Human papillomavirus infection is an important etiological factor in squamous cell carcinoma of the anus (SCCA). Different histological variants of anal carcinomas displaying squamous differentiation, previously classified as separate tumours, were recently reclassified as SCCA by the WHO. In our recent study the presence of HPV was detected by PCR in biopsy specimens of 42 different anal tumours, including SCCA and its histological variants (n=22), adenocarcinomas (n=5), tubulovillous adenomas (n=5) and anal condylomas (n=10). HR HPV16 (high risk - HR) was detected in 18 of SCCA specimens (81.8%). All histological variants, i.e. tumours with basaloid, squamous and mixed histological patterns, were represented among the HPV-positive cancers. Four tumours (18.2%) were HPV negative. Low-risk (LR) HPV types were not detected within the SCCA group. HPV16 was identified in one adenocarcinoma, while four cases were HPV negative. Two adenomas showed presence of HPV16; one showed simultaneous positivity for HPV33. The remaining three tumours were HPV negative. Seven anal condylomas (70%) were LR HPV 6 and/or 11 positive, while three were HPV negative. The presence of HR HPV types was not observed in anal condylomas. Our results provide further evidence in support of the etiological role of HR HPV infection in the development of SCCA regardless of its histological appearance.
- MeSH
- Alphapapillomavirus genetika izolace a purifikace MeSH
- dospělí MeSH
- financování organizované MeSH
- globiny chemická syntéza MeSH
- hybridizace in situ MeSH
- infekce papilomavirem komplikace MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory anu patologie virologie MeSH
- polymerázová řetězová reakce MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinocelulární karcinom patologie virologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
Styrene 7,8-oxide (SO), a reactive metabolic intermediate of the industrial chemical styrene, binds covalently at nucleophilic amino acid residues of blood proteins in vivo and in vitro. In this study, SO adducts with cysteine, lysine, and histidine were synthesized, characterized, and then used as authentic standards to assign and quantitate the SO adducts in globin incubated with SO. S-(2-Hydroxy-1-phenylethyl)cysteine and S-(2-hydroxy-2-phenylethyl)cysteine were prepared by direct alkylation of cysteine with (R)-SO or (S)-SO. To prepare the SO adducts with lysine and histidine, Nalpha-Boc-protected amino acids were alkylated with (R)-SO or (S)-SO followed by deprotection of the Boc group to obtain Nepsilon-(2-hydroxy-1-phenylethyl)lysine and Nepsilon-(2-hydroxy-2-phenylethyl)lysine as well as Npi-(2-hydroxy-1-phenylethyl)histidine, Npi-(2-hydroxy-2-phenylethyl)histidine, Ntau-(2-hydroxy-1-phenylethyl)histidine, and Ntau-(2-hydroxy-2-phenylethyl)histidine. The individual regioisomers were isolated from their mixtures by semipreparative HPLC, and their structure was assigned using NMR techniques. The SO-modified globin, isolated from human hemoglobin incubated in vitro with racemic SO at a molar ratio SO/globin of 100:1 or 10:1, was digested with pronase and subjected to LC/MS and GC/MS analysis. All known regioisomers of the SO adducts were detected, with S-(2-hydroxy-1-phenylethyl)cysteine, Nepsilon-(2-hydroxy-1-phenylethyl)lysine, and Ntau-(2-hydroxy-2-phenylethyl)histidine being the most abundant in the modified globin. Deuterated analogues of the SO adducts were employed as internal standards. The SO-amino acid adducts described here appear to be suitable biomarkers for long-term exposures to styrene or SO.
- MeSH
- biologické markery MeSH
- cystein chemie MeSH
- epoxidové sloučeniny chemická syntéza chemie metabolismus MeSH
- financování organizované MeSH
- globiny chemická syntéza chemie metabolismus MeSH
- histidin chemie MeSH
- látky znečišťující životní prostředí chemie metabolismus MeSH
- lidé MeSH
- lysin chemie MeSH
- magnetická rezonanční spektroskopie MeSH
- monitorování životního prostředí MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- stereoizomerie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Check Tag
- lidé MeSH
- MeSH
- akatalázie diagnóza epidemiologie patofyziologie MeSH
- anemie diagnóza epidemiologie etiologie MeSH
- diagnostické techniky molekulární metody statistika a číselné údaje MeSH
- finanční podpora výzkumu jako téma MeSH
- globiny dějiny chemická syntéza zásobování a distribuce MeSH
- Heinzova tělíska MeSH
- hemoglobinopatie diagnóza epidemiologie etiologie MeSH
- lidé MeSH
- mutace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
