Appendix 1*) For Essential Information Very Well Illustrated in Google and Wikipedia *) in Support of the Text with Literature Citations. Referrals to illustrations in Appendix 2. Cancer in the Plant. The insertion of the Agrobacterium tumefaciens circular plasmid T (transferred) DNA into the genome of its new host, the plant (Gelvin BS. Microbiol Molecular Biol Rev 2003;67:16–37). The plant cancer “crown gall” (agrocallus; Agrobacterial crown gall) consists of malignantly transformed cells replicating the agrobacterial T DNA plasmid (reviewed in postscript Table XXXV). For reference: Koncz C Mayerhofer R Koncz-Kálmán Zs et al EMBO J 1990;9:1337–1346. Transfer of potentially oncogenic bacterial genes and proteins to patients: Septicemic Bacteroides enterotoxigenic (Sinkovics J G & Smith JP Cancer 1970;25:663–671; Viljoen KS et al PLoS One 2015;10(3):e0119462); Bartonella bacilliformis etc (Guy L et al PLoS Genet 2013;9(3):e1003393; Harms A & Dehio C Clin Microbiol Rev 2012;25:42–78; Llosa M et al Trends Microbiol 2012;20:355–9; Minnick MF et al PLoS Negl Trop Dis 2014;6(7):e2919); Helicobacter pylori (Bonsor DA et al J Biol Chem 2015;pii:jbc.M115.641829; Su YL et al J Immunol 2015;194:3997–4007; Vaziri F et al Pathog Dis 2015;73(3). pii.ftu021); Porphyromonas gingivalis (Katz J et al Int J Oral Sci 2011;3:209–215); Tuberculous infections with A. tumefaciens in patients (Ramirez FC et al Clin Infect Dis 1992;15:938–940). DNA-binding Antibodies. DNA- (or RNA-) binding proteins use zink finger motifs, leucine zippers and winged (beta-sheet loops) helix-turn helix motifs (HTH, two helices separated by the loop, RNA/DNA-binding domains) in recognition of RNA/DNA receptors for attachment. Pro-apoptotic protein p53 is commonly attached to DNA (vide infra). Advanced multicellular organism established a fundamental relationship between DNA genes and circulating antibodies, which overlapped the pre-existing miR activity for posttranslational gene expression. One of the best examples is played out in the pathogenesis of the T cell lymphoma mycosis fungoides and Sézary syndrome (that may also hide the underlying retroviral pathogen/passenger presumed to be there by Dorothea Zucker Franklin) (Proc Natl Adad Sci 1991;88:7630–7634; 1997;94:6403–6407). One of the inducer oncogenes of mycosis fungoides is TOX (thymocyte selection-associated high mobility group protein box gene), which normally regulates T cell differentiation. © Springer International Publishing Switzerland 2016 559 J.G. Sinkovics, RNA/DNA and Cancer, DOI 10.1007/978-3-319-22279-0 560 Appendix 1*) For Essential Information Very Well Illustrated in Google and Wikipedia Overexpressed TOX induces mycosis fungoides tumor cell proliferation and migration. The TOX protein mRNA is under the control of miR-223 through specific domain alignment to its 3′ UTR (untranslated region) in the AGO complex. High blood levels of miR-223 bring about the cessation of mycosis fungoides tumor cell growth. The production of tumor initiator high mobility group (HMG) DNA-binding protein is targeting its own DNA genes of T cell dediffer- entiation and homing; it is switched off by a specific miR (Huang Y et al Oncotarget 2014;5:4418–4425; McGirt L et al J Invest Dermatol 2014; 134:1101–1107; O’Flaherty E & Kaye J BMC Genomics 2003;4:13). Continuous Replication of the Trypanosoma in liquid media. Not in the insect’sgut, but in the blood stream of its mammalian host, the slender Trypanosoma cell is fed primarily on sugar. This protozoan is also capable to synthesize glucose-6-phosphate. Growing in vitro in suspension, its speed of replication is dependent on the concen- tration of sugar in the liquid media. The stress responsive heat shock proteins (Hsp90) work in cell survival pathways in the protozoa, but became oncoproteins in multicel- lular, incl. human, hosts. Questions still incompletely answered: In the rapidly growing T. brucei, sugar metabolism is warburgian? Insulin-like growth factor receptor (IGFR) is overexpressed? Hsp90 promotes growth; is there growth dependence on Hsp90? Intranuclear Ki-67 is overexpressed? Telomers are capped after each cell division? Hsp90 inhibitors (geldanamycin analogs) induced trypanosomal death due to heat shock. Positive answers would mean that the unicellular protozoan’s rapid growth is comparable to that of a cancer cell. Cooperative studies of Ludwig Maximilian University (LMU); Institut National des Sciences Appliqueés (INSA), Université Toulouse; Centre National de la Recherche Scientifique (CNRS), Université Bordeaux. Allmann S et al Biol Chem 2013;288:18494–18505. Van Reet N et al Exp Parasitol 2011;128:285–290. Meyer KJ & Shapiro TA J Infect Dis 2013;208:489–499 http:// www.pasteur.fr/ip/easysite/pasteur/en/research/scientific-department/parasitology; http:/ phys.org/news/2013-07-parasite-sugar.html; http://www.ncbi.nlm.nih.gov/pubmed/? term=trypanosoma+liquid++culture Faculty Biology, Ludwig-Maximilians- UniversitätMünchen; Biozentrum, Grosshadernerstrasse 2–4, D82152 Martinsried, Germany. The Johns Hopkins University School of Medicine, Baltimore, USA. Stem Cells Ascend from the bottom of the Lieberkühn crypt to renew themselves and release somatic cells to function as epithelial cells of the mucous membrane (reviewed in Table I). S. Yamanaka Lentivirally Transferred four stem cell genes (oct4; sox2; klf4; c-myc) for reprogramming human differentiated cells into pluripotential stem cells; re-differentiation of pluripotential stem cells into differentiated cell could be induced. http://syntheticdaisies.blogspot.com/2012/10/the-spawn-of-gurdons-frogs.html. Dictyostelia amoebae. The Amoebozoan Dictyostelium discoideum exists in many life forms: in sexual cycle, in vegetative cycle, and in social cycle. Its discoidin is a fibronectin; its tiger genes encode histocompatibility complexes; it uses Appendix 1*) For Essential Information Very Well Illustrated in Google and Wikipedia 561 ERK/MAPKK signaling “cell survival pathways” (extracellular signal regulated kinase; mitogen-activated protein kinase kinase). MAPKK becomes a proto-oncogene in vertebrate mammalian (human) cells: in ras- (rat sarcoma) transformed cancer cells. Members of the D. discoideum clade (D. purpureum, D. fasciculatum) are comparable in their genomics and proteomics. Evolutionarily they separated from their common ancestor 600–800 mya and in comparison to the yeast, doubled their number of protein-coding genes up to 12,000 (Loomis WE Methods Mol Biol 2013;983:39–58). The other social amoeba, Acytostelium sub- globosum emerges as a different species, which increased its chromosome number up to 18, but not because it has become diploid. The starving D. discoideum forms a conditionally multicellular fruiting body with spore ball on a stalk. It is the migratory slug cells that either form the fruiting body or the stalk. The fruiting body represents the germ cells and the stalk consists of the terminally differentiated somatic cells. The A. subglobosum does not differentiate its stem cells to a stalk; its stalk is a-cellular. The cellulose synthase gene builds the cell-free stalk. If “The differentiation of mortal or sacrificed somatic cells from reproductive germ cells was the key event for the establishment and diversification of multicellular systems” (Urushihara H et al BMC Genomics 2015;16(1):80), then D. subglobosum should be regarded evolutionarily more ancient than D. discoideum. A. subglobosum and D. discoideum are casting light to the beginning of a decisive process in the development of multicellularity. The Dd-MRP4 mitochondrial ribosomal protein is able to induce in human cancer cells the process of programmed cell death (apoptosis). Mitochondrial ribosomes are of ancient bacterial derivation. The Dd-mrp4 gene product protein in D. discoideum is the major initiator of cell dif- ferentiation (induced by starvation). Differentiation induction is achieved by the Dd-MRP4 protein through its entry into the nucleus for activation of its target genes (miR genes?). Another unrelated and different D. discoideum ribosomal protein is S4 (Dd-RPS4). It is homologous to the human chromosome X-linked cytoplasmic ribosomal protein S4 (Hs-RPS4X) in 66% identity and 92% similarity in their aa sequence (Maeda Y Biomolecules 2015;5:113–120). Amphioxus I, prominent among them is Branchiostoma floridae. Possesses notochord and primordial nervous system consisting of intraabdominal sensory cells and notochord nerve cells connected with axons and synapses. An advanced neuro- chemical network releases and circulates cholinergic and GABAergic/glycinergic (gamma aminobutyric acid) molecular mediators. The amphioxus’ achaete scute homologues (Ash) exist conserved up to Homo (Lu TM et al Development 2012;139:2020–2030). The Ash genes may act as proto-oncogenes subject to malignant transformation. The achaete scute homolog basic helix loop helix gene (ash) and the delta ligand Notch pathway evolved at this site. The adult amphioxus preserves its notochord, whereas tunicate larvae of Ciona lose their cordate charac- teristics through metamorphosis into adulthood. The amphioxus frontal eye spot reveals photoreceptor Joseph cells with many homologies to camera-type lens eyes of jawless (lamprey) to jawed (sharks) vertebrates (Candiani S et al BMC Neurosci 2012;13:59; Lu TM et al Development 2012;139:2020–2030; Vopalensky P et al 562 Appendix 1*) For Essential Information Very Well Illustrated in Google and Wikipedia Proc Natl Acad Sci 2012;109:15383–15388). The amphioxus and the sponge Amphimedon qeenslandica share