Radiation therapy is an established modality in the treatment of head and neck cancer patients. Compromised wound healing in irradiated tissues is a common and challenging clinical problem. The pathophysiology and underlying cellular mechanisms including the complex interaction of cytokines and growth factors are still not understood completely. In this review, the current state of research regarding the pathomechanisms of compromised wound healing in irradiated tissues is presented. Current and possible future treatment strategies are critically reviewed.

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BackgroundThe inflammatory response clinically observed after radiation has been described to correlate with elevated expression of cytokines and adhesion molecules by endothelial cells. Therapeutic compensation for this microvascular compromise could be an important approach in the treatment of irradiated wounds. Clinical reports describe the potential of adipose-derived stem cells to enhance wound healing, but the underlying cellular mechanisms remain largely unclear.MethodsHuman dermal microvascular endothelial cells (HDMEC) and human adipose-derived stem cells (ASC) were cultured in a co-culture setting and irradiated with sequential doses of 2 to 12 Gy. Cell count was determined 48 h after radiation using a semi-automated cell counting system. Levels of interleukin-6 (IL-6), basic fibroblast growth factor (FGF), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined in the supernatants using enzyme-linked immunosorbent assay (ELISA). Irradiated HDMEC and ASC as well as non-irradiated co-cultures, HDMEC or ASC respectively were used as controls.ResultsCell count was significantly reduced in irradiated co-cultures of HDMEC and ASC compared to non-irradiated controls. Levels of IL-6, FGF, ICAM-1 and VCAM-1 in the supernatants of the co-cultures were significantly less affected by external radiation in comparison to HDMEC.ConclusionThe increased expression of cytokines and adhesion molecules by HDMEC after external radiation is mitigated in the co-culture setting with ASC. These in vitro changes seem to support the clinical observation that ASC may have a stabilizing effect when injected into irradiated wounds.

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Background MicroRNAs (miRNA) recently evolved as potential cancer biomarkers. Therefore, the aim of the present study was to evaluate the prognostic impact of eight miRNAs connected to oral squamous cell carcinoma (OSCC). Method Expression levels of hsa‐mir‐21‐5p, hsa‐mir‐29b‐3p, hsa‐mir‐31‐5p, hsa‐mir‐99a‐5p, hsa‐mir‐99b‐3p, hsa‐mir‐100‐5p, hsa‐mir‐143‐3p and hsa‐mir‐155‐5p were analyzed in tumor tissue (n = 36) and healthy oral mucosal tissue (n = 17) and correlated with clinical variables. Results of the study cohort were validated in an OSCC cohort of The Cancer Genome Atlas. Results Increased hsa‐mir‐99b‐3p expression level showed a tendency toward advanced tumor stages, and high levels of hsa‐mir‐100‐5p expression were associated with extracapsular extension. While a high expression level of hsa‐mir‐99b‐3p was associated with better survival, a high expression level of hsa‐mir‐100‐5p was correlated with a poorer survival in the study cohort. Conclusion Our results indicate that hsa‐mir‐99b‐3p and hsa‐mir‐100‐5p may serve as novel prognostic biomarkers in OSCC.