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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, lung lesions were found in male A/J mice 24 wk after intraperitoneal injection of 1-nitropyrene (1-NP). The lesions were classified into three categories: alveolar/bronchiolar hyperplasia, adenoma, and adenocarcinoma. The proliferation kinetics of cells in the lesions were evaluated by assessing proliferating cell nuclear antigen (PCNA) expression and silver-staining nucleolar organizer regions (AgNORs). Furthermore, the role of the Ki-ras gene in tumorigenesis was studied by detecting point mutations in Ki-ras codons 12, 13, and 61 by polymerase chain reaction and sequence analysis. The PCNA-positive rates (+/- standard deviations) in various samples were as follows: 0% for specimens from six untreated animals and six uninvolved areas, 4.26 +/- 3.94% for 19 hyperplasias (hyperplasias vs normal lung tissue, P < 0.01), 13.24 +/- 6.35% for 25 adenomas (adenomas vs hyperplasias, P < 0.01), and 38.0 +/- 9.63% for four adenocarcinomas (adenocarcinomas vs adenomas, P < 0.01). The corresponding mean AgNOR scores were as follows: 1.10 +/- 0.05 for the untreated animals, 1.32 +/- 0.09 for the uninvolved areas, 1.72 +/- 0.59 for the hyperplasias (hyperplasias vs normal lung tissue, P > 0.05), 2.74 +/- 0.70 for the adenomas (adenomas vs hyperplasias, P < 0.01), and 5.22 +/- 0.62 for the adenocarcinomas (adenocarcinomas vs adenomas, P < 0.01). Ki-ras gene mutations were identified in three of four (75%) adenocarcinomas, six of 23 (26%) adenomas, and two of 17 (12%) hyperplasias. No mutations were found in normal lung tissue. The most frequent Ki-ras mutation was an arginine (CGA)AT --> GC transition at codon 61 in exon 2. The PCNA-positive rates and AgNOR scores of cases with Ki-ras mutations were higher than those without an identified mutation (P < 0.05). Ki-ras mutations at codon 61 (Arg) may therefore influence the growth or development of 1-NP-induced lung lesions in A/J mice.
Mol Carcinog 1998 Aug
PMID:Ki-ras mutation and cell proliferation of lung lesions induced by 1-nitropyrene in A/J mice. 972 18

Carcinoma arising in pleomorphic adenoma of the salivary gland is a rare tumor, and its molecular aspects are unknown. Recent studies have revealed that malignant transformation of various human cancers may involve two different genetic alterations: inactivation of the p16 gene, which is a putative tumor suppressor gene, and genetic instability represented by microsatellite instability (MSI). However, so far, molecular investigations including p16 gene alteration and MSI have not been performed on carcinoma arising in pleomorphic adenoma. Both inactivation of the p16 gene and MSI were studied using DNA extracted from paraffin-embedded sections of carcinoma arising in pleomorphic adenoma. Samples also were analyzed for cyclin D1 gene amplification, which is thought to have oncogenic effects similar to those with inactivation of the p16 gene. One case showed the homozygous deletion of the p16 gene in the carcinoma, although hypermethylation of the p16 gene and amplification of the cyclin D1 gene were not observed in any cases. In two of four cases, MSI was observed. One case in two showed MSI in both the pleomorphic adenoma and the carcinoma. Results of this study suggest that two different genetic alterations, the inactivation of the p16 gene and genetic instability, play roles in the malignant transformation of carcinoma in pleomorphic adenoma. The MSI observed in the adenoma suggests that genetic alterations occur in pleomorphic adenoma.
Diagn Mol Pathol 1998 Aug
PMID:Deletion of the p16 gene and microsatellite instability in carcinoma arising in pleomorphic adenoma of the parotid gland. 991 33

In addition to their role in steroidogenesis in the male, testicular Leydig cells constitutively express large amounts of the peptide relaxin-like factor (RLF), also known as Ley-IL. The Leydig cell-derived RLF belongs to the insulin-like superfamily, which also includes relaxin, insulin and the insulin-like growth factors, and within the testis is a specific marker of Leydig cells. Little information is available either on the regulation of gene expression or on the function of this Leydig cell-derived peptide. In the present study we have investigated the expression pattern of human RLF in patients with rare Leydig cell hyperplasia and adenoma. The expression of both mRNA and protein appear to be decreased in hyperplastic Leydig cells, whereas in the Leydig cell adenomas studied, large central areas of the adenoma were devoid of RLF mRNA and protein. Only Leydig cells located at the periphery of the adenoma displayed expression of RLF, with full agreement between in-situ hybridization and immunohistochemistry. It thus appears that the expression of the RLF gene and its products are down-regulated in Leydig cell hyperplasia and adenoma, consistent with a concomitant dedifferentiation of these cells.
Mol Hum Reprod 1999 Feb
PMID:Expression of relaxin-like factor is down-regulated in human testicular Leydig cell neoplasia. 1006 64

