Medizinische Universität Graz - Research portal
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SHR Neuro Cancer Cardio Lipid Metab Microb
Heiduschka, G; Lill, C; Schneider, S; Seemann, R; Kornek, G; Schmid, R; Kotowski, U; Thurnher, D.
The effect of cilengitide in combination with irradiation and chemotherapy in head and neck squamous cell carcinoma cell lines.
Strahlenther Onkol. 2014; 190(5): 472-479.
Doi: 10.1007/s00066-014-0600-x
Web of Science
PubMed
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- Leading authors Med Uni Graz
- Thurnher Dietmar
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- Abstract:
- Integrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors under clinical evaluation, cilengitide is the most promising compound. However, little is known about the cellular processes induced during cilengitide therapy in combination with irradiation and cisplatin in head and neck squamous cell carcinoma (HNSCC). The cytostatic effect of cilengitide was assessed by proliferation assay in the three HNSCC cell lines SCC25, FaDu and CAL27. Combination experiments with cisplatin and irradiation were performed. Possible synergistic effects were calculated in combination index (CI) analyses. Colony forming inhibition was investigated in clonogenic assays. Real-time PCR arrays were used to evaluate target protein gene expression patterns. Flow cytometry was used to detect apoptosis. Used alone, cilengitide has only minor cytotoxic effects in HNSCC cell lines. However, combination with cisplatin resulted in synergistic growth inhibition in all three cell lines. Irradiation showed synergism in short-term experiments and in colony forming assays, an additive effect was detected. Real-time PCR assay detected downregulation of the antiapoptotic protein Bcl-2 after exposure of cells to cilengitide. Cilengitide in combination with cisplatin and irradiation may be a feasible option for the treatment of patients with head and neck cancer. However, further investigations are required to understand the exact mechanism that leads to synergistic cytotoxicity.
- Find related publications in this database (using NLM MeSH Indexing)
- Antineoplastic Agents - pharmacology
- Apoptosis - drug effects Apoptosis - radiation effects
- Carcinoma, Squamous Cell - pathology
- Cell Line, Tumor -
- Cell Proliferation -
- Cell Survival - drug effects Cell Survival - radiation effects
- Cisplatin - pharmacology
- Combined Modality Therapy -
- Down-Regulation - genetics
- Humans -
- Integrins - antagonists & inhibitors
- Otorhinolaryngologic Neoplasms - pathology
- Proto-Oncogene Proteins c-bcl-2 - genetics
- Real-Time Polymerase Chain Reaction -
- Snake Venoms - pharmacology
- Tumor Stem Cell Assay -
- Find related publications in this database (Keywords)
- Cytotoxicity
- Cell lines
- Drug synergism
- Real-time PCR
- Clonogenic assays