**Abbreviations / Glossary**

The redox state of tumor cells is frequently disrupted and this is difficult to reproduce in ground-based cultures [70-72]. Hence, redox-dependent drug metabolism in tumors may be uniquely modeled in microgravity. Many of the genes most commonly associated with microgravity-related changes have been identified to have roles in cell cycling, which is critical for both carcinogenesis and responses to radiation damage. EGR1 (Early growth response protein 1; also referred to as Zif268, zinc finger protein 225; and NGFIA, nerve growth factorinduced protein A) is a tumor suppressor transcription factor for differentiation and mitogen‐ esis. MYC encodes for a transcription factor with roles in cell cycle progression, apoptosis and cellular transformation [73]. Karyopherin alpha 2 (KPNA2) promotes tumorigenicity through up-regulation of c-MYC [74]. In endothelial cells grown in microgravity KPNA2 was shown to up-regulated in both adherent cells and multicellular conglomerates at 5 days in simulated microgravity, but down-regulated in multicellular conglomerates at 7 days [35]. HSP70 family members such as HSPA1A have been found to be critical to cellular homeostasis and cancer cell survival[75]. Integrin, Beta 4 (ITGB4) is the receptor for laminin and has been found to be

108 Biotechnology

up-regulated in thyroid cancer cells and MCTS grown on RPM for 24 hours [33].

Similar to the results of the current meta-analysis, Nislow et al. 2014 found spaceflight has subtle but significant effects on core cellular processes including growth control via RNA and ribosomal biogenesis, metabolism, modification and decay pathways. Furthermore, significant roles for DNA repair and replication, response to pH signaling, control of gene expression, and mitochondrial function were observed. The yeast chemogenetic analysis of spaceflight samples strongly implicates DNA and RNA damage as the major ground based analogs of spaceflight stress. Given the unique, and substantial radiation exposure in space, this is consistent with major radiation-mediated effects which may mimic cancer related effects.

Suppression of the immune system has been thought to be an important side-effect of micro‐ gravity exposure [1, 2, 31, 76]. Recently, a global gene expression analysis of human T cells after 1.5 h of stimulation by Con A and anti-CD28 in the LEUKIN spaceflight has identified immediate early genes whose transcription are inhibited in microgravity [31]. The transcrip‐ tion of immediate early genes is inhibited in T cells activated in microgravity, which may be involved in the molecular basis of spaceflight immunosuppression. NF-κB is known to regulate transcription in most mammalian cells and plays a key role in immune responses to antigens, cytokines, UV radiation, oxidized LDL, free radicals, etc. [77-81]. CREB, a cAMP-responsive transcription factor, regulates immune genes including IL-2, IL-6, IL-10, and TNF-α. CREB also promotes survival and proliferation to T-cells, monocytes, and macrophages [82]. EGR1 and MYC, which are among the 48 most significantly down-regulated by microgravity in the T cell activation study are identified as the putative major space genes in the current study (Table 2).

This analysis shows a commonality of gene changes and pathways between different micro‐ gravity models. As data is systematically accumulated, this type of analysis will allow even more meaningful analysis. A key question is whether the unique environment of the ISS induces biological changes of commercial translational value to enhance ground-based health care? In which areas does ISS provide a specific advantage over ground-based biological simulations to direct strategic planning of space based biological science? Within and between ground-based microgravity simulations, can we identify areas where specific techniques are DAVID: Database for Annotation, Visualization and Integrated Discovery EGR1: Early growth response protein 1 GO: Gene Ontology HARV: High Aspect Rotating Vessel HUVEC: Human Umbilical Vein Endothelial Cells ISS: International Space Station KPNA2: Karyopherin alpha 2 MT-1, -2: Metallotionin-I and –II RCCS: Rotating Cell Culture System ROS: Reactive oxygen species RPM: Random Positioning Machine RWV: Rotating Wall Vessel STRING: Search Tool for the Retrieval of Interacting Genes/Proteins TXNIP: Thioredoxin-interacting protein
