Online monitoring and image-guided treatment of chemoresistant micrometastases
化疗耐药微转移的在线监测和图像引导治疗
基本信息
- 批准号:9148171
- 负责人:
- 金额:$ 18.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-09-23 至 2018-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdenocarcinoma CellAntigen TargetingBindingBiological MarkersBiological ModelsCalibrationCancer cell lineCarcinomatosisCell Culture TechniquesCell DeathCell membraneCell surfaceCellsChemosensitizationClinicClinicalComplementComplexDepositionDevelopmentDiseaseDisease ResistanceDisseminated Malignant NeoplasmDrug KineticsDrug resistanceEnsureEpidermal Growth Factor ReceptorEpithelial ovarian cancerExcisionFeedbackFlow CytometryFluorescenceGoalsGreater sac of peritoneumHealthImageImaging technologyImmunoconjugatesIn VitroInformaticsIntestinesLeadLeftMalignant NeoplasmsMembraneMethodsMicrometastasisMicroscopicModalityModelingMolecularMolecular TargetMonitorMorbidity - disease rateOperative Surgical ProceduresOrganOutcomeOvarianPancreatic Ductal AdenocarcinomaPatientsPelvic cavity structurePeritonealPharmaceutical PreparationsPhototoxicityPolymerase Chain ReactionProcessProtocols documentationReceptor Protein-Tyrosine KinasesRecurrenceRegimenResearchResidual stateResistanceResolutionReverse TranscriptionSalvage TherapySeriesSiteSourceSpecificityStagingSurface AntigensTestingTherapeutic AgentsTherapeutic IndexTimeTissuesTrainingTranslatingValidationWorkXenograft Modelarmbasebioimagingcancer cellcancer therapychemotherapydesigndosimetryimage guidedimaging agentimaging biomarkerimaging modalityimaging probeimprovedin vivomicroscopic imagingminimally invasivemodel developmentmolecular imagingmortalitymouse modelneoplastic cellnovelnovel therapeuticsoptical imagingoverexpressionpersonalized cancer therapyradio-sensitizesresponsestandard caresystemic toxicitytargeted imagingtherapeutic targetthree dimensional cell culturethree-dimensional modelingtooltumoruptake
项目摘要
DESCRIPTION (provided by applicant): Despite advances in cytoreductive surgery and chemotherapy, survival of metastatic epithelial ovarian cancer and pancreatic ductal adenocarcinoma remain dismal due in part to chemoresistant micrometastases undetectable by traditional imaging modalities. Both of these diseases involve peritoneal carcinomatosis, that is, extensive tumor studding of the peritoneal cavity and its resident organs. To address these "invisible" tumors, we introduce a series of cancer cell-targeted, activatable imaging and therapeutic agents integrated with cellular-resolution, multi-molecular fluorescence microendoscopy. We developed near-infrared photocytotoxic immunoconjugates (PICs) that target cell membrane molecules overexpressed by cancer cells, including the epidermal growth factor receptor, to serve as an imaging probe and combined photodynamic and anti-molecular therapeutic agent for tumor-targeted, activatable photoimmunotherapy (taPIT). The photodynamic and fluorescence components become de-quenched (activated) upon cancer cell binding, internalization and processing. This strategy overcomes off-target phototoxicity-including bowel phototoxicity-the major clinical obstacle for photoactivated treatments in complex sites such as the pelvic cavity. This proposal builds on our prior work that shows the PIC binds ovarian micrometastases with 93% sensitivity and 93% specificity in vivo, enabling accurate recognition of tumors as small as 30 �m and selective destruction of micrometastases. We propose to further develop this platform to specifically address chemoresistant micrometastases, which represent a critical niche in cancer therapy. Current clinical imaging technologies cannot resolve microscopic tumor deposits left behind by surgery and chemotherapy, and there are limited treatment options for patients with recurrent, chemoresistant tumors. We anticipate that this new paradigm for microendoscopy-guided taPIT will complement current treatment modalities for patients with advanced-stage disease and those receiving salvage therapies.
