Kravtsov, P* Dotaz Zobrazit nápovědu
A series of 2-piperazin-1-yl-quinazolines were synthesized and evaluated for their antiaggregative activity. The synthesized small molecule compounds have potently inhibited platelet aggregation in vitro and blocked FITC-Fg binding to αIIbβ3 integrin in a suspension of washed human platelets. The key αIIbβ3 protein-ligand interactions were determined in docking experiments and some correlations have been observed between values of the affinity and docking scores.
- MeSH
- agregace trombocytů účinky léků MeSH
- chinazoliny chemie farmakologie MeSH
- inhibitory agregace trombocytů chemie farmakologie MeSH
- lidé MeSH
- ligandy MeSH
- piperaziny chemie farmakologie MeSH
- simulace molekulového dockingu MeSH
- trombocytový glykoproteinový komplex IIb-IIIa metabolismus MeSH
- trombocyty cytologie účinky léků metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Clear cell mesothelioma is uncommon and shows predominance of clear cells with resemblance to clear cell carcinomas. Clinicopathologic and molecular descriptions of clear cell mesothelioma remained limited. In this study, we identified an index patient with clear cell mesothelioma, confirmed by immunohistochemical and ultrastructural studies. Targeted next-generation sequencing revealed the presence of an inactivating VHL mutation. We then systematically searched for VHL-mutant mesotheliomas in a comprehensive genomic profiling database of 1532 mesotheliomas. Collectively, we identified a cohort of four VHL-mutant clear cell mesotheliomas, including three peritoneal and one pleural tumors from three females and one male, with age range of 47-68 (median 63) years. Histologically, each tumor showed a microcystic to tubulopapillary architecture with prominent clear cells. By next-generation DNA sequencing, each of the four clear cell mesotheliomas harbored inactivating VHL mutations, while lacking other alterations typical of mesotheliomas such as BAP1, NF2, SETD2, CDKN2A, CDKN2B, TP53, and PTEN. By using low-pass whole genome sequencing on the index case and targeted next-generation sequencing on the remaining three cases, we identified extensive loss of heterozygosity throughout the genome but consistently sparing chromosomes 5, 7, and 20, characteristic of genomic near-haploidization. In summary, clear cell mesotheliomas were characterized by inactivating VHL mutations and genomic near-haploidization and appeared to represent a distinct clinicopathologic and molecular category of mesotheliomas. Our findings implicate VHL in the pathogenesis of a subset of mesotheliomas, particularly those with clear cell morphology.
- MeSH
- chromozomální aberace MeSH
- genomika MeSH
- haploidie MeSH
- lidé středního věku MeSH
- lidé MeSH
- maligní mezoteliom * MeSH
- mezoteliom * genetika MeSH
- mutace MeSH
- nádorový supresorový protein VHL genetika MeSH
- nádory plic * genetika MeSH
- senioři MeSH
- thiolesterasa ubikvitinu genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
- MeSH
- adjuvancia imunologická MeSH
- antigeny bakteriální aplikace a dávkování MeSH
- bakteriální polysacharidy aplikace a dávkování MeSH
- biologické modely MeSH
- časové faktory MeSH
- difterický toxoid aplikace a dávkování MeSH
- hlodavci MeSH
- křečci praví MeSH
- krysa rodu rattus MeSH
- lymfatické uzliny imunologie MeSH
- morčata imunologie MeSH
- myši MeSH
- plazmatické buňky MeSH
- rozpustnost MeSH
- tetanový toxoid aplikace a dávkování MeSH
- tvorba protilátek MeSH
- Yersinia pestis imunologie MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- krysa rodu rattus MeSH
- morčata imunologie MeSH
- myši MeSH
- zvířata MeSH
AIMS: The distinction between benign and malignant thyroid nodules has important therapeutic implications. Our objective was to develop an assay that could classify indeterminate thyroid nodules as benign or suspicious, using routinely prepared fine needle aspirate (FNA) cytology smears. METHODS: A training set of 375 FNA smears was used to develop the microRNA-based assay, which was validated using a blinded, multicentre, retrospective cohort of 201 smears. Final diagnosis of the validation samples was determined based on corresponding surgical specimens, reviewed by the contributing institute pathologist and two independent pathologists. Validation samples were from adult patients (≥18 years) with nodule size >0.5 cm, and a final diagnosis confirmed by at least one of the two blinded, independent pathologists. The developed assay, RosettaGX Reveal, differentiates benign from malignant thyroid nodules, using quantitative RT-PCR. RESULTS: Test performance on the 189 samples that passed quality control: negative predictive value: 91% (95% CI 84% to 96%); sensitivity: 85% (CI 74% to 93%); specificity: 72% (CI 63% to 79%). Performance for cases in which all three reviewing pathologists were in agreement regarding the final diagnosis (n=150): negative predictive value: 99% (CI 94% to 100%); sensitivity: 98% (CI 87% to 100%); specificity: 78% (CI 69% to 85%). CONCLUSIONS: A novel assay utilising microRNA expression in cytology smears was developed. The assay distinguishes benign from malignant thyroid nodules using a single FNA stained smear, and does not require fresh tissue or special collection and shipment conditions. This assay offers a valuable tool for the preoperative classification of thyroid samples with indeterminate cytology.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA metabolismus MeSH
- nádory štítné žlázy diagnóza MeSH
- odchylka pozorovatele MeSH
- prediktivní hodnota testů MeSH
- tenkojehlová biopsie MeSH
- uzly štítné žlázy diagnóza MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- validační studie MeSH
