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Corrigendum: Initial report of a clinical trial evaluating the safety and efficiency of neoadjuvant camrelizumab and apatinib in patients with recurrent high-grade gliomas: A prospective, phase II, single-arm study 更正:评估新辅助卡雷珠单抗和阿帕替尼治疗复发性高级别胶质瘤患者安全性和有效性的临床试验的初步报告:一项前瞻性II期单臂研究
Pub Date : 2022-07-01 DOI: 10.4103/glioma.glioma_19_22
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引用次数: 0
Associations of O6-methylguanine-DNA methyltransferase promoter methylation status with age and 1p/19q codeletion status in isocitrate dehydrogenase mutation gliomas based on an Asian cohort: A narrative review 基于亚洲队列的异柠檬酸脱氢酶突变胶质瘤O6甲基鸟嘌呤DNA甲基转移酶启动子甲基化状态与年龄和1p/19q共缺失状态的相关性:叙述性综述
Pub Date : 2022-07-01 DOI: 10.4103/glioma.glioma_25_22
Xu Wang, Mingzhi Han
The expression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) can lead to tumor cell resistance to alkylating agents. Glioblastomas with isocitrate dehydrogenase mutation (IDHmut) were reported to have significantly higher MGMT promoter methylation, which predicted improved outcomes after temozolomide treatment. However, the MGMT methylation status in IDHmut glioma remains controversial. To further explore the associations of MGMT promoter methylation status with other molecular features in IDHmut gliomas, in this work, we analyzed the relationship of MGMT promoter methylation status with 1p/19q codeletion status and age in IDHmut gliomas based on a large Asian (Chinese) cohort. We found that there was no significant difference in MGMT methylation status in IDHmut 1p/19q-codeleted oligodendrogliomas compared to IDHmut astrocytomas, in either primary or recurrent cases. Moreover, the MGMT methylation status was not associated with age. The difference compared to previous research which indicated the MGMT methylation status differed significantly among IDHmut glioma might be caused by differences between populations, indicating that routine assessment of MGMT methylation status in oligodendrogliomas may still be necessary.
DNA修复蛋白O6甲基鸟嘌呤DNA甲基转移酶(MGMT)的表达可导致肿瘤细胞对烷化剂的耐药性。据报道,具有异柠檬酸脱氢酶突变(IDHmut)的胶质母细胞瘤具有显著更高的MGMT启动子甲基化,这预示着替莫唑胺治疗后的预后改善。然而,在IDHmut神经胶质瘤中MGMT甲基化状态仍然存在争议。为了进一步探讨IDHmut胶质瘤中MGMT启动子甲基化状态与其他分子特征的关系,在这项工作中,我们基于一个大型亚洲(中国)队列分析了IDHmutt胶质瘤中的MGMT启动基因甲基化状态与其1p/19q共缺失状态和年龄的关系。我们发现,在原发性或复发性病例中,与IDHmut星形细胞瘤相比,IDHmut1p/19q编码的少突胶质瘤的MGMT甲基化状态没有显著差异。此外,MGMT甲基化状态与年龄无关。与先前的研究相比,这种差异表明IDHmut胶质瘤中的MGMT甲基化状态存在显著差异,这可能是由人群之间的差异引起的,这表明对少突胶质瘤中MGMT甲基状态的常规评估可能仍然是必要的。
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引用次数: 0
Brain metastases treated with CyberKnife and TomoTherapy: A report of three cases 射波刀联合断层疗法治疗脑转移瘤3例报告
Pub Date : 2022-07-01 DOI: 10.4103/glioma.glioma_23_22
Li Zhu, Y. Li, Xiangyu Kong, Anna Mu, Ye Zhang, Liping Chen, Xia Li
This study aimed to compare the safety and efficacy of CyberKnife (CK) versus TomoTherapy for the treatment of brain metastases (BMs). Three cases of BM treated at our hospital – two with CK and one with TomoTherapy – were compared and analyzed. Both treatments showed good therapeutic effects, but CK was more effective. No radiation-related adverse reactions were observed in the three patients. It is concluded that both CK and TomoTherapy can effectively control target lesions by allowing a higher dose in a single treatment while minimizing damage to surrounding normal brain tissue. This can reduce the total number of treatments needed, improve the prognosis of patients, and save medical resources.
本研究旨在比较CyberKnife(CK)与TomoTherapy治疗脑转移瘤(BM)的安全性和有效性。对在我院接受治疗的三例BM——两例采用CK,一例采用TomoTherapy——进行了比较和分析。两种治疗方法均显示出良好的疗效,但CK治疗效果更佳。三名患者均未观察到与辐射相关的不良反应。结论是,CK和TomoTherapy都可以通过在单一治疗中允许更高剂量来有效控制靶病变,同时最大限度地减少对周围正常脑组织的损伤。这可以减少所需的治疗总数,改善患者的预后,并节省医疗资源。
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引用次数: 0
Research progress of drug resistance mechanisms to temozolomide in glioblastoma: A narrative review 替莫唑胺在胶质母细胞瘤中的耐药机制研究进展
Pub Date : 2022-07-01 DOI: 10.4103/glioma.glioma_24_22
Allen Lu
Glioblastoma multiforme (GBM) is the most common malignant tumor in the adult central nervous system, and surgery combined with radiotherapy and chemotherapy represents the main treatment regimens. Temozolomide (TMZ) is currently the first-line chemotherapeutic agent used in GBM therapy and is widely used subsequent with surgical resection of GBM. TMZ can significantly prolong the survival time of patients with glioma. However, the high incidence of resistance to TMZ, which seriously affects the overall outcome of GBM treatment, is a serious concern facing clinicians. The mechanisms of resistance to TMZ in patients with GBM include biological processes involving DNA damage repair, cellular autophagy, glioma stem cells, and the tumor microenvironment. Therefore, exploring the mechanisms inducing GBM resistance to TMZ treatment and how to effectively reduce TMZ resistance and improve its efficacy has become an urgent question. This review summarizes the effects and mechanisms of TMZ resistance in the treatment of glioma. It is hoped that intensive investigation of the mechanisms of resistance of TMZ to GBM can lay the foundation for successful outcomes in patients with GBM.
多形性胶质母细胞瘤(GBM)是成人中枢神经系统最常见的恶性肿瘤,手术联合放化疗是主要的治疗方案。替莫唑胺(Temozolomide, TMZ)是目前GBM治疗的一线化疗药物,在GBM手术切除后广泛使用。TMZ能显著延长胶质瘤患者的生存时间。然而,TMZ的高耐药发生率严重影响GBM治疗的整体效果,是临床医生面临的一个严重问题。GBM患者对TMZ的耐药机制包括DNA损伤修复、细胞自噬、胶质瘤干细胞和肿瘤微环境等生物学过程。因此,探索GBM对TMZ耐药的机制,如何有效降低TMZ耐药,提高其疗效已成为迫切需要解决的问题。本文就TMZ耐药在胶质瘤治疗中的作用及机制作一综述。希望通过深入研究TMZ对GBM的耐药机制,为GBM患者的成功治疗奠定基础。
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引用次数: 0
Interactive relationship between neuronal circuitry and glioma: A narrative review 神经回路与神经胶质瘤的互动关系:叙述性综述
Pub Date : 2022-04-01 DOI: 10.4103/glioma.glioma_15_22
Jie Liu, Wei Shi, Yu Lin
Glioma is the most common primary central nervous system tumor. Despite extensive basic research on the tumor, the overall therapeutic effect of glioma remains unsatisfactory. Glioma grows within the framework of complex neural circuitry, which influences both neural network and tumor biology. On the one hand, the growth of gliomas continuously invades and destroys normal neural structures, which stimulate the dynamic remodeling of neural networks to maintain neural function. On the other hand, glioma can also induce neurons to form synaptic connections with it to promote tumor growth. Interventions targeting the interaction between gliomas and the neuronal circuitry provide opportunities for both tumor therapy and neuroplasticity at the same time. Noninvasive brain stimulation (NiBS) technology can actively regulate the excitability of targeted brain regions which can actively induce the remodeling of neural function and may perturb the interference of neuronglioma synapses. This article will review the interaction between gliomas and neural networks, including tumor-induced neuroplasticity, neuron-glioma synaptic connections, and the application and prospect of NiBS techniques.
