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

A case of a 58-year-old woman with an unusual variant of malignant islet-cell tumor showing oncocytic features is described. Using the light microscopy technique, the tumor appeared comprised of solid nests of uniform cells with abundant, eosinophilic cytoplasm and round nuclei with granular chromatin. Ultrastructurally, the cells contained numerous abnormal mitochondria, dilated rough endoplasmic reticulum, and scattered dense-core neurosecretory granules, often associated with cytoplasmic filaments. Tumor cells were focally immunoreactive for insulin, glucagon, and somatostatin and diffusely immunoreactive for alpha 1-antitrypsin as assayed by the avidin--biotin technique. The tumor was immunonegative for human chorionic gonadotropin, gastrin, adrenocorticotropic hormone, and serotonin. The patient exhibited some of the clinical features associated with glucagonoma syndrome, including diabetes mellitus and chronic diarrhea. The tumor behaved in a malignant fashion, with widespread lymphatic involvement and bony metastases at the time of presentation. This report of an oncocytic islet-cell carcinoma supports the concept of oncocytic differentiation in islet-cell tumors in a fashion analagous to oncocytic carcinoids.
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PMID:Functioning oncocytic islet-cell carcinoma. Report of a case with electron-microscopic and immunohistochemical confirmation. 300 44

The clinical features of eight women and three men with nonfunctioning islet cell carcinoma of the pancreas were reviewed. The mean patient age was 58 years (range 44 to 75 years). Weight loss and abdominal pain were the most frequent presenting symptoms. An abdominal mass was palpable in five patients. At operation regional or distant metastases were present in 82% of patients. Only 18% of patients underwent resection for potential cure. All tumors proved histologically to be neuroendocrine in origin. Immunohistochemical staining showed positive reactivity for neuron-specific enolase and chromogranin in all tumors studied but was negative for insulin, glucagon, and somatostatin. Focal positivity for pancreatic polypeptide was seen in one tumor. Nine patients with unresectable disease at operation were available for follow-up. Mean survival for the entire group was 23 +/- 7.2 months (range 4 to 72 months). Survival differences between women and men appeared to favor women but were not statistically significant. Postoperative regional or systemic chemotherapy also had no significant effect on patient survival although two of the longest survivors (36 and 72 months) had received adjunctive chemotherapy. Nonfunctioning islet cell neoplasms are locally aggressive, have a propensity for early metastases, and are rarely resectable for cure. Unlike pancreatic exocrine carcinomas, endocrine malignancies may respond favorably to adjunctive chemotherapy.
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PMID:Nonfunctioning malignant neuroendocrine tumors of the pancreas. 302 43

The v-fps oncoprotein was expressed in a pre-neoplastic, growth factor-dependent Chinese hamster lung fibroblast line (CCL39) to study its effect on growth controls and on the induction of malignancy. Two transfectants were characterized which expressed low (39FPS-8) or high (51FPS-6) levels of P130gag-f ps protein-tyrosine kinase activity. 39FPS-8 cells still arrested in quiescence when deprived of growth factors, but developed an increased sensitivity to the mitogenic actions of epidermal growth factor (20-fold) and alpha-thrombin (50-fold), although not to insulin. In contrast, 51FPS-6 cells completely escaped growth controls, divided in serum-free medium, and were insensitive to further growth factor stimulation. Both transfectants produced rapidly growing tumors in nude mice that formed pulmonary metastases from a subcutaneous site, unlike the parental cells which are non-metastatic. 51FPS-6 cells were comparatively more efficient than 39FPS-8 cells in colonizing the lungs after intravenous inoculation. The v-fps tyrosine kinase therefore induces a partial to complete relaxation of growth factor-mediated controls on the CCL39 cell cycle, with the extent of factor independence reflecting the amount of P130gag-f ps synthesized. This reduction in growth factor requirements correlates with the capacity of v-fps to confer the attributes of metastatic tumors upon preneoplastic CCL39 fibroblasts. We speculate that increased sensitivity to growth factor stimulation represents a common mechanism by which tumor cells acquire metastatic properties.
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PMID:v-fps protein-tyrosine kinase coordinately enhances the malignancy and growth factor responsiveness of pre-neoplastic lung fibroblasts. 328 Oct 93

