A Screening Method for the ALK Fusion Gene in NSCLC

Lung cancer research has recently made significant progress in understanding the molecular pathogenesis of lung cancer and in developing treatments for it. Such achievements are directly utilized in clinical practice. Indeed, the echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase (ALK) fusion gene was first described in non-small cell lung cancer in 2007, and a molecularly targeted drug against the fusion was approved in 2011. However, lung cancer with the ALK fusion constitutes only a small fraction of lung cancers; therefore, efficient patient selection is crucial for successful treatment using the ALK inhibitor. Currently, RT-PCR, fluorescent in situ hybridization (FISH), and immunohistochemistry are commonly used to detect the ALK fusion. Although FISH is currently the gold standard technique, there are no perfect methods for detecting these genetic alterations. In this article, we discuss the advantages and disadvantages of each method and the possible criteria for selecting patients who are more likely to have the ALK fusion. If we can successfully screen patients, then ALK inhibitor treatment will be the best example of personalized therapy in terms of selecting patients with an uncommon genotype from a larger group with the same tumor phenotype. In other words, the personalized therapy may offer a new challenge for current clinical oncology

Patient-derived mouse models of cancer need to be orthotopic in order to evaluate targeted anti-metastatic therapy.

Patient-derived xenograft (PDX) mouse models of cancer are emerging as an important component of personalized precision cancer therapy. However, most models currently offered to patients have their tumors subcutaneously-transplanted in immunodeficient mice, which rarely metastasize. In contrast, orthotopic-transplant patient-derived models, termed patient-derived orthotopic xenografts (PDOX), usually metastasize as in the patient. We demonstrate in the present report why orthotopic models are so important for the patient, since primary and metastatic tumors developed in an orthotopic model can have differential chemosensitivity, not detectable in standard subcutaneous tumor models. A subcutaneous nude mouse model of HER-2 expressing cervical carcinoma was not sensitive to entinostat (a benzamide histone deactylase inhibitor), which also did not inhibit primary tumor growth in a PDOX model of the same tumor. However, in the PDOX model, entinostat alone significantly reduced the metastatic tumor burden, compared to the control. Thus, only the PDOX model could be used to discover the anti-metastatic activity of entinostat for this patient. The results of the present report indicate the importance of using mouse models that can recapitulate metastatic cancer for precisely individualizing cancer therapy

Successful Extracorporeal Life Support for Life-threatening Hypercapnia with Bronchiolitis Obliterans after Allogeneic Hematopoietic Stem Cell Transplantation

Bronchiolitis obliterans (BO) is a disease with a poor prognosis, and a key factor that limits long-term survival after allogeneic hematopoietic stem cell transplantation (HSCT). We here report a case of a 31-year woman with acute lymphatic leukemia, which was treated by chemotherapy and HSCT, and consequently developed BO 2 years after HSCT. A non-tuberculous mycobacterial infection occurred and showed gradual exacerbation. She started taking anti-mycobacterial drugs, but lost appetite, felt tired and finally lost consciousness one month after beginning medication. Arterial blood gas revealed marked hypercapnia. Using extracorporeal life support (ECLS), the carbon dioxide concentration was reduced and her consciousness recovered. To our knowledge, this is the first case in which ECLS was successfully used for hypercapnia in a patient with BO

Indium-bearing paragenesis from the Nueva Esperanza and Restauradora veins, Capillitas mine, Argentina

The Nueva Esperanza and Restauradora are two of the twenty-three veins described at Capillitas mine, an epithermal precious-and base-metal vein deposit located in northern Argentina. Capillitas is genetically linked to other minera-lizations of the Farallón Negro Volcanic Complex, which hosts several deposits. These include two world-class (La Alumbrera and Agua Rica) and some smaller (e.g., Bajo El Durazno) porphyry deposits, and a few epithermal deposits (Farallón Negro, Alto de la Blenda, Cerro Atajo and Capillitas). The main hypogene minerals found at these two veins include pyrite, sphalerite, galena, chalcopyrite, tennantite-(Zn) and tennantite-(Fe). Accessory minerals comprise hübnerite, gold, silver, stannite, stannoidite and mawsonite, and also diverse indium-and tellurium-bearing minerals. Quartz is the main gangue mineral. Indium participates in the structure of sphalerite, tennantite-(Zn), ishiharaite and an indium-bearing mineral, still under study, the former being the most abundant of these phases. The chemical composition of sphalerite shows very low concentrations of Fe and a wide range in indium contents from below the detection limit (0.03 wt. %) to values close to 22 wt. %. Atomic proportions of In and Cu correlate positively at a ratio In: Cu = 1: 1 atoms per formula unit. Cadmium reaches up to 0.68 wt. %. Other analyzed elements (Ge, As, Se, Ag, Sn, Te, Au, Pb and Bi) are systematically below their respective detection limits. Indium-bearing tennantite-(Zn) (up to 0.24 wt. % In) is rare and restricted to the area where ishiharaite appears. Ishiharaite and the unclassified indium-bearing mineral are extremely scarce and host up to 10 and 30 wt. % In, respectively. The zoning in sphalerite and the variable indium content of the different bands could be ascribed to significant fluctuation in the composition of the fluids (possibly pulses). They are evidenced by the presence of a high f Te2 mineral, like calaverite, and a low f Te2 phase, such as silver, within the same stage, with local periodic increments on In and Cu that could also be associated with recurring reactivation of fractures.Fil: Marquez Zavalia, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Vymazalová, Anna. Czech Geological Survey; República ChecaFil: Galliski, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Watanabe, Yasushi. Mining Museum of Akita University; JapónFil: Murakami, Hiroyasu. No especifíca

