Oncometabolites: tailoring our genes

Increased glucose metabolism in cancer cells is a phenomenon that has been known for over 90 years, allowing maximal cell growth through faster ATP production and redistribution of carbons towards nucleotide, protein and fatty acid synthesis. Recently, metabolites that can promote tumorigeneis by altering the epigenome have been identified. These ‘oncometabolites’ include the tricarboxylic acid cycle metabolites succinate and fumarate, whose levels are elevated in rare tumours with succinate dehydrogenase and fumarate hydratase mutations, respectively. 2-Hydroxyglutarate is another oncometabolite; it is produced de novo as a result of the mutation of isocitrate dehydrogenase, and is commonly found in gliomas and acute myeloid leukaemia. Interestingly, the structural similarity of these oncometabolites to their precursor metabolite, α-ketoglutarate, explains the tumorigenic potential of these metabolites, by competitive inhibition of a superfamily of enzymes called the α-ketoglutarate-dependent dioxygenases. These enzymes utilize α-ketoglutarate as a cosubstrate, and are involved in fatty acid metabolism, oxygen sensing, collagen biosynthesis, and modulation of the epigenome. They include enzymes that are involved in regulating gene expression via DNA and histone tail demethylation. In this review, we will focus on the link between metabolism and epigenetics, and how we may target oncometabolite-induced tumorigenesis in the future

Development of colon cancer after liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis

Between February 26, 1981, and July 30, 1987, 36 patients underwent orthotopic liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis. Three of the 36 recipients died within 3 mo because of graft nonfunction or surgical complications. The other 33 (92%) lived for at least 1 yr. Two of the 33 died after 12 and 14 mo, respectively, of recurrent cholangiocarcinoma that was not diagnosed before transplantation. Four other patients died of recurrent liver failure (three cases) or immunoblastic sarcoma (one case) after 14, 21, 36 and 44 mo. Twenty‐seven (75%) of the patients are still alive 23 to 81 mo after transplantation. Two patients have been diagnosed as having colorectal cancer 11 and 21 mo respectively, after transplantation, for an overall incidence of 5.6% (2 of 36) and a corrected incidence of 6.5% (2 of 31) if the three early deaths and two later deaths caused by cholangiocarcinomas are excluded. It is not known whether colorectal malignancies were present but undetected at the time of transplantation or whether they developed afterward. It is clear that patients who undergo liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis should have careful follow‐up of the colon, including colonoscopy and multiple biopsies of the colorectal mucosa. Whether proctocolectomy should be considered prophylactically after liver transplantation is an unresolved issue.(HEPATOLOGY 1990;11:477–480.) Copyright © 1990 American Association for the Study of Liver Disease

Search for magnetic monopoles using proportional counters filled with helium gas

Slow magnetic monopoles in cosmic rays have been searched at sea level with the detector which consists of seven layers of proportional counters filled with a mixture of He + 20% CH4. The velocities and the energy losses of the incident particles are measured. The upper limit of flux for the monopoles in the velocity range of 1 x 0.001 Beta 4 x 0.001 is 2.78 x 10 to the minus 12th power square centimeters sr sec of 90% confidence level

Partial melting and segregation behavior in a superplastic Si3N4/Al-Mg alloy composite

科研費報告書収録論文(課題番号:07455252・基盤研究(B)(2)・H7～H9/研究代表者:小池, 淳一/αTi-Al固溶体における異常高温強化

Fabrication, characterization and its local reflection properties of a metal-mirror microcavity with high concentrated PIC J-aggregates

We have investigated reflection properties of light-matter strong coupling in a planar metal-mirror microcavity with highly concentrated PIC J-aggregates. Large vacuum Rabi-splitting ranging from 100 to 250 meV is obtained depending on the concentration of the J-aggregates. The factors for providing these large Rabi-splitting will be discussed based on its concentration dependence. We also present our recent study focused on microscopic reflection properties of the microcavity. We have improved microscope optics which enables us to measure local reflection spectra within 0.3-m-diameter area. Observation of incident-light-angle dependence becomes possible. We found existence of micrometer-scale inhomogeneity in the Rabi-splitting (e.g. ±10% in a region), which will be interpreted mainly by the spatial distribution of J’s in the active layer

A new ultra high energy gamma ray telescope at Ohya mine

The search for ultra high energy gamma rays coming from point sources is one of the main experimental aims. A fast air shower timing system was constructed at ICRR for the study of the angular resolution of the system and operated approximately half a year. The characteristics of the surface array of Ohya air shower telescope is described

Bacillus-Shaped Deposits Composed of Hexahedrally Based Crystals in Human Dental Calculus

In human supra- and subgingival calculus, bacillus-shaped deposits showing various rocky-pile forms composed of hexahedrally based crystals were observed by scanning electron microscopy. The crystal size measured approximately 0.1 - 1.5 μm. The electron probe microanalysis always detected calcium, phosphorous, and magnesium. Their molar ratios resembled those of magnesium-containing whitlockite and moreover the crystals also gave the electron diffraction pattern of whitlockite. The bacillus-shaped deposits happened to coexist with the intracellular calcifying microorganisms, furthermore, oral microorganisms partially replaced by the hexahedrally based crystals were found. The crystal deposits were never seen in the surface layers of calculus exposed to the oral cavity, but occurred in the innermost layers and intra-spaces of supragingival and ledge-type subgingival calculus and in the outer layers of deep subgingival calculus