α-Tocopheryl succinate stabilizes the structure of tumor vessels by inhibiting angiopoietin-2 expression

α-Tocopheryl succinate (TS) is a tocopherol derivative and has multifaceted anti-cancer effects; TS not only causes cancer cell-specific apoptosis but also inhibits tumor angiogenesis. Although TS has the potential to be used as a well-tolerated anti-angiogenic drug, it is still unclear which step of the angiogenic process is inhibited by TS. Here, we show that TS inhibits the expression of angiopoietin (Ang)-2, which induces destabilization of vascular structure in the initial steps of the angiogenic process. In mouse melanoma cells, TS treatment decreased mRNA and extracellular protein levels of Ang-2; however, the mRNA level of Ang-1, which stabilizes the vascular structure, remained unchanged. Furthermore, aorta ring and Matrigel plug angiogenesis assays indicated that the conditioned medium from TS-treated cells (CM-TS) inhibited neovascularization and blood leakage from the existing blood vessels, respectively. Following immunohistochemical staining of the vessels treated with CM-TS, imaging studies showed that the vascular endothelial cells were highly packed with pericytes. In conclusion, we found that TS inhibits Ang-2 expression and, consequently, stabilizes the vascular structure during the initial step of tumor angiogenesis

Pathobiology of Human Uterine Leiomyosarcoma for Development of Novel Diagnosis and Clinical Therapy

Uterine sarcomas comprise a group of rare tumours with differing tumour pathobiology, natural history and response to clinical treatment. Diagnosis is often made following surgical treatment for presumed malignant mesenchymal tumours and benign tumours. Currently pre-operative diagnosis does not reliably distinguish between malignant mesenchymal tumours, Uterine Leiomyosarcoma (U-LMS) and benign tumours including Leiomyomas (LMA). U-LMS is the most common sarcoma but other subtypes include endometrial stromal sarcoma (low grade and high grade), undifferentiated uterine sarcoma and adeno sarcoma. Clinical trials have shown no definite survival benefit for adjuvant radiotherapy or chemotherapy, and have been hampered by the rarity and heterogeneity of these tumour types. There is a role of adjuvant treatment in carefully selected cases following multidisciplinary discussion at U-LMS reference centres. In patients with metastatic LMS then systemic chemotherapy can be considered. Accordingly, it is necessary to analyse risk factors associated with human U-LMS, in order to establish a treatment method. Proteasome β-subunit 9 (PSMB9)/β1i-deficient mice spontaneously develop U-LMS, with a disease prevalence of ~37% by 12 months of age. We found PSMB9/β1i expression to be absent in human U-LMS, but present in human LMA. Therefore, defective PSMB9/β1i expression may be one of the risk factors for human U-LMS. PSMB9/β1i is a potential diagnostic-biomarker for human U-LMS, and may be targeted-molecule for a new therapeutic approach. Keywords: PSMB9/β1i; Diagnosis; Mesenchymal tumour; Leiomyosarcoma; Leiomyom

The somatic mutations in Interferon-γ signal molecules in human uterine leiomyosarcoma

Human uterine leiomyosarcoma (U-LMS) is neoplastic malignancy that typically arises in tissues of mesenchymal origin. The identification of novel molecular mechanism leading to human U-LMS formation and the establishment of new therapies has been hampered by several critical points. We earlier reported that mice with a homozygous deficiency for proteasome beta subunit 9 (Psmb9)/β1i, an interferon (IFN)-γ inducible factor, spontaneously develop U-LMS. The use of research findings of the experiment with mouse model has been successful in increasing our knowledge and understanding of how alterations, in relevant oncogenic, tumour suppressive, and signaling pathways directly impact sarcomagenesis. The IFN-γ pathway is important for control of tumour growth and invasion and has been implicated in several malignant tumours. In this study, experiments with human tissues revealed a defective expression of PSMB9/β1i in human U-LMS that was traced to the IFN-γ pathway and the specific effect of somatic mutations of JANUS KINASE (JAK) 1 molecule or promoter region on the locus cording PSMB9/β1i gene. Understanding the molecular mechanisms of human U-LMS may lead to identification of new diagnostic candidates or therapeutic targets against human U-LMS

Complete Genome Sequence of blaIMP–6-Positive Metakosakonia sp. MRY16-398 Isolate From the Ascites of a Diverticulitis Patient

