Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “APUD Cells”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMedDate not supplied

The neuroendocrine phenotype, cellular plasticity, and the search for genetic switches: redefining the diffuse neuroendocrine system.

The term neuroendocrine has been used to define cells that secrete their products in a regulated manner, in response to a specific stimulus. The neuroendocrine system includes neurons and endocrine cells sharing a common phenotypic program characterized by the expression of markers such as neuropeptides, chromogranins, neuropeptide processing enzymes SPC2 and SPC3 (subtilase-like pro-protein convertases) or dense core secretory granules. Various theories such as the APUD (amine precursor uptake decarboxylation) concept, the diffuse neuroendocrine system (DNES) or the paraneuron concept have been put forth to classify neuroendocrine cells as a cohesive group. Neuroendocrine characteristics have been used as evidence of a common embryological origin for normal and neoplastic cells. However, it is now recognized that neuroendocrine characteristics can be observed in various cell types, such as immunocytes, that are not of a common embryological origin with either neurons or endocrine cells. We propose to redefine previous "neuroendocrine" concepts to include the notion that activation of specific genetic switches can lead to the expression of a partial or full neuroendocrine phenotype in a variety of cell types, including immune cells.

Animals↗
PubMed2003

[Endocrine markers of cellular immunity: defining the endocrine phenotype].

The term neuroendocrine has been used to define cells that secrete their products in a regulated manner, in response to a specific stimulus. The neuroendocrine system includes neurons and endocrine cells sharing a common phenotypic program characterized by the expression of markers such as neuropeptides, chromogranins, neuropeptide processing enzymes SPC2 and SPC3 (subtilase-like pro-protein convertases) or dense core secretory granules. Various theories such as the APUD (amine precursor uptake decarboxylation) concept, the diffuse neuroendocrine system (DNES) or the paraneuron concept have been put forth to classify neuroendocrine cells as a cohesive group. Neuroendocrine characteristics have been used as evidence of a common embryological origin for normal and neoplastic cells. However, it is now recognized that neuroendocrine characteristics can be observed in various cell types, such as immunocytes, that do not share a common embryological origin with either neurons or endocrine cells. We propose to redefine previous "neuroendocrine" concepts to include the notion that activation of specific genetic switches can lead to the expression of a partial or full neuroendocrine phenotype in a variety of cell types, including immune cells.

Animals↗
PubMed1985

Small cell lung cancer, endocrine cells of the fetal bronchus, and other neuroendocrine cells express the Leu-7 antigenic determinant present on natural killer cells.

Small cell lung cancer is distinguished from other lung cancer histologic types by possessing a variety of neuroendocrine properties. Anti-Leu-7 is a monoclonal antibody that recognizes a 110,000-dalton molecular weight glycoprotein initially described on natural killer cells and subsequently reported on a variety of normal and malignant neural and neuroendocrine cell types. We have found intense anti-Leu-7 binding to a large number of small cell lung cancers, while other lung cancer types were negative or showed only weak and focal binding. Other antigens expressed by natural killer cells, lymphocytes, and monocytes were never or less often expressed on small cell lung cancer cells. In addition, we report for the first time anti-Leu-7 binding by carcinoids, carotid body tumors, pheochromocytomas, endocrine cells of the fetal bronchus and the adult intestine, and select pancreatic islet cells. Anti-Leu-7 binding by small cell lung cancer is consistent with a derivation from pulmonary precursor cells, and anti-Leu-7 staining is clinically useful for the identification of human neuroendocrine tumors of the amine precursor uptake and decarboxylation ("APUD") type.

Antibodies, Monoclonal↗
PubMed1992

Pharmacological characterization of regulation of phosphoinositide metabolism by recombinant 5-HT2 receptors of the rat.

