In My View

The focus of the Naval War College Review Winter 2010 issue on the maritime strategic perspective in the Pacific elicits fresh contemplation on the role of the U.S. Navy’s aircraft carriers as global American representatives and thus as effec- tive and necessary tools of foreign policy and diplomacy in the new era of un- constrained, and literally “asymmetric,” confrontations of nations and factions

Patient-derived orthotopic xenograft models for cancer of unknown primary precisely distinguish chemotherapy, and tumor-targeting S. typhimurium A1-R is superior to first-line chemotherapy.

Cancer of unknown primary (CUP) is a recalcitrant disease with poor prognosis because it lacks standard first-line therapy. CUP consists of diverse malignancy groups, making personalized precision therapy essential. The present study aimed to identify an effective therapy for a CUP patient using a patient-derived orthotopic xenograft (PDOX) model. This paper reports the usefulness of the PDOX model to precisely identify effective and ineffective chemotherapy and to compare the efficacy of S. typhimurium A1-R with first-line chemotherapy using the CUP PDOX model. The present study is the first to use a CUP PDOX model, which was able to precisely distinguish the chemotherapeutic course. We found that a carboplatinum (CAR)-based regimen was effective for this CUP patient. We also demonstrated that S. typhimurium A1-R was more effective against the CUP tumor than first-line chemotherapy. Our results indicate that S. typhimurium A1-R has clinical potential for CUP, a resistant disease that requires effective therapy

The combination of temozolomide-irinotecan regresses a doxorubicin-resistant patient-derived orthotopic xenograft (PDOX) nude-mouse model of recurrent Ewing's sarcoma with a FUS-ERG fusion and CDKN2A deletion: Direction for third-line patient therapy.

The aim of the present study was to determine the usefulness of a patient-derived orthotopic xenograft (PDOX) nude-mouse model of a doxorubicin-resistant metastatic Ewing's sarcoma, with a unique combination of a FUS-ERG fusion and CDKN2A deletion, to identify effective drugs for third-line chemotherapy of the patient. Our previous study showed that cyclin-dependent kinase 4/6 (CDK4/6) and insulin-like growth factor-1 receptor (IGF-1R) inhibitors were effective on the Ewing's sarcoma PDOX, but not doxorubicin, similar to the patient's resistance to doxorubicin. The results of the previous PDOX study were successfully used for second-line therapy of the patiend. In the present study, the PDOX mice established with the Ewing's sarcoma in the right chest wall were randomized into 5 groups when the tumor volume reached 60 mm3: untreated control; gemcitabine combined with docetaxel (intraperitoneal [i.p.] injection, weekly, for 2 weeks); irinotecan combined with temozolomide (irinotecan: i.p. injection; temozolomide: oral administration, daily, for 2 weeks); pazopanib (oral administration, daily, for 2 weeks); yondelis (intravenous injection, weekly, for 2 weeks). All mice were sacrificed on day 15. Body weight and tumor volume were assessed 2 times per week. Tumor weight was measured after sacrifice. Irinotecan combined with temozolomide was the most effective regimen compared to the untreated control group (p=0.022). Gemcitabine combined with docetaxel was also effective (p=0.026). Pazopanib and yondelis did not have significant efficacy compared to the untreated control (p=0.130, p=0.818). These results could be obtained within two months after the physician's request and were used for third-line therapy of the patient

Spallation and fragmentation cross sections for 168 MeV/nucleon Xe 136 ions on proton, deuteron, and carbon targets

The spallation and fragmentation reactions of Xe136 induced by proton, deuteron, and carbon targets at 168 MeV/nucleon were studied at RIKEN Radioactive Isotope Beam Factory via the inverse kinematics technique. A wide range of isotopic distributions of the reaction cross sections has been obtained and systematically analyzed by using the Particle and Heavy Ion Transport code System (PHITS) including dynamical and intranuclear cascade processes plus evaporation process, the semi-empirical parametrization for residue cross sections in spallation reactions (SPACS) and empirical parametrization of fragmentation cross sections (EPAX), and the deuteron-induced reaction analysis code system (DEURACS) incorporating the deuteron breakup effect. The carbon target has exhibited strong potential to produce light-mass isotopes far away from the projectile, in comparison to proton and deuteron targets. This may be attributed to the possible higher excitation energies of the prefragment induced by heavier target. It is demonstrated that the deuteron target has advantages to produce isotopic chains very close to the projectile and also the neutron-rich nuclei in other isotopic chains far away from the projectile, due basically to its structure property and the effect of the breakup neutron in the peripheral collision processes. The proton target has the advantage of being able to produce isotopes produced via charge-pickup reactions in comparison to other targets. The prediction powers of various calculation codes are examined with respective to the experimental isotopic distributions. The target and energy dependences of the produced mass distributions are also discussed

