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NCI CANCERLIT^® Search: Islet Cell Carcinoma - October 2002

National Cancer Institute^®
Last Modified: October 1, 2002

Neuropilin-2 is a novel marker expressed in pancreatic islet cells and endocrine pancreatic tumours.
[Insulinoma with hyperproinsulinemia: a two cases report]
Radioguided surgery for gastrinoma: a case report.
[Pancreatic neuroendocrine tumors: how far have we gone ahead?]
ACTH-secreting islet cell tumor of the pancreas presenting as bilateral ovarian tumors and Cushing's syndrome.
[Glucagonoma: evolution and treatment]
Processed electroencephalographic changes associated with hypoglycemia during the resection of an insulinoma.
Immunocytochemical localization of prohormone convertase 1/3 and 2 in pancreatic islet cells and islet cell tumors.
Identification of a human insulinoma cDNA encoding a novel mammalian protein structurally related to the yeast dibasic processing protease
Immunohistochemical assessment of an asymptomatic glucagonoma in a patient with hypergastrinemia and marked antral angiodysplasia.
[Morphologic and functional study of a human insulin-secreting cell line]

Table of Contents

1
UI - 12210066
AU - Cohen T; Herzog Y; Brodzky A; Greenson JK; Eldar S; Gluzman-Poltorak Z;
TI - Neufeld G; Resnick MB Neuropilin-2 is a novel marker expressed in pancreatic islet cells and endocrine pancreatic tumours.
SO - J Pathol 2002 Sep;198(1):77-82
AD - Department of Pathology, Carmel Medical Center and Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.
Neuropilin-2 (NP-2) is a cell surface transmembrane protein originally characterized as a receptor for the type 3 semaphorins, and more recently for a number of vascular endothelial growth factor (VEGF) isoforms. NP-2 expression has been recently localized to a subset of neuroendocrine cells in the gastrointestinal tract. The aim of this study was to define the expression pattern of NP-2 in normal pancreatic islets and to determine the utility of NP-2 expression as a diagnostic marker of pancreatic endocrine tumours. Paraffin-embedded tissue sections from 30 endocrine pancreatic tumours (EPTs) and from normal pancreas were immunostained with a rabbit polyclonal antibody generated towards NP-2. Nineteen of the tumours were hormonally functional (nine insulinomas, nine gastrinomas, and one glucagonoma). The NP-2 staining pattern was correlated with islet cell hormone expression. In addition, NP-2 expression was evaluated in other normal neuroendocrine tissues and neuroendocrine neoplasms. In normal pancreas, NP-2 stained a distinct subset of islet cells situated primarily at the islet periphery. Double immunohistochemical staining revealed co-localization with glucagon-expressing cells. Moderate to strong NP-2 staining was present in 27 of 30 EPTs. Serial staining of the pancreatic tumours with insulin, gastrin, glucagon, pancreatic polypeptide (PP) or somatostatin did not reveal a distinct pattern of co-localization. NP-2 expression was not detected in neuroendocrine cells outside the gastroenteropancreatic system, or in their corresponding neoplasms, except for focal staining in one bronchial carcinoid tumour. In conclusion, the vast majority of EPTs examined expressed NP-2, suggesting its utility as a diagnostic marker for these tumours. The function of NP-2 in islet cell biology or tumourigenesis remains to be elucidated. Copyright 2002 John Wiley & Sons, Ltd.

2
UI - 12193882
AU - Gury H; Rio F; Neamtu D; Boivin S
TI - [Insulinoma with hyperproinsulinemia: a two cases report]
SO - Ann Endocrinol (Paris) 2002 Jun;63(3):240-2
AD - Service de medecine D, Hopitaux civils, 68024 Colmar Cedex, France.
We report two cases of insulinoma with increased serum proinsulin levels and with normal insulin levels.Clinically, the two patients show typical symptoms of insulinoma, but serum insulin levels are normal.Only high levels of serum proinsulin allow us to retain the diagnosis of insulinoma. The new insulin assays using monoclonal antibodies are very specific for insulin and though can not detect isolated high proinsulin levels. So proinsulin assay is useful when diagnosing insulinoma.

