Academic literature on the topic 'Tumoroïde'
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Journal articles on the topic "Tumoroïde"
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Yankaskas, Chris, Brittany Balhouse, Colin Paul, Shyanne Salen, Sybelle Djikeng, Pradip Shahi Thakuri, Mark Kennedy, Matt Dallas, and David Kuninger. "Abstract 160: Derivation and long-term maintenance of patient-derived tumoroid lines in a defined, serum-free medium." Cancer Research 83, no. 7_Supplement (April 4, 2023): 160. http://dx.doi.org/10.1158/1538-7445.am2023-160.
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Abstract In vitro cancer research often fails to translate to the clinic, in part due to the use of traditional 2D cancer cell lines as models, which fail to resemble primary cancer cells by a variety of measures, including high mutational burden. An emerging solution to this problem is to replace traditional cell lines with patient tissue-derived cells expanded in 3D, also known as tumoroids or cancer organoids. We developed a defined, serum- and conditioned medium-free system, GibcoTM OncoProTM Tumoroid Culture Medium, that can be used to derive stable tumoroid lines from a variety of tissue sources and maintains the phenotype and genotype of patient-derived tumor cells. By supplementing the base medium with indication-specific growth factors, tumoroid lines were derived from colorectal, lung, and endometrial cancers from both fresh surgical resections and cryopreserved primary cancer cells. To demonstrate the utility of these patient-derived cells as long-term in vitro models, colorectal and lung tumoroid lines were derived from multiple donors and cultured for up to 50 passages. Brightfield microscopy, cell counts, and next-generation sequencing were used to assess maintenance of tumoroid morphology, growth rate, gene expression patterns, and genomic mutations. Patient-derived tumoroid cultures adopted donor-specific morphologies that were maintained during long-term culture. Cell doubling time tended to stabilize within the first few passages as cultures established, was donor-dependent, and averaged around 65 hours for colorectal tumoroids - on par with that of traditional 2D cancer cell lines - and 90-100 hours for lung and endometrial tumoroids, respectively. Importantly, tumoroid lines maintained their gene expression pattern for over 20,000 human RefSeq genes during long-term culture, with correlation between initial tumor material and late-passage samples of R>0.8. Distinct molecular subtypes of colorectal cancer were preserved in cultured tumoroids. The allelic frequency of single nucleotide variations (SNVs) in 161 highly relevant cancer genes was also highly correlated (R>0.9) between uncultured tissue and late-passage tumoroids. Within SNVs, transition/transversion mutation ratios were conserved. Tumoroids were cryopreserved and recovered during this study, demonstrating that biobanking of colorectal and lung tumoroids should not impact their long-term stability. Finally, a subset of the derived colorectal and lung tumoroids were tested and shown to be tumorigenic in mice, where subsequent histology of the tumor was similar to that of in vitro cultures. Altogether, tumoroid derivation and culture in this novel medium enables the long-term preservation of patient-specific cellular genotype and phenotype, which should allow for expansion, biobanking, and performance of experimental repeats within the same patient tissue-derived cultures across labs and over time. Citation Format: Chris Yankaskas, Brittany Balhouse, Colin Paul, Shyanne Salen, Sybelle Djikeng, Pradip Shahi Thakuri, Mark Kennedy, Matt Dallas, David Kuninger. Derivation and long-term maintenance of patient-derived tumoroid lines in a defined, serum-free medium [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 160.
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Alvarez, Janet, Wini Zambare, Chao Wu, Paulina Bleu, Aron Bercz, Baby Satravada, Ritika Kundra, et al. "An online rectal cancer tumoroid biorepository: A resource to facilitate multimodal data integration." Journal of Clinical Oncology 42, no. 3_suppl (January 20, 2024): 159. http://dx.doi.org/10.1200/jco.2024.42.3_suppl.159.
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159 Background: Advancing genetic and computational technologies have increased the complexity and quantity of data available in the field of rectal cancer research. As such, there is a need for a centralized source of data to aid and organize current research efforts. To this end, our team has created a unique online biorepository of rectal cancer tumoroids which may serve as a resource for a community of researchers. Methods: The rectal cancer tumoroid biorepository was created in cBioPortal in 2015. Organoids were derived from patient tumor samples (tumoroids). These samples represented multiple treatment timepoints and included primary, recurrent, and metastatic tumors. These tumoroids were further analyzed by various assays such as MSK-IMPACT and IC50 (to fluorouracil, FOLFOX, and FOLFIRI) to obtain patient-specific genomic and chemosensitivity data. A tumoroid profile was then created in cBioPortal for each sample. Clinical information was collected by chart review and annotated into the tumoroid profiles using the unique features of cBioPortal. These included interactive filters and graphical depictions of patient demographics, clinical and pathologic staging, treatment course, clinical response, overall survival, and disease-free survival. Results were organized in an intuitive visual display for convenient analysis. Novel features such as chemosensitivity plots and an interactive patient timeline were incorporated as well. Results: In total, 401 rectal cancer tumoroids have been derived from 177 unique patients. Approximately 32% of the tumoroids were from patients 50 years or younger, and 63% of patients have a treatment naïve sample in our repository. Ten percent of tumoroids were derived from T1-T2 tumors, 56% from T3 tumors, and 17% from T4 tumors. Additionally, 14% of tumoroids were derived from primary tumor recurrences while 6% were derived from metastases. Of the 78% of tumoroids with completely annotated clinical data, 8% were MSI-H, 11% were clinical complete responders, and 5.5% were pathologic complete responders. Lastly, complete IC50 data with clinical correlates has been established for 20% of tumoroids. These data show that tumoroids with a high sensitivity to chemotherapy (FOLFOX) correlated with a 3.3-fold increase in clinical complete response rates in the corresponding patients (p=0.0263). Conclusions: Integrating histopathological, clinicogenomic, and tumoroid response data, this expanding online resource provides a platform to identify valid biomarkers for patient treatment response. This publicly available biorepository built within cBioPortal is intuitive and flexible to accommodate and organize a wide range of data and has the potential to serve as an important resource in rectal cancer research.
