MYCN Silencing by RNA Interference Induces Neurogenesis and Suppresses Proliferation in Models of Neuroblastoma with Resistance to Retinoic Acid

Neuroblastoma (NB) is the most common solid tumor in childhood. Twenty percent of patients display MYCN amplification, which indicates a very poor prognosis. MYCN is a highly specific target for an NB tumor therapy as MYCN expression is absent or very low in most normal cells, while, as a transcription factor, it regulates many essential cell activities in tumor cells. We aim to develop a therapy for NB based on MYCN silencing by short interfering RNA (siRNA) molecules, which can silence target genes by RNA interference (RNAi), a naturally occurring method of gene silencing. It has been shown previously that MYCN silencing can induce apoptosis and differentiation in MYCN amplified NB. In this article, we have demonstrated that siRNA-mediated silencing of MYCN in MYCN-amplified NB cells induced neurogenesis in NB cells, whereas retinoic acid (RA) treatment did not. RA can differentiate NB cells and is used for treatment of residual disease after surgery or chemotherapy, but resistance can develop. In addition, MYCN siRNA treatment suppressed growth in a MYCN-amplified NB cell line more than that by RA. Our result suggests that gene therapy using RNAi targeting MYCN can be a novel therapy toward MYCN-amplified NB that have complete or partial resistance toward RA

Photoinduced charge and spin dynamics in strongly correlated electron systems

Motivated by photoinduced phase transition in manganese oxides, charge and spin dynamics induced by photoirradiation are examined. We calculate the transient optical absorption spectra of the extended double-exchange model by the density matrix renormalization group (DMRG) method. A charge-ordered insulating (COI) state becomes metallic just after photoirradiation, and the system tends to recover the initial COI state. The recovery is accompanied with remarkable suppression of an antiferromagnetic correlation in the COI state. The DMRG results are consistent with recent pump-probe spectroscopy data.Comment: 5 pages, 4 figure

Magnetic phase diagram of the S=1/2 antiferromagnetic zigzag spin chain in the strongly frustrated region: cusp and plateau

We determine the magnetic phase diagram of the antiferromagnetic(AF) zigzag spin chain in the strongly frustrated region, using the density matrix renormalization group method. We find the magnetization plateau at 1/3 of the full moment accompanying the spontaneous symmetry breaking of the translation, the cusp singularities above and/or below the plateau, and the even-odd effect in the magnetization curve. We also discuss the formation mechanisms of the plateau and cusps briefly.Comment: 4 pages, 8 figures, revised version, to appear in J.Phys.Soc.Jp

Polarized far-infrared and Raman spectra of SrCuO2 single crystals

We measured polarized far-infrared reflectivity and Raman scattering spectra of SrCuO$_2$ single crystals. The frequencies for infrared-active modes were determined using an oscillator-fitting procedure of reflectivity data. The Raman spectra were measured at different temperatures using several laser energies $\omega_L$. In addition to eight of twelve Raman active modes, predicted by factor-group analysis, we observed a complex structure in the Raman spectra for polarization parallel to the {\bf c}-axis, which consists of Raman-allowed A$_g$ symmetry modes, and B$_{1u}$ LO infrared-active (Raman-forbidden) modes of the first and higher order as well as their combinations. The Raman-forbidden modes have a stronger intensity at higher $\omega_L$ than the Raman-allowed ones. In order to explain this resonance effect, we measured the dielectric function and optical reflection spectra of SrCuO$_2$ in the visible range. We show that the Raman-allowed A$_g$ symmetry modes are resonantly enhanced when a laser energy is close to $E_0$, while Raman-forbidden (IR-active) modes resonate strongly for laser line energies close to the electronic transition of higher energy gaps.Comment: to be published in Physica

Application of the density matrix renormalization group method to finite temperatures and two-dimensional systems