Enhanced dielectric response by disordered nanoscale/mesoscopic insulators

Enhancement of the dielectric response of insulators by disorder is theoretically proposed, where the quantum interference of electronic waves through the nanoscale/mesoscopic system and its change due to external perturbations control the polarization. In the disordered case with all the states being localized, the resonant tunneling, which is topologically protected, plays a crucial role, and enhances the dielectric response by a factor 30~40 compared with the pure case. Realization of this idea with accessible materials/structures is also discussed.Comment: 4 pages including 3 figures; minor revision; a high-resolution figure available at http://appi.t.u-tokyo.ac.jp/~sonoda/papers.htm

Spatial Domain Resource Sharing for Overlapping Cells in Indoor Environment

As microcell wireless systems become more widespread, intercell interference among the access points will increase due to the limited frequency resource. In the overlapping cell scenario, radio resources should be shared by multiple cells. Although time and frequency resource sharing has been described in many papers, there is no detailed report on dynamic spatial resource sharing among multiple cells for microcell wireless systems. Thus, we present the effectiveness of spatial resource sharing among two access points. We introduce two scenarios based on the zero forcing method; one is the primary-secondary AP scenario and the other is the cooperative AP scenario. To evaluate the transmission performance of spatial resource sharing, channel matrices are measured in an indoor environment. The simulation results using the measured channel matrices show the potential of spatial resource sharing

What motivated medical students and residents to become radiation oncologists in Japan?—Questionnaire report by the radiotherapy promotion committee of JASTRO

This study aimed to clarify the motivations and timing of the decision to become radiation oncologists. Materials and methods: We conducted an online survey for new members of the Japanese Society for Radiation Oncology (JASTRO). Results: The response rate was 43.3%. Data of the 79 respondents who wanted to obtain a board-certification of JASTRO were analysed. We divided the respondents into two groups: Group A, those who entered a single radiation oncology department, and Group B, those who joined a radiology department in which the radiation oncology department and diagnostic radiology department were integrated. The most common period when respondents were most attracted to radiation oncology was “5th year of university” in Group A and “2nd year of junior residency” and “senior residency” in Group B. Furthermore, 79.5% of Group A and 40% of Group B chose periods before graduation from a university with a significant difference. The most common period when respondents made up their minds to become radiation oncologists was “2nd year of junior residency” in both groups. Internal medicine was the most common department to consider if they did not join the radiation oncology or radiology department. Conclusion: To increase the radiation oncologists, it is crucial to enhance clinical training in the fifth year of university for Group A and to continue an active approach to maintain interest in radiation oncology until the end of junior residency. In Group B facilities, it is desirable to provide undergraduates more opportunities to come in contact with radiation oncology

Corticosterone Induces Rapid Spinogenesis via Synaptic Glucocorticoid Receptors and Kinase Networks in Hippocampus

BACKGROUND: Modulation of dendritic spines under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT) secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrated the mechanisms of rapid effect (∼1 h) of CORT on the density and morphology of spines by imaging neurons in adult male rat hippocampal slices. The application of CORT at 100-1000 nM induced a rapid increase in the density of spines of CA1 pyramidal neurons. The density of small-head spines (0.2-0.4 µm) was increased even at low CORT levels (100-200 nM). The density of middle-head spines (0.4-0.5 µm) was increased at high CORT levels between 400-1000 nM. The density of large-head spines (0.5-1.0 µm) was increased only at 1000 nM CORT. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR), abolished the effect of CORT. Blocking a single kinase, such as MAPK, PKA, PKC or PI3K, suppressed CORT-induced enhancement of spinogenesis. Blocking NMDA receptors suppressed the CORT effect. CONCLUSIONS/SIGNIFICANCE: These results imply that stress levels of CORT (100-1000 nM) drive the spinogenesis via synaptic GR and multiple kinase pathways