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  • Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans

    Abstract Full Text
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    JAMA. 2015; 314(17):1850-1860. doi: 10.1001/jama.2015.13134

    This article investigates mechanisms for cancer resistance in elephants and compares cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome.

  • JAMA November 3, 2015

    Figure 2: Group A and Group B TP53 Retrogenes in the African Elephant

    A maximum likelihood phylogeny was used to cluster the sequenced TP53 retrogene clones and to confirm the number of unique genes uncovered in the African elephant genome. The phylogeny allows for visualization of TP53 retrogene similarity to one another as well as their relationship to the ancestral TP53 sequence in the elephant and hyrax. The capillary sequenced clones from this study are shown as black circles and published sequences from GenBank are shown as red squares. Gene identifiers and genomic coordinates are given in eTable 2 in the Supplement. Phylogenic analysis reveals at least 18 distinct clusters of processed TP53 copies (shown as colored blocks numbered 1 to 18). These clusters fall into 2 groups, labeled group A and group B. The branch labeled “elephant” is the coding sequence of the ancestral TP53, and “hyrax” represents the coding sequences from the hyrax TP53. The hyrax, on the upper left, is used as the outgroup to show that the hyrax and elephant ancestral TP53 sequences are more similar to each other than to the retrogenes, and also that the retrogenes evolved after the split between hyrax and elephant. The distances between the retrogene sequences display their relationship based on sequence similarity but do not represent precise evolutionary time estimates. These data were generated with DNA from 1 elephant to control for polymorphic bases between individual elephants.
  • JAMA November 3, 2015

    Figure 3: African Elephant and Human Peripheral Blood Lymphocytes and Sensitivity to Ionizing Radiation

    A, The percentage of late apoptosis (annexin V positive [AV+] and propidium iodide positive [PI+]) and B, early apoptosis (AV+PI−) in elephant peripheral blood lymphocytes compared with human peripheral blood lymphocytes in response to 2 Gy and 6 Gy of ionizing radiation are graphed. Significant differences computed with a 2-sided t test between human and elephant at 0, 5, 10, 18, and 24 hours are indicated. Error bars represent 95% CIs. C, Representative scatter plots from flow cytometry are shown from the 0- and 18-hour time points. NT indicates no treatment.aP < .001.bPanel A: NT at 10 hours, P = .008. Panel B: NT at 0 hours, P = .002; 2 Gy at 5 hours, P = .003; 6 Gy at 5 hours, P = .004.cP = .03.
  • JAMA November 3, 2015

    Figure 5: Visualization of Apoptosis and DNA Damage in Human and Elephant Cells After Ionizing Radiation

    DAPI, a nuclear stain that binds to DNA (blue), and phospho-histone H2AX foci (green) labeled peripheral blood lymphocytes (PBLs) 5 hours after 2 Gy of ionizing radiation show similar amounts of DNA damage. Apoptosis, rarely observed in the human cells, is visualized in the elephant cells (blue arrowheads indicate apoptotic cells with DNA fragmentation, identified by nuclear blebbing). Images displayed at 40× magnification.
  • JAMA November 3, 2015

    Figure 7: Asian Elephant Cells and DNA Damage Response

    A, An example is shown of percentage of annexin V–positive (AV+) (apoptotic) lymphocytes from a 17-year-old Asian elephant compared with AV+ lymphocytes from an 18-year-old human 18 hours after ionizing radiation exposure. Error bars represent 95% CIs and significant differences computed with a 2-sided t test are indicated. B, Evidence of p21 protein expression is seen 5 hours after 2 Gy of ionizing radiation in Asian elephant lymphocytes. C, The apoptotic response in Asian elephant lymphocytes is shown to decrease with age (P = .002 by linear regression and P < .001 by Jonckheere-Terpstra tests). A single elephant of each indicated age was tested in triplicate. GAPDH indicates glyceraldehyde 3-phosphate dehydrogenase, a protein-loading control.aP = .006.bP < .001.
  • Evolutionary Adaptations to Risk of Cancer: Evidence From Cancer Resistance in Elephants

    Abstract Full Text
    JAMA. 2015; 314(17):1806-1807. doi: 10.1001/jama.2015.13153
  • JAMA November 3, 2015

