Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The somatostatin analogue octreotide (SMS 201-995) inhibits secretion and growth of certain tumor cells, and current efforts are directed toward the elucidation of its mode of antiproliferative action. In this study, the effect of octreotide on the growth of ZR-75-1 human breast cancer cells has been characterized in immunodeficient nude mice and in cell culture. These results have been related to the expression of somatostatin receptors in vivo and in vitro. Continuous infusion of 10 micrograms/kg/h of octreotide yielded plasma levels of 5.7 ng/ml and elicited highly significant growth inhibitory effects on solid ZR-75-1 breast tumors in nude mice. After 2 and 4 weeks of treatment, tumor volumes in the octreotide group were 39.1 and 36.7% of those of control animals treated with vehicle, respectively. Autoradiographic studies demonstrated that 8 of 12 ZR-75-1 tumors studied were somatostatin receptor positive. When ZR-75-1 tumor cells were exposed in vitro to nanomolar concentrations of octreotide, a dose-dependent inhibition of cell growth was observed in the presence of 5% fetal calf serum or under serum-free conditions using epidermal growth factor, insulin-like growth factor type I, or insulin as growth stimulus. In parallel receptor-binding experiments, ZR-75-1 cells were shown to express specific high-affinity somatostatin receptors (Kd value = 0.9 nM, Bmax = 6000 sites/cell). From these experiments, we conclude that octreotide is a powerful inhibitor of ZR-75-1 tumor cell growth in nude mice and in culture. This inhibitory action of octreotide and the presence of somatostatin receptors on ZR-75-1 tumor cells in vitro and in vivo suggest a direct, somatostatin receptor-mediated effect of octreotide.
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PMID:Antiproliferative effects of the somatostatin analogue octreotide (SMS 201-995) on ZR-75-1 human breast cancer cells in vivo and in vitro. 132 89

A patient with metastatic VIP-producing pancreatic tumor was successfully treated with subcutaneous octreotide, an analogue of somatostatin, for more than 4 years. The profuse diarrhea was rapidly controlled and the plasma concentrations of the hormones (VIP, neurotensin, gastrin, pancreatic polypeptide) fell to nearly normal within 2 months. Because of asymptomatic increase in tumor size, we added chemotherapy 2 years later. Since the drug is rapidly effective and well tolerated, it will probably become the therapy of choice in this syndrome.
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PMID:[Long-term therapy of a metastasizing pancreatic vipoma using the somatostatin derivative octreotide]. 132 86

The significance of the enterochromaffin-like (ECL) cell as a critical endocrine regulator of gastric fundic mucosal function has only recently been recognized. Although the percentage of these cells present in the human fundic mucosa is less than that in rodents, the observation that they secrete histamine and are probably important modulators of parietal cell function has resulted in their attaining some considerable biological significance. The further identification of gastrin and somatostatin receptors on the surface of the ECL cells has suggested that other neurohormonal influences may be significant in the regulation of parietal cell function, utilizing the ECL cell as an intermediate modifier. While abnormalities of ECL cells in the human stomach (hyperplasia/neoplasia) have been mostly confined to observations in patients with pernicious anemia and atrophic gastritis, the recent recognition of hyperplasia in pharmacotherapeutically induced achlorhydric or hypochlorhydric states has excited considerable interest. It has been proposed that the generation of luminal hypo- or achlorhydria by powerful acid inhibitory pharmacotherapy may result in hypergastrinemia. This condition is responsible initially for the development of hyperplasia and, subsequently, possibly even neoplasia of the ECL system of the fundic mucosa. This phenomenon seems to be prevalent in rodents but has so far been only rarely observed in humans, e.g., pernicious anemia, atrophic gastritis. In particular, patients with the gastrinoma component of the multiple endocrine neoplasia type I syndrome exhibit ECL-cell hyperplasia and neoplasia after exposure to acid inhibitory pharmacotherapy. It is therefore likely that an underlying genomic phenomenon is necessary prior to the induction of hyperplasia and subsequent neoplastic transformation. The scientific evaluation of the relationship between gastrin, ECL-cell function, and the development of hyperplasia and neoplasia may provide some important information in regard to the molecular evolution of gastrointestinal neuroendocrine disease states. It is possible that the future pharmacotherapy of acid secretory disease may require regulation not only of parietal cell but of ECL-cell function.
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PMID:The pathobiology of the human enterochromaffin-like cell. 134 Oct 78

