Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors report their experience with resection of small bowel carcinoid tumors associated with diffuse hepatic metastases. Nine patients were operated during the last ten years. A carcinoid syndrome was present biologically in every case and clinically in 8 cases. The tumor was removed in every case, either by right hemicolectomy (n = 6), or by small bowel resection (n = 3). Postoperative mortality and morbidity were nil. Adjuvant therapy included hepatic chemo-embolization and long-term therapy by a long-acting somatostatin analog. Five patients died during the period of follow-up and 4 patients were alive at the end of the study. Resection of small bowel carcinoid tumor is indicated even when the liver is involved by diffuse metastases to prevent the risk of small bowel occlusion, and to promote hepatic chemoembolization as subsequent therapy against the carcinoid syndrome and metastatic spread. Moreover, the procedure can participate in the selection of cases for orthotopic liver transplantation, when conservative therapy fails to control the carcinoid syndrome.
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PMID:[Resection of carcinoid tumors of the small intestine is still indicated in the presence of disseminated hepatic metastases]. 168 80

We examined the role of the potent vasoactive kinin substance-P (SP) in flushing derived from various causes. SP was measured in plasma after acetone/ether extraction using an antiserum directed at the carboxy-terminal 5-11 amino acid region of undecapeptide SP. The antiserum had less than 1% cross-reaction with the other neurokinins, neurokinin-A and neuropeptide-K, that derive from the beta-preprotachykinin gene and share carboxy-terminal residues. Basal and pentagastrin-stimulated SP levels were measured in 22 healthy controls, 11 patients with histologically proven carcinoid tumors, 8 patients with tumors other than carcinoid, and 7 patients with idiopathic flushing (IF). Basal SP levels were less than 10 pg/mL in normal subjects. All patients with midgut carcinoid tumors had SP levels greater than 25 pg/mL, as did 7 of 8 patients with noncarcinoid tumors and 5 of 7 patients with IF. Using 50 pg/mL as the cutoff point, the sensitivity was 63% for detection of a tumor, and 100% of nontumor patients were excluded. Pentagastrin administration uniformly induced flushing and caused a rise in SP levels greater than 150 pg/mL in 5 of 10 patients with carcinoid tumors, 3 of 8 with noncarcinoid tumors, and 0 of 7 with IF, i.e. a SP rise of more than 100 pg/mL suggests a tumor. Administration of somatostatin (150 micrograms) 0.5 h before the pentagastrin abolished flushing in all carcinoid patients and reduced SP levels, but not into the normal range. Long term treatment with SMS significantly reduced flushing and lowered SP levels, but did not restore these to normal. We conclude that 90% of patients with carcinoid/noncarcinoid tumor have raised COOH-terminal SP levels. A basal level above 50 pg/mL or a pentagastrin-stimulated rise of more than 100 pg/mL distinguishes carcinoid from IF. The dissociation between SP concentrations and flushing suggests that SP may not be the only kinin involved in the flushing associated with carcinoid tumors.
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PMID:Plasma substance-P in neuroendocrine tumors and idiopathic flushing: the value of pentagastrin stimulation tests and the effects of somatostatin analog. 169 75

Ninety-nine carcinoid tumors of the duodenum were studied. Seventy-seven patients were followed up for a mean period of 65 months, 20 tumors were autopsy findings, and two patients were unavailable for follow-up. Sixteen tumors (21%) produced metastases, all discovered initially; 3 patients (4%) died from metastatic disease (mean survival, 37 months postoperatively). Features associated with metastatic risk were involvement of muscularis propria, size greater than 2 cm, and the presence of mitotic figures. For 51 tumors, there was no correlation between immunohistochemical somatostatin and history of diarrhea, cholelithiasis, or diabetes mellitus (somatostatin syndrome). Five tumors were associated with Zollinger-Ellison syndrome and had immunohistochemical gastrin, but in the others there was no correlation between ulcer disease and gastrin positivity. Duodenal carcinoids are indolent, especially when small and localized to the submucosa. Immunohistochemical identification of somatostatin and gastrin has little clinical relevance.
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PMID:Carcinoid tumors of the duodenum. A clinicopathologic study of 99 cases. 169 55