胶质瘤是最常见的原发性中枢神经系统肿瘤。尽管对神经胶质瘤进行了广泛的基础研究,但神经胶质瘤的总体治疗效果仍不令人满意。胶质瘤生长在复杂神经回路的框架内,影响神经网络和肿瘤生物学。一方面,胶质瘤的生长不断侵袭和破坏正常的神经结构,刺激神经网络的动态重塑以维持神经功能。另一方面,胶质瘤还可以诱导神经元与其形成突触连接,促进肿瘤生长。针对胶质瘤和神经元回路之间相互作用的干预措施同时为肿瘤治疗和神经可塑性提供了机会。无创脑刺激(NiBS)技术可以主动调节靶向脑区的兴奋性,从而积极诱导神经功能的重塑,并可能干扰神经胶质瘤突触的干扰。本文将综述神经胶质瘤与神经网络的相互作用,包括肿瘤诱导的神经可塑性、神经胶质瘤突触连接以及NiBS技术的应用和前景。
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引用次数: 0
Cerebral CD1a positive Rosai–Dorfman disease with coexistent granulomatous angiitis: A case report 脑CD1a阳性Rosai-Dorfman病并发肉芽肿性脉管炎1例
Pub Date : 2022-04-01 DOI: 10.4103/glioma.glioma_9_22
S. Shinde, A. Shenoy
Rosai–Dorfman disease (RDD) is a nonneoplastic histiocytic proliferation. RDD is CD1a negative as opposed to Langerhans cell histiocytosis (LCH). The lesion was positive for CD1a immunohistochemistry in our RDD patient, suggesting an overlap with LCH. In addition, our case exhibited granulomatous angiitis (GA) on microscopy. We report the first triad of coexistent intracranial RDD-LCH-GA. A 30-year-old man presented with seizures, limb weakness, and violent behavior for 3 months. There was no fever, lymphadenopathy, or hepatosplenomegaly. Laboratory test results were normal. Radioimaging revealed an 8.6 cm × 7.4 cm × 3.2 cm mass in the parietotemporal lobe. It was hypointense on T1W1 and hypointense on T2W1, suggestive of glioma or tumefactive demyelination. A subtotal resection was performed. Histopathology exhibited mature lymphocytes, plasma cells, and histiocytes with emperipolesis. Vessels showed transmural granulomatous inflammation. Fungal and mycobacterial stains were negative. Immunohistochemistry revealed positivity for CD68, S100, and CD1a. The patient refused to undergo postoperative adjuvant radiotherapy. He remained asymptomatic for 6 months but was lost to follow-up thereafter. RDD-LCH concurrence may represent a clonal transformation in a common precursor histiocyte. Coexistent GA requires resection followed by steroid or cyclophosphamide therapy to prevent disease progression.
Rosai–Dorfman病(RDD)是一种非肿瘤性组织细胞增殖。RDD是CD1a阴性,与Langerhans细胞组织细胞增多症(LCH)相反。在我们的RDD患者中,病变的CD1a免疫组织化学阳性,表明与LCH重叠。此外,我们的病例在显微镜下表现出肉芽肿性血管炎(GA)。我们报告了颅内RDD-LCH-GA共存的第一个三联征。一名30岁的男子表现为癫痫发作、四肢无力和暴力行为长达3个月。没有发烧、淋巴结病或肝脾肿大。实验室检测结果正常。放射成像显示顶颞叶有8.6厘米×7.4厘米×3.2厘米的肿块。T1W1低强度,T2W1低强度提示神经胶质瘤或肿胀性脱髓鞘。进行了次全切除术。组织病理学表现为成熟淋巴细胞、浆细胞和组织细胞伴犬瘟热。血管显示透壁肉芽肿性炎症。真菌和分枝杆菌染色均为阴性。免疫组化显示CD68、S100和CD1a阳性。患者拒绝接受术后辅助放射治疗。他在6个月内一直没有症状,但随后失去了随访。RDD-LCH并发可能代表常见前体组织细胞中的克隆转化。共存的GA需要切除,然后进行类固醇或环磷酰胺治疗,以防止疾病进展。
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引用次数: 0
Postoperative radiotherapy with concomitant temozolomide plus anlotinib for newly diagnosed glioblastoma: Study protocol for a multicenter, double-blind, randomized phase II trial 术后放疗联合替莫唑胺加安洛替尼治疗新诊断的胶质母细胞瘤:一项多中心、双盲、随机II期试验的研究方案
Pub Date : 2022-04-01 DOI: 10.4103/glioma.glioma_17_22
Yuanyuan Chen, Baiqiang Dong, Guihong Liu, Pengfei Sun, Meihua Li, Xuejun Yang, Shiyu Feng, Liang-liang Wang, Y. Hua, Ming Zhao, Yanhui Liu, J. Ran, Lianlian Qiao, Xueguan Lu, Hao Jiang, Deqiang Mao, Junxin Wu, Xianming Li, Wei Zheng, Zhigang Liu, Song Lin, M. Deng, Qunying Yang, Chengcheng Guo, Jing Li, Zhongyan Chen
Background and Aim: Postoperative radiotherapy with concomitant temozolomide (TMZ) followed by ≤ six cycles of adjuvant TMZ chemotherapy (Stupp regimen) is the standard treatment for newly diagnosed glioblastoma (GBM); however, its effectiveness is limited. Anlotinib inhibits both tumor angiogenesis and tumor cell proliferation by targeting multiple kinases, and showing promising results in preclinical GBM models. We designed a Phase II trial to assess the efficacy and safety of the Stupp regimen plus anlotinib. Methods/Design: This is a multicenter, double-blind, randomized, placebo-controlled trial with an expected 150 patients randomly assigned 1:1 ratio to receive TMZ-based radiochemotherapy with anlotinib (Stupp regimen + anlotinib) or placebo (Stupp regimen + placebo). Postoperative patient recruitment will begin in July 2021, the analysis of primary outcome measures will be completed in July 2023, and the study will finish in July 2024. Major eligibility criteria include histologically confirmed newly diagnosed GBM and an Eastern Cooperative Oncology Group performance score ≤2. Other criteria for inclusion include age ≥18 years and lack of significant comorbidity. In this study, the primary endpoint will be the median progression-free survival (PFS). Secondary endpoints include 1-year overall survival rate, PFS at 6 months, overall response rate, duration of response, disease control rate, quality of life, and toxicity. The protocol has received approval from Sun Yat-sen University Cancer Center Ethics Committee (Approval No. B2021-073-01; approved on April 19, 2021). Discussion: Updated treatment modalities are required for newly diagnosed GBM. Our proposed treatment modality of the Stupp regimen combined with anlotinib therapy are waiting conclusion. Trial Registration: This study was registered with ClinicalTrials.gov under identifier NCT04959500 on July 13, 2021.
背景和目的:术后放疗伴用替莫唑胺(TMZ),然后≤6个周期的TMZ辅助化疗(Stupp方案)是新诊断的胶质母细胞瘤(GBM)的标准治疗方法;然而,它的有效性是有限的。安洛替尼通过靶向多种激酶抑制肿瘤血管生成和肿瘤细胞增殖,并在临床前GBM模型中显示出有希望的结果。我们设计了一项II期试验来评估Stupp方案加安洛替尼的疗效和安全性。方法/设计:这是一项多中心、双盲、随机、安慰剂对照试验,预计150名患者按1:1的比例随机分配,接受基于TMZ的安洛替尼放射化疗(Stupp方案+安洛替尼)或安慰剂(Stupp方案+安慰剂)。术后患者招募将于2021年7月开始,主要结果指标的分析将于2023年7月完成,研究将于2024年7月结束。主要资格标准包括组织学确诊的新诊断GBM和东部肿瘤协作组绩效得分≤2。纳入的其他标准包括年龄≥18岁和无明显合并症。在这项研究中,主要终点将是中位无进展生存期(PFS)。次要终点包括1年总生存率、6个月PFS、总有效率、反应持续时间、疾病控制率、生活质量和毒性。该方案已获得中山大学癌症中心伦理委员会的批准(批准号B2021-073-01;于2021年4月19日批准)。讨论:新诊断的GBM需要更新治疗方式。我们提出的Stupp方案联合安洛替尼治疗模式尚待结论。试验注册:本研究于2021年7月13日在ClinicalTrials.gov注册,标识符为NCT04959500。
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引用次数: 0
Overcoming T-cell exhaustion in glioblastoma: A narrative review 克服胶质母细胞瘤中的T细胞耗竭:叙述性综述
Pub Date : 2022-04-01 DOI: 10.4103/glioma.glioma_16_22
Xuya Wang, Xisen Wang, Jiabo Li
Immunotherapy is typically ineffective against glioblastoma (GBM) due to inherent and adaptive resistance. Initial immunotherapy results for GBM have been disappointing. In this regard, T-cell exhaustion is a major barrier to successful treatment. The recognition of exhausted CD8+ T cell (Tex) pedigree is currently undergoing a paradigm shift. This review introduces major findings in this field to provide an up-to-date perspective on epigenetic, transcriptional, metabolic, and spatial heterogeneity, as well as interactions with tumor microenvironment cells of anti-tumoral CD8+ Tex from the following aspects: (i) Epigenetic and transcriptional mechanisms underlying T-cell exhaustion, (ii) Metabolic factors underpinning T-cell exhaustion, (iii) Contribution of multiple cell types to T-cell exhaustion, (iv) Occurrence of T-cell exhaustion at multiple locations, and (v) T-cell exhaustion may not always be terminal. These novel insights afford a wide range of new therapeutic approaches to overcome T-cell exhaustion in GBM.
