Novel Oral Derivative UD-017, a Highly Selective CDK7 Inhibitor, Exhibits Anticancer Activity by Inducing Cell-Cycle Arrest and Apoptosis in Human Colorectal Cancer

Objective: This study aimed to investigate the anticancer profile of a new cyclin-dependent kinase 7 (CDK7) inhibitor, UD-017, by examining its mechanism of action using HCT-116 colorectal cancer cells. Methods: The anticancer properties of UD-017 were assessed using several assays, including in vitro kinase, proliferation, and apoptosis assays, western blot analysis, and an in vivo xenograft mouse model. Results: UD-017 significantly inhibited CDK7 activity (IC50 = 16 nM) with high selectivity in an in vitro kinase assay testing a panel of over 300 proteins and lipid kinases. UD-017 also inhibited the growth of HCT-116 cells (GI50 = 19 nM) and inhibited the phosphorylation of various downstream mediators of CDK7 signaling. In cell cycle and apoptosis assays using HCT-116 cells, UD-017 increased the number of cells in both G1 and G2/M phases and induced apoptosis. In vivo, UD-017 inhibited tumor growth in an HCT-116 xenograft mouse model by 33%, 64%, and 88% at doses of 25, 50, and 100 mg/kg, respectively, with clear dose-dependency. Co-administration of 5-FU and 50 mg/kg UD-017 had a strong synergistic effect, as reflected in the complete inhibition of tumor growth. Conclusion: CDK7 may play a major role in colorectal cancer growth by regulating the cell cycle and apoptosis. UD-017 is a promising candidate therapeutic agent for the treatment of cancer involving CDK7 signaling

最重度知的障害をもつ対象者の自己選択に対する支援 : サービスに対する対象者の肯定的評価を「幸福の表情」から判断する試み

本研究の目的は,辛島らにより客観的測定道具としての妥当性が証明された「幸福の表情」の出現回数(静止画像の枚数)を測定することで,対象者が活動を自己選択する方法を示すことである.対象者は身体障害者療護施設に入所する27歳の女性である.物を操作する活動には関心をしめさず,嬉しいという肯定的表示は乏しい.方法は6つの活動(バイブレータ,グルグル回るおもちゃをみて楽しむあそび,バネのモビール,ぬいぐるみを投げてあそぶ(1),ぬいぐるみを投げて遊ぶ(2),ぬいぐるみを投げてあそぶ(3))を提示から感情の表示までを5秒間ビデオ撮影し,PCに接続させてDV gate stillにて0.5秒間隔で静止画像とした.判断者は5名で,それぞれの判断者は1活動につき10枚の静止画像から「幸福の表情」を判断し,それらの合計枚数を6つの活動で比較した.その結果,ぬいぐるみを投げてあそぶ(3)が20枚で,他の活動と比較し「幸福の表情」の出現が有意に多く(p<0.05),対象者は他の活動と比べてぬいぐるみ(3)に対して肯定的評価を強く示し,自己選択したと判断された.The purpose of this study is to demonstrate that a subject can present the method of self-choosing in activities, measuring how many times the subject\u27s \u27facial expressions of happiness\u27 occurs (the number of the still pictures), which Karashima, et al. has demonstrated its validity as a tool of objective measure. The subject is a 27 year-old female institutionalized at the facility for the disabled. The subject seldom shows her interest in operational activities and exhibits her positive expressions as happy. The method is that the scenes from 6 activities (operating a vibrator, operating a toy which rotates its part, operating a mobile, the activity of throwing a stuffed animal(1), the activity of throwing a stuffed animal(2), the activity of throwing a stuffed animal(3)) being presented to the subject were videotaped for 5 seconds to demonstrate her expression of emotion. Then, the still pictures were made every 0.5 seconds using DV gate still through PC. Five judges individually selected \u27facial expressions of happiness\u27 from 10 still pictures per each activity and compared the total number among 6 activities. The result shows that in the activity of throwing a stuffed animal(3) \u27facial expressions of happiness\u27 occurred significantly as 20 still pictures in total selected by the judges (p<0.05), compared to other 5 activities. It demonstrates that the subject evaluated the activity of throwing a stuffed animal(3) most positively and performed her self-choosing