Apudoma was found in the gall bladder removed in a 76-year-old woman because of the chronic calculous cholecystitis exacerbation. Carcinoid syndrome was absent clinically. Histologically, the tumour was a poorly differentiated carcinoid with areas of small cell and polymorphic carcinoma. Argyrophilic Pasquale reaction in the tumour cells was negative, electron microscopically small neurosecretory granules were found. Numerous ACTH-reactive cells and single serotonin-reactive cells were revealed in the tumour parenchyma by means of immunohistochemical PAP-method using antibodies against ACTH, serotonin, calcitonin, somatostatin, insulin, glucagon, P-substance. Focal hyperplasia and intestinal metaplasia of epithelium with the increase of the number of argyrophilic, ACTH-reactive cells were observed outside the tumour.
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PMID:[A poorly differentiated apudoma of the gallbladder]. 170 8

Development of effective treatment for patients with carcinoid tumors has been hampered by lack of an experimental model. The authors have established the only long-term cell line of a functioning human pancreatic carcinoid tumor (BON) that produces tumors in nude mice. In this study the authors examined the effect of three agents, alpha-interferon (IFN), a somatostatin analog, SMS 201-995 (SMS), and an inhibitor of polyamine biosynthesis, alpha-difluoromethylornithine (DFMO), on the growth of BON tumors. BON was implanted bilaterally as 3-mm2 pieces (subcutaneously [sc]) into male BALB/c nude mice. In the first study, 23 mice were randomized to four groups: control, IFN (1 x 10(6) units, sc, four times a day), IFN + SMS (300 micrograms/kg, intraperitoneally, three times a day), and IFN + 3% DFMO in drinking water. Treatments were initiated on day of tumor implantation. In the second study, mice were randomized to six groups: control, IFN, SMS, DFMO, IFN + SMS, IFN + DFMO, and IFN + SMS + DFMO. Treatments were started on day 15 after tumor implantation. Tumor area and body weights were measured weekly. In both studies mice were killed on day 28 after BON implantation and tumors removed, weighed, and analyzed for DNA and RNA content. In the first study, IFN either alone or in combination with SMS or DFMO suppressed BON tumor growth. When treatment was initiated after established tumor growth (study 2), however, the only effective treatments for suppression of growth of BON were IFN + DFMO and IFN + DFMO + SMS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Novel therapy for the treatment of human carcinoid. 170 83

The authors have established a long-term tissue culture cell line (BON) derived from a metastatic human carcinoid tumor of the pancreas. The cells have been in continuous passage for 46 months. Tissue culture cells produce tumors in a dose-dependent fashion after SC inoculation of cell suspensions in athymic nude mice. BON tumors, grown in nude mice, are histologically identical to the original tumor; they possess gastrin and somatostatin receptors, synthesize serotonin and chromogranin A, and have a doubling time of approximately 13 days. The antiproliferative effects of the long-acting somatostatin analogue, SMS 201-995 (300 micrograms/kg, t.i.d.), and 2% alpha-difluoromethylornithine on BON xenografts in nude mice were examined. Tumor size was significantly decreased by day 14 of treatment with either agent and at all points of analysis thereafter until the animals were killed (day 33). In addition, tumor weight, DNA, RNA, and protein contents were significantly decreased in treated mice compared with controls. Establishment of this human carcinoid xenograft line, BON, provides an excellent model to study further the biological behavior of carcinoid tumors and the in vivo effect of chemotherapeutic agents on tumor growth.
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PMID:Establishment and characterization of a human carcinoid in nude mice and effect of various agents on tumor growth. 171 29

The use of a somatostatin analogue (SMS 201-995) has greatly facilitated the treatment of patients with the midgut carcinoid syndrome. Clinical studies have shown that SMS reduces the peripheral levels of tumour-produced serotonin (5-HT) and tachykinins, e.g. neuropeptide K (NPK), basally and after pentagastrin provocation. Some studies have indicated an inhibitory effect of SMS on tumour cell growth as well. In the present study we have investigated the effects of SMS on four different human midgut carcinoid tumours maintained in long term culture. Media levels of 5-HT and NPK-LI in tumour cell cultures decreased rapidly during incubation with SMS (10(-8)-10(-10) M) in all four tumours studied without evidence for tachyphylaxis (up to 6 weeks observation period). SMS treatment (10(-8) M) during 4 days reduced the media concentrations of 5-HT by 56%, while the intracellular contents of 5-HT were decreased by 27% indicating dual inhibitory effects on synthesis and secretion of 5-HT from tumour cells. The DNA contents of cultures were not affected by SMS (10(-8) M or 10(-10) M) treatment for 4 or 14 days. When tumour cell cultures were challenged with isoprenaline (IP) (10(-6) M) no reduction of the IP induced release of 5-HT could be detected after pretreatment of tumour cell cultures with SMS (10(-8) M) for 1 h, 4 h or 4 days. These studies provide evidence for a direct action of the somatostatin analogue on midgut carcinoid tumour cells, reducing both synthesis and secretion of hormones from tumour cells. This effect appears not to be related to inhibition of tumour cell growth. The inhibition of 5-HT secretion from tumour cells by SMS seems to operate via a second messenger system different from the one mediating the beta-adrenoceptor stimulated release of 5-HT.
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PMID:The effect of a somatostatin analogue on the release of hormones from human midgut carcinoid tumour cells. 171 51