3
UI - 12365386
AU - Albertario S; Forti P; Bianchi C; Morone G; Tinozzi FP; Moglia P; Abelli
TI - M; Benedetti M; Aprile C Radioguided surgery for gastrinoma: a case report.
SO - Tumori 2002 May-Jun;88(3):S41-3
AD - Istituto di Chirurgia Generale e dei Trapianti d'Organo, Universita degli Studi di Pavia, Italy.
AIMS AND BACKGROUND: Gastrinomas are the most common neuroendocrine tumors of the duodenopancreatic region. Surgical resection is the primary type of radical treatment. METHODS AND STUDY DESIGN: At the Institute of General, Gastrointestinal and Breast Surgery we treated a patient with a duodenal gastrinoma that was diagnosed and localized by means of selective celiac-mesenteric angiography and labelled octreotide scintigraphy. Surgery was performed using a radioguided technique; in this way we easily detected the small tumor and discovered another tracer-uptaking lesion that turned out to be a metastatic lymph node. RESULTS: Surgical resection is the ideal treatment for sporadic gastrinoma: it improves quality of life, prolongs survival, and reduces the incidence of metastases, with a modest percentage of complications and practically zero mortality. Meanwhile, medical treatment is being reevaluated, particularly in the case of metastatic disease or polyendocrine MEN1 syndrome. A fundamental aspect in the management of gastrinomas is tumor localization. Endoscopic ultrasonography and labeled octreotide scintigraphy (Ostreoscan) proved to be more effective than the usual imaging modalities. Intraoperative ultrasonography gastroscopy for duodenal transillumination and repeated measurement of blood gastrin levels should be performed intraoperatively in the surgical treatment of gastrinomas. CONCLUSIONS: The clinical application of radioguided surgery for tracer-uptaking endocrine tumors is still controversial. In our case the decision to use this method was influenced by the fear that the patient's obesity and the effects of previous surgery could hamper the identification of the small tumor.

4
UI - 12060541
AU - Molina Villaverde R; Gonzalez Baron M
TI - [Pancreatic neuroendocrine tumors: how far have we gone ahead?]
SO - Rev Clin Esp 2002 May;202(5):269-71
AD - Servicio de Oncologia Medica, Hospital La Paz, Madrid, Spain.

5
UI - 12068175
AU - Oberg KC; Wells K; Seraj IM; Garberoglio CA; Akin MR
TI - ACTH-secreting islet cell tumor of the pancreas presenting as bilateral ovarian tumors and Cushing's syndrome.
SO - Int J Gynecol Pathol 2002 Jul;21(3):276-80
AD - Department of Pathology and Human Anatomy, Loma Linda University and Medical Center, California 92350, USA.
A 41-year-old woman presented with hirsutism, a pelvic mass, and Cushing's syndrome. Imaging studies revealed bilateral ovarian masses and a solid and cystic mass within the pancreas. Partial pancreatectomy, bilateral oophorectomy, and excision of several peritoneal tumor nodules were performed. Pathological examination revealed a neuroendocrine islet cell tumor of the pancreas with bilateral ovarian metastases. The tumor was immunoreactive for ACTH, chromogranin, neuron-specific enolase, and keratin. The patient received postoperative chemotherapy and has been disease-free for 6 years. To our knowledge, this is the first reported case of an ACTH-secreting pancreatic neuroendocrine tumor presenting as bilateral ovarian metastases.

6
UI - 12194691
AU - Carvajal C; Azabache V; Lobos P; Ibarra A
TI - [Glucagonoma: evolution and treatment]
SO - Rev Med Chil 2002 Jun;130(6):671-6
AD - Clinica Las Condes y Facultad de Medicina de la Universidad de Chile, Santiago de Chile. coloclc@entelchile.net
Glucagonomas are alpha pancreatic islet cell tumors that, when they are active, produce a syndrome characterized by necrolytic migratory erythema, diabetes mellitus, weight loss, anemia, glossitis, thromboembolism, neuropsychiatric disturbances and hyperglucagonemia. We report a 43 years old male presenting with a five years history of dermatological lesions, associated with weight loss, glossitis and onicodystrophy. Serum glucagon was 2200 pg/ml and a CAT scan showed a tumor in the tail of the pancreas. The tumor was surgically excised but one year later, hepatic metastases were found. These were excised surgically, treated with long acting octeotride and finally treated with radiotherapy using Y-DOTATOC. In the last control in November, 2001, the patient is asymptomatic.

7
UI - 12357174
AU - Hausman LM
TI - Processed electroencephalographic changes associated with hypoglycemia during the resection of an insulinoma.
SO - Anesthesiology 2002 Oct;97(4):1013-4
AD - Department of Anesthesiology, The Mount Sinai School of Medicine, New York, New York 10029, USA. Laurence.Hausman@mssm.edu

8
UI - 11484919
AU - Tomita T
TI - Immunocytochemical localization of prohormone convertase 1/3 and 2 in pancreatic islet cells and islet cell tumors.
SO - Pancreas 2001 Aug;23(2):172-6
AD - Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City 66160, USA.
Peptide hormones are synthesized as bigger prohormones, which are processed posttranslationally into smaller active hormones. Proinsulin and proglucagon are processed into insulin and glucagon by prohormone convertase (PC) 1/3 and 2. The current study was performed to test a hypothesis that there may be some difference in immunoreactive PC levels between normal islet cells and islet cell tumors, as the latter contain more prohormones than the former. All islet cell tumors, including insulinomas, gastrinomas, glucagonomas, pancreatic polypeptide-omas (PP-omas), and nonfunctioning islet cell tumors, contain fewer PCs than normal islet cells. The smaller PC levels in islet cell tumors may be responsible for the higher levels of prohormones in islet cell tumors, and the smaller levels of PCs in islet cell tumors may be another distinguishing characteristic of islet cell tumors.

