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)

N-Bromoacetyl-[125I]T4(BrAc[125I]T4) was used as affinity label to identify type I 5'-deiodinase (5'-D) in human thyroid glands. Affinity labeled proteins were analyzed by autoradiography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Human thyroid microsomes labeled with BrAc[125I]T4 showed the most prominent radiolabeled band of protein at a mol wt of approximately 27,000 (p27). BrAc[125I]T4 incorporations into p27 were significantly higher in both Graves' and follicular adenomas than in normal thyroids. On the other hand, four cases out of five carcinomas were lower than the least value of normal thyroids. Furthermore, an excellent correlation was observed between 5'-D activities and quantities of p27 in all cases (r = 0.96; P less than 0.001). Labeling of p27 was strongly inhibited by preferred type I 5'-D substrate rT3, but to a lesser extent by poor substrate T4 or T3, and the type I 5'-D inhibitor, propylthiouracil and iopanoic acid, also inhibited the p27 labeling in normal and various diseases. In addition, the rate of enzyme inactivation by BrAcT4 equaled the rate of p27 labeling. These data suggest that p27 may be a type I 5'-D itself or at These data suggest that p27 may be a type I 5'-D itself or at least the substrate-binding subunit of this enzyme in human thyroid, and that both Graves' and follicular adenoma thyroids contain larger amounts of it, and papillary adenocarcinoma thyroids smaller than normal amounts.
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PMID:Identification of a 27-kilodalton protein with the properties of type I iodothyronine 5'-deiodinase in human thyroid gland. 174 Apr 87

INK4 and CIP/KIP are two distinct families of cyclin-dependent kinase (CDK) inhibitors implicated in mediating a wide range of cell growth control signals. We have created p18(INK4c)-deficient mice. These mice develop gigantism and widespread organomegaly. The pituitary gland, spleen, and thymus are disproportionately enlarged and hyperplastic. T and B lymphocytes develop normally in p18-deficient mice, but both exhibit increased cellularity and a higher proliferative rate upon mitogenic stimulation. Loss of p18, like that of p27, but not other CDK inhibitor genes, leads to a gradual progression from intermediate lobe pituitary hyperplasia in young mice to an adenoma by 10 months of age with a nearly complete penetrance. Mice lacking both p18 and p27, like mice chimeric for Rb deficiency, invariably died from pituitary adenomas by 3 months. Hence, p18 and p27 mediate two separate pathways to collaboratively suppress pituitary tumorigenesis, likely by controlling the function of Rb.
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PMID:CDK inhibitors p18(INK4c) and p27(Kip1) mediate two separate pathways to collaboratively suppress pituitary tumorigenesis. 974 66

The cell cycle is controlled in part by cyclin-dependent kinases (CDKs), which are activated by forming complexes with cyclins. CDKs phosphorylate certain substrates to facilitate the proliferating cells through the cell cycle. CDK inhibitors (CDKIs) such as p27 inhibit cyclin-CDK complexes and function as a negative cell cycle regulator. The overexpression of the positive regulators (cyclins) or the underexpression of the negative regulators including p27 has been seen in a variety of neoplasms, but their role and interaction in thyroid carcinogenesis is yet to be established. We studied the expression of cyclins D1 and E, and the CDKI, p27 by immunohistochemistry in 116 cases, including 59 cases of follicular variant of papillary carcinoma (FVPC) and 57 cases of follicular adenoma (FA). The positive staining was divided into four grades: 1+ if less than 10%, 2+ if 11% to 25%, 3+ if 26% to 50%, and 4+ if greater than 50% of the nuclei of tumor cells stained positively. Cyclin D1 expression was seen in 37 (63%) FVPC and 34 (60%) FA. Cyclin E-positive cells were seen in 51 (86%) FVPC and 47 (82%) FA. No significant differences in the grade of cyclins D1 (P = .261) and E (P = .284) staining was seen between FVPC and FA. Of the 59 FVPC, 53 (89%) showed p27-positive cells; of these, 33 were 1+, nine were 2+, seven were 3+ and only four were 4+ positive. Conversely, all 57 FA were p27 positive, 53 were 4+, and four were 3+ positive. This difference in the grade of p27 staining between FVPC and FA was statistically significant (P < .001). This study shows a significant underexpression of p27 in FVPC compared with FA, suggesting that a decrease in p27 expression plays a more important role than overexpression of cyclins D1 and E alone in thyroid carcinogenesis and that p27 immunostaining may be helpful in the diagnosis of FVPC.
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PMID:The role of cell cycle regulatory proteins, cyclin D1, cyclin E, and p27 in thyroid carcinogenesis. 982 12

