Translational Application of Magnetic Hyperthermia Therapy with Adjuvant Therapies for Glioblastoma
磁热疗法与辅助疗法在胶质母细胞瘤中的转化应用
基本信息
- 批准号:10308036
- 负责人:
- 金额:$ 67.49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-12-01 至 2022-09-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdjuvant TherapyAftercareAnimal ModelAnimalsAutopsyBrainBrain NeoplasmsCanis familiarisCell DeathClinicalClinical ResearchClinical TrialsComputer ModelsDNA Double Strand BreakDataDepositionDoseEffectivenessEuropeanExcisionExposure toExternal Beam Radiation TherapyFinite Element AnalysisFormulationFoundationsGenerationsGlioblastomaGliomaHeat shock proteinsHeatingHistopathologyHumanHyperthermiaImageInjectionsIronMagnetic Resonance ImagingMagnetismMalignant NeoplasmsMalignant neoplasm of brainMeasuresMethodologyModelingMusNanotechnologyNormal CellNormal tissue morphologyOral AdministrationOryctolagus cuniculusPatientsPenetrationPilot ProjectsPrognosisRadiation therapyRecurrenceRodentSafetySolidStudy of magneticsTechnologyTemperatureTissuesToxic effectTreatment EfficacyTumor DebulkingWorkantitumor effectbasebioluminescence imagingbrain tissuecancer cellchemoradiationchemotherapyclinical translationclinically relevantdesigneffective therapyfractionated radiationhyperthermia treatmenthyperthermia tumor treatmentimage guidedimaging modalityimprovedinnovationiron oxide nanoparticlemagnetic dipolemagnetic fieldnanoparticle deliveryneoplastic cellradiation effectsafety and feasibilitytemozolomidetherapy resistanttissue injurytooltranslation to humanstranslational applicationstranslational potentialtreatment planningtreatment responsetumortumor microenvironment
项目摘要
Project Summary/Abstract
Glioblastoma (GBM) remains a fatal brain cancer for which there is no cure. Maximal safe tumor resection
combined with adjuvant therapies such as fractionated external beam radiation therapy (RT) and temozolomide
(TMZ) chemotherapy, known as chemoradiation (CRT), has provided the greatest benefit to GBM patients.
However, local recurrence occurs in most patients due to invasive therapy-resistant infiltrating cancer cells at
the tumor margin. Magnetic hyperthermia therapy (MHT) is a powerful nanotechnology-based treatment that
may enhance the effects of CRT. MHT consists of local heat generation in the tumor region through direct
delivery of magnetic iron-oxide nanoparticles (MIONPs) that are activated by exposure to an external alternating
magnetic field (AMF) that is safe to normal cells. The AMF interacts with the magnetic dipoles of the MIONPs to
generate local heat and hyperthermia. Human clinical trials have demonstrated overall survival benefits of MHT
with fractionated RT in recurrent GBM resulting in European approval. Current MHT strategies, however,
require high concentrations of nontargeted MIONPs (>100 mg/ml; 50-100mg Fe/g of tumor) delivered by
injection with leakback and without image-guided control of energy deposition. As a result, normal tissue
injury limits MHT effectiveness and treatment of the infiltrative tumor margins is poorly defined, which
compromises MHT efficacy. Our proposal is designed to address these challenges and optimize the translational
potential for enhanced MHT of GBM in combination with CRT using both small and large animal models, with
clinical proof-of-concept demonstration in spontaneous canine gliomas. We have recently completed a pilot study
in spontaneous canine gliomas demonstrating feasibility and safety of image-guided MIONP delivery alone. We
hypothesize that image-guided MHT will enhance CRT of GBM. Key innovations of our proposal are to: 1)
evaluate the enhancement of CRT by MHT in mouse GBM models with an innovative proprietary MIONP
formulation that requires 20-fold lower Fe concentration in tumors for more effective treatment than current
approved MIONPs; 2) optimize image-guided MIONP delivery and MHT treatment planning with computational
modelling in a rabbit brain tumor model; 3) enhance thermal treatment at the infiltrative tumor margins by
controlling power deposition with innovative AMF power application that will also limit off target heating; and, 4)
complete a clinically relevant proof-of-concept study of our MHT approach in a spontaneous canine glioma
model. We have Preliminary Data that demonstrate intracranial hyperthermia with a 3-fold increase in TMZ