9
UI - 2154467
AU - Smeekens SP; Steiner DF
TI - Identification of a human insulinoma cDNA encoding a novel mammalian protein structurally related to the yeast dibasic processing protease Kex2.
SO - J Biol Chem 1990 Feb 25;265(6):2997-3000
AD - Howard Hughes Medical Institute, Chicago, Illinois.
We have identified a human insulinoma cDNA (PC2) that encodes a protein homologous to the precursor processing Kex2 endoprotease of yeast by using a polymerase chain reaction to detect and amplify conserved sequences within the catalytic site. The 638-residue amino acid sequence of PC2 begins with a cleavable signal peptide, indicating that it enters the secretory pathway, and contains a 282-residue domain that is homologous to the catalytic modules of both Kex2 and the related bacterial subtilisins. Within this region 49 and 27% of the amino acids are identical to those in the aligned Kex2 and subtilisin BPN' sequences, respectively, and the catalytically essential Asp, His, and Ser residues are all conserved. Northern blot analysis revealed the presence of 2.8- and 5.0-kilobase hybridizing bands in mRNA from the insulinoma. The PC2 protein also shows great similarity to the incomplete NH2-terminal sequence of the human furin gene product, a putative membrane-inserted receptor-like molecule. We propose that PC2 is a member of a family of mammalian Kex2/subtilisin-like proteases that includes members involved in a number of specific proteolytic events within cells, including the processing of prohormones.

10
UI - 11277423
AU - Weitgasser R; Sungler P; Hauser-Kronberger C; Dietze O; Sattlegger P;
TI - Hacker GW Immunohistochemical assessment of an asymptomatic glucagonoma in a patient with hypergastrinemia and marked antral angiodysplasia.
SO - Appl Immunohistochem Mol Morphol 2001 Mar;9(1):92-6
AD - Department of Medicine I, Institute of Pathology, Landeskliniken Salzburg, Austria, EU.
A 58-year-old patient had been treated for recurrent gastritis. Numerous gastroscopies indicated hemorrhagic gastritis combined with increasingly severe anemia. The patient was admitted with a hemoglobin of 4.4 g/dL. Gastroscopy showed marked antral angiodysplasia. Serum samples for gastrin were taken and found to be elevated (170-250 U/mL). The search for a gastrin-producing tumor with abdominal ultrasound, computed tomography, octreotide scan, and secretin test was negative, but angiography detected a pancreas tumor with a 2-cm diameter. Partial pancreatectomy and partial gastrectomy were performed. Immunohistochemical examination of the tumor did not show a gastrinoma but did show glucagon-reactive tissue. Further tumors or elevated plasma hormone levels were not detected, and a multiple endocrine neoplasia type I syndrome could be excluded. We thus found antral angiodysplasia with hypergastrinemia leading to detection of a glucagonoma diagnosed by immunohistochemistry. After more than 4 years of follow-up, the patient is without any symptoms or signs of relapse or secondary hormone syndrome.

11
UI - 3022894
AU - Thivolet C; Chatelain P; Haftek M; Durand A; Pugeat M
TI - [Morphologic and functional study of a human insulin-secreting cell line]
SO - C R Acad Sci III 1986;303(10):381-6
Monolayer cell cultures were obtained from a human insulinoma (HIN) after collagenase digestion. HIN cells were initially plated on extracellular matrix (ECM) secreted by bovine corneal endothelial cells. Capsular integrity from cell clusters quickly interrupted and cell began to migrate as adhesive sheets onto ECM. After 2 months on ECM cell attachment and proliferation occurred on plastic allowing cloning of cells by limiting dilution. 9 clones were successfully cultured for 7 months with 20 subsequent passages. Immunoreactivity for insulin by indirect immunofluorescence typical secretory granules by electron microscopy and stable amounts of immunoreactive insulin in culture media suggest that HIN cells are beta cell related. One clone HIN D8 when challenged for half an hour with either 30 mM glucose, 1 mM isobutyl Methylxanthine 4 mM Tolbutamide, 10(-6) M glucagon responded respectively with a 1.5, 2, 3 and 1.5 fold increase in insulin output. Population doubling time of HIN D8 was 42 hrs. Establishment of such insulin secreting cell lines provides a valuable tool for diabetes research.

The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.

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