Increased Rac1 activity and Pak1 overexpression are associated with lymphovascular invasion and lymph node metastasis of upper urinary tract cancer

<p>Abstract</p> <p>Background</p> <p>Lymphovascular invasion (LVI) and lymph node metastasis are conventional pathological factors associated with an unfavorable prognosis of urothelial carcinoma of the upper urinary tract (UC-UUT), but little is known about the molecular mechanisms underlying LVI and nodal metastasis in this disease. Rac1 small GTPase (Rac1) is essential for tumor metastasis. Activated GTP-bound Rac1 (Rac1 activity) plays a key role in activating downstream effectors known as Pak (21-activated kinase), which are key regulators of cytoskeletal remolding, cell motility, and cell proliferation, and thus have a role in both carcinogenesis and tumor invasion.</p> <p>Methods</p> <p>We analyzed Rac1 activity and Pak1 protein expression in matched sets of tumor tissue, non-tumor tissue, and metastatic lymph node tissue obtained from the surgical specimens of 108 Japanese patients with UC-UUT.</p> <p>Results</p> <p>Rac1 activity and Pak1 protein levels were higher in tumor tissue and metastatic lymph node tissue than in non-tumor tissue (both <it>P </it>< 0.0001). A high level of Rac1 activity and Pak1 protein expression in the primary tumor was related to poor differentiation (<it>P </it>< 0.05), muscle invasion (<it>P </it>< 0.01), LVI (<it>P </it>< 0.0001), and lymph node metastasis (<it>P </it>< 0.0001). Kaplan-Meier survival analysis showed that an increase of Rac1 activity and Pak1 protein was associated with a shorter disease-free survival time (<it>P </it>< 0.01) and shorter overall survival (<it>P </it>< 0.001). Cox proportional hazards analysis revealed that high Rac1 activity, Pak1 protein expression and LVI were independent prognostic factors for shorter overall and disease-free survival times (<it>P </it>< 0.01) on univariate analysis, although only Pak1 and LVI had an influence (<it>P </it>< 0.05) according to multivariate analysis.</p> <p>Conclusions</p> <p>These findings suggest that Rac1 activity and Pak1 are involved in LVI and lymph node metastasis of UC-UUT, and may be prognostic markers for this disease.</p

A Case of Multicentric Castleman's Disease Having Lung Lesion Successfully Treated with Humanized Anti-interleukin-6 Receptor Antibody, Tocilizumab

This report presents the case of a patient demonstrating multicentric Castleman's disease (MCD) with a lung lesion that was successfully treated with an anti-interleukin-6 receptor antibody, tocilizumab in combination with corticosteroid and tacrolimus. A 43-yr-old female with abnormal shadows on a chest X-ray was referred to the hospital for further examination. She was diagnosed as having MCD based on the characteristic pathology of inguinal lymph node, lung lesions, laboratory data, and undifferentiated arthritis. Corticosteroid and rituximab therapy did not fully ameliorate the symptoms; thus, the therapeutic regimen was changed to include tocilizumab, oral corticosteroid and tacrolimus. This regimen resulted in clinical remission and the dose of tocilizumab and corticosteroid could be tapered. Tocilizumab in combination with corticosteroid and tacrolimus may therefore be a beneficial treatment regimen for lung lesions associated with MCD

Research Activities in the Department of Occupational Therapy

Even though the purpose of the services provided by occupational therapy is to help and to support the daily life of clients, the actual services extend to a wide range of daily activities. Thus, research in occupational therapy covers a wide range of activities which can be modified and changed according to the needs of clients. Research activities conducted by clinical psychologists and English teachers who staff the Department of Occupational Therapy at Aino University are also summarized below. [1. Research in Occupational Therapy for Physically Handicapped.] We are involved in a study of the efficient motion analysis in the activity of daily life (ADL) in part with the staff of the Department of Clinical Engineering. We analyze the muscle tone under various locomotive operations by quantifying muscle tone with surface electro-myography (EMG). We have studied the brain network related to memory and learning in the training tasks that enable effective learning skills and their clinical application

High-dose Chemotherapy with Peripheral Blood Stem Cell Transplantation for Patients with Poor PrognosisAdvanced Germ Cell Tumor

SUMMARYAbout one half of all advanced germ cell tumor( GCT) patients with poor prognosis defined by the InternationalGerm Cell Cancer Collaborative Group (IGCCCG) die of cancer. We evaluated salvage high-dosechemotherapy (HDCT) with peripheral blood stem cell transplantation (PBSCT) for patients with poorprognosis advanced GCT in Dokkyo Medical University. Three patients with poor prognosis advanced GCTwere treated with HDCT as salvage chemotherapy. Two patients had primary testicular GCT and one patienthad primary mediastinal GCT. Treatment responses were pathological complete remission( CR) in one,surgical CR in one and partial remission (PR) in one. Effectiveness and side effects of HDCT with PBSCTfor poor prognosis cases with advanced GCT were shown in this study. However, further accumulation ofthese studies is needed

