Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ca2+ and Ca(2+)-binding proteins are involved in running the cell cycle. Ca2+ spikes and signals from integrin-activated focal adhesion complexes and Ca2+ receptors on the cell surface along with cyclic AMP begin the cycle of cyclin-dependent protein kinases (PKs). These transiently expressed PKs stimulate the coordinate expression of DNA-replicating enzymes, activate replication enzymes, inactivate replication suppressors (e.g., retinoblastoma susceptibility protein), activate the replicator complexes at the end of the G1 build-up, and when replication is complete they and a Ca2+ spike trigger mitotic prophase. Another Ca2+ surge at the end of metaphase triggers the destruction of the prophase-stimulating PKs and starts anaphase. Ca2+ finally stimulates cytoplasmic division (cytokinesis). However, Ca2+ does more than this in epithelial cells, such as those lining the colon, and skin keratinocytes. These cells also need Ca2+, integrin signals, and only a small amount (e.g., 0.05-0.1 mM) of external Ca2+ to start DNA replication. Signals from their surface Ca2+ receptors trigger a combination of differentiation and apoptosis ("diffpoptosis") when external Ca2+ concentration reaches their setpoints. The skin's steep, upwardly directed, Ca2+ gradient has a low concentration in the basal layer to allow stem and precursor keratinocytes to proliferate, and higher concentrations in the suprabasal layers to trigger the differentiation-apoptosis ("diffpoptosis") mechanism that converts granular cells into protective, hard-shelled, dead corneocytes. A similar Ca2+ gradient may exist in the colon crypt allowing the stem cell and its amplifying transit or precursor offspring to cycle in the lower parts of the crypt, while stopping proliferation and stimulating terminal differentiation in the upper crypt and flat mucosa. Raising the amount of Ca2+ in fecal water above a critical level reduces proliferation and thus colorectal carcinogenesis in normal rats and some high-risk humans. But during carcinogenesis the Ca2+ sensors malfunction or their signals become ineffective: high Ca2+ does not stop, and may even stimulate, the proliferation of initiated mutants. Therefore, Ca2+ may either not affect, or even promote, the growth of epithelial cells in carcinogen-initiated rat colon and human adenoma patients. Clearly, a much greater understanding of how Ca2+ controls the proliferation and differentiation of epithelial cells and why initiated cells lose their responsiveness to Ca2+ are needed to assess the drawbacks and advantages of using Ca2+ as a chemopreventor.
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PMID:Calcium-cell cycle regulator, differentiator, killer, chemopreventor, and maybe, tumor promoter. 853 13

Unilateral neck exploration (UNE) is a controversial approach to the treatment of primary hyperparathyroidism (PHP), and most surgeons favor bilateral neck exploration. The aim of this study was to assess the value of ultrasonography, sestamibi scintigraphy, and intraoperative measurement of urinary cyclic AMP (UcAMP) or 1-84 PTH in 200 patients undergoing unilateral neck exploration under local anesthesia. Conditions for UNE were (1) a presumed solitary adenoma detected by ultrasonography, (2) no thyroid disease, and (3) no family history of PHP or multiple endocrine neoplasia. Patient's consent was obtained for conversion to bilateral exploration according to surgical and biologic findings. Sensitivity of ultrasonography was 92.5%. Sestamibi scintigraphy, performed in 70 patients, was less sensitive than ultrasonography (80%). Persistent PHP was accurately detected by intraoperative measurement of UcAMP or 1-84 PTH in all cases. At follow-up, 96.0% of the patients were cured either after unilateral neck exploration only (90.5%), or after conversion into bilateral exploration. Ultrasonography and intraoperative measurement of 1-84 PTH allow unilateral neck exploration with excellent results in a selected group of patients with PHP.
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PMID:Values of ultrasonography, sestamibi scintigraphy, and intraoperative measurement of 1-84 PTH for unilateral neck exploration of primary hyperparathyroidism. 867 59

We report two new cases of hyperparathyroidism during lithium therapy. The patients were a 50-year-old male and a 48-year-old female under lithium for bipolar disease. Both developed osteoporosis without fractures and laboratory test abnormalities consistent with moderate hyperparathyroidism. Although only 30 or so cases of lithium-associated hyperparathyroidism have been reported, as many as 10 to 15% of lithium-treated patients may have laboratory test evidence of hyperparathyroidism. Typically, urinary calcium excretion is normal, serum phosphate levels are moderately decreased and cyclic AMP levels are normal. An adenoma is the most common lesion. Surgery is usually required in patients whose clinical and laboratory test abnormalities persist despite discontinuation of the drug. Lithium-associated hyperparathyroidism may be due to dysregulation of the caliostat, a feedback loop that subordinates parathyroid hormone secretion to serum calcium levels. Little is known about lithium-induced osteoporosis. Trabecular bone was predominantly affected in one of our patients and cortical bone in another.
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PMID:Hyperparathyroidism during lithium therapy. Two new cases. 908 49

Growth hormone (GH) disorders are characterized with clinical presentation of GH excess or deficiency. The pathogenesis and pathophysiology of GH disorders have been extensively studied with the sake of recent development of sensitive immunoassays and molecular cell biology. Highly sensitive immunoassays for GH have revealed the normal and abnormal GH secretory dynamics even under the detectable levels by conventional radioimmunoassay. Glucose loading clearly suppressed GH levels less than 1ng/ml in normal subjects. Clinical utility of insulin like growth factor-I (IGF-I) for diagnosing GH disorders was also evaluated. We have established the age- and sex-matched reference values of IGF-I and IGF binding protein-3 (IGFBP-3) in Japanese. Both IGF-I and IGFBP-3 had the similar diagnostic values for GH deficiency. Genetic alterations in GH secreting pituitary adenomas have been extensively studied. Gs alpha mutation has been found in about 30-40% of acromegaly. The prevalence of this mutation was previously considered low but recent studies showed even higher incidence in Japan. Other oncogenic mutations were considered rare in acromegaly. It is noteworthy that GH secreting adenoma tissues had high content of activated cyclic AMP responsive element-binding proteins (CREB). We have identified new mutation in GH-1 gene in patients with familial isolated GH deficiency type II, which resulted in the skipping of exon 3.
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PMID:[Recent progress in the diagnosis of growth hormone (GH) disorders]. 931 Dec 56

Chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI) is an orphan nuclear receptor essential for neurogenesis, organogenesis, and cell fate determination. CYP17 gene transcription has recently been shown to be activated by SF-1 (steroidogenic factor-1) binding to a cyclic AMP-responsive sequence within the promoter region of the gene, and inhibited by COUP-TF binding to the sequence. Thus, COUP-TF and SF-1 act as a transcriptional repressor and activator, respectively, of CYP17 gene expression. Transcriptional repression by COUP-TFI is mediated by corepressors, N-CoR (nuclear receptor-corepressor) and SMRT (silencing mediator for retinoid and thyroid hormone-receptor), whereas transcriptional activation by SF-1 is mediated by coactivator SRC-1 (steroid receptor coactivator-1). We therefore examined the expression of COUP-TFI, SF-1, SRC-1, N-CoR, and SMRT in a variety of adrenocortical adenomas and compared the results with CYP17 mRNA levels. We found significantly high COUP-TFI mRNA expression in nonfunctional adenomas (n=8: 220+/-16%; normal 96+/-4%), a deoxycorticosterone-producing adenoma (n=1: 200%), and a pre-clinical Cushing's adenoma (n=1: 280%), intermediate COUP-TFI expression in cortisol-producing adenomas (n=8: 63+/-5%), and low COUP-TFI expression in aldosterone-producing adenomas (n=8: 49+/-4%). In contrast to COUP-TFI, SF-1 mRNA expression did not vary significantly among adrenals. We did not detect the expected negative correlation between COUP-TFI and CYP17 mRNA levels in adrenocortical adenomas. High COUP-TFI expression was associatedwith a nonfunctioning phenotype. Interestingly, the pattern of COUP-TFI expression was similar to the profile of N-CoR expression, but not of SMRT expression. These results indicate that COUP-TFI and N-CoR may play a role in steroidogenesis by human adrenocortical adenomas.
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PMID:COUP-TFI expression in human adrenocortical adenomas: possible role in steroidogenesis. 985 3

The term adrenal incidentaloma refers to an adrenal mass occasionally and unexpectedly discovered by an abdominal imaging procedure performed for reasons a priori unrelated to adrenal dysfunction. The prevalence of adrenal incidentalomas as discovered by computed tomographic scan examination is estimated to be between 1% and 4%. The vast majority of these lesions are of adrenocortical origin, most often adenomas. Identification of steroid or catecholamine-secreting tumors is important but usually solved with appropriate endocrinologic investigations. A difficult problem, however, is to distinguish between benign and malignant primary or secondary tumors. Size less than 4 cm and an unenhanced computed tomographic attenuation under 10 Hounsfield Units (HU) are findings in favor of a benign adrenocortical adenoma, as is a positive NP 59 scintigraphic examination. The pathogenesis of adrenal tumors is not well understood. However, alterations of the cyclic AMP signalling pathway have recently been observed in benign adrenocortical lesions and molecular defects associated with insulin-like growth factor-II overexpression in malignant adrenocortical tumors.
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PMID:Adrenal incidentalomas. 1179 Sep 82

Human thyroid cells proliferate during development and in adults in response to physiologic and pathologic stimuli. Under normal conditions, they turn over about once every 8 years. The main physiologic regulators are thyrotropin and iodide and, in disease, thyroid-stimulating and thyroid-blocking antibodies. Growth factors modulate proliferation in vitro, but their role in vivo is still unknown. Mitogenic effects are mediated via three major pathways: the cyclic AMP, protein tyrosine kinase, and the Ca(2+) phosphatidylinositol cascades. In this review, the role of these cascades in hyperthyroidism, congenital thyroid defects, and autonomous adenoma is analyzed.
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PMID:Control of thyroid cell proliferation and goitrogenesis. 1840 72

Cyclooxygenase-2 (COX-2) inhibition prevents adenoma formation in humans and mouse models of colon cancer. The selective COX-2 inhibitor celecoxib reduces COX-2 and prostaglandin E(2) (PGE(2)) expression and adenomas in the intestine of Min/+ mice after treatment for several weeks, but prolonged treatment increases PGE(2) production, resulting in drug-resistant tumor formation and transforming growth factor beta (TGFbeta)-dependent intestinal fibrosis. In this study, we examined pathways that regulate COX-2 expression and suppress chronic intestinal inflammation. We show that NF-kappaB signaling was inhibited in the ileum of Min/+ mice receiving long-term treatment with celecoxib. This effect was associated with inhibition of TGFbeta-associated kinase-1 and IkappaB kinase alpha/beta activities and reduced expression of the Toll-like receptor (TLR) 2 and TLR4 that enhance colonic barrier function. Additionally, we observed reduced activities of protein kinases c-Jun NH(2)-terminal kinase 1 and protein kinase A and transcription factor cyclic AMP-responsive element binding protein, regulators of COX-2 expression, which cross-talk with NF-kappaB. In ileum subjected to long-term celecoxib treatment, we noted relatively higher expression of COX-2, vascular endothelial growth factor, and interleukin-1beta in Paneth cells, whereas NF-kappaB and COX-2 were more strongly expressed by an expanded population of stromal myofibroblasts. Our findings argue that celecoxib resistance is an acquired adaptation to changes in the crypt microenvironment that is associated with chronic intestinal inflammation and impaired acute wound-healing responsiveness.
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PMID:Persistent cyclooxygenase-2 inhibition downregulates NF-{kappa}B, resulting in chronic intestinal inflammation in the min/+ mouse model of colon tumorigenesis. 2048 34

Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease.
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PMID:Clinicopathological correlates of adrenal Cushing's syndrome. 2604 61

Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease.
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PMID:Clinicopathological correlates of adrenal Cushing's syndrome. 2609 10


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