminated endocrine system of man. A contribution of pathology].

The disseminated (or diffuse) endocrine system is composed of many single cells and small groups of cells disseminated in the whole organism, capable of producing biogenic amines and polypeptide hormones. They are also called APUD cells and were first detected in the mucosa of the intestinal tract, where they occur in highest concentration. Carcinoids are tumors of disseminated endocrine cells which sometime retain their hormone-producing capacity. These hormones are key factors in the control of numerous bodily functions; some are transported by way of the bloodstream, while others probably exercise their functions only within the tissue immediately adjacent to the producing cells (paracrine function). It is an interesting fact that almost identical hormones are found within the brain and within the peripheral autonomic nervous system, where they act as neural transmitters.

APUD Cells↗
PubMed1979

Does the cancer accompanying acanthosis nigricans contain endocrine cells of the APUD series?

Following the publication of Hage & Hage, who believe that gastric cancers accompanying malignant acanthosis nigricans might constitute a specific group of carcinomas in which cells from parts of the tumor arise from the APUD-series of endocrine cells, carcinomas of 2 patients with malignant acanthosis nigricans were subjected to investigation. There were no APUD-cells in the adenocarcinomas studied but they were present in the overlying mucosa. It is known, moreover, that internal carcinomas not accompanying malignant acanthosis nigricans may contain APUD cells.

APUD Cells↗
PubMed1979

Embryology of the diffuse neuroendocrine system and its relationship to the common peptides.

The diffuse neuroendocrine system is constituted by the cells, now more than 40 in number, of the central and peripheral divisions of the amine precursor uptake and decarboxylation (APUD) series. At one time presumed to be derived from a common "neural" ancestor, all are now deemed to be "neuroendocrine-programmed," arising either in the embryonic epiblast itself or in one of its principal descendants. The APUD cells produce more than 35 physiologically active peptides and a small number of equally active amines. Within the last 3 years, 17 of these peptides have been identified jointly in endocrine cells and in neuronal cell bodies or processes. Sharing in this way a neural and an endocrine location and site of production, they are called the "common peptides." The diffuse neuroendocrine system is to be regarded as a third division of the nervous system, whose products suppress, amplify, or modulate the activities of the other two divisions. The relationship of its products to the cells and processes of these two divisions is currently the object of intensive inquiry.

APUD Cells↗
PubMed1980

Neuroendocrinoma of the jejunum: electron microscopic and biochemical analysis.

A 56-year-old woman presented with a sudden, severe hemorrhage per rectum. Angiography localized a jejunal tumor, which was excised. Light microscopy suggested a neuroendocrine tumor, but neither a smooth muscle tumor nor a lymphoma could be excluded. Electron microscopy showed dense cored, single membrane bound secretory granules 150--220 nm in diameter; myofilaments were not observed. Biochemical analysis of tumor tissue yielded considerable amounts of catecholamines. VMA, 5-HIAA, and metanephrines. These combined ultrastructural and biochemical observations establish the diagnosis of neuroendocrine tumor; however, in this case neither type of information is sufficiently specific to define the tumor as either a paraganglioma or a carcinoid. Although paraganglia and mucosal endocrine cells in the GI are currently thought to constitute distinct cell types, they share numerous structural and functional properties, and they are both thought to be part of the APUD cell system. These parallels and similarities are shared by the neoplasms derived from them which often display features of both. In the absence of specific granule types or specific substances isolated from tumor tissue, only the application of specific immunocytochemistry techniques may allow the precise "functional" classification of such tumors.

APUD Cells↗
PubMed1984

Prostatic adenocarcinoma with carcinoidal features producing adrenocorticotropic syndrome. Immunohistochemical study and review of the literature.

An autopsy case of disseminated, military-type, composite adenocarcinoma and carcinoid tumor associated with adrenocorticotropic syndrome is discussed. Prostatic origin and functional activity were demonstrated by immunohistochemical techniques. Of interest in this case is that the tumor had the characteristics of amine precursor uptake and decarboxylation (APUD) cells and also kept the antigenicity of its prostatic origin. The APUD system perhaps should be considered as one form of functional differentiation of cells of different origin rather than an exclusive derivative of the neural crest.

ACTH Syndrome, Ectopic↗
PubMed1980

Obesity and the development of the diffuse neuroendocrine system.

The diffuse neuroendocrine system may play a critical role in the events of both adaptation for impending famine and of arousal from the opioid-induced conservation state. This may occur by means of the opioid and anti-opioid peptides of APUD cells acting in conjunction with shifts in biogenic amine uptake and release.

APUD Cells↗
PubMed1982

Neuroendocrine cells of the lung. An overview of morphologic characteristics and development.