Over the past few years the usefulness of some somatostatin's analogues in the treatment of intestinal tract endocrine tumors has been demonstrated. Notwithstanding, the results obtained are variable. The case of a carcinoid tumor with a hepatic metastasis is presented and its clinical as well as its biochemical and its morphological results are evaluated after treatment with octreotide over a seven months period. It is important to highlight the great clinical improvement obtained at the beginning of treatment. Treatment was not effective in the control of tumor progression. After the injection of such a drug, a decrease in serotonin and 5-hydroxy-indoleacetic acid serum levels was observed as well as a reduction in the urinary metabolite. It is concluded that octreotide is very useful for the symptomatic treatment of carcinoid syndrome.
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PMID:[Treatment with octreotide (SMS 201-995) in a case of intestinal carcinoid tumor]. 138 Jan 73

A 54-year-old man underwent a radical nephrectomy for a presumed renal cell carcinoma. The tumor was large, showed areas of cystic degeneration and calcification, and had completely obliterated the normal renal parenchyma. The light microscopic appearance was atypical for renal cell carcinoma, and when electron microscopy revealed innumerable neurosecretory granules a diagnosis of carcinoid tumor was made. The tumor cells were argentaffin- and argyrophil-negative but were chromogranin-, neuron-specific enolase-, and leu-7-positive. When tested with a battery of antibodies against specific polypeptide hormones, the tumor exhibited diffuse pancreatic polypeptide and focal somatostatin immunoreactivity. Our case represents only the 16th case of carcinoid tumor of the kidney to be reported and the first with demonstrated pancreatic polypeptide immunoreactivity. The predominantly trabecular histology, nonreactivity with silver stains, and immunohistochemical profile of this case are common characteristics of hindgut carcinoids, suggesting that, like rectal carcinoids, renal carcinoids are tumors of hindgut endocrine cells.
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PMID:Carcinoid tumor of the kidney with morphologic and immunohistochemical profile of a hindgut endocrine tumor: report of a case. 172 13

Malignant carcinoid tumours with the carcinoid syndrome has over the years presented a therapeutic challenge. The patients might not only die from tumour progression but also from symptoms relating to hormone overproduction and the specific cardiac disease, e.g. right heart fibrosis and failure. Surgery has been the treatment of choice in local disease, but when liver metastases have developed other treatment procedures must be considered. Conventional chemotherapy has been of little beneficial value, with response rates of only 10-30%, whereas a new somatostatin analogue, octreotid, is effective in controlling clinical symptoms but not tumour progression. Interferon treatment was introduced in 1982 by our group, and we are now presenting treatment results of 130 patients with histologically verified malignant carcinoid tumours and liver metastases. One hundred and eleven patients were treated with a median dose of 6 mega units (MU) of interferon alpha, five times weekly (dose range 3-9 MU), whereas 29 patients received conventional chemotherapy. Forty-seven out of 111 patients (42%) treated with interferon alpha demonstrated a significant biochemical response and 15% demonstrated more than 50% reduction in tumour size. In another 43 (39%) patients stabilization of the carcinoid disease have been noted, whereas 21 (19%) showed progressive disease. The median duration of response was 34 months. Subjective responses with improvement of diarrhoea, flush and/or bronchoconstriction were noticed in 76 patients (68%). The 19 patients treated with chemotherapy demonstrated only 10% biochemical response, lasting for only 3-5 months. The survival analysis demonstrates a median survival of only 8 months in the group of patients treated with chemotherapy, compared to 80+ months (P less than 0.001) in the groups treated with interferon alpha. Interferon adverse reactions of fatigue, weight loss and anaemia were manageable. Neutralizing interferon antibodies were documented in 5-15% of the patients. Interferon alphas are active in patients with malignant carcinoid tumours. Clinical symptoms are significantly reduced following reduction of circulating hormones. Interferon might also have an impact on survival in this group of patients. The side-effects are moderate and managed by dose adjustments.
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PMID:The role of interferons in the management of carcinoid tumours. 183 59


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