Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007095 (carcinoid)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A radioimmunoassay of human pancreastatin was developed using a rabbit antiserum that selectively recognized the C-terminal amidated end of the peptide, and it was used for the identification of the molecular forms of pancreastatin in human gut (stomach, duodenum, small intestine, colon) and endocrine tumor extracts (liver metastasis of a gastrinoma and a medullary carcinoma of thyroid, one nonsecreting pancreatic tumor, one recurrence of a gut carcinoid, one vipoma and one insulinoma). In all gut extracts, a gel filtration chromatography revealed the presence of three peaks of pancreastatin-like immunoreactivity. The predominant form eluted with an apparent molecular weight higher than that of pancreastatin. This form was also predominant in the endocrine tumors analyzed, except in the insulinoma, where a lower molecular weight form predominated. The high molecular form was further purified from a liver metastasis of a gastrinoma. The pancreastatin-like immunoreactivity eluted in all the chromatographical systems (reverse-phase, ion exchange) as a single peak that was finally purified to homogeneity and sequenced. The sequence of the first 29 N-terminal amino acids was obtained unambiguously and corresponded to the sequence 210-238 of chromogranin A. Considering the selectivity of the assay used for peptide identification, this major form was identified as the fragment 210-301 of chromogranin A. It is likely that the predominant form of pancreastatin in human gut extracts and noninsular tumors is a 92 amino acid peptide.
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PMID:Chromogranin A(210-301) is the major form of pancreastatin-like material in human gut extracts and endocrine tumors. 798 7

The presence of somatostatin receptors has been demonstrated in various endocrine tumors as well as in normal tissues. We recently have cloned five human somatostatin receptor subtypes (SSTR1-SSTR5). These mRNAs are expressed in a tissue-specific manner. In this study, we have determined the somatostatin receptor subtypes expressed in various endocrine tumors using a reverse transcriptase polymerase chain reaction method. In two cases of glucagonoma and its metastatic lymph nodes in one case, all the SSTR subtype mRNAs except SSTR5 mRNA were expressed. In four cases of insulinoma, SSTR1 and SSTR4 mRNAs were detected, but SSTR2 mRNA was not detected in one case and SSTR3 mRNA was not detected in two cases, indicating a heterogeneous expression of SSTR subtypes in insulinomas. Interestingly, SSTR3 mRNA, which is highly expressed in rat pancreatic islets, is not expressed in normal human pancreatic islets, while SSTR1, SSTR2, and SSTR4 mRNAs are expressed. In three cases of pheochromocytoma, SSTR1 and SSTR2 mRNAs were detected, showing an expression pattern identical to that of normal adrenal gland. In a carcinoid, SSTR1 and SSTR4 mRNAs were detected. We have also found that human SSTR2 shows a high affinity for SMS 201-995, which has been used clinically for the treatment of endocrine tumors. Since SMS 201-995 was effective in the treatment of a patient with glucagonoma in which SSTR2 mRNA was present, but had no effect in a patient with carcinoid in which SSTR2 mRNA was not detected, this study suggests that the efficacy of SMS 201-995 may depend, at least in part, on the expression of SSTR2 in tumors.
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PMID:Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine tumors. 813 73

The authors report their experience with octreotide in 20 patients (median age 57 years, 10 M, 10 F) from 1984 to 1991; 16 had metastatic APUDoma: 1 PPoma with VIPoma, 1 glucagonoma, 5 gastrinoma including 1 associated to PP-oma, 9 mid-gut carcinoid; 3 patients had multiple-endocrine neoplasia type I (MEN-I) with Zollinger-Ellison syndrome (ZES) and 1 patient a non-metastatic VIPoma. Octreotide (200-750 micrograms/day) was administered bid or tid with regular laboratory controls and morphological assessment. There was a striking improvement of symptoms, particularly in the carcinoid group (reduction of flushing in all patients and of diarrhoea in 3/5), in the patient with gastrinoma + acromegaly (regression of congestive heart failure) and in the patient with non-metastatic VIPoma. The hormonal markers were markedly reduced, particularly gastrin, PP (except in the patient with PPoma + VIPoma), VIP, GH and Somatomedin-C and urinary 5HIAA in 4/9 patients with carcinoid. There was only one partial regression of metastases (gastrinoma) and 4 apparent stabilizations of tumour growth, in the 16 metastatic cases. Among them, 4 patients died: 1 glucagonoma, 1 PPoma + VIPoma, 2 mid-gut carcinoids after a treatment of 5, 16, 30, 36 months, respectively. The patient with acromegaly + ZES died after 6 years of treatment at age 81. A patient with prolactinoma, resected insulinoma, hyperparathyroidism and ZES was not improved by a short course of octreotide (hypoglycemia); he died later of recurrent insulinoma. In conclusion, octreotide is a useful drug to control most of the symptoms related to gut endocrine tumours; it may inhibit tumour growth.
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PMID:Use of octreotide in the treatment of digestive neuroendocrine tumours. Seven year experience in 20 cases including 9 cases of metastatic midgut carcinoid and 5 cases of metastatic gastrinoma. 826 71

