Uterine Carcinosarcoma in a 2-year-old Female Wistar Hannover GALAS Rat

Carcinosarcomas are rare tumors in humans as well as rats and most commonly occur in the uterus. Recently, we observed a case of incidental carcinosarcoma of the uterus in a female Wistar Hannover GALAS [BrlHan:WIST@ Jcl (GALAS)] rat at 2 years of age. Histopathologically, the tumor was characterized by an admixture of malignant epithelial and nonepithelial elements. The carcinomatous components represented a type of endometrial carcinoma, consisting of glandular and solid proliferation of large-sized tumor cells. Prominent mitoses and tumor cell invasion were observed. The sarcomatous components were characterized by multifocal proliferation of severe atypical cells with cartilage matrix and were diagnosed as chondrosarcoma. Transitions between carcinomatous and sarcomatous components were observed, and many tumor cells in the solid lesion showed immunohistochemical reactivity with both cytokeratin and vimentin. Based on these findings, this tumor was diagnosed as a uterine carcinosarcoma. This is the first report of uterine carcinosarcoma in Wistar Hannover GALAS [BrlHan:WIST@Jcl (GALAS)] rats

Development of a Scheme and Tools to Construct a Standard Moth Brain for Neural Network Simulations

Understanding the neural mechanisms for sensing environmental information and controlling behavior in natural environments is a principal aim in neuroscience. One approach towards this goal is rebuilding neural systems by simulation. Despite their relatively simple brains compared with those of mammals, insects are capable of processing various sensory signals and generating adaptive behavior. Nevertheless, our global understanding at network system level is limited by experimental constraints. Simulations are very effective for investigating neural mechanisms when integrating both experimental data and hypotheses. However, it is still very difficult to construct a computational model at the whole brain level owing to the enormous number and complexity of the neurons. We focus on a unique behavior of the silkmoth to investigate neural mechanisms of sensory processing and behavioral control. Standard brains are used to consolidate experimental results and generate new insights through integration. In this study, we constructed a silkmoth standard brain and brain image, in which we registered segmented neuropil regions and neurons. Our original software tools for segmentation of neurons from confocal images, KNEWRiTE, and the registration module for segmented data, NeuroRegister, are shown to be very effective in neuronal registration for computational neuroscience studies

Integration of In Vivo Genotoxicity and Short-term Carcinogenicity Assays Using F344 gpt Delta Transgenic Rats: In Vivo Mutagenicity of 2,4-Diaminotoluene and 2,6-Diaminotoluene Structural Isomers

An important trend in current toxicology is the replacement, reduction, and refinement of the use of experimental animals (the 3R principle). We propose a model in which in vivo genotoxicity and short-term carcinogenicity assays are integrated with F344 gpt delta transgenic rats. Using this model, the genotoxicity of chemicals can be identified in target organs using a shuttle vector λ EG10 that carries reporter genes for mutations; short-term carcinogenicity is determined by the formation of glutathione S-transferase placenta form (GST-P) foci in the liver. To begin validating this system, we examined the genotoxicity and hepatotoxicity of structural isomers of 2,4-diaminotoluene (2,4-DAT) and 2,6-diaminotoluene (2,6-DAT). Although both compounds are genotoxic in the Ames/Salmonella assay, only 2,4-DAT induces tumors in rat livers. Male F344 gpt delta rats were fed diet containing 2,4-DAT at doses of 125, 250, or 500 ppm for 13 weeks or 2,6-DAT at a dose of 500 ppm for the same period. The mutation frequencies of base substitutions, mainly at G:C base pairs, were significantly increased in the livers of 2,4-DAT–treated rats at all three doses. In contrast, virtually no induction of genotoxicity was identified in the kidneys of 2,4-DAT–treated rats or in the livers of 2,6-DAT–treated rats. GST-P–positive foci were detected in the livers of rats treated with 2,4-DAT at a dose of 500 ppm but not in those treated with 2,6-DAT. Integrated genotoxicity and short-term carcinogenicity assays may be useful for early identifying genotoxic and nongenotoxic carcinogens in a reduced number of experimental animals

Decline in Left Ventricular Ejection Fraction during Follow-up in Patients with Severe Aortic Stenosis

Objectives: The aim of this study was to investigate the prognostic impact of the decline in left ventricular ejection fraction (LVEF) at 1-year follow-up in patients with severe aortic stenosis (AS) managed conservatively. Background: No previous study has explored the association between LVEF decline during follow-up and clinical outcomes in patients with severe AS. Methods: Among 3, 815 patients with severe AS enrolled in the multicenter CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry in Japan, 839 conservatively managed patients who underwent echocardiography at 1-year follow-up were analyzed. The primary outcome measure was a composite of AS-related deaths and hospitalization for heart failure. Results: There were 91 patients (10.8%) with >10% declines in LVEF and 748 patients (89.2%) without declines. Left ventricular dimensions and the prevalence of valve regurgitation and atrial fibrillation or flutter significantly increased in the group with declines in LVEF. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the group with declines in LVEF than in the group with no decline (39.5% vs. 26.5%; p 10% declines in LVEF at 1 year after diagnosis had worse AS-related clinical outcomes than those without declines in LVEF under conservative management. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140

Antiproliferative effect of a novel mTOR inhibitor temsirolimus contributes to the prolonged survival of orthotopic esophageal cancer-bearing mice

Esophageal squamous cell carcinoma (ESCC) remains one of the most aggressive cancers with poor prognosis regardless of a several reports that indicate a better therapeutic efficacy using some new chemotherapeutic agents. Recent drug development has contributed to an improved specificity to suppress mTOR activity by which many types of malignancies can be explosively progressed. Temsirolimus (CCI-779, TricelTM) is one of recently synthesized analogs of rapamycin and has provided better outcomes for patients with renal cell carcinoma. In this study, we experimentally evaluated an efficacy of targeting mTOR by temsirolimus for ESCC treatment, with an assessment of its survival advantage using an advanced ESCC animal model. First, we confirmed that the expression of phosphorylated mTOR was increased in 46 of 58 clinical ESCC tumor tissues (79.3%) and appeared to get strengthened with tumor progression. All of ESCC cell lines used in this study revealed an increase of mTOR phosphorylation, accompanied with the upregulation of hypoxia inducible factor-I alpha (HIF-1 alpha), one of the critical effectors regulated by mTOR. Temsirolimus treatment apparently suppressed the activation of mTOR and its downstream effectors, resulting in the reduced ability of ESCC cell proliferation. Finally, the weekly administration of temsirolimus significantly diminished the size of subcutaneous tumors (vehicle, 3261.6 +/- 722.0; temsirolimus, 599.2 +/- 122.9; p = 0.007) in nude mice and effectively prolonged orthotopic esophageal cancer-bearing mice (median survival periods: control, 31 d; temsirolimus, 43 d; p = 0.0024). These data suggests that targeting mTOR by temsirolimus may become a therapeutic alternative for esophageal cancer, with a contribution to a better outcome

The Plant Organelles Database 2 (PODB2): An Updated Resource Containing Movie Data of Plant Organelle Dynamics

The Plant Organelles Database (PODB) was launched in 2006 and provides imaging data of plant organelles, protocols for plant organelle research and external links to relevant websites. To provide comprehensive information on plant organelle dynamics and accommodate movie files that contain time-lapse images and 3D structure rotations, PODB was updated to the next version, PODB2 (http://podb.nibb.ac.jp/Organellome). PODB2 contains movie data submitted directly by plant researchers and can be freely downloaded. Through this organelle movie database, users can examine the dynamics of organelles of interest, including their movement, division, subcellular positioning and behavior, in response to external stimuli. In addition, the user interface for access and submission has been enhanced. PODB2 contains all of the information included in PODB, and the volume of data and protocols deposited in the PODB2 continues to grow steadily. Moreover, a new website, Plant Organelles World (http://podb.nibb.ac.jp/Organellome/PODBworld/en/index.html), which is based on PODB2, was recently launched as an educational tool to engage members of the non-scientific community such as students and school teachers. Plant Organelles World is written in layman's terms, and technical terms were avoided where possible. We would appreciate contributions of data from all plant researchers to enhance the usefulness of PODB2 and Plant Organelles World

Effects of Continuous Small Talk in Primary School Foreign Language Classes on Students' Speech Performance and Their Self-efficacy

departmental bulletin pape

Non-clinical studies for oncology drug development

Non-clinical studies are necessary at each stage of the development of oncology drugs. Many experimental cancer models have been developed to investigate carcinogenesis, cancer progression, metastasis, and other aspects in cancer biology and these models turned out to be useful in the efficacy evaluation and the safety prediction of oncology drugs. While the diversity and the degree of engagement in genetic changes in the initiation of cancer cell growth and progression are widely accepted, it has become increasingly clear that the roles of host cells, tissue microenvironment, and the immune system also play important roles in cancer. Therefore, the methods used to develop oncology drugs should continuously be revised based on the advances in our understanding of cancer. In this review, we extensively summarize the effective use of those models, their advantages and disadvantages, ranges to be evaluated and limitations of the models currently used for the development and for the evaluation of oncology drugs