Paired healthy & tumor organoid Biobank B15PON
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ABSTRACT:
PROVIDER: EGAS00001005865 | EGA |
REPOSITORIES: EGA
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Project description:B16PON consists of a panel of organoids (three-dimensional cell cultures) of premalignant epithelial cells of the colon and rectum. These organoids are derived from adenomas that are resected during a colonoscopy procedure. These can be propagated indefinitely and can be used to answer different research questions.
| EGAS00001005937 | EGA
Project description:VUmc_organoids consists of a panel of organoids (three-dimensional cell cultures) of both normal, premalignant and cancer epithelial cells of the colon. These organoids were resected during a colonoscopy procedure or a surgical procedure. These organoids, derived from tumor as well as healthy tissue, can be propagated indefinitely and can be used to answer different research questions.
| EGAS00001005947 | EGA
Project description:In Rspondin-based three-dimensional cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. Here we report the establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma (CRC) patients. For most, organoids were also generated from adjacent normal tissue. Organoids closely resemble the original tumor. The spectrum of genetic changes within the 'living biobank' agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43, rather than in APC. Organoid technology may fill the gap between cancer genetics and patient trials, complement cell line- and xenograft-based drug studies and allow personalized therapy design. Self-renewal of the intestinal epithelium is driven by Lgr5 stem cells located in crypts. We have recently developed a long-term culture system that maintains basic crypt physiology. Wnt signals are required for the maintenance of active crypt stem cells. Indeed, the Wnt agonist R-spondin1 induces dramatic crypt hyperplasia in vivo. R-spondin-1 is the ligand for Lgr5. Epidermal growth factor (EGF) signaling is associated with intestinal proliferation, while transgenic expression of Noggin induces a dramatic increase in crypt numbers. The combination of R-spondin-1, EGF, and Noggin in Matrigel sustains ever-expanding small intestinal organoids, which display all hallmarks of the original tissue in terms of architecture, cell type composition, and self-renewal dynamics. We adapted the culture condition for long-term expansion of human colonic epithelium and primary colonic adenocarcinoma, by adding nicotinamide, A83-01 (Alk inhibitor), Prostaglandin E2 and the p38 inhibitor SB202190. Of note, a two-dimensional culture method for cells from normal and malignant primary tissue has been described by Schlegel and colleagues. Here, we explore organoid technology to routinely establish and phenotypically annotate ‘paired organoids’ derived from adjacent tumor and healthy epithelium from CRC patients.
2015-05-07 | E-GEOD-65253 | biostudies-arrayexpress
Project description:In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal (CRC) patients. For most, organoids were also generated from adjacent normal tissue. The organoids closely resemble the original tumor. The spectrum of genetic changes observed within the 'living biobank' agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to robotized, high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43 (rather than in APC). Organoid technology may fill the gap between cancer genetics and patient trials, complement cell line- and xenograft-based drug studies and allow personalized therapy design. We generated organoids from healthy tissue and coloncarcinoma tissue. The organoids were trypsinized, plated in matrigel and overlaid with medium. After three days, RNA was isolated using Qiagen RNAeasy. Medium conditions are the same for all organoids, irrespective of their origin.
2015-05-07 | E-GEOD-64392 | biostudies-arrayexpress
Project description:In Rspondin-based three-dimensional cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. Here we report the establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma (CRC) patients. For most, organoids were also generated from adjacent normal tissue. Organoids closely resemble the original tumor. The spectrum of genetic changes within the 'living biobank' agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43, rather than in APC. Organoid technology may fill the gap between cancer genetics and patient trials, complement cell line- and xenograft-based drug studies and allow personalized therapy design.
2015-05-07 | GSE65253 | GEO
Project description:We investigated temporal proteomic changes of human cerebral organoids during neuroanl differentiations. TMT-based quantitative proteomics analysis of cerebral organoids at multiple time potins (day 0, 25, 43, 70 and 120) was performed using two-dimensional nanoflow liquied chromatography-tandem mass spectrometry (2D-nLC-MS/MS).
2024-03-15 | PXD041173 | Pride
Project description:In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal (CRC) patients. For most, organoids were also generated from adjacent normal tissue. The organoids closely resemble the original tumor. The spectrum of genetic changes observed within the 'living biobank' agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to robotized, high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43 (rather than in APC). Organoid technology may fill the gap between cancer genetics and patient trials, complement cell line- and xenograft-based drug studies and allow personalized therapy design.
2015-05-07 | GSE64392 | GEO
Project description:Kidney tumours are among the most common solid tumours in children, comprising several distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. The malignant rhabdoid tumour organoids represent the first organoid model for tumours of non-epithelial origin. The tumour organoids retain key properties of native tumours, useful for revealing patient-specific drug vulnerabilities. We further demonstrate that organoid cultures derived from Wilms tumours consist of multiple different cell types, including epithelial, stromal and blastemal-like. Our organoid biobank captures the cellular heterogeneity of paediatric kidney tumours, providing a representative collection of well-characterized models for basic cancer research, drug-screening, and personalized medicine.
2019-09-18 | GSE137544 | GEO
Project description:Tongue cancer (TC) is the most frequent and a serious type of oral cancer with major clinical challenges such as lymph node metastasis and the appearance of chemotherapy resistant cells. Thus, development of diagnostic and therapeutic strategies to target these malignant cancer cells is urgently required. Here, we describe a novel and highly efficient method to generate human TC organoids, thereby creating a TC organoid biobank with primary and metastatic TC from 28 patients with diverse ages and cancer stages. These organoid lines can be expanded, passed, stored frozen for long periods, and they can reproduce original TC tissues in vitro and in xenograft models. The organoids showed different properties among patients with respect to the proliferation capacity and susceptibility to cisplatin, a commonly used chemotherapeutic agent in TC therapy. This suggests that TC organoids are useful for accurate risk grading and predicting the prognosis at early stages of TC, which is difficult to diagnose clinically. Thus, human TC organoids are useful for profiling TCs, which will lead to drug development against metastatic and chemotherapy-resistant TCs.
2024-09-13 | GSE145057 | GEO
Project description:Ovarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of OC are limited and hard to establish. We present a novel protocol that enables efficient derivation and long-term expansion of OC organoids. Utilizing this protocol, we have established 56 organoid lines from 32 patients, representing the spectrum of ovarian neoplasms, including non-malignant borderline tumors, as well as mucinous, clear-cell, endometrioid, low- and high-grade serous carcinomas. OC organoids recapitulate histological and genomic features of the pertinent lesion from which they were derived, illustrating intra- and inter-patient heterogeneity, and can be genetically modified. We show that OC organoids can be used for drug screening assays and capture different tumor subtype responses to the gold standard platinum-based chemotherapy, including acquisition of chemoresistance in recurrent disease. Finally, OC organoids can be xenografted, enabling in vivo drug sensitivity assays. Taken together, this demonstrates their potential application for research and personalized medicine.
| EGAS00001003073 | EGA