Development of Gd(III)-Pt(II) MR Probes for Tandem Detection & Chemotherapy
用于串联检测的 Gd(III)-Pt(II) MR 探针的开发
基本信息
- 批准号:9759560
- 负责人:
- 金额:$ 3.98万
- 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:2019-05-01 至 2023-04-30
- 项目状态:已结题
- 来源:
- 关键词:Antineoplastic AgentsApoptosisAreaBindingBiologicalBiological AssayBiological ModelsBladderBreastBreast Cancer cell lineCancer DetectionCell LineCellsCervicalChadCircular DichroismCisplatinClinicalComplexContrast MediaCytoplasmDNADNA BindingDNA Binding AgentDNA RepairDetectionDevelopmentDevelopmental Therapeutics ProgramEnsureEvaluationExposure toFailureFundingHead and neck structureHemolysisHomidium BromideIn VitroInductively Coupled Plasma Mass SpectrometryInjectionsLaboratoriesLifeLungMagnetic Resonance ImagingMeasuresMedicineMetalsMissionModelingMolecularMonitorMusNonionizing RadiationOvarianPatientsPenetrationPropertyProteinsReportingResearchResearch Project GrantsResistanceResolutionRotationSolid NeoplasmStimulusStructureTemperatureTimeToxic effectTranslational ResearchUnited States National Institutes of HealthXenograft ModelXenograft procedureanti-canceranticancer treatmentcalf thymus DNAcancer cellcancer therapychemotherapycytotoxicitydesigneffective therapyexperimental studyhearing impairmentimaging probeimprovedin vitro testingin vivoin vivo evaluationin vivo monitoringinterestmagnetic fieldmeltingmetal complexmolecular imagingmouse modelnovelpatient populationpredicting responseprofessorrenal damageresponseside effectsoft tissuespatiotemporalstemsuccesstheranosticstooltranslational impacttumoruptake
项目摘要
Cisplatin is one of the most widely used chemotherapeutics for solid tumors. Despite its clinical utility,
cisplatin suffers from significant off target toxicity. Additionally, it is susceptible to chemoresistance through
several mechanisms, most commonly by decreased accumulation. Patients prescribed cisplatin typically
undergo two cycles of therapy (six weeks total) before the tumor is reevaluated for a response. During this time,
patients are exposed to significant toxicity without knowing if the treatment is effective. Furthermore, if the tumor
does not respond to cisplatin, a crucial period of time has been wasted when a more effective treatment could
have been prescribed instead. If there were a tool that could predict whether or not a tumor will respond to Pt(II)
chemotherapy, it could mitigate patient exposure to harmful side effects and help ensure the best treatment
option is prescribed. Currently, there is no such tool, which makes this issue a critical unmet need in medicine.
Clinically approved Gd(III) MR contrast agents (CAs) provide a versatile platform for developing Gd(III)-
Pt(II) theranostic agents that can predict if tumors are susceptible to Pt(II) chemotherapy and provide
simultaneous anti-cancer therapy and detection through MR imaging. The Meade lab is a pioneer in the
development of bioresponsive Gd(III) MR CAs that “turn on” by an increase in relaxivity through modulation of
one or more inner sphere parameters. One such parameter is 𝜏R, the rotational correlation time. A large increase
in 𝜏R, which occurs when CAs bind to large biomolecules, results in a drastic increase in relaxivity, which is seen
as brighter contrast in an MR image. By coordinating a cis-dichloroplatinum(II) moiety to Gd(III) CAs, the resulting
Gd(III)-Pt(II) compounds will mimic cisplatin. As such, the agents can bind DNA, giving them anti-cancer
properties and increasing the relaxivity for brighter MR contrast. The change in relaxivity occurs only when DNA
is bound, therefore these agents can be used to predict whether or not tumors of interest are susceptible to
treatment with cisplatin. If no contrast increase is observed, the agents were not able to enter the cells and bind
DNA, therefore the tumor likely will not respond to therapy. All agents synthesized will be tested in vitro in cisplatin
sensitive and resistant cell lines and MR images will be obtained. The agents will be screened in an additional
50+ breast cancer cell lines in the laboratory of Professor Dai Horiuchi at Northwestern. The agents will also be
tested in vivo in murine models with cisplatin sensitive and resistant flank xenografts.
This proposed project adheres to the mission statement and funding plans of the NIH. The research
seeks to develop novel molecular imaging probes as tools to predict tumor response to cisplatin therapy and
then provide simultaneous anti-cancer therapy and monitoring by MR imaging. Currently, there is no effective
way to predict if a tumor will respond to cisplatin therapy, therefore success in this project would help solve a
critical unmet need. Because cisplatin is widely used and has high toxicity, this project has the potential to
drastically improve the quality of treatment for a large population of patients.
