Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cystic islet cell tumors of the pancreas are extremely rare. The authors report their personal experience with two cases of nonfunctioning cystic endocrine neoplasms. The tumor was diagnosed preoperatively in one case by ultrasonography (US)-guided fine-needle aspiration cytology, while in the other it was identified only in the surgical specimen after a clinical-radiologic diagnosis of pancreatic mucinous cystic tumor. Immunohistochemical assay showed positivity for the generic neuroendocrine markers (neuron specific enolase, or NSE, synaptophysin, and chromogranin A) in both cases and also for glucagon in one case. The neoplasms were resected by distal pancreatectomy with splenectomy and intermediate pancreatectomy respectively. Both patients are alive and recurrence-free 6 mo and 2.5 yr, respectively, after surgery. The authors also review the existing literature, discussing the pathogenesis of such tumors and the imaging techniques and surgical strategies adopted in their management.
 ...
PMID:Cystic islet cell tumors of the pancreas. A clinico-pathological report of two nonfunctioning cases and review of the literature. 132 29

90 primary breast carcinomas and 18 metastases were immunostained for c-erbB-2 protein and neuron specific enolase. 30 tumours were c-erbB-2 negative and NSE positive, 23 tumours were NSE negative and c-erbB-2 positive. 1 tumour expressed focal immunoreactivity for both markers. 54 of the 108 tumours (50%) did not express either marker. Hormone immunoreactivity was present in single cells and in small groups of cells in 18 of the 31 NSE positive tumours. Bombesin, neurotensin and prealbumin were present in 4 cases each, followed by beta-endorphin and VIP in 3 cases each, leu-enkephalin in 2 cases and gastrin, serotonin, substance P, glucagon and somatostatin in 1 case each. None of 10 NSE negative breast carcinomas were comprised of cells expressing immunoreactivity for hormones. By immunoelectron microscopic examination the c-erbB-2 protein was shown to be present on the cell membrane, on smooth areas, microvilli and in coated pits. Immunoreactivity was also expressed in vesicles in cytoplasm and along rough endoplasmic reticulum. The study shows that c-erbB-2 protein expression and neuroendocrine activity are present in different tumour cell populations. This supports the hypothesis that the presence of c-erbB-2 protein, indicating an elevated cellular tyrosine kinase activity with stimulation of growth, intracellular Ca++, and phosphatidylinositol derivates, means that the same cell does not need regulation of the same factors by stimulation of peptide hormone receptors. Thus the production of autocrine and paracrine factors is switched off.
 ...
PMID:C-erbB-2 protein and neuroendocrine expression in breast carcinomas. 167 29

A 54 year old woman suffered from acromegaly due to a pancreatic islet cell tumour producing GHRH. The tumour was demonstrated on CT scan. The diagnosis was established from elevated plasma levels of GHRH, GH and prolactin, and by the lack of signs of a pituitary adenoma in trans-sphenoidal surgery. Acromegaly was cured by tumour removal. Light microscopically, the tumour showed a medullary and microlobular pattern. The cells were large and often cuspidal. Small granules were found in semi-thin sections. Small aggregations of amyloid fibres were seen, mostly around capillaries. Immunocytochemistry revealed GHRH, NSE, neurotensin, serotonin, VIP and PP. S 100 was positive only in nerve fibres. Staining for GH, ACTH, calcitonin, alpha-HCG, beta-HCG, insulin, glucagon, gastrin, substance P, bombesin and somatostatin was negative. Ultrastructure showed oval partly lobulated nuclei with small nucleoli, moderate amounts of rough endoplasmic reticulum, many free ribosomes, some large Golgi fields and small numbers of secretory granules measuring 150 nm or, in a few cells, 650 nm. Only 4 other cases of pancreatic endocrine tumours causing acromegaly by ectopic GHRH secretion are described in the literature and these were similar to our case in many respects.
 ...
PMID:Morphology of a GHRH producing pancreatic islet cell tumour causing acromegaly. 301 79

Ten cases of cerebellar haemangioblastoma were studied using the immunoperoxidase technique for glial fibrillary acidic protein (GFAP), Factor VIII-related antigen (F8RA), Ulex europeus agglutinin 1 (UEA-1), S-100 protein, neurone-specific enolase (NSE), leucocyte common antigen, synaptophysin, chromogranin and eight polypeptide hormones (bombesin, pancreatic polypeptide, somatostatin, thyroglobulin, calcitonin, glucagon, insulin and gastrin). GFAP and S-100 were demonstrated at the periphery of all tumours and in small groups of cells in the centre of four cases. Most of these cells had the morphology of reactive astrocytes but some had the appearance of stromal cells. In general stromal cells gave negative results. F8RA and UEA-1 stained the endothelial cells in each case but there was no stromal cell reactivity. NSE was present in the stromal cell component of all tumours. There was no staining for synaptophysin, for chromogranin, or any of the polypeptide hormones. It therefore appears that some haemangioblastomas contain an admixed non-neoplastic astrocytic element. NSE, F8RA and UEA-1 staining demonstrates that the endothelial and stromal cell parts of the tumour are antigenically distinct. Recent reports of polypeptide hormone expression cannot be confirmed and it is therefore unlikely that stromal cells originate from primitive peptidergic neurones.
 ...
PMID:Haemangioblastoma. An immunohistochemical study of ten cases. 339 96