Recent immunohistochemical analysis of cell cycle-related proteins such as p27, a cell cycle inhibitory protein, and Ki-67, a proliferation marker, indicated their possible values in predicting the biologic behavior of various human neoplasms. In this study, we performed an immunohistochemical analysis of p27 and Ki-67 in 42 adrenocortical neoplasms (12 adrenocortical carcinomas, 24 adrenocortical adenomas) and 6 normal adrenal glands to evaluate their possible values in diagnosing adrenocortical malignancy and in predicting the biologic behavior of carcinomas. We detected Ki-67 and p27 immunoreactivity in the nuclei of all of our cases, and we observed a significant negative correlation (r = -0.572, P < .001) between the p27 and Ki-67 labeling indexes (LIs). The LIs of p27 and Ki-67 were 61.7+/-2.6 and 0.28+/-0.08 in the normal adrenal cortex and 59.4+/-6.5 and 0.33+/-0.11 in the adenomas, respectively, with no significant differences between the LIs of the adenomas and normal adrenals. The LIs of p27 and Ki-67 in the carcinomas were 48.9+/-7.5 and 630+/-6.21, respectively. The LI of p27 in the carcinomas was significantly lower than that in the adenomas. The LI of Ki-67 in the carcinomas was significantly higher than that in the adenomas (P < .01). Among carcinoma cases, the Ki-67 LI in living cases tended to be lower than that in deceased cases, and the p27 LI in living cases tended to be higher than that in deceased cases, but these differences did not reach statistical significance. These results indicated that decreased p27 protein expression might cause increased cell proliferation in adrenocortical carcinoma cells in combination with other positive and/or negative regulators of the cell cycle. These results also suggested that immunohistochemical analysis of p27 and Ki-67 might be useful in distinguishing between adrenocortical adenoma and carcinoma
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PMID:Expression of cell cycle inhibitor p27 and Ki-67 in human adrenocortical neoplasms. 987 46

The expression of E2F-1 in human colorectal carcinomas was examined immunohistochemically, and the correlation of E2F-1 expression with clinicopathological findings and with the expression of p27(Kip1) was analyzed to elucidate the role of E2F-1 in the development and progression of colorectal carcinomas. In nonneoplastic mucosa, a small number of epithelial cells in the proliferative zone were weakly positive for E2F-1. Weak expression of E2F-1 was detected in many adenoma cells. Most of the colorectal carcinomas expressed E2F-1 at various levels, and strong expression of E2F-1 was detected in 56% (49/88) of the cases. There was no correlation between the expression of E2F-1 and any clinicopathological parameters such as tumor stage, depth of tumor invasion and lymph node metastasis. Reduced expression of p27(Kip1) was confirmed to be significantly correlated with deep tumor invasion and presence of metastasis. No correlation was evident between overexpression of E2F-1 and reduced p27(Kip1) expression.
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PMID:Expression of cell-cycle-regulating transcription factor E2F-1 in colorectal carcinomas. 1073 78

