6623 research outputs found
Sort by
A tumor metastasis-associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity （TWIST1特異的ヘルパーT細胞の活性化を応用したがん免疫療法に関する研究）
Full text linkAlthough neoantigens are one of the most favorable targets in cancer immunotherapy, it is less versatile and costly to apply neoantigen-derived cancer vaccines to patients due to individual variation. It is, therefore, important to find highly immunogenic antigens between tumor-specific or associated antigens that are shared among patients. Considering the cancer immunoediting theory, immunogenic tumor cells cannot survive in the early phase of tumor progression including two processes: elimination and equilibrium. We hypothesized that highly immunogenic molecules are allowed to be expressed in tumor cells after an immune suppressive tumor microenvironment was established, if these molecules contribute to tumor survival. In the current study, we focused on TWIST1 as a candidate for highly immunogenic antigens because it is upregulated in tumor cells under hypoxia and promotes tumor metastasis, which is observed in the late phase of tumor progression. We demonstrated that TWIST1 had an immunogenic peptide sequence TWIST1140-162 , which effectively activated TWIST1-specific CD4+ T-cells. In a short-term culture system, we detected more TWIST1-specific responses in breast cancer patients compared with in healthy donors. Vaccination with the TWIST1 peptide also showed efficient expansion of TWIST1-reactive HTLs in humanized mice. These findings indicate that TWIST1 is a highly immunogenic shared antigen and a favorable target for cancer immunotherapy.博士（医学）旭川医科大
Pathophysiological Commonality Between Irritable Bowel Syndrome and Metabolic Syndrome: Role of Corticotropin-releasing Factor-Toll-like Receptor 4-Proinflammatory Cytokine Signaling
Full text linkThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Irritable bowel syndrome (IBS) displays chronic abdominal pain with altered defecation. Most of the patients develop visceral hypersensitivity possibly resulting from impaired gut barrier and altered gut microbiota. We previously demonstrated that colonic hyperpermeability with visceral hypersensitivity in animal IBS models, which is mediated via corticotropin-releasing factor (CRF)-Toll-like receptor 4 (TLR4)-proinflammatory cytokine signaling. CRF impairs gut barrier via TLR4. Leaky gut induces bacterial translocation resulting in dysbiosis, and increases lipopolysaccharide (LPS). Activation of TLR4 by LPS increases the production of proinflammatory cytokines, which activate visceral sensory neurons to induce visceral hypersensitivity. LPS also activates CRF receptors to further increase gut permeability. Metabolic syndrome (MS) is a cluster of cardiovascular risk factors, including insulin resistance, obesity, dyslipidemia, and hypertension, and recently several researchers suggested the possibility that impaired gut barrier and dysbiosis with low-grade systemic inflammation are involved in MS. Moreover, TLR4-proinflammatory cytokine contributes to the development of insulin resistance and obesity. Thus, the existence of pathophysiological commonality between IBS and MS is expected. This review discusses the potential mechanisms of IBS and MS with reference to gut barrier and microbiota, and explores the possibility of existence of a pathophysiological link between these diseases with a focus on CRF, TLR4, and proinflammatory cytokine signaling. We also review epidemiological data supporting this possibility, and discuss the potential of therapeutic application of the drugs used for MS to IBS treatment. This notion may pave the way for exploring novel therapeutic approaches for these disorders
保健師の個別支援における看護過程の課題 －アセスメント力向上を目指したアクションリサーチを通して－
Full text link本研究は保健師の個別支援における看護過程の課題を明らかにすることを目的とした．アクションリサーチのフィールド3地区で個別支援におけるアセスメント力向上を目指し，看護過程の講義と事例検討を２～４回行った．初回介入後にフォーカスグループインタビュー（FGI）を実施し新任期・中堅前期の保健師27名が参加した．３地区のFGIの複合分析から看護過程の課題10カテゴリを抽出した．アセスメントでは【地域での生活のイメージを広げられない】，【地域で暮らす家族の力を見極められない】，【判断の根拠となる情報が取れない】，【保健師自身が持つ価値観に当てはめて考えてしまう】，【一つひとつの情報をアセスメントし全体の統合が難しい】，診断では【今だけにフォーカスし時間軸で看護問題を捉えられない】，【その場でアセスメントしきれずニーズを特定できない】課題が挙げられた．これらの課題が，【ニーズが曖昧なまま試行錯誤し支援している】，【関係が途切れない介入の仕方への迷いがある】という真のニーズを捉えた支援を困難にし，【支援の方向性への確信が持てない】評価の課題へと看護過程全体に影響を及ぼすことが示唆された．
今後は，多面的な情報収集と自身の価値観から脱却した包括的アセスメントおよび看護問題を特定していく思考プロセスの獲得に向けた事例検討が必要と考える