The antitumor activity of CS-1008, a humanized agonistic anti-human death receptor (DR) 5 antibody, was investigated in preclinical models.
Cytotoxicity of CS-1008 was evaluated in a several human ...tumor cell lines as well as primary human hepatocytes in vitro. To evaluate antitumor efficacy, athymic nude mice were inoculated with human colorectal tumor COLO 205, pancreatic tumor MIA PaCa-2 or non-small-cell lung carcinoma NCI-H2122 and CS-1008 was i.v. administered. The combination effects of CS-1008 with gemcitabine or docetaxel (Taxotere) against MIA PaCa-2 or NCI-H2122 were evaluated in vivo, respectively.
CS-1008 inhibited the growth of tumor cell lines with DR5 expression, including COLO 205, NCI-H2122, MIA PaCa-2 and renal cell adenocarcinoma ACHN in vitro with antibody cross-linkage. Using COLO 205, apoptosis induction was confirmed by annexin V staining. Weekly administration of CS-1008 resulted in the inhibition of COLO 205 tumor growth as well as MIA PaCa-2 in vivo. CS-1008 in combination with gemcitabine or docetaxel demonstrated enhanced antitumor activity against MIA PaCa-2 or NCI-H2122 cells, respectively. Unlike tumor necrosis factor-related apoptosis-inducing ligand, CS-1008 did not induce cell death in human primary hepatocytes.
CS-1008 has a selective toxicity toward tumor cells expressing DR5 and the potential for antitumor efficacy in human malignancies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We report the fabrication of 10 m-class (Ba, Na)Fe2As2 long round wires and coils using these round wires. Round wires are fabricated by powder-in-tube (PIT) method and hot-isostatic-press (HIP) ...technique. To increase Ic keeping the diameter of the wire constant, the cross section area of the superconducting core is enlarged by changing the dimensions of metal sheaths. At 4.2 K under a high field of 100 kOe, Jc of a short segment of HIP wire reaches 42 kAcm-2, which is comparable to the highest Jc of IBS round wires of 44 kAcm-2. Furthermore, Ic of the HIP wire at 4.2 K under 10 kOe and 100 kOe reaches 95 A and 54 A, respectively, which is about twice the value of the previous report. We also fabricated a small demonstration superconducting coil using 12.5 m long PIT wires by HIP method. Ic of the whole coil is ∼60 A under the self-field, and magnetic field at the center of the coil reaches 2.6 kOe. The coil generated the magnetic field of 43 Oe/A, which is almost consistent with the calculated field from the coil dimensions.
Magnetic excitations and magnetic structure of EuRbFe4As4 were investigated by inelastic neutron scattering (INS), neutron diffraction, and random phase approximation (RPA) calculations. Below the ...superconducting transition temperature Tc=36.5 K, the INS spectra exhibit the neutron spin resonances at Qres=1.27(2) and 1.79(3)Å−1. They correspond to the Q=(0.5,0.5,1) and (0.5,0.5,3) nesting wave vectors, showing three-dimensional nature of the band structure. The characteristic energy of the neutron spin resonance is Eres=17.7(3) meV corresponding to 5.7(1)kBTc. Observation of the neutron spin resonance mode and our RPA calculations in conjunction with the recent optical conductivity measurements are indicative of the s± superconducting pairing symmetry in EuRbFe4As4. In addition to the neutron spin resonance mode, upon decreasing temperature below the magnetic transition temperature TN=15 K, the spin wave excitation originating in the long-range magnetic order of the Eu sublattice was observed in the low-energy inelastic channel. Single-crystal neutron diffraction measurements demonstrate that the magnetic propagation vector of the Eu sublattice is k=(0,0,0.25), representing the three-dimensional antiferromagnetic order. Linear spin wave calculations assuming the obtained magnetic structure with the intra- and interplane nearest neighbor exchange couplings of J1/kB=−1.31 K and Jc/kB=0.08 K can reproduce quantitatively the observed spin wave excitation. Our results show that superconductivity and long-range magnetic order of Eu coexist in EuRbFe4As4, whereas the coupling between them is rather weak.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
In ZrP1.25Se0.75, the superconducting transition temperature Tc is increased from 5.8 K to 7.6 K when Sc atoms are partially substituted for Zr atoms having almost the same atomic radius as Sc atoms. ...Transport measurements show that holes are doped with substituting Sc atoms. The density of states in (Zr, Sc)P1.25Se0.75 is derived from band structure calculations and its implication in the doping behaviour and the increase of Tc is discussed.
We conducted the coincidence measurement of α particles inelastically scattered from 20Ne at 0° and decay charged particles in order to search for the alpha-particle condensed state. We compared the ...measured excitation-energy spectrum and decay branching ratio with the statistical-decay-model calculations, and found that the newly observed states at Ex=23.6, 21.8, and 21.2 MeV in 20Ne are strongly coupled to a candidate for the 4α condensed state in 16O. This result presents the first strong evidence that these states are the candidates for the 5α condensed state.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
It is shown that the maximum superconducting transition temperature, Tc for ZrP1.25Se0.75 is increased from 5.8 K to 7.2 K by partially substituting a non-magnetic rare earth atom Lu for Zr and on ...the other hand is decreased by substituting other non-magnetic rare earth atoms Y and La. Obviously, Tc is raised when lattice constants in the a-axis and the c-axis increase with replacing Zr. Its implications for further increasing Tc are discussed.
