Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway

<p>Abstract</p> <p>Background</p> <p>Melanomas are highly malignant and have high metastatic potential; hence, there is a need for new therapeutic strategies to prevent cell metastasis. In the present study, we investigated whether statins inhibit tumor cell migration, invasion, adhesion, and metastasis in the B16BL6 mouse melanoma cell line.</p> <p>Methods</p> <p>The cytotoxicity of statins toward the B16BL6 cells were evaluated using a cell viability assay. As an experimental model, B16BL6 cells were intravenously injected into C57BL/6 mice. Cell migration and invasion were assessed using Boyden chamber assays. Cell adhesion analysis was performed using type I collagen-, type IV collagen-, fibronectin-, and laminin-coated plates. The mRNA levels, enzyme activities and protein levels of matrix metalloproteinases (MMPs) were determined using RT-PCR, activity assay kits, and Western blot analysis, respectively; the mRNA and protein levels of vary late antigens (VLAs) were also determined. The effects of statins on signal transduction molecules were determined by western blot analyses.</p> <p>Results</p> <p>We found that statins significantly inhibited lung metastasis, cell migration, invasion, and adhesion at concentrations that did not have cytotoxic effects on B16BL6 cells. Statins also inhibited the mRNA expressions and enzymatic activities of matrix metalloproteinases (MMPs). Moreover, they suppressed the mRNA and protein expressions of integrin α₂, integrin α₄, and integrin α₅and decreased the membrane localization of Rho, and phosphorylated LIM kinase (LIMK) and myosin light chain (MLC).</p> <p>Conclusions</p> <p>The results indicated that statins suppressed the Rho/Rho-associated coiled-coil-containing protein kinase (ROCK) pathways, thereby inhibiting B16BL6 cell migration, invasion, adhesion, and metastasis. Furthermore, they markedly inhibited clinically evident metastasis. Thus, these findings suggest that statins have potential clinical applications for the treatment of tumor cell metastasis.</p

Creation and use of a composite polyurethane-expanded polytetrafluoroethylene graft for hemodialysis access.

The Thoratec (Vectra) polyurethane vascular access graft (TPVA) is among the most recent additions to the list of materials used to construct prosthetic grafts for vascular access during hemodialysis. We give the TPVA very high marks, and recognize the utility of such a graft for use in hemodialysis. However, the strong elasticity of this graft can lead to unexpected complications after suturing. We devised a new surgical method using a TPVA-ePTFE (expanded polytetrafluoroethylene) composite graft, substituting the anastomosis section of the TPVA with a portion of ePTFE graft material, and have been able to overcome most of the TPVA's potential problems. We herein describe the technique.</p

A Research on a New Science Curriculum Development Based on ‘Nature Of Science’ Ⅲ : Reconstruction of a Coherence Science Curriculum from Elementary School to Upper Secondary School

本研究は，新しい科学観を取り入れた小学校から高等学校までの理科カリキュラムを開発することを目的としており，今年度は３年次にあたる。これまでの成果と課題をもとに，初等・中等教育で一貫して「科学の本質」を学ぶためのフレームワーク構築に向け，小学校から高等学校を通じて系統的に取り扱うことが可能な内容について検討を行った。 中学校における実践からは，理科教師が，科学者コミュニティーによる知，政策決定者や教師たちによる教えるべき知，児童・生徒の発達段階や文脈などを考慮した教える知，について可能な限り熟知する必要があることが示唆された。また，論証活動を行う際の，教師の振る舞い方も重要であることも明らかとなった。 また，小学校における実践では，学年による差異はあるものの，見たことや考えたことの違いを次第に意識化させることによって，観察や実験等のレポートの書き方の指導にも繋がることが明らかとなった。 以上の実践より，科学の本質を初等・中等教育で一貫して教えるためには，これまでの実践の視点の変容に基づく教師による授業方略の在り方や投げ込み的教材を使用する教師の意図が，いかに重要であるかを示唆している。This study develops a new science curriculum for elementary to upper secondary schools which include the concept of the “Nature of Science”. We examined possible content to build a systematic framework for mentioned above science education. The practice at junior high school shows that teachers should be familiar with scholarly knowledge, knowledge to be taught by the policy makers and teachers, and taught knowledge which students understand through learning along with the students’ ages and contexts. The teacher’s behavior in argumentation by pupils is also important. The practice at elementary school shows that perceptions of the crucial distinction between inference and observation lead students to write good reports. These practices exemplify that teaching Nature of Science consistently to elementary and lower secondary students should largely depend on the teachers’ methods of instruction and what material they develop from a new viewpoint

Elevated exhaled nitric oxide in anaphylaxis with respiratory symptoms

Background: Anaphylaxis is a serious type I allergic reaction that occurs suddenly and can result in death, but it is sometimes difficult to differentiate from other diseases, and physicians must rely on symptoms alone for its diagnosis. Meanwhile, fractional exhaled nitric oxide (FeNO) concentration, used in assessing airway inflammation in bronchial asthma, is known to be affected by atopic disposition. The possible role of FeNO measurements was evaluated in patients with anaphylaxis. Methods: FeNO was measured in 52 adult patients (17–78 years old, median age 41.5 years) in whom anaphylaxis occurred. These measurements were made within 24 h after onset and after about one month when the patients were symptom-free. In some of these patients, FeNO was measured a third time, two months or more after onset. Results: The FeNO level in the 52 patients was not significantly different in measurement made within 24 h of onset of anaphylaxis and after one month. However, excluding 9 patients who also had asthma history, the FeNO level in the remaining 43 patients decreased significantly from within 24 h of onset (36.7 ± 27.5 ppb) to one month later (28.8 ± 19.5 ppb). Of these 43 patients, this phenomenon was evident in a group that had respiratory symptoms (31 patients), but it was not seen in a group that did not have respiratory symptoms (12 patients). Conclusions: Elevation of FeNO was related to respiratory symptoms observed in anaphylactic patients without asthma. Although the mechanism of increased FeNO level is unclear, its usefulness for diagnosis of anaphylaxis must be examined in prospective studies

Comparative studies of irinotecan-loaded polyethylene glycol-modified liposomes prepared using different PEG-modification methods

AbstractRecently, a polyethylene glycol (PEG)-modification method for liposomes prepared using pH-gradient method has been proposed. The differences in the pharmacokinetics and the impact on the antitumor effect were examined; however the impact of PEG-lipid molar weight has not been investigated yet. The main purpose of this study is to evaluate the impact of PEG-lipid molar weight against the differences in the pharmacokinetics, the drug-release profile, and the antitumor effect between the proposed PEG-modification method, called the post-modification method, and the conventional PEG-modification method, called the pre-modification method. Various comparative studies were performed using irinotecan as a general model drug. The results showed that PEG-lipid degradation could be markedly inhibited in the post-modification method. Furthermore, prolonged circulation time was observed in the post-modification method. The sustained drug-release was observed in the post-modification method by the results of the drug-releasing test in plasma. Moreover, a higher antitumor effect was observed in the post-modification method. It was also confirmed that the same behaviors were observed in all comparative studies even though the PEG molecular weight was lower.In conclusion, the post-modification method has the potential to be a valuable PEG-modification method that can achieve higher preservation stability of PEG-lipid, prolonged circulation time, and higher antitumor effect with only half the amount of PEG-lipid as compared to the pre-modification method. Furthermore, it was demonstrated that PEG5000-lipid would be more desirable than PEG2000-lipid since it requires much smaller amount of PEG-lipid to demonstrate the same performances