Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatostatin (SS) receptor status was investigated in the tumor tissues from 62 patients with carcinoid tumors and 15 patients with islet cell carcinomas using receptor autoradiography techniques with two different iodinated somatostatin analogues as radioligands, a [Leu8, DTrp22, Tyr25]somatostatin-28 and a somatostatin octapeptide, Tyr3-octreotide. The carcinoid tumors were either primaries (n = 32) or metastases (n = 43), sampled as surgical specimens or as small needle liver biopsies. Fifty-four of 62 carcinoid patients had SS receptor-positive tumors (87%). All 15 islet cell carcinoma patients had positive tumors (4 primaries, 11 metastases), i.e., 3 vipomas, 3 insulinomas, 2 glucagonomas, 1 gastrinoma, 2 polyfunctional tumors, and 4 nonfunctioning tumors. Saturation and competition experiments on tissue sections revealed saturable, high affinity binding sites pharmacologically specific for bioactive SS analogues. In a majority of the tumors, the receptors were densely distributed and were always homogeneously found in the whole tumor. All except two tumors were labeled with both radioligands. Multiple liver metastases (n = 16) from three different patients were all shown to contain a comparable amount of receptors. SS receptors could be demonstrated even in very small tissue samples of liver metastases obtained by percutaneous liver biopsies (mean weight, 6.8 mg). The majority of the eight SS receptor-negative carcinoids were mainly bronchial carcinoids (n = 5), usually poorly differentiated. On the contrary, SS receptor-positive cases were never found to be anaplastic. All tumors except one from patients pretreated with octreotide (3 days to 3.8 years) were SS receptor positive. In the majority of carcinoids or islet cell carcinomas, the SS receptor status correlated with the in vivo biochemical response (hormone inhibition) to octreotide. These data demonstrate (a) the high prevalence of SS receptors in the primary tumors of both carcinoids and islet cell carcinomas, (b) their presence in metastases as well, (c) their continuous expression even during long term octreotide therapy, (d) the possibility of measuring SS receptors in percutaneous needle liver biopsies, and (e) the evidence of their functionality. This study therefore suggests that tumoral SS receptors may be the likely molecular basis for octreotide action and may be an important parameter for predicting the therapeutic efficacy of SS analogues in carcinoids and islet cell carcinomas.
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PMID:Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas. 216 86

The effect of an octapeptide analogue of somatostatin, octreotide, on tumor blood flow was evaluated with angiography in eight patients with hepatic endocrine tumors; one patient had primary intrahepatic gastrinoma, two patients had hepatic metastases from gastrinomas, two patients had VIPomas (vasoactive intestinal polypeptide-secreting tumor), and three patients had carcinoid tumors. Octreotide caused a marked decrease in tumor blood flow in two patients with gastrinomas and two with VIPomas. One patient could not be evaluated due to the lack of a tumor blush on a control angiogram. In patients with carcinoid tumors, octreotide caused a slight reduction in blood flow through the tumors in two patients, while there was no change in one patient. Octreotide markedly decreased gastrin and gastric acid secretion in two of three patients with gastrinomas, lowered VIP and stopped the diarrhea in patients with VIPomas, and controlled symptoms in two of three patients with carcinoid tumors. The vasoactive effect of octreotide on hepatic endocrine tumors may be a direct action on tumor blood supply or secondary to inhibition of the endocrine tumor cell secretion and consequent decreased blood flow.
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PMID:Effect of somatostatin analogue (octreotide) on blood flow to endocrine tumors metastatic to the liver: angiographic evaluation. 217 Oct 15

