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[
    {
      "Title": [
        [
          "替莫唑胺通过上调PD-L1促进GBM细胞的免疫逃逸。",
          "Temozolomide promotes immune escape of GBM cells via upregulating PD-L1."
        ]
      ],
      "Content": [
        [
          "多形性胶质母细胞瘤(GBM)是最常见的恶性原发性脑肿瘤,预后不良,目前有效的治疗策略仍然有限。",
          "Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor with poor prognosis, and currently effective therapeutic strategies are still limited."
        ],
        [
          "虽然替莫唑胺(TMZ)常用于GBM治疗,其作用机制已得到很好的表征,但其副作用需要全面研究。",
          "Although temozolomide (TMZ) is commonly used for GBM therapy and its mechanism was well characterized, while its side effects were required comprehensive investigation."
        ],
        [
          "在本研究中,我们发现TMZ攻击的GBM细胞强烈抑制激活的外周血单核细胞(PBMC)中的促炎细胞因子表达,这依赖于增强的CD274转录(编码PD-L1),但不依赖于其他免疫检查点,",
          "In the present study, we revealed that TMZ-challenged GBM cells strongly suppressed pro-inflammatory cytokines expression in activated periphery blood mononuclear cells (PBMC), which depended on enhanced transcription of CD274 (encoding PD-L1), but not other immune checkpoints,"
        ],
        [
          "例如CD276,HVEM和galectin-9。",
          "such as CD276, HVEM and galectin-9."
        ],
        [
          "此外,在TMZ处理的GBM细胞中,膜PD-L1的丰度也增加。",
          "Moreover, abundance of membranous PD-L1 was also increased in TMZ-treated GBM cells."
        ],
        [
          "当短发夹RNA(shRNA)敲低PD-L1表达时,TMZ处理的GBM细胞对PBMC的抑制作用变弱,表明PD-L1对TMZ处理的GBM细胞的免疫抑制能力至关重要。",
          "When PD-L1 expression was knocked down by short hairpin RNA (shRNA), inhibitory effect of TMZ-treated GBM cells on PBMC became weakened, suggesting that PD-L1 was crucial for immune inhibition capacity of TMZ-treated GBM cells."
        ],
        [
          "另外,放线菌素D在TMZ攻击后降低GBM细胞中的PD-L1表达,表明PD-L1诱导发生在转录水平。",
          "Additionally, actinomycin D reduced PD-L1 expression in GBM cells after TMZ challenge, indicating that PD-L1 induction occurred at transcriptional level."
        ],
        [
          "免疫印迹结果表明STAT3信号传导参与TMZ介导的PD-L1诱导,并且使用STAT3抑制剂VI或STAT3shRNA观察到PD-L1的减毒表达。",
          "The immunoblotting results demonstrated that STAT3 signaling was involved in TMZ-mediated PD-L1 induction, and attenuated expression of PD-L1 was observed using STAT3 inhibitor VI or STAT3 shRNA."
        ],
        [
          "最后,动物研究表明,TMZ和PD-1抗体疗法的组合强烈抑制肿瘤生长并实现GBM小鼠的存活率提高。",
          "Finally, the animal study showed that combination of TMZ and PD-1 antibody therapy strongly inhibited tumor growth and achieved the improved survival rate of GBM mice."
        ],
        [
          "因此,本研究揭示了经典化疗药物TMZ促进GBM细胞免疫逃逸,即使TMZ联合PD-1抗体治疗也未进一步提高复发性GBM患者的生存率,与传统治疗方法相比,而我们的动物研究提供了证据表明TMZ的组合",
          "Accordingly, this study revealed the classical chemotherapy drug TMZ promoted GBM cells immune escape, even TMZ combine with PD-1 antibody treatment not further improve survival ratio of recurrent GBM patients compared with traditional therapy methods, while our animal study provided evidence that combination of TMZ"
        ],
        [
          "和PD-1抗体是治疗GBM的一种有前景的方法,这些相互矛盾的结果表明,提高PD-1抗体的递送效率可以发挥强大的联合治疗效果。",
          "and PD-1 antibody was a promising way to treat GBM, these contradictory results indicate improving the PD-1 antibody delivery efficiency can exert strong combinational therapy outcomes."
