Pulmonary small cell carcinoma (SCLC) is usually diagnosed in small biopsy or cytological specimens based on cytomorphology; however in ambiguous cases diagnosis requires additional support by immunohistochemistry. While TP53 and RB1 alterations with secondary overexpression of p16 are mainstay events in SCLC pathogenesis, diagnostic value of p16-positivity in the diagnosis of SCLC has not yet been fully investigated. We examined the expression of p16, CD56, synaptophysin (SYP), chromogranin A and thyroid transcription factor-1 (TTF1) in a series of pulmonary and extrapulmonary small cell carcinomas, pulmonary carcinoids and non-small cell lung carcinomas, and compared diagnostic performance of these markers in the diagnosis of SCLC. P16 was positive in 95 of 101 SCLCs, and displayed highest diagnostic sensitivity of ~94%. Composite biomarkers CD56+p16+TTF1 and CD56+p16+SYP were both able to detect correctly all SCLC cases. Importantly, three (~3%) SCLC cases completely negative for all conventional markers displayed diffuse positivity for p16. CD56 and p16 demonstrated highest concordance between paired small biopsy and cytology specimens. 50% of squamous cell carcinomas, ~41% of adenocarcinoma/NSCLC-favour adenocarcinoma cases, and ~93% of extrapulmonary small cell carcinomas also showed p16-positivity. Combination of CD56, p16 and TTF1 produced diagnostic classifier that outperformed best single marker CD56 in differential diagnosis between SCLC and NSCLC. In conclusion, in the appropriate morphological context p16 represents a useful supplementary marker for diagnosis of SCLC, even in cases where only cytological material is available.
- MeSH
- biopsie MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- geny p16 fyziologie MeSH
- imunohistochemie metody MeSH
- karcinoid diagnóza patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- malobuněčný karcinom diagnóza patologie MeSH
- nádorové biomarkery metabolismus MeSH
- nádory plic patologie MeSH
- nemalobuněčný karcinom plic patologie MeSH
- plíce patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinocelulární karcinom diagnóza patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
T-2 toxin is a worldwide trichothecenetoxin and can cause various toxicities.T-2 toxin is involved in G1 phase arrest in several cell lines but molecular mechanism is still not clear. In present study, we used rat pituitary GH3 cells to investigate the mechanism involved in cell cycle arrest against T-2 toxin (40 nM) for 12, 24, 36 and 48 h as compared to control cells. GH3 cells showed a considerable increase in reactive oxygen species (ROS) as well as loss in mitochondrial membrane potential (△Ym) upon exposure to the T-2 toxin. Flow cytometry showed a significant time-dependent increase in percentage of apoptotic cells and gel electrophoresis showed the hallmark of apoptosis oligonucleosomal DNA fragmentation. Additionally, T-2 toxin-induced oxidative stress and DNA damage with a time-dependent significant increased expression of p53 favors the apoptotic process by the activation of caspase-3 in T-2 toxin treated cells. Cell cycle analysis by flow cytometry revealed a time-dependent increase ofG1 cell population along with the significant time-dependent up-regulation of mRNA and protein expression of p16 and p21 and significant down-regulation of cyclin D1, CDK4, and p-RB levels further verify the G1 phase arrest in GH3 cells. Morphology of GH3 cells by TEM clearly showed the damage and dysfunction to mitochondria and the cell nucleus. These findings for the first time demonstrate that T-2 toxin induces G1 phase cell cycle arrest by the involvement of p16/Rb pathway, along with ROS mediated oxidative stress and DNA damage with p53 and caspase cascade interaction, resulting in apoptosis in GH3 cells.
