Relevant bibliographies by topics / Patient-derived organoids

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  1. Journal articles
  2. Dissertations / Theses
  3. Book chapters
  4. Conference papers

Academic literature on the topic 'Patient-derived organoids'

Author: Grafiati
Published: 15 April 2023

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Journal articles on the topic "Patient-derived organoids"

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Maier, Christopher Fabian, Lei Zhu, Lahiri Kanth Nanduri, Daniel Kühn, Susan Kochall, May-Linn Thepkaysone, Doreen William, et al. "Patient-Derived Organoids of Cholangiocarcinoma." International Journal of Molecular Sciences 22, no. 16 (August 12, 2021): 8675. http://dx.doi.org/10.3390/ijms22168675.

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Cholangiocarcinoma (CC) is an aggressive malignancy with an inferior prognosis due to limited systemic treatment options. As preclinical models such as CC cell lines are extremely rare, this manuscript reports a protocol of cholangiocarcinoma patient-derived organoid culture as well as a protocol for the transition of 3D organoid lines to 2D cell lines. Tissue samples of non-cancer bile duct and cholangiocarcinoma were obtained during surgical resection. Organoid lines were generated following a standardized protocol. 2D cell lines were generated from established organoid lines following a novel protocol. Subcutaneous and orthotopic patient-derived xenografts were generated from CC organoid lines, histologically examined, and treated using standard CC protocols. Therapeutic responses of organoids and 2D cell lines were examined using standard CC agents. Next-generation exome and RNA sequencing was performed on primary tumors and CC organoid lines. Patient-derived organoids closely recapitulated the original features of the primary tumors on multiple levels. Treatment experiments demonstrated that patient-derived organoids of cholangiocarcinoma and organoid-derived xenografts can be used for the evaluation of novel treatments and may therefore be used in personalized oncology approaches. In summary, this study establishes cholangiocarcinoma organoids and organoid-derived cell lines, thus expanding translational research resources of cholangiocarcinoma.
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Lee, Chansu, Sung-Noh Hong, Eun-Ran Kim, Dong-Kyung Chang, and Young-Ho Kim. "Epithelial Regeneration Ability of Crohn’s Disease Assessed Using Patient-Derived Intestinal Organoids." International Journal of Molecular Sciences 22, no. 11 (June 2, 2021): 6013. http://dx.doi.org/10.3390/ijms22116013.

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Little is known about the ability for epithelial regeneration and wound healing in patients with inflammatory bowel diseases. We evaluated the epithelial proliferation and wound healing ability of patients with Crohn’s disease (CD) using patient-derived intestinal organoids. Human intestinal organoids were constructed in a three-dimensional intestinal crypt culture of enteroscopic biopsy samples from controls and CD patients. The organoid-forming efficiency of ileal crypts derived from CD patients was reduced compared with those from control subjects (p < 0.001). Long-term cultured organoids (≥6 passages) derived from controls and CD patients showed an indistinguishable microscopic appearance and culturing behavior. Under TNFα-enriched conditions (30 ng/mL), the organoid reconstitution rate and cell viability of CD patient-derived organoids were significantly lower than those of the control organoids (p < 0.05 for each). The number of EdU+ cells was significantly lower in TNFα-treated organoids derived from CD patients than in TNFα-treated control organoids (p < 0.05). In a wound healing assay, the unhealed area in TNFα-treated CD patient-derived organoids was significantly larger than that of TNFα-treated control organoids (p < 0.001). The wound healing ability of CD patient-derived organoids is reduced in TNFα-enriched conditions, due to reduced cell proliferation. Epithelial regeneration ability may be impaired in patients with CD.
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Weeber, Fleur, Marc van de Wetering, Marlous Hoogstraat, Krijn K. Dijkstra, Oscar Krijgsman, Thomas Kuilman, Christa G. M. Gadellaa-van Hooijdonk, et al. "Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases." Proceedings of the National Academy of Sciences 112, no. 43 (October 12, 2015): 13308–11. http://dx.doi.org/10.1073/pnas.1516689112.