描述(由申请人提供):尽管在细胞减少手术和化疗方面取得了进展,但转移性上皮性卵巢癌和胰腺导管腺癌的生存率仍然很低,部分原因是传统成像方式无法检测到化疗耐药微转移。这两种疾病都涉及腹膜癌,即腹膜腔及其常驻器官的广泛肿瘤。为了解决这些“看不见”的肿瘤,我们引入了一系列针对癌细胞的、可激活的成像和治疗剂,并结合了细胞分辨率、多分子荧光显微内镜。我们开发了近红外光细胞毒性免疫偶联物(PICs),其靶向癌细胞过度表达的细胞膜分子,包括表皮生长因子受体,作为成像探针和联合光动力和抗分子治疗剂,用于肿瘤靶向,可激活光免疫治疗(taPIT)。在癌细胞结合、内化和加工过程中,光动力和荧光成分被去淬灭(激活)。这种策略克服了脱靶光毒性,包括肠道光毒性,这是光激活治疗复杂部位(如盆腔)的主要临床障碍。我们之前的研究表明,PIC在体内结合卵巢微转移瘤具有93%的敏感性和93%的特异性,能够准确识别小至30 μ m的肿瘤并选择性地破坏微转移瘤。我们建议进一步开发这个平台,专门针对化疗耐药微转移,这代表了癌症治疗的一个关键利基。目前的临床成像技术无法解决手术和化疗留下的显微肿瘤沉积物,并且对于复发性化疗耐药肿瘤患者的治疗选择有限。我们期待这种显微内镜引导下的taPIT新模式将补充目前晚期疾病患者和接受补救性治疗的患者的治疗模式。
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 }}
Bryan Quilty Spring其他文献
Bryan Quilty Spring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('Bryan Quilty Spring', 18)}}的其他基金
Disease-homing light delivery by engineering bioluminescent immune cells for whole body precision photomedicine
通过工程生物发光免疫细胞进行疾病引导光传输,用于全身精准光医学
- 批准号:
10578425 - 财政年份:2023
- 资助金额:
$ 18.64万 - 项目类别:
Multiplexed and dynamically targeted photoimmunotherapy of heterogeneous, chemoresistant micrometastases guided by online in vivo optical imaging of cell-surface biomarkers
由细胞表面生物标志物在线体内光学成像引导的异质性、耐药性微转移的多重动态靶向光免疫疗法
- 批准号:
10617176 - 财政年份:2020
- 资助金额:
$ 18.64万 - 项目类别:
Multiplexed and dynamically targeted photoimmunotherapy of heterogeneous, chemoresistant micrometastases guided by online in vivo optical imaging of cell-surface biomarkers
由细胞表面生物标志物在线体内光学成像引导的异质性、耐药性微转移的多重动态靶向光免疫疗法
- 批准号:
10358581 - 财政年份:2020
- 资助金额:
$ 18.64万 - 项目类别:
Hyperspectral Microendscopy to Monitor VEGF During Pancreatic Cancer Therapy
高光谱显微内窥镜监测胰腺癌治疗期间的 VEGF
- 批准号:
8165997 - 财政年份:2010
- 资助金额:
$ 18.64万 - 项目类别:
Hyperspectral Microendscopy to Monitor VEGF During Pancreatic Cancer Therapy
高光谱显微内窥镜监测胰腺癌治疗期间的 VEGF
- 批准号:
8003695 - 财政年份:2010
- 资助金额:
$ 18.64万 - 项目类别:
Hyperspectral Microendscopy to Monitor VEGF During Pancreatic Cancer Therapy
高光谱显微内窥镜监测胰腺癌治疗期间的 VEGF
- 批准号:
8309787 - 财政年份:2010
- 资助金额:
$ 18.64万 - 项目类别:
Core B: Biological Models, Multiplexed Optical Biopsy, Molecular Pathology, and Biostatistics Core
核心 B:生物模型、多重光学活检、分子病理学和生物统计学核心
- 批准号:
10705164 - 财政年份:1999
- 资助金额:
$ 18.64万 - 项目类别:
Core B: Biological Models, Multiplexed Optical Biopsy, Molecular Pathology, and Biostatistics Core
核心 B:生物模型、多重光学活检、分子病理学和生物统计学核心
- 批准号:
10494489 - 财政年份:1999
- 资助金额:
$ 18.64万 - 项目类别:
相似海外基金
Assessing The Impact of Heparanase and NDST2 Expression on Non-Small Cell Lung Adenocarcinoma Cell Motility
评估乙酰肝素酶和 NDST2 表达对非小细胞肺腺癌细胞运动的影响
- 批准号:
449570 - 财政年份:2020
- 资助金额:
$ 18.64万 - 项目类别:
Studentship Programs
Analysis of cancer metastasis and invasion mechanism using a new lung adenocarcinoma cell line.
使用新的肺腺癌细胞系分析癌症转移和侵袭机制。
- 批准号:
16K10689 - 财政年份:2016
- 资助金额:
$ 18.64万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Acquisition strategy of tumor-specific markers using established micropapillary pattern pulmonary adenocarcinoma cell line
使用已建立的微乳头模式肺腺癌细胞系获取肿瘤特异性标志物的策略
- 批准号:
26460441 - 财政年份:2014
- 资助金额:
$ 18.64万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The antibetic drug metformin inhibits esophageal adenocarcinoma cell proliferation in vitro and in vivo.
抗生素药物二甲双胍在体外和体内抑制食管腺癌细胞增殖。
- 批准号:
25860540 - 财政年份:2013
- 资助金额:
$ 18.64万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
The cell permeable peptide inhibits pancreatic ductal adenocarcinoma cell proliferations and can be used as the molecular targeting dru
细胞通透肽抑制胰腺导管腺癌细胞增殖,可作为分子靶向药物
- 批准号:
25461969 - 财政年份:2013
- 资助金额:
$ 18.64万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Basic Research for elucidation of chemo-resistance in mucinous adenocarcinoma cell.
阐明粘液腺癌细胞化疗耐药性的基础研究。
- 批准号:
22791532 - 财政年份:2010
- 资助金额:
$ 18.64万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
TAS::75 0849::TAS IN THIS PHASE I SBIR THE BREAST CANCER ADENOCARCINOMA CELL LI
TAS::75 0849::TAS 在这一阶段 I SBIR 乳腺癌腺癌细胞 LI
- 批准号:
8164743 - 财政年份:2010
- 资助金额:
$ 18.64万 - 项目类别:
Role of Endothelin-1 in osteoblastic bone metastasis produced by a human lung adenocarcinoma cell line
Endothelin-1 在人肺腺癌细胞系产生的成骨细胞骨转移中的作用
- 批准号:
19790127 - 财政年份:2007
- 资助金额:
$ 18.64万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
CONNEXIN 43 EXPRESSION IN ADENOCARCINOMA CELL LINE
连接蛋白 43 在腺癌细胞系中的表达
- 批准号:
6972483 - 财政年份:2004
- 资助金额:
$ 18.64万 - 项目类别:
The mechanisms of highly metastetic capasity in highly metastatic subpopulations of lung adenocarcinoma cell line and these clinical applications
肺腺癌细胞系高转移亚群的高转移能力机制及临床应用
- 批准号:
15590831 - 财政年份:2003
- 资助金额:
$ 18.64万 - 项目类别:
Grant-in-Aid for Scientific Research (C)