PubMed · 4344353
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1972-11-18. Diazoxide.. https://pubmed.ncbi.nlm.nih.gov/4344353/
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We have characterized the biosynthetic origin of somatostatin-14 (SS-14), SS-28, and pro-SS[1-10] from pro-SS (PSS) in 1027B2 rat islet tumor cells. Because these cells lack regulated secretion and show unresponsiveness of the SS gene to cAMP, we have additionally carried out morphological and functional studies to elucidate the molecular defect in cAMP signalling and to localize the sites of PSS maturation along the secretory pathway. Cell extracts and secretion media were analysed by high performance liquid chromatography and specific C- and N-terminal radioimmunoassays. Electron microscopic sampling of 1027B2 cell cultures showed that most cells had very few dense core secretory granules for heterogeneous sizes. The cells expressed the endoproteases furin, PC1, and PC2 and contained large quantities of fully processed SS-14 and SS-28 with very little unprocessed PSS (ratio SS-14:SS-28:PSS = 39:51:10%). They secreted high concentrations of SS-14, SS-28, and PSS[1-10] constitutively along with PC1 and PC2. Pulse-chase studies demonstrated that PSS is rapidly (within 15 min), and efficiently processed to SS-14, SS-28, and PSS[1-10] via separate biosynthetic pathways: PSS --> SS-14 + 8 kDa; PSS --> SS-28 + 7 kDa; PSS --> PSS[1-10]. Monensin reduced intracellular SS-like immunoreactivity without altering processing efficiency. Transfection with the catalytic subunit of protein kinase A (PKA-C) activated SS promoter-CAT activating indicating that the defect in cAMP-dependent signaling in 1027B2 cells lies at the level of PKA-C. PKA-C overexpression failed to alter the ratio of processed SS-14 and SS-28. These results demonstrate that SS-14, SS-28, and PSS[1-10] are independently synthesized from PSS and that efficient precursor processing can occur within the constitutive secretory pathway in the relative absence of dense core secretory vesicles.
BACKGROUND: Octreotide, a long-acting somatostatin analogue, has demonstrated clinical utility in patients with carcinoid syndrome and malignant islet cell tumors of the pancreas. Prior studies have reported a greater than expected incidence of cholelithiasis in patients treated with octreotide for acromegaly. This study attempted to determine the incidence and morbidity of cholelithiasis in a group of patients with metastatic carcinoid or malignant pancreatic islet cell tumors who were receiving chronic therapy with octreotide. METHODS: Forty-four of 55 patients on investigational protocols with octreotide were eligible for chart review; 10 patients were excluded due to prior cholecystectomy and 1 patient due to asymptomatic cholelithiasis at presentation. Patients fell into three treatment groups. The low dose (LD) group was comprised of 17 patients receiving 150 microg of subcutaneous octreotide 3 times a day. Twenty-one patients received high dose (HD) therapy comprised of 500 microg given 3 times a day. The low dose-high dose (LD-HD) group was comprised of 6 patients who had their dose escalated from 150 microg to 225-500 microg of octreotide 3 times a day. RESULTS: The overall incidence of cholelithiasis and/or gallbladder sludge was found to be 52.3% in all 3 treatment groups. Three of the 44 patients (6.8%) had symptomatic disease requiring emergency cholecystectomy. Five other patients underwent elective or incidental gallbladder surgery. The incidence of cholelithiasis in the LD, LD-HD, and HD groups was 35.3%, 66.6%, and 61.9%, respectively. The incidence of acute cholecystitis in the three groups was 11.8%, 0%, and 4.8%, respectively. CONCLUSIONS: Although greater than 50% of patients receiving octreotide developed cholelithiasis, a much smaller percentage of patients had symptomatic gallbladder disease. Patients receiving chronic octreotide treatment require monitoring for the development of gallstones. However, prophylactic cholecystectomy is not indicated, unless it is performed in conjunction with bowel resection or cytoreductive hepatic surgery.
Acinar cell carcinoma (ACC) and islet cell tumor (ICT), both rare pancreatic neoplasms, can be diagnosed accurately and rapidly with the use of imaging-guided fine-needle aspiration biopsies. The specific cytologic features of these tumors are described in a series of 17 patients, and histologic and immunocytochemical correlations are discussed. Important cytologic findings in ACC are loosely cohesive clusters with cells having uniform nuclei and prominent nucleoli, cytoplasm is finely granular and eosinophilic. Islet cell tumors show many single cells, occasional rosettes, uniform nuclei, sometimes binucleate, dense basophilic cytoplasm. Chromogranin is often positive (80%) in ICT. Trypsin and chymotrypsin were often positive (71%) in ACC. Histology was confirmatory in all cytology cases. The recognition of cytologic features in conjunction with immunocytochemical studies can increase the diagnostic sensitivity for these two rare tumors.