Background: Thyroid tumors have mutations of the ras oncogenes, although the prognostic and diagnostic significance of this remains unclear. Usually, thyroid follicular adenoma, follicular carcinoma, and papillary carcinoma are easy to differentiate histologically. Occasionally, follicular carcinoma may be difficult to separate from the follicular variant of papillary carcinoma, and a molecular test to help differentiate the two would be critical, as their behavior and clinical management differ. In earlier reports, K- ras mutations have been suggested as such a marker. Methods and Results: To study genetic differences between thyroid tumors, the authors examined 79 cases (58 papillary carcinomas, 12 follicular carcinomas, and 9 adenomas) for the presence of a K-ras mutation in codon 12 by polymerase chain reaction and restriction endonuclease digestion. Only six papillary carcinomas (12%) showed a K-ras mutation; no mutations were detectable in the other thyroid tumors. Conclusion: K-ras mutation analysis does not help differentiate thyroid tumor types.
Mol Diagn 1998 Sep
PMID:Can Different Thyroid Tumor Types Be Distinguished by Polymerase Chain Reaction-Based K-ras Mutation Detection? 1008 71

Aldosterone secretion in most patients with aldosterone-producing adenomas (APAs) is typically unresponsive to angiotensin II stimulation (AII-unresponsive, AII-U). In some patients, however, plasma aldosterone increases in response to AII stimulation (AII-responsive, AII-R). This differential aldosterone responsiveness could be related to the levels of type 1 AII receptors (AT1R) in the APA. To test this hypothesis, plasma aldosterone levels in response to upright posture and/or sequential high- and low-salt diets were measured by radioimmunoassay in nine patients with APAs. AT1R mRNA levels in the adenomas were quantified by competitive reverse transcription-polymerase chain reaction and correlated to the cellular composition of the adenoma. Two patients were categorised as AII-R by an increase of plasma aldosterone greater than 50% over the baseline. The remaining seven patients who had blunted plasma aldosterone responses were classified as AII-U. Histologically, the AII-R APAs consisted predominantly of zona glomerulosa (ZG)-like cells (> 90%), while the AII-U APAs contained zona fasciculata (ZF)-like cells ranging from 28 to 72%. There was an inverse relationship between the levels of AT1R mRNA in the APA and the percentage of ZF-like cells in the adenoma (n = 9, r = 0.73, P < 0.05). In situ hybridisation findings demonstrated that AT1R mRNA was more uniform and intensive in ZG-like cells than in ZF-like cells. These results suggest that heterogenous aldosterone responsiveness to angiotensin in APAs is histologically dependent and related to the differential expression of AT1R mRNA in the adenoma.
Mol Cell Endocrinol 1999 Jun 25
PMID:Differential expression of type 1 angiotensin II receptor mRNA and aldosterone responsiveness to angiotensin in aldosterone-producing adenoma. 1043 22

The aim of this study was to investigate the ontogeny of localization of 11betaHSD-2 protein in the human adrenal gland. In addition, we have investigated the effects of abnormal adrenal function on 11betaHSD-2 by determining the pattern of localization of 11betaHSD-2 protein, and the amount and level of expression of 11betaHSD-2 mRNA and protein in human adrenal cortical carcinoma and adenoma. In the human foetal adrenal gland 11betaHSD-2 immunoreactivity (11betaHSD-2-ir) was detected in the foetal zone, whereas in normal adult adrenal glands 11betaHSD-2-ir was not detected by immunocytochemistry. In adrenal cortical carcinoma and adenoma, 11betaHSD-2-ir was detectable in specific regions, which have been identified as steroid synthesizing cells using 3betaHSD-ir as a marker. In adrenal cortical carcinoma and adenoma, 11betaHSD-2 mRNA and 11betaHSD-2 protein were detected by nuclease protection analysis and by western blot analysis, respectively. In summary, 11betaHSD-2-ir was detected in the foetal zone of the mid-gestation human foetal adrenal, whereas, 11betaHSD-2-ir was not detectable in the postnatal or normal adult adrenal gland. 11BetaHSD-2 protein and mRNA was induced in adult human adrenal cortical carcinoma and adenoma. The induction of expression of 11betaHSD-2 in the adrenal cortex suggests a possible role in regulating abnormal adrenal steroidogenic function in these patients.
Mol Cell Endocrinol 1999 Aug 20
PMID:Expression of 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD-2) in the developing human adrenal gland and human adrenal cortical carcinoma and adenoma. 1050 2