Sandostatin is a drug of immense importance in the management of NETs of the gastrointestinal tract. Its effect in some syndromes is life-saving, in particular in VIPoma. Dramatic effects have also been reported in the glucagonoma syndrome. The quality of life is considerably improved in the carcinoid syndrome and it is potentially life-saving in carcinoid crises. The drug is effective in gastrinomas, but other therapy is more effective. Its value is controversial in insulinoma although some patients are clearly improved. Not all patients respond and this may be related to the abundance of Sandostatin receptors on the tumour or simply to tumour bulk. There is no clear-cut evidence that Sandostatin has an anti-tumour effect in these patients.
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PMID:Effects of sandostatin on neuroendocrine tumours of the gastrointestinal system. 839 96

Gastrointestinal endocrine tumors consist of pancreatic endocrine neoplasms and carcinoid tumors. Except for insulinoma, a majority of gastrointestinal endocrine tumors are malignant. With improved medical treatment of syndromes of hormonal excess, growth of the primary tumor and metastatic spread has increasingly become an important determinant of long-term survival. Although few randomized, prospective data are available given the rare occurrence of malignant gastrointestinal endocrine tumors, surgery appears to be the only potentially curative treatment for malignant endocrine tumors, and complete resection of localized or regional nodal metastases provides the highest probability of cure. Surgery may also be the most effective treatment for hepatic metastases if most or all of the tumor can be resected, and patients with solitary, localized metastatic disease appear to benefit most. Symptoms from extensive metastases may respond to chemotherapy or octreotide. Gastrointestinal endocrine tumors are generally indolent, slow-growing neoplasms, and when symptoms are adequately controlled, patients can live comfortably and productively for many years with metastatic disease.
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PMID:Gastrointestinal endocrine cancers and nodal metastasis: biologic significance and therapeutic implications. 878

We evaluated a hand-held scintillation detector for intra-operative localisation of somatostatin-receptor-positive tumours in situ, and after excision, as an addition to preoperative scintigraphy with [111In-DTPA-Phe1]octreotide. Using the hand-held detector, the suspect tumour/normal tissue ratio R(in situ) between measurements was calculated for 23 patients with neuroendocrine tumours. The count rates of excised tumour and normal tissue were also measured ex vivo and their ratio R(ex vivo) was calculated. In midgut carcinoid (MC) patients (all scintigraphy positive), 4/29 macroscopically identified tumours gave false R(in situ). Tumour/blood 111In activity (T/B) ratios measured in a gamma counter were all high (27-650). In patients with medullary thyroid carcinoma (8/10 scintigraphy positive), misleading R(in situ) were found in 4/37 macroscopically identified tumours. T/B ratios were lower (3-39) than those seen in MC patients. 2/4 patients with endocrine pancreatic tumours (EPTs) had positive scintigraphy, reliable intra-operative measurements, and very high T/B ratios (910-1,500). 1 patient with a gastric carcinoid had correct R(in situ) and R(ex vivo), with high T/B ratios (71-210). 1 patient with sporadic insulinoma had negative scintigraphy and 1 patient with neuroendocrine carcinoma of the uterus also had low T/B ratios. In most cases, in situ measurements added little information to preoperative scintigraphy and surgical findings. The very high T/B ratios seen in MC tumours and some EPTs seem promising for future radiotherapy via somatostatin receptors.
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PMID:Radioisotope-guided surgery in patients with neuroendocrine tumours. 881 80