最重度知的障害をもつ対象者の自己選択に対する支援 : サービスに対する対象者の肯定的評価を「幸福の表情」から判断する試み

本研究の目的は,辛島らにより客観的測定道具としての妥当性が証明された「幸福の表情」の出現回数(静止画像の枚数)を測定することで,対象者が活動を自己選択する方法を示すことである.対象者は身体障害者療護施設に入所する27歳の女性である.物を操作する活動には関心をしめさず,嬉しいという肯定的表示は乏しい.方法は6つの活動(バイブレータ,グルグル回るおもちゃをみて楽しむあそび,バネのモビール,ぬいぐるみを投げてあそぶ(1),ぬいぐるみを投げて遊ぶ(2),ぬいぐるみを投げてあそぶ(3))を提示から感情の表示までを5秒間ビデオ撮影し,PCに接続させてDV gate stillにて0.5秒間隔で静止画像とした.判断者は5名で,それぞれの判断者は1活動につき10枚の静止画像から「幸福の表情」を判断し,それらの合計枚数を6つの活動で比較した.その結果,ぬいぐるみを投げてあそぶ(3)が20枚で,他の活動と比較し「幸福の表情」の出現が有意に多く(p<0.05),対象者は他の活動と比べてぬいぐるみ(3)に対して肯定的評価を強く示し,自己選択したと判断された.The purpose of this study is to demonstrate that a subject can present the method of self-choosing in activities, measuring how many times the subject\u27s \u27facial expressions of happiness\u27 occurs (the number of the still pictures), which Karashima, et al. has demonstrated its validity as a tool of objective measure. The subject is a 27 year-old female institutionalized at the facility for the disabled. The subject seldom shows her interest in operational activities and exhibits her positive expressions as happy. The method is that the scenes from 6 activities (operating a vibrator, operating a toy which rotates its part, operating a mobile, the activity of throwing a stuffed animal(1), the activity of throwing a stuffed animal(2), the activity of throwing a stuffed animal(3)) being presented to the subject were videotaped for 5 seconds to demonstrate her expression of emotion. Then, the still pictures were made every 0.5 seconds using DV gate still through PC. Five judges individually selected \u27facial expressions of happiness\u27 from 10 still pictures per each activity and compared the total number among 6 activities. The result shows that in the activity of throwing a stuffed animal(3) \u27facial expressions of happiness\u27 occurred significantly as 20 still pictures in total selected by the judges (p<0.05), compared to other 5 activities. It demonstrates that the subject evaluated the activity of throwing a stuffed animal(3) most positively and performed her self-choosing

リハビリテーション医療系大学生における学業および大学生活適応尺度の作成

現在、高等学校卒業者のおよそ50%が大学へ進学している一方、休学・中退者の数は増え続けており、社会問題化している。文科省は休学・退学の要因として、高校と大学教育のギャップが生む『学業不振』を挙げている。必ずしも学業に重きをおかない、多様な価値観を持った学生のグローバル化が背景にある中、リハビリテーション医療系大学生は、一方で明確に学業をクリアすることを求められるという特徴がある。本研究の目的は、リハビリテーション医療系大学生を対象にした、学業および大学生活適応尺度を作成することである。作業療法学教員2名によって精選された35項目に対して、学生122名に反応を求めた。探索的因子分析の結果、感情・心理因子(6項目)、積極性因子(6項目)、適合感因子(4項目)、他者性因子(3項目)、自己対処因子(3項目)の5因子構造が得られた。信頼性に関しては,Cronbach α係数は高値を示し、因子間相関ではすべての因子間に有意な正の相関が見られ、一定の内的整合性、信頼性は保たれていた。Recently about 50 percent of the new graduates from high school enroll to university. However, the number of temporary absent or drop out students from university continue to grow up, and it becomes a social issue now. Ministry of Education, Culture, Sports, Science and Technology states that one of the factor of long term absence and dropping out from the university is poor academic performance that occurs from educational gap between high school and university . While the students with various senses of values are increasing, it\u27s important to give fixed academic performance for the student who try to be a rehabilitation related occupation. The purpose of this study is to develop the scale of relationship between academic performance and adaptation skill in university life for the OT students of Shijonawate&#8212;gakuen University.122 OT students were involved to answer the 35 questions which were selected by 2 OT teachers of the university. As a result of searching factor analysis, 5 factors which are consisted by feeling and psychological factor(6 items),initiative factor (6 items),feeling of conformity factor(4 items), other related factor(3 items) and self-cooping factors(3 items).The reliability by the Cronbach of coefficient shows high score and meaningful equilateral correlation among the factors also shows significantly high