Transfection of 5-HT2 receptor cDNA in 293 cells induced the expression of a protein binding domain, exhibiting the classical 5-HT2 receptor transduction mechanism. Both [3H]DOB and [3H]spiperone high affinity binding sites were present in membranes of sense but not of antisense, 5-HT2 receptor cDNA transfected cells. Addition of 1 microM 5-HT induced a time-dependent increase of phosphoinositide (PI) metabolism in sense but not in antisense, 5-HT2 receptor cDNA transfected cells. Graded concentrations of 5-HT and of different serotonergic agonists showed different potencies (DOI greater than 5-HT greater than quipazine greater than DOM greater than alpha-methyl-5-HT greater than 8-OH-DPAT greater than 2-methyl-5-HT greater than CGS-12066B) in stimulating turnover of PI in cells transfected with cDNA encoding for 5-HT2 receptors of the rat. The ability of different antagonists to inhibit 5-HT-stimulated turnover of PI bore a direct relationship with their potency to inhibit 5-HT2 receptor binding in cells transfected with 5-HT2 receptor cDNA (spiperone greater than ketanserin greater than ritanserin greater than mianserin greater than haloperidol). Preincubation of transfected 293 cells with pertussis toxin failed to modify either 5-HT- or DOI-induced activation of metabolism of PI. Pretreatment of transfected 293 cells with DOI (100 nM) for 2 hr or more, significantly reduced activation of turnover of PI elicited by graded doses of 5-HT. When the transfected 293 cells were exposed to DOI (100 nM) for 12 hr and the challenge was performed after a 2-hr wash-out period, the desensitization of the response to 5-HT was virtually abolished.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Ectopic ACTH syndrome in APUD tumors.

Rapidly progressing hypercorticism was observed in 2 patients with malignant neoplasms, a 72-year-old man with anaplastic small cell carcinoma and a 48-year-old woman with a primary apudoma of the liver. Both patients were treated with chemotherapy in conventional doses. Both patients developed acute dyspnea and sudden death, 7 and 10 days, respectively, after chemotherapy was given. The possibility that patients with ectopic adrenocorticotropic hormone (ACTH) secretion are excessively vulnerable to chemotherapy is raised and judicious management urged.

ACTH Syndrome, Ectopic↗
PubMed1979

[Hormonal multiplicity of an apudoma of the lung and pancreas. Characterization of the different peptides in the tumoral extracts (author's transl)].

The capacity which the cells of some tumors have of synthesizing, storing, and releasing hormonal polypetides constitutes the basic characteristic of the neoplasms of the APUD system. On many occasions these polypeptides are released as hormonal precursors of high molecular weight, with a minimal biological action in comparison with the real hormone (big ACTH, big gastrin, etc.), and they have no clinical expressivity. On other occasions they reproduce, however, the clinical syndrome of the hormone released in excess. The production of multiple hormones by a single tumor is not a common event. Here we present the case of a patient with an oat-cell carcinoma of the lung and a carcinoma of the pancreas, both histopathologically primitive. In this patient a syndrome of inadequate secretion of antidiuretic hormone was detected. By means of radioimmunoassay techniques, the existence of antidiuretic hormone, ACTH with a predominance of the components of high molecular weight (big ACTH and beta-LPH) and MSH was demonstrated in the tumoral extracts from the lung, pancreas, and from a mediastinal metastatic lymph node. While the concentrations of ACTH were much greater in the lung than in the pancreas, the opposite occurred for the antidiuretic hormone. The synthesis of MSH by the hypophyseal gland or by tumors is not at present recognized, but rather is considered as a degradation product during the process of extraction. The APUD system makes up the morphologic substrate of the syndromes of familiar multiple endocrine adenomatosis. The present case could represent a variant of sporadic multiple endocrine neoplasms which would have the same anatomical basis.

Adrenocorticotropic Hormone↗
PubMed1986

[Carcinoid of ectopic pancreas tissue--islet cell tumor].

A case of islet cell tumor--carcinoid of the ectopic pancreas is reported. The patient had been operated six times because of recurrent abdominal tumor mass and intermittent hypoglycemic coma. The first five operations were done with the diagnosis of mesotheliosarcoma by pathology. The last operation was done in our hospital with the final diagnosis of carcinoid--islet cell tumor. In addition to the light microscopic view, several diagnostic features were observed as follows: Under electron microscopy, membrane bound secretive granules were present in the tumor cytoplasm. Neither brush-like microvilli nor lumen formation of the mesothelioma were found. By immunohistochemistry, positive granules to immunoperoxidase stain of insulin were observed in some tumor cytoplasm. By laboratory test, levels of blood 5-hydroxytryptamine and urinary 5-hydroxyindolacetic acid were elevated. Sometimes it is difficult to differentiate carcinoid from islet cell tumor only by morphology, because both are derived from the same origin during the embryonic development which is probably related to the endocrine system from the embryonic foregut. The latter arises from the neuro-ectoderm and belongs to APUD system.

Abdominal Neoplasms↗
PubMedDate not supplied

Neuroendocrine carcinomas with multiple immunoreactive peptides and melanin production.

Two primary neuroendocrine skin carcinomas, one bronchial carcinoma, and one typical medullary thyroid carcinoma have been shown by immunohistochemical and electron microscopy to contain two or more immunoreactive peptides as well as melanosomes and premelanosomes. Of the battery of antisera tested, somatostatin was the only material present in all four tumors; calcitonin and ACTH were present in three of the four neoplasms. Neurosecretory granules on the one hand and melanosomes on the other were more readily identifiable in separate cells. However, in at least 2 cases, individual cells were thought to contain both types of structures. Of the various explanations possible, we choose to interpret these tumors as complex neuroendocrine carcinomas comprising cellular populations capable of synchronous production of immunoreactive peptides and melanin. since melanocytes are members of the dispersed neuroendocrine (APUD) system, these observations may not appear entirely surprising. Note-worthy, however, is that melanin synthesis seemingly remains a synchronously available option to neoplastic neuroendocrine cell populations of possibly diverse histogenesis that are actively engaged in the production of multiple hormonal peptides. We consider that these phenomena represent yet another facet of neoplastic multidirectional differentiation. It is possible that the determination of immunoreactive peptides as "markers" may play a future role in the diagnosis, therapy, and prognosis of these and similar tumors and in the study of the dysplasias that may precede them.

Adrenocorticotropic Hormone↗
PubMed1985

Benign clear cell (sugar) tumor of the lung. A light microscopic, histochemical, and ultrastructural study with a review of the literature.

A case of a benign clear cell "sugar" tumor of the lung is reported. Light microscopy showed a uniform proliferation of clear cells filled with abundant glycogen. At the ultrastructural level, tumor cells were rich in free monogranular and rosette-forming glycogen, but no membrane-bound glycogen was demonstrated. Some cells showed plasma membrane interdigitations, microvilli, and macula occludens-type junctions. Many polymorphic secretory and sporadic haloed neurosecretory-like granules were observed, but argyrophil stains as well as a large set of immunohistochemical reactions specific for APUD derivation had negative results. A literature review of this puzzling entity with particular emphasis on the histogenetic hypotheses is presented, and a derivation from epithelial nonciliated bronchiolar (Clara) cells or epithelial serous cells is suggested.

Adult↗
PubMed1985

[Electron microscopic and biochemical characteristics of the hormonal activity of small-cell lung cancer].

An electron microscopic study of small-cell carcinoma of the human lung showed that tumors identified by light microscopy as small-cell lung cancer were, in actual fact, histologically heterogenous, ranging from those free from any signs of specific cell differentiation, neoplasms with endocrine differentiation, squamous cell cancer, adenocarcinomas to tumors with mixed cell differentiation. Elevated blood-ACTH concentrations occur in patients with tumors which do not incorporate cells with endocrine differentiation. In such cases, activation of ACTH synthesis may be due to hyperfunction and hyperplasia of apudocytes (elements of a diffuse endocrine system--the APUD system) of the lung or other organs in response to tumor growth.

Adrenocorticotropic Hormone↗
PubMed1989

[Nonulcerogenic gastrinoma of the pancreas].

Non-beta-cell adenoma of the islet apparatus in the pancreas was described. The tumor measured 8 X 4 X 4 cm. Histological examination revealed its mixed structure. The tumor was composed of trabecular and solid structures, adenoma-like rosettes, and pericytial muffs. APUD-amyloid was found in its stroma. Application of a specific immunoperoxidase technique and electron microscopy provided good evidence for the fact that the tumor consisted of gastrin-producing cells. In view of clinical features, the tumor was regarded as gastrinoma.

Adult↗
PubMed1975

Hydrosmotic effect of angiotensin II in the toad skin: role of cyclic AMP.

The mechanism of action of the hydrosmotic response of the isolated skin of the toad Bufo arenarum Hensel to angiotensin II was studied by means of an indirect pharmacological approach. Angiotensin II (2.10(-10) M), vasopressin (2.10(-13) M) and theophylline (10(-4) and 10(-3) M) in subliminal doses produced a significant increase on water permeability when added in different paired combinations. Angiotensin II (2.10(-7) M) and vasopressin (2.10(-8) M) in doses producing significant effects on water permeability increased the response to submaximal doses of epinephrine (10(-6) M) but not to higher doses (10(-5) M). Acid pH (6.4) and prostaglandin E1 (2.10(-7) M) reduced significantly the hydrosmotic response to angiotensin II, but in contrast with the toad bladder, the effect was not completely abolished. Present results support the view that the hydrosmotic effect of angiotensin II in toad skin is mediated by the adenylate cyclase - cyclic AMP system.