Because of its widespread distribution within the nervous system and gastroenteropancreatic (GEP) system, and its diverse physiological inhibitory actions on various gastrointestinal functions, including endocrine and exocrine secretion, motility, liver and splanchnic blood flow and absorption, native somatostatin has been viewed as a possible therapy for many diseases. However, its short duration of action and consequent limited clinical usefulness have been overcome with the availability of Sandostatin (octreotide, Sandoz Ltd), a long-acting, synthetic octapeptide analog of the naturally occurring hormone. Sandostatin represents a significant advance in the treatment of growth hormone (GH) and thyrotropin (TSH)-secreting pituitary tumors and GEP endocrine tumors (carcinoid tumor, VIPoma, glucagonoma, insulinoma, and gastrinoma). Preclinical in vitro and animal studies have shown the antineoplastic activity of the compound. Moreover, because of a possible direct effect on somatostatin receptor-positive endocrine tumor cells and an indirect effect whereby Sandostatin lowers GH, insulin-like growth factor type 1 (IGF-1), and numerous gastrointestinal peptides, Sandostatin may prove useful as an adjunctive therapy in cancer patients. In vivo labeling of somatostatin receptor-positive tumors with radiolabeled somatostatin analogs now allows localization of such tumors and their metastases. In addition, targeted irradiation of these tumors by beta particle-emitting isotopes attached to such somatostatin analogs may become possible. The use of Sandostatin in acute esophageal variceal bleeding, pancreatic pseudocysts, gastrointestinal, and pancreatic external fistulae, short bowel syndrome, dumping syndrome and acquired immunodeficiency syndrome (AIDS)-related refractory hypersecretory diarrhea has provided encouraging results.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Future medical prospects for Sandostatin. 220 87

In the present study of 45 patients with Zollinger-Ellison syndrome, the frequency and clinical importance of the release of multiple gastrointestinal peptides were assessed prospectively. During an initial evaluation, extent of gastrinoma, clinical symptoms, disease duration, and presence or absence of multiple endocrine neoplasia, type I (MEN-I) were assessed. All patients had determinations of fasting plasma gastrin, human pancreatic polypeptide, motilin, neurotensin, and somatostatin; 35 had determinations of insulin and gastrin-releasing peptide and 21 had determinations of glucagon. A plasma elevation of additional peptides besides gastrin was detected in 62%, with 44% having one, 18% having two, and 0% having three additional peptides elevated. Motilin was elevated in 29%, human pancreatic polypeptide in 27%, neurotensin in 20%, and gastrin-releasing peptide in 10%, whereas insulin, glucagon, and somatostatin were not elevated in any patient. The presence or absence of elevation of any peptide did not differ in patients with or without MEN-I, with gastrinoma size, with the presence or absence of metastatic disease, or with various clinical symptoms. Patients were assessed yearly for clinical evidence of a secondary symptomatic pancreatic endocrine tumor syndrome with a median follow-up of 146 and 84 months from onset or diagnosis, respectively. Only one patient (2% of patients) developed a second syndrome (rate, 2 patients per 100 patients observed for 10 years). These results demonstrate that the plasma elevation of multiple gastrointestinal peptides is common in patients with Zollinger-Ellison syndrome; however, the rate of developing a second symptomatic pancreatic endocrine tumor syndrome is much lower than generally believed. Furthermore, no evidence is found to support the conclusions that the detection of the plasma elevation of these peptides is clinically important in assessing MEN-I status, disease extent, or presence of metastatic disease or that elevated levels of motilin, neurotensin, gastrin-releasing peptide, or human pancreatic peptide are associated with any distinct clinical symptoms. Therefore, we recommend that plasma concentrations of these additional gastrointestinal peptides should not be assessed routinely but rather only if new symptoms develop.
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PMID:Multiple hormone elevations in Zollinger-Ellison syndrome. Prospective study of clinical significance and of the development of a second symptomatic pancreatic endocrine tumor syndrome. 222 72

Chromogranin A (Cg A) is a protein that is coreleased with peptide hormones from gut endocrine cells and tumors. Plasma levels of Cg A, pepsinogen group I, and gastrin were measured in 31 patients with gastrinoma. Mean Cg A level in 10 patients with gastrinoma who were not operated on was 169 +/- 32 ng/mL, while in 9 control patients it was 28 +/- 5 ng/mL. In 18 patients with gastrinoma with residual tumor after total gastrectomy, the mean Cg A level was 45 +/- 6 ng/mL, and in 10 patients with normal gastrin levels after total gastrectomy and tumor excision, the mean Cg A level was 40 +/- 4 ng/mL. In 7 patients in whom pregastrectomy and postgastrectomy Cg A levels were measured, the mean reduction was 94 +/- 27 ng/mL, or 66%. There was no correlation between Cg A levels and amount of tumor, presence of metastases, or multiple endocrine neoplasia type I syndrome. There was a significant correlation between Cg A and pepsinogen I levels but no correlation between Cg A and gastrin levels. The results suggest that the elevated plasma Cg A levels in patients with gastrinoma are determined primarily by the trophic effects of gastrin on gastric enterochromaffinlike cells rather than by corelease from the gastrin-producing tumor itself.
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PMID:Source of plasma chromogranin A elevation in gastrinoma patients. 232 9

Progastrin and all of its processing products were measured in serum from 48 patients with Zollinger-Ellison syndrome, 42 patients with duodenal ulcers, and 34 normal subjects. A processing-independent gastrin analysis and a conventional radioimmunoassay for the biologically active alpha-amidated gastrins were used. In serum from normal subjects, 87% (median; range, 27%-160%) of all progastrin products were alpha-amidated gastrins, whereas they constituted only 39% (15%-130%) in serum from patients with duodenal ulcers (p less than 0.01) and 46% (16%-100%) in serum from gastrinoma patients (p less than 0.01). A significantly lower percentage of alpha-amidated gastrin was found in patients with hepatic metastases (23%) than in patients with apparently benign tumors (54%). Chromatography of serum showed that large progastrin molecules occurred mainly in patients with malignant tumors, whereas smaller glycine-extended precursors dominated in patients with benign tumors. The results indicate that the total progastrin product reflects tumor synthesis of gastrin better than conventional measurements of alpha-amidated gastrin. Moreover, the results suggest that a low degree of processing of progastrin could serve as a predictor of a malignant clinical course at an early stage of the disease.
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PMID:Progastrin in serum from Zollinger-Ellison patients. An indicator of malignancy? 233 86

The nuclear DNA content of 17 pancreatic neuroendocrine tumors was measured from paraffin-embedded tissue with flow cytometry. The tumors were classified by immunostaining with antisera for synaptophysin, insulin, gastrin, glucagon, pancreatic polypeptide, somatostatin, and vasoactive intestinal polypeptide. Eight (47%) of the 17 tumors were aneuploid, and two (12%) were multiploid (had two aneuploid stemlines of cells). Seven of the eight insulinomas, one of the four gastrinomas, and two of the four nonspecified neuroendocrine tumors had an abnormal nuclear DNA content. The DNA indices of the aneuploid and multiploid cases ranged from 1.13 to 1.93, and three cases had a DNA index greater than 1.50. During the follow-up for up to 16 years (mean, 7 years), one patient with diploid nonspecified tumor died of the disease, another patient with a multiploid gastrinoma had metastatic disease develop, and a third patient with a multiploid nonspecified tumor was alive with the disease. The authors conclude that many neuroendocrine tumors of the pancreas have an abnormal nuclear DNA content as measured by DNA flow cytometry. DNA multiploid pancreatic neuroendocrine tumors may be associated with a less favorable clinical course, but this needs to be confirmed in additional studies.
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PMID:DNA ploidy in pancreatic neuroendocrine tumors. 234 35

