brain tumors

脑肿瘤
  • 文章类型: Case Reports
    室管膜下巨细胞星形细胞瘤(SEGA)是良性的,生长缓慢,经常与结节性硬化症(TSC)相关的非侵袭性肿瘤。诊断前应仔细考虑肿瘤的位置和患者的年龄。考虑SEGA作为鉴别诊断,即使在没有TSC的成年患者中,是必不可少的。在目前的情况下,一名22岁男性出现进行性头痛,头晕,和模糊的视野。放射学检查证实了肿瘤的部位,甲状腺转录因子1在神经节细胞成分中呈阳性表达,随着TSC1和TSC2中缺乏种系突变,导致SEGA的最终诊断没有TSC。
    Subependymal giant cell astrocytomas (SEGAs) are benign, slow-growing, noninvasive tumors frequently associated with the tuberous sclerosis complex (TSC). The tumor\'s location and the patient\'s age should be considered carefully before diagnosis. Considering SEGA as a differential diagnosis, even in adult patients without TSC, is essential. In the present case, a 22-year-old male presented with a progressive headache, dizziness, and blurring of vision. Radiological investigations confirmed the site of the tumor, and a positive expression of thyroid transcription factor 1 in the ganglion cell component, along with the absence of germline mutation in TSC1 and TSC2, led to the final diagnosis of SEGA without TSC.
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  • 文章类型: Journal Article
    胶质母细胞瘤(GBM)是一种严重的脑肿瘤,致死率高。它生长迅速,大多数时候导致对传统治疗如化疗和放疗和手术的抵抗。生物多样性,除了代表人类福祉的重要资源之外,提供了几种天然化合物,显示出作为抗癌药物的巨大潜力。其中许多正在被广泛研究,并通过降低增殖率显着减慢GBM的进展,迁移,和炎症,也通过调节氧化应激。这里,一些天然化合物的使用,比如葱葱,succisapratensis,还有Dianthus超级巴士,被探索以解决GBM;他们展示了他们对细胞数量减少的影响,部分由细胞周期静止给出。此外,据报道,细胞迁移能力降低,通过形态细胞骨架的变化来完成,这甚至突出了间质-上皮转化。此外,代谢研究显示诱导的细胞氧化应激调节和大量的代谢重排。因此,研究人员提出了一种新的治疗选择,以克服常规治疗的局限性,从而改善患者的预后.
    Glioblastoma (GBM) is a severe form of brain tumor that has a high fatality rate. It grows aggressively and most of the time results in resistance to traditional treatments like chemo- and radiotherapy and surgery. Biodiversity, beyond representing a big resource for human well-being, provides several natural compounds that have shown great potential as anticancer drugs. Many of them are being extensively researched and significantly slow GBM progression by reducing the proliferation rate, migration, and inflammation and also by modulating oxidative stress. Here, the use of some natural compounds, such as Allium lusitanicum, Succisa pratensis, and Dianthus superbus, was explored to tackle GBM; they showed their impact on cell number reduction, which was partially given by cell cycle quiescence. Furthermore, a reduced cell migration ability was reported, accomplished by morphological cytoskeleton changes, which even highlighted a mesenchymal-epithelial transition. Furthermore, metabolic studies showed an induced cell oxidative stress modulation and a massive metabolic rearrangement. Therefore, a new therapeutic option was suggested to overcome the limitations of conventional treatments and thereby improve patient outcomes.
