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)

A 46-year-old woman with acromegaly and hyperthyroidism due to a pituitary adenoma. She had high serum thyroid-stimulating hormone (TSH) levels and very high serum growth hormone (GH) levels. Transsphenoidal removal of the tumor, post-operative irradiation, frontal craniotomy for removal of residual tumor and large-dose bromocriptine therapy were carried out consecutively. After therapy, serum GH levels gradually decreased, but not to the normal range, and serum TSH levels remained at inappropriately normal levels. Using immunoperoxidase techniques, GH-, TSH- and follicle-stimulating hormone (FSH)-containing cells were demonstrated in the adenoma. A long-acting somatostatin analogue (SMS 201-995, 600 micrograms/day) suppressed the serum GH level to the normal range with a concomitant suppression of TSH. Furthermore, the paradoxical serum GH responses to TRH and LH-RH were slightly improved. No important subjective side-effects were noted. Therefore, SMS 201-995 appeared to be a very effective drug in this patient with a GH- and TSH-producing pituitary tumor.
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PMID:Effect of a long-acting somatostatin analogue (SMS 201-995) on a growth hormone and thyroid stimulating hormone-producing pituitary tumor. 186 12

A 42-year-old woman had acromegaly and a large macroadenoma with supra- and parasellar extension. Her GH levels (median 85 ng/ml, range 63-170 ng/ml) were not responsive to TRH (200 micrograms iv), GHRH (100 micrograms iv) and bromocriptine (Br 2.5 mg po) acute tests; Sm-C level was 8 U/ml. She was treated with octreotide (SMS) (up to 1500 micrograms daily) for 3 months. No changes of clinical, biochemical and radiological findings were seen, therefore she underwent transsphenoidal surgery. After surgery, hypopituitarism and diabetes insipidus appeared: GH levels remained high (median 45 ng/ml; range 37-56 ng/ml), but became responsive to Br acute test. The patient was given SMS again, and this resulted in clinical improvement, marked reduction of GH and Sm-C levels and slight shrinkage of the residual tumor. Speculative hypotheses about this previously unreported phenomenon might be either an excess of both GHRH and somatostatin, caused by a primary increase of dopaminergic tone, or a primary excess only of GHRH; in both cases the surgical lesion of the hypothalamic-pituitary region might have impaired the neurohormones inflow to the residual pituitary and so let SMS and Br exert their inhibitory actions on GH secretion.
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PMID:Resistance to a long-acting somatostatin analog (SMS 201-995) reversed by surgery in acromegaly. 227 11

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

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In-pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.
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PMID:A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome. Assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide. 792 88

Somatostatin analogue scintigraphy represents a new technique employing radiolabelled peptides to detect specific receptor-bearing lesions. 111Indium diethylene-triaminopentaacetic acid-linked octreotide (111In-DTPA-D-Phe1-octreotide), also known as [111In]pentetreotide or OctreoScan, is now established in the management of patients with neueroendocrine gastrointestinal tract and pancreatic tumours, and has proved effective in localizing disease sites in lung, breast and medullary thyroid carcinomas, lymphomas, meningiomas and others. In these conditions (a) the imaging of all disease sites at a single sitting (in a proportion of patients) thereby making further investigations unnecessary, (b) the localization of otherwise unexpected metastatic deposits and (c) the detection of residual disease not found by other means suggest that [111In]pentetreotide may be a useful adjunct in the diagnostic evaluation of patients with somatostatin receptor-bearing tumours.
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PMID:Radiolabelled somatostatin analogue scintigraphy in oncology. 882 83