由于固有的和适应性的耐药性,免疫治疗通常对胶质母细胞瘤(GBM)无效。GBM的初步免疫治疗结果令人失望。在这方面,T细胞耗竭是成功治疗的主要障碍。对耗竭的CD8+T细胞(Tex)谱系的识别目前正在经历一个范式转变。这篇综述介绍了该领域的主要发现,从以下方面对表观遗传学、转录、代谢和空间异质性,以及抗肿瘤CD8+Tex与肿瘤微环境细胞的相互作用提供了最新的视角:(i)T细胞耗竭的表观遗传学和转录机制,(iii)多种细胞类型对T细胞耗竭的贡献,(iv)在多个位置发生T细胞耗竭,以及(v)T细胞耗竭可能并不总是终末的。这些新的见解为克服GBM中的T细胞耗竭提供了一系列新的治疗方法。
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引用次数: 0
Advanced modalities and surgical theories in glioma resection: A narrative review 胶质瘤切除术的先进模式和手术理论综述
Pub Date : 2022-04-01 DOI: 10.4103/glioma.glioma_14_22
Jiahe Guo, Yiming Li, Kai Zhang, Jiabo Li, Ping Liu, Hao-lang Ming, Yi Guo, Sheng-ping Yu
Surgical resection is the core of the comprehensive treatment of glioma. However, with infiltrative growth features, glioma often invades the surrounding area, making surgical resection more difficult. This review introduces relevant topics presented at the World Federation of Neurosurgical Societie Foundation Asian Congress of Neurological Surgeons (ACNS) Minimally Invasive Neurosurgery Web Seminar in 2022. First, we review assistive surgical techniques' characteristics, advantages, and disadvantages. Second, we summarize some state-of-the-art surgical views in glioma resection. Advanced modalities and surgical theories in glioma resection make better “maximum safe resection” achievable.
手术切除是胶质瘤综合治疗的核心。然而,胶质瘤具有浸润性生长特征,经常侵犯周围区域,使手术切除更加困难。这篇综述介绍了2022年世界神经外科学会联合会基金会亚洲神经外科医生大会(ACNS)微创神经外科网络研讨会上提出的相关主题。首先,我们回顾了辅助外科技术的特点、优点和缺点。其次,我们总结了一些最先进的神经胶质瘤切除术的观点。神经胶质瘤切除术的先进模式和手术理论可以实现更好的“最大限度安全切除”。
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引用次数: 0
The role of collagens in glioma: A narrative review 胶原在神经胶质瘤中的作用:综述
Pub Date : 2022-04-01 DOI: 10.4103/glioma.glioma_11_22
Yi Wang, Toshiya Ichinose, M. Nakada
Glioma is the most common brain tumor in the central nervous system and characterized by diffuse invasion into adjacent brain tissue. The extracellular matrix (ECM) is an essential component of the tumor microenvironment and it contributes to tumor progression through close interactions with glioma cells. Accumulated evidence has indicated that collagen levels, which are the most critical components of the ECM, are elevated in gliomas and collagen contributes to glioma progression. In this review, we provide a comprehensive summary of the roles of various collagens in glioma. A better understanding of the interactions of various collagens with glioma cells may provide new therapeutic strategies for gliomas.
胶质瘤是中枢神经系统中最常见的脑肿瘤,其特征是弥漫性侵犯邻近的脑组织。细胞外基质(ECM)是肿瘤微环境的重要组成部分,它通过与神经胶质瘤细胞的密切相互作用促进肿瘤进展。积累的证据表明,作为ECM最关键成分的胶原蛋白水平在胶质瘤中升高,胶原蛋白有助于胶质瘤的进展。在这篇综述中,我们对各种胶原蛋白在神经胶质瘤中的作用进行了全面的总结。更好地了解各种胶原与神经胶质瘤细胞的相互作用可能为神经胶质瘤的治疗提供新的策略。
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引用次数: 0
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Glioma
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