Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This case report describes a patient with pancreatic cholera caused by a vasoactive intestinal polypeptide-producing pancreatic tumor. The case presents several unusual characteristics of this disease. The primary tumor was a mucinous adenocarcinoma of the pancreas. The serum vasoactive intestinal polypeptide level of 2400 pmol/L is the highest reported. At this vasoactive intestinal polypeptide level, the somatostatin analogue SMS 201-995 at doses up to 2 mg/24 h did not control the 21 L/24 h stool output. Fecal incontinence due to a manometrically documented hypotonic internal anal sphincter occurred. Using surgically created stomas, the segmental gastrointestinal fluid and sodium losses were shown to be greatest from the jejunum, whereas potassium losses from the colon and small intestine were equal. The cellular mechanism for the small intestinal potassium secretion is not known.
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PMID:Pancreatic cholera syndrome due to a vasoactive intestinal polypeptide-producing tumor: further insights into the pathophysiology. 282 45

Signs and symptoms of Cushing's syndrome developed rapidly after total gastrectomy in a 37-yr-old man with a metastatic gastrin-secreting islet cell carcinoma. Argyrophilic tumor cells in a lymph node removed during operation immunostained for gastrin and ACTH. Treatment for more than 6 months with the somatostatin analog SMS 201-995 (300 micrograms/day) greatly reduced serum gastrin levels and normalized plasma ACTH and cortisol levels and urinary cortisol excretion, and the signs and symptoms of Cushing's syndrome disappeared. The size of the primary tumor in the head of the pancreas, which had grown rapidly before SMS 201-995 therapy, stabilized after 6 months of treatment with the analog. We conclude that SMS 201-995 can reduce ACTH as well as gastrin secretion from islet cell carcinomas as well as control tumor growth.
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PMID:Successful treatment with SMS 201-995 of Cushing's syndrome caused by ectopic adrenocorticotropin secretion from a metastatic gastrin-secreting pancreatic islet cell carcinoma. 284 25

We have examined the effects of the somatostatin analogue (SMS 201-995) in 10 patients with gastrinoma syndrome. Four had hepatic metastases, one had a tumor in a peripancreatic lymph node, two had resectable intrahepatic and intraduodenal gastrinomas, and in three the primary tumor was not found. Acutely, SMS 201-995 decreased acid secretion and restored the BAO/MAO ratio to normal in eight of eight patients. Basal and secretin-stimulated gastrin responses were suppressed but not normalized in eight of eight patients. Suppression of endogenous gastrin restored responsiveness to exogenous gastrin. Treatment for up to 12 months with SMS 201-995 controlled symptoms in six of eight patients, suppressed serum gastrin in three of five, and suppressed acid secretion in three of three patients. Treatment with SMS 201-995 in three patients for 5 months decreased tumor secretion of gastrin and diminished basal acid secretion, an effect that persisted in two of three patients 48 hours after withdrawal of SMS. In patients with metastatic disease who had high levels of gastrin, SMS treatment for 5 to 12 months did not inhibit tumor growth or decrease gastrin levels. SMS treatment arrested progression of tumor growth only in patients who had a reduction in gastrin and gastric acid secretion. We conclude that SMS may be useful in the management of gastrinoma patients by decreasing hypersecretion of gastrin and gastric acid and, over a longer term, may even change tumor capacity to release gastrin and gastric acid secretion. SMS may thus be useful as a palliative agent and as an adjunct to conventional treatment of the gastrinoma syndrome. SMS does not appear to shrink tumor mass in patients with very high basal gastrin levels.
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PMID:Somatostatin analogue (SMS 201-995) in patients with gastrinomas. 290 62

Six new cell lines have been established from human neuroblastomas. Cell line SMS-KAN, from primary tumor before therapy, and line SMS-KANR, from bone marrow after chemotherapy and radiotherapy, were established from the same patient. Cell lines SMS-KCN (from primary tumor before any therapy) and SMS-KCNR (from bone marrow after chemotherapy) were established from another patient. Two other lines (SMS-MSN and SMS-SAN) were established from different patients before any therapy was given. Cell lines established from recurrent disease after chemotherapy (SMS-KANR and SMS-KCNR) had significantly shorter doubling times and increased plating efficiencies compared to those of cell lines derived from the same patient before chemotherapy (SMS-KAN and SMS-KCN). All cell lines contained tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and dopamine-beta-hydroxylase. Measurable amounts of choline acetyltransferase were also detected in SMS-KAN and SMS-KANR. Karyotype analysis showed all cell lines except SMS-MSN to be pseudodiploid with modal numbers of 46 and deletions of the short arm of chromosome 1; SMS-MSN had a modal number of 57-58 chromosomes. All cell lines had double-minute chromosomes, except SMS-KANR, which had abnormally banding regions. These new cell lines provide in vitro models of neuroblastoma suitable for the study of differences in neuroblastoma cell populations before chemotherapy as compared to the cell populations that proliferate after therapy.
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PMID:Characterization of human neuroblastoma cell lines established before and after therapy. 345 56