With the introduction of longer-acting somatostatin analogues symptomatic relief is easy to achieve in patients with functionally active endocrine tumours and will be further facilitated by still longer-acting formulations. The consequences of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome can be prevented by all proton-pump inhibitors currently on the market. Despite the various antiproliferative strategies that have been offered to patients with metastatic disease, available data are controversial and, more importantly, are supported by few prospective and controlled studies. Most experts agree that surgery with curative extirpation of the primary in the absence of metastases and tumour debulking in metastatic disease should be intended wherever possible. Controversy concerns residual disease. According to our view, any further antiproliferative strategy should consider the growth characteristics and biology of a given tumour (Figure 4). In the case of rapid progression, chemotherapy should be offered if tumours originate from the pancreas or reveal an undifferentiated histology. In contrast, chemotherapy should not be offered to patients with well-differentiated non-functional or functional tumours (carcinoid syndrome) arising from the intestine. The same applies for patients with tumours with no or only slow growth within an given observation period of 3-12 months. These patients should be treated only symptomatically. Patients with tumours of slow progression might favourably respond to long-acting somatostatin analogues. We start with octreotide and offer patients not responding to octreotide monotherapy additional IFN alpha. If further tumour progression takes place, hepatic artery embolization is the next step (Figure 5) followed by chemotherapy, the latter in patients with tumours of pancreatic origin only. This strategy recognizes the severity of side-effects of the different therapeutic modalities and starts with octreotide because of its very few side-effects. Other groups start with chemoembolization followed by octreotide, alpha-interferon or its combinations (Ahlman et al, 1996). Ongoing studies will, it is hoped, answer the question of the ideal sequence of therapeutic strategies. Every available patient with metastasised gastrointestinal endocrine tumours should be included in one of the ongoing European multicentre trials.
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PMID:Gastrointestinal endocrine tumours: medical management. 911 20

The surgical resection of medulloblastoma (MB), the most frequent malignant brain tumor in children, often remains subtotal. To estimate the response to further treatment the residual tumor is monitored by CT or MRI. The interpretation of both imaging techniques is complicated by disturbances resulting from surgery and radiation. Our study searched for alternative imaging techniques and asked the following questions. 1) Do MB express somatostatin receptors (SSTR), 2) is SSTR scintigraphy a sensitive imaging technique for the follow-up and the detection of vital tumor tissue in children with MB, and 3) do the results of SSTR scintigraphy correlate with the in vitro analysis of MB tissue by SSTR autoradiography. We analyzed the SSTR status in 20 children with MB, aged 1 to 15 years. Sixteen SSTR scintigraphies using Indium-111-DTPA-D-Phel-pentetreotide were performed in 14 children. MB tissue of 14 children was analyzed by SSTR autoradiography using Iodine-125-Tyr3-octreotide. In 8 cases SSTR were measured by both methods in vivo and in vitro. In comparison with conventional imaging, results of SSTR scintigraphy were true positive in 7 of 7 patients, true negative in 9 of 9 patients, including one patient with false positive findings in MRI, false negative in only one patient with small spinal metastases (diameter < 3 mm) and false positive in none of the analyzed patients. In all cases with residual tumor (n = 3) and suspected relapse (n = 4) the diagnosis could be confirmed (n = 4) or excluded (n = 3), consistent with the results of MRI and tumor histology. All MB tissues analyzed by SSTR autoradiography (n = 14) showed an extremely high density of SSTR ranging from 4047 to 15526 dpm/mg MB tissue. MB (n = 8) which were analyzed by SSTR scintigraphy and autoradiography demonstrated consistent results in evaluation by both methods. In cases where the integrity of the blood-brain barrier was tested by Tc-99m-DTPA scintigraphy (n = 10), the SSTR-to-brain scintigraphy index confirmed the tumor specificity of radionuclide uptake. We conclude that 1) MB tissue expresses a particularly high density of SSTR, 2) the high density of SSTR in autoradiography correlates with a sensitive imaging of these tumors by SSTR scintigraphy, 3) SSTR scintigraphy might be a valuable imaging method for detection of vital MB tissue in patients with residual tumor or relapse.
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PMID:A possible role for somatostatin receptor scintigraphy in the diagnosis and follow-up of children with medulloblastoma. 954 55

