Association of ABCC2 −24C>T Polymorphism with High-Dose Methotrexate Plasma Concentrations and Toxicities in Childhood Acute Lymphoblastic Leukemia

<div><p>Methotrexate (MTX) is a key agent for the treatment of childhood acute lymphoblastic leukemia (ALL). Increased MTX plasma concentrations are associated with a higher risk of adverse drug effects. ATP-binding cassette subfamily C member 2 (ABCC2) is important for excretion of MTX and its toxic metabolite. The <i>ABCC2</i> −24C>T polymorphism (rs717620) reportedly contributes to variability of MTX kinetics. In the present study, we assessed the association between the <i>ABCC2</i> −24C>T polymorphism and methotrexate (MTX) toxicities in childhood ALL patients treated with high-dose MTX. A total of 112 Han Chinese ALL patients were treated with high-dose MTX according to the ALL-Berlin-Frankfurt-Muenster 2000 protocol. Our results showed that presence of the <i>−24T</i> allele in <i>ABCC2</i> gene led to significantly higher MTX plasma concentrations at 48 hours after the start of infusion, which would strengthen over repeated MTX infusion. The <i>−24T</i> allele in <i>ABCC2</i> gene was significantly associated with higher risks of high-grade hematologic (leucopenia, anemia, and thrombocytopenia) and non-hematologic (gastrointestinal and mucosal damage/oral mucositis) MTX toxicities. This study provides the first evidence that the <i>−24T</i> allele in <i>ABCC2</i> gene is associated with the severity of MTX toxicities, which add fresh insights into clinical application of high-dose MTX and individualization of MTX treatment.</p></div

Association of ATP-binding cassette subfamily C member 2 (<i>ABCC2</i>) gene −24C>T genotype with methotrexate (MTX) toxicity grades.

<p>Association of ATP-binding cassette subfamily C member 2 (<i>ABCC2</i>) gene −24C>T genotype with methotrexate (MTX) toxicity grades.</p

Characteristics of patients.

<p>Characteristics of patients.</p

Incidence of methotrexate (MTX) toxicity by ATP-binding cassette subfamily C member 2 (<i>ABCC2</i>) gene −24C>T genotype.

<p>Incidence of methotrexate (MTX) toxicity by ATP-binding cassette subfamily C member 2 (<i>ABCC2</i>) gene −24C>T genotype.</p

Methotrexate (MTX) plasma concentrations by single nucleotide polymorphism (SNP) genotypes of ATP-binding cassette subfamily C member 2 (<i>ABCC2), ABCC4 and ABCG2</i>.

<p>MTX plasma concentrations were measured at 48<i>ABCC4</i> rs9516519 (<i>A</i>), <i>ABCC4</i> rs868853 (<i>B</i>), <i>ABCC4</i> rs2274407 (<i>C</i>), <i>ABCC2</i> rs3740065 (<i>D</i>), <i>ABCG2</i> rs2231137 (<i>E</i>).</p

Effects of ATP-binding cassette subfamily C member 2 (<i>ABCC2</i>) gene −24C>T genotype and time on methotrexate (MTX) plasma concentration.

<p>Effects of ATP-binding cassette subfamily C member 2 (<i>ABCC2</i>) gene −24C>T genotype and time on methotrexate (MTX) plasma concentration.</p

Self-Assembled Incorporation of Modulated Block Copolymer Nanostructures in Phase-Change Memory for Switching Power Reduction

Phase change memory (PCM), which exploits the phase change behavior of chalcogenide materials, affords tremendous advantages over conventional solid-state memory due to its nonvolatility, high speed, and scalability. However, high power consumption of PCM poses a critical challenge and has been the most significant obstacle to its widespread commercialization. Here, we present a novel approach based on the self-assembly of a block copolymer (BCP) to form a thin nanostructured SiO_<i>x</i> layer that locally blocks the contact between a heater electrode and a phase change material. The writing current is decreased 5-fold (corresponding to a power reduction by 1/20) as the occupying area fraction of SiO_<i>x</i> nanostructures is increased from a fill factor of 9.1% to 63.6%. Simulation results theoretically explain the current reduction mechanism by localized switching of BCP-blocked phase change materials

Methotrexate (MTX) plasma concentrations by ATP-binding cassette subfamily C member 2 (<i>ABCC2</i>) −24C>T polymorphism genotypes.

<p>MTX plasma concentrations were measured at 48<i>ABCC2</i> −24C>T polymorphism genotypes alone (<i>A</i>) or further stratified by gender (<i>B</i>). *<i>p</i><0.05 vs CC.</p

Flexible One Diode-One Phase Change Memory Array Enabled by Block Copolymer Self-Assembly

Flexible memory is the fundamental component for data processing, storage, and radio frequency communication in flexible electronic systems. Among several emerging memory technologies, phase-change random-access memory (PRAM) is one of the strongest candidate for next-generation nonvolatile memories due to its remarkable merits of large cycling endurance, high speed, and excellent scalability. Although there are a few approaches for flexible phase-change memory (PCM), high reset current is the biggest obstacle for the practical operation of flexible PCM devices. In this paper, we report a flexible PCM realized by incorporating nanoinsulators derived from a Si-containing block copolymer (BCP) to significantly lower the operating current of the flexible memory formed on plastic substrate. The reduction of thermal stress by BCP nanostructures enables the reliable operation of flexible PCM devices integrated with ultrathin flexible diodes during more than 100 switching cycles and 1000 bending cycles

Estimates of Forest Biomass Carbon Storage in Liaoning Province of Northeast China: A Review and Assessment

<div><p>Accurate estimates of forest carbon storage and changes in storage capacity are critical for scientific assessment of the effects of forest management on the role of forests as carbon sinks. Up to now, several studies reported forest biomass carbon (FBC) in Liaoning Province based on data from China's Continuous Forest Inventory, however, their accuracy were still not known. This study compared estimates of FBC in Liaoning Province derived from different methods. We found substantial variation in estimates of FBC storage for young and middle-age forests. For provincial forests with high proportions in these age classes, the continuous biomass expansion factor method (CBM) by forest type with age class is more accurate and therefore more appropriate for estimating forest biomass. Based on the above approach designed for this study, forests in Liaoning Province were found to be a carbon sink, with carbon stocks increasing from 63.0 TgC in 1980 to 120.9 TgC in 2010, reflecting an annual increase of 1.9 TgC. The average carbon density of forest biomass in the province has increased from 26.2 Mg ha⁻¹ in 1980 to 31.0 Mg ha⁻¹ in 2010. While the largest FBC occurred in middle-age forests, the average carbon density decreased in this age class during these three decades. The increase in forest carbon density resulted primarily from the increased area and carbon storage of mature forests. The relatively long age interval in each age class for slow-growing forest types increased the uncertainty of FBC estimates by CBM-forest type with age class, and further studies should devote more attention to the time span of age classes in establishing biomass expansion factors for use in CBM calculations.</p></div