Two-Neutron Halo is Unveiled in ^{29}F

We report the measurement of reaction cross sections (σ_{R}^{ex}) of ^{27,29}F with a carbon target at RIKEN. The unexpectedly large σ_{R}^{ex} and derived matter radius identify ^{29}F as the heaviest two-neutron Borromean halo to date. The halo is attributed to neutrons occupying the 2p_{3/2} orbital, thereby vanishing the shell closure associated with the neutron number N=20. The results are explained by state-of-the-art shell model calculations. Coupled-cluster computations based on effective field theories of the strong nuclear force describe the matter radius of ^{27}F but are challenged for ^{29}F

In-beam γ-ray spectroscopy of Te 136 at relativistic energies

The reduced transition probability B(E2;01+→21+) to the first excited 2+ state of the neutron-rich nucleus Te136, with two protons and two neutrons outside the doubly magic Sn132 core, was measured via Coulomb excitation at relativistic energies at the RIKEN Radioactive Isotope Beam Factory. A value of B(E2)=0.191(26) e2b2 was extracted from the measured inelastic scattering cross section on an Au target taking into account the contributions from both Coulomb and nuclear excitations. In addition, an upper limit for the transition strength to a 2+ state of mixed-symmetry character in the excitation energy range of 1.5-2.2 MeV was determined and compared to the predictions of various theoretical calculations. Because of the high statistics gathered in the present experiment the error of the deduced B(E2) value is dominated by the systematic uncertainties involved in the analysis of Coulomb excitation experiments at beam energies around 150 MeV/u. Therefore, the latter are for the first time assessed in detail in the present work

Vesicular glutamate release from central axons contributes to myelin damage

Neuronal activity can lead to vesicular release of glutamate. Here the authors demonstrate that vesicular release of glutamate occurs in axons during ischemic conditions, and that an allosteric modulator of GluN2C/D is protective in models of ischemic injury

Increased Levels of Leukocyte-Derived MMP-9 in Patients with Stable Angina Pectoris

Objective: There is a growing interest for matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in plasma as novel biomarkers in coronary artery disease (CAD). We aimed to identify the sources of MMP-8, MMP-9, TIMP-1 and TIMP-2 among peripheral blood cells and further explore whether gene expression or protein release was altered in patients with stable angina pectoris (SA). Methods: In total, plasma MMP-9 was measured in 44 SA patients and 47 healthy controls. From 10 patients and 10 controls, peripheral blood mononuclear cells (PBMC) and neutrophils were isolated and stimulated ex vivo. MMPs, TIMPs and myeloperoxidase were measured in plasma and supernatants by ELISA. The corresponding gene expression was measured by real-time PCR. Results: Neutrophils were the dominant source of MMP-8 and MMP-9. Upon moderate stimulation with IL-8, the neutrophil release of MMP-9 was higher in the SA patients compared with controls (p,0.05). In PBMC, the TIMP-1 and MMP-9 mRNA expression was higher in SA patients compared with controls, p,0.01 and 0.05, respectively. There were no differences in plasma levels between patients and controls except for TIMP-2, which was lower in patients, p,0.01. Conclusion: Measurements of MMPs and TIMPs in plasma may be of limited use. Despite similar plasma levels in SA patients and controls, the leukocyte-derived MMP-9 and TIMP-1 are significantly altered in patients. The findings indicate that th

Shell structure of the neutron-rich isotopes Co 69,71,73

The structures of the neutron-rich Co69,71,73 isotopes were investigated via (p,2p) knockout reactions at the Radioactive Isotope Beam Factory, RIKEN. Isotopes of interest were studied using the DALI2 γ-ray detector array combined with the MINOS target and tracker system. Level schemes were reconstructed using the γ-γ coincidence technique, with tentative spin-parity assignments based on the measured inclusive and exclusive cross sections. Comparison with shell-model calculations using the Lenzi-Nowacki-Poves-Sieja LNPS and PFSDG-U interactions suggests coexistence of spherical and deformed shapes at low excitation energies in the Co69,71,73 isotopes. The distorted-wave impulse approximation (DWIA) framework was used to calculate the single-particle cross sections. These values were compared with the experimental findings