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Tumor organoids are 3D cultures of cancer cells. They can be derived from the tumor of each individual patient, thereby providing an attractive ex vivo assay to tailor treatment. Using patient-derived tumor organoids for this purpose requires that organoids derived from biopsies maintain the genetic diversity of the in vivo tumor. In this study tumor biopsies were obtained from 14 patients with metastatic colorectal cancer (i) to test the feasibility of organoid culture from metastatic biopsy specimens and (ii) to compare the genetic diversity of patient-derived tumor organoids and the original tumor biopsy. Genetic analysis was performed using SOLiD sequencing for 1,977 cancer-relevant genes. Copy number profiles were generated from sequencing data using CopywriteR. Here we demonstrate that organoid cultures can be established from tumor biopsies of patients with metastatic colorectal cancer with a success rate of 71%. Genetic analysis showed that organoids reflect the metastasis from which they were derived. Ninety percent of somatic mutations were shared between organoids and biopsies from the same patient, and the DNA copy number profiles of organoids and the corresponding original tumor show a correlation of 0.89. Most importantly, none of the mutations that were found exclusively in either the tumor or organoid culture are in driver genes or genes amenable for drug targeting. These findings support further exploration of patient-derived organoids as an ex vivo platform to personalize anticancer treatment.
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Valeri, Nicola. "Abstract IA010: Patient derived organoids in precision oncology." Cancer Research 82, no. 23_Supplement_1 (December 1, 2022): IA010. http://dx.doi.org/10.1158/1538-7445.crc22-ia010.

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Abstract Limits in the predictive power of molecular profiling and shortcomings of some pre-clinical models used in drug development represent important obstacles hampering the success of personalized medicine and drug discovery. LGR5+ stem cells can be isolated from a number of organs and propagated as epithelial organoids in vitro. Mouse and human organoids have been used to study the physiology and neoplastic transformation of the liver, pancreas, bowel and prostate among other organs. During my talk, I will highlight opportunities, limitations and potential clinical applications of patient-derived organoids in personalized oncology, emphasizing strengths and hurdles in the use of the organoid technology in forward and reverse translational cancer research. In particular, I will stress the importance of patient-derived organoids as pre-clinical tools to define mechanisms of drug resistance and to design novel drug combinations. Citation Format: Nicola Valeri. Patient derived organoids in precision oncology [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr IA010.
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McQueeney, Kelley E., Patrick Bhola, Sarah J. Hill, and Anthony Letai. "Abstract 4309: Early apoptotic measurements of patient-derived organoids predict patient response to therapy." Cancer Research 83, no. 7_Supplement (April 4, 2023): 4309. http://dx.doi.org/10.1158/1538-7445.am2023-4309.

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Abstract The use of imperfect models and ex vivo culture systems to try to predict patient drug response represents an enormous bottle neck in cancer treatment. Nonetheless, determining how effective an approved drug will be for an individual cancer patient, as well as identifying novel compounds that may be beneficial to a specific population often requires the use of primary tumor cells. Patient-derived organoids represent an intermediate between primary tumor cells, whose limited supply may hinder reliable drug testing, and cell lines, which often do not reflect what happens in vivo. Herein, we describe the development of a novel assay platform, termed 3D-DBP (3D dynamic BH3 profiling), to detect early apoptotic measurements in ovarian cancer patient-derived organoids and present evidence that this method can be used to predict patient response to therapy. We have optimized the use of patient-derived organoids from 16 individual tumors in a microscopy-based imaging assay. We image the BH3 peptide-induced release of cytochrome c from mitochondria, which indicates permeabilization of the outer mitochondrial membrane, in intact organoids. The less cytochrome c retained in each organoid, the more primed that organoid is for apoptosis. By comparing results of drug-treated and untreated cells, we can identify drugs that cause a significant increase in apoptotic priming in organoids. In the 16 patient-derived organoids investigated this 3D DBP technique was an effective means of predicting patient response to carboplatin therapy. In summary, we have not only created a means of visualizing drug response in intact organoids, but also have demonstrated its clinical utility. Citation Format: Kelley E. McQueeney, Patrick Bhola, Sarah J. Hill, Anthony Letai. Early apoptotic measurements of patient-derived organoids predict patient response to therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4309.
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Sondorp, Luc H. J., Vivian M. L. Ogundipe, Andries H. Groen, Wendy Kelder, Annelies Kemper, Thera P. Links, Robert P. Coppes, and Schelto Kruijff. "Patient-Derived Papillary Thyroid Cancer Organoids for Radioactive Iodine Refractory Screening." Cancers 12, no. 11 (October 31, 2020): 3212. http://dx.doi.org/10.3390/cancers12113212.