昭和南海地震震源域-四国沖～紀伊半島沖-の構造変化

BE12-54講演要旨 / ブルーアース2012（2012年3月22日～23日, 東京海洋大学品川キャンパス

Structural variation from off Shikoku to the Kii Peninsula related to various earhthquake phenomena

南海トラフで繰り返し発生する巨大地震の中には、東海・東南海・南海地震が連動して発生する超巨大地震のケースがあることが指摘されている。このような超巨大地震について、どのような場合に連動し、あるいは非連動性巨大地震となるのかを明らかにすることが必要である。連動型地震の滑り域の範囲がどこまで広がるかを見積もることが重要な課題であり、そのためには南海トラフから沈み込むフィリピン海プレートの形状およびプレート境界周辺の構造、地震活動に関する詳細かつ高精度な情報が必要である。また、南海地震単独で発生した場合についても、深部および浅部低周波地震発生域まで含めた正確な破壊の広がりの把握、複雑な破壊分布の原因を明らかにするために南海地震破壊域とその縁辺での地殻構造や地震活動は重要な情報となる。平成20年度は日向灘、平成21年度は四国沖で調査を実施し、平成22年度は調査海域を東方の紀伊半島沖まで拡大し、沈み込み帯の地殻構造、巨大地震の発生、地震活動の相互関係の解明を目的として、南海・地震破壊域における沈み込みに関する詳細な構造のイメージングおよび地震のアスペリティに関する構造を明らかにするためのデータの取得、および西南日本の付加体先端部付近で発生している低周波地震や微動を含む自然地震観測を実施した。 　本講演では、四国沖?紀伊半島沖の平成21~22年度の調査結果について述べる。平成21年10月、および平成22年10~11月、（独）海洋研究開発機構の海洋調査船「かいれい」によって短周期海底地震計各々180台と大容量チューンドエアガン（7800cu. in.)を用いた屈折法・広角反射法探査を実施した（図１）。海底地震計設置期間中に自然地震観測も実施した。四国沖では21観測点、紀伊半島沖では20観測点による約9ヶ月間の長期地震観測も実施した（一部実施中）。なお、本調査は文部科学省からの受託研究「東海・東南海・南海地震の連動性評価のための 調査観測・研究」の個別研究テーマ「南海トラフ域海域地震探査・地震観測」（平成20年度から受託）の一環として実施した。 　一部の調査測線の解析の結果、足摺岬沖から日向灘に向かって約6km/sの古い付加体を示す岩体の分布が海側に張り出していること、また、SK05の構造モデルによると、SK03とSK02の中間付近からSK01付近までの付加堆積物が極端に薄いことなど、トラフ平行方向に構造変化があることがわかり、破壊様式の違いに関係する構造ではないかと考えられる。また、測線延長上のHi-net陸上観測点のデータを加えた海陸統合解析を実施しており、これにより深部低周波地震現象と構造との関連性が明らかになると期待されるC11-10発表要旨, 日本地震学会2011年度秋季大会（2011年10月12日～15日, 静岡県静岡市

Prominent reflector beneath around the segmentation boundary between Tonankai-Nankai earthquake area

In the Nankai Trough subduction seismogenic zone, the Nankai and Tonankai earthquakes had often occurred simultaneously, and caused a great event. In most cases, first break of such large events of Nankai Trough usually begins from southwest off the Kii Peninsula so far. The idea of split Philippine Sea plate between the Kii Peninsula and the Shikoku Island, which explains seismicity, tectonic background, receiver function image and historical plate motion, was previously suggested. Moreover, between the Kii Peninsula and the Shikoku Island, there is a gap of deep low-frequency events observed in the belt-like zone along the strike of the subducting Philippine Sea plate. In 2010 and 2011, we conducted the large-scale high-resolution wide-angle and reflection (MCS) seismic study, and long-term observation from off Shikoku and Kii Peninsula. Marine active source seismic data have been acquired along grid two-dimensional profiles having the total length of ~800km/year. A three-dimensional seismic tomography using active and passive seismic data observed both land and ocean bottom stations have been also performed. From those data, we found a possible prominent reflector imaged in the offshore side in the Kii channel at the depth of ~18km. The velocity just beneath the reflector cannot be determined due to the lack of ray paths. Based of the amplitude information, we interpret the reflector as the forearc Moho based on the velocity gap (from ~6.4km/s to ~7.4km/s). However, the reflector is shallower than the forearc Moho of other area along the Nankai Trough. Similar reflectors are recognized along other seismic profiles around the Kii channel. In this presentation, we will show the result of structure analysis to understand the peculiar structure including the prominent reflector around the Kii channel. Relation between the structure and the existence of the segmentation of the Nankai megathrust earthquake or seismic gap of the deep low-frequency events will be also discussed. This study is part of 'Research concerning Interaction Between the Tokai, Tonankai and Nankai Earthquakes' funded by Ministry of Education, Culture, Sports, Science and Technology, Japan.Poster abstract T43C-2670 presented at 2013 Fall Meeting, AGU, San Francisco, Calif., 9-13 Dec