concentration within GBM tumors, leading to a robust antitumor effect with increased survival after MHT + CRT
in a therapy-resistant rodent glioma model. Overall, this interdisciplinary work will provide a solid foundation for
meaningful clinical translation of MHT with CRT for treatment of GBM. Imaging methods that correlate tumor
heat distribution after MHT will be developed for translation to human patients.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Constantinos George Hadjipanayis其他文献
Constantinos George Hadjipanayis的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Constantinos George Hadjipanayis', 18)}}的其他基金
dMRI-guided pre-operative planning for supra-total resection of high-grade gliomas
dMRI引导的高级别胶质瘤超全切除术前规划
- 批准号:
10635099 - 财政年份:2023
- 资助金额:
$ 67.49万 - 项目类别:
Translational Application of Magnetic Hyperthermia Therapy with Adjuvant Therapies for Glioblastoma
磁热疗法与辅助疗法在胶质母细胞瘤中的转化应用
- 批准号:
10737738 - 财政年份:2019
- 资助金额:
$ 67.49万 - 项目类别:
Translational Application of Magnetic Hyperthermia Therapy with Adjuvant Therapies for Glioblastoma
磁热疗法与辅助疗法在胶质母细胞瘤中的转化应用
- 批准号:
10599714 - 财政年份:2019
- 资助金额:
$ 67.49万 - 项目类别:
Translational Application of Magnetic Hyperthermia Therapy with Adjuvant Therapies for Glioblastoma
磁热疗法与辅助疗法在胶质母细胞瘤中的转化应用
- 批准号:
9916087 - 财政年份:2019
- 资助金额:
$ 67.49万 - 项目类别:
Translational Application of Magnetic Hyperthermia Therapy with Adjuvant Therapies for Glioblastoma
磁热疗法与辅助疗法在胶质母细胞瘤中的转化应用
- 批准号:
10054965 - 财政年份:2019
- 资助金额:
$ 67.49万 - 项目类别:
Translational Application of Magnetic Hyperthermia Therapy with Adjuvant Therapies for Glioblastoma
磁热疗法与辅助疗法在胶质母细胞瘤中的转化应用
- 批准号:
10730272 - 财政年份:2019
- 资助金额:
$ 67.49万 - 项目类别:
Improving extent of glioblastoma resection by combining volumetric MRSI and 5-ALA
结合体积 MRSI 和 5-ALA 提高胶质母细胞瘤切除范围
- 批准号:
8699970 - 财政年份:2014
- 资助金额:
$ 67.49万 - 项目类别:
HSV-Mediated Chemoradiosensitivity Human Glioma Model
HSV介导的化学放射敏感性人类神经胶质瘤模型
- 批准号:
7263982 - 财政年份:2006
- 资助金额:
$ 67.49万 - 项目类别:
HSV-Mediated Chemoradiosensitivity Human Glioma Model
HSV介导的化学放射敏感性人类神经胶质瘤模型
- 批准号:
7145786 - 财政年份:2006
- 资助金额:
$ 67.49万 - 项目类别:
HSV-Mediated Chemoradiosensitivity Human Glioma Model
HSV介导的化学放射敏感性人类神经胶质瘤模型
- 批准号:
7503347 - 财政年份:2006
- 资助金额:
$ 67.49万 - 项目类别:
相似海外基金
Countering sympathetic vasoconstriction during skeletal muscle exercise as an adjuvant therapy for DMD
骨骼肌运动期间对抗交感血管收缩作为 DMD 的辅助治疗
- 批准号:
10735090 - 财政年份:2023
- 资助金额:
$ 67.49万 - 项目类别:
The ESCAPE clinical trial of circulating tumor DNA to guide adjuvant therapy in chemo-resistant triple negative breast cancer
循环肿瘤 DNA 指导化疗耐药三阴性乳腺癌辅助治疗的 ESCAPE 临床试验
- 批准号:
494901 - 财政年份:2023
- 资助金额:
$ 67.49万 - 项目类别:
Operating Grants
A Type I Hybrid Effectiveness-Implementation Trial to Evaluate a Navigation-Based Multilevel Intervention to Decrease Delays Starting Adjuvant Therapy Among Patients with Head and Neck Cancer
一项 I 型混合有效性实施试验,用于评估基于导航的多级干预措施,以减少头颈癌患者开始辅助治疗的延迟
- 批准号:
10714537 - 财政年份:2023
- 资助金额:
$ 67.49万 - 项目类别:
Multi-modal machine learning to guide adjuvant therapy in surgically resectable colorectal cancer
多模式机器学习指导可手术切除结直肠癌的辅助治疗
- 批准号:
10588103 - 财政年份:2023
- 资助金额:
$ 67.49万 - 项目类别:
Efficacy of ethanol adjuvant therapy after resection of malignant soft tissue tumors
恶性软组织肿瘤切除术后乙醇辅助治疗的疗效
- 批准号:
22K09407 - 财政年份:2022
- 资助金额:
$ 67.49万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of immune response cells and development of novel adjuvant therapy for sublingual immunotherapy
免疫应答细胞的鉴定和舌下免疫治疗新型辅助疗法的开发
- 批准号:
21KK0287 - 财政年份:2022
- 资助金额:
$ 67.49万 - 项目类别:
Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
Pursuing molecular biomarkers to guide adjuvant therapy for HPV+ head and neck cancers after transoral robotic surgery
寻找分子生物标志物来指导经口机器人手术后 HPV 头颈癌的辅助治疗
- 批准号:
10357120 - 财政年份:2022
- 资助金额:
$ 67.49万 - 项目类别:
Biomarker research using two prospective studies on preoperative and postoperative adjuvant therapy for pancreatic cancer
使用两项关于胰腺癌术前和术后辅助治疗的前瞻性研究进行生物标志物研究
- 批准号:
21K08700 - 财政年份:2021
- 资助金额:
$ 67.49万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Personalized Resistant Starch as an Adjuvant Therapy for Pediatric Inflammatory Bowel Disease
个性化抗性淀粉作为小儿炎症性肠病的辅助治疗
- 批准号:
437315 - 财政年份:2020
- 资助金额:
$ 67.49万 - 项目类别:
Studentship Programs
Tailored adjuvant therapy in POLE-mutated and p53-wildtype early stage endometrial cancer (TAPER)
POLE 突变和 p53 野生型早期子宫内膜癌 (TAPER) 的定制辅助治疗
- 批准号:
435603 - 财政年份:2020
- 资助金额:
$ 67.49万 - 项目类别:
Operating Grants














{{item.name}}会员