Distinct proteins complexed with somatostatin and the somatostatin analogue BIM-23014C were revealed in human breast cancer cells using the cross-linking assay. One BIM-23014C-specific complex (Mr 57,000) was observed in MCF-7 (monolayer, nodule, and tumor) and T47D. Growth inhibition of MCF-7 tumor xenografts by BIM-23014C was dose related in the 6-day subrenal capsule assay. Three complexes (Mr 27,000, 42,000, and 57,000) were detected in MDA-MB-231, and no complex was visible in HBL-100. No correlation was found between receptors for BIM-23014C and epidermal growth factor in these lines. Twenty-seven of 30 human breast tumors (90%) had at least one BIM-23014C receptor. Sixteen had three complexes (Mr 27,000, 42,000, and 57,000). Six had the two complexes (Mr 27,000 and 57,000), two had Mr 42,000 and 57,000 complexes, two had just the Mr 27,000 complex, and one had just the Mr 42,000 complex. The presence of the three BIM-23014C receptors was positively correlated (P less than 0.05) to the low amount of sex steroid receptors (less than 20 fmol/mg) [seven of eight (estrogen receptor negative, progesterone receptor negative) versus four of 14 (estrogen receptor positive, progesterone receptor positive)]. Another positive correlation was established between the absence of progesterone receptors and the presence of these three complexes [12 of 16 (progesterone receptor negative) versus four of 14 (progesterone receptor positive)]. This high percentage of BIM-23014C receptor-positive biopsies and its inhibitory activity would support its clinical potential for the treatment of breast cancer.
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PMID:Molecular heterogeneity of somatostatin analogue BIM-23014C receptors in human breast carcinoma cells using the chemical cross-linking assay. 134 85

AR4-2J, a rat pancreatic acinar-tumor cell line, was used to investigate long-term effects of basic fibroblast growth factor (bFGF) and somatostatin on pancreatic cancer cells. We observed that bFGF stimulated cell proliferation when cells were cultured in serum-free medium. The effect was dose-dependent with half-maximal and maximal effects at 25 pM and I nM bFGF, respectively. The somatostatin analog SMS 201-995 (SMS) decreased the growth-promoting effect of bFGF. The maximal effect was observed at I nM SMS and the half-maximal effect at 20 pM SMS. Characterization of bFGF receptor-binding properties with [125I]bFGF revealed that AR4-2J cells exhibited 2 classes of bFGF binding site with respective KD values of 47 pM and 3 nM and binding capacities of 14 fmol and 0.9 pmol/10(6) cells. High-affinity receptors correlated with bFGF stimulation of AR4-2J cell growth, suggesting that the effects of bFGF are receptor-mediated.
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PMID:Basic fibroblast growth factor induces proliferation of a rat pancreatic cancer cell line. Inhibition by somatostatin. 134 15

A variety of vasoactive substances including biogenic amines, neuropeptide Y, somatostatin, enkephalin, ACTH, corticotropin-releasing hormone, growth hormone releasing hormone, vasoactive intestinal peptide, calcitonin, and atrial natriuretic factor have been extracted from intra-adrenal and extra-adrenal pheochromocytomas in men. Some of them appear to play an important role for the development of hypertension or clinical serious symptoms. However, informations on the molecular forms of other substances in pheochromocytomas are still limited, and precise amount of the peptides or hormones in the tumors has not yet been quantitated. Numerous in vitro or in vivo studies of this documented neoplasm over the years have been reviewed in this manuscript. Clinical analyses of early diagnosis, localization diagnosis, treatment of multiple endocrine neoplasia, preoperative and operative treatments are also evaluated in this paper. These informations will probably provide additional evidence for the multi-secretory APUD cells of neural crest origin and will contribute the therapy in patients with pheochromocytoma.
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PMID:[Pheochromocytoma--basic and clinical analyses]. 134 92

A case of duodenal somatostatinoma is described in a patient with Von Recklinghausen neurofibromatosis. The patient presented with exocrine pancreatic insufficiency, probably due to distal obstruction of the pancreatic duct by the tumor. Preoperative evaluation with calcium-pentagastrin and tolbutamide stimulation tests were nondiagnostic. At laparotomy, local excision of the tumor was performed. Pathological findings were compatible with duodenal somatostatinoma, causing pancreatic fibrosis. Somatostatin extracted from the tumor coeluted with the somatostatin-14 standard on high performance liquid chromatography (HPLC).
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PMID:Exocrine pancreatic insufficiency and pancreatic fibrosis due to duodenal somatostatinoma in a patient with neurofibromatosis. 134 57

