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

The glucagonoma syndrome occurs in some but not all patients with a benign or malignant islet cell tumor and hyperglucagonemia. Manifestations may include anemia, diabetes mellitus, pruritic skin rash, glossitis, stomatitis, weight loss, diarrhea, flexible fingernails, venous thromboses, low plasma amino acid levels, and coarse folds of the jejunum and ileum. Most patients are postmenopausal women, but men and women ages 40 to 65 have been affected. The course is variable depending upon the nature of the underlying tumor. Twenty-two cases of probable glucagonoma syndrome have been reported; twelve documented with glucagon levels. The hyperglucagonemia results from elevation of the proglucagon and true glucagon immunoreactive fractions of pancreatic glucagon. Management of the rash can be accomplished rarely with topical or systemic antibiotics or corticosteroids. If the tumor is resectable, surgery reverses the syndrome. Patients with metastatic disease have responded to streptozotocin and DTIC.
 ...
PMID:The glucagonoma syndrome and its management. 20 9

A 34-year-old man presented with classic glucagonoma syndrome manifested by weight loss, dermatitis, stomatitis, anemia, and mild diabetes mellitus. The diagnosis of glucagonoma was made by light and electron microscopic demonstration of a metastatic alpha cell carcinoma in a liver biopsy specimen. Plasma glucagon concentration was abnormally high. The patient also had symptoms and signs of involvement of the central nervous system. Radionuclide and CAT scans of the brain, negative CSF cytology and myelography excluded the possibility of metastases or other space-occupying lesions. Glucagon was demonstrated in the CSF. We postulate that the neurologic symptoms were due to direct or indirect effect of this hormone on the brain. Following therapy with streptozotocin and 5-fluorouracil, the patient had a subjective and objective clinical and hormonal remission of his disease including amelioration of his neurological impairment.
 ...
PMID:Neurologic involvement in glucagonoma syndrome: response to combination chemotherapy with 5-fluorouracil and streptozotocin. 22 32

We report three new cases of glucagonoma revealed, 6 to 12 months after its onset, by non-specific and misleading skin lesions associated in all 3 cases with diabetes mellitus, severe deterioration of the general condition and hyperglucagonaemia. Non-invasive methods, such as ultrasonography and computerized tomography (CT), are most helpful to locate the pancreatic tumour. Phlebography with tiered venous blood sampling is useful in difficult cases. A false positive result has been recorded with arteriography. Ultrasonography and CT have yielded two false negative results. The alpha-chain of the chorionic gonadotrophin hormone has limited value in the diagnosis of malignant glucagonoma. Treatment is surgical, but despite it, the prognosis is severe (two of our three patients died), due to the risk of thromboembolism, to cachexia and to metastases that are frequent at the time of diagnosis.
 ...
PMID:[The glucagonoma syndrome. 3 new cases]. 141 Aug 82

We report the results of transcatheter intraarterial perfusion of liver with the emulsion of iodized oil and cytostatics performed as palliative treatment in three patients with hepatic metastases of pancreatic endocrine tumors. Two patients had insulinoma and one patient had glucagonoma. They were also treated by medical therapy from the time the diagnosis was made. Intraarterial perfusion of the liver was achieved by Lipiodol emulsified with streptozotocin and 5-fluorouracil. Regarding these three patients therapeutic responses were different in duration of hormone secretion decrease. Relief of hypoglycemic attacks and a significant decrease of plasma immunoreactive insulin concentration within 12 months without any additional therapy was observed in the patient with insulinoma (case no. 2). This patient had slightly increased immunoreactive glucagon concentration from the time of diagnosis. A decrease of immunoreactive insulin levels in other patient with insulinoma and an increase in plasma glucose to the euglycemic range during two months allowed a reduction of doses of somatostatin analogue and diazoxide. Due to rapid progression of the disease, intraarterial perfusion of liver was repeated three months later with the same results. Remission of symptoms was partial in the case of glucagonoma. Immunoreactive glucagon levels were not changed and there was no significant benefit of the treatment. Intraarterial perfusion of liver with iodized oil and cytostatics could be an effective, safe and repeatable method of palliating symptoms of malignant pancreatic tumors, especially in inoperable but nonterminal cases. It could allow reduction of additional medical therapy, but success of the treatment is not predictable.
 ...
PMID:Improvement of metastatic endocrine tumors of the pancreas by hepatic artery chemoembolization. 144 92

Pancreatic tumours of transgenic mice carrying a glucagon-promoted simian virus 40 (SV40) T antigen oncogene have been analysed by histological, histochemical, ultrastructural and radioimmunological means. Seven transgenic mice were examined revealing dysplastic and neoplastic lesions in the endocrine pancreas. Four tumours were identified, one of which metastasized to periadrenal spaces and paravertebral lymph nodes. Benign tumours were composed of argyrophilic, endocrine cells reactive to a range of antibodies against neuroendocrine markers (neuron-specific enolase, protein gene product 9.5, chromogranin A, synaptophysin and protein 7B2) and different fragments of the proglucagon molecule (glucagon, glicentin, glucagon-like polypeptides 1 and 2). A few tumour cells expressed pancreatic polypeptide, somatostatin or insulin. Conventional ultrastructural analysis and immunogold labelling revealed typical glucagon-immunoreactive alpha granules which co-stored glicentin and glucagon-like polypeptides 1 and 2. The malignant primary tumour and its metastases were composed mainly of cells which did not show immunoreactivity for neuroendocrine markers or peptides. Atypical, glucagon-immunogold labelled granules were detected at electron microscopy in differentiated tumour cells and C-type retroviral particles in the largest tumour population of degranulated cells. The transgene-encoded oncoprotein SV40 large T-antigen was detected in the nuclei of well-differentiated tumour cells and in alpha cells of some dysplastic islets. All tumour-bearing mice showed high levels of circulating glucagon-like immunoreactivity. Transgenic mice harbouring the glucagon-promoted SV40 T antigen oncogene may provide a model for human glucagonoma.
 ...
PMID:Glucagonomas of transgenic mice express a wide range of general neuroendocrine markers and bioactive peptides. 167 63