        ]
      ],
      "UID": "31285949",
      "Date": "2019-07-11",
      "Links": {
        "pubmed": "31285949",
        "pmc": "PMC6610056"
      },
      "Authors": "Silu.Wang,Fuli.Yao,Xianghe.Lu,Qun.Li,Zhipeng.Su,Jong-Ho.Lee,Chengde.Wang,Linyong.Du",
      "JournalTitle": "American journal of cancer research"
    },
    {
      "Title": [
        [
          "对EGFR抑制的抗性机制揭示了人GBM中的代谢脆弱性。",
          "Mechanisms of resistance to EGFR inhibition reveal metabolic vulnerabilities in human GBM."
        ]
      ],
      "Content": [
        [
          "表皮生长因子受体基因(EGFR)的扩增代表胶质母细胞瘤(GBM)中最常见的遗传病变之一,然而,靶向该信号传导途径的疗法在临床上失败。",
          "Amplification of the epidermal growth factor receptor gene (EGFR) represents one of the most commonly observed genetic lesions in glioblastoma (GBM), however, therapies targeting this signaling pathway have failed clinically."
        ],
        [
          "在这里,使用人类肿瘤,原发性患者来源的异种移植物(PDX)和GBM的鼠模型,我们证明EGFR抑制导致肿瘤细胞的侵袭增加。",
          "Here, using human tumors, primary patient-derived xenografts (PDXs), and a murine model for GBM, we demonstrate that EGFR inhibition leads to increased invasion of tumor cells."
        ],
        [
          "此外,EGFR抑制剂处理的GBM表现出改变的氧化应激,增加的脂质过氧化作用和产生有毒的脂质过氧化产物。",
          "Further, EGFR inhibitor-treated GBM demonstrate altered oxidative stress, with increased lipid peroxidation, and generation of toxic lipid peroxidation products."
        ],
        [
          "确定具有升高的醛脱氢酶(ALDH)水平的肿瘤细胞亚群包含在EGFR抑制剂处理的GBM中观察到的显着比例的侵袭性细胞。",
          "A tumor cell subpopulation with elevated aldehyde dehydrogenase (ALDH) levels were determined to comprise a significant proportion of the invasive cells observed in EGFR inhibitor-treated GBM."
        ],
        [
          "我们对新诊断的GBM中ALDH1A1蛋白的分析显示,在69%(35/51)的病例中可检测到ALDH1A1表达,但肿瘤细胞的百分比相对较低。",
          "Our analysis of ALDH1A1 protein in newly diagnosed GBM revealed detectable ALDH1A1 expression in 69% (35/51) of the cases, but in relatively low percentages of tumor cells."
        ],
        [
          "对EGFR抑制剂治疗前后配对的人GBM的分析显示EGFR扩增的肿瘤中ALDH1A1表达增加(p <0.05,n = 13个肿瘤对),并且在鼠GBM中ALDH1A1-高克隆比ALDH1A1对EGFR抑制更具抗性。",
          "Analysis of paired human GBM before and after EGFR inhibitor therapy showed an increase in ALDH1A1 expression in EGFR-amplified tumors (p&lt;0.05, n=13 tumor pairs), and in murine GBM ALDH1A1-high clones were more resistant to EGFR inhibition than ALDH1A1"
        ],
        [
          "低克隆。",
          "-low clones."
        ],
        [
          "我们的数据将ALDH水平鉴定为具有高侵袭能力,改变的氧化应激和对EGFR抑制的抗性的GBM细胞的生物标志物,并揭示其抑制应限制GBM侵袭的治疗靶标。",
          "Our data identify ALDH levels as a biomarker of GBM cells with high invasive potential, altered oxidative stress, and resistance to EGFR inhibition, and reveal a therapeutic target whose inhibition should limit GBM invasion."
        ]
      ],
      "UID": "31270152",
      "Date": "2019-07-23",
      "Links": {
        "pubmed": "31270152",
        "pii": "1535-7163.MCT-18-1330",
        "doi": "10.1158/1535-7163.MCT-18-1330"
      },
      "Authors": "Andrew.McKinney,Olle R.Lindberg,Jane R.Engler,Katharine Y.Chen,Anupam.Kumar,Henry.Gong,Kan V.Lu,Erin F.Simonds,Timothy F.Cloughesy,Linda M.Liau,Michael.Prados,Andrew W.Bollen,Mitchel S.Berger,Joseph T C.Shieh,C David.James,Theodore P.Nicolaides,William H.Yong,Albert.Lai,Monika E.Hegi,William A.Weiss,Joanna J.Phillips",
      "JournalTitle": "Molecular cancer therapeutics"
    },
    {
      "Title": [
        [
          "替莫唑胺抗性原代GBM干细胞样细胞和复发性GBM的比较转录组学分析鉴定碳酸酐酶CA2基因作为抗性因子的上调。",
          "Comparative Transcriptomic Analysis of Temozolomide Resistant Primary GBM Stem-Like Cells and Recurrent GBM Identifies Up-Regulation of the Carbonic Anhydrase <i>CA2</i> Gene as Resistance Factor."
        ]
      ],
      "Content": [
        [
          "大约95%的胶质母细胞瘤(GBM)患者显示肿瘤复发,使他们的治疗选择有限,因为复发性肿瘤最常耐受一线化疗标准替莫唑胺(TMZ)。",
          "About 95% of patients with Glioblastoma (GBM) show tumor relapse, leaving them with limited therapeutic options as recurrent tumors are most often resistant to the first line chemotherapy standard Temozolomide (TMZ)."
        ],
        [
          "为了鉴定涉及TMZ抗性的分子途径,分离,表征和选择原代GBM干细胞样细胞(GSC)用于体外TMZ抗性。",
          "To identify molecular pathways involved in TMZ resistance, primary GBM Stem-like Cells (GSCs) were isolated, characterized, and selected for TMZ resistance in vitro."
        ],
        [
          "随后,进行RNA测序分析并显示在TMZ抗性干细胞样细胞中总共49个差异表达的基因(| log2倍变化|> 0.5并且调整的<p>  - 值<0.1)。",
          "Subsequently, RNA sequencing analysis was performed and revealed a total of 49 differentially expressed genes (|log2-fold change| &gt; 0.5 and adjusted <i>p</i>-value &lt; 0.1) in TMZ resistant stem-like cells compared"
        ],
        [
          "到他们匹配的DMSO对照细胞。",
          "to their matched DMSO control cells."
        ],
        [
          "在上调基因中,我们将碳酸酐酶2(CA2)鉴定为与胶质瘤恶性肿瘤和患者存活相关的候选基因。",
          "Among up-regulated genes, we identified carbonic anhydrase 2 (CA2) as a candidate gene correlated with glioma malignancy and patient survival."
        ],
        [
          "值得注意的是,我们描述了CA2不仅在TMZ抗性GSC中对mRNA和蛋白质水平的一致上调,而且在患者匹配的第一次出现和复发肿瘤的临床样本中也是如此。",
          "Notably, we describe consistent up-regulation of CA2 not only in TMZ resistant GSCs on mRNA and protein level, but also in patient-matched clinical samples of first manifest and recurrent tumors."
        ],
        [
          "与碳酸酐酶抑制剂乙酰唑胺(ACZ)共处理使细胞对TMZ诱导的细胞死亡敏感。",
          "Co-treatment with the carbonic anhydrase inhibitor Acetazolamid (ACZ) sensitized cells to TMZ induced cell death."
        ],
        [
          "累积地,我们的发现说明了CA2作为复发性GBM中的化学增敏靶标的潜力,并提供了治疗相关的抑制CA2以克服TMZ诱导的化学抗性的理论基础。",
          "Cumulatively, our findings illustrate the potential of CA2 as a chemosensitizing target in recurrent GBM and provide a rationale for a therapy associated inhibition of CA2 to overcome TMZ induced chemoresistance."
        ]
      ],
      "UID": "31262047",
      "Date": "2019-07-02",
      "Links": {
        "pubmed": "31262047",
        "pii": "cancers11070921",
        "doi": "10.3390/cancers11070921"
      },
      "Authors": "Ricarda.Hannen,Martin.Selmansberger,Maria.Hauswald,Axel.Pagenstecher,Andrea.Nist,Thorsten.Stiewe,Till.Acker,Barbara.Carl,Christopher.Nimsky,Jörg Walter.Bartsch",
      "JournalTitle": "Cancers"
    }
  ]


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