Research Briefs

Research Briefs Cancer Cook-Off; Faculty of 1000 | Interdisciplinary Research; Sir2, In Flagrante Delicto Cancer Cook-Off © 2003 National Academy of Sciences, USA In a departure from traditional Texas barbecue, researchers at Rice University and the University of Texas MD Anderson Cancer Center, both in Houston, recently showed that they could literally cook cancer cells to death, using nanotechnology. Rice bioengineer Jennifer West and colleagues demonstrated that an injection of so-called nanoshells (110-nm silica spheres coated with a thin layer of gold), when irradiated with near-infrared light, can raise tissue temperatures about 37°C to a depth of 6 mm, destroying subcutaneous tumors in mice.1 Such a shallow depth will not likely kill larger human tumors buried deep within the body, says Walter Scott, thoracic surgeon at the Fox Chase Cancer Center in Philadelphia. But J. Donald Payne, president and CEO of Houston-based Nanospectra Biosciences, which West cofounded, says the company has data demonstrating deeper penetration. He adds that fiber optic delivery can hit regions inaccessible to external radiation. West has unpublished data showing that nanoshells can be targeted using conjugated antibodies or by taking advantage of leaky vascularization around tumors. "We've shown that we can inject the nanoshells intravenously and target them to the tumor site, and that that therapy also works very nicely," West says. Payne predicts that the company will begin human clinical trials to treat mesothelioma, a deadly lung cancer, within 12 to 18 months. --Jeffrey M. Perkel 1. L.R. Hirsch et al., "Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance," Proc Natl Acad Sci, E-pub ahead of print, Nov. 3, 2003,doi:10.1073/pnas.2232479100. Sir2, in flagrante delicto Courtesy of Ronen Marmorstein Ponce de Leon would have wanted a map that's this clear. Chemists at Philadelphia's Wistar Institute recently resolved two crystal structures of yHst2, the yeast homolog of the silencing information regulator, Sir2. In October, Ronen Marmorstein and colleagues reported the full-length crystal structure of yHst2, one of the class III histone deacetylases known as sirtuins.1 Comparison with other sirtuin protein structures reveals a conserved catalytic core and varied C- and N-terminal domains, giving the proteins functional specificity. More recently, Marmorstein's group captured the structure of yHst2 with its two substrates, NAD+ and a histone peptide.2 In this catalytic snapshot, a truncated yHst2 already had moved the acetyl group from an 11-residue histone peptide to the ADP-ribose of NAD+. This "allows us to visualize both [substrates] at the same time at high resolution," says Marmorstein. Designing small molecules to manipulate Sir2's actions may allow scientists to exploit its relationships to metabolism, gene silencing, and ultimately aging. Leonard Guarente, MIT biologist and co-founder of Elixir Pharmaceuticals, Cambridge, Mass., first characterized Sir2. "Structural information will be invaluable to us," he says, "as we try to design activators of Sir2." --Maria W. Anderson References 1. K. Zhao et al., "Structure and autoregulation of the yeast Hst2 homolog of Sir2," Nat Struct Biol, 10:864-71, October 2003. 2. K. Zhao et al., "Structure of the yeast Hst2 protein deacetylase in ternary complex with 2'-O-Acetyl ADP ribose and histone peptide," Structure, 11:1403-11, November 2003. Faculty of 1000 | Interdisciplinary Research These papers were selected from multiple disciplines from the Faculty of 1000, a Web-based literature awareness tool (www.facultyof1000.com). O. Gozani et al., "The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor," Cell, 114:99-111, 2003. "A motif common to several chromatin-remodeling proteins, termed plant homeodomain (PHD) finger, binds specifically to different phosphatidylinositol phosphates in vitro. ... Interestingly, the PHD finger of the candidate tumor suppressor gene, ING2, is able to interact with PtdIns5P in vivo and this binding regulates the ability of ING2 to trigger p53-dependent apoptotic pathways." --Giampietro Schiavo, Imperial Cancer Research Fund M. Houde et al., "Phagosomes are competent organelles for antigen cross-presentation," Nature, 425:402-6, Sept. 25, 2003. "This article and a back-to-back paper from Guermonprez et al. [Nature, 425:397-402] provide a mechanistic explanation for the phenomenon of cross-priming. ... that the endoplasmic reticulum and phagosomes fuse, and that these fusion-derived phagosomes possess all the machinery required for the export of proteins to the cytosol, the re-import of peptides, and the loading of newly synthesized MHC class I molecules." --Shiv Pillai, Harvard Medical School Y.M. Yamashita et al., "Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome," Science, 301:1547-50, Sept. 12, 2003. "Drosophila germline stem-cell fate is maintained or lost by the architecture of the stem-cell division process. A ring of germline stem cells surround the hub cell. ... Intracellular mechanisms acting on the stem-cell centrosome ensure perpendicular mitotic spindles, so that one daughter cell remains in the hub-cell niche and stays a stem cell, while the other displaced cell differentiates." --Sally Temple, Albany Medical College function sendData() { document.frm.pathName.value = location.pathname; result = false if (document.frm.score[0].checked) result = true; if (document.frm.score[1].checked) result = true; if (document.frm.score[2].checked) result = true; if (document.frm.score[3].checked) result = true; if (document.frm.score[4].checked) result = true; if (!result) alert("Please select") return result; } .myradio{background-color : #94bee5} Please indicate on a 1 - 5 scale how strongly you would recommend this article to your colleagues? Not recommended 1 2 3 4 5 Highly recommended Please register your vote

Research Briefs

Research Briefs

Cancer Cook-Off; Faculty of 1000 | Interdisciplinary Research; Sir2, In Flagrante Delicto

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