The authors report a case of a suspected pure pancreatic polypeptide-secreting neuroendocrine carcinoma of the gallbladder. The tumor was initially interpreted as an adenocarcinoma of the gallbladder, but was found to have a neuroendocrine component after review. The pathology supports the view that a primitive epithelial stem cell can express both epithelial and neuroendocrine characteristics and can differentiate into both an adenocarcinoma and a neuroendocrine carcinoma. Upon recurrence, the tumor produced symptoms due to local growth, but eventually metastasized and led to the death of the patient within 4 years. The patient was treated with chemoembolization followed by the long-acting somatostatin analog octreotide acetate. The high serum level of pancreatic polypeptide may have contributed to cholestasis and cholelithiasis. Earlier measurement of serum hormone levels and identification of high pancreatic polypeptide levels may have suggested the presence of residual tumor and led to closer follow-up, imaging studies, and therapy.
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PMID:Pancreatic polypeptide hypersecretion associated with a neuroendocrine carcinoma of the gallbladder. 989 73

A 41-year-old male presented with progressive visual defects, acromegaly and hyperthyroidism. After clinical evaluation a giant GH/TSH-secreting pituitary adenoma was diagnosed. Administration of the somatostatin analog octreotide at doses of 150 microg s.c. per day inhibited the secretion of both GH and TSH. A three-week treatment with octreotide prior to surgery led to slight visual improvement and CT scan showed some new necrotic areas within the tumor mass. Transcranial surgery was performed. By immunohistochemical analyses of the adenoma tissue GH, prolactin and beta-chorionic gonadotropin were detected; TSH was negative. Electron microscopy revealed an undifferentiated, monomorphous adenoma with morphological features of an acidophil stem cell adenoma such as the presence of misplaced exocytoses, fibrous bodies and mitochondrial gigantism. However, the tumor cells contained small secretory granules (up to 250 nm) accumulated along the cell membrane characteristic of thyrotrope cells. Furthermore, some adenoma cells were fusiform with long cytoplasmic processes resembling thyrotropes. Two months after the operation CT scan revealed a large residual tumor. Serum GH and TSH levels had increased again and the TSH level was even higher than before the treatment. The patient died suddenly, most probably of lethal arrhythmia. Specimens of the adenoma tissue obtained at autopsy confirmed the previous findings with the exception of positive immunostaining for TSH which was found in less than 1% of the adenoma cells. This undifferentiated, monomorphous GH/TSH-secreting pituitary adenoma represents an entity that is unusual both in its ultrastructural features and clinical manifestations suggesting a cytogenesis from an early, undifferentiated stem cell.
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PMID:Clinical and morphological features of undifferentiated monomorphous GH/TSH-secreting pituitary adenoma. 1036 9

The somatostatin analog octreotide was administered prior to transsphenoidal surgery in three patients with tumors that extended to the suprasellar space and one side of the cavernous sinus. Octreotide, 100 micrograms twice a day, was subcutaneously injected for 2 weeks. Octreotide administration reduced the serum growth hormone (GH) levels in these patients from 82 to 22 ng/ml, from 148 to 12 ng/ml, and from 129 to 9 ng/ml. The tumor size shrank by about 50%, and the suprasellar extension disappeared in two patients. The main tumor was sharply dissected from the normal pituitary gland at surgery. Intracavernous portions were removed using a curette. Postoperatively, GH levels were less than 5 ng/ml in two patients, and 8.5 ng/ml in one patient. Follow-up magnetic resonance imaging revealed a small residual tumor in one side of the cavernous sinus in all patients. Follow-up GH levels were less than 5 ng/ml in one patient, and less than 2 ng/ml in two patients treated with bromocriptine. Preoperative administration of octreotide for 2 weeks reduced tumor volume and allowed near-total surgical resection of invasive macroadenomas without compromising the treatment course. Residual tumor due to intracavernous extension can be managed with bromocriptine or gamma knife radiosurgery.
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PMID:Preoperative short-term administration of octreotide for facilitating transsphenoidal removal of invasive growth hormone-secreting macroadenomas. 1043 77


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