A Label-Free, Many-Parameter Benchtop Platform for Functionally-Preserved, Viable Cancer Stem Cell Isolation and Biomarker Discovery to Probe Urothelial Carcinoma of the Bladder
A Label-Free, Many-Parameter Benchtop Platform for Functionally-Preserved, Viable Cancer Stem Cell Isolation and Biomarker Discovery to Probe Urothelial Carcinoma of the Bladder
批准号:
10086817
负责人:
Karthik Ratna Balakrishnan
金额:
$5.5万
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
项目状态:
已结题
起止时间:
2019-09-20 至 2021-08-31
关键词:
AddressBenchmarkingBiological AssayBiological MarkersBladder NeoplasmCD44 geneCalibrationCell LineCell SeparationCell SurvivalCell TherapyCellsCellular AssayCessation of lifeCisplatinClinicalDetectionDevelopmentEarly DiagnosisFlow CytometryFluorescenceFluorescence-Activated Cell SortingGenerationsGenesGrowthHeterogeneityLabelLeadMaintenanceMalignant - descriptorMalignant NeoplasmsMalignant neoplasm of urinary bladderMarker DiscoveryMasksMicrofluidicsMolecularMonitorOutcomePainPatient-Focused OutcomesPatientsPhasePopulationPopulation ControlPropertyQuantitative Reverse Transcriptase PCRRegulationResistanceSamplingScreening for cancerSorting - Cell MovementSystemTechnologyTestingTimeTransitional Cell CarcinomaTransurethral ResectionUnited StatesUniversitiesUrinary tractUrineUrotheliumValidationWalkingXenograft procedurebasebiomarker discoverybiomarker identificationbiomarker panelbladder Carcinomabladder transitional cell carcinomacancer cellcancer stem cellcancer subtypeschemotherapeutic agentearly detection biomarkersimprovedinsightinstrumentmedical schoolsnovelnovel therapeuticspreservationscreeningstem-like celltargeted treatmenttherapy developmenttooltraittreatment optimizationtumor
中文摘要
Nodexus先前开发的NX One系统利用节点孔传感电检测(非孔传感)
英文摘要
Nodexus’ previously developed NX One system leverages node-pore sensing electrical detection (non-
marker-based) and fluorescence-based marker detection of cells in combination with low-shear microfluidic
valving for viable cell sorting and single-cell isolation. In this proposal, we highlight a new instrument that
integrates our demonstrated node-pore sensing (“NPS”) single-cell isolation with label-free multi-marker
screening for the quickly emerging cancer stem cell (CSC) space, efficient biomarker discovery and
functional studies for targeted therapy development would be transformative, but easy access to viable,
functionally-preserved live single-cells is not possible using any single commercial instrument. While
the platform will eventually be applicable across more cancer subtypes, our initial point of entry into this sector
focuses on urothelial carcinoma of the bladder (UCB). Urothelial carcinoma of the bladder is the most common
malignancy of the urinary tract, with >600,000 living with bladder cancer and ~79,030 new cases and 16,870
deaths per year in the United States. From extensive conversations with experts in the field, we have found
critical pain points related to UCB that the Nodexus platform can address.
CSCs are a subpopulation within a heterogeneous mixture of cancer cells that have enhanced pro-
malignant properties, but the contribution of specific markers to stem cell-like traits and their clinical utility as
biomarkers have not been conclusively determined, making targeted therapy for these cells extremely
challenging. A better understanding of the molecular mechanisms underlying urothelial CSC regulation and
identification of key molecules associated with CSC generation and maintenance are pivotal for the
determination of universally accepted, clinically-accurate biomarkers for early cancer detection and monitoring
following transurethral resection of bladder tumor (TURBT) as well as the development of effective targeted
therapies.
The complexity with studying CSCs is immensely increased due to the heterogeneity within tumors and
the variance in CSC-like traits and functional importance in different cancer subtypes. Conclusive confirmation
of marker-associated functionality will open the door for targeted therapy development. Further studies of
comprehensive panels of markers performed simultaneously will provide significant value for downstream
studies for conclusive biomarker identification and optimized therapies. Critically, the functional relevance of
such markers must be evaluated and understood; this requires being able to comprehensively screen for
numerous markers, isolate single-cell populations to unveil masked heterogeneity, and perform downstream
functional studies (e.g. growth, invasion, and resistance to chemotherapeutic agents) on these viable,
functionally-preserved isolated single-cells. While existing technologies, such as FACS, MACS, and CyTOF have
provided tremendous value within the broader space, none provide label-free easy access to extensively
characterized, live, functionally preserved single CSCs in a manner that the Nodexus platform will offer.
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批准号:10172022
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项目类别:
-
资助金额:$24.88万
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财政年份:2019
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负责人:Karthik Ratna Balakrishnan
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依托单位:
国内基金
海外基金
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批准号:70571028
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项目类别:面上项目
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资助金额:16.5万元
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批准年份:2005
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负责人:杨印生
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依托单位: