Epidermal growth factor receptor mutation in combination with expression of MIG6 alters gefitinib sensitivity

<p>Abstract</p> <p>Background</p> <p>Epidermal growth factor receptor (EGFR) signaling plays an important role in the regulation of cell proliferation, survival, metastasis, and invasion in various tumors. Earlier studies showed that the EGFR is frequently overexpressed in non-small-cell lung cancer (NSCLC) and EGFR mutations at specific amino acid residues in the kinase domain induce altered responsiveness to gefitinib, a small molecule EGFR tyrosine kinase inhibitor. However, the mechanism underlying the drug response modulated by EGFR mutation is still largely unknown. To elucidate drug response in EGFR signal transduction pathway in which complex dynamics of multiple molecules involved, a systematic approach is necessary. In this paper, we performed experimental and computational analyses to clarify the underlying mechanism of EGFR signaling and cell-specific gefitinib responsiveness in three H1299-derived NSCLC cell lines; H1299 wild type (H1299WT), H1299 with an overexpressed wild type EGFR (H1299EGFR-WT), and H1299 with an overexpressed mutant EGFR L858R (H1299L858R; gefitinib sensitive mutant).</p> <p>Results</p> <p>We predicted and experimentally verified that Mig6, which is a known negative regulator of EGFR and specifically expressed in H1299L858R cells, synergized with gefitinib to suppress cellular growth. Computational analyses indicated that this inhibitory effect is amplified at the phosphorylation/dephosphorylation steps of MEK and ERK.</p> <p>Conclusions</p> <p>Thus, we showed that L858R receptor mutation in combination with expression of its negative regulator, Mig6, alters signaling outcomes and results in variable drug sensitivity.</p

PARP Inhibitor PJ34 Suppresses Osteogenic Differentiation in Mouse Mesenchymal Stem Cells by Modulating BMP-2 Signaling Pathway

Poly(ADP-ribosyl)ation is known to be involved in a variety of cellular processes, such as DNA repair, cell death, telomere regulation, genomic stability and cell differentiation by poly(ADP-ribose) polymerase (PARP). While PARP inhibitors are presently under clinical investigation for cancer therapy, little is known about their side effects. However, PARP involvement in mesenchymal stem cell (MSC) differentiation potentiates MSC-related side effects arising from PARP inhibition. In this study, effects of PARP inhibitors on MSCs were examined. MSCs demonstrated suppressed osteogenic differentiation after 1 μM PJ34 treatment without cytotoxicity, while differentiation of MSCs into chondrocytes or adipocytes was unaffected. PJ34 suppressed mRNA induction of osteogenic markers, such as Runx2, Osterix, Bone Morphogenetic Protein-2, Osteocalcin, bone sialoprotein, and Osteopontin, and protein levels of Bone Morphogenetic Protein-2, Osterix and Osteocalcin. PJ34 treatment also inhibited transcription factor regulators such as Smad1, Smad4, Smad5 and Smad8. Extracellular mineralized matrix formation was also diminished. These results strongly suggest that PARP inhibitors are capable of suppressing osteogenic differentiation and poly(ADP-ribosyl)ation may play a physiological role in this process through regulation of BMP-2 signaling. Therefore, PARP inhibition may potentially attenuate osteogenic metabolism, implicating cautious use of PARP inhibitors for cancer treatments and monitoring of patient bone metabolism levels

カテイ ソウゴウ キョウカショ ニオケル セイカツ カダイ ノ トリアツカイ : ショクヒン ノ アンゼンセイ ショク ト エイヨウ イセイカツ ブンカ イフク ノ サイズ ヒョウジ ニ カンスル キジュツ ノ コウサツ