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  • 文章类型: Journal Article
    接受脑肿瘤手术切除的患者经常表现出一系列的血液动力学波动,需要仔细的液体管理。本研究旨在评估流体反应性动态预测因子的可行性,例如deltadown(DD),主动脉流速时间积分变异性(VTIAoV),上腔静脉塌陷指数(SVCCI),接受脑肿瘤神经外科手术的患者。
    在这项前瞻性研究中,纳入了30例计划接受选择性神经外科手术切除脑肿瘤的患者。生命体征的基线测量,麻醉参数,和研究变量在诱导后记录。随后,患者在20分钟内接受了10mL/kg胶体的液体推注,并在加载后重复测量。数据表示为平均值±标准偏差。正态分布的连续变量使用学生t检验进行比较,P<0.05被认为具有统计学意义。使用Pearson系数分析(r)评估变量对液体反应性的预测能力。
    在30名患者中,22人被确定为体积响应者(R),8人是无应答者(NR)。DD>5mmHg有效区分R和NR(P<0.001),具有良好的预测能力(r=0.759)。SVCCI>38%的R与NR(P<0.001),具有良好的可预测性(r=0.994)。同样,VTIAov>20%也是一个很好的预测因子(P<0.05;r=0.746)。
    我们的研究表明,大多数接受脑肿瘤手术切除的患者表现出液体反应性。在评估的变量中,SVCCI>38%是一个很好的预测指标,其次是VTIAoV>20%和DD>5mmHg,用于评估该人群的体液状态。
    UNASSIGNED: Patients undergoing surgical resection of brain tumors frequently exhibit a spectrum of hemodynamic fluctuations necessitating careful fluid management. This study aimed to evaluate the feasibility of dynamic predictors of fluid responsiveness, such as delta down (DD), aortic velocity time integral variability (VTIAoV), and superior vena cava collapsibility index (SVCCI), in patients undergoing neurosurgery for brain tumors.
    UNASSIGNED: In this prospective study, 30 patients scheduled to undergo elective neurosurgery for brain tumor resection were enrolled. Baseline measurements of vitals, anesthetic parameters, and study variables were recorded post-induction. Subsequently, patients received a fluid bolus of 10 mL/kg of colloid over 20 min, and measurements were repeated post-loading. Data were presented as mean ± standard deviation. The normally distributed continuous variables were compared using Student\'s t-test, with P < 0.05 considered statistically significant. The predictive capability of variables for fluid responsiveness was assessed using Pearson\'s coefficient analysis (r).
    UNASSIGNED: Of the 30 patients, 22 were identified as volume responders (R), while eight were non-responders (NR). DD >5 mmHg effectively distinguished between R and NR (P < 0.001), with a good predictive ability (r = 0.759). SVCCI >38% differentiated R from NR (P < 0.001), with excellent predictability (r = 0.994). Similarly, VTIAoV >20% was also a good predictor (P < 0.05; r = 0.746).
    UNASSIGNED: Our study revealed that most patients undergoing surgical resection of brain tumors exhibited fluid responsiveness. Among the variables assessed, SVCCI >38% emerged as an excellent predictor, followed by VTIAoV >20% and DD >5 mm Hg, for evaluating fluid status in this population.
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  • 文章类型: Journal Article
    精确评估脑肿瘤的血管异质性对诊断至关重要。分级,预测进展,指导治疗决策。然而,目前,高分辨率成像方法明显短缺。在这里,我们建议使用极简右旋糖酐修饰的Fe3O4纳米粒子(Dextran@Fe3O4NPs)进行对比增强的磁敏感加权成像(CE-SWI),用于脑肿瘤血管的超高分辨率标测.右旋糖酐@Fe3O4NP是在室温下通过简单的共沉淀方法制备的,并表现出小的流体动力学尺寸(28nm),良好的溶解性,优异的生物相容性,和高横向弛豫率(r2*,在9.4T磁场下159.7mM-1s-1)。Dextran@Fe3O4NP增强的SWI可以将脑血管的对比度噪声比(CNR)提高到注射前的2.5倍,并实现了直径小至0.1mm的微血管的超高空间分辨率可视化。这种先进的成像能力不仅可以对扩大的肿瘤周围引流血管和肿瘤内微血管进行详细的标测,而且还有助于在带有C6细胞的大鼠胶质母细胞瘤模型中灵敏地成像检测血管通透性恶化。我们提出的Dextran@Fe3O4NPs增强的SWI为脑肿瘤的精确治疗提供了强大的成像技术,具有巨大的临床翻译潜力。