New human adenovirus (HAdV)-54 causes epidemic keratoconjunctivitis (EKC) and is virologically close to and has occasionally been detected as HAdV-8. Taking HAdV-54 into account, we re-determined ...HAdV type in EKC samples to determine its epidemiology in Japan, and examined the virological features of HAdV-54.
HAdV type was re-determined in 776 conjunctival swabs from Japan and 174 from six other countries, obtained between 2000 and 2009. Using 115 HAdV strains obtained before 1999, trends regarding HAdV-8 and HAdV-54 were also determined. In addition, immunochromatography (IC) kit features, DNA copy numbers and viral isolation of HAdV-54 in samples were evaluated.
Recently, HAdV-37 and HAdV-54 have been the major causative types of EKC in Japan. HAdV-54 has been isolated each year since 1995, whereas HAdV-8 has become less common since 1997, although it remains the most common cause of EKC in the six other countries investigated where HAdV-54 is yet to be detected. HAdV-54 is comparable to other EKC-related HAdV types in terms of IC kit sensitivity and DNA copy numbers, although HAdV-54 grows more slowly on viral isolation.
EKC due to HAdV-54 can result in epidemics; therefore, it should be accurately diagnosed and monitored as an emerging infection worldwide.
Abstract Background Calcineurin-inhibitor–induced pain syndrome (CIPS) was used as a reference in the literature as reflex sympathetic dystrophy syndrome related to calcineurin inhibitors. Much of ...the literature describes CIPS that occurred after kidney and bone marrow transplantation. We describe a rare case of CIPS in induction immunosuppression before kidney transplantation, under administration of an anti-rheumatoid drug. Methods A 53-year-old woman had pre-status of ABO-incompatible living kidney transplantation. The patient had rheumatoid arthritis, but that was well-controlled with salazosulfapyridine as an anti-rheumatoid drug. Fourteen days before transplantation, she received induction immunosuppressive therapy consisting of tacrolimus (TAC) and mycophenolate mofetil (MMF) and she stopped taking salazosulfapyridine. The third day after that treatment, she had a high fever, fatigue, and joint pains of the knees, elbows, and wrists. Results When the patient stopped taking TAC and MMF and started taking salazosulfapyridine again, she soon recovered. Next, we challenged same induction immunosuppression therapy with administration of salazosulfapyridine; however, the patient had the same symptom. We considered that the symptom was caused by TAC or MMF, and we did not challenge-test each drug. We found that taking only TAC caused the same symptom for the patient. Also, we challenged cyclosporine (CsA) with MMF and confirmed that she did not have the symptom. Conclusions We decided that drugs of the induction immunosuppression therapy were CsA, MMF, prednisolone, and basiliximab. The patient received induction therapy with plasmapheresis and rituximab in addition to the above-mentioned drugs, and we performed ABO-incompatible kidney transplantation for her. The post-surgical course was good, without acute rejection, and she had no pain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Extranodal marginal zone B-cell lymphoma (EMZL) is the most common subtype of conjunctival lymphoma, though its molecular mechanisms of pathogenesis are largely unknown. We attempted to explore the ...association of the renin-angiotensin system (RAS) and (pro)renin receptor (PRR) in the pathogenesis of conjunctival lymphoma.
Surgically removed conjunctiva EMZL samples were used for gene expression, and immunohistochemical and immunofluorescence analyses of (P)RR and RAS components. Human B-lymphoblast IM-9 cells were treated with prorenin or angiotensin II (Ang II), and gene expression levels were analyzed using real-time quantitative PCR (qPCR). In addition, immunofluorescence analysis of EMZL samples was used to evaluate the in vivo expression of those components.
Gene expression and immunohistochemical analyses revealed the expression of RAS components, including (P)RR and angiotensin II type 1 receptor (AT1R), in EMZL tissues. Double-labeling analyses demonstrated that (P)RR and AT1R were detected in cells positive for CD20, a marker for B-cells, where they colocalized with prorenin and angiotensinogen, respectively. Prorenin stimulation of human B-lymphoblast IM-9 cells increased mRNA expression levels of fibroblast growth factor 2 (FGF2), while angiotensin II treatment upregulated the expression levels of basigin (BSG), matrix metallopeptidase (MMP)2, 9, and 14, which were abolished by (P)RR and AT1R blockades, respectively. Immunofluorescence analyses of clinical samples showed colocalizations of (P)RR and AT1R with the products of these upregulated genes.
The present study suggests that activation of (P)RR and AT1R is associated with the pathogenesis of conjunctival EMZL by stimulating the production of FGF2 and MMPs.
We report the Ca substitution effect of the Fe-based superconductor EuRbFe4As4 with 1144-type structure (crystal system: tetragonal, space group: P4/mmm (No. 123)), in order to elucidate the ...relationship between the superconductivity and the magnetic order. The lattice constant systematically changed with the Ca concentration x. By Ca-substitution, the magnetic order is suppressed, while Tc is almost unchanged. The results indicate that the superconductivity of EuRbFe4As4 is not sensitive to the magnetic order.
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