In 54 lesions of gastric adenomas consisting of 31 low-grade adenomas (LGAs) and 23 high-grade adenomas (HGAs), 28 intramucosal carcinomas (IMCs), and 23 carcinomas invading the submucosa (SMCs), the expression of cell-cycle regulatory gene products (p53, p21/waf1, p27/kip1, and Ki-67) was studied using immunohistochemical techniques. Several lesions were also analyzed by the fluorescence in situ hybridization method. The overexpression of p53 was found in no LGAs and in 9% of HGAs, whereas a considerable number of cases showed an overexpression in IMCs (39%) and SMCs (43%). A reduced expression of p21/waf1 was present in only 4% of HGAs. Superficial eccentric positivity was present in all LGAs and 74% of HGAs, whereas it was present in 46% of IMCs and 4% of SMCs. P53-positive and p21/waf1-negative lesions, which were supposed to have a mutated p53 gene, were observed in no LGAs, in 4% of HGAs, in 11% of IMCs, and in 26% of SMCs. The expression of cyclin E was more frequently present in carcinomas than in adenomas. However, no high expression of cyclin E was observed among the adenomas. A reduced expression of p27/kip1 was encountered more frequently in carcinoma than adenoma. By a semiquantitative evaluation comparing adenoma and carcinoma in the same stomach, the increased degrees of both p21/waf1 and cyclin E were highlighted. A chromosome gain was detected among 7% of the adenomas and 85% of the carcinomas. In conclusion, the expressions of p53, p21/waf1, p27/kip1, and cyclin E were considered to be of great value for estimating the dysplastic progression of gastric adenomas. Especially, various aspects of protein expression, including its distribution and semiquantitative evaluation of positive cells, and a combined analysis with several proteins, may thus be useful as possible markers of dysplastic evolution in gastric adenomas.
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PMID:Expressions of cell-cycle regulatory gene products in conventional gastric adenomas: possible immunohistochemical markers of malignant transformation. 1074 68

p27(Kip1) is a cyclin-dependent kinase inhibitor that negatively regulates cell proliferation. This study was designed to evaluate the roles of p27(Kip1) in gallbladder carcinogenesis and the prognostic value of p27(Kip1) in patients with gallbladder carcinoma. p27(Kip1) expression was examined immunohistochemically in surgically resected specimens of 8 normal epithelia, 8 adenomyomatosis lesions, 6 precancerous adenomas, and 37 carcinomas of the gallbladder. Decreased p27(Kip1) expression (<50% nuclear staining) was observed in 16 of the 37 (43%) gallbladder carcinomas, but not in any specimen of normal epithelium, adenomyomatosis, or adenoma. The fact that all of the adenomas showed normal p27(Kip1) expression suggests that decreased p27(Kip1) expression is probably not an early event in gallbladder carcinogenesis. Decreased p27(Kip1) expression was significantly associated with less marked tumor cell differentiation (P =.017), lymphatic invasion (P =.046), lymph node metastasis (P =.007), and advanced TNM stage (stage IV vs. stage I, P =.026; stage IV vs. stage II, P =.005). This suggests that down-regulation of p27(Kip1) expression is a late event in gallbladder carcinogenesis, possibly promoting tumor progression and metastasis. Kaplan-Meier curves showed that decreased p27(Kip1) expression was significantly associated with shorter overall survival (P =.001) in patients with gallbladder carcinomas who had undergone radical surgery. Cox's proportional hazards model revealed decreased p27(Kip1) expression to be an independent predictor for death (P =.034; risk ratio, 3.9; 95% confidence interval, 1.1-13.7). In conclusion, decreased p27(Kip1) expression significantly correlates with tumor progression and predicts poor prognosis in gallbladder carcinomas.
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PMID:p27(Kip1) expression in normal epithelia, precancerous lesions, and carcinomas of the gallbladder: association with cancer progression and prognosis. 1079 81