    The precise assessment of vascular heterogeneity in brain tumors is vital for diagnosing, grading, predicting progression, and guiding treatment decisions. However, currently, there is a significant shortage of high-resolution imaging approaches. Herein, we propose a contrast-enhanced susceptibility-weighted imaging (CE-SWI) utilizing the minimalist dextran-modified Fe3O4 nanoparticles (Dextran@Fe3O4 NPs) for ultrahigh-resolution mapping of vasculature in brain tumors. The Dextran@Fe3O4 NPs are prepared via a facile coprecipitation method under room temperature, and exhibit small hydrodynamic size (28 nm), good solubility, excellent biocompatibility, and high transverse relaxivity (r2*, 159.7 mM-1 s-1) under 9.4 T magnetic field. The Dextran@Fe3O4 NPs-enhanced SWI can increase the contrast-to-noise ratio (CNR) of cerebral vessels to 2.5 times that before injection and achieves ultrahigh-spatial-resolution visualization of microvessels as small as 0.1 mm in diameter. This advanced imaging capability not only allows for the detailed mapping of both enlarged peritumoral drainage vessels and the intratumoral microvessels, but also facilitates the sensitive imaging detection of vascular permeability deterioration in a C6 cells-bearing rat glioblastoma model. Our proposed Dextran@Fe3O4 NPs-enhanced SWI provides a powerful imaging technique with great clinical translation potential for the precise theranostics of brain tumors.
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  • 文章类型: Journal Article
    血脑屏障(BBB)是一个选择性的半渗透层,至关重要的是保护大脑免受外部病原体和有毒物质的侵害,同时保持离子稳态和充足的营养供应。然而,这对药物穿透BBB以有效靶向脑肿瘤提出了重大挑战。磁共振引导激光间质热疗法(MRg-LITT)是一种微创技术,可利用热能烧灼颅内病变,有可能暂时破坏BBB。这进一步打开了可能的治疗窗口以增强患者结果。这里,我们回顾了MRg-LITT对BBB和血肿瘤屏障(BTB)的影响以及BBB破坏的持续时间。研究表明,MRg-LITT由于其微创性质而有效,精确的肿瘤靶向,并发症发生率低。尽管中断持续时间因研究而异,平均中断高峰在消融后的最初两周内,随后呈现逐渐下降.然而,需要对随访时间延长的较大群体进行进一步研究,以更准确地确定中断持续时间.此外,评估毒性和淋巴系统的破坏对于规避与该程序相关的潜在风险至关重要.
    The blood-brain barrier (BBB) is a selectively semi-permeable layer, crucial in shielding the brain from external pathogens and toxic substances while maintaining ionic homeostasis and sufficient nutrient supply. However, it poses a significant challenge for drugs to penetrate the BBB in order to effectively target brain tumors. Magnetic resonance-guided laser interstitial thermal therapy (MRg-LITT) is a minimally invasive technique that employs thermal energy to cauterize intracranial lesions with the potential to temporarily disrupt the BBB. This further opens a possible therapeutic window to enhance patient outcomes. Here, we review the impact of MRg-LITT on BBB and blood tumor barrier (BTB) and the duration of the BBB disruption. Studies have shown that MRg-LITT is effective due to its minimally invasive nature, precise tumor targeting, and low complication rates. Although the disruption duration varies across studies, the average peak disruption is within the initial two weeks post-ablation period and subsequently exhibits a gradual decline. However, further research involving larger groups with extended follow-up periods is required to determine disruption duration more accurately. In addition, evaluating toxicity and glymphatic system disruption is crucial to circumvent potential risks associated with this procedure.
