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

Endocrine pancreatic tumors (EPTs) are rare but have a remarkably better prognosis than adenocarcinoma of the pancreas. Patients with EPTs benefit from surgical and medical therapy, which may alleviate symptoms due to hormonal excess and increase survival. Patients with large or malignant EPTs with infiltrative disease may suffer from local complications, including gastrointestinal bleeding and obstruction and involvement of the superior mesenteric (SMV) and portal (PV) veins. Among 31 patients with operable and large or malignant EPTs, 7 had hormone-producing syndromes (insulin, glucagon), and 24 had clinically nonfunctioning EPTs. Surgery in these patients included vascular reconstruction of the SMV/PV (n = 4), resection of infiltrated adjacent organs (n = 5; stomach, transverse colon), or resection of concomitant liver metastases (n = 3). Four patients with conspicuously large insulinomas, and three with glucagonoma were successfully operated on with alleviation of hormonal symptoms. Among the 24 nonfunctioning EPTs, 5 patients had been explored earlier and their tumors judged inoperable due to locally invasive disease or misdiagnosis as pancreatic adenocarcinoma. The operations were performed with no mortality and low morbidity. We conclude that large and malignant EPTs with limited spread of disease may benefit from a combination of medical and surgical therapy.
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PMID:Surgical strategy for large or malignant endocrine pancreatic tumors. 1103 6

We report a patient with insulinoma associated with Zollinger-Ellison syndrome. A 67-year-old woman was first admitted to our hospital for an abdominal mass. Abdominal computed tomography (CT) revealed a large pancreatic tumor, which was then diagnosed as an unresectable pancreatic adenocarcinoma. At the age of 71, she presented symptoms of hypoglycemia. Fasting blood glucose was 21 mg/dl and plasma immunoreactive insulin level was 846 microU/ ml. Plasma gastrin, glucagon, vasoactive intestinal polypeptide and somatostatin levels were all normal. At the age of 73, hypoglycemic attacks occurred more frequently and she was admitted to our hospital. Abdominal CT scan showed multiple liver metastases. Chemotherapy with 5-fluorouracil and doxorubicin was performed. Three months later, she had an emergency laparotomy because of a perforated duodenal ulcer. Plasma gastrin level was 1,960 pg/ml at that time. Gastric hypersecretion was well controlled with a proton pump inhibitor (lansoprazole) but she died of widespread cancer dissemination 8 years after her first admission. On autopsy, histologic examination revealed a mixed acinar-endocrine carcinoma of the pancreas. Immunohistochemical stains were positive for insulin, gastrin, and alpha1-antitrypsin.
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PMID:Insulinoma with subsequent association of Zollinger-Ellison syndrome. 1139 7

We report a case of a human gastric composite tumor occurring seven years after a partial gastrectomy for a low grade B cell MALT lymphoma. Histological examination of the tumor revealed two intimately intermingled components: 1. A moderately to poorly differentiated tubulo-acinar adenocarcinoma with signet-ring cells; and 2. Isolated or clustered small neuroendocrine cells without atypia expressing chromogranin A, somatostatin and/or glucagon, serotonin (5-HT) and, the 5-HT2B receptors. In addition to immunohistochemical detection, the presence of 5-HT2B receptors was shown pharmacologically through [125I]-DOI binding. Since 5-HT2B receptors have been demonstrated to have autocrine functions and, mitogenic and transforming properties, these results suggest a role of 5-HT in neuroendocrine malignant transformation. On the other hand, the expression of somatostatin and the detection by reverse transcriptase polymerase chain reaction (RT-PCR) of somatostatin receptor subtypes 2, 3, and 5, which have been shown to be involved in tumor regression, might account for the long evolution of this case (> 5 yr). This case illustrates the importance of local humoral modulation in tumor growth. Moreover, ultrastructural results favor a unique origin of the tumor cells from one amphicrine cell type.
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PMID:Histological, immunohistochemical, ultrastructural and biochemical study of human gastric composite tumor: expression of the serotonin-2B receptor by the neuroendocrine component. 1147 72