p27 (Kip1) plays regulatory roles in the cell cycle by inhibiting the activity of cyclin dependent kinases (CDKs). This immunohistochemical study is aimed at elucidating the expression of p27 in human pituitary and in various types of pituitary adenomas in order to clarify its role in the regulation of proliferation. Sixteen normal pituitary glands and 179 human pituitary adenomas were used for immunohistochemical studies. The tissues were fixed in 10% formalin and embedded in paraffin. Indirect peroxidase method was performed after heat-induced antigen retrieval using a monoclonal antibody against p27 protein. p27 protein was expressed in the nuclei of all 16 normal human pituitary glands. p27 protein was also expressed in 128 of 179 cases of pituitary adenomas (71.5%). A marked decrease of p27 expression was noted in ACTH-secreting adenomas, 8/20 (40.0%), compared with other types of pituitary adenomas--GH-secreting adenomas, 35/46 (76.1%); PRL-secreting adenomas, 22/33 (66.7%); TSH-secreting adenomas, 8/11 (72.7%); and nonfunctioning adenomas, 55/69 (79.7%). These results suggest that p27 may play some role in the regulation of proliferation in all types of pituitary adenomas. The lower levels of p27 in ACTH-secreting adenoma is of particular interest with respect to the intermediate lobe-derived pituitary tumor developed in p27 knockout mice.
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PMID:Immunohistochemical analysis of p27 (Kip1) in human pituitary glands and in various types of pituitary adenomas. 1157 84

Although cyclin E gene amplification is reported to be an important event in various cancers, it is rarely found in human colorectal cancers. As one of the candidate factors of other mechanisms relating to cyclin E, we analyzed cyclin E-dependent kinase activity in colorectal cancer. Protein levels of cyclin E, its catalytic subunit, cyclin-dependent kinase 2 (Cdk2), and p21 and p27 were determined by western blot or immunohistochemistry in 27 colorectal cancers and 10 colorectal adenomas, and compared with adjacent normal colonic mucosa. Enzymatic activity of cyclin E-Cdk2 complex in the colorectal neoplasm was measured using in-gel kinase assay using glutathione S-transferase-retinoblastoma (GST-Rb) fusion protein as substrate, and compared with that of normal mucosa. We clearly showed that although the protein level of cyclin E in colorectal cancer and adenoma was similar to that of adjacent normal mucosa, cylin E-dependent kinase activity was increased in all the cases of colorectal cancers and 90% of colorectal adenomas. The relative kinase activity was significantly higher in colorectal cancer (3.7 +/- 1.7 -fold) than colorectal adenomas (2.0 +/- 0.8-fold) (P < 0.004). The relative expression level of Cdk2 protein in cancer was significantly higher than adenoma (4.4 +/- 2.4 vs 2.7 +/- 1.3, P < 0.04), and p21 and p27 were not detected in colorectal cancer and notably decreased in adenoma. The results of this study strongly suggest that activation of cyclin E-dependent kinase activity may play an important role in colorectal cancer, and its level appears to be related to increased Cdk2 and decreased p21 and p27 amounts rather than cyclin E protein level.
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PMID:Activation of cyclin E-dependent kinase activity in colorectal cancer. 1168 May 95

Expression of the cyclin-dependent kinase inhibitor p27(Kip1) (p27) is frequently reduced in human colorectal cancer, and this correlates with poor patient prognosis. To clarify the role of p27 in gastrointestinal (GI) cancer, we measured p27 expression, as well as the effect of germline deletion of p27, in 3 different mouse models of GI neoplasia. p27 expression was frequently reduced in GI tumors arising in 1,2-dimethylhydrazine (DMH) treated mice, and in Apc mutant Min/+ mice, but not in GI tumors arising in Smad3 mutant mice. Germline deletion of p27 resulted in accelerated tumor development and increased tumor cell proliferation in both DMH treated and Min/+ mice, but not in Smad3 mutant mice. p27 deficiency also led to increased adenoma to adenocarcinoma progression. These results indicate that reduction of p27 cooperates with mutations in Apc but not in Smad3 during GI tumorigenesis. Thus, tumor suppression by p27 is contingent on the specific oncogenic pathway that drives tumor development.
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PMID:Pathway-specific tumor suppression. Reduction of p27 accelerates gastrointestinal tumorigenesis in Apc mutant mice, but not in Smad3 mutant mice. 1208 50


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