Adenylyl Cyclases↗
PubMed1982

Experience of the National Cancer Institute (USA) in the treatment and biology of small cell lung cancer.

This retrospective study deals with 168 patients with small cell lung cancer (SCLC) who were treated at the NCI March 1973 and July 1977 with intensive chemotherapy. Results showed that 12 per cent of all the patients were disease-free for more than 40 months (25% of the limited disease and 3% of the extended stage disease patients which were treated. Complete remission was essential to prolonged survival. The development of a complete remission was favored by a satisfactory initial general condition, localised disease or presence of only one site of metastatic disease. Initial treatment included the following combinations: cyclophosphamide, methotrexate and CCNU. High doses are necessary. However, above a certain level, the toxicity increased without a corresponding increment in activity. Addition of another association without cross-resistance (vincristine-adriamycine-natulan or VP-16 and isophosphamide) may induce a complete remission in cases where only a partial remission was obtained initially. In limited disease, radiotherapy seemed to prolong disease-free survival. This lead the authors to study the use of initial radiotherapy, at the rate of 40 grays in 3 weeks in 15 fractions, at the same time as chemotherapy. The radiotherapist must take certain precautions in the use of this double treatment: reshaped fields and insertion of a spinal cord block above 2 000 rads. In extended disease, thoracic irradiation seemed to be of no benefit. Pilot studies are not underway using intensive chemotherapy with multiple tumor site irradiation and autologous marrow implants 48 per cent of all patients with SCLC will develop cerebral metastatic disease (44% intracranial, 13% leptomeningeal, 9% epidural). At 30 months, 75 percent of those who did not receive prophylactic irradiation developed cerebral disease whereas only 40 per cent of the patients who received a prophylactic dose of 30 grays developed cerebral disease. Inspite of the indisputable but incomplete local benefit of prophylactic brain irradiation, it did not prolong survival. Important biological studies are underway at the NCI. - Cell clone cultures have been established. These were enhanced by the addition of arginine vasopressive (AVP) and bombesine. These two substances may be considered as markers of APUD system and are secreted by the SCLC. Bombesine has been isolated in all the cultures tested. This possible marker was perhaps responsible for the anorexia and cachexia in these patients. - These cultures have allowed for identification of deletion 3p (14-23) chromosome anomalies in all the samples examined. - In vitro chemotherapy studies of these cultures have been carried out. Their correlation with clinical results were encouraging (100% negative p/n; 75% positive p/n). - Lastly, monoclonal AC have been prepared. Inspite of their imperfect specificity and heterogeneity with regard to tumor cells, their potential advantages were considerable.

Antineoplastic Agents↗
PubMed1993

[A case of carcinoid tumor of the breast].

A rare tumor of the mammary gland, built up of argyrophilic cells, with numerous metastases in the axillary lymph nodes is reported. Histochemical and electron-microscopic studied unequivocally demonstrated that this tumor belonged to the APUD system. The possible histogenesis of carcinoid tumor of the mammary gland is briefly discussed.

Apudoma↗
PubMedDate not supplied

Superficial undifferentiated small cell carcinoma of the esophagus showing an interesting growing pattern in histology.

We report a case of superficial undifferentiated small cell carcinoma of the esophagus. The histology of the tumor was interesting; there was squamous cell differentiation within the epithelial layer and undifferentiated small cells growing within the submucosal layer. The tumor had a negative Grimelius reaction, suggesting no differentiation into a hormone-producing carcinoma known as an apudoma (Amine Precursor Uptake and Decarboxylation (APUD)). The serum levels of ACTH and calcitonin were within normal limits. As the patient was elderly and had a history of pleural tuberculosis causing poor pulmonary function, and owing to the fulminant nature of this carcinoma, he underwent blunt dissection of the esophagus by posterior mediastinal gastric pull-up. The patient recovered quickly and was able to be discharged with a good quality of life until the tumor recurred as a liver metastasis 6 months later.