Several case reports have emphasized that esophageal carcinoid tumors are associated with a poor prognosis. To expand our knowledge about the pathology and biologic behavior of these rare tumors, we reviewed the clinicopathologic and immunohistochemical findings of four cases of primary esophageal carcinoid. The age of the patients ranged from 48 to 82 years (mean 63 years; median 61 years). The lower segment of the esophagus was involved in two cases and the mid segment was involved in one case. The sizes of the tumors ranged from 0.3 cm to 3.5 cm. Two tumors were confined to the lamina propria and two invaded into the muscular wall. Two tumors appeared polypoid, whereas the remaining two were incidental findings and associated with adenocarcinoma arising in a background of Barrett esophagus. The adenocarcinoma was superficially invasive in one case, whereas it penetrated the muscular wall in the other. All four carcinoid tumors were immunoreactive with chromogranin and synaptophysin. There was focal expression of serotonin in two cases, glucagon in one case, and pancreatic polypeptide in one case. Endocrine cell hyperplasia was noted in both the Barrett esophagus and the invasive adenocarcinoma. One patient died secondary to postoperative pneumonia. Three patients are alive and disease free at 1, 6, and 23 years status post therapy. None of the patients had metastatic disease. These findings show that esophageal carcinoids are associated with a favorable prognosis. They arise in two settings: (1) a single large polypoid tumor or (2) an incidental finding and in association with adenocarcinoma arising in the background of Barrett esophagus. The presence of endocrine cell hyperplasia in the Barrett mucosa and the adenocarcinoma supports the hypothesis that these lesions arise from a common stem cell.
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PMID:Carcinoid tumor of the esophagus: a clinicopathologic study of four cases. 1191 32

We report a unique case of gallbladder adenocarcinoma associated with florid neuroendocrine cell nests and extensive Paneth cell metaplasia that has not been described previously. The patient was a 79-yr-old woman with a pedunculated, polypoid mass in the gallbladder. Microscopically, the mass was composed at tumor cells showing tubular and papillary growth patterns, consistent with well-differentiated adenocarcinoma. One-third or more of the tumor cell showed Paneth cell appearance. Goblet cell-type tumors were also intermingled. In addition, neuroendocrine cell nests, that were connected to the neoplastic glands, were scattered throughout the stroma. lmmunohistochemically, the labeling index of MIB-1 in adenocarcinoma cells including Paneth cell-type carcinoma cells was approx 40%. Neuron-specific enolase, chromogranin A, and synaptophysin were positive in the neuroendocrine cells forming solid nests and intermingled within neoplastic glands. They were immunopositive for serotonin but negative for insulin, glucagon, somatostatin, and pancreatic polypeptide (PP). Although MIB-1-positive neuroendocrine cell nests were very few with weak staining, we think that the neuroendocrine cell nests were neoplastic in nature. The formation of the multifocal neuroendocrine nests may be a consequence of the trophic effects of unknown substance(s), which can promote serotonin producing neuroendocrine cells to proliferate. We postulate that Paneth cell-type carcinoma cells may be intimately related to such substance(s) in our case.
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PMID:Gallbladder Adenocarcinoma with Florid Neuroendocrine Cell Nests and Extensive Paneth Cell Metaplasia. 1211 61

The aim of this study was to investigate the role and function of somatostatin, glucagon and gastrin in 35 colorectal adenocarcinoma and 25 liver metastases. The investigation was carried out at the electron immunocytochemistry level. Our results showed that well-differentiated tissues have the highest somatostatin levels compared to poorly-differentiated tumors while glucagon levels remain high. We also found gastrin immunoreactivity in cell membranes of poorly-differentiated primary adenocarcinoma tissues and in liver metastases. Low somatostatin expression, high glucagon expression and the presence of gastrin were found in tumors of poor grading and therefore poor prognosis.
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PMID:Immunoelectron study of somatostatin, gastrin and glucagon in human colorectal adenocarcinomas and liver metastases. 1217 92

To clarify whether scattered endocrine cells in pancreatic ductal adenocarcinoma are neoplastic or not, we immunohistochemically studied 29 cases of invasive pancreatic ductal adenocarcinomas, 17 with metastases, for chromogranin A, insulin, glucagon, pancreatic polypeptide, serotonin, gastrin, laminin, and Ki-67. Endocrine cells were found in primary sites in 24 cases (82.3%), where endocrine cells showed at least a visibly close location to adjacent islet cells. Although endocrine cells in neoplastic glands were within the neoplastic basement membrane, endocrine cells were not seen in invasive sites beyond the pancreas where islets were not present. Endocrine cells in neoplastic glands were reactive for two or three of the islet hormones in all cases, and different types of hormonal reactivity was recognized in the same neoplastic gland or the same cluster of neoplastic glands in 22 (91.7%) cases, thus suggesting a close relation with islets. Ki-67 did not stain any endocrine cells in ten of the adenocarcinomas studied. In three (10.3%) cases, endocrine cells were found in the intraductal extensions. They may have pre-existed in non-neoplastic ducts. In 17 cases with metastatic sites, all but one had no endocrine cells in the metastases. Serotonin-positive cells were found in one metastatic lymph node in one case. We concluded that most endocrine cells seen in ductal adenocarcinomas of the pancreas are non-neoplastic and are derived from the surrounding islets. Some neoplastic endocrine cells may exist, though their frequency is low.
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PMID:Immunohistochemical study of endocrine cells in ductal adenocarcinoma of the pancreas. 1224 21

