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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin binding and insulin receptor gene expression have been assessed in cultured fetal (WI38) and SV40 transformed fetal (WI38/VA13) human fibroblasts to determine whether transformation influences the expression of insulin receptors. The transformed cell line had virtually no insulin binding and extremely low levels of insulin receptor mRNA. No apparent gene deletion or rearrangement was detected and therefore the marked decrease in insulin receptor gene expression seen in WI38/VA13 cells is an important example of negative regulation of insulin receptor gene expression. This cell line could serve as a model for studies of the mechanism for negative regulation of insulin receptor gene expression. Overexpression of the insulin receptor gene in these cells may reveal insights into the role of the insulin receptor in tumor biology.
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PMID:Loss of insulin binding and insulin receptor mRNA in a transformed human fetal fibroblast cell line. 197 37

Insulin-producing tumors of the pancreas are characterised by clinical symptoms and the lack of correlation between serum insulin and blood glucose concentrations. CT and angiography are major diagnostic procedures. Surgical therapy prefers enucleation of the tumor together with the capsule. Today blind resections can be avoided.
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PMID:[Insulinoma--diagnosis and therapy]. 198 96

We report a patient with pregnancy-induced lymphocytic adenohypophysitis complicated by postpartum painless thyroiditis. A 27-year-old female noticed visual field defect in the 36th week of pregnancy. After delivery in the 39th week by cesarean section, she was admitted for close examination. Goiter was not palpable, and postpartum galactorrhea was not observed. Routine examination revealed no abnormal findings. On October 8, 1989, magnetic resonance imaging (MRI) revealed a tumor image (height 22.4mm) from the sella turcia to suprasellar cistern with a lower signal intensity than that of the white matter on T1 weighted images and a high signal intensity on T2 weighted images. Gd-DTPA contrast images showed a symmetrical and homogeneous tumor image at the same site. However, the posterior lobe of the pituitary gland appeared normal. These findings suggested lymphocytic adenohypophysitis. The LH was less than 0.3mIU/ml. The FSH (7.8mIU/ml), PRL (12ng/ml), GH (1.6ng/ml) and cortisol (10 micrograms/dl) levels were normal. T4 was 5.3 micrograms/dl, T3 67ng/dl, fT4 0.53ng/dl, which indicated mild hypothyroidism, but the TSH was normal. TRH test showed a slight increase in TSH and no response of PRL. Insulin tolerance test showed delayed response of GH and normal response of cortisol. LHRH test revealed no response of LH and delayed response of FSH. Anti-GH3 cell antibody and anti-thyroglobulin antibody were positive, but the anti-AtT20 cell antibody was negative. Since visual disturbance improved, and slight reduction in the mass (height 20.1mm) was confirmed by MRI after delivery on October 21, her course was observed without treatment. After 1 month, the LH became detectable, but the PRL and cortisol decreased to 2.5ng/ml and 6.0 micrograms/dl, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of pregnancy-induced lymphocytic adenohypophysitis complicated by postpartum painless thyroiditis]. 207 Aug 91

The human chondrosarcoma cell line (HCS-2/8) established by our group expresses cartilage phenotypes such as production of cartilage-type proteoglycans and collagen type II, but its tumorigenicity is low. To develop an in vitro experimental system for studies of human chondrosarcomas, a new immortal cell line of human chondrosarcoma, named HCS-2/A, was established from the same tumor. HCS-2/A cells proliferated with a doubling time of 3 1/2 days in a medium containing 20% fetal bovine serum (FBS). This growth rate was comparable to that of HCS-2/8 cells. However, HCS-2/A cells proliferated more rapidly than HCS-2/8 cells in the presence of 2-10% FBS. Like HCS-2/8 cells, HCS-2/A cells had a polygonal shape in sparse cultures and became spherical as they reached confluence, after which they formed nodules composed of multilayered cells and a large quantity of extracellular matrix showing strong metachromasia. The nodules formed by HCS-2/A cells were thicker and also larger in diameter than those formed by HCS-2/8 cells. Electron microscopically, the cells in the nodules resembled chondrocytes in vivo, but each cell had an irregular-shaped nucleus which is a characteristics of tumor cells. The cells actively synthesized "cartilage-specific" large proteoglycans and their level of proteoglycan synthesis was comparable to that of HCS-2/8 cells. Insulin, which stimulates proteoglycan and DNA syntheses in cultured chondrocytes, markedly increased proteoglycan synthesis in HCS-2/A cells. On the other hand, the hormone only slightly increased proteoglycan synthesis in HCS-2/8 cells. Insulin also stimulated DNA synthesis in cultured HCS-2/A cells, but not in HCS-2/8 cells. Immunostaining revealed that HCS-2/A cells produced type-II collagen but not type-I collagen. However, the level of collagen synthesis of HCS-2/A cells was lower than that of HCS-2/8 cells. Inoculation of HCS-2/A cells into athymic mice resulted in the formation of chondrosarcomas that grew faster than those arising from HCS-2/8 cells.
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PMID:Establishment from a human chondrosarcoma of a new immortal cell line with high tumorigenicity in vivo, which is able to form proteoglycan-rich cartilage-like nodules and to respond to insulin in vitro. 207 Dec 32

Chromogranin-A (CgA), as measured in the circulation by RIA, has emerged as a useful probe of exocytotic sympathoadrenal activity in man as well as of the presence and extent of neuroendocrine neoplasia. Here we studied, using a sensitive RIA, the distribution of CgA immunoreactivity in normal human neuroendocrine tissues. Furthermore, to investigate whether these normal tissue sources measurably contribute to plasma CgA, we measured plasma CgA, catecholamine, and other polypeptide hormone responses to selective stimuli of secretion at several sites within the neuroendocrine system. Immunoreactive CgA was ubiquitous in human neuroendocrine tissues, in rank order of concentration (micrograms per g wet wt): adrenal medulla greater than pituitary greater than pancreas greater than stomach greater than small intestine (jejunoileum) greater than brain (frontal cortex) greater than parathyroid greater than thyroid. Quantitatively, neuroendocrine tissues other than the adrenal medulla possessed only 0.04-25% of the immunoreactivity found in the adrenal medulla. Insulin-induced hypoglycemia, a potent stimulus of adrenomedullary secretion, resulted in 1.7- and 14-fold rises in plasma CgA and epinephrine, respectively. However, insulin-induced hypoglycemia failed to perturb plasma CgA in three bilaterally adrenalectomized patients, suggesting that the adrenal medulla is the source of plasma CgA elevation during hypoglycemia in normal subjects. Cell type-selective secretagogue stimulation of normal endocrine secretory cells other than the adrenal medulla (pituitary, pancreas, gut, thyroid, and parathyroid) induced measurable increments in the concentrations of the resident peptide hormones, but left plasma CgA unperturbed. Nonselective stimulation of a wide variety of endocrine secretory cells with pentagastrin elevated plasma CgA 1.4-fold. However, restriction of pentagastrin's targets by coinfusion of calcium abolished the effect on plasma CgA. Hence, within the normal human neuroendocrine system, only selective stimulation of the adrenal medulla is likely to elevate plasma CgA under physiological or pharmacological circumstances. This is consistent with our finding of the adrenal medulla as the quantitatively major normal neuroendocrine tissue source of CgA immunoreactivity.
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PMID:Neuroendocrine sources of chromogranin-A in normal man: clues from selective stimulation of endocrine glands. 211 38