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Danen, Erik H. J. "Abstract 5226: A 3D ECM embedded tumoroid platform for testing antibody drugs and engineered TCRs for immune oncology." Cancer Research 84, no. 6_Supplement (March 22, 2024): 5226. http://dx.doi.org/10.1158/1538-7445.am2024-5226.
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Abstract We developed a screening platform for immune oncology using an assay based on automated image guided injection of tumoroids in wells of multi-well plates preloaded with a collagen-rich ECM. The identical x-y-z position and size of the ECM-embedded tumoroids in each well facilitates automated real time confocal microscopy and quantitative image analysis algorithms. The model is used to generate quantitative data for T cell recruitment to tumoroids and killing of tumoroids by T cells. We have applied this to screening a panel of CD3:Her2 bispecific antibodies (BsAb) binding with different affinities to CD3 or Her2 or displaying high affinity interactions with different epitopes on Her2. Exposure to fresh, non-activated peripheral blood mononuclear cell (PBMC) derived T cells shows an initial phase of random T cell movement throughout the ECM followed by a BsAb-dependent phase of active T cell recruitment to tumoroids (day 2-4) and a subsequent phase of tumoroid killing (day 4-6). We show that the wave of T cell recruitment following initial T cell-tumoroid contact involves chemotactic signaling. Decreased affinity at the Her2 or CD3 arm can be compensated for by increasing BsAb concentrations. However, we detect major differences in efficacy for different high affinity epitopes. I.e., of two BsAbs interacting with high affinity with distinct Her2 epitopes and each causing effective tumor cell killing in 2D co-culture, only one was able to trigger a wave of T cell recruitment and subsequent tumoroid killing in 3D. We have applied the same setup to testing the efficacy of T cells expressing engineered TCRs aimed at application in adoptive T-cell therapy. Kinetics of experiments using these activated engineered T cells are considerably shorter (24 hours instead of ~6 days) but show a similar pattern of T cell recruitment and subsequent tumoroid killing. We demonstrate successful generation of quantitative data for T cell recruitment and tumoroid killing for engineered T cells targeting tumor antigens expressed on TNBC and uveal melanoma tumoroids. Citation Format: Erik H. J. Danen. A 3D ECM embedded tumoroid platform for testing antibody drugs and engineered TCRs for immune oncology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5226.
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Zambare, Wini, Chao Wu, Hannah Kalvin, Hanchen Huang, Sara Yoder, Michael Del Latto, Maria Kierstead, et al. "Abstract A012: Development of a translational tumoroid-organoid platform revealing tumor-specific radiosensitization in rectal cancer using matched patient-derived models." Clinical Cancer Research 31, no. 2_Supplement (January 26, 2025): A012. https://doi.org/10.1158/1557-3265.targetedtherap-a012.
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Abstract Background: Radiation therapy in rectal cancer treatment is limited by variable tumor responses among patients and harmful effects on normal tissues. We developed a translational human tumoroid-organoid platform to assess novel tumor-specific strategies for radiation sensitization using matched patient-derived models. Methods: Fifteen rectal cancer-derived tumoroids and three matched normal tissue-derived organoids were established from patients, representing primary tumors, metastases, and recurrences. Four tumoroids were derived from a single patient, encompassing different disease stages: primary tumor and splenic metastasis (pre-progression), and rectal and vaginal recurrences (post-progression). To evaluate tumor-specific radiation sensitizers, both tumoroids and their matched normal organoids were treated with 5-fluorouracil (5-FU), one of four DNA damage repair inhibitors (DDRis; ATMi, DNA-PKi, PARPi, or ATRi), or a DMSO control. Following treatment, samples were irradiated, and cell viability was measured. We assessed intrinsic radiation sensitivity under control conditions and radiosensitizer efficacy using a linear regression model with log-transformed cell viability as the outcome. Whole-exome sequencing characterized the mutation profiles of the tumoroids. Results: Intrinsic radiosensitivity was heterogeneous among tumoroids, with a 10–28% decrease in cell growth per unit increase in radiation dose. Critically, when comparing tumoroids to their matched normal organoids, we observed greater sensitization in tumoroids across all cases and for all DDRis, demonstrating tumor-specific radiosensitization. The most potent radiosensitizer relative to DMSO was DNA-PKi in 7 tumoroids, ATMi in 4 tumoroids, and PARPi in 1 tumoroid. Tumoroids derived after disease progression exhibited increased resistance to radiation and a diminished degree of sensitization with DDRi treatment compared to pre-progression tumoroids. Despite variations in radiation sensitivity and DDRi responses, the genetic profiles of the tumoroids remained largely unchanged. Conclusion: We developed a translational ex vivo tumoroid-organoid platform using matched patient-derived models to test tumor-specific radiation sensitizers in rectal cancer. This platform allowed us to determine tumor-specific sensitization by directly comparing tumoroids with matched normal organoids, demonstrating greater sensitization in tumoroids. Our findings highlight the potential of this platform to uncover precise, tumor-selective treatment options, improve patient responses, reduce toxicity, and address resistant tumors in patients with disease progression. Citation Format: Wini Zambare, Chao Wu, Hannah Kalvin, Hanchen Huang, Sara Yoder, Michael Del Latto, Maria Kierstead, Satoru Meguro, Xi