The detection of chromogranins (Cg) by immunohistochemistry and serology represents a new in vitro diagnostic tool for endocrine tumours. We have recently reported on the feasibility of targeting chromogranin A (CgA) for in vivo detection of pituitary adenomas by immunoscintigraphy (ISG). The scintigraphic procedure, based on an anti-CgA monoclonal antibody and on the avidin-biotin three-step method (Cg-3S-ISG), was evaluated on a group of 29 consecutive patients with known or suspected endocrine tumours other than pituitary adenomas, i.e. medullary thyroid carcinoma, carcinoid, insulinoma and parathormone- or ACTH-producing tumours. Primary tumours (10) and recurrences (16) were visualised in 26 patients, whereas conventional imaging techniques (planar radiography, computerised tomography, magnetic resonance imaging and ultrasonography) failed to detect the tumour sites in ten of the same (Cg-3S-ISG-positive) patients. Therefore, these preliminary results indicate that Cg-3S-ISG, the first immunological method able to detect endocrine tumours in vivo, has a higher diagnostic accuracy than conventional imaging techniques (93.1% compared with 65.5%).
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PMID:In vivo imaging of chromogranin A-positive endocrine tumours by three-step monoclonal antibody targeting. 885 41

Calcium infusion has been advocated as a provocative test for the diagnosis of some endocrine tumors of the pancreas and gastrointestinal tract (gastrinoma, insulinoma, intestinal carcinoids). The release of gastrin from gastrinoma tissue is very sensitive to alterations in the serum calcium level, and the calcium infusion test is recommended in Zollinger-Ellison syndrome when the results of secretin stimulation are equivocal. The calcium provocative test in the detection of insulinoma and carcinoid tumors is less reliable than other safer and simpler procedures. Intravenous injection of calcium followed by pentagastrin stimulates the release of somatostatin in patients with somatostatinoma and offers a reliable means for establishing the diagnosis of this tumor. Calcium administration has not proven to be useful in the diagnosis of other endocrine tumors of the digestive system.
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PMID:Use of calcium provocative test in the diagnosis of gastroenteropancreatic endocrine tumors. 906 35

We report on the culture of human insulinoma cells derived from a 32-year-old male patient with hyperinsulinism due to an insulinoma of the pancreas. A single-cell suspension was made by passing insulinoma fragments through a fine-gauge stainless-steel mesh. Cluster-forming insulinoma cells resembling pancreatic islets grew in the presence of fibroblasts. The insulinoma cell clusters could be differentiated from fibroblasts by using in situ pan optic staining and specific immunocytochemical staining (anti-human insulin and anti-human insulinoma monoclonal antibody (mAb) D24). mAb D24 was generated using insulinoma cells as antigen for immunization of a Balb/C mouse and cell fusion by the hybridoma cell technique. The anti-insulinoma cell mAb recognized a 32 kDa protein on immunoblot analysis of neuroendocrine tumor cells. D24 mAb also reacted immunohistochemically with normal pancreatic beta-cells and tumors such as vipoma, gastrinoma and carcinoid. Insulinoma cell clusters separated from fibroblasts by micromanipulation and plated into multiwell culture dishes exhibited an insulin-secretion rate of approximately 30 U/100 cells per 24 h with no insulin-secretory response to elevated glucose concentration. Purified insulinoma cells incubated with 1 ng/ml human nerve growth factor expressed neurofilament and neurite extension. These findings together with earlier observations in animal models suggest that human pancreatic beta-cells share some properties with neurons and are related to other neuroendocrine cells in the gastrointestinal tract.
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PMID:Culture of human insulinoma cells: development of a neuroendocrine tumor cell- and human pancreatic islet cell-specific monoclonal antibody. 958 3

Chemotherapy of neuroendocrine tumors must be improved. The most widely used regimen, which combines streptozotocin with fluorouracil, commonly obtains poor results. The best response rate that has been reported for carcinoid tumors is 33%. From July 1991 through September 1994, 18 patients who had advanced neuroendocrine tumors-including nine carcinoid tumors, seven neuroendocrine tumors of unknown primary site, one insulinoma, and one paraganglioma-were treated with a regimen of dacarbazine, 400 mg/m2/day, plus fluorouracil, 1 g/m2/day, with leucovorin, 200 mg/m2/day, for 2 days every 21 days (DTIC-LVFU2 protocol). The results were assessed according to the World Health Organization criteria of toxicity and response. Toxicity was moderate. The most severe side effects were grade 3 vomiting in two patients, grade 3 leukopenia in three patients, and grade 3 mucositis in one patient. The overall response rate was 27%, with only one partial response for carcinoid tumors but one complete and three partial responses for the other tumor types. Efficacy was insufficient in patients who had carcinoid tumors but the combination of dacarbazine with fluorouracil and leucovorin could be an effective regimen for the treatment of neuroendocrine tumors of unknown primary site.
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PMID:Dacarbazine, fluorouracil, and leucovorin in patients with advanced neuroendocrine tumors: a phase II trial. 962 88


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