Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia

KIT is a type-III receptor tyrosine kinase that contributes to cell signaling in various cells. Since KIT is activated by overexpression or mutation and plays an important role in the development of some cancers, such as gastrointestinal stromal tumors and mast cell disease, molecular therapies targeting KIT mutations are being developed. In acute myeloid leukemia (AML), genome profiling via next-generation sequencing has shown that several genes that are mutated in patients with AML impact patients’ prognosis. Moreover, it was suggested that precision-medicine-based treatment using genomic data will improve treatment outcomes for AML patients. This paper presents (1) previous studies regarding the role of KIT mutations in AML, (2) the data in AML with KIT mutations from the HM-SCREEN-Japan-01 study, a genome profiling study for patients newly diagnosed with AML who are unsuitable for the standard first-line treatment (unfit) or have relapsed/refractory AML, and (3) new therapies targeting KIT mutations, such as tyrosine kinase inhibitors and heat shock protein 90 inhibitors. In this era when genome profiling via next-generation sequencing is becoming more common, KIT mutations are attractive novel molecular targets in AML.     

Microstructure and analysis of oxide scales formed on Cr-Si-Ni compacts in air and H2O-containing atmosphere

The purpose of this study was to characterize the oxide scales formed on various Cr-Si-Ni compacts at 1273 K in air and H₂O-containing atmosphere by TEM. It was found that CrSi₂-(5-20)mass%Ni compacts form double layer scales, consisting of an outer Cr₂O₃ layer and an inner SiO₂ layer. The oxide scale changed from SiO₂- to Cr₂O₃-based scale with an increase in the Ni concentration. However, it was observed that the oxide scale formed in H₂O-containing atmospheres showed local SiO₂ growth into the substrate. This result suggests that the inward oxidant diffusion promotes the local growth of SiO₂ in the H₂O-containing atmospheres.     

Structure and viscoelastic properties of segmented polyurethane blends

Structure and viscoelastic properties of segmented polyurethanurea (SPU) blends were investigated. The glass transition temperature (T_g) of poly(tetramethylene glycohol) (PTMG) in a soft-segment block of the component SPU increased with decreasing molecular weight of PTMG. The blend samples showed two T_gs of PTMG in the temperature dispersions of the loss modulus (E″) and loss tangent (tan δ). The value of E′ in the leathery region for the blend specimens was trongly affected by the morphology. The blends were considered to have a morphology where PTMG differing in molecular weight was localized. © 1996 John Wiley & Sons, Inc.     

Microbial synthesis and properties of poly(3-hydroxybutyrate-co-4-hydroxybutyrate)

Microbial synthesis of copolymers of [R]-3-hydroxybutyrate (3HB) and 4-hydroxybutyrate (4HB), P(3HB-co-4HB), by Alcaligenes eutrophus, Alcaligenes latus, and Comamonas acidovorans from various carbon sources has been studied. The copolyester compositions varied from 0 to 100 mol% 4HB, depending on the microorganism and the combination of carbon substrates supplied. The thermal and physical properties of compositions with 0–100 mol% 4HB were investigated. The copolyesters represented a wide variety of polymeric materials, from hard crystalline plastic to very elastic rubbers, depending on composition. The copolyester films with high 4HB fractions (64–100 mol% 4HB) exhibited the characteristics of a thermoplastic elastomer, and the tensile strength increased from 17 to 104 MPa as the 4HB fraction increased. The enzymatic degradation of P(3HB-co-4HB) films was studied in an aqueous solution of extracellular polyhydroxybutyrate (PHB) depolymerase from Alcaligenes faecalis or lipase from Rhizopus delemer. The erosion rate of P(3HB-co-4HB) films was strongly dependent on the copolymer composition. In addition, environmental degradation of P(3HB-co-4HB) films in sea water was investigated.     

Effect of roughness as determined by atomic force microscopy on the wetting properties of PTFE thin films

The influence of film roughness on the wetting properties of vacuum-deposited polytetrafluorethylene (PTFE) thin films has been investigated using atomic force microscopy (AFM) and contact angle goniometry. Surface roughness has been characterized by atomic force microscopy in terms of RMS roughness (R_q) and fractal dimensions. A contact angle correlation with surface roughness, as determined by AFM, is evident from these results, which are discussed on the basis of wetting theory. The results also confirm that the high water contact angles (as high as 150°) recently observed at the surface of a new water repulsive coating material (mixture of PTFE and binder) are because of surface roughness. Such measurements clarify the effect of nanometer-size surface asperities on the wetting properties of hydrophobic coating.     

Evaluation of drug toxicity with hepatocytes cultured in a micro-space cell culture system

A micro-space cell culture system was recently developed in which cells such as hepatocytes can be cultured and formed into a multicellular three-dimensional (3D) architecture. In this study, we assessed the performance of HepG2 cells cultured in this micro-space cell culture system in a drug toxicity test, and evaluated the effects of micro-space culture on their hepatocyte-specific functions. The micro-space cell culture facilitated the formation of 3D HepG2 cell architecture. HepG2 cells cultured in a micro-space culture plate exhibited increased albumin secretion and enhanced mRNA expression levels of cytochrome P450 (CYP) enzyme compared to those cultured in a monolayer culture. When the cells were exposed to acetaminophen, a hepatotoxic drug, the damage to the HepG2 cells grown in micro-space culture was greater than the damage to the HepG2 cells grown in monolayer culture. In addition, human primary hepatocytes grown in micro-space culture also exhibited increased albumin secretion, enhanced CYP mRNA expression levels and increased sensitivity to acetaminophen compared to those grown in monolayer culture. These results suggest that this micro-space culture method enhances the hepatocyte-specific functions of hepatocytes, including drug-metabolizing enzyme activities, making hepatocytes grown in the micro-space culture system a useful tool for evaluating drug toxicity in vitro.     

