LATS1/2 kinases trigger self-renewal of cancer stem cells in aggressive oral cancer

Cancer stem cells (CSCs), which play important roles in tumor initiation and progression, are resistant to many types of therapies. However, the regulatory mechanisms underlying CSC-specific properties, including self-renewal, are poorly understood. Here, we found that LATS1/2, the core Hippo pathway-kinases, were highly expressed in the oral squamous cell carcinoma line SAS, which exhibits high capacity of CSCs, and that depletion of these kinases prevented SAS cells from forming spheres under serum-free conditions. Detailed examination of the expression and activation of LATS kinases and related proteins over a time course of sphere formation revealed that LATS1/2 were more highly expressed and markedly activated before initiation of self-renewal. Moreover, TAZ, SNAIL, CHK1/2, and Aurora-A were expressed in hierarchical, oscillating patterns during sphere formation, suggesting that the process consists of four sequential steps. Our results indicate that LATS1/2 trigger self-renewal of CSCs by regulating the Hippo pathway, the EMT, and cell division

Observations of hard X-rays of auroral origin with Polar Patrol Balloons No. 8 and 10

In the Polar Patrol Balloon (PPB) project, two balloons named PPB-8 and -10 were launched in rapid succession to form a cluster of balloons during their flight on January 13, 2003, from Syowa Station, Antarctica. In order to make the two-dimensional images for auroral X-rays and to obtain the energy spectra of auroras with energy range from 30 keV to 778 keV, the same instruments for hard X-rays were installed on PPB-8 and -10, respectively. These detection systems observed several auroral X-ray events during the flight. In particularly on January 25, 2003, strong auroral events were detected at about 0919 UT by PPB-10 and at 0927 UT by PPB-8. The aurora observed by PPB-10 was observed after about 8 min by PPB-8 located a 650 km west of PPB-10. The energy spectra of the bright aurora at 0919 UT and 0927 UT for PPB-10 and -8 is obtained as E0 = (78+-5) keV and (70+-5) keV, respectively

Biodistribution and Pharmacokinetics of O-Palmitoyl Tilisolol, a Lipophilic Prodrug of Tilisolol, after Intravenous Administration in Rats

The purpose of this study was to modify the biodistribution and pharmacokinetics of tilisolol, a β-blocker, using the palmitoyl prodrug approach. After intravenous administration of tilisolol and O-palmitoyl tilisolol in rats, drug concentrations were determined in blood, bile, urine, and several tissues. The concentration-time profiles of tilisolol and O-palmitoyl tilisolol were analyzed pharmacokinetically. The blood concentrations of O-palmitoyl tilisolol after intravenous administration of O-palmitoyl tilisolol were about 10-fold higher than those of tilisolol after intravenous administration of tilisolol. The biliary excretion rates of O-palmitoyl tilisolol and tilisolol after intravenous administration of O-palmitoyl tilisolol were about 10- to 100-fold larger than those of tilisolol after intravenous administration of tilisolol. In addition, the hepatic uptake clearance of O-palmitoyl tilisolol after intravenous administration of O-palmitoyl tilisolol was 3.6-fold higher than that of tilisolol after the intravenous administration of tilisolol. In the in vitro experiments, it was demonstrated that the distribution ratios between blood cells and plasma (blood/plasma) of O-palmitoyl tilisolol and tilisolol was 95.7 and 55.5%, respectively. These findings suggest that O-palmitoyl tilisolol exists as a binding form with biological components, especially blood cells, in systemic circulation. In conclusion, the palmitoyl prodrug approach is useful as a drug delivery system to deliver the parent drug to the liver

Analysis of Factors Hindering the Dissemination of Medical Information Standards

Many medical information standards are not widely used in Japan, and this hinders the promotion of the use of real-world data. However, the complex intertwining of many factors hindering the dissemination of medical information standards makes it difficult to solve this problem. This study analyzed and visualized relationships among factors that inhibit the dissemination of medical information standards. Five medical informatics experts affiliated with universities and hospitals were interviewed about the factors that hinder the dissemination of medical information standards in Japan. The presented factors were analyzed using the interpretive structural modeling (ISM) method and the decision-making trial and evaluation laboratory (DEMATEL) method. We found that legislation and reliability were important inhibiting factors for the dissemination of medical information standards in Japan. We also found a six-layered structure in which reliability was satisfied when legislation was in place and expectations and personal information were resolved. The DEMATEL analysis indicated the relationships and classifications of factors hindering the dissemination of medical information standards. Since the adoption of medical information standards does not directly lead to revenue for medical institutions, it is possible to meet the expectation of improving the quality of medical care by ensuring legislation and reliability, that is, ensuring the dependability of medical treatment. The results of this study visually show the structure of the factors and will help solve the problems that hinder the effective and efficient spread of standards. Solving these problems may support the efficient use of real-world data