The density matrix renormalization group (DMRG) method and its applications to finite temperatures and two-dimensional systems are reviewed. The basic idea of the original DMRG method, which allows precise study of the ground state properties and low-energy excitations, is presented for models which include long-range interactions. The DMRG scheme is then applied to the diagonalization of the quantum transfer matrix for one-dimensional systems, and a reliable algorithm at finite temperatures is formulated. Dynamic correlation functions at finite temperatures are calculated from the eigenvectors of the quantum transfer matrix with analytical continuation to the real frequency axis. An application of the DMRG method to two-dimensional quantum systems in a magnetic field is demonstrated and reliable results for quantum Hall systems are presented.Comment: 33 pages, 18 figures; corrected Eq.(117

Fractional S^z excitation and its bound state around the 1/3 plateau of the S=1/2 Ising-like zigzag XXZ chain

We present the microscopic view for the excitations around the 1/3 plateau state of the Ising-like zigzag XXZ chain. We analyze the low-energy excitations around the plateau with the degenerating perturbation theory from the Ising limit, combined with the Bethe-form wave function. We then find that the domain-wall particles carrying $S^z=\pm 1/3$ and its bound state of $S^z=\pm 2/3$ describe well the low-energy excitations around the 1/3 plateau state. The formation of the bound state of the domain-walls clearly provides the microscopic mechanism of the cusp singularities and the even-odd behavior in the magnetization curve.Comment: 13 pages, 15 figure

Lipid-peptide nanocomplexes for mRNA delivery in vitro and in vivo

Despite recent advances in the field of mRNA therapy, the lack of safe and efficacious delivery vehicles with pharmaceutically developable properties remains a major limitation. Here, we describe the systematic optimisation of lipid-peptide nanocomplexes for the delivery of mRNA in two murine cancer cell types, B16-F10 melanoma and CT26 colon carcinoma as well as NCI-H358 human lung bronchoalveolar cells. Different combinations of lipids and peptides were screened from an original lipid-peptide nanocomplex formulation for improved luciferase mRNA transfection in vitro by a multi-factorial screening approach. This led to the identification of key structural elements within the nanocomplex associated with substantial improvements in mRNA transfection efficiency included alkyl tail length of the cationic lipid, the fusogenic phospholipid, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and cholesterol. The peptide component (K16GACYGLPHKFCG) was further improved by the inclusion of a linker, RVRR, that is cleavable by the endosomal enzymes cathepsin B and furin, and a hydrophobic motif (X-S-X) between the mRNA packaging (K16) and receptor targeting domains (CYGLPHKFCG). Nanocomplex transfections of a murine B16-F10 melanoma tumour supported the inclusion of cholesterol for optimal transfection in vivo as well as in vitro. In vitro transfections were also performed with mRNA encoding interleukin-15 as a potential immunotherapy agent and again, the optimised formulation with the key structural elements demonstrated significantly higher expression than the original formulation. Physicochemical characterisation of the nanocomplexes over time indicated that the optimal formulation retained biophysical properties such as size, charge and mRNA complexation efficiency for 14 days upon storage at 4 °C without the need for additional stabilising agents. In summary, we have developed an efficacious lipid-peptide nanocomplex with promising pharmaceutical development properties for the delivery of therapeutic mRNA

Entanglement Perturbation Theory for Antiferromagnetic Heisenberg Spin Chains

A recently developed numerical method, entanglement perturbation theory (EPT), is used to study the antiferromagnetic Heisenberg spin chains with z-axis anisotropy $\lambda$ and magnetic field B. To demonstrate the accuracy, we first apply EPT to the isotropic spin-1/2 antiferromagnetic Heisenberg model, and find that EPT successfully reproduces the exact Bethe Ansatz results for the ground state energy, the local magnetization, and the spin correlation functions (Bethe ansatz result is available for the first 7 lattice separations). In particular, EPT confirms for the first time the asymptotic behavior of the spin correlation functions predicted by the conformal field theory, which realizes only for lattice separations larger than 1000. Next, turning on the z-axis anisotropy and the magnetic field, the 2-spin and 4-spin correlation functions are calculated, and the results are compared with those obtained by Bosonization and density matrix renormalization group methods. Finally, for the spin-1 antiferromagnetic Heisenberg model, the ground state phase diagram in $\lambda$ space is determined with help of the Roomany-Wyld RG finite-size-scaling. The results are in good agreement with those obtained by the level-spectroscopy method.Comment: 12 pages, 14 figure