    Figure 1: Cancer Incidence Across Species by Body Size and Life Span

    The mammalian species studied span the striped grass mouse to the elephant. Cancer incidence is not associated with mass and life span, as shown by the logistic regression (model fit shown as blue line; 95% CIs shown as dashed lines). Each data point in the graph is supported by a minimum of 10 necropsies for the included mammals (San Diego Zoo) and 644 annotated deaths for elephants (Elephant Encyclopedia database). The risk of cancer depends on both the number of cells in the body and the number of years over which those cells can accumulate mutations; therefore, cancer incidence is plotted as a function of mass × life span. All data with 95% CIs are presented in eTable 1 in the Supplement.
  • JAMA November 3, 2015

    Figure 6: p21 and p53 Protein Expression After Ionizing Radiation

    Western blot at the indicated time points after ionizing radiation shows p21 and p53 protein expression in elephant and human lymphocytes. The p53 antibody detects only nonphosphorylated protein. GAPDH indicates glyceraldehyde 3-phosphate dehydrogenase, a protein-loading control; PBL, peripheral blood lymphocyte; NT, no treatment.
  • JAMA November 3, 2015

    Figure 4: Apoptosis Response Relative to Number of Copies of TP53

    Percentage of apoptosis is shown for peripheral blood lymphocytes treated with 2 Gy of ionizing radiation from 10 individuals with Li-Fraumeni syndrome (with 1 functioning TP53 allele), 10 healthy controls (with 2 TP53 alleles), and 1 African elephant tested in 3 independent experiments (with 40 TP53 alleles). Ionizing radiation–induced apoptosis increased proportionally with additional copies of TP53 and inversely correlated with cancer risk. Experiments performed in quadruplicate for each individual and each colored box represents the mean percentage of cells in late apoptosis as measured by flow cytometry (percentage of annexin V–positive [AV+] and propidium iodide–positive [PI+] treated cells minus AV+PI+ untreated cells). The healthy control lymphocytes underwent more apoptosis than those from LFS patients (P < .001), and elephant lymphocytes underwent more apoptosis than those from healthy controls (P < .001 by 2-sided t test). Horizontal lines indicate the combined mean for all data points in each group with error bars indicating 95% CIs.
  • Methicillin-Resistant Staphylococcus aureus Skin Infections From an Elephant Calf—San Diego, California, 2008

    Abstract Full Text
    JAMA. 2009; 301(18):1872-1874. doi:
  • Initiating End-of-Life Discussions With Seriously Ill Patients: Addressing the "Elephant in the Room"

    Abstract Full Text
    JAMA. 2000; 284(19):2502-2507. doi: 10.1001/jama.284.19.2502
  • TP53 Gene and Cancer Resistance in Elephants

    Abstract Full Text
    JAMA. 2016; 315(16):1788-1789. doi: 10.1001/jama.2016.0440
  • TP53 Gene and Cancer Resistance in Elephants

    Abstract Full Text
    JAMA. 2016; 315(16):1789-1790. doi: 10.1001/jama.2016.0446
  • TP53 Gene and Cancer Resistance in Elephants

    Abstract Full Text
    JAMA. 2016; 315(16):1789-1789. doi: 10.1001/jama.2016.0449
  • TP53 Gene and Cancer Resistance in Elephants—Reply

    Abstract Full Text
    JAMA. 2016; 315(16):1790-1791. doi: 10.1001/jama.2016.0457
  • The Physiology of the Elephant

    Abstract Full Text
    JAMA. 1937; 108(9):756-756. doi: 10.1001/jama.1937.02780090068036
  • Articulating the Elephant Man: Joseph Merrick and His Interpretors

    Abstract Full Text
    JAMA. 1993; 269(10):1314-1315. doi: 10.1001/jama.1993.03500100114045
  • The Wild Goose Chase and the Elephant's Relevance

    Abstract Full Text
    JAMA. 1986; 256(2):256-257. doi: 10.1001/jama.1986.03380020118037
  • `Elephant Man' had more than neurofibromatosis

    Abstract Full Text
    JAMA. 1982; 248(9):1032-1033. doi: 10.1001/jama.1982.03330090008003