Such cultures essentially behave as a coculture where cells are in symbiotic relationship with each other and might produce factors that can modulate the functions of the other cell types. This has been confirmed by intermediate filament glial fibrillary acidic protein, a marker for astrocytic differentiation that was up-regulated in 3D and NS compared to 2D cultures. It is a well known fact that astrocytes play a trophic role in supporting neurons. Factors secreted by astrocytes generally belong to the FGF, TGF and EGF families that play an important role in early neurogenesis. Members of these families act as potent mitogens for multipotential neural progenitors and have been implicated in the regulation of several aspects of neurogenesis. Therefore up-regulation of members of these cytokine families in 3D and NS in this study is not surprising. The identification and validation of a few cytokines as three-dimensionality ONX-0914 Proteasome inhibitor biomarkers that are ubiquitous among cells from different tissue types needs to be done. Overall, cytokines gene expression results in this study support the notion that 3D cultured cells in various formats are different from their 2D counterparts. Furthermore, up-regulated cytokines’ transcripts, independent of culture format, have been identified; this group of 13 cytokines commonly up-regulated in cells cultured in polystyrene scaffolds and neurospheres are suggesting potential for any or a combination from this list to serve as threedimensionality biomarkers. These results are supportive of further cytokine identification and in vitro/in vivo validation studies with cells from non-neural tissue. Loss of the DNA mismatch repair system by genetic alterations leads to an increased mutation rate in short, tandemly repeated sequences, termed microsatellites. This phenomenon, commonly referred to as microsatellite instability, is presented by length variations in tracts of mono- or polynucleotides. Clinically, MSI is found in.90% of patients affected by the hereditary non-polyposis colorectal carcinoma syndrome, as well as in several sporadic malignancies including tumors of the colorectum, the stomach and the endometrium, where it is found in up to 15% of cases. When comparing with microsatellite stable tumors, there is some evidence for –at least partial– immunological growth control in MSI cancers, like the dense local lymphocytic infiltration, the increased apoptotic tumor cell number, and the low number of distant metastases that leads to an improved overall patient survival. Beyond that, there is evidence that MMR deficient cells are intrinsically resistant to methylating agents and to some antimetabolites, including the chemotherapeutic drug 5-Fluorouracil, which is standard in adjuvant treatment of colorectal carcinoma. In the multistep process of carcinogenesis, mutations affecting genes, whose alterations are advantageous to the tumor cell, will be positively selected. In MSI+ cancers, several genes being especially prone to MSI have been identified with the transforming growth factor beta receptor II being one of the first. Other examples of so-called MSI target genes frequently mutated in CRC include Caspase-5, ACVR2, and AIM2.