Aims Papillary renal neoplasm with reverse polarity (PRNRP) is a newly defined entity with distinct histomorphology and recurrent KRAS mutation. It has been estimated to constitute 4% of previously diagnosed papillary renal cell carcinoma (PRCC). Renal papillary adenoma (PA) is suggested to be the precursor of PRCC. This study aimed to investigate the association between PRNRP and PA, particularly the morphologically similar type D PA. Methods and results Nephrectomy specimens of PRCC and PA from our 10‐year pathology archives were retrieved and reviewed. GATA3 immunohistochemistry and RAS/BRAF testing were performed in all cases reclassified as PRNRP and all PAs with sufficient materials. Overall, PRNRP accounted for 9.1% (10 of 110) of PRCC and there was no recurrence/metastasis with a mean follow‐up period of 39 months. Three novel morphological features were described, including clear cell change, mast cell infiltration and metaplastic ossification. Nine of the 10 PRNRPs showed diffuse and strong GATA3 expression and KRAS missense mutations at codon 12. One case exhibited moderate GATA3 staining on 80% of the tumour cells and RAS/BRAF wild‐type. In a total of 73 PAs, 11 were classified as type D. GATA3 expression was significantly more frequent in type D versus non‐type D PAs (100 versus 35%, P < 0.01). KRAS missense mutations were identified in six of eight (75%) of the type D PAs but none of the 18 non‐type D PAs. Conclusions Type D PA was different from other types of PA and represented an analogue or a small‐sized PRNRP for their identical morphology, immunophenotype and molecular signature.
ObjectiveThere is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke.DesignRetrospective.SettingWe conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database.ParticipantsAmong 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio <80%. Also, 355 were excluded due to history of atrial fibrillation, valvular heart disease or coagulopathy. Therefore, 1884 patients were included in our final analysis.InterventionsPatients were categorised into two groups based on whether clopidogrel or aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010.Primary and secondary outcome measuresThe primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke.ResultsCompared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, p<0.001, number needed to treat: 8) and recurrent stroke (HR=0.54, 95% CI 0.42 to 0.69, p<0.001, number needed to treat: 9) after adjustment of relevant covariates.ConclusionsAmong patients with an ischaemic stroke while taking aspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation.
Sp1 is a basic transcriptional factor that binds to the GC-rich region in the promoter of the target gene. It is involved in transcription of numerous genes by recruiting transcriptional factors to the promoters of target genes. In this study, we found in vivo and in vitro that Hsp90␣ was recruited to the GC-rich region of the 12(S)-lipoxygenase promoter through interaction with Sp1 in A431 cells by employing DNA affinity immunoprecipitation assay and chromatin immunoprecipitation assay. When Hsp90␣ was inhibited by geldanamycin (GA, a specific inhibitor of the Hsp90 family) or by siRNA of Hsp90␣ (to block its activity or to knockdown protein levels), respectively, luciferase activity (driven by the 12(S)-lipoxygenase promoter) and both mRNA and protein levels of 12(S)-lipoxygenase were reduced significantly in cells. In addition, the effect of GA was abolished when the Sp1 binding sites of 12(S)-lipoxygenase were mutated in A431 cells. Interestingly, binding of Sp1 to the 12(S)-lipoxygenase promoter was also decreased upon GA treatment in cells. In conclusion, our results indicate that Sp1 interacts with Hsp90␣ to recruit it to the promoter of 12(S)-lipoxygenase and then to regulate gene transcription by modulating the binding ability of Sp1 to promoters.Sp1 is one of the first transcription factors purified and cloned from mammalian cells (1, 2). It can recognize and specifically bind to GC-rich sites within the simian virus 40 promoter via three Cys 2 His 2 zinc finger motifs localized at its C-terminal region to regulate the transcription of the target genes (3, 4). In addition to the zinc finger domain of the C-terminal region, the N-terminal regions of the Sp1 are much more variable and contain transcriptional activation or repression domains (5, 6). Sp1 is generally considered as a factor that primarily determines the core activity of the promoter by direct interaction with other factors of the basal transcriptional machinery and by cooperation with several transcriptional activators such as CRSP, p300/CBP, steroidogenic factor-1 (SF-1), vitamin D3 receptor, and TAFII130 (7-12). Recent studies reveal that both DNA binding ability and transactivational activity of Sp1 may be influenced by the post-translational modification of Sp1 such as phosphorylation, glycosylation, and acetylation (13,14). Previous studies indicate that Sp1 is phosphorylated by casein kinase II, which has been reported to repress Sp1 activity, and by DNA-dependent protein kinase and CDKII, to positively regulate the transactivity and DNA binding affinity of . In addition, glycosylation of Sp1 was found to regulate the proteasome-dependent degradation, and it is acetylated to regulate the DNA binding affinity or transactivation (19 -24). Therefore, post-translational modification on Sp1, because of interaction with other factors, may play an important role in the regulation of Sp1 activity.Hsp90, a constituent molecular chaperone, is an abundant protein, comprising 2% of total cellular proteins under non-stress conditions. It is essent...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.