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Expression of HIF-1 and ubiquitin in conventional renal cell carcinoma: relationship to mutations of the von Hippel-Lindau tumor suppressor gene 总被引:2,自引:0,他引:2
Conventional clear cell renal cell carcinomas (cRCC) have mutations of the von Hippel-Lindau (VHL) tumor suppressor gene at 3p25 in approximately 50% of cases. The VHL gene normally regulates ubiquitin-mediated proteolysis of hypoxia-inducible factor 1alpha (HIF-1alpha); in cell lines, VHL inactivation blocks HIF-1alpha proteolysis, resulting in increased HIF-1 expression. This study was undertaken to investigate the relationship between VHL mutations and the expression of ubiquitin and HIF-1alpha in cRCC. Eleven cRCC were studied with microsatellite analysis for 3p deletions and with sequencing for VHL mutations. Immunohistochemistry was performed for HIF-1alpha and ubiquitin. Deletions at 3p25 were found in 10 tumors, and VHL mutations were identified in 6 of these cases. There was staining for ubiquitin and HIF-1alpha in all tumors with VHL mutations. Among the five cases without VHL mutations, staining for ubiquitin or HIF-1alpha was not present in three cases but was present in two tumors, both of which had 3p deletions. The findings support a role for VHL mutations promoting cRCC development by an impairment of HIF-1alpha proteolysis. The findings also suggest that a 3p tumor suppressor gene other than VHL may also influence HIF-1alpha degradation and that there is an additional tumorigenic pathway for cRCC that does not involve VHL or HIF-1. 相似文献
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H F Seigler W W Shingleton R S Metzgar C E Buckley P M Bergoc D S Miller B F Fetter M B Phaup 《Surgery》1972,72(1):162-174
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Three cases of cervical carcinoma with an adenoid cystic pattern were studied by light and electron microscopy. All were found to be compatible with the histologic picture of adenoid cystic carcinoma in other body sites. Although there was some variability in the pattern among the tumors, areas of each exhibited a cribriform appearance characterized by small cells with sparse cytoplasm arranged around cystic gland-like lumina. Only one tumor displayed cylindromatous formations similar to those described by Billroth. Two of the tumors were associated with foci of squamous cell carcinoma while the third contained areas suggestive of such a component. Electron microscopic examination showed varied morphology of the cysts, manifested by true glandlike lumina, extracellular spaces containing replicated basement membrane or enclosed stroma. In view of the observed diversity in the light and electron microscopic morphology of adenoid cystic carcinomas of the cervix, it is apparent that this tumor is not a distinct histologic entity. Accordingly, it is recommended that the terminology "cervical carcinoma with adenoid cystic pattern" be utilized. 相似文献
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Long-term efficacy of argon laser trabeculoplasty 总被引:3,自引:0,他引:3
B J Shingleton C U Richter A R Bellows B T Hutchinson R J Glynn 《Ophthalmology》1987,94(12):1513-1518
Long-term efficacy of 360 degrees argon laser trabeculoplasty was studied in 118 eyes of 93 patients with uncontrolled chronic open-angle glaucoma. The mean intraocular pressure (IOP) decrease was 8.9 +/- 5.4 mmHg (mean +/- standard deviation [SD] in 71 eyes at 1 year, 9.3 +/- 4.3 mmHg (mean +/- SD) in 51 eyes at 3 years, and 10.3 +/- 3.9 mmHg (mean +/- SD) in 28 eyes at 5 years. The probability of success at 4 years (decrease in IOP greater than or equal to 3 mmHg, IOP less than or equal to 19 mmHg, stable visual field, stable optic nerve, and no further laser or surgical intervention) was 52%. Pretreatment IOP, diagnosis, previous operations, age, and sex were not significant determinants for success or failure. Eyes receiving argon laser trabeculoplasty before cataract surgery maintained control of IOP after surgery. Failure was most common in the first year after treatment (23%), and thereafter failure occurred at a rate of 7 to 10% per year. 相似文献
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