Somatostatin and its analogs are antiproliferative in a wide range of normal and neoplastic tissues. In this study we investigated the effect of octreotide (SMS 201-995) on the invasion and growth of three follicular thyroid cancer (FTC) cell lines from one patient in vitro and in vivo. FTC133 was established from the primary tumor, FTC236 from a cervical lymph node metastasis, and FTC238 from a lung metastasis. Invasion was the ability of tumor cells to penetrate 8-microns pore polycarbonate membranes coated with Matrigel. Invasion and proliferation were analyzed using the MTT assay. For in vivo experiments, athymic nude mice were sc inoculated with 500,000 calls of FTC133. The animals were treated twice daily with octreotide sc (100-300 micrograms/kg). RIA studies yielded dose-dependent high plasma levels of octreotide (3.43-6.5 ng/mL). Octreotide had a biphasic effect, enhancing growth at low concentrations (1-10 nmol/mL) and inhibiting it at high concentrations (100 nmol to 1 mumol/mL). Octreotide had also a dose-dependent biphasic effect on the invasion of FTC, inhibiting the invasion of all follicular thyroid cancer lines at high concentrations. However, it affected invasion less than growth. Octreotide (10 nmol/mL) stimulated the invasion of FTC133 by 13%, whereas stimulation was lower in both FTC metastases (FTC236, 6%; FTC238, 7%; P < 0.01). At higher concentrations (100 nmol to 1 mumol/mL), octreotide inhibited invasion of FTC133 by 17% (FTC236, 15%; FTC238, 17%; P < 0.01). During a 3-week treatment period, octreotide had no antiproliferative effect on the growth of FTC133 cells in nude mice. In conclusion, octreotide at low concentrations stimulates and at high concentrations inhibits the growth and invasion of follicular thyroid cancer cells in culture. However, it has no effect on the growth of FTC cells in animal experiments. Thus, the value of octreotide as an antitumoral agent in follicular thyroid cancer must be critically questioned.
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PMID:Somatostatin analog octreotide inhibits the growth of differentiated thyroid cancer cells in vitro, but not in vivo. 867 90

Autotaxin (ATX) is a newly found autocrine tumor cell motility-stimulating factor. ATX is a member of the ecto-phosphodiesterase I (PD-I)/ nucleotide pyrophosphatase family. PD-Ialpha was found as a brain-type ecto-phosphodiesterase I/nucleotide pyrophosphatase. ATX and PD-Ialpha are alternative splicing products from one gene. ATX stimulates motility of A2058 melanoma cells in vitro; however, it has not been known if PD-Ialpha/ATX is expressed in naturally occurred human tumors. In this study, we examined the expression of the human PD-Ialpha/ATX gene in human neuroblastoma tumor tissues and the motility stimulating activity of recombinant ATX on neuroblastoma cells and investigated its transcriptional regulatory mechanism in a human neuroblastoma cell line. The PD-Ialpha/ATX gene was expressed in the primary tumor tissues from neuroblastoma patients to varying degrees. This gene is also expressed in the SMS-KAN neuroblastoma cell line. We identified both isoforms, PD-Ialpha and ATX, in these tumor tissues and SMS-KAN cells. The recombinant ATX stimulated the motility of SMS-KAN cells at low nanomolar concentration. We situated the promoter region, which is essential for its transcription in SMS-KAN cells, at -287 to -254 nucleotides by the promoter activity assay. The gel-shift assay revealed that there exists a nuclear protein in SMS-KAN cells that binds this region. These new insights about autocrine tumor cell motility-stimulating protein will help us to understand the metastatic mechanism of human neuroblastoma.
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PMID:Expression and transcriptional regulation of the PD-Ialpha/autotaxin gene in neuroblastoma. 919 34