| 1. |
- Zupancic, M, et al.
(författare)
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Analysis of Human Papillomavirus (HPV) and Polyomaviruses (HPyVs) in Adenoid Cystic Carcinoma (AdCC) of the Head and Neck Region Reveals Three HPV-Positive Cases with Adenoid Cystic-like Features
- 2022
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- An aetiological role of human papillomavirus (HPV) and/or human polyomaviruses (HPyVs) has been proposed in adenoid cystic carcinoma (AdCC). Moreover, HPV-related multiphenotypic carcinoma (HMSC) was recently introduced as an emerging entity of the sinonasal region. Here, we primarily want to study the role of HPV/HPyV in a large AdCC cohort and, secondly, possibly identify and characterize HMSC. Tumour DNA from 68 patients initially diagnosed with AdCC between 2000 and 2012 was, therefore, tested for 27 HPV types and 10 HPyVs. HPV DNA-positive samples were micromorphologically re-evaluated, further stained for p16INK4a, S100, p63 and CD117 and tested for the presence of the MYB-NFIB fusion transcript. Notably, no samples were HPyV-positive, while one sinonasal and two tonsillar carcinomas were HPV- and p16-positive. After re-evaluating the micromorphology, immunohistochemistry and presence of fusion transcripts, all tumours had the same appearance and fitted within the diagnosis of HMSC, but in all these three cases, the morphology of the HMSC and basaloid squamous cell carcinoma was overlapping. We conclude that HPV and HPyV have no major role in AdCC. However, based on our data, we also suggest that HMSC should be considered as a basaloid variant of squamous cell carcinoma, and not its own entity, until better characterized.
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| 2. |
- Kostopoulou, ON, et al.
(författare)
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Targeted Therapy of HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy between CDK4/6, PI3K and Sometimes FGFR Inhibitors, but Rarely between PARP and WEE1 Inhibitors
- 2022
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus positive (HPV+) tonsillar and base of tongue squamous cell carcinoma (TSCC/BOTSCC) have a favorable outcome, but upon relapse, survival is poor and new therapeutical options are needed. Recently, we found synergistic effects by combining the food and drug administration approved (FDA) phosphoinositide 3-kinase (PI3K) and fibroblast-growth-factor-receptor (FGFR) inhibitors BYL719 and JNJ-42756493 on TSCC cell lines. Here this approach was extended and Cyclin-Dependent-Kinase-4/6 (CDK4/6) and Poly-ADP-ribose-polymerase (PARP) and WEE1 inhibitors PD-0332991, and MK-1775 respectively were also examined. HPV+ CU-OP-2, -3, -20, and HPV− CU-OP-17 TSCC cell lines were treated with either BYL719 and JNJ-42756493, PD-0332991 BMN-673 and MK-1775 alone or in different combinations. Viability, proliferation, and cytotoxicity were followed by WST-1 assays and the IncuCyte S3 Live® Cell Analysis System. All inhibitors presented dose-dependent inhibitory effects on tested TSCC lines. Synergy was frequently obtained when combining CDK4/6 with PI3K inhibitors, but only sometimes or rarely when combining CDK4/6 with FGFR inhibitors or PARP with WEE1 inhibitors. To conclude, using CDK4/6 with PI3K or FGFR inhibitors, especially PD-0332991 with BYL719 presented synergy and enhanced the decrease of viability considerably, while although dose dependent responses were obtained with PARP and WEE1 inhibitors (BMN-673 and MK-1775 resp.), synergy was rarely disclosed.
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