Neoplastic proliferations of neuroendocrine cells (NE) may occur throughout the entire GI tract but affect particularly appendix and ileum ("midgut carcinoids"), rectum ("hindgut carcinoids"), as well as stomach and the duodenum ("foregut carcinoids"). Only more exceptionally, they arise in the esophagus, jejunum and colon. The NE tumors encompass a heterogeneous gross and microscopic structural spectrum, ranging from inconspicuous microproliferations ("mucous membrane nevi") to bulky tumor masses. Their growth patterns are usually characteristic and easily recognized. In doubtful cases their NE differentiation becomes established by a characteristic silver affinity, by the ultrastructurally observed presence of characteristic "endocrine" secretion granules, and by immunohistochemically detectable occurrence of "pan-NE markers" (neuron-specific enolase, chromogranins, and synaptophysin), biogenic amines (mainly serotonin), and neurohormonal peptides. Foregut carcinoids usually contain serotonin, gastrin, and somatostatin, midgut carcinoids often only serotonin and tachykinins, whereas the hindgut carcinoids as a rule are multihormonal with a wide spectrum of hormonal peptides, including even insulin. Most GI NE tumors are found in the appendix (50%) and the ileum (30%). Practically all (98%) of the appendiceal NE tumors are benign. They have recently been proposed as arising from apparently Schwann-cell-related NE cells in the submucosa, whereas the ileal--and probably also all the other non-appendiceal NE tumors--are derived from the totipotential cells in epithelial crypts of the mucosa. Among the ileal NE neoplasms a large number can metastasize and result in a fatal outcome. The ability to metastasize is related to the size and to the multiplicity of the primary tumors at the time of initial diagnosis and, to some extent, to their histopathologic growth pattern. Now, some relationship between the prognosis and the cytochemically assessed nuclear DNA content of the NE tumor cells has also been established; not less than about 1/4 to 1/3 seem to be aneuploid. Almost 90% of the rectal carcinoids are benign. Exceptionally, a highly malignant NE neoplasms can arise from the colon/rectum--as well as from the esophagus--composed of NE cells of small and intermediate size. The NE tumors of the stomach are often composed of ECL (enterochromaffin-cell-like) cells; such ECL cell carcinoids are related to atrophic gastritis with pernicious anemia; experimentally, they can be induced by hypergastrinemia in rats. Duodenal carcinoids often contain psammoma bodies and can be associated with neurofibromatosis.
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PMID:Neuroendocrine tumors of the gastrointestinal tract. 329 Aug 66

After sc implantation into BALB/c nude mice, factor-dependent and premalignant Chinese hamster lung fibroblasts (CCL39) developed into tumors that occasionally disseminated and produced pulmonary metastases. Unlike CCL39 cells that required several growth factors (insulin, alpha-thrombin, epidermal growth factor) to proliferate in culture, metastatic tumor cells divided autonomously in serum-free medium. The re-implantation of independently isolated primary tumors revealed that they comprised factor-independent clones present at a variable frequency, as well as malignant clones that disseminated to the lungs after sc or iv inoculation. The resulting metastases invariably contained cells that were able to divide in serum-free medium and that presumably represented the progeny of autonomous variants populating the primary tumors. Among ten CCL39 variants selected in vitro for reduced growth factor requirements, two were metastatic upon sc and iv inoculation. These cell lines were the only ones that replicated rapidly in the absence of growth factors. Unlike myc transfectants, CCL39 fibroblasts that were transformed with an activated Harvey ras oncogene or that were infected with polyomavirus were both metastatic and autonomous. Taken together, these observations are consistent with the notion that the metastatic potential of CCL39 tumor cells coincides with their ability to obviate growth factor requirements and thus to divide in an autonomous fashion.
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PMID:Coincidental acquisition of growth autonomy and metastatic potential during the malignant transformation of factor-dependent CCL39 lung fibroblasts. 335 98

One patient with benign and another with malignant pheochromocytoma have been studied in an attempt to elucidate the effect of increased catecholamines on the response of blood sugar, unesterified fatty acids, insulin and growth hormone to a glucose load. The presence of increased catecholamines in both patients appeared to produce increased fasting plasma unesterified fatty acid levels, carbohydrate intolerance and an unusual plasma growth hormone response to glucose. There was no interference with the normal decrease in plasma unesterified fatty acids after glucose ingestion. The malignant tumour, but not the benign one, was associated with low plasma insulin levels.After removal of the benign tumour the fasting unesterified fatty acid levels became normal. In addition, following glucose ingestion there appeared to be a more normal plasma insulin and growth hormone response and improved glucose tolerance. After removal of the primary malignant tumour it is noteworthy that the distant metastases secreted abnormal amounts of both adrenaline and noradrenaline.
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PMID:Hormonal and metabolic studies in pheochromocytoma. 542 31

We reviewed our personal experience with insulin-secreting carcinoma of the pancreas to determine the clinical course and the role of surgery in this disease. Seventeen patients with high-grade metastatic carcinoma were treated at our institution between 1957 and 1982. To this series we have added 45 cases of metastatic carcinoma reported in the literature. All patients had symptoms with manifestations of hypoglycemia. Patients with metastatic insulin-secreting carcinoma had an average age of 48.5 years, with male predominance. The average duration of symptoms at presentation was 2.0 years. The tumors were usually single and averaged 6.2 cm. All tumors had metastases, most commonly to the liver and/or lymph nodes. The median disease-free survival after curative resection was 5 years. The recurrence rate was 63%, with the median interval to recurrence 2.8 years, and the median survival with recurrent tumor was 19 months. Palliative resection was associated with a median survival of 4 years, and biopsy only, 11.0 months. Insulin-secreting carcinomas are slow-growing tumors with significant metastatic potential. Surgical resection of primary and metastatic tumors represents the treatment of choice when possible. Long-term follow-up is required.
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PMID:Metastatic insulin-secreting carcinoma of the pancreas: clinical course and the role of surgery. 609 77

Eighty-one primary ovarian carcinoids and intraovarian metastases from six mid-gut carcinoids were examined for the presence of tumor cells immunoreactive with antisera raised against various neurohormonal peptides, mostly of gastroenteropancreatic (GEP) origin. Twenty of the primary and two of the metastatic carcinoids contained such tumor cells. The incidence of tumors with any kind of neurohormonal peptide immunoreactive tumor cells was 53% in the trabecular carcinoids, and 42% in the strumal carcinoids, whereas the incidence was much lower (7%) in the insular type. Immunoreactive pancreatic polypeptide (PP), glucagon, enkephalin, and somatostatin were those neurohormonal peptides most commonly observed in the tumor cells of the primary carcinoids. Those less commonly found were substance P, calcitonin, VIP, neurotensin, beta-endorphin, and ACTH. Four metastatic carcinoids were nonreactive with all the antisera used. Cells storing immunoreactive insulin, glucagon, PP, VIP, gastrin, substance P, or enkephalin were found in one of the two remaining metastatic carcinoids; in the other only gastrin-immunoreactive tumor cells were observed. The occurrence and distribution of tumor cells storing the neurohormonal peptides in ovarian carcinoids are discussed in relation to their possible origin in the ovary and to carcinoids in the gut.
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PMID:Neurohormonal peptides in ovarian carcinoids: an immunohistochemical study of 81 primary carcinoids and of intraovarian metastases from six mid-gut carcinoids. 611 50

A 57-year-old man first noted tender subcutaneous nodules on his extremities and abdomen. Six months later symptoms of insulin hypersecretion became evident and hyperinsulinemia was documented. An exploratory laparotomy revealed an islet cell tumor measuring 12 cm in diameter extending anteriorly from head of the pancreas with metastases in the liver. Evidence of parathyroid and pituitary hormone hypersecretion suggests that the insulinoma may be part of a multiple endocrine neoplasia syndrome. Histological examination of the subcutaneous nodules revealed the characteristic histology of nodular fat necrosis. This is the first report of the association of an insulin-secreting islet cell carcinoma with subcutaneous nodular fat necrosis.
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PMID:Association of insulinoma with subcutaneous nodular fat necrosis. 616 10

Syrian hamsters were rendered diabetic with intraperitoneal streptozotocin and were maintained in the diabetic state for a minimum of 14 days. A hamster islet cell tumor was transplanted subcutaneously with a prompt return of water intake (38 +/- 9.1 ml/day to 7.1 +/- 2.2 ml/day, mean +/- SD), urine glucose (4.8 +/- 0.84 g/day to less than 250 mg/day), urine output (37.4 +/- 10.9 ml/day to 7.6 +/- 2.1 ml/day), blood glucose (297 +/- 31.9 mg/dl to 87.6 +/- 28 mg/dl), and weight gain (1.0 to 0.8 g/day) to normal control levels. Histologic examination of the engrafted tumors revealed a well encapsulated tumor with no evidence of metastatic disease. The transplanted insulinomas maintained well differentiated histologic features without evidence of necrosis. Immunopathologic studies failed to reveal any evidence of either humoral or cell mediated immunity directed toward the allograft. Each animal was successfully transplanted with a 1 mm tumor explant. A single rodent tumor donor provided adequate material for engraftment for five recipients. The transplanted insulinomas maintained full functional and enzymatic capabilities. Similar studies utilizing the hamster insulinoma engrafted into the athymic nude mouse showed amelioration of the same diabetic symptomatology. Many of the technical difficulties encountered with whole organ and isolated islet transplantation encourages development of a more practical model. These experimental results suggest an alternative method for supplying the diabetic with an endogenous insulin source.
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PMID:Transplantation of insulinoma into the diabetic Syrian hamster. 624 54


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