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  • 文章类型: Journal Article
    背景:放射性坏死是放射肿瘤学的常见并发症,而机制和风险因素还有待充分探索。因此,我们进行了系统评价,以了解发病机理并确定显着影响发育的因素。
    方法:我们根据PRISMA指南使用PubMed,奥维德,和WebofScience数据库。完整的搜索策略可以作为PROSPERO(CRD42023361662)上的预注册协议找到。
    结果:我们纳入了83项研究,大多数涉及健康动物(n=72,86.75%)。在不同的研究和设置中,大鼠30Gy和小鼠50Gy的高剂量半球形辐射反复导致放射性坏死。较高的剂量和较大的照射体积与较早的发作有关。分割的时间表证明在预防放射性坏死方面的有效性有限。不同的解剖脑结构以各种方式响应于照射。白质似乎比灰质更脆弱。年龄更小,更多进化的动物物种,遗传背景也是重要因素,而性是无关紧要的。只有13.25%的研究是在携带原发性脑瘤的动物身上进行的,目前尚无关于脑转移的研究.
    结论:本系统综述确定了显著影响放射性坏死诱导的各种因素。目前的研究状况忽视了脑肿瘤动物模型的应用,即使患有脑恶性肿瘤的患者构成了接受脑照射的最大群体。在开发用于翻译实现的实验性放射性坏死模型时,应主要解决后一个方面。
    BACKGROUND: Radionecrosis is a common complication in radiation oncology, while mechanisms and risk factors have yet to be fully explored. We therefore conducted a systematic review to understand the pathogenesis and identify factors that significantly affect the development.
    METHODS: We performed a systematic literature search based on the PRISMA guidelines using PubMed, Ovid, and Web of Science databases. The complete search strategy can be found as a preregistered protocol on PROSPERO (CRD42023361662).
    RESULTS: We included 83 studies, most involving healthy animals (n = 72, 86.75 %). High doses of hemispherical irradiation of 30 Gy in rats and 50 Gy in mice led repeatedly to radionecrosis among different studies and set-ups. Higher dose and larger irradiated volume were associated with earlier onset. Fractionated schedules proved limited effectiveness in the prevention of radionecrosis. Distinct anatomical brain structures respond to irradiation in various ways. White matter appears to be more vulnerable than gray matter. Younger age, more evolved animal species, and genetic background were also significant factors, whereas sex was irrelevant. Only 13.25 % of the studies were performed on primary brain tumor bearing animals, no studies on brain metastases are currently available.
    CONCLUSIONS: This systematic review identified various factors that significantly affect the induction of radionecrosis. The current state of research neglects the utilization of animal models of brain tumors, even though patients with brain malignancies constitute the largest group receiving brain irradiation. This latter aspect should be primarily addressed when developing an experimental radionecrosis model for translational implementation.
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  • 文章类型: Journal Article
    目前用于脑肿瘤治疗的常规化疗方法在靶向药物递送中具有低效率并且通常具有非靶标毒性。开发针对大多数无法治愈的疾病的稳定有效的药物递送载体是紧迫的生物医学挑战之一。我们已经开发了聚合物纳米颗粒(NPs)与改进的替莫唑胺(TMZ)递送用于有前途的脑肿瘤治疗,对阳离子壳聚糖和阴离子果胶的带相反电荷的多糖的聚电解质复合物进行合理设计。NPs的直径(30至330nm)和ζ电位(-29至73mV)根据生物聚合物的初始质量比而变化。对天然NP的纳米力学参数的评估表明,杨氏模量从58到234kPa变化,附着力从-0.3到-3.57pN变化。通过红外光谱和动态流变学提出了基于离子官能团之间离子相互作用的NPs形成的可能机理。对TMZ吸附的参数和动力学的研究使得有可能鉴定出在模拟身体内部环境的模型液体中最有效地固定和释放活性物质的化合物。在一系列获得的NP中,选择基于相等比例的果胶-壳聚糖(0.1重量%)的聚电解质载体作为最有效的TMZ递送。这表明了治疗脑肿瘤的一种有希望的方法。