Tumor metastasis requires highly motile cells that can respond to appropriate stimuli. A2058 human melanoma cells were shown previously to secrete a highly potent autocrine motility factor (AMF) that stimulates chemokinetic movement. We have shown that the insulin polypeptides (IPs; insulin-like growth factors I and II [IGF-I, -II] and insulin) stimulated A2058 cell chemotaxis and chemokinesis. We now report that the IPs and AMF stimulate locomotion in other human malignant cell lines. Insulin (100 nM) induced motility of up to 50% of the magnitude of the AMF response in human carcinoma lines MDA-231 (breast), T24 (bladder), and OVCAR3 (ovarian). The tumorigenic and metastatic 5R Haras-transfected rat embryo fibroblast cell line responded to insulin with both chemotaxis and chemokinesis and was 100% of that seen for AMF. The ED50 for IGF-I in the carcinoma cell lines was in the order of I nM, but the magnitude of the responses at this concentration was 40% of the AMF-stimulated response, with the exception of the A2058 cells, which were maximally stimulated at I nM. IGF-II induced maximal motility of 75 to 130% of the AMF-stimulated response in the carcinoma lines with ED50 of less than or equal to 10 nM. IGF-II-stimulated motility in the carcinoma lines was predominantly chemotactic by modified checkerboard analysis. Cell pretreatment with pertussis toxin inhibited 90-100% of AMF-induced motility, whereas migration to the IPs was not pertussis toxinsusceptible. In growth studies, IGF-I induced mitogenesis up to 140% of basal media control growth. In general, maximal growth stimulation was seen at 100 nM IGF-I, and optimal migration was seen at 10 nM IGF-I. The IGFs are secreted by normal stroma in a number of organs that are common sites for primary and metastatic disease. Therefore, we suggest that IPs may be important homing and mitogenic signals for tumor cells in the process of invasion and metastasis and that the differential motility stimulation and respective mechanisms of action by these physiologically important agents may underlie the diversity of the metastatic process.
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PMID:Heterogeneity of the motility responses in malignant tumor cells: a biological basis for the diversity and homing of metastatic cells. 211 98

Insulin resistance is a cause for morning hyperglycemia seen in diabetic patients. Other reasons for morning hyperglycemia should be eliminated by performing an insulin response test. Once insulin resistance has been established as the cause of hyperglycemia, a step-by-step process should be used to establish the cause of the insulin resistance. Common causes of insulin resistance include hyperadrenocorticism, acromegaly, hyperthyroidism, and obesity. Hepatic disease, renal insufficiency, and sepsis are other causes of insulin resistance in practice. Less common causes include insulin antibodies, pregnancy, neoplasia, hyperandrogenism, and pheochromocytoma. If the underlying cause cannot be found or resolved, then increased doses of insulin are required to manage the hyperglycemia.
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PMID:Problems in diabetes mellitus management. Insulin resistance. 213 77

Expression of hormones in endocrine tumors and derived cell lines of transgenic mice carrying insulin-promoted oncogenes has been investigated by histochemical, immunohistochemical, ultrastructural, and radioimmunologic means. Tumors of the pancreas, small intestine, mesentery, and liver were examined. Insulin-immunoreactive cells were prevalent in pancreatic tumors, with a significant subpopulation of pancreatic polypeptide-immunoreactive elements. Conventional ultrastructural and immunogold analysis identified insulin-storing beta granules in pancreatic tumor cells. In contrast, the largest immunoreactive subpopulation of intestinal tumors expressed secretin (53% of total cells), followed by proglucagon-related peptides (15%), glucose-dependent insulinotropic polypeptide (7%), gastrin (7%), pancreatic polypeptide (2%), neurotensin (2%), and somatostatin (1%). No detectable immunoreactivity for either insulin or serotonin was observed. Electron microscopy and immunogold labeling showed that intestinal tumor cells contained secretin-storing S-type granules. Lymph node and liver tumors contained secretin-immunoreactive cells with ultrastructural features similar to those of intestinal tumors. In addition, high levels of circulating insulinlike and secretinlike immunoreactants were detectable. Analogous hormone profiles were identified in tumor cell lines and culture media. Large T-antigen immunoreactivity was detected in all the nuclei of neoplastic cells, as well as in insulin-immunoreactive elements of non-neoplastic islets and pancreatic ducts and in some secretin-immunoreactive cells of small intestinal mucosa. These data indicate that neuroendocrine tumors arise both in beta cell and S-cell subpopulations of transgenic mice.
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PMID:Development of neuroendocrine tumors in the gastrointestinal tract of transgenic mice. Heterogeneity of hormone expression. 216 28