A 22-year-old woman with a "hot" thyroid nodule who was being treated with minocycline for severe acne vulgaris is presented. A partial thyroidectomy specimen revealed a black adenoma. Microscopically, the black pigment was found in the follicular cells and the colloid of the adenoma. The pigment was bleached with potassium permanganate and was Fontana-Masson stain positive. It was negative for iron, periodic acid-Schiff, and acid-fast Ziehl-Neelsen stains. All these feature suggest a melanin-like pigment. However, electron microscopic examination revealed a dense osmophilic material present within the lysosomes of the follicular cells. No melanosomes were present. Twenty-six previously reported cases are reviewed, and the possible mechanisms for the deposition of the pigment in the adenoma and its relation to minocycline degradation products are discussed.
Appl Immunohistochem Mol Morphol 2000 Mar
PMID:Black thyroid adenoma. Clinical, histochemical, and ultrastructural features. 1093 53

A panel of antibodies composed of the cytokeratins (CKs), vimentin, and actin was applied to 114 minor salivary gland tumors to evaluate its diagnostic value. The results revealed that luminal cells of intercalated duct-like structures, such as those seen in pleomorphic adenoma, basal cell adenoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma, expressed CKs 7, 8, 14, and 19. The outer cells of these structures exhibited vimentin or vimentin plus muscle-specific actin, but rarely CK14, which is seen particularly in pleomorphic adenoma, in the tubular type of basal cell adenoma, and seldom in the tubular type of adenoid cystic carcinoma. Modified myoepithelial cells of pleomorphic adenoma and myoepithelioma exhibited a variable immunoprofile. CKs 7 and 8 were also observed in acinar cell adenocarcinoma and polymorphous low-grade adenocarcinoma with vimentin in the latter. CK13 was expressed only by canalicular adenoma and mucoepidermoid carcinoma cells. This study showed that the panel of antibodies employed is effective in distinguishing among salivary gland tumors.
Appl Immunohistochem Mol Morphol 2000 Sep
PMID:Application of immunohistochemistry to the diagnosis of salivary gland tumors. 1098 71

Mendelian tumour syndromes are caused by rare mutations, which usually lead to protein inactivation. Few studies have determined whether or not the same genes harbour other, more common variants, which might have a lower penetrance and/or cause mild disease, perhaps indistinguishable from sporadic disease and accounting for a considerable proportion of the unexplained inherited risk of tumours in the general population. Germline variants at the APC locus are excellent candidates for explaining why some individuals are predisposed to colorectal adenomas, but do not have the florid phenotype of familial adenomatous polyposis. We have screened 164 unrelated patients with 'multiple' (3-100) colorectal adenomas for germline variants throughout the APC gene, including promoter mutations. In addition to three Ashkenazi patients with I1307K, we found seven patients with the E1317Q variant. E1317Q is significantly associated with multiple colorectal adenomas (OR = 11. 17, 95% CI = 2.30-54.3, p < 0.001), accounting for approximately 4% of all patients with multiple colorectal adenomas. In addition, four patients with truncating APC variants in exon 9 or in the 3' part of the gene were identified. Germline APC variants account for approximately 10% of patients with multiple adenomas. Unidentified predisposition genes almost certainly exist. We argue that it is worthwhile to screen multiple adenoma patients for a restricted number of germline APC variants, namely the missense changes E1317Q and I1307K (if of Ashkenazi descent), and, if there is a family history of colorectal tumours, for truncating mutations 5' to exon 5, in exon 9 and 3' to codon 1580.
Hum Mol Genet 2000 Sep 22
PMID:Germline APC variants in patients with multiple colorectal adenomas, with evidence for the particular importance of E1317Q. 1100 24

We evaluated the effects of calcium-entry blockers on parathyroid hormone (PTH) secretion by human parathyroid adenoma cells in vitro. Nifedipine and bamidipine inhibited PTH secretion, while diltiazem had no significant effect. Cytosolic calcium concentrations were measured by use of the calcium-sensitive fluorescent dye fluo-3 with confocal laser scanning microscopy. Nifedipine increased the cytosolic concentration of calcium, whereas diltiazem decreased it. Results suggest that, in parathyroid adenoma cells, regulation of PTH secretion with respect to intracellular calcium concentration would be maintained despite differing response of intracellular calcium concentration following exposure to calcium-entry blockers.
Res Commun Mol Pathol Pharmacol 1999
PMID:In vivo effects of calcium entry blockers on human parathyroid adenoma cells with special reference to calcium sensing ability and the hormone secretion. 1112 11


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