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Patients with well-differentiated thyroid cancer, especially papillary thyroid cancer (PTC), are treated with surgical resection of the thyroid gland. This is followed by post-operative radioactive iodine (I131), resulting in total thyroid ablation. Unfortunately, about 15-33% of PTC patients are unable to take up I131, limiting further treatment options. The aim of our study was to develop a cancer organoid model with the potential for pre-treatment diagnosis of these I131-resistant patients. PTC tissue from thirteen patients was used to establish a long-term organoid model. These organoids showed a self-renewal potential for at least five passages, suggesting the presence of cancer stem cells. We demonstrated that thyroid specific markers, a PTC marker, and transporters/receptors necessary for iodine uptake and thyroid hormone production were expressed on a gene and protein level. Additionally, we cultured organoids from I131-resistant PTC material from three patients. When comparing PTC organoids to radioactive iodine (RAI)-refractory disease (RAIRD) organoids, a substantial discordance on both a protein and gene expression level was observed, indicating a treatment prediction potential. We showed that patient-derived PTC organoids recapitulate PTC tissue and a RAIRD phenotype. Patient-specific PTC organoids may enable the early identification of I131-resistant patients, in order to reduce RAI overtreatment and its many side effects for thyroid cancer patients.
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Koedoot, Esmee, Inez van Weersch, Gakuro Harada, Masahiko Watanabe, Hamdy Warda, Hideaki Kyan, Yasmine Abouleila, et al. "Abstract 157: Patient in the lab: Down-scaling patient-derived organoid screening for diagnostic purposes." Cancer Research 83, no. 7_Supplement (April 4, 2023): 157. http://dx.doi.org/10.1158/1538-7445.am2023-157.

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Abstract Colorectal cancer (CRC) is the third leading cause of cancer and cancer-related death. A large fraction of the CRC patients diagnosed with de novo metastatic disease do not benefit from standard of care and experience substantial side effects. Therefore, there is an urgent need for preclinical models that help predict patient response in the clinic. Patient-derived organoids (PDOs or HUB Organoids®) represent a significant breakthrough as preclinical models as they are directly established from patient tissue and faithfully recapitulate patient disease. HUB Organoid Technology can already be applied to preclinical drug screening, however, to provide direct patient benefit the turnaround time between patient diagnosis and PDO-based results must be shortened. In collaboration with Yamaha Motor, the Yamaha CELL HANDLERTM has been validated to automatically pick-and-place with high accuracy a significantly reduced number of organoids per screening plate, compared to standard procedures. In addition, an image-based readout was developed that enables a precise quantification of organoid number ensuring high assay quality. Organoid responses to chemotherapy and targeted agents were validated using this newly automated system, confirming comparable PDO-patient drug sensitivity profiles, and known drug responses based on genetic dependencies. In summary we describe the development of an automated workflow that combines patient-representative HUB Organoids and state-of-the-art robotics by Yamaha CELL HANDLER. This workflow down-scales the number of organoids needed per screening well and allows to efficiently predict patient response, thereby reducing the diagnostic turnaround time and increasing patient benefits. Citation Format: Esmee Koedoot, Inez van Weersch, Gakuro Harada, Masahiko Watanabe, Hamdy Warda, Hideaki Kyan, Yasmine Abouleila, Takahiko Kumagai, Yuichi Hikichi, René Overmeer, Jeanine Roodhart, Kiyotaka Matsuno, Carla Verissimo, Sylvia F. Boj. Patient in the lab: Down-scaling patient-derived organoid screening for diagnostic purposes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 157.
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Costales-Carrera, Alba, Asunción Fernández-Barral, Pilar Bustamante-Madrid, Orlando Domínguez, Laura Guerra-Pastrián, Ramón Cantero, Luis del Peso, Aurora Burgos, Antonio Barbáchano, and Alberto Muñoz. "Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue." Cancers 12, no. 8 (August 15, 2020): 2302. http://dx.doi.org/10.3390/cancers12082302.

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Colon and rectal tumors, often referred to as colorectal cancer, show different gene expression patterns in studies that analyze whole tissue biopsies containing a mix of tumor and non-tumor cells. To better characterize colon and rectal tumors, we investigated the gene expression profile of organoids generated from endoscopic biopsies of rectal tumors and adjacent normal colon and rectum mucosa from therapy-naive rectal cancer patients. We also studied the effect of vitamin D on these organoid types. Gene profiling was performed by RNA-sequencing. Organoids from a normal colon and rectum had a shared gene expression profile that profoundly differed from that of rectal tumor organoids. We identified a group of genes of the biosynthetic machinery as rectal tumor organoid-specific, including those encoding the RNA polymerase II subunits POLR2H and POLR2J. The active vitamin D metabolite 1α,25-dihydroxyvitamin D3/calcitriol upregulated stemness-related genes (LGR5, LRIG1, SMOC2, and MSI1) in normal rectum organoids, while it downregulated differentiation marker genes (TFF2 and MUC2). Normal colon and rectum organoids share similar gene expression patterns and respond similarly to calcitriol. Rectal tumor organoids display distinct and heterogeneous gene expression profiles, with differences with respect to those of colon tumor organoids, and respond differently to calcitriol than normal rectum organoids.
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Verissimo, Carla S., Lidwien Smabers, Emerens Wensink, Esmee Koedoot, Maarten Huismans, Celia Higuera Barón, Ricardo Korporaal, et al. "Abstract 4112: Patient derived organoids predict clinical response: A patient in the lab." Cancer Research 82, no. 12_Supplement (June 15, 2022): 4112. http://dx.doi.org/10.1158/1538-7445.am2022-4112.