In 1947, a patient with metastatic islet cell tumor was treated for intractable ulcer disease at the University of Chicago Medical Center. Eight years later, in retrospect, it was recognized that he and another patient had the Zollinger-Ellison syndrome (ZE). From 1947 until the present, 30 patients with the ZE syndrome have been treated at this institution. Twenty-one (70%) were male and 9 (30%) were female. Their ages ranged from 24 to 76 years. Most (79%) had abdominal pain, however, melena (42%), hematemesis (33%), and severe diarrhea (35%) were prominent as well. Symptoms were present for a mean of 5.8 years before diagnosis. Over their entire clinical course, duodenal ulcers occurred in 96% of patients, gastric ulcers in 24%, jejunal ulcers in 29%, esophageal ulcers in 6%, and stomal ulcerations in 58%. Eleven (38%) of all gastrinomas were proved to occur in the duodenum; 10 (34%) were pancreatic in origin, including 3 with the MEN I syndrome; 3 (10%) were extrapancreatic and extraduodenal in origin, and no tumor was found in 5 (17%). Each of the 3 patients with MEN I developed a proven pancreatic islet cell carcinoma with metastases as well as hyperparathyroidism and a pituitary lesion. Of 27 patients who were explored for gastrinoma, tumor was found in 20 (74%). Excluding patients with MEN who had multiple lesions throughout the pancreas, all tumors were found in the "gastrinoma triangle." Total gastrectomy was performed in 10 (37%) of 27 of all patients who were explored, in 5 (71%) of 7 when no tumor was found, and in only 5 (25%) of 20 when tumor was present. Operative mortality was 15% (4 of 27) but no death has occurred since 1974. Long-term survival has followed both tumor resection or total gastrectomy in selected individuals (including 1 patient with known multiple liver metastases who is alive 18 years after liver biopsy and total gastrectomy); however, since malignant gastrinomas were present in 46% of all patients (or 57% in whom tumor was found) and since local metastases can sometimes be removed, we favor an aggressive approach to localization and resection when liver metastases or other distant metastases are not found. Duodenal gastrinomas are particularly favorable for resection for cure. They were malignant in only 36% and their metastases were nodal in each of 4 cases. The major problem is finding them since they are often small and "occult."(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Gastrinomas: a 42-year experience. 236 40

A somatostatin analog (SMS 201-995) was used to treat symptomatic patients with a residual tumor burden of gastrinoma or medullary thyroid carcinoma and pathologic elevations of circulating marker peptides associated with these neuroendocrine tumors. Possible inhibitory effects of the analog on marker peptides, patients' symptoms, or tumor progression were studied in a dose-response protocol and during several months of self-injection of SMS 201-995. Both patients reported remarkable relief of secretory diarrhea and other symptoms, and serum gastrin was successfully suppressed by increasing doses of the analog. However, no effect was seen in reduction of hypercalcitoninemia. Morphologic imaging of residual tumor showed no progression of medullary thyroid carcinoma during treatment and, in the case of hepatic gastrinoma metastases, remarkable tumor regression was confirmed. No toxicity or glucose intolerance was experienced. Somatostatin analog shows promise for palliative management of endocrinologic symptoms due to neuroendocrine tumors, and an inhibitory effect can be measured in some but not all peptide markers. Further evidence of its negative trophic effect on tumor blood flow may suggest an antineoplastic potential, as well as palliative use of this new treatment.
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PMID:Somatostatin analog: effects on hypergastrinemia and hypercalcitoninemia. 243 92

In the Pittsburgh series of 1,000 orthotopic liver transplants (OLTx), from January 1981 to July 1987, the indication for transplantation in five patients consisted of unresectable hepatic metastases arising from endocrine tumors of gastrointestinal origin: glucagonoma, two patients; carcinoid, two, and gastrinoma, one patient. Three patients underwent resection of the primary tumor (two distal pancreatectomies and one ileal resection) at the time of the hepatic transplantation. All patients underwent extensive nodal dissection. Three of the five patients are alive with no evidence of residual disease after a median follow-up study of 12 months. Hepatic transplantation broadens the concept of radical excision of tumor and may be considered as a potential therapeutic approach for some highly selected instances of unresectable hepatic metastases arising from endocrine tumors of the intestine and pancreas.
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PMID:Transplantation of the liver for metastatic endocrine tumors of the intestine and pancreas. 253 98


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