顺铂是应用最广泛的实体肿瘤化疗药物之一。尽管它有临床用途,
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 }}
Casey Adams其他文献
Casey Adams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('Casey Adams', 18)}}的其他基金
Development of Gd(III)-Pt(II) MR Probes for Tandem Detection & Chemotherapy
用于串联检测的 Gd(III)-Pt(II) MR 探针的开发
- 批准号:
9921198 - 财政年份:2019
- 资助金额:
$ 3.98万 - 项目类别:
相似国自然基金
Epac1/2通过蛋白酶体调控中性粒细胞NETosis和Apoptosis在急性肺损伤中的作用研究
- 批准号:LBY21H010001
- 批准年份:2020
- 资助金额:0.0 万元
- 项目类别:省市级项目
基于Apoptosis/Ferroptosis双重激活效应的天然产物AlbiziabiosideA的抗肿瘤作用机制研究及其结构改造
- 批准号:81703335
- 批准年份:2017
- 资助金额:20.0 万元
- 项目类别:青年科学基金项目
双肝移植后Apoptosis和pyroptosis在移植物萎缩差异中的作用和供受者免疫微环境变化研究
- 批准号:81670594
- 批准年份:2016
- 资助金额:58.0 万元
- 项目类别:面上项目
Serp-2 调控apoptosis和pyroptosis 对肝脏缺血再灌注损伤的保护作用研究
- 批准号:81470791
- 批准年份:2014
- 资助金额:73.0 万元
- 项目类别:面上项目
Apoptosis signal-regulating kinase 1是七氟烷抑制小胶质细胞活化的关键分子靶点?
- 批准号:81301123
- 批准年份:2013
- 资助金额:23.0 万元
- 项目类别:青年科学基金项目
APO-miR(multi-targeting apoptosis-regulatory miRNA)在前列腺癌中的表达和作用
- 批准号:81101529
- 批准年份:2011
- 资助金额:22.0 万元
- 项目类别:青年科学基金项目
放疗与细胞程序性死亡(APOPTOSIS)相关性及其应用研究
- 批准号:39500043
- 批准年份:1995
- 资助金额:9.0 万元
- 项目类别:青年科学基金项目
相似海外基金
Development of an apoptosis biosensor for monitoring of breast cancer
开发用于监测乳腺癌的细胞凋亡生物传感器
- 批准号:
10719415 - 财政年份:2023
- 资助金额:
$ 3.98万 - 项目类别:
Milk fat globule-EGF factor 8 and hepatocyte apoptosis-induced liver wound healing response
乳脂肪球-EGF因子8与肝细胞凋亡诱导的肝脏创面愈合反应
- 批准号:
10585802 - 财政年份:2023
- 资助金额:
$ 3.98万 - 项目类别:
Interrogating the Fgl2-FcγRIIB axis on CD8+ T cells: A novel mechanism mediating apoptosis of tumor-specific memory CD8+ T cells
询问 CD8 T 细胞上的 Fgl2-FcγRIIB 轴:介导肿瘤特异性记忆 CD8 T 细胞凋亡的新机制
- 批准号:
10605856 - 财政年份:2023
- 资助金额:
$ 3.98万 - 项目类别:
Novel targeted therapy for FGFR inhibitor-resistant urothelial cancer and apoptosis based therapy for urothelial cancer
FGFR抑制剂耐药性尿路上皮癌的新型靶向治疗和基于细胞凋亡的尿路上皮癌治疗
- 批准号:
23K08773 - 财政年份:2023
- 资助金额:
$ 3.98万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Mechanistic analysis of apoptosis induction by HDAC inhibitors in head and neck cancer
HDAC抑制剂诱导头颈癌凋亡的机制分析
- 批准号:
23K15866 - 财政年份:2023
- 资助金额:
$ 3.98万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Interrogating the Fgl2-FcgRIIB axis: A novel mechanism mediating apoptosis of tumor-specific memory CD8+ T cells
探究 Fgl2-FcgRIIB 轴:介导肿瘤特异性记忆 CD8 T 细胞凋亡的新机制
- 批准号:
10743485 - 财政年份:2023
- 资助金额:
$ 3.98万 - 项目类别:
Investigating the role of apoptosis-resistance and the tumor environment on development and maintenance of sacrococcygeal teratomas
研究细胞凋亡抗性和肿瘤环境对骶尾部畸胎瘤发生和维持的作用
- 批准号:
10749797 - 财政年份:2023
- 资助金额:
$ 3.98万 - 项目类别:
The effects of glucose on immune cell apoptosis and mitochondrial membrane potential and the analysis of its mechanism by which glucose might modulate the immune functions.
葡萄糖对免疫细胞凋亡和线粒体膜电位的影响及其调节免疫功能的机制分析。
- 批准号:
22K09076 - 财政年份:2022
- 资助金额:
$ 3.98万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
XAF1 IN P53 SIGNALING, APOPTOSIS AND TUMOR SUPPRESSION
P53 信号传导、细胞凋亡和肿瘤抑制中的 XAF1
- 批准号:
10583516 - 财政年份:2022
- 资助金额:
$ 3.98万 - 项目类别:
Role of Thioredoxin system in regulation of autophagy-apoptosis cross talk in neurons: Uncovering Novel Molecular Interactions.
硫氧还蛋白系统在神经元自噬-凋亡串扰调节中的作用:揭示新的分子相互作用。
- 批准号:
RGPIN-2019-05371 - 财政年份:2022
- 资助金额:
$ 3.98万 - 项目类别:
Discovery Grants Program - Individual