「家庭総合」教科書における生活課題の記述を検討し,今後改善すべき点をあげた。食品の安全性については食の安全性に関する新たな課題を取り上げること,食と栄養については高校生の食生活の実践を促すための具体例を,衣生活文化については実習例を多く取りあげること,サイズ表示に関しては的確な記述が求められる。The purpose of this study was to analyze subjects of living in Integrated Home Economics. The results were as follows: 1. The new subjects about safety of food are necessary to learn. 2. Food and nutrition have to be described with specific ezample to practice for high school students. 3. Culture of clothing life are necessary to learn with the practical lerarning. 4. The size indication of clothing have to be described accurately.国立情報学研究所『研究紀要公開支援事業』により電子化

天然染料による綿布の濃色で堅牢な染色

To improve the hypochromicity and fastness, the method of mordant dyeing of cotton fabric with six natural dyes was investigated. Combined utilizations of several metal salts for pre-mordanting, addition of some cationic surfactants to the pre-mordanting solution, pre-treatment of the fabric with oil of Turky red, control of pH of the dyeing solutions and duplicate mordanting with the same or different metal salts, resulted in the drastic progress. Effective methods were found for the improvements of the dyeings with ukon (Curcuma longa), madder(Rubia cordifolia) and leaf green extracts of Mulberry (Moru bonbeis) of the last of which main components were several chlorophills. Especially, leaf green extract was hypochromically and fastly dyed on cotton for the first time in the history of dyeing

「緩和ケアを推進する看護師教育プログラム」の評価 : 修了者およびその上司への調査から

京都府立医科大学医学部看護学科京都府立医科大学附属病院看護部京都府立医科大学看護実践キャリア開発センター京都府立医科大学附属病院地域医療推進部School of Nursing, Kyoto Prefectural University of MedicineDepartment of Nursing, University Hospital Kyoto Prefectural University of MedicineKyoto Prefectural University of Medicine, Career Development Center for NursingPromotion Division of Regional Medicine, University Hospital Kyoto Prefectural University of Medicine　本研究の目的は、「緩和ケア実践看護師養成コース（以下Aコース）」「在宅緩和ケア推進看護師養成コース（以下Bコース）」を受講した修了者とその上司への調査からプログラム評価および看護実践への活用状況を指標にしてプログラムを評価することである。【方法】平成27～31年度の間に京都府立医科大学看護実践キャリア開発センターが開催する「緩和ケアを推進する看護師教育プログラム」のAコースまたはBコースを受講した修了者25名のうち、調査時点で受講時と同じ施設・病院で就労を継続している21名（Aコース14名、Bコース7名）、とその上司21名（Aコース14名、Bコース7名）を研究対象者とした。修了生の施設・病院に質問紙を郵送し、令和3年7月～8月に無記名の自記式質問紙調査を行った。調査項目は、基本属性、カリキュラムについて、教育目標について、受講内容の適切性について、学習内容の臨床での活用について、とした。なお所属する大学の医学倫理審査委員会の承認を得て実施した（ERB-E-444）。【結果】回答者は、Aコース修了者9名、Aコース上司7名、Bコース修了者5名、Bコース上司3名であった。受講した修了者の評価においては、プログラムの内容についてAコースの8割以上が、Bコースの全員が（とても・まあまあ）適切としている。自己能力の発揮状況について、Aコースは4～6割、Bコースについては4～8割ができているとしている。　上司からの評価では、両コースとも受講した講義・演習・実習が7割程度現在の看護実践に役立っていると答えた。期待される能力については両コースとも8割以上が現在の看護活動に活きていると答えた。【結論】平成27年度から開始された「緩和ケアを推進する看護師教育プログラム」に対して、受講した修了者とその上司に，研修が有用であったかを問うたところ、受講した修了者はプログラムの内容が看護の実践で活かされていると実感していることが明らかとなった。さらに、上司は、受講した修了者が研修を踏まえた看護実践ができていると評価していることが明らかになった。修了者、上司の評価からプログラムの効果を評価することができた