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Abstract Colorectal cancer (CRC) is the third leading cause of cancer and cancer-related death. A large fraction of the CRC patients diagnosed with de novo metastatic disease do not benefit from the standard of care but still experience substantial side effects. Therefore, there is the urgency for a new model to predict clinical response. Adult epithelial stem cell (ASC) -derived organoids are proving to be a major breakthrough in pre-clinical models. ASC-derived organoids can be developed from healthy as well as diseased tissue, including cancer lesions and therefore are often referred to as patient-derived organoids (PDOs or HUB Organoids࣪). These model is established directly from patient tissue, represent the tissue of origin and faithfully recapitulate patient disease in vitro and can be propagated for drug testing in a matter of weeks. PDOs bridges the gap between the lab and the clinic and effectively bring a “patient in the lab.” In this study we aimed to validate the predictive value of PDOs in the stratification of metastatic CRC (mCRC) patients for treatment with chemotherapeutic agents. PDOs from mCRC tissues were established following our optimized procedures and drug screening was performed. Clinical response was compared with PDO drug response and the best predicting drug response parameters (growth rate (GR), GRmax, GR50 and area under the curve) were identified. The patient response was evaluated by the percentage of change in size of the target lesions on response scans (% size change), best Response Evaluation Criteria in Solid Tumors (RECIST) response and progression-free survival (PFS). Importantly, we validated the predictive value of organoids towards fluorouracil (5-FU). We are validating these results in a large trial. Current efforts to further expand our PDO and drug sensitivity biobank will enable the implementation of the personalized HUB Organoid Technology to accurate and fast predict of the treatment response to improve clinical outcome of mCRC patients. Citation Format: Carla S. Verissimo, Lidwien Smabers, Emerens Wensink, Esmee Koedoot, Maarten Huismans, Celia Higuera Barón, Ricardo Korporaal, Emma Teal, Katerina-Chara Pitsa, Edwin van Oosten, Roshni Nair, Liselot Valkenburg, Geert Cirkel, Anneta Brousali, Jorieke Salij, René Overmeer, Manon Braat, Sjoerd Elias, Robert Vries, Onno Kranenburg, Miriam Koopman, Sylvia F. Boj, Jeanine Roodhart. Patient derived organoids predict clinical response: A patient in the lab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4112.
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Pernik, Mark N., Cylaina E. Bird, Jeffrey I. Traylor, Diana D. Shi, Timothy E. Richardson, Samuel K. McBrayer, and Kalil G. Abdullah. "Patient-Derived Cancer Organoids for Precision Oncology Treatment." Journal of Personalized Medicine 11, no. 5 (May 17, 2021): 423. http://dx.doi.org/10.3390/jpm11050423.

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The emergence of three-dimensional human organoids has opened the door for the development of patient-derived cancer organoid (PDO) models, which closely recapitulate parental tumor tissue. The mainstays of preclinical cancer modeling include in vitro cell lines and patient-derived xenografts, but these models lack the cellular heterogeneity seen in human tumors. Moreover, xenograft establishment is resource and time intensive, rendering these models difficult to use to inform clinical trials and decisions. PDOs, however, can be created efficiently and retain tumor-specific properties such as cellular heterogeneity, cell–cell and cell–stroma interactions, the tumor microenvironment, and therapeutic responsiveness. PDO models and drug-screening protocols have been described for several solid tumors and, more recently, for gliomas. Since PDOs can be developed in clinically relevant time frames and share many characteristics of parent tumors, they may enhance the ability to provide precision oncologic care for patients. This review explores the current literature on cancer organoids, highlighting the history of PDO development, organoid models of glioma, and potential clinical applications of PDOs.
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Dissertations / Theses on the topic "Patient-derived organoids"

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Raimondi, Giulia. "Broadening Adenoviral Oncolysis in PDAC: Interrogation of Patient-Derived Organoids for personalized virotherapy and modulation of miRNA content to boost adenoviral potency." Doctoral thesis, Universitat de Barcelona, 2020. http://hdl.handle.net/10803/671205.