A novel species of carbapenemase-producing Enterobacteriaceae (CPE) was isolated from a patient diagnosed with sigmoid colon diverticulitis. At first, laboratory testing suggested it was Klebsiella oxytoca or Pantoea sp.; however, a complete genome sequence of the isolate, MRY16-398, revealed that it could be novel species, most similar to [Kluyvera] intestini, of which taxonomic nomenclature is still under discussion. Orthologous conserved gene analysis among 42 related bacterial strains indicated that MRY16-398 was classified as the newly proposed genus Metakosakonia. Further, MRY16-398 was found to harbor the blaIMP-6 gene-positive class 1 integron (In722) in plasmid pMRY16-398_2 (IncN replicon, 47.4 kb in size). This finding implies that rare and opportunistic bacteria could be potential infectious agents. In conclusion, our results highlight the need for continuous monitoring for CPE even in nonpathogenic bacteria in the nosocomial environment

Potential role of LMP2 as an anti-oncogenic factor in human uterine leiomyosarcoma: Morphological significance of calponin h1

Uterine leiomyosarcoma (LMS) is a highly metastatic smooth muscle neoplasm for which calponin h1 is suspected to have a biological role as a tumor-suppressor. We earlier reported that LMP2-null mice spontaneously develop uterine LMS through malignant transformation of the myometrium, thus implicating this protein as an anti-tumorigenic candidate as well. In the present study, we show that LMP2 may negatively regulate LMS independently of its role in the proteasome. Moreover, several lines of evidence indicate that although calponin h1 does not directly influence tumorigenesis, it clearly affects LMP2-induced cellular morphological changes. Modulation of LMP2 may lead to new therapeutic approaches in human uterine LMS.ArticleFEBS LETTERS. 586(13):1824-1831 (2012)journal articl

Density of juvenile of tri-spine horseshoe crab Tachypleus tridentatus in the Sone Estuary, Kitakyushu, Japan, with notes on sediment particle sizes in habitats and breeding areas

2016年7月16–18日に福岡県北九州市曽根干潟においてカブトガニの幼体密度・成長段階組成および幼体生息場所・成体産卵場所の底質を調査した．また，海岸に打ち上げられたカブトガニ成体の遺骸のサイズおよび性についても調査した．貫川河口南に生息する幼体の前体幅は8.0–52.0mm (N=68)であった．カブトガニ幼体の密度は875個体/haであった．幼体の密度は岸側から沖に向かうほど著しく低下したが，底質の中央粒径値には差がほとんどみられなかった．打ち上げられた成体の遺骸55個体の前体幅を測定した結果，215.0–377.0mmであった．性比は雄40％，雌56％であり，残りの4％は雌雄を判別できなかった．遺骸には尾剣が折れた個体，卵が体内に残存している個体がみられた．曽根干潟の北方に位置する吉田海岸から南に位置する松山埋立地までの産卵に利用されている7地点の底質は中央粒径値が0.77–2.58mmの砂・礫であった．このことから，曽根干潟では粒径の大きい底質においても産卵が行われていることが明らかとなった．The density and composition of developmental stages of juveniles of the tri-spine horseshoe crab Tachypleus tridentatus (Leach, 1819) and sedimentary environment of juveniles' habitats and adults' breeding areas were investigated at the Sone tidal flat, Fukuoka Prefecture during 16 to 18 July, 2016. The sizes and sexes of dead adults beached on the shore were also examined. The carapace width of juveniles collected at the mouth of the Nuki River ranged from 8.0 to 52.0mm (N=68). The density of juveniles was about 875indiv./ha, with the density decreasing in the offshore direction. However, mean diameters of sedimentary particles did not differ considerably among five line transects set up from the inshore to offshore. The carapace width of beached dead adults ranged from 215.0 to 377.0mm (N=55) with sex proportions of 40% male, 56% female, and 4% unidentified. Some dead adults bore a broken tail spine or contained eggs in the bodies. Mean sizes of sedimentary particles at the seven breeding areas located along the inner part of the flat ranged 0.77 to 2.58mm, and tended to be more coarse than at other breeding areas in Japan.本研究は公益財団法人福武財団「平成28，29年度瀬戸内海文化研究・活動支援助成」によって行われたのでここに感謝を記す