Extensive pancreatectomy (EP) may increase the resection rate of pancreatic adenocarcinoma (PA). Unfortunately, EP often results in unstable diabetes. Recently, islet autotransplantation (auto-Tx) has offered the potential to prevent this metabolic disorder. Because of the fear of contamination of prepared islets by malignant cells, this procedure has so far not been used as a treatment for PA. We herein report a case of a 63-year-old nondiabetic patient who underwent EP combined with islet auto-Tx in an emergency operation following histologically proved R(0)-resection for PA (pT(3)pN(1)G(2)). Islets were isolated from the excised pancreas using a continuous digestion filtration device. The resultant preparation was injected into the portal vein. Owing to the moderate fasting hyperglycemia, postoperative exogenous insulin therapy was necessary (26 U/d). After discharge, the patient's daily insulin dose was gradually reduced. At 1-year follow-up the fasting C-peptide level was 0.66 ng/mL, and an oral glucose tolerance test (oGTT) and an intravenous (IV) glucagon stimulation (GS) showed functioning engrafted islets. The K-ras mutations were detected in the paraffin-embedded PA, but not in the prepared islets or in the peripheral blood. Computed tomographic (CT) imaging revealed neither local tumor recurrence nor liver metastases. At 2-year follow-up, the patient was on a balanced food regimen and gaining weight. Although he remains insulin-dependent (16 U/d), he is metabolically stable (HbA(1)(c) 5.9%). The fasting C-peptide level is 0.68 ng/mL. The peak value of C-peptide in response to oGTT was 0.92 ng/mL and to GS 0.89 ng/mL. At this time Ca19-9 and CEA are increased to 35.3 U/mL and 19.2 ng/mL, respectively. The patient died 2.5 years after operation owing to tumor recurrence. There was no evidence for liver metastases. We postulate that histologic evaluation (R(0)-resection) and detection of K-ras mutations may be useful techniques. However, islet auto-Tx after EP for adenocarcinoma should only be regarded for rescue therapy. Studies on strategies to exclude possible contamination of islet tissue with carcinoma cells are critically important.
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PMID:Islet autotransplantation combined with pancreatectomy for treatment of pancreatic adenocarcinoma: a case report. 1519 92

Small cell carcinomas of the uterine cervix are rare tumors with an aggressive behavior. Although these tumors can exhibit neuroendocrine differentiation, the criteria for neuroendocrine differentiation are subjective and not well defined. In this study, the authors tentatively defined small cell neuroendocrine carcinoma (SCNEC) as a tumor composed of small cells with at least two of the following: argyrophilic cytoplasm, chromogranin A immunoreactivity, and synaptophysin immunoreactivity. We found 10 cases fulfilling these requirements. Five of the 10 tumors were composed mainly of small ("oat") cells and 5 of mainly larger "intermediate" cells. The majority of both subtypes showed an insular pattern. Three of the 10 SCNECs were pure, whereas the other seven were mixed with adenocarcinoma and/or squamous cell carcinoma or cervical intraepithelial neoplasia. In addition to the definitional markers noted earlier, the tumors were immunoreactive for serotonin (6 cases), somatostatin, gastrin, glucagon, and pancreatic polypeptide. No tumors were immunoreactive for cytokeratin 20. Human papillomavirus (HPV)-18 was detected in all of the pure tumors and both the SCNEC and adenocarcinomatous components in four of the mixed tumors. No other types of HPV were detected. The tumors showed a relatively low frequency of loss of heterozygosity for representative tumor suppressor gene sites; p53 mutations were found in only one case.
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PMID:Small cell neuroendocrine carcinomas of the uterine cervix: a histological, immunohistochemical, and molecular genetic study. 1538 6

The aim of this study was to investigate the ultrastructural appearance of mirror biopsies from primary colorectal adenocarcinomas combined with serotonin, vasoactive intestinal polypeptide, bombesin, somatostatin and glucagon expression in order to clarify the histology and immunology of these tissues compared with colorectal adenocarcinomas. The investigation was carried out in 90 cases of mirror biopsies by electron microscope immunocytochemistry. The ultrastructural study revealed that some cases (30%) of mirror biopsies were characterized by the presence of intracellular changes compared to normal tissues. The most significant of them were the presence of swollen abnormal mitochondria and the increased number of the secretory cells. The above enzymic and secretory changes were confirmed by electron immunogold results. Bombesin and VIP appeared to be located in enterochromaffin-like (ECL) endocrine cells primarily responsible for the production of serotonin. Somatostatin was located in D cells while we found numerous glucagon (EG) immunoreactive cells. In conclusion, low somatostatin expression, high glucagon and serotonin expression and the ectopic secretion of VIP and bombesin neuropeptides in mirror biopsies indicate the preneoplastic nature of these tissues and may be useful for the optimal treatment of patients with colorectal adenocarcinoma.
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PMID:Electron immunocytochemical demonstration of serotonin, vasoactive intestinal polypeptide, bombesin, somatostatin and glucagon in mirror biopsies from primary colorectal adenocarcinoma. 1559 39


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