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The general goal of this thesis has been to progress oncolytic adenovirus therapy for PDAC, by the incorporation of novel preclinical models to test for patient-specific responses and the generation of oncolytic adenoviruses with enhanced therapeutic index. The two main objectives have been the following: i) Evaluate patients-derived organoids (PDOs) technology as a platform to screen for personalized virotherapy in vitro 1) Establishment of a battery of PDOs from PDAC and normal pancreatic tissues, and evaluation of their applicability in the study of adenoviral infection; 2) Screening of a battery of PDOs to identify individual sensitivities to virotherapies, and the effects derived from the combination with chemotherapy; 3) Study virotherapy-responses in metastasis originated from PDOs xenografted in mice; (ii) Improve oncolytic adenovirus potency by modulation of miRNAs deregulated in PDAC 4) Screening of aberrantly expressed miRNAs sensitizing viral oncolysis in PDAC via CRISPR/Cas9 system; 5) Generation of a miRNA sponge-adenovirus and evaluation of its oncolytic effects in vitro and in vivo; 6) Modulation of miRNA levels with the THZ1 transcriptional inhibitor, and assessment of the effects of its combination with oncolytic adenoviruses.
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Seitlinger, Joseph. "Optimisation d’un modèle d’organoïde de cancer du poumon vascularisé dérivé de patient à des fins de médecine de précision." Electronic Thesis or Diss., Strasbourg, 2022. http://www.theses.fr/2022STRAJ022.

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Malgré les nombreuses avancées récentes, le cancer du poumon est la première cause de mortalité par cancer à travers le monde. Chaque année de nouvelles molécules thérapeutiques sont développées pour lutter contre cette maladie dont le pronostic demeure sombre. Le développement de la médecine de précision doit permettre d’en améliorer l’efficacité. Dans cette perspective, nous avons optimisé un modèle d’organoïde dérivé de patients atteints de cancer du poumon. Dans ce travail, nous avons pu montrer que notre modèle est reproductible et qu’il mime la tumeur du patient. Enfin, la formation d’un réseau vasculaire au niveau de l’organoïde est possible : celui-ci peut infiltrer l’organoïde formé, mais peut également se développer à partir de l’organoïde pour infiltrer le micro-environnement. Le modèle que nous mettons en avant répond donc au cahier des charges d’un modèle d’Avatar patient. Les tests de molécules thérapeutiques ou d’irradiation que nous réalisons actuellement nous permettrons de définir si ce modèle est compatible avec une future utilisation en pratique clinique pour améliorer la prise en charge des patients atteints de cancer du poumon
Despite numerous recent advances, lung cancer is the leading cause of cancer mortality worldwide. Every year, new therapeutic drugs are developed to fight this disease whose prognosis remains poor. The development of precision medicine should make it possible to improve its effectiveness. In this perspective, we have optimized an organoid model derived from lung cancer patients. In this work, we were able to show that our model is reproducible and that it mimics the patient's tumor. Finally, the formation of a vascular network at the level of the organoid is possible : it can infiltrate the formed organoid but can also grow from the organoid to infiltrate the microenvironment. The model that we put forward thus meets the specifications of a patient Avatar model. The tests of therapeutic drugs or irradiation that we are currently carrying out will allow us to define if this model is compatible with a future use in clinical practice to improve the management of patients diagnosed with lung cancer
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Morice, Pierre-Marie. "Evaluation de la déficience de la recombinaison homologue et de la réponse des tumeurs ovariennes aux inhibiteurs de PARP grâce à l'utilisation de modèles de culture 3D en vue du développement d'un test prédictif Identifying eligible patients to PARP inhibitors: from NGS-based tests to promising 3D functional assays Automated scoring for assessment of RAD51-mediated homologous recombination in patient-derived tumor organoids of ovarian cancers Risk of myelodysplastic syndrome and acute myeloid leukemia related to PARP inhibitors: a combined approach using a safety meta-analysis of placebo randomized controlled trials and the World Health Organization's pharmacovigilance database The long non-coding RNA ‘UCA1’ modulates the response to chemotherapy of ovarian cancer through direct binding to miR-27a-5p and control of UBE2N levels." Thesis, Normandie, 2020. http://www.theses.fr/2020NORMC414.

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Chaque année, plus de 150 000 décès sont associés aux cancers épithéliaux de l’ovaire dans le monde, notamment en raison du développement d’une résistance à la chimiothérapie. Environ la moitié de ces cancers présentent des altérations moléculaires provoquant une déficience de la réparation de l’ADN par recombinaison homologue (HRD) qui les sensibilise à l’action des inhibiteurs de la protéine PARP (PARPi). A ce jour, il n’existe pas de test capable d’appréhender le phénotype HRD dans sa globalité, limitant ainsi l’accès à ces traitements. Dans ce contexte, nous avons entrepris de mettre au point des tests fonctionnels basés sur l’utilisation d’explants tumoraux tranchés puis sur l’utilisation d’organoïdes tumoraux dérivés de tumeurs ovariennes de patientes chimio-naïves ou antérieurement traitées. La culture d’explants s’est révélée inappropriée pour la réalisation de ces tests et nous avons alors focalisé nos travaux sur les organoïdes tumoraux. Ces derniers ont été exposés au carboplatine (traitement de 1e ligne) et à deux inhibiteurs de PARP (l’olaparib et le niraparib) utilisés en traitement d’entretien. En parallèle, nous avons collecté les données cliniques des patientes (survie, intervalle sans platine, RECIST, traitements) afin d’évaluer le potentiel prédictif de ces modèles. Les organoïdes tumoraux établis ont répondu de façon hétérogène aux différents médicaments testés, et nos résultats montrent que les tests réalisés sur les organoïdes sont capables d’identifier des patientes présentant un niveau de résistance élevé au carboplatine, suggérant que ce test fonctionnel pourrait présenter un intérêt prédictif vis-à-vis de ce médicament. Concernant le potentiel prédictif des organoïdes vis-à-vis des PARPi, des profils de sensibilité variés ont été identifiés, mais la corrélation avec la réponse clinique reste à établir par des études menées sur des échantillons de tumeurs issus de patientes traitées par ces médicaments
Worldwide each year, more than 150 000 women die from epithelial ovarian cancer largely due to emergence of resistance to chemotherapy. Approximately half of these cancers display molecular alterations that cause deficiency of DNA repair via homologous recombination (HRD), which confer sensitivity to PARP protein inhibitors (PARPi). To date, there is no test capable of fully identifying the HRD phenotype, thus limiting access to these treatments. In this context, we are developing functional assays based on the use of tumor explant slices and then, on the use of tumor organoids derived from ovarian tumors of chemotherapy-naive or previously treated patients. The culture of explants was unsuitable for this application and we then focused our work on tumor organoids. Tumor organoids were exposed to carboplatin (first-line treatment) and two PARP inhibitors (olaparib and niraparib) used for maintenance therapy. In parallel, we collected clinical data from patients (survival, platinum-free interval, RECIST, treatments) to evaluate the predictive potential of these models. The established tumor organoids responded heterogeneously to different drugs, and our results show that the organoid-based assay is capable of identifying patients highly resistant to carboplatin, suggesting that this functional assay could have a predictive value for patients treated with carboplatin. Regarding the potential of organoids in predicting PARPi response, multiple sensitivity profiles have been identified, but the correlation with clinical response has yet to be determined by studies conducted on tumor samples from patients treated with these drugs
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Johansson, Seiko. "Patient-derived organoid culture for 3D culture of colorectal cancer, renal cancer and osteosarcoma." Thesis, Uppsala universitet, Institutionen för kvinnors och barns hälsa, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-391043.

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It is always important to choose appropriate anticancer drugs for cancer patients. At RCL, a division of Uppsala university hospital, drug resistance profiles of patients are evaluated by a cell viability assay called FMCA. However, the number of anticancer drugs that can be evaluated by the FMCA is dependent on the number of viable cancer cells from tissues that can be obtained from each individual patient. Therefore, improvement of cell viability methods is an important issue at RCL. This study was performed to improve the FMCA method by organoid culture from colorectal cancer, renal cancer and osteosarcoma to increase the number of cancer cells. As results, it was successful to expand cryopreserved patient cancer cells to organoids to acquire more cells than before expansion. Organoids showed rounded structure in microscopy images. Thereafter, FMCA was performed on organoids as well as on thawed cryopreserved cancer cells from the original sample. Those results showed that original cancer cells, cryopreserved original cancer cells and expanded organoids derived from those cryopreserved cells had similar resistance profiles. It was also discovered that the organoids secreted VEGF under the cultivation. From those results, it can be concluded that organoids are representative of the original cancer from the patients. It is however needed to improve organoid culture methods, and to further confirm organoids by protein expression analysis and DNA analysis.
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Yamamoto, Takehito. "Chemosensitivity of Patient-Derived Cancer Stem Cells Identifies Colorectal Cancer Patients with Potential Benefit from FGFR Inhibitor Therapy." Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/263523.

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GRASSI, LUDOVICA. "Development of preclinical models for Renal Cell Carcinoma." Doctoral thesis, 2018. http://hdl.handle.net/11573/1086689.

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Renal Cell Carcinoma (RCC) is the most common form of kidney tumor, accounting for approximately 3% of all adult malignancies. To date, RCC is still a difficult disease to diagnose and treat. Although the surgery is the standard therapy for localized tumors, one quarter of patients who underwent nephrectomy, relapse within three years. Moreover, one third of patients arrives with metastases at diagnosis. Unfortunately, the metastatic disease is generally characterized by therapy resistance and very poor outcomes. So far, the lack of valid preclinical RCC models has hampered the discovery of valuable diagnostic and prognostic biomarkers and predictive indicators of therapy response for improving patients' management. In the project, we focused our efforts on the optimization of new patient-derived preclinical models for RCC. We first isolated heterogeneous undifferentiated cell populations responsible for tumor propagation and cancer therapy resistance. By performing a phosphoproteomic analysis we identified a protein signature predictive of cancer progression that would help to select patients more likely to relapse after surgery and who may benefit of adjuvant therapy. We then established an orthotopic patient-derived xenograft (PDX) model that faithfully recapitulate grading, histology and molecular characteristics of the parental tumors. The PDX model proved to be an indicator of bad prognosis and patient tumor could be propagated for up to seventh generation in mice. These findings support the possibility to use PDXs as a platform for patient monitoring and for drug testing. Finally, we were able to establish and characterize, for the first time, long term organoid cultures from normal and tumor samples. All together, these three new models provide innovative and valuable tools for RCC research, suggesting many potential applications for reproducing disease progression models, for biomarkers discovery and drug testing.
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Book chapters on the topic "Patient-derived organoids"

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Kdimati, Said, Florian Bürtin, Michael Linnebacher, and Christina Susanne Mullins. "Patient-Derived Organoids for In Vivo Validation of In Vitro Data." In Methods in Molecular Biology, 111–26. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2788-4_8.

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Tu, Mei-Juan, Colleen M. Yi, Gavin M. Traber, and Ai-Ming Yu. "Bioengineered RNA Therapy in Patient-Derived Organoids and Xenograft Mouse Models." In Methods in Molecular Biology, 191–206. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2441-8_10.

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Soroka, Carol J., David N. Assis, and James L. Boyer. "Patient-Derived Organoids from Human Bile: An In Vitro Method to Study Cholangiopathies." In Methods in Molecular Biology, 363–72. New York, NY: Springer New York, 2019. http://dx.doi.org/10.1007/978-1-4939-9420-5_24.

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Green, Sara, Mie S. Dam, and Mette N. Svendsen. "Patient-Derived Organoids in Precision Oncology – Towards a Science of and for the Individual?" In Personalized Medicine in the Making, 125–46. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-74804-3_7.

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Lefferts, Juliet W., Vera Boersma, Marne C. Hagemeijer, Karima Hajo, Jeffrey M. Beekman, and Erik Splinter. "Targeted Locus Amplification and Haplotyping." In Methods in Molecular Biology, 31–48. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2819-5_2.

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AbstractTargeted locus amplification (TLA) allows for the detection of all genetic variation (including structural variation) in a genomic region of interest. As TLA is based on proximity ligation, variants can be linked to each other, thereby enabling allelic phasing and the generation of haplotypes. This allows for the study of genetic variants in an allele-specific manner. Here, we provide a step-by-step protocol for TLA sample preparation and a complete bioinformatics pipeline for the allelic phasing of TLA data. Additionally, to illustrate the protocol, we show the ability of TLA to re-sequence and haplotype the complete cystic fibrosis transmembrane (CFTR) gene (> 200 kb in size) from patient-derived intestinal organoids.
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Burkhart, Richard A., Lindsey A. Baker, and Hervé Tiriac. "Testing Susceptibility of Patient-Derived Organoid Cultures to Therapies: Pharmacotyping." In Methods in Molecular Biology, 253–61. New York, NY: Springer New York, 2018. http://dx.doi.org/10.1007/978-1-4939-7847-2_19.

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Mariappan, Aruljothi, Theda Knauth, Roberto Pallini, and Jay Gopalakrishnan. "A Three-Dimensional Organoid Culture System to Model Invasive Patterns of Patient-Derived Glioma Stem Cells." In Neuromethods, 139–58. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2720-4_8.

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Feng, Liang, Wenmei Yang, Hui Zhao, Jamie Bakkum-Gamez, Mark E. Sherman, and Nagarajan Kannan. "Protocol for the Detection of Organoid-Initiating Cell Activity in Patient-Derived Single Fallopian Tube Epithelial Cells." In Methods in Molecular Biology, 445–54. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-1979-7_30.

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Mukherjee, Anubhab, Aprajita Sinha, Maheshree Maibam, Bharti Bisht, and Manash K. Paul. "Organoids and Commercialization." In Organoids [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.104706.

