Obtaining patient-derived cancer organoid cultures via fine-needle aspiration.
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ABSTRACT:
SUBMITTER: Phifer CJ
PROVIDER: S-EPMC7758553 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Patient-derived cancer organoids hold great potential to accurately model and predict therapeutic responses. Efficient organoid isolation methods that minimize post-collection manipulation of tissues would improve adaptability, accuracy, and applicability to both experimental and real-time clinical settings. Here we present a simple and minimally invasive fine-needle aspiration (FNA)-based organoid culture technique using a variety of tumor types including gastrointestinal, thyroid, melanoma, and kidney. This method isolates organoids directly from patients at the bedside or from resected tissues, requiring minimal tissue processing while preserving the histologic growth patterns and infiltrating immune cells. Finally, we illustrate diverse downstream applications of this technique including in vitro high-throughput chemotherapeutic screens, in situ immune cell characterization, and in vivo patient-derived xenografts. Thus, routine clinical FNA-based collection techniques represent an unappreciated substantial source of material that can be exploited to generate tumor organoids from a variety of tumor types for both discovery and clinical applications.
| S-EPMC7415927 | biostudies-literature
Project description:Our organoid generation technique has allowed for the development of downstream organoid applications. Here, we detail an accessible, straightforward protocol for immunofluorescent staining and imaging of thyroid cancer organoids, particularly those with tumor de-differentiation. Immunofluorescence is a powerful tool to help understand the localization of cell types within organoids and determine the interactions between those cells. As organoids have been shown to recapitulate patient tumor morphology, immunofluorescent staining and imaging of organoids allows for enhanced understanding of near in vivo structures. For complete details on the use and execution of this protocol, please refer to Lee et al. (2020) and Vilgelm et al. (2020).
| S-EPMC8182106 | biostudies-literature
Project description:ObjectivesMost previous studies have analyzed bacteria in tumors using resected pancreatic cancer (PC) tissues, because it is difficult to obtain tissue samples from unresectable advanced PC. We aimed to determine whether minimal tissue obtained by endoscopic ultrasound-guided fine-needle aspiration is useful for microbiome analysis.MethodsThirty PC and matched duodenal and stomach tissues (N = 90) were prospectively collected from 30 patients who underwent endoscopic ultrasound-guided fine-needle aspiration. Bacterial DNA was extracted, and 16S rRNA sequencing was performed. The primary outcome was the success rate of bacterial detection in tumors. Bacterial diversity and structure were investigated.ResultsThe bacterial detection rates were 80%, 100%, and 97% in PC, gastric, and duodenal samples, respectively. Pancreatic cancer tissues showed a lower α-diversity and a significantly different microbial structure than stomach and duodenal tissues. Proteobacteria were more abundant, whereas Firmicutes, Bacteroidetes, and Fusobacteria were less abundant in PC tissues than in stomach and duodenal tissues. Acinetobacter was more abundant in PC tissues than in stomach and duodenal tissues, and Delftia was more frequently detected in resectable PC.ConclusionsEndoscopic ultrasound-guided fine-needle aspiration samples were valuable for PC microbiome analysis, revealing that the bacterial composition of PC is different from that of the stomach and duodenum.
| S-EPMC9257056 | biostudies-literature
Project description:PURPOSE:Cancer treatment is limited by inaccurate predictors of patient-specific therapeutic response. Therefore, some patients are exposed to unnecessary side effects and delays in starting effective therapy. A clinical tool that predicts treatment sensitivity for individual patients is needed. EXPERIMENTAL DESIGN:Patient-derived cancer organoids were derived across multiple histologies. The histologic characteristics, mutation profile, clonal structure, and response to chemotherapy and radiation were assessed using bright-field and optical metabolic imaging on spheroid and single-cell levels, respectively. RESULTS:We demonstrate that patient-derived cancer organoids represent the cancers from which they were derived, including key histologic and molecular features. These cultures were generated from numerous cancers, various biopsy sample types, and in different clinical settings. Next-generation sequencing reveals the presence of subclonal populations within the organoid cultures. These cultures allow for the detection of clonal heterogeneity with a greater sensitivity than bulk tumor sequencing. Optical metabolic imaging of these organoids provides cell-level quantification of treatment response and tumor heterogeneity allowing for resolution of therapeutic differences between patient samples. Using this technology, we prospectively predict treatment response for a patient with metastatic colorectal cancer. CONCLUSIONS:These studies add to the literature demonstrating feasibility to grow clinical patient-derived organotypic cultures for treatment effectiveness testing. Together, these culture methods and response assessment techniques hold great promise to predict treatment sensitivity for patients with cancer undergoing chemotherapy and/or radiation.