若年認知症支援の会「愛都(アート)の会」の活動から作業療法士の役割を考える

若年認知症は老年期の認知症とは異なった特徴を持つが,社会的認知は低く利用可能なサービスが少ないのと同時に,患者は現状のサービス適応が困難である.そのため家族の介護負担は大きく,患者を取り巻く問題は複雑になる.このような中で,我々は,若年認知症支援の会「愛都の会」を発足させ,月に1回の頻度で,ミニ講演会と家族の交流会を開催し,並行してデイサービスを実施して,若年認知症患者の社会参加活動の支援を行っている.サポーターとしてボランティアで参加している作業療法士は,主にデイサービスでの援助を行っている.疾患や病期によって症状や行動が異なる若年認知症患者に対して,個々の状態を評価し,個別に適した活動や対応を選択するためにも,作業療法士が関わる意義は大きい.Early-onset dementia has characteristics that are different to those of late-onset dementia; for such patients, there are few services available at present to help adaptation. Therefore, the care burden falling on the patients family is big, and the problems surrounding the patient become complicated. We started a series of once a month meetings where we help early-onset dementia patients and families by holding a mini-lecture and interactions of families and in parallel carry out a day service that helps the social participation of early-onset dementia patients. Occupational therapists participate by a volunteer and do support by providing day service. The significance that an occupational therapist participates is great, and we evaluate the individual states of early-onset dementia patients finding that symptom and actions are different according to the disorder and stage of the disease, and we choose activities that are suitable for individuals

作業目標を効率よく達成する作業遂行が認知機能面に及ぼす影響

注意の制御能力の低下から作業活動の持続が困難な対象者には、作業活動の一部の工程の反復練習をおこなうことも治療的に意味がある. 注意の制御能力の低下の一因に、ワーキングメモリを要する機能が不活発な影響も関与しているのではないかと推察した. 本研究では、作業活動の一部の工程を反復した作業課題よりも幾つかの工程を積み重ねて作業遂行することでワーキングメモリに関与する機能の活発化を仮定した. 健常成人10名を対象に4工程からなる箱つくりと、工程の一部を反復した箱の展開図を繰り返し作成する作業課題をおこない、作業後のワーキングメモリ機能に着目した認知機能検査を比較検討した. 4工程を順番に実施する箱つくりにおいて、対象者自身で効率の良い動作を制御する機会が増え、記憶の保持と処理が並列的におこなわれたことからワーキングメモリの機能に着目した認知機能検査に影響を与えた.It is therapeutic to practice some processes of occupation action repeatedly to the subject that persistence of working action is difficult from degradation of ability for control of care, and there is a meaning. We speculated whether the mechanism which needed working memory in a cause of degradation of ability for control of care did not contribute to inanimate influence either. We supposed functional activation to contribute to working memory by we piled up some processes than the occupation problem that repeated some processes of working action by this study, and accomplishing occupation. We did an occupation problem we repeated development of the box which repeated a box structure comprising four processes and a portion of a process for ten normal adults, and to make, and comparison reviewed the cognitive function examination that paid its attention to working memory mechanism after occupation. The opportunities that controlled good movement of the efficiency of we increased by, subject oneself in a box structure to carry out four processes in turn, and mnemonic containment and disposal affected the cognitive function examination that paid its attention to mechanism of working memory from what was done multiply

利き手・非利き手での到達把持動作での予測的な戦略の検討 : Preshaping出現時点に着目して

本研究の目的は3つある. 一つは、健常成人を対象に、利き手・非利き手の到達把持動期間中のPreshaping出現時点の比較. 二つ目は、利き手と非利き手のSTEF遂行時間の比較. 3つ目はPreshaping出現時点とSTEF遂行時間の検討である. 結果、Preshaping出現時点は利き手が、非利き手よりも有意に遅延していた. STEF遂行時間では、利き手が非利き手よりも遂行時間が有意に速かった. また、これらPreshaping出現時点とSTEF遂行時間では負の相関を示した。利き手は、非利き手よりも運動経験が豊富であることから予測的なPreshaping出現が遅れていてもFeed-Forwardによる誤差が少なく、運動表出は円滑と行えていると考えられた. 非利き手では、運動経験が利き手よりも劣る為、Preshapingを早期に出現させ、視覚・体性感覚によるFeed-Backにより調整する必要が生じていることが考えられた.This study has three purposes. One examined the comparison at the Preshaping appearance time of the dominant hand and non-dominant hand. Two examined the comparison at the STEF accomplishment time of dominant hand and non-dominant hand. Three examined the Preshaping appearance time and elaborate operation capability, and relevance. In Pre-shaping, a dominant hand was more significantly than a non-dominant hand delayed. As for the STEF accomplishment time, dominant was significantly quicker in accomplishment time than a non-dominant hand. Preshaping appearance time and STEF execution time had negative correlation. With its dominant hand, just before contact was considered that it can perform movement processing smoothly from movement experience being abundant. With non-dominant hand, since movement experience was inferior to dominant hand, it was thought according to making Pre-shaping appear at an early stage that it was adjusting for vision and somatic sensation information