Aged↗
PubMed1979

A cytochemical and immunofluorescence study of endocrine cells in the gut of the ascidian Styela clava.

Strong secretin-like immunofluorescence has been demonstrated in endocrine-like cells from the gastric epithelium of Styela. These cells also stain with lead haematoxylin and exhibit a brilliant formaldehyde-induced fluorescence, but do not show any other cytochemical features characteristics of the mammalian APUD series. Tests with antisera to glucagon, gastrin and somatostatin all proved negative. In the oesophagus tests with all four antisera proved negative. The significance of these results is discussed in relation to the phylogeny of vertebrate gastro-intestinal hormones.

Animals↗
PubMed1983

Typical and atypical carcinoids within the pulmonary APUD tumor spectrum.

The behavior of pulmonary APUD tumors is not constant; management is controversial, and morphology has reached its limit as a tool for prognostic assessment and therapeutic planning. We have studied 24 patients with carcinoids; 17 patients with typical carcinoids presented with Stage I disease, but one patient later died most probably of small cell undifferentiated lung cancer (SCLC). Seven patients with atypical carcinoids included three with Stage III cancers, one patient with simultaneous bilateral carcinoids, and one patient with simultaneous adenocarcinoma. Of 17 patients with typical carcinoids, 16 or 92% are disease free or died of unrelated causes. Of seven patients with atypical carcinoids, five or 71% are disease free. Tumor doubling time of atypical carcinoids, was 79.6 months (45 to 120) or six times shorter than that of typical carcinoids (p less than 0.05). Two of the three deaths from cancer were probably from SCLC and one from a synchronous adenocarcinoma. Review of diagnostic material from 12 patients with SCLC who survived a mean of 41 months (24 to 134) showed that diagnosis had rested on cytology alone in four patients and that, in seven patients, the quality or extent of the original diagnostic material was adequate to make the diagnosis of a malignant tumor but inadequate to permit reclassification. Tumor cells from 11 patients with carcinoids (seven typical and four atypical) and 28 patients with SCLC had DNA measurement by image analysis. The mean DNA content of typical and atypical carcinoids and SCLC is 1.17, 1.25, and 1.94 respectively (p less than 0.001). These findings strongly suggest a relationship between DNA content and atypia or malignancy in APUD lung tumors. We conclude that there are at least two levels of virulence among carcinoids represented by typical and atypical carcinoids. The prognosis for treated Stage I typical and atypical carcinoids is excellent. When deaths occur, they are from systemic cancer. Current evidence indicates that DNA measurements by image analysis may help to discriminate levels of malignancy among APUD pulmonary cancers and thereby help to clarify therapeutic controversies.

Adenocarcinoma↗
PubMed2001

[Correlation between cell-functional differentiation phenotype and pathobiological behavior of gastric carcinoma].

OBJECTIVE: To demonstrate the correlation between cell-functional differentiation features and invasion, metastasis of gastric carcinoma (GC) by establishing a new classification based on cell-functional differentiation. METHODS: According to the direction and condition of cell-functional differentiation, 361 gastric carcinomas were divided into five types to show their respective pathobiological behavior. RESULTS: (1) Absorptive functional differentiation type (AFDT): 22.7%(82). 13.6% of the male patients developed liver metastasis, (2) Mucin-secreting functional differentiation type (MSFDT): 15%(54). 98.1% of GC showed serosa invasion, (3) Absorptive and mucin-producing double functional differentiation type (AMPFDT): 49.9% (180). Women infliction (34.4%) and estrogen receptor (ER) expression (71.7%) in this group were more common than in the other types (P < 0.01). 19.4% of these female patients were complicated with ovarian metastasis, (4) Specific functional differentiation type (SFDT): 3.6%(13). 69.2% of these tumors derived from (high) A (amine content) + (high) P (precursor) U (uptake from the ambient medium) + (presence of) D (decarboxylase) (APUD) system and (5) non-functional differentiation type (NFDT): 8.9%(32). 59.4% developed lymphatic metastasis. The 5-year survival rates of these types were 58.5%, 28.6%, 24.7%, 60.0% and 28.1%, respectively. CONCLUSION: This new cell-functional classification of gastric cancer is helpful by indicating their pathobiological behavior and characteristics of invasion and metastasis. Further study is needed to clarify the correlation between cell-functional differentiation phenotypes and their relevant genotypes as well as the inherent relationship between the biological behavior.

Cell Differentiation↗