CONSTRUCT AND USE INFORMATION-INTENSIVE SYSTEM(RADIATION/PARTICLE THERAPY DATABASE) BY USING STANDARD TECHNIQUE

Purpose of this system simplifies to manage information on radiation therapy for a long term consistently, case report, and extraction of treatment results number. Electronic Medical Record system(EMR) was replaced from a past CPOE system in October, 2006. Patients\u27 case history and passage information are entered to EMR. This time, EMR and AMIDAS were made to cooperate and it achieved new function to store information of Patient, radiation/particle therapy treatment, and follow-up automatically from EMR to AMIDAS. Furthermore, report that we developed a new web-based aggregate analysis system to manage radiation/particle therapy data stored in AMIDAS. National Institute of Radiological Sciences (NIRS) is a hospital located in Chiba and a single radiation department which has 100 beds and 200 outpatients daily. The diagnosis specialized in the radiation/particle therapy. In 1961, radiation therapy by X rays was begun at NIRS. In addition, particle therapy(carbon ion) was begun in 1994, and about 5,600 examples were treated by March, 2010. NIRS is a research institute, so disease information on radiation therapy, content of treatment, and information on prognosis are important information for a clinical research. History of radiation/particle therapy database system (AMIDAS: Advanced Medical Information Database System) was constructed in 1999, and operation was begun in 2000.HL7 was used for communicate EMR and AMIDAS. The firefox web browser was used for AMIDAS user-interface. AMIDAS achieved following three functions. 1)Function to complement details for treatment information which is not inputted by EMR. 2) Function to support report writer of heavy particle therapy executed twice a year. 3) Function to display calculated survival rate image by doctors\u27 interested grouping method. Kaplan-Meier method is adopted for computational method of survival rate curve. Numerical result was displayed on a browser as an image, it enabled to use it for secondary use. In addition, the significant difference authorization function by grouping that user had freely specified was added. The user becomes unnecessary the dual input of data by making EMR and AMIDAS cooperate, and an efficiency improvement of work and the accuracy improvement of data were able to be achieved. Moreover, AMIDAS improved user\u27s convenience, flexibility and able to extract at high speed for the aggregate of treatment data, making patient list, and authorization between groups(analysis between classification of stages and TNM classification value) for user\u27s interested points and different disease sites.ESTRO2

Development and Evaluation of PACS -a Parallel Operation System with Improved Fault-tolerance-

We developed the dual PACS to enforce the robustness and the redundancy. These PACSs were made by two different vendors. We assumed that we had to continue the service with-out serious problems. By the different systems, users can se-lect the suitable interface, and the systems become inevitable for the hospital information system.MEDINFO200

Experience of Transfer Work of PACS Image Data in Multivendor Environment

The Heavy Particle Medical Science Center, affiliated to the National Institute of Radiological Sciences, began archiving digital medical images from 1995, and launched film-less operation from August 2005. Then, in fiscal 2006, PACS was changed into the duplex configuration to upgrade the server equipment and avoid problems. Before starting system operation, the image data managed by the old image system were transferred to the new image management system. The applicable data were approximately 12 million images obtained from approximately 130,000 cases of examination, and the categories of modality were CR, CT, DR, ES, MR, NM, PET, RF, SC, US, XA, and OT. The data transfer work was completed in approximately three months using the Q/R connection of DICOM. We repeated a procedure which extracts images UID from both the source and destination systems after the transfer has finished, compares them with each other, surveys causes if any differences are found, corrects the data appropriately, and stores the data again. The primary cause of such differences was that the management method of images including the multi-frame type (especially on a per-examination basis) was different depending on the system.The 5th KOREA-JAPAN Joint Meeting on Medical Physic

The first Japanese implementation of IHE-ITI EUA/PSA and the Impact of Visual Integration

In Japan, two PCs (for example: EMR and PACS viewer) are commonly used for the Hospital Information System in one clinical unit. Many physicians have to enter a user ID and password to login to these systems. To solve the troublesome manipulation, we developed the function of the IHE-ITI En-terprise User Authentication (EUA) and Patient Synchronized Applications (PSA). We developed middle-ware for the EUA/PSA to reduce the implementation load among the EMR, PACS-viewer, report-viewer, radiation scheduling sys-tem and radiation information system. The EUA/PSA was based on the HL7 CCOW standard and did not support multi PCs. So we enhanced the EUA/PSA mechanism for use with several PCs. We realized that EUA/PSA were essential in a multi-system environment. Our middle-ware resolved the complexities of the application implementation. The estab-lished guideline was useful to unify the user interfaces of each application. We found that the EUA/PSA function will be inevitable for visual integration.MEDINFO200

Open Source Radiotherapy Viewer with Verification and Approval Function for DICOM-RT Object in IHE-RO Workflow

Learning Object:To understand the principal of the DICOM-RT object and the suitabledisplay methods for the dose distribution and beam data To understand a viewing function of DICOM-RT Objects and the IHE workflow of the radiotherapy To study how to confirm the radiation planning and the dose distribution of the target and issue the approvalAbstract:Purpose:To verify the dose distribution and treatment plan is very import and inevitable for a radiation oncologist. We developed the viewing software that can display the radiotherapy data (DICOM-RT Object) for a physician. The physician can issued the approval of the radiation plan by using this software.Methods:The software was written by the java and can be updated by the Java Web Start function in a hospital. We decide that this software is distributed under the open source criteria.Results:Physicians can easily display the DICOM-RT Object (RT image, RT plan and structure set) and also share the information. If he confirmed a treatment, he can change the approval status of the DICOM-RT Object.Discussion:Using this software, radiation oncologist can confirm the treatment plan and dose distribution quickly and issue the approval of the treatment with the DICOM approval module. This process conforms to the IHE-RO scheduled workflow that is investigated by the IHE-Japan RO group.RSNA\u2706 92th Scientific Assembly and Annual Meetin