| S-EPMC6726566 | biostudies-literature
Project description:Paired FNA and CBX specimens were prospectively collected from 37 breast cancers before any systemic therapy during a biomarker discovery study at The University of Texas M. D. Anderson Cancer Center. We identified 293 probe sets overexpressed in core biopsies; these included five highly coexpressed gene clusters (metagenes) corresponding to immune functions and extracellular matrix components. We compared gene expression profiles of pairs of fine-needle (stroma-poor) and core-needle (stroma-rich) biopsies from 37 cancers to identify stroma-associated genes
2011-10-31 | GSE32518 | GEO
Project description:This is a stage-matched case control study. Cases with clinical diagnosis of Inflammatory Breast Cancer (IBC) were selected after reviewing all medical records of the 440 FNA samples. IBC was defined as signs of erythema and edema (peau d’orange) involving at least one third of the skin and rapid clinical presentation. Presence of tumor emboli in the dermal lymphatics of the involved skin in the pathology report was not required for inclusion as IBC. Controls were selected to match for T stage, all T4a-c tumors in the data set were included as controls. IBC breast cancer are all T4d breast cancer. We examined if gene expression differences exist between IBC and stage-matched Non-IBC stratified according to hormone receptor and HER2 status.
2011-07-01 | GSE22597 | GEO
Project description:BackgroundTo compare the sampling adequacy and diagnostic efficiency of ultrasound-guided fine-needle aspiration with 22-, 25-gauge needles and capillary sampling with 22-gauge needle in the biopsy of cervical lymph node.MethodsA total of 130 cervical lymph nodes from 103 patients were consecutively included in the prospective study. Each suspected lymph node was aspirated with a 22-gauge needle, capillary sampled with a 22-gauge needle and aspirated with a 25-gauge needle. The adequacy rates and nondiagnostic rates of obtained specimen were calculated.ResultsOf the 130 suspected lymph nodes, there were 77 lymph nodes<6.0 mm and 53 lymph nodes≥6.0mm in the smallest dimension. Both FNA22G and FNC22G got significantly higher sampling adequacy than FNA25G for the total lymph nodes. For lymph nodes<6.0 mm, the sampling adequacy was significantly higher with FNA22G than with FNA25G for each parameter and the cumulative score (all P<0.05), while no difference were seen between FNA22G and FNC22G, and between FNC22G and FNA25G. There were higher nondiagnostic rates for FNA25G compared with FNA22G and FNC22G in all lymph nodes and in each size subgroups. FNA25G yielded more diagnostically inadequate specimens than FNA22G and FNC22G did in the total lymph nodes (P=0.002), in lymph nodes<6.0 mm (P=0.014), and in those ≥ 6.0 mm (P=0.000).ConclusionsFNA22G and FNC22G obtained more diagnostically adequate specimens than FNA25G in cervical lymph nodes. FNA22G and FNC22G may be more suitable than FNA25G in diagnosing cervical lymph nodes. FNA22G and FNC22G may yield specimens with similar quality.
| S-EPMC8079778 | biostudies-literature
Project description:This is a stage-matched case control study. Cases with clinical diagnosis of Inflammatory Breast Cancer (IBC) were selected after reviewing all medical records of the 440 FNA samples. IBC was defined as signs of erythema and edema (peau d’orange) involving at least one third of the skin and rapid clinical presentation. Presence of tumor emboli in the dermal lymphatics of the involved skin in the pathology report was not required for inclusion as IBC. Controls were selected to match for T stage, all T4a-c tumors in the data set were included as controls. IBC breast cancer are all T4d breast cancer. We examined if gene expression differences exist between IBC and stage-matched Non-IBC stratified according to hormone receptor and HER2 status. Pre-treatment FNA from primary tumors were obtained and RNA extracted and hybridized to Affymetrix microarrays according to manufacturer protocol.
2011-07-01 | E-GEOD-22597 | biostudies-arrayexpress
Project description:Paired FNA and CBX specimens were prospectively collected from 37 breast cancers before any systemic therapy during a biomarker discovery study at The University of Texas M. D. Anderson Cancer Center. We identified 293 probe sets overexpressed in core biopsies; these included five highly coexpressed gene clusters (metagenes) corresponding to immune functions and extracellular matrix components. We compared gene expression profiles of pairs of fine-needle (stroma-poor) and core-needle (stroma-rich) biopsies from 37 cancers to identify stroma-associated genes Pre-treatment paird matched FNA and CBX from primary tumors were obtained and RNA extracted and hybridized to afymetrix microarrays according to manufacturer protocol.
2011-10-31 | E-GEOD-32518 | biostudies-arrayexpress
Project description:Breast biopsy consists in the collection of cells or tissue fragments from a breast lesion and their analysis by a pathologist. There are several types of breast biopsy defined on the basis of the type of needle used: fine-needle aspiration and biopsy performed with a spring-based needle. This article focuses on fine-needle aspiration performed under sonographic guidance.It is used mainly to assess cysts that appear to contain vegetations or blood or that are associated with symptoms; lesions and solid nodules that are not unequivocally benign; and axillary lymph nodes that appear suspicious on physical examination and/or sonography.In addition to distinguishing between benign and malignant lesions, ultrasound guided fine-needle aspiration also plays an important role in tumor grading and in immunocytochemical identifying specific tumor markers. This article describes the technique used and the possible causes of false negative and false positive findings. Despite its limitations, fine-needle aspiration has become a fundamental tool for the identification and preoperative management of malignant breast lesions.
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