Fifty-one adrenal pheochromocytomas and 14 paragangliomas were evaluated for somatostatin (SRIH) receptor content with in vitro autoradiography on tissue sections from surgically removed tumors, using iodinated 125I[Tyr]3 octreotide as radioligand. Thirty-seven of 51 pheochromocytomas were SRIH receptor positive (73%), as well as 13 of 14 paragangliomas (93%). These SRIH receptors were of high affinity, pharmacologically specific for SRIH and localized on the tumor tissue. Using in vivo imaging techniques with radiolabeled SRIH analogs, paragangliomas could be visualized in five patients, as well as pheochromocytomas in two of three patients. All tumors tested subsequently in vitro (n = 7) were shown to contain SRIH receptors. A majority of pheochromocytomas were also shown to have a high tumoral SRIH content as measured by immunohistochemical techniques. Detection of SRIH messenger RNA in pheochromocytomas by in situ hybridization indicated that the SRIH was produced in the tumors. A weak inverse correlation was observed between SRIH receptor status and tumoral SRIH content, suggesting that SRIH receptors may be down-regulated by high levels of endogenous SRIH in some tumors. There was no correlation between the SRIH receptor status and sex, age, tumor size, benign vs. malignant tumor, or urinary metanephrine excretion. These tumors were also analyzed for allelic losses on various chromosomes and showed significant loss of heterozygosity (LOH) on chromosomes 1p, 3p, 17p, and 22q. All eight tumors with LOH on chromosome 1p were SRIH receptor positive (100%), whereas only 6 of 11 tumors without LOH on 1p (55%) were SRIH receptor positive, suggesting a correlation between LOH on 1p and SRIH receptor positive status. SRIH receptors thus represent a consistent pathobiochemical marker for most of these adrenal and extra-adrenal tumors. In addition, these receptors may be of potential interest for the in vivo localization of these tumors.
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PMID:In vitro and in vivo detection of somatostatin receptors in pheochromocytomas and paragangliomas. 134 24

Scintigraphy with 123I-Tyr-3-octreotide has several major drawbacks as regards its metabolic behavior, its cumbersome preparation and the short physical half-life of the radionuclide. The use of another radiolabeled analog of somatostatin, 111In-DTPA-D-Phe-1-octreotide, has consequently been proposed. DTPA-D-Phe-1-octreotide can be radiolabeled with 111In in an easy single-step procedure. DTPA-D-Phe-1-octreotide is cleared predominantly via the kidneys. Fecal excretion of radioactivity amounts to only a few percent of the administered radioactivity. For the radiation dose to normal tissues, the most important organs are the kidneys, the spleen, the urinary bladder, the liver and the remainder of the body. The calculated effective dose equivalent is 0.08 mSv/MBq. Optimal 111In-DTPA-D-Phe-1-octreotide scintigraphic imaging of various somatostatin receptor-positive tumors was obtained 24 hr after injection. In the six patients studied, tumor localization with 123I-Tyr-3-octreotide and with 111In-DTPA-D-Phe-1-octreotide were found to be similar. However, the normal pituitary is more frequently visualized with the latter radiopharmaceutical. In conclusion, 111In-DTPA-D-Phe-1-octreotide appears to be a sensitive somatostatin receptor-positive tissue-seeking radiopharmaceutical with some remarkable advantages: easy preparation, general availability, appropriate half-life and absence of major interference in the upper abdominal region, because of its renal clearance. Therefore, 111In-DTPA-D-Phe-1-octreotide may be suitable for use in SPECT of the abdomen, which is important in the localization of small endocrine gastroenteropancreatic tumors.
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PMID:Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide. 134 39

We report the case of a 42 year old man in whom orthotopic liver transplantation was performed successfully for unresectable hepatic metastases of a bronchial carcinoid tumor. Prior to transplantation, somatostatin therapy, pulmonary lobectomy, and systemic chemotherapy (streptozotocin and fluorouracil) were performed. After 9 months there were no signs of clinical or biological recurrence. Orthotopic liver transplantation might be indicated for unresectable and limited liver metastases of neuroendocrine tumor.
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PMID:[Orthotopic liver transplantation for metastases of bronchial carcinoid tumor]. 134 69


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