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Organoids are 3D miniature tissue mimics and have been effectively used for various purposes, including disease modeling, various drug screening, mechanism of pathogenesis, stem cell research, and tumor immunology. Organoids are as varied as the body\'s tissues and organs and have enormous economic potential. They can open new ways to tailored therapy and precision medicine. In clinical investigations, patient-derived organoids have been used to predict patient responses to therapeutic regimens and perhaps improve cancer treatment outcomes. Recent developments in stem cell research and genomic technologies have led to breakthrough innovations in organoid bioengineering, large-scale manufacturing, biobanking, and commercialization. This chapter reviews the notion of organoid biobanking, companies involved and the commercialization aspect, and ethical considerations.
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Wang, Jia, Xiaoying Feng, Zhichao Li, Yongsong Chen, and Weiren Huang. "Patient-derived organoids as a model for tumor research." In Progress in Molecular Biology and Translational Science. Elsevier, 2022. http://dx.doi.org/10.1016/bs.pmbts.2022.03.004.

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Conference papers on the topic "Patient-derived organoids"

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Verduin, M., A. Hoeben, L. Ackermans, D. Eekers, C. Hubert, J. Rich, V. Tjan-Heijnen, and M. Vooijs. "PO-340 Tumour heterogeneity in patient-derived glioblastoma organoids." In Abstracts of the 25th Biennial Congress of the European Association for Cancer Research, Amsterdam, The Netherlands, 30 June – 3 July 2018. BMJ Publishing Group Ltd, 2018. http://dx.doi.org/10.1136/esmoopen-2018-eacr25.852.

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Calandrini, Camilla, Frans Schutgens, Rurika Oka, Thanasis Margaritis, Tito Candelli, Luka Mathijsen, Carola Ammerlaan, et al. "Abstract IA27: Patient-derived organoids in pediatric cancer research." In Abstracts: AACR Special Conference on the Advances in Pediatric Cancer Research; September 17-20, 2019; Montreal, QC, Canada. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.pedca19-ia27.

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Ren, Xiaoyu. "The culture and application of patient-derived tumour organoids." In International Conference on Biological Engineering and Medical Science (ICBIOMed2022), edited by Gary Royle and Steven M. Lipkin. SPIE, 2023. http://dx.doi.org/10.1117/12.2669049.

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Puca, Loredana, Rohan Bareja, Reid Shaw, Wouter Karthaus, Dong Gao, Chantal Pauli, Juan Miguel Mosquera, et al. "Abstract 992: Patient-derived tumor organoids of neuroendocrine prostate cancer." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-992.

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Rosati, Rachele, Hallie A. Swan, Laura Scolaro, Kateryna Krytska, John M. Maris, Franz X. Schaub, and Carla Grandori. "Abstract 2625: Patient derived organoids to guide personalized neuroblastoma treatment." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-2625.

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Kim, Seok-Young, Dong Hwi Kim, Hyeong-Seok Joo, Mi Ran Yun, Ji Yeon Lee, Sang Min Kim, Hyunki Kim, Min Hee Hong, Hye Ryun Kim, and Byoung Chul Cho. "Abstract 38: NSCLC patient-derived organoids to guide personalized therapy." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-38.

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Kim, Seok-Young, Dong Hwi Kim, Hyeong-Seok Joo, Mi Ran Yun, Ji Yeon Lee, Sang Min Kim, Hyunki Kim, Min Hee Hong, Hye Ryun Kim, and Byoung Chul Cho. "Abstract 38: NSCLC patient-derived organoids to guide personalized therapy." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-38.

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Spiller, Erin, Roy Lau, Sarah Choung, and Shannon M. Mumenthaler. "Abstract A18: High-content 3D image analysis of patient-derived organoids." In Abstracts: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; February 11-14, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1557-3265.pdx16-a18.

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Karkampouna, Sofia, Federico la Manna, Maria R. De Filippo, Mirjam Kiener, Marta De Menna, Eugenio Zoni, Joel Grosjean, et al. "Abstract B18: Patient-derived xenograft and organoids models of prostate cancer." In Abstracts: AACR Special Conference on the Evolving Landscape of Cancer Modeling; March 2-5, 2020; San Diego, CA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.camodels2020-b18.

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Khan, Syamantak, June Ho Shin, Ning Cheng, Calvin Kuo, John Sunwoo, and Guillem Pratx. "Abstract B08: High-resolution positron emission microscopy of patient-derived tumor organoids." In Abstracts: AACR Special Conference on the Evolving Landscape of Cancer Modeling; March 2-5, 2020; San Diego, CA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.camodels2020-b08.

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