Tissue Processing-Sequencing Facility
组织处理测序设备
基本信息
- 批准号:10703039
- 负责人:
- 金额:$ 91.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:Adrenal Gland NeoplasmsAdrenal MassAffectAliquotAscitesBasic ScienceBiologicalBiopsyBladderBladder NeoplasmBloodBlood specimenBody FluidsCancer Gene MutationCancer PatientCancer cell lineCarbon DioxideCell Culture TechniquesCell LineCellular Metabolic ProcessChestClear CellClinicalClinical ResearchClinical TreatmentClinical TrialsCollaborationsCollectionCommunicationCyst FluidDNADNA analysisDNA sequencingDataDatabasesDetectionDiseaseDrug ScreeningElectron MicroscopyElementsEnsureEquipment and supply inventoriesErlotinibFluorescent in Situ HybridizationFormalinFreezingFutureGene ExpressionGenesGenetic studyGenitourinary systemGenomeGlutaralGoalsHeartHereditary Leiomyomatosis and Renal Cell CancerHouse miceHumanImmunohistochemistryImmunoprecipitationImmunotherapyIncubatorsInheritedKaryotypeKaryotype determination procedureKidneyKidney NeoplasmsLaboratoriesLaboratory FindingLightLiquid substanceMalignant NeoplasmsMalignant neoplasm of prostateMalignant neoplasm of urinary bladderMetastatic Neoplasm to Lymph NodesMethodsMethylationMitochondrial DNAMolecularMolecular EpidemiologyMolecular TargetMusMutationMutation AnalysisNitrogenNorthern BlottingNuclearNude MiceOperative Surgical ProceduresOrganellesOther GeneticsOxygenOxygen ConsumptionPaperPapillaryPathway interactionsPatientsPharmaceutical PreparationsPharmacodynamicsPheochromocytomaPlasmaPolymorphism AnalysisProceduresProcessProstateProstate carcinomaProstatic NeoplasmsProteinsProteomicsPublishingRNAReactive Oxygen SpeciesReagentRecording of previous eventsRenal Cell CarcinomaRenal carcinomaResearchResearch PersonnelResourcesReverse Transcriptase Polymerase Chain ReactionSalivaSamplingScientistSecureSerumSingle Nucleotide PolymorphismSiteSpecimenSterilitySuccinate DehydrogenaseSurgical PathologySyndromeTechniquesTestingThe Cancer Genome AtlasTherapeutic AgentsTimeTissue BanksTissue SampleTissuesTuberous SclerosisTumor TissueUnited States National Institutes of HealthUrineUrogenital CancerUrologic CancerUrologic OncologyUterine FibroidsWestern BlottingWhole BloodXenograft ModelXenograft procedureaccurate diagnosisbench to bedsidebevacizumabbladder Carcinomabladder surgerycancer biomarkerscancer typecentral databaseclinical centercomparative genomic hybridizationepidemiology studyexomeexome sequencingextracellulargene discoveryinhibitorkidney surgerykinase inhibitormetabolomicsmolecular targeted therapiesnew therapeutic targetnext generationpharmacokinetics and pharmacodynamicspreservationprospectiveprotein expressionprotein metabolitetissue processingtumortumorigenesiswhole genome
项目摘要
The Tissue Processing and Sequencing Facility (TPSF) is essential in providing support and resources for the Urologic Oncology Branch (UOB) and for our collaborators. The TPSF handles every biospecimen that is generated within the UOB, processes each specimen in order to preserve biomolecules, keeps an accurate inventory of each procurement, and assists in the scientific analysis of select specimens, for the ultimate goal of elucidating biological pathways relating to kidney, prostate, and bladder cancers. The TPSF processes tissue from nearly 100% of UOB surgeries, as well as a subset of biopsies and other procedures. Typically, there are 3 to 8 surgeries and 10 to 20 biopsies per week, resulting in tissue samples procured from over 400 patients per year, including kidney, prostate, and bladder carcinomas, adrenal tumors, uterine leiomyomas, lymph node metastases, and other specimens relating to sporadic and familial urologic cancer syndromes. Tissue is always procured in cooperation with Surgical Pathology, to ensure proper handling and accurate diagnosis. Tissue is snap frozen, preserved in formalin or glutaraldehyde, or processed for biomolecule (DNA, RNA, protein, metabolite) purification and analysis. In addition, DNA, serum, and plasma are regularly prepared from blood samples taken from patients with inherited syndromes. Whole blood or RNA may also be procured and stored from select patients. Over two dozen blood samples may be processed per week. Finally, the core also procures and processes urine, ascites or thoracic fluids, cyst fluids, saliva, and other body fluids. Frozen samples are stored in liquid nitrogen or in a -80 degree centigrade freezer. Specimens are assigned a de-identified lab number and entered into a secure database, Labmatrix. Approximately 2,000 tissue and 800 blood specimens have been procured and processed within the past year. The entire UOB tissue repository contains in excess of 25,000 tissue samples, and DNA from over 5,000 blood samples and 800 tumors. Most of the samples were