The therapeutic principles in the management of endocrine gastroenteropancreatic (GEP) tumours include surgical extirpation of the primary tumour in the absence of metastases and medical control of symptoms in the preoperative phase. In the presence of metastases only palliative procedures are available. Tumour growth might be controlled by surgical procedures as debulking of tumour masses, medically by chemotherapy and more recently by new developments as a long-acting somatostatin analogue (SMS 201-995) and alpha-interferon. Their efficacy is currently evaluated in prospective studies. In contrast to inhibition of growth symptoms derived from excessive hormone production by GEP tumours can be well controlled. SMS 201-995 effectively prevents or at least improves flush and diarrhoea in the carcinoid syndrome, disabling diarrhoea in the Verner-Morrison syndrome and migratory erythema in the glucagonoma syndrome. SMS acts by inhibition of hormone release from the tumour and by a direct mechanism at the site of the target cell via SMS receptors present on tumour and target cells. For control of acid hypersecretion in gastrinoma patients omeprazole is superior to all former and present alternatives and replaced total gastrectomy completely. A similarly effective drug to prevent hypoglycaemia due to uncontrolled insulin release from insulinomas is not available since neither SMS nor diazoxide are effective in every insulinoma patient.
 ...
PMID:Therapeutic strategies in the management of endocrine GEP tumours. 170 88

Because of its widespread distribution within the nervous system and the gastro-enteropancreatic (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, a long-acting, synthetic octapeptide analogue of the naturally occurring hormone. Sandostatin represents a significant advance in the treatment of GH and TSH secreting pituitary tumours and GEP endocrine tumours (carcinoid tumour, 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 tumour cells and indirect effect whereby Sandostatin lowers GH, IGF-1 and numerous gastrointestinal peptides, Sandostatin may prove useful as an adjunctive therapy in cancer patients. In vivo labelling of somatostatin receptor-positive tumours with radiolabelled somatostatin analogues now allows localisation of such tumours and their metastases. Moreover, targeted irradiation of these tumours by beta particle emitting isotopes attached to such somatostatin analogues may become possible. The use of Sandostatin in acute oesophageal variceal bleeding, pancreatic pseudocysts, gastrointestinal and pancreatic external fistulae, short bowel syndrome, dumping syndrome and AIDS-related refractory hypersecretory diarrhea has provided encouraging results. Preliminary reports indicate efficacy of Sandostatin in psoriasis, autonomic neuropathy (postprandial and orthostatic hypotension) and its ability to reduce height velocity in tall adolescents. The ultimate role of Sandostatin as a therapeutic agent in these disorders is being explored in prospective clinical trials.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Future medical prospects for Sandostatin. 198 Jul 78

After an acute episode of pancreatitis, a 63-year-old man was found to have a pancreatic glucagonoma. The tumor was resected without evidence of metastases. Three years later he had symptoms of uncontrolled diabetes, no skin lesions, and diarrhea and was found to have a pancreatic pseudocyst and multiple hepatic metastases. Glucagon concentrations were raised but were suppressible by glucose and somatostatin and responded to arginine stimulation. He was treated for 6 months with octreotide (Sandostatin), which reduced his symptoms; the pseudocyst resolved, but liver metastases continued to grow. Although spontaneous resolution of the pseudocyst is possible, this case appears to illustrate differences in sensitivity of endocrine and exocrine tissues to suppression by Sandostatin.
 ...
PMID:Somatostatin analogue in treatment of coexisting glucagonoma and pancreatic pseudocyst: dissociation of responses. 216 87

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)
 ...
PMID:Future medical prospects for Sandostatin. 220 87

Endocrine pancreatic tumors are slowly growing neuroendocrine neoplasms with a malignant potential which may cause symptoms such as hypoglycemia, multiple ulcers, diarrhea, flush, hyperglycemia and skin rash. A prospective study was performed on 84 patients with endocrine pancreatic tumors. In 59 patients (70%) the tumors were malignant. Of the 84 patients, 23 had insulinomas, 25 gastrinomas, 20 nonfunctioning tumors, 14 the WDHA syndrome, 1 somatostatinoma and 1 glucagonoma. The median age at diagnosis was 53 years and the median delay from first symptom to diagnosis was 2 years. The most common site of the pancreatic primary tumor was the tail (41%), and metastases were most frequently located in the liver (60%) and lymph nodes (44%). Plasma chromogranin A + B was elevated in 94%, serum pancreatic polypeptide (PP) in 74%, plasma neurotensin in 67% and serum gastrin in 62%. Serum HCG-alpha and -beta subunits were elevated in 41 and 30% respectively, all except 3 having a verified malignant tumor. The median survival from first symptom and diagnosis was 14.2 and 8.7 years respectively. Patients with MEN-1 had a significantly better survival from diagnosis than sporadic cases (median 15.1 versus 5.8 years). Patients who received interferon after failing chemotherapy had a significantly better survival than those given chemotherapy alone (5-year survival 65 and 50% respectively).
 ...
PMID:Neuroendocrine pancreatic tumors. Clinical findings in a prospective study of 84 patients. 247 25


1 2 3 4 5 6 7 8 9 Next >>