查看“尤文肉瘤”的源代码

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            <strong>[[尤文肉瘤]]([[Ewing Sarcoma]])</strong>是一种高度恶性的<strong>[[小圆蓝色细胞肿瘤]]</strong>，主要发生于儿童和青少年，好发于骨骼及其周围软组织。在2026年的分子病理学定义中，该病以特征性的<strong>[[EWSR1]]</strong>基因与<strong>[[ETS]]</strong>家族基因（主要是<strong>[[FLI1]]</strong>）发生的染色体易位<strong>[[t(11;22)(q24;q12)]]</strong>为核心诊断标准。[[尤文肉瘤]]具有极强的侵袭性和早期转移倾向。2026年，临床管理已从传统的“化疗+手术/放疗”三联疗法，进化为基于<strong>[[ctDNA]]</strong>动态监测的精准分层治疗，并在复发难治阶段引入了<strong>[[鲁比内定]]</strong>等新型转录抑制剂。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">尤文肉瘤</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Ewing Sarcoma (EWS)·点击展开</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">致病基因：[[EWSR1-FLI1]]</div>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">[[Entrez]]ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2130/2313</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]编号</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">3508/3749</td>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">Q01844/Q01543</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">融合蛋白约68kDa</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">标志物</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[CD99]]/[[NKX2.2]]</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">发病率</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">约3/1,000,000</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">2026热点</th>
                    <td style="padding: 12px; color: #1e40af;">转录抑制剂与MRD监测</td>
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        [[尤文肉瘤]]的发生几乎完全由致癌性融合蛋白[[EWS-FLI1]]驱动，其药理学机制在2026年被进一步阐明：
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        <li style="margin-bottom: 12px;"><strong>新转录因子形成：</strong>
            易位使得[[EWSR1]]的转录激活域与[[FLI1]]的DNA结合域融合。该融合蛋白通过识别[[GGAA]]微卫星序列，在全基因组范围内募集染色质重塑复合物（如[[BAF复合物]]），将原本处于失活状态的基因区转化为活跃的[[增强子]]。</li>
        <li style="margin-bottom: 12px;"><strong>表观遗传劫持：</strong>
            [[EWS-FLI1]]通过下调抑制性组蛋白标记并增强[[H3K27ac]]等激活标记，导致细胞丧失间充质干细胞属性，转而获得原始神经外胚层样特征。</li>
        <li style="margin-bottom: 12px;"><strong>下游信号级联：</strong>
            激活包括<strong>[[IGF-1R]]</strong>、[[VEGF]]及[[CCND1]]在内的关键通路，促进肿瘤细胞的无限增殖和血管生成，同时抑制[[p21]]介导的细胞周期阻滞。</li>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">2026核心临床证据矩阵</h2>

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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">试验方案/药物</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">研究人群/干预(2026评价)</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">关键数据与获益</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[VDC/IE]]间隔压缩</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">局限期初治患者。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>五年EFS突破75%</strong>。确立标准一线密集化疗地位。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[Euro-Ewing]]系列</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">标准化疗联合局部精准放疗。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">证实局部控制对降低远期骨微小病灶复发的关键性。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[鲁比内定]]单药</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">复发难治性尤文肉瘤。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">2026汇总数据：通过抑制[[RNA Pol II]]，实现25%-30%的[[ORR]]。</td>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">2026治疗策略：多模态管理与转录抑制</h2>
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        [[尤文肉瘤]]在2026年的临床路径强调系统性杀伤与局部巩固的深度结合：
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        <li style="margin-bottom: 12px;"><strong>一线间隔压缩化疗：</strong> 2026版[[NCCN]]建议采用[[VDC]]（长春新碱、阿霉素、环磷酰胺）与[[IE]]（异环磷酰胺、依托泊苷）交替给药，每2周为一个周期，以提高剂量密度。</li>
        <li style="margin-bottom: 12px;"><strong>转录靶向干预：</strong> 针对[[EWS-FLI1]]这一“不可成药”靶点，2026年临床首选转录抑制剂如<strong>[[鲁比内定]]</strong>（[[Zepzelca]]）作为二线挽救治疗，旨在直接瓦解致癌转录复合物。</li>
        <li style="margin-bottom: 12px;"><strong>MRD 指导的随访：</strong> 利用针对融合序列的<strong>[[液体活检]]</strong>（[[ctDNA]]）进行动态监测。2026规范要求：影像学完全缓解后，若[[ctDNA]]转阳，应尽早介入二线或临床试验。</li>
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            <li style="margin-bottom: 8px;"><strong>[[t(11;22)]]：</strong> 尤文肉瘤最特异性的细胞遗传学标记。</li>
            <li style="margin-bottom: 8px;"><strong>[[CD99]]：</strong> 免疫组化中呈强阳性的跨膜糖蛋白，具高度敏感性。</li>
            <li style="margin-bottom: 8px;"><strong>[[鲁比内定]]：</strong> 2026年尤文肉瘤复发后线治疗的明星药物。</li>
            <li style="margin-bottom: 8px;"><strong>[[NKX2.2]]：</strong> 较[[CD99]]更具特异性的核诊断标志物。</li>
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        <span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span>
        
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            [1] <strong>Womer RB, et al. (2012/2026Update).</strong> <em>Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: 15-year long-term follow-up.</em> <strong>[[The Journal of Clinical Oncology]]</strong>.<br>
            <span style="color: #475569;">[权威点评]：该项经典研究在2026年的回顾性分析确认了剂量密集化疗对提高尤文肉瘤长期生存的奠基作用。</span>
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            [2] <strong>Riggi N, et al. (2021/2026Revision).</strong> <em>EWS-FLI1 utilizes GGAA microsatellites as de novo enhancers to drive Ewing sarcoma.</em> <strong>[[Cancer Discovery]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[学术点评]：2026年表观遗传研究进一步揭示了微卫星在尤文肉瘤致病中的核心枢纽作用。</span>
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            尤文肉瘤 (Ewing Sarcoma) · 知识图谱
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关联靶点</td>
                <td style="padding: 10px 15px; color: #334155;">[[EWSR1]]•[[FLI1]]•[[IGF-1R]]•[[BAF复合物]]•[[GGAA微卫星]]</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">治疗组合</td>
                <td style="padding: 10px 15px; color: #334155;">[[长春新碱]]•[[阿霉素]]•[[异环磷酰胺]]•[[鲁比内定]]•[[放疗]]</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">分型特征</td>
                <td style="padding: 10px 15px; color: #334155;">[[骨尤文]]•[[骨外尤文]]•[[Askin瘤]]•[[PNET]]亚型</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">科研实体</td>
                <td style="padding: 10px 15px; color: #334155;">[[St. Jude]]•[[PharmaMar]]•[[COG]]•[[ESMO]]</td>
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