• 2018-07
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  • 2019-08
  • A main strategy of regenerative medicine is the construction


    A main strategy of regenerative medicine is the construction of a biocompatible scaffold that, in combination with living SAR 405 and/or bioactive molecules, replaces, regenerates or repairs damaged cells or tissue (Perán et al., 2012; López-Ruiz et al., 2012). Growth factors are commonly used to enhance the scaffold\'s bioactivity and facilitate tissue growth and regeneration. The rationale of incorporating growth factors within a construct, is to allow the surrounding cells to attach to the scaffold via surface receptor binding, activate their signaling pathways and dictate them to migrate, proliferate, differentiate and synthesize proteins during tissue regeneration (Lutolf and Hubbell, 2005). Thus further SAR 405 studies to evaluate the effect of the incorporation of AB235 to bio-compatible scaffolds could have important clinical application in the near future.
    Acknowledgments Macarena Peran was supported first by the Spanish Ministry of Education through the National Human Resources Mobility National Plan I-D+i 2008–2011 and continued with a grant from Jaen University, Spain. J.A.M.: Junta de Andalucía, excellence project number CTS-6568. Work in the laboratory of J.C.I.B. was supported by grants from TERCEL-ISCIII-MINECO, Fundacion Cellex, CIBER-BBN, The Leona M. and Harry B. Helmsley Charitable Trust, G. Harold and Leila Y. Mathers Charitable Foundation and The Ellison Medical Foundation.
    Introduction Cancer of the head and neck is the sixth most common cancer worldwide, with over 500,000 new cases diagnosed worldwide annually. Over 90% of the cancers in the head and neck region are squamous cell carcinomas (HNSCCs). Despite advances in HNSCC diagnosis and treatment, mortality rates have remained high due to frequent development of locoregional recurrences and distant metastases. Patients with advanced stage HNSCC are most often treated with chemoradiation, i.e. the concurrent application of systemic cisplatin combined with locoregional radiotherapy. However, only 50–60% of the patients is cured (Akervall et al., 2004; Pignon et al., 2000) and there are currently no suitable parameters to predict a long-lasting curative response. Gene expression profiling on biopsies taken prior to chemoradiation did not result in gene sets with predictive significance (Pramana et al., 2007). It is generally hypothesized that not the bulk of cells in the tumor determines curative response, but only a small subpopulation, most likely the one that is referred to as the cancer stem cell (CSC) population. Recent studies have demonstrated that both hematological (Bonnet and Dick, 1997) and solid tumors (Al Hajj et al., 2003) contain such a small subpopulation of cells. CSCs are able to self-renew and give rise to all differentiated cell lineages in a tumor. Several lines of evidence suggest that the CSC population is slow-cycling, possesses high levels of active detoxification pumps and DNA repair systems, and is therefore intrinsically resistant to anticancer treatments (Bao et al., 2006). It was postulated that the CSCs originate from tissue stem cells that undergo a malignant transformation as a result of genetic changes (Rosland et al., 2009; Shiras et al., 2007; Teng et al., 2011). Such a model has been proposed for squamous carcinogenesis as well (Leemans et al., 2011). The mucosal epithelium is formed by adjacent clonal units that consist of a single stem cell, multiple transit-amplifying cells and several layers of more differentiated cells. It is generally assumed that the stem cells reside in the basal cell layer. This tissue organization is retained in moderately and well differentiated squamous cell carcinomas. Mutations in the stem cells in the normal mucosal epithelium seem the initiating events in cancer development (Leemans et al., 2011). Over the past decade, CSCs from multiple solid tumor types have been isolated based on differential expression of protein markers on the cell membrane. CD44 is such a widely explored CSC enrichment marker. The CD44 protein is the cell surface receptor for hyaluronic acid (Aruffo et al., 1990) and mediates cell–cell and cell–matrix interactions. It was shown that the cancer stem cell concept is also relevant for HNSCC by demonstrating that CD44(+) cells are much more tumorigenic after serial transplantation in an immunodeficient mouse model than CD44(−) cells (Prince et al., 2007).