Targeting delivery of lipocalin 2-engineered mesenchymal stem cells to colon cancer in order to inhibit liver metastasis in nude mice

One of the major obstacles in cancer therapy is the lack of anticancer agent specificity to tumor tissues. The strategy of cell-based therapy is a promising therapeutic option for cancer treatment. The specific tumor-oriented migration of mesenchymal stem cells (MSCs) makes them a useful vehicle to deliver anticancer agents. In this study, we genetically manipulated bone marrow-derived mesenchymal stem cells with their lipocalin 2 (Lcn2) in order to inhibit liver metastasis of colon cancer in nude mice. Lcn2 was successfully overexpressed in transfected MSCs. The PCR results of SRY gene confirmed the presence of MSCs in cancer liver tissue. This study showed that Lcn2-engineered MSCs (MSC-Lcn2) not only inhibited liver metastasis of colon cancer but also downregulated the expression of vascular endothelial growth factor (VEGF) in the liver. Overall, MSCs by innate tropism toward cancer cells can deliver the therapeutic agent, Lcn2, and inhibit cancer metastasis. Hence, it could be a new modality for efficient targeted delivery of anticancer agent to liver metastasis. © 2015, International Society of Oncology and BioMarkers (ISOBM)

Search for direct CP-violation in K+- --> pi+-pi0pi0 decays

A search for direct CP-violation in K+- --> pi+-pi0pi0 decays based on 47.14 million events has been performed by the NA48/2 experiment at the CERN SPS. The asymmetry in the Dalitz plot linear slopes A_g=(g^+ - g^-)/(g^+ + g^-) is measured to be A_g=(1.8 +- 2.6).10^{-4}. The design of the experiment and the method of analysis provide good control of instrumental charge asymmetries in this measurement. The precision of the result is limited by statistics and is almost one order of magnitude better than that of previous measurements by other experiments.Comment: 14 page

Apparatus for a Search for T-violating Muon Polarization in Stopped-Kaon Decays

The detector built at KEK to search for T-violating transverse muon polarization in K+ --> pi0 mu+ nu (Kmu3) decay of stopped kaons is described. Sensitivity to the transverse polarization component is obtained from reconstruction of the decay plane by tracking the mu+ through a toroidal spectrometer and detecting the pi0 in a segmented CsI(Tl) photon calorimeter. The muon polarization was obtained from the decay positron asymmetry of muons stopped in a polarimeter. The detector included features which minimized systematic errors while maintaining high acceptance.Comment: 56 pages, 30 figures, submitted to NI

Search for the Rare Decay KL --> pi0 ee

The KTeV/E799 experiment at Fermilab has searched for the rare kaon decay KL--> pi0ee. This mode is expected to have a significant CP violating component. The measurement of its branching ratio could support the Standard Model or could indicate the existence of new physics. This letter reports new results from the 1999-2000 data set. One event is observed with an expected background at 0.99 +/- 0.35 events. We set a limit on the branching ratio of 3.5 x 10^(-10) at the 90% confidence level. Combining the results with the dataset taken in 1997 yields the final KTeV result: BR(KL --> pi0 ee) < 2.8 x 10^(-10) at 90% CL.Comment: 4 pages, three figure

A new measurement of direct CP violation in two pion decays of the neutral kaon

The NA48 experiment at CERN has performed a new measurement of direct CP violation, based on data taken in 1997 by simultaneously collecting K_L and K_S decays into pi0pi0 and pi+pi-. The result for the CP violating parameter Re(epsilon'/epsilon) is (18.5 +/- 4.5(stat)} +/- 5.8 (syst))x10^{-4}.Comment: 18 pages, 6 figure

Measurements Of The Decay Kl → E+e-μ+μ-

Several 132 KL → e+e- μ+ μ- events were observed from the 1997 and 1999 runs of the KTeV experiments, with an estimated background of 0.8 events. In the first measurement of the parameter α using this decay mode, it was found that α=-1.59±0.37. No evidence was found for CP-violating contributions to the KLγ*γ* interaction.9014141801/1141801/5Wolfenstein, L., (1983) Phys. Rev. Lett., 51, p. 1945Belanger, G., Geng, C.Q., (1991) Phys. Rev. D, 43, p. 140Buras, A.J., Fleischer, R., (1998) Advanced Ser. Direct. High Energy Phys., 15, p. 65Uy, Z.E.S., (1991) Phys. Rev. D, 43, p. 802D'Ambrosio, G., Isidori, G., Portolès, J., (1998) Phys. Lett. B, 423, p. 385Alavi-Harati, A., (2001) Phys. Rev. Lett., 87, p. 71801. , KTeV CollaborationAlavi-Harati, A., (2001) Phys. Rev. Lett., 86, p. 5425. , KTeV CollaborationUy, Z.E.S., (2002) Eur. Phys. J. C, 23, p. 113Alavi-Harati, A., (2001) Phys. Rev. Lett., 87, p. 111802. , KTeV CollaborationHamm, J.C., (2002), Ph.D. thesis, The University of Arizona(Fermilab Report No. fERMILAB-THESIS-2002-09)Alavi-Harati, A., (1999) Phys. Rev. Lett., 83, p. 922. , KTeV CollaborationAlavi-Harati, A., (2000) Phys. Rev. D, 61, p. 072006. , KTeV CollaborationBrown, C., (1996) Nucl. Instrum. Methods Phys. Res., Sect. A, 369, p. 248Quinn, G.B., (2000), Ph.D. thesis, The University of ChicagoBarker, A.R., Huang, H., Toale, P.A., Engle, J., hep-ph/0210174Bergström, L., Massó, E., Singer, P., (1983) Phys. Lett., 131 B, p. 229Fanti, V., (1999) Phys. Lett. B, 458, p. 553. , NA48 Collaboratio