    Conventional chemotherapeutic approaches currently used for brain tumor treatment have low efficiency in targeted drug delivery and often have non-target toxicity. Development of stable and effective drug delivery vehicles for the most incurable diseases is one of the urgent biomedical challenges. We have developed polymer nanoparticles (NPs) with improved temozolomide (TMZ) delivery for promising brain tumor therapy, performing a rational design of polyelectrolyte complexes of oppositely charged polysaccharides of cationic chitosan and anionic pectin. The NPs\' diameter (30 to 330 nm) and zeta-potential (-29 to 73 mV) varied according to the initial mass ratios of the biopolymers. The evaluation of nanomechanical parameters of native NPs demonstrated changes in Young\'s modulus from 58 to 234 kPa and adhesion from -0.3 to -3.57 pN. Possible mechanisms of NPs\' formation preliminary based on ionic interactions between ionogenic functional groups were proposed by IR spectroscopy and dynamic rheology. The study of the parameters and kinetics of TMZ sorption made it possible to identify compounds that most effectively immobilize and release the active substance in model liquids that simulate the internal environment of the body. A polyelectrolyte carrier based on an equal ratio of pectin-chitosan (0.1% by weight) was selected as the most effective for the delivery of TMZ among a series of obtained NPs, which indicates a promising approach to the treatment of brain tumors.
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  • 文章类型: Journal Article
    磁共振成像(MRI)在脑肿瘤分类中的应用受到传统诊断程序复杂、耗时的制约,主要是因为需要对几个地区进行全面评估。然而,深度学习(DL)的进步促进了自动化系统的开发,该系统可以改善医学图像的识别和评估,有效应对这些困难。卷积神经网络(CNN)已经成为图像分类和视觉感知的坚定工具。这项研究引入了一种创新的方法,将CNN与混合注意力机制相结合,对原发性脑肿瘤进行分类,包括神经胶质瘤,脑膜瘤,垂体,和无肿瘤病例。所提出的算法经过了来自文献中有据可查的基准数据的严格测试。它与建立的预训练模型如Xception、ResNet50V2、Densenet201、ResNet101V2和DenseNet169。该方法的性能指标显著,分类准确率为98.33%,准确率和召回率为98.30%,F1评分为98.20%。实验发现强调了新方法在识别最常见类型的脑肿瘤方面的优越性。此外,该方法表现出良好的泛化能力,使其成为医疗保健准确有效地诊断大脑状况的宝贵工具。
    The application of magnetic resonance imaging (MRI) in the classification of brain tumors is constrained by the complex and time-consuming characteristics of traditional diagnostics procedures, mainly because of the need for a thorough assessment across several regions. Nevertheless, advancements in deep learning (DL) have facilitated the development of an automated system that improves the identification and assessment of medical images, effectively addressing these difficulties. Convolutional neural networks (CNNs) have emerged as steadfast tools for image classification and visual perception. This study introduces an innovative approach that combines CNNs with a hybrid attention mechanism to classify primary brain tumors, including glioma, meningioma, pituitary, and no-tumor cases. The proposed algorithm was rigorously tested with benchmark data from well-documented sources in the literature. It was evaluated alongside established pre-trained models such as Xception, ResNet50V2, Densenet201, ResNet101V2, and DenseNet169. The performance metrics of the proposed method were remarkable, demonstrating classification accuracy of 98.33%, precision and recall of 98.30%, and F1-score of 98.20%. The experimental finding highlights the superior performance of the new approach in identifying the most frequent types of brain tumors. Furthermore, the method shows excellent generalization capabilities, making it an invaluable tool for healthcare in diagnosing brain conditions accurately and efficiently.
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  • 文章类型: Journal Article
    转移RNA(tRNA)在蛋白质合成中的基本功能是众所周知的。最近的研究揭示了tRNA经历的各种化学修饰,这对各种细胞过程至关重要。这些修饰对于蛋白质的精确和有效翻译是必需的,并且在基因表达调控和细胞应激反应中也起着重要作用。这篇综述探讨了tRNA修饰和失调在各种脑疾病的病理生理学中的作用。包括癫痫,中风,神经发育障碍,脑肿瘤,老年痴呆症,和帕金森病。通过对现有研究的综合分析,我们的研究旨在阐明tRNA失调与脑部疾病之间的复杂关系.这强调了在这一领域进行持续探索的迫切需要,并提供了宝贵的见解,可以促进创新的诊断工具和治疗方法的发展。最终改善应对复杂神经系统疾病的个体的预后。
    Transfer RNAs (tRNAs) are well-known for their essential function in protein synthesis. Recent research has revealed a diverse range of chemical modifications that tRNAs undergo, which are crucial for various cellular processes. These modifications are necessary for the precise and efficient translation of proteins and also play important roles in gene expression regulation and cellular stress response. This review examines the role of tRNA modifications and dysregulation in the pathophysiology of various brain diseases, including epilepsy, stroke, neurodevelopmental disorders, brain tumors, Alzheimer\'s disease, and Parkinson\'s disease. Through a comprehensive analysis of existing research, our study aims to elucidate the intricate relationship between tRNA dysregulation and brain diseases. This underscores the critical need for ongoing exploration in this field and provides valuable insights that could facilitate the development of innovative diagnostic tools and therapeutic approaches, ultimately improving outcomes for individuals grappling with complex neurological conditions.
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  • 文章类型: Journal Article
    脑肿瘤如成胶质细胞瘤对免疫检查点阻断治疗有抗性,主要是由于肿瘤中有限的T细胞浸润。这里,我们显示,小鼠患有颅内肿瘤表现出系统性免疫抑制和T细胞在骨髓隔离,导致脑肿瘤中T细胞浸润减少。在荷瘤小鼠中,升高的血浆皮质酮通过糖皮质激素受体驱动T细胞隔离。由糖皮质激素诱导的T细胞动力学介导的免疫抑制和随后的肿瘤生长促进可以通过肾上腺切除术来消除。糖皮质激素激活抑制剂或糖皮质激素受体拮抗剂的给药,和T细胞特异性糖皮质激素受体缺失的小鼠。T细胞中的CCR8表达在荷瘤小鼠中以糖皮质激素受体依赖性方式增加。此外,趋化因子CCL1和CCL8是CCR8的配体,在荷瘤小鼠的骨髓免疫细胞中高度表达以募集T细胞。这些结果表明,脑肿瘤诱导的糖皮质激素激增和T细胞中的CCR8上调导致骨髓中的T细胞螯合,损害抗肿瘤免疫反应。靶向糖皮质激素受体-CCR8轴可能为颅内肿瘤的治疗提供有希望的免疫治疗方法。
    Brain tumors such as glioblastomas are resistant to immune checkpoint blockade therapy, largely due to limited T cell infiltration in the tumors. Here, we show that mice bearing intracranial tumors exhibit systemic immunosuppression and T cell sequestration in bone marrow, leading to reduced T cell infiltration in brain tumors. Elevated plasma corticosterone drives the T cell sequestration via glucocorticoid receptors in tumor-bearing mice. Immunosuppression mediated by glucocorticoid-induced T cell dynamics and the subsequent tumor growth promotion can be abrogated by adrenalectomy, the administration of glucocorticoid activation inhibitors or glucocorticoid receptor antagonists, and in mice with T cell-specific deletion of glucocorticoid receptor. CCR8 expression in T cells is increased in tumor-bearing mice in a glucocorticoid receptor-dependent manner. Additionally, chemokines CCL1 and CCL8, the ligands for CCR8, are highly expressed in bone marrow immune cells in tumor-bearing mice to recruit T cells. These findings suggested that brain tumor-induced glucocorticoid surge and CCR8 upregulation in T cells lead to T cell sequestration in bone marrow, impairing the anti-tumor immune response. Targeting the glucocorticoid receptor-CCR8 axis may offer a promising immunotherapeutic approach for the treatment of intracranial tumors.
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