Seven cases of PCNP were studied; 5 females and 2 males, ages ranging from 21 to 68 years (mean 39). All had asymptomatic masses located in the head (3), body (2), isthmus (1) and tail (1). In 4 of them fine-needle aspiration (FNA) was done and showed a diagnostic pattern with papillary clusters as well as isolated epithelial cells with monomorphic appearance, round nuclei and inconspicuous nucleoli; 5 cases had a surgical resection and only 2 a biopsy due to unresectable tumors. Histologically, they showed the typical features of PCNP with solid, papillary, trabecular and cystic patterns. IHQ studies showed positivity for cytokeratin (n = 5), alpha-1-antitrypsin (n = 4), monoclonal NSE (n = 3), chromogranin (n = 3) and estrogen receptors (n = 1). All cases were negative for insulin, glucagon, somatostatin, EMA and CEA. DNA analysis done with an image analyzer showed 4 diploid tumors, 2 diploid-tetraploid an 1 aneuploid tumor. One patient died because of postoperative complications and the remaining 6 are alive with a mean follow-up of 17 months (2-36). We emphasize the diagnostic appearance of the tumor on FNA, and the low grade malignant potential of this neoplasm supported by the predominance of diploid tumors. Our IHQ findings suggest both an exocrine and endocrine differentiation.
 ...
PMID:[Papillary and cystic tumors of the pancreas. Clinico-pathological, cytopathological, immunohistochemical, and nuclear ploidy study]. 808 43

Two cases are described of an unusual form of primary adenocarcinoma of the pancreas characterized histologically by their striking resemblance with a neuroendocrine neoplasm. The tumors were composed of a population of relatively small, uniform cells arranged in sheets admixed with small microglandular structures resulting in a cribriform pattern of growth. The tumor cells displayed scant cytoplasm with indistinct cell borders and round to oval nuclei with irregular clumping of chromatin and small, inconspicuous nucleoli. Immunohistochemical studies in both cases showed positivity of the neoplastic cells with CAM 5.2 antibodies and negative staining with a battery of neuroendocrine-related markers including chromogranin, NSE and synaptophysin, as well as with a variety of peptide hormones including insulin, glucagon, vasoactive intestinal polypeptide, gastrin and serotonin. Ultrastructural examination revealed a cohesive population of cells forming abortive glandular lumens lined by imperfectly formed microvilli and showing well-developed junctional complexes. No dense core neurosecretory granules or zymogen granules could be identified in any of the cells, supporting a ductal type of differentiation for these tumors. The main importance of recognizing this rare variant of pancreatic adenocarcinoma lies in avoiding misdiagnosis with other primary and metastatic neuroendocrine neoplasms of this organ. Immunohistochemical and ultrastructural examination will be of value in such cases for differential diagnosis.
 ...
PMID:Microglandular carcinoma of the pancreas: immunohistochemical and ultrastructural study of an unusual variant of pancreatic carcinoma that may closely resemble a neuroendocrine neoplasm. 916 70

Medullary thyroid carcinoma (MTC) is an APUDoma (APUD refers to amine precursor uptake and decarboxylation) arising from the parafollicular cells. Diarrhoea has been reported in some 30% of patients, variously attributed to excess production of calcitonin (CT), serotonin (5-HT), vasoactive intestinal peptide (VIP) or other factors. The regulatory factors in MTC were examined employing immunocytochemistry and RIA to tumours and their extracts. The patients were followed up for more than 15 years. CT and calcitonin gene-related peptide were universally expressed in all the tumours. The neuroendocrine markers chromogranin A (and its fragments pancreastatin and WE-14), neurone-specific enolase, protein gene product 9.5 and carcino-embryonic antigen were found in the majority of MTCs and might be useful as immunocytochemical markers. 5-HT, substance P, neurokinin A, glucagon and VIP could not be detected, excluding them as candidates in the diarrhoea of MTC.
 ...
PMID:Regulatory peptides and other neuroendocrine markers in medullary carcinoma of the thyroid. 907 85

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is characterized by hyperinsulinism and profound hypoglycemia, with most children requiring pancreatic resection. The histological classification of PHHI is controversial. Most authors acknowledge the existence of focal areas of islet cell proliferation (adenomatosis) in 30%-50% of cases and a diffuse disorganisation of islet architecture, termed "nesidiodysplasia," in others. De Lonlay et al. reported that cases with adenomatosis are focal with normal remainder of pancreas and that focal and diffuse disease can be differentiated intraoperatively, on the basis of increased beta-cell nuclear size found only in the diffusely abnormal pancreas. We have examined pancreatic histology in a blinded controlled study of PHHI patients. Pancreatic tissue was obtained at autopsy from 60 normal subjects (age 17 weeks gestation to 76 years) and from surgical specimens of 31 PHHI patients. Sections from PHHI subjects (n = 294 blocks) and control sections were stained with hematoxylin and eosin, insulin, glucagon, somatostatin, NSE, cytokeratin 19, and vimentin. Three sections from each PHHI patient were randomly chosen for further analysis. Age-matched control (n = 34) and PHHI sections (n = 66) were examined, with the identity of subjects concealed. A diagnosis of normal histology, adenomatosis, or diffuse nesidiodysplasia was recorded for each section. The presence of large beta-cell nuclei (>19 microm), ductuloinsular complexes, and centroacinar cell proliferation was noted. Of a total of 65 subjects examined (34 control and 31 PHHI), 37 subjects were identified as normal on both sections examined. All the control cases were correctly identified as normal and none had large beta-cell nuclei or centroacinar cell proliferation. Of 31 PHHI patients, 28 were identified as abnormal, either on the basis of abnormal architecture and/or abnormally large beta-cell nuclei. Three patients were identified as normal in both sections. Fifteen of 31 patients had diffuse nesidiodysplasia only. Of 13 patients with areas of adenomatosis, 2 had resection of a nodule with adenomatosis present in most of the tissue removed at surgery. Nine patients had a diagnosis of adenomatosis in one section and a diagnosis of diffuse nesidiodysplasia in the other sections from nonadjacent pancreas. Only 2 of 31 PHHI cases had adenomatosis on one section examined and normal pancreas on the other section examined. Large beta-cell nuclei were variably found in PHHI sections. Only 5 of 15 patients with diffuse nesidiodysplasia had large nuclei in both sections examined. Centroacinar cell proliferation was identified in 12 PHHI subjects, 6 with adenomatosis and diffuse nesidiodysplasia and 6 with diffuse changes only. It was patchy in distribution within sections and present in only one section in 7 of the 12 subjects. In summary, we have shown that a blinded observer could differentiate control and PHHI pancreatic tissue. Only 2 of 31 patients (6%) had focal adenomatosis with normal nonadjacent pancreas, the majority (24 of 31) had diffuse nesidiodysplasia affecting the remainder of their pancreas, with 38% (9 of 24) also having areas of adenomatosis. Large beta-cell nuclei did not reliably identify those with diffuse disease in this study. There was evidence of significant ductal and centroacinar proliferation in 39% of PHHI cases, which was not observed in any of the controls. We have shown that PHHI subjects have a spectrum of pancreatic histological abnormalities, from no abnormality to diffuse subtle changes to florid adenomatosis. Patients could not be segregated into subtypes for different operative intervention despite the availability of full immunohistochemical staining.
 ...
PMID:Histologic findings in persistent hyperinsulinemic hypoglycemia of infancy: Australian experience. 1100 Mar 31

Neuroendocrine tumors are an interesting group of neoplasmas of the digestive system. A possibility of appearance of syndromes connected with hormonal activity is their common feature. Some of them are not hormonally active and they do not manifest hormonal hyperactivity. The authors present 2 patients with malignant neuroendocrine pancreatic tumors in whom the lack of clinical syndromes connected with overproduction of hormone resulted in the establishment of the diagnosis in an advanced stage of the disease. The tumors were not clinically active but immunohistochemical examinations revealed the presence of hormones in cytoplasmatic granules. Both patients had positive immunostaining for VIP, NSE and chromogranin. Moreover, in one of the patients positive staining for ACTH and glucagon and in another for PGP 9.5 was obtained.
 ...
PMID:[Neuroendocrine pancreatic tumors]. 1504 16

Large cell neuroendocrine carcinoma of the urinary bladder is rare. In the last five years, we have had the opportunity to see this type of cancer in an 88-year-old and in a 66-year-old males. In both cases, transurethral resection of carcinoma of the bladder was carried out. In the first case, urothelial carcinoma was detected and deeper in the bladder wall, large cell neuroendocrine carcinoma structures were found. In the second case, the bladder was only infiltrated with large cell neuroendocrine carcinoma. Both tumors expressed NSE, CD56 and synaptophysin. Other markers, such as those against calcitonin, chromogranin, PP, VIP, serotonin, gastrin, glucagon and somatostatin did not react with the tumor. In the first case, no tumor dissemination was found; in the second case, clinical methods confirmed dissemination into the liver, left adrenal gland, spleen and paracaval lymph nodes. Given his age, the first patient only received symptomatic therapy. The other patient underwent chemotherapy and his condition is stable. Paraneoplastic manifestations of the tumors were not clinically found. Histogenetic origin of neuroendocrine tumors is not fully clarified. In some cases, tumor development is thought to be associated with Brunns nests, cystitis cystica and urothelial carcinoma stem cells.
 ...
PMID:[Primary large cell neuroendocrine carcinoma of the urinary bladder]. 2364 13


1