Characterization of electrical properties and photosensitivity of SnS thin films prepared by the electrochemical deposition method

Using the electrochemical deposition (ECD) method, we prepared tin sulfide thin films, which are suitable for the absorption layer in solar cells because of its bandgap energy (1 eV). We first optimized pulse-form biasing for ECD by characterizing deposited samples with scanning electron microscope, Auger electron spectroscopy and X-ray diffraction measurements. Then, we investigated the electrical properties of deposited SnS thin films and the properties of contacts with several different metals. Furthermore, we observed the photoconductivity of the films by means of photoelectrochemical measurements. From these results, we confirmed that the SnS thin films show p-type conduction.     

Inhibition of xanthine oxidase activity by an oxathiolanone derivative of quercetin

An oxathiolanone derivative of rutin could be produced in the stomach after the ingestion of rutin containing foods, and the oxathiolanone derivative could be hydrolysed to an oxathiolanone derivative of quercetin (quercetin-oxathiolanone) in the intestine. Quercetin-oxathiolanone as well as quercetin inhibited xanthine oxidase. Approximately 0.05 μM quercetin-oxathiolanone inhibited the activity by 50%, whereas 50% inhibition by quercetin was observed at approximately 0.4 μM. The results suggested that quercetin-oxathiolanone can be used as an effective inhibitor of xanthine oxidase and that the ingestion of rutin-rich foods may be useful to prevent the increase in the blood concentration of uric acid.     

β-phase transformation and thermoelectric power in FeSi2 and Fe2Si5 based alloys containing small amounts of Cu

The effects of Cu addition on the β phase formation rate and the thermoelectric power in various FeSi₂ and Fe₂Si₅ based alloys was examined. The peritectoid reaction (a+→β) in FeSi₂ alloys was initially enhanced by the addition of Cu but it became slower for longer annealing times. The retained metallic ε was harmful for the thermoelectric power. The inherent thermoelectric properties of (FeSi₂)_99−XMn₁Cu_X (X=0–1.O at.%), (FeSi₂)_99−X Co₁Cu_X (X=0–1.0 at.%) alloys were attained after the elimination of ε. In the case of eutectoid reaction (→β+Si). Differential thermal analysis, X-ray diffraction and microscopic observation clearly confirmed that the eutectoid reaction rate was drastically enhanced by the addition of a small amount of Cu and its rate decreased with decreasing Cu content. The rate also depends on the annealing temperature and reached a maximum at about 1073 K for most alloys. The addition of only 0.1 at.% Cu was still very effective even in Mn or Co doped alloys. The thermoelectric power of these alloys increased very quickly with annealing time. Their final values decreased with Cu content and saturated at 0.2 at.% Cu. The value of the 0.1 at.% Cu added alloy was higher than that of both the conventional p- and a-type FeSi₂ based alloys. These results suggest that the Fe₂Si₅ alloys with a small amount of Cu may be attractive as new thermoelectric materials.     

C57BL/KsJ-db/db-Apc Mice Exhibit an Increased Incidence of Intestinal Neoplasms

The numbers of obese people and diabetic patients are ever increasing. Obesity and diabetes are high-risk conditions for chronic diseases, including certain types of cancer, such as colorectal cancer (CRC). The aim of this study was to develop a novel animal model in order to clarify the pathobiology of CRC development in obese and diabetic patients. We developed an animal model of obesity and colorectal cancer by breeding the C57BL/KsJ-db/db (db/db) mouse, an animal model of obesity and type II diabetes, and the C57BL/6J-Apc(Min/+) (Min/+) mouse, a model of familial adenomatous polyposis. At 15 weeks of age, the N9 backcross generation of C57BL/KsJ-db/db-Apc(Min/+) (db/db-Min/+) mice developed an increased incidence and multiplicity of adenomas in the intestinal tract when compared to the db/m-Min/+ and m/m-Min/+ mice. Blood biochemical profile showed significant increases in insulin (8.3-fold to 11.7-fold), cholesterol (1.2-fold to 1.7-fold), and triglyceride (1.2-fold to 1.3-fold) in the db/db-Min/+ mice, when compared to those of the db/m-Min/+ and m/m-Min/+ mice. Increases (1.4-fold to 2.6-fold) in RNA levels of insulin-like growth factor (IGF)-1, IRF-1R, and IGF-2 were also observed in the db/db- Min/+ mice. These results suggested that the IGFs, as well as hyperlipidemia and hyperinsulinemia, promoted adenoma formation in the db/db-Min/+ mice. Our results thus suggested that the db/db-Min/+ mice should be invaluable for studies on the pathogenesis of CRC in obese and diabetes patients and the therapy and prevention of CRC in these patients.