The detailed morphology of pulmonary neuroendocrine (NE) cells has been defined only during the last decade. The purpose of this paper is to review the main morphologic features of the NE cells, to review the methods and techniques used for their identification, and to discuss the development and functional significance of these cells. The main emphasis is on NE cells in human lung, but where appropriate, studies in animal lungs are also included. NE cells are present in the airway epithelium of human and various animal species and occur singly as well as in clusters called neuroepithelial bodies (NEB). The general cytochemical features (common to both single NE cells and NEB) include cytoplasmic argyrophilia, fluorogenic amine content, positive staining with lead-hematoxylin, and masked metachromasia. These staining properties are similar to those found in APUD cells scattered in various tissues. More specific cell markers are immunoreactivity to peptide hormones (bombesin, calcitonin, leu-enkephalin) identified so far in NE cells of human lung, and immunoreactivity to serotonin found in both human and animal lungs. At the ultrastructural level, NE cells are characterized by the presence of cytoplasmic dense core granules (90-150 nm in diameter), which are considered the storage site of amine and peptide hormones. The distinctive feature of NEB, not found with single NE cells, is the presence of nonmyelinated nerve endings in contact with granulated cells, and positive staining for acetylcholinesterase. The single NE cells are scattered throughout the tracheobronchial epithelium, whereas NEB are found only within the intrapulmonary airways. In postnatal lungs, both the single NE cells and NEB appear concentrated in small peripheral airways. In developing human lung, the first NE cells appear at 8 weeks' gestation, when all other epithelial cells are still undifferentiated. The development and cytodifferentiation of NE cells progresses in a centrifugal direction. By the end of the glandular period, single and groups of NE cells are found along the entire length of primitive bronchial epithelium. Based on differences in the size and morphology of cytoplasmic granules, three distinct types of NE cells can be recognized. During terminal stages of development, NE cells appear in small peripheral airways and primitive saccules. The functional considerations include the possible role of NE cells as endocrine, paracrine, or receptosecretory cells involved in neurohormonal regulation of pulmonary vascular or bronchial responses, and possible function of NEB as intrapulmonary hypoxia-sensitive chemoreceptors.

APUD Cells↗
PubMed1975

Observations on the fine structure, enzyme histochemistry, and innervation of parathyroid gland and ultimobranchial body of Chthonerpeton indistinctum (Gymnophiona, Amphibia).

Fine structural and enzyme histochemical observations on ultimobranchial body and parathyroid gland of the caecilian Chthonerpeton are presented. The cell clusters and follicles of the ultimobranchial body consist mainly of granulated cells which are termed C-cells and obviously belong to the APUD cell series. In the larger follicles additional possibly exhausted degranulated cells and replacement cells occur. A rich supply of nerve fibres has been found in this gland. Frequently nerve terminals were observed to come into synaptic contact with the C-cells. Two categories of nerve fibres occur: a) fibres containing large polymorphic electron dense granules (probably purinergic fibres), b) fibres containing small electron transparent vesicles and a few electron dense granules (probably cholinergic fibres). The parathyroid gland consists of elongated cells (one cell type) poor in organelles and often containing fields of glycogen and lipid droplets. The cells are further characterized by fair amounts of lysosomal enzymes; they are interconnected by maculae adhaerentes and occludentes. No nerves and blood vessels have been found in the parathyroid gland of Chthonerpeton.

Acid Phosphatase↗
PubMed1989

A study of the ultrastructure of the intestines of mice experimentally infected with S. mansoni and treated with praziquantel.

The present experimental work studied the ultrastructural changes occurring in the intestines of mice infected with S. mansoni and treated with praziquantel. Mild degenerative changes of the intestinal cells together with degranulation of the APUD cells were observed. The enterochromaffin cells in the intestines secrete serotonin which is a vaso constrictor and a strong stimulator of the smooth muscles. A possible explanation of the side effects of praziquantel is thus offered.

Animals↗
PubMed1977

Production of calcitonin, adrenocorticotropic hormone, and beta-melanocyte-stimulating hormone in tumors derived from amine precursor uptake and decarboxylation cells.

The tumor production of human calcitonin (CT) was examined by radioimmunoassay, and it was found that 50 of 85 (59%) tumor tissues collected at random contained immunoreactive CT. These tumors were grouped as to whether they were derived from the amine precursor uptake and decarboxylation (APUD) series. The group that was derived from APUD cells showed appreciable amounts of CT in 30 of 31 (97%) of these tumors or in 20 of 21 (95%) when the medullary carcinomas of the thyroid were excluded. However, of the non-APUD group of tumors only 20 of 54 (37%) were found to contain CT, so that the difference between these two groups was highly significant (p less than 0.001). Of the tumors with ectopic adrenocorticotropic hormone-melanocyte-stimulating hormone production, 12 of 14 were shown to contain CT. These data indicate that CT is a common product of the APUD tumors and that tumor production of CT is often associated with that of adrenocorticotropic hormone and beta-melanocyte-stimulating hormone.

APUD Cells↗
PubMed1992

The presence of immunoreactive vertebrate bioactive peptide substances in hemocytes of the freshwater snail Viviparus ater (Gastropoda, Prosobranchia).

1. Using an immunocytochemical procedure a wide range of immunoreactive vertebrate bioactive peptides (BAPs) has been found in hemocytes of Viviparus ater: bombesin, calcitonin, CCK-8, CCK-39, GH, glucagon, insulin, oxytocin, neurotensin, secretin, serotonin, somatostatin, substance P, vasopressin, and VIP. 2. No immunostaining was observed for antigastrin and antithyroglobulin antibodies. 3. The presence of BAP-like molecules in hemocytes suggests a correlation between hemocyte and APUD cells and is evidence of a relationship between the neuroendocrine and the immune systems.

APUD Cells↗