Search for direct CP violation in the decays K\pm \to 3\pi\pm

We report a measurement of the direct CP violation asymmetry parameter $A_g$ in charged kaon decays $K^\pm\to\pi^\pm\pi^+\pi^-$ by the NA48/2 experiment at the CERN SPS. The experiment has been designed not to be limited by systematics in the asymmetry measurement. Using $1.67\times 10^9$ such decays collected during the 2003 run, the charge asymmetry in the Dalitz plot linear slope parameter $g$ has been measured to be $A_g=(1.7\pm2.9)\times 10^{-4}$. The precision of the result is limited by the statistics used.Comment: 14 pages, 5 figure

Positive selection of wharton�s jelly-derived CD105+ cells by MACS technique and their subsequent cultivation under suspension culture condition: A simple, versatile culturing method to enhance the multipotentiality of mesenchymal stem cells

Objective: Wharton�s jelly (WJ), an appropriate source of mesenchymal stem cells (MSCs), has been shown to have a wide array of therapeutic applications. However, the WJ-derived MSCs are very heterogeneous and have limited expression of pluripotency markers. Hence, improvement of their culture condition would promote the efficiency of WJ-MSCs. This study aims to employ a simple method of cultivation to obtain WJ-MSCs which express more pluripotency markers. Methods: CD105+ cells were separated by magnetic-associated (activated) cell sorting from umbilical cord mucous tissue. CD105+ cells were added to Methocult medium diluted in α-minimum essential medium (α-MEM) and seeded in poly(2-hydroxyethyl methacrylate) (poly-HEMA)-coated plates for suspension culture preparation. Differentiation capacity of isolated cells was evaluated in the presence of differentiation-inducing media. The expression of pluripotency markers such as Oct3/4, Nanog, and Sox2 was also analyzed by RT-PCR and western blot techniques. Moreover, immunocytochemistry was performed to detect alpha-smooth muscle actin (antigene) (α-SMA) protein. Results: WJ-MSCs grew homogeneously and formed colonies when cultured under suspension culture conditions (Non-adhesive WJ-MSCs). They maintained their growth ability in both adherent and suspension cultures for several passages. Non-adhesive WJ-MSCs expressed Oct3/4, Nanog, and Sox2 both at transcriptional and translational levels in comparison to those cultured in conventional adherent cultures. They also expressed α-SMA protein. Discussion: In this study, we isolated WJ-MSCs using a slightly modified culture condition. Our simple non-genetic method resulted in a homogeneous population of WJ-MSCs, which highly expressed pluripotency markers. Conclusion: In the future, more multipotent WJ-MSCs can be harnessed as a non-embryonic source of MSCs in MSC-based cell therapy. © W. S. Maney & Son Ltd 2015

A Clinical and Molecular Genetic Study of 50 Families with Autosomal Recessive Parkinsonism Revealed Known and Novel Gene Mutations

In this study, the role of known Parkinson�s disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria. For disease gene/mutation identification, multiplex ligation-dependent probe amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing assays were carried out. A total of 116 patients (50 families) were examined. Fifty-four patients (46.55; 22 families) were found to carry pathogenic mutations in known genes while a novel gene, not previously associated with parkinsonism, was found mutated in a single family (2 patients). Pathogenic mutations, including missense, nonsense, frameshift, and exon rearrangements, were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion, variable phenotypic expressivity was seen across all families. © 2017, Springer Science+Business Media New York

A Clinical and Molecular Genetic Study of 50 Families with Autosomal Recessive Parkinsonism Revealed Known and Novel Gene Mutations

In this study, the role of known Parkinson�s disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria. For disease gene/mutation identification, multiplex ligation-dependent probe amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing assays were carried out. A total of 116 patients (50 families) were examined. Fifty-four patients (46.55; 22 families) were found to carry pathogenic mutations in known genes while a novel gene, not previously associated with parkinsonism, was found mutated in a single family (2 patients). Pathogenic mutations, including missense, nonsense, frameshift, and exon rearrangements, were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion, variable phenotypic expressivity was seen across all families. © 2017, Springer Science+Business Media New York