Insulin and insulin-like growth factors (IGFs) are anabolic effectors in many tissues and cultured cells, including astrocytes and neurons. Receptors for insulin and IGFs are found throughout the human brain. We examined the level of insulin and IGF receptors on membranes prepared from surgical specimens of tumor (astrocytomas and glioblastomas) and normal human brain. Specific binding (per 100 micrograms membrane protein) of insulin was less than 5% in all normal and tumor samples. Specific binding of IGF-I to 12 normal brain specimens ranged from 1-8%. IGF-I binding to 18 glioma specimens ranged from 2-25%. Scatchard analyses of IGF-I binding confirmed increased IGF-I-binding sites in some glial tumors vs. normal brain, but detected no difference in affinity characteristics. Cross-linking of [125I]IGF-I demonstrated that glioma tissue expressed the same lower mol wt (approximately 118 kDa) alpha-subunit as the normal brain confirming the neural origin of the cells expressing the IGF-I receptor. IGF-binding proteins (approximately 40 kDa) were also found in the membranes of some of the glioma but none of the normal brain specimens. In cell lines derived from glioma specimens, IGF binding was readily detectable (4-10% specific binding), but insulin binding was barely detectable (0-03%) in every line examined. The size of the IGF-I alpha-subunit in the cultured cells was larger (approximately 133 kDa) than that in the original tissue. Most glioma cell lines exhibited an IGF-I dose-dependent stimulation of thymidine incorporation into DNA, and partially purified IGF-I receptors from these cells exhibited a dose-dependent stimulation of the autophosphorylation of the beta-subunit. We conclude that human glioma cells have functional IGF-I receptors and suggest a role for this receptor in glioma cell growth.
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PMID:Insulin-like growth factor-I receptors in human glial tumors. 216 27

The relationships of the expression of hepatic low-density lipoprotein (LDL) receptors (apo B,E receptors) to several plasma hormone concentrations were examined in 15 fasted women aged 37-75 years (mean, 57 years), who were undergoing laparotomy for non-neoplastic disease. No subject had clinical or biochemical evidence of familial hypercholesterolemia, renal disease, hepatic disease, or endocrine disease. Hepatic apo B,E receptor expression was quantified in vitro as the EDTA-suppressible binding of 125I-labeled human LDL (15 micrograms protein/ml) by liver homogenate at 37 degrees C; values were 23-75 ng LDL protein/mg cell protein (mean, 47 ng/mg). Receptor expression was strongly correlated with plasma estrone concentration (rs = +0.70, P = 0.035), but was unrelated to the concentrations of testosterone, thyroxine, free triiodothyronine, cortisol, sex hormone-binding globulin (SHBG) or cortisol-binding globulin. Insulin and estradiol concentrations were mostly very low. The correlation of receptor expression with plasma total estrone concentration reflected associations with both the albumin-bound (rs = +0.78, P = 0.014) and unbound (rs = +0.80, P = 0.009) fractions, but not with the SHBG-bound fraction (rs = -0.22, P = 0.574), of this hormone. As the non-SHBG-bound fractions of gonadal steroids are considered to be the biologically active components, these results are consistent with experimental evidence that the synthesis of apo B,E receptors in hepatocytes is stimulated by estrogens, and suggest that circulating estrone may be the major hormonal determinant of receptor expression in fasted middle-aged/elderly women.
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PMID:Hormonal determinants of apolipoprotein B,E receptor expression in human liver. Positive association of receptor expression with plasma estrone concentration in middle-aged/elderly women. 217 65


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