Intratumoral functional connectivity with implications on synaptogenesis and aphasia recovery in adult astrocytic WHO II-III glioma

瘤内功能连接对成人星形细胞 WHO II-III 神经胶质瘤突触发生和失语恢复的影响

• 批准号: 10614531
• 负责人: Shawn L. Hervey-Jumper
• 金额: $ 20.01万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10614531
• 关键词: Activities of Daily Living; Adult; Adult Glioma; Affect; Age; American; Aphasia; Area; Astrocytes; Astrocytoma; Biology; Brain; California; Cell Proliferation; Cells; Clinical; Clinical Trials Design; Coculture Techniques; Cognition; Cognitive; Communication; Competence; DLG4 gene; Data; Development; Diagnosis; Education; Environment; Epilepsy; Excision; Funding; Genetic; Glioblastoma; Glioma; Goals; Hippocampus; Human; Language; Literature; Longevity; Mediating; Motor; Neurobiology; Neurologic; Neurons; Neurosciences; Non-aphasic; Patients; Physiology; Population; Process; Quality of life; Radiation; Research; Research Proposals; Sampling; San Francisco; Scientist; Seizures; Site; Synapses; Synapsins; System; Testing; Time; Training; Universities; Validation; Work; Xenograft procedure; aphasia recovery; disability; driving force; experience; experimental study; functional disability; functional outcomes; functional status; human subject; neural; neural circuit; neuro-oncology; neuronal excitability; pre-clinical; programs; synaptogenesis; tumor; tumor progression

PROJECT SUMMARY: Over 700,000 Americans are currently living with a glioma and 65 new patients are diagnosed every day. Factors influencing survival include patient age, WHO grade, and extent of tumor resection, however it is increasingly understood that functional status such as language, cognition, and the ability to communicate impacts longevity. While the survival time of some patients is short, many with WHO grade II and III tumors and favorable genetics will survive for 20 years or longer. Throughout this survival period, over 70% of patients experience functional disabilities that reduce quality of life and survival. This has shifted both research and clinical questions beyond survival to include functional outcomes. The fundamental goal of my research program is to study the bidirectional mechanisms by which gliomas interface with functional cognitive networks. There is strong evidence in the preclinical literature that neuronal activity impacts tumor progression, but this is unstudied from a functional capacity in humans. Little is known about the mechanisms by which gliomas affect functional cognitive networks. For example, the precise organization of language within the perisylvian language network is highly variable and the cellular mechanism behind what makes some areas functionally relevant remains unknown. Functionally relevant regions (as determined by direct cortical stimulation) have increased functional connectivity with surrounding brain. It has been shown recently that distinct astrocyte subpopulations within gliomas contribute to synaptogenesis, however their organization within the tumor and functional significance in humans remains unknown. It is therefore possible that glioma-neural interactions in part mediated by synaptogenic glioma cells may be a driving force behind these connections and co-localize within regions with high functional connectivity. In this research proposal I will study functional connectivity within dominant hemisphere perisylvian WHO II-III astrocytic gliomas to determine whether synaptogenic glioma cells are enriched within regions of elevated functional connectivity. The results of the experiments in this proposal will offer a sharper and more accurate account of how synaptogenesis in adult gliomas contributes to aphasia recovery. These experiments conducted in the robust academic environment of University of California San Francisco and encompass scientific and education aims covering both neuro circuit dynamics and glioma biology. Furthermore, they will contribute to my training plan, which will focus on establishing competence in 1) neural circuit physiology, 2) the neurobiology of aphasia recovery, 3) human subject testing, and 4) design of the clinical trial trials that will ultimately enable clinical validation of my hypothesis. The aims of my training plan are to further my training in translational neuro-oncology toward becoming an independent R01-funded scientist with a research program focused the mechanisms by which gliomas influence cognition.

项目摘要： 目前有超过70万美国人患有神经胶质瘤，每次诊断出65名新患者 天。影响生存的因素包括患者年龄，谁等级和肿瘤切除程度，但是 越来越了解功能状态，例如语言，认知和交流能力 影响寿命。虽然某些患者的生存时间很短，但许多患者患有II级和III级肿瘤 有利的遗传学将存活20年或更长时间。在整个生存期间，超过70％的患者 经历功能障碍，可以降低生活质量和生存。这已经改变了研究和 超出生存的临床问题，包括功能结果。我研究的基本目标 程序是研究与功能认知网络的胶质瘤接口的双向机制。 临床前文献中有强有力的证据表明神经元活动会影响肿瘤的进展，但这是 从人类的功能能力中没有研究。 关于神经胶质瘤影响功能认知网络的机制知之甚少。为了 例如，perisylvian语言网络中语言的精确组织高度可变，并且 使某些领域与功能相关的原因背后的细胞机制仍然未知。在功能上 相关区域（由直接皮质刺激确定）与 周围的大脑。最近已经显示，神经胶质瘤内不同的星形胶质细胞亚群有助于 为了突触发生，但是它们在肿瘤内的组织和人类的功能意义仍然存在 未知。因此，可能是由突触神经胶质瘤细胞介导的部分胶质瘤神经相互作用 可能是这些连接背后的推动力，并在功能高的区域内共定位 连接性。在这项研究建议中，我将研究主要半球内的功能连通性 perisylvian who II-III星形胶质细胞神经胶质瘤确定突触神经胶质瘤细胞是否富含在内 功能连通性升高的区域。本提案中的实验结果将提供更清晰的 更准确地说明了成人神经胶质瘤中的突触发生如何有助于失语症恢复。这些 在加利福尼亚大学旧金山大学和 涵盖神经电路动力学和神经胶质瘤生物学的涵盖科学和教育的目的。 此外，他们将为我的培训计划做出贡献，该计划将着重于建立能力1） 电路生理学，2）失语症恢复的神经生物学，3）人类受试者测试，4）设计 临床试验最终将对我的假设进行临床验证。我的培训计划的目的是 为了进一步培训转化神经肿瘤学，成为一名独立的R01资助的科学家 研究计划的重点是神经胶质瘤影响认知的机制。

项目成果

Seizure outcome after resection of insular glioma: a systematic review, meta-analysis, and institutional experience.

• DOI: 10.3171/2022.8.jns221067
• 发表时间: 2023-05-01
• 期刊: JOURNAL OF NEUROSURGERY
• 影响因子: 4.1
• 作者: Zhang, John J. Y.;Lee, Keng Siang;Wang, Doris D.;Hervey-Jumper, Shawn L.;Berger, Mitchel S.
• 通讯作者: Berger, Mitchel S.

Readability of Online Neuro-Oncology-Related Patient Education Materials from Tertiary-Care Academic Centers.

来自三级护理学术中心的在线神经肿瘤学相关患者教育材料的可读性。

• DOI: 10.1016/j.wneu.2019.11.109
• 发表时间: 2020
• 期刊: World neurosurgery
• 影响因子: 2
• 作者: Ammanuel,SimonG;Edwards,CalebS;Alhadi,Rasheed;Hervey-Jumper,ShawnL
• 通讯作者: Hervey-Jumper,ShawnL

Detection of glioma infiltration at the tumor margin using quantitative stimulated Raman scattering histology.

• DOI: 10.1038/s41598-021-91648-8
• 发表时间: 2021-06-09
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Pekmezci M;Morshed RA;Chunduru P;Pandian B;Young J;Villanueva-Meyer JE;Tihan T;Sloan EA;Aghi MK;Molinaro AM;Berger MS;Hervey-Jumper SL
• 通讯作者: Hervey-Jumper SL

Convergence of heteromodal lexical retrieval in the lateral prefrontal cortex.

• DOI: 10.1038/s41598-021-85802-5
• 发表时间: 2021-03-18
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Aabedi AA;Kakaizada S;Young JS;Kaur J;Wiese O;Valdivia C;Krishna S;Weyer-Jamora C;Berger MS;Weissman DH;Brang D;Hervey-Jumper SL
• 通讯作者: Hervey-Jumper SL

Exercise improves health-related quality of life sleep and fatigue domains in adult high- and low-grade glioma patients.

• DOI: 10.1007/s00520-021-06566-2
• 发表时间: 2022-02
• 期刊: SUPPORTIVE CARE IN CANCER
• 影响因子: 3.1
• 作者: Miklja, Zachary;Gabel, Nicolette;Altshuler, David;Wang, Lin;Hervey-Jumper, Shawn L.;Smith, Sean
• 通讯作者: Smith, Sean