- MeSH
- buněčné linie MeSH
- buněčný cyklus účinky léků fyziologie MeSH
- geny p16 účinky léků fyziologie MeSH
- hypofýza účinky léků metabolismus ultrastruktura MeSH
- krysa rodu rattus MeSH
- retinoblastomový protein biosyntéza MeSH
- signální transdukce účinky léků fyziologie MeSH
- T-2 toxin toxicita MeSH
- viabilita buněk účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Virová infekce je příčinou nejméně 15 % všech lidských malignit. Jedním z nejvýznamnějších onkogenních virů je lidský papilomavirus (HPV), který hraje roli ve vývoji karcinomu vaginy, vulvy, penisu, anu a hlavy/krku. Výskyt v těchto lokalizacích, zvláště karcinomů tonzily, se zvyšuje. Karcinomy hlavy a krku mající vztah k HPV představují skupinu nádorů odlišnou od nádorů, u nichž je rizikovým faktorem kouření a alkohol. V současné době je jasné, že podskupinu nádorů hlavy a krku tvoří sexuálně přenosná onemocnění s rozdílnou patogenezí, klinickou a patologickou charakteristikou. Stav HPV je pro nádory hlavy a krku silným nezávislým faktorem pro predikci přežití. Zvyšující se výskyt nádorů hlavy a krku mající souvislost s HPV vede k vývoji nových strategií v léčbě těchto nádorů.
Viral infection is known to cause at least 15% of all malignancies affecting humans. One of the most important oncogenic viruses, human papillomavirus (HPV), plays a role in the development of vaginal carcinoma as well as of vulvar, penis, anal, and head and neck cancers. The occurrence rates in these locations, particularly of tonsillar cancers, are increasing. Head and neck cancers related to HPV infection are a group of tumours differing from the tumours known to be related to the risk factors smoking and alcohol consumption. It is currently obvious that a subset of head and neck tumours are sexually transmitted diseases with differing pathologies, and clinical and pathological characteristics. HPV status is a strong independent predictor of survival of patients with head and neck tumours. The increasing rates of head and neck tumours associated with HPV give rise to new strategies in the treatment of these tumours.
- Klíčová slova
- karcinomy hlavy a krku, lidský papilomavirus, virová karcinogeneze,
- MeSH
- dospělí MeSH
- geny p16 fyziologie MeSH
- infekce papilomavirem komplikace patologie terapie MeSH
- lidé MeSH
- nádory hlavy a krku etiologie mikrobiologie terapie MeSH
- prognóza MeSH
- vakcíny proti papilomavirům terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
p16(INK4a), p15(INK4b), p18(INK4c) and p19(INK4d) comprise a family of cyclin-dependent kinase inhibitors and tumor suppressors. We report that the INK4 proteins share the ability to arrest cells in G1, and interact with CDK4 or CDK6 with similar avidity. In contrast, only p18 and particularly p19 are phosphorylated in vivo, and each of the human INK4 proteins shows unique expression patterns dependent on cell and tissue type, and differentiation stage. Thus, the INK4 proteins harbor redundant as well as non-overlapping properties, suggesting distinct regulatory modes, and diverse roles for the individual INK4 family members in cell cycle control, cellular differentiation, and multistep oncogenesis.
- MeSH
- buněčná diferenciace účinky léků MeSH
- cyklin-dependentní kinasa 4 MeSH
- cyklin-dependentní kinasa 6 MeSH
- cyklin-dependentní kinasy * antagonisté a inhibitory metabolismus MeSH
- fosforylace MeSH
- G1 fáze MeSH
- geny p16 fyziologie MeSH
- inhibitor p15 cyklin-dependentní kinasy MeSH
- inhibitor p16 cyklin-dependentní kinasy MeSH
- inhibitor p18 cyklin-dependentní kinasy MeSH
- inhibitor p19 cyklin-dependentní kinasy MeSH
- inhibitory enzymů * MeSH
- kompetitivní vazba MeSH
- lidé MeSH
- multigenová rodina * genetika MeSH
- nádorové buňky kultivované MeSH
- nádorové supresorové proteiny * MeSH
- orgánová specificita MeSH
- protein-serin-threoninkinasy antagonisté a inhibitory metabolismus MeSH
- proteiny buněčného cyklu * MeSH
- protoonkogenní proteiny * MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- rekombinantní fúzní proteiny genetika MeSH
- stanovení celkové genové exprese MeSH
- teratokarcinom metabolismus patologie MeSH
- transportní proteiny genetika metabolismus MeSH
- tretinoin farmakologie MeSH
- vazba proteinů MeSH
- Check Tag
- lidé MeSH
