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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 313 - 325 (13page)
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Purpose The p38 mitogen-activated protein kinase (MAPKs) play a crucial role in the production of pro-inflammatory cytokines and over-expression of it increase cytokines which promote cancer. Among four isoforms, p38α has been well studied in head and neck squamous cell carcinoma (HNSCC) and other cancers as a therapeutic target. p38δ has recently emerged as a potential disease-specific drug target. Elevated serum p38α level in HNSCC was reported earlier from our lab. This study aims to estimate the levels of p38 MAPK-isoforms in the serum of HNSCC and design peptide inhibitor targeting the same. Materials and Methods Levels of p38 MAPK isoforms in the serum of HNSCC and healthy controls were quantified by surface plasmon resonance technology. The peptide inhibitor for p38 MAPK was designed by molecular modeling using Grid-based Ligand Docking with Energetics tools and compared with known specific inhibitors. Results We have observed highly elevated levels of all four isoforms of p38 MAPK in serum of HNSCC patients compared to the control group. Further, serum p38α, p38β, and p38δ levels were down regulated after therapy in follow-up patients, while p38γ showed no response to the therapy. Present study screened designed peptide WFYH as a specific inhibitor against p38δ. The specific inhibitor of p38δ was found to have no effect on p38α due to great structural difference at ATP binding pocket. Conclusion In this study, first time estimated the levels of p38 MAPK isoforms in the serum of HNSCC. It can be concluded that p38 MAPK isoforms can be a diagnostic and prognostic marker for HNSCC and p38δ as a therapeutic target.
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참고문헌 (15)
참고문헌 신청
Kamangar F / 2006 / Patterns of cancer incidence, mortality, and prevalence across five continents : defining priorities to reduce cancer disparities in different geographic regions of the world / J Clin Oncol 24:2137~2150
Risco A / 2012 / New insights into the p38gamma and p38delta MAPK pathways / J Signal Transduct 2012:520289
Gill K / 2012 / Quantification of p38alphaMAP kinase : a prognostic marker in HNSCC with respect to radiation therapy / Clin Chim Acta 413:219~225
Gill K / 2013 / Development of peptide inhibitor as a therapeutic agent against head and neck squamous cell carcinoma(HNSCC)targeting p38alpha MAP kinase / Biochim Biophys Acta 1830:2763~2769
Gill K / 2014 / The rational design of specific peptide inhibitor against p38alpha MAPK at allosteric-site: a therapeutic modality for HNSCC / PLoS One 9:e101525
Risco A / 2012 / New insights into the p38gamma and p38delta MAPK pathways / J Signal Transduct 2012:520289
Gill K / 2012 / Quantification of p38alphaMAP kinase : a prognostic marker in HNSCC with respect to radiation therapy / Clin Chim Acta 413:219~225
Gill K / 2013 / Development of peptide inhibitor as a therapeutic agent against head and neck squamous cell carcinoma(HNSCC)targeting p38alpha MAP kinase / Biochim Biophys Acta 1830:2763~2769
Gill K / 2014 / The rational design of specific peptide inhibitor against p38alpha MAPK at allosteric-site: a therapeutic modality for HNSCC / PLoS One 9:e101525
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