セイジン カンゴガク ジッシュウ オヨビ ロウネン カンゴガク ジッシュウ ニオイテ カンゴガクセイ ガ ケンガク マタハ ジッシ シタ カンゴ キホン ギジュツ ノ ジッタイ ガクセイ ニヨル ジコヒョウカ チョウサ ノ ブンセキヨリ

看護系大学一校の成人看護学実習および老年看護学実習における看護学生の看護基本技術についてその見学または実施状況を明らかにし, 今後の講義・演習の内容や, 実習カリキュラムと実習施設, 実習指導の在り方等を検討するための基礎資料とすることを目的に, 文献等から選定した看護基本技術118項目の「見学」または「指導者の助言・監督下で実施」について調査した. 同大学で領域別看護学実習を履修した4年生のうち協力の得られた79名(回答率98.8%)のデータを分析した結果, 成人看護学実習・老年看護学実習の全般において, 環境整備, 清潔ケア, バイタルサイン測定, 病態・症状観察等の看護基本技術を見学または実施した学生が過半数を超えた. 一方, 呼吸, 排泄, 与薬, 救急, 症状・生体機能管理, 感染予防面の看護基本技術の見学または実施は, 全体の4分の1程度にとどまった. 学生が, 多様な治療を受ける患者の看護を学ぶことを通し, 臨地実習の場で見学や実施したことを振り返り, そして現象を関連付けて理解できる実習を編成することの重要性が示唆された.The purpose of this survey is to identify the current status of fundamental nursing skills performed by nursing students in adult and gerontological nursing practicums incorporated as part of a four-year baccalaureate nursing program. There were 118 survey items about fundamental nursing skills selected from the related literature. For each fundamental nursing skill the respondents were asked to answer, "have observed demonstration of this skill", "have performed this skill under the supervision of clinical nurse instructors" or "have not had any chance for observation or performance". Seventy-nine senior students (response rate: 98.8%) agreed to fill in and submit the survey sheet. The survey showed that more than half of the respondents had observed demonstration of, or had performed under supervision, such fundamental skills as management of the environment of care (cleanliness and safety of hospital beds and rooms), personal and hygiene care, vital sign measurement, assessment and monitoring of signs and symptoms in either adult or gerontological nursing practicum, or in both. In addition, about less than one-fourths of the respondents reported that they had observed demonstration of, or had performed under supervision, skills like respiratory care, elimination care, medication, monitoring and maintenance of vital functions and infection control. These results indicate the importance of arranging nursing practicums in such a way that students can learn a variety of nursing interventions and clinical skills in diverse care settings. Furthermore, nursing students need to be encouraged to learn through observation, performance under supervision and reflection so that they can understand the meaning of a variety of interconnected phenomena

Photochemistry of CS2/Cl complexes-combined pulse radiolysis-laser flash photolysis studies

Complexes of chlorine atoms and carbon disulfide (CS2) were produced by pulse radiolysis of CS2 in halocarbons and photochemical reactions were studied by laser flash photolysis. Excitation of CS2/Cl complexes resulted in rapid and permanent photobleaching. The photobleaching of CS2/Cl complexes is due to intermolecular chlorine atom abstraction in CCl4 with a quantum yield of 0.04, while that ascribed to hydrogen atom abstraction in 1,2-dichloroethane has a quantum yield of 0.21. The effects of additives are discussed based on the bond dissociation energy

Reaction of CS2/Cl complexes with alcohols studied by pulse radiolysis

The reactivity and selectivity of carbon disulfide-chlorine atom complex (CS2/Cl) for hydrogen atom abstraction from various alcohols were studied by pulse radiolysis technique in carbon tetrachloride at room temperature. The measured absolute rate constants were in the range from 4.0×106 for methanol to 3.5×107 dm3 mol−1 s−1 for cyclopentanol. The hydrogen abstraction selectivity was calculated based on the analysis of partial reactivities. The tertiary/primary selectivities were determined to be 8.2 for α-position and 6.8 for β-position of alcohols