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Imatinib (IMT), a specific tyrosine kinase inhibitor (TKI), has drastically changed the treatment strategy for Ph+ ALL (Philadelphia chromosome-positive acute lymphoblastic leukemia). However, TKI resistance remains a serious problem for patient prognosis. Here, a Ph+ ALL cell line NphA2 and the IMT-resistant subline NphA2/STIR were analyzed to identify a potential novel treatment strategy. We also examined other Ph+ ALL cells, MR87 and its IMT-resistant subline, MR87/STIR. IMT induced apoptosis of NphA2 and MR87 but had no effect on resistant sublines. Increased phosphorylated ERK and BCL2, but not BCL-XL, were observed in NphA2/STIR compared with NphA2. NphA2/STIR but not NphA2 was moderately sensitive to U0126, an ERK inhibitor. Interestingly, SP600125, a JNK inhibitor, was potent in cell growth inhibition and apoptosis induction of both parental and IMT-resistant NphA2 and MR87 cells. Moreover, NphA2 and MR87 and their IMT-resistant sublines were sensitive to ABT-199, a specific BCL2 inhibitor. The combination of SP600125 and ABT-199 synergistically suppressed both parental and IMT-resistant cells, including one with T315I mutation, suggesting that Ph+ ALL exhibits high sensitivity to ABT-199 and SP600125 regardless of TKI resistance. This combination might be a possible therapeutic strategy for Ph+ ALL in the future. Keywords: Ph+ ALL, Imatinib-resistance, JNK inhibitor, BCL2 inhibitor, Synergistic action

Patients in the chronic phase (CP) of chronic myelogenous leukemia (CML) have been treated successfully following the advent of ABL kinase inhibitors, but once they progress to the blast crisis (BC) phase the prognosis becomes dismal. Although mechanisms underlying the progression are largely unknown, recent studies revealed the presence of alterations of key molecules for hematopoiesis, such as AML1/RUNX1. Our analysis of 13 BC cases revealed that three cases had AML1 mutations and the transcript levels of wild-type (wt.) AML1 were elevated in BC compared with CP. Functional analysis of representative AML1 mutants using mouse hematopoietic cells revealed the possible contribution of some, but not all, mutants for the BC-phenotype. Specifically, K83Q and R139G, but neither R80C nor D171N mutants, conferred upon BCR-ABL-expressing cells a growth advantage over BCR-ABL-alone control cells in cytokine-free culture, and the cells thus grown killed mice upon intravenous transfer. Unexpectedly, wt.AML1 behaved similarly to K83Q and R139G mutants. In a bone marrow transplantation assay, K83Q and wt.AML1s induced the emergence of blast-like cells. The overall findings suggest the roles of altered functions of AML1 imposed by some, but not all, mutants, and the elevated expression of wt.AML1 for the disease progression of CML.

In the aftermath of the Great East Japan Earthquake, the Japanese government recognized an urgent need to construct a national archive system to store information related to the earthquake to ensure effective analysis and handover of such information. Therefore, some regional libraries are archiving the materials using Online Public Access Catalog (OPAC). Such archives contain valuable information; however, it is difficult for most people to source valuable information from an archive as a majority of the material comprises documents with no background, such as white papers, planning papers, handbills, and free papers. In this study, we propose a new digital archive concept aimed for efficient utilization of digital materials adopting the Soft Systems Methodology framework. It is a new concept that connects primary material to new secondary material. The new concept was developed in collaboration with the Iwate Prefectural Library. And we developed a prototype system to verify the feasibility of the framework. We verified that the system has suitable functionality to promote the utilization of the materials, which assisted in solving the problem of the OPAC. [ABSTRACT FROM AUTHOR]

The article discusses research which investigates the expression of recombinant alpha and beta tubulins from the yew Taxus cuspidata and analyzes the microtubule assembly in the presence of taxol. Topics discussed include isolation of taxol from the yew Taxus brevifolia, cloning of the complimentary DNA (cDNA)for both tubulins from Taxus cuspidata and the human embryonic kidney cell line HEK293T, and concludes less senitivity of microtubule from cuspidata to taxol than that from HEK293T.

Thermodynamic characteristics of a dimer liquid crystal comprising a relatively long spacer −O(CH2CH2O)6− were investigated. The contour length of the flexible spacer (∼25 Å) exceeds that of the hard segments (∼18 Å). The compound exhibits a nematic mesophase (N) between the crystal (C) and the isotropic melt (I) over a sizably wide temperature range (∼80 °C). Thermodynamic quantities such as thermal expansion coefficient , isothermal compressibility , thermal pressure coefficient (/), and the volume change Vat the CN and NI interphase were carefully determined by the PVTmeasurements. The transition entropies due to volume expansion were estimated by the well-known relation SVV. The latent entropies (Str)Pfor both CN and NI transitions were estimated according to the Clapeyron relation from the PVTand DTA data. The magnitude of the constant-volume entropy changes (Str)Vcalculated was found to be about 50−60% of the corresponding values of (Str)P. These results were consistent with the previous 2H NMR observations that the chain segments adopt a nematic conformation in the LC state. The thermodynamic role of the flexible segment in determining the phase transitions has been critically discussed. [ABSTRACT FROM AUTHOR]

It has been reported that poly(β-phenethyl l-aspartate) (PPLA) exhibits irreversible inversion from right-handed to left-handed helixes in a solid state at 130–140 °C from the results of circular dichroism measurement and X-ray diffraction. On the other hand, it is well known that semicrystalline chiral polymers show shear piezoelectricity due to their asymmetric crystal structure. The results of macroscopic shear piezoelectric measurement include information on macroscopic and microscopic properties due to the helix structure of the chain molecules. However, in general, no direct correspondence has been reported between the macroscopic piezoelectric properties and crystal characteristics because of the existence of a unique complex high-order structure in polymer films. We measured the temperature dependence of the piezoelectricity of a PPLA film in order to obtain more information concerning the helix inversion process. As a result, the sign inversion of the piezoelectric constant was observed at the temperature at which the helix inversion took place. It was also shown that the macroscopic orientation of the crystalline structure was maintained in the PPLA film after the sign inversion, even though molecular motion such as the segmental motion and side-chain motion of PPLA molecules was activated. [ABSTRACT FROM AUTHOR]