14 research outputs found

    Maladie de Castleman: Localisation inhabituelle du thorax

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    La maladie de Castleman est une affection rare qui peut toucher le thorax. La localisation diaphragmatique est exceptionnelle. Nous rapportons le cas d’une patiente de 47 ans, chez qui une thoracotomie exploratrice a permis l’exérèse d’une masse du sinus médiastinal antérieur droit, en continuité avec le diaphragme et dont l’histologie est en faveur de la maladie de Castleman de type hyalino-vasculaire. Les particularités cliniques,radiologiques et évolutives ont été revues.Key words: Maladie de Castleman, localisation, thorax, exérèse, chirurgi

    PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function.

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    Expansion of antigen-experienced CD8+ T cells is critical for the success of tumour-infiltrating lymphocyte (TIL)-adoptive cell therapy (ACT) in patients with cancer1. Interleukin-2 (IL-2) acts as a key regulator of CD8+ cytotoxic T lymphocyte functions by promoting expansion and cytotoxic capability2,3. Therefore, it is essential to comprehend mechanistic barriers to IL-2 sensing in the tumour microenvironment to implement strategies to reinvigorate IL-2 responsiveness and T cell antitumour responses. Here we report that prostaglandin E2 (PGE2), a known negative regulator of immune response in the tumour microenvironment4,5, is present at high concentrations in tumour tissue from patients and leads to impaired IL-2 sensing in human CD8+ TILs via the PGE2 receptors EP2 and EP4. Mechanistically, PGE2 inhibits IL-2 sensing in TILs by downregulating the IL-2Rγc chain, resulting in defective assembly of IL-2Rβ-IL2Rγc membrane dimers. This results in impaired IL-2-mTOR adaptation and PGC1α transcriptional repression, causing oxidative stress and ferroptotic cell death in tumour-reactive TILs. Inhibition of PGE2 signalling to EP2 and EP4 during TIL expansion for ACT resulted in increased IL-2 sensing, leading to enhanced proliferation of tumour-reactive TILs and enhanced tumour control once the cells were transferred in vivo. Our study reveals fundamental features that underlie impairment of human TILs mediated by PGE2 in the tumour microenvironment. These findings have therapeutic implications for cancer immunotherapy and cell therapy, and enable the development of targeted strategies to enhance IL-2 sensing and amplify the IL-2 response in TILs, thereby promoting the expansion of effector T cells with enhanced therapeutic potential

    Anticancer Activity of 2α, 3α, 19β, 23β-Tetrahydroxyurs-12-en-28-oic Acid (THA), a Novel Triterpenoid Isolated from Sinojackia sarcocarpa

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    BACKGROUND: Natural products represent an important source for agents of cancer prevention and cancer treatment. More than 60% of conventional anticancer drugs are derived from natural sources, particularly from plant-derived materials. In this study, 2α, 3α, 19β, 23β-tetrahydroxyurs-12-en-28-oic acid (THA), a novel triterpenoid from the leaves of Sinojackia sarcocarpa, was isolated, and its anticancer activity was investigated both in vitro and in vivo. PRINCIPAL FINDINGS: THA possessed potent tumor selected toxicity in vitro. It exhibited significantly higher cytotoxicity to the cancer cell lines A2780 and HepG2 than to IOSE144 and QSG7701, two noncancerous cell lines derived from ovary epithelium and liver, respectively. Moreover, THA showed a dose-dependent inhibitory effect on A2780 ovary tumor growth in vivo in nude mice. THA induced a dose-dependent apoptosis and G2/M cell cycle arrest in A2780 and HepG2 cells. The THA-induced cell cycle arrest was accompanied by a downregulation of Cdc2. The apoptosis induced by THA was evident by induction of DNA fragmentation, release of cytoplasmic Cytochrome c from mitochondria, activation of caspases, downregulation of Bcl-2 and upregulation of Bax. CONCLUSION: The primary data indicated that THA exhibit a high toxicity toward two cancer cells than their respective non-cancerous counterparts and has a significant anticancer activity both in vitro and in vivo. Thus, THA and/or its derivatives may have great potential in the prevention and treatment of human ovary tumors and other malignancies

    がん化学療法を受けている療養者のセルフマネジメントに関する研究の動向と課題

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    【目的】外来で化学療法を受ける療養者が急増し, 症状マネジメントが療養の場である在宅に移行してい る. 看護者には対象者の能力を引き出し, 症状マネジメント力を高める支援が求められている. 本研究の目的 は, がん化学療法を受けている療養者のセルフマネジメントに関連する2002年から2006年までの原著論文 を分析し, 研究課題を明確にすることである. 【方法】「医学中央雑誌」を使用し,“化学療法”“通院治療” “セルフマネジメント”をキーワードに検索を行い, 研究デザイン, 方法, 内容の分析を行った. 【結果】 該当文献は35論文であり, 研究デザインは因子探索研究, 種類は質的研究が約60%を占めていた. 研究内容 は, 化学療法の副作用が療養者の身体, 心理・精神, 社会に与える影響とその対処の現象を明らかにした研究 が45.7%であり, 次いで, セルフマネジメントを促進する介入効果の研究25.7%であった. 家族を対象とした 研究やエビデンスレベルの高い研究は少ない状況であった. 【結語】心理・教育的介入, 家族およびソー シャルサポートを焦点としたエビデンスレベルの高い研究が必要であることが示唆された
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