collected at the NIH Clinical Center, and full patient histories are incorporated into Labmatrix. A future goal is for all clinical and laboratory findings to be incorporated into Labmatrix to provide an accessible resource for all of our studies from bench to bedside. A key function of the TPSF is to support clinical trials within the Branch. This past year we handled samples from patients in several clinical trials that are open to accrual: Bevacizumab and Erlotinib for patients with metastatic papillary kidney cancer or HLRCC, a Met kinase inhibitor INC280 for patients with papillary kidney cancer, a HIF2 inhibitor for patients with VHL, PANVAC-BCG vs. BCG for patients with high grade bladder cancer, and Durvalumab and Vicinium for patients with high grade bladder cancer. Several new clinical trials are also currently being established. Blood and/or urine samples are processed at regular intervals, for the purpose of investigating pharmacodynamic and phamacokinetic effects of the drugs, as well as other cancer biomarkers. Many of the tumor samples from kidney and bladder surgeries are procured under sterile conditions to establish new cell cultures and mouse xenografts. We have generated over 300 kidney cancer cell lines, 92 of which have been extensively characterized for cancer gene mutations. Lines have been generated from hereditary kidney cancer syndromes (BHD, SDHB, SDHD, VHL, BAP1, HPRC, and HLRCC) and from rare kidney cancer types (chromophobe, TFE-3 RCC, and medullary RCC) that provide unique reagents. In the last year, about a dozen kidney tumors and a few prostate and bladder tumors have been placed in cell culture and/or in SCID/BEIG or nude mice, with a subset of these growing viably in the short-term and a small number (two this year) that become immortal. These lines are invaluable for studying both the molecular basis of tumorigenesis and prospective therapies. In a recent study, a subset of our lines were subjected to drug screening. Cell lines are kept in standard carbon dioxide or low oxygen incubators or stored in liquid nitrogen, and mice are housed in an appropriate on-site facility. Some lines have been extensively characterized by nuclear and mitochondrial DNA sequencing and copy number of selected genes, array CGH, karyotype, methylation, real-time PCR, Western blotting, oxygen consumption and extracellular acidification rate, and metabolomics. The collection of DNA samples for the detection and characterization of germline disease mutations has been at the heart of the gene discovery process in the UOB. Several dozen blood samples per year are analyzed by DNA sequencing including next-generation whole exome, whole genome, and targeted gene sequencing, comparative genome hybridization (CGH) analysis, fluorescent in-situ hybridization (FISH), and/or other genetic studies. We continue to use these techniques to discover new mutations, deletions, translocations, and amplifications. Both frozen and formalin-fixed tissues from kidney, prostate, and bladder cancers that have been processed by the TPSF have been characterized extensively within the UOB by immunohistochemistry, quantitative PCR, expression microarrays, Northern and Western blotting, immunoprecipitation, and nuclear and mitochondrial DNA sequencing. Glutaraldehyde-fixed tissues have been used for electron microscopy, in order to characterize subcellular organelles. Proper handling of our surgical specimens has been an essential factor in assuring the best quality laboratory results. The UOB is also involved in providing aliquots of many of its procured tumor tissues and blood samples to collaborating laboratories. The Branch has long-standing collaborations in which we distribute tissue to other laboratories for cell culture and immunotherapy for kidney cancer patients, analysis of kidney cancer cellular markers, cancer gene mutation analysis, protein and RNA studies of adrenal masses (pheochromocytomas), and molecular epidemiology studies of prostate cancers. We participated in several Cancer Genome Atlas (TCGA) projects, by contributing clear cell, chromophobe and papillary renal tumors as well as prostate tumors. The sizeable biospecimen collection amassed by the UOB over the last 35 years provides an invaluable resource for both basic and clinical research regarding kidney, prostate and bladder cancers.
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)
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{{ truncateString('Cathy D Vocke', 18)}}的其他基金
相似海外基金
FUNCTIONAL/MORPHOLOGIC IMAGING OF THE ADRENAL MASS
肾上腺肿块的功能/形态学成像
- 批准号:
3185476 - 财政年份:1986
- 资助金额:
$ 91.73万 - 项目类别:
FUNCTIONAL/MORPHOLOGIC IMAGING OF THE ADRENAL MASS
肾上腺肿块的功能/形态学成像
- 批准号:
3185474 - 财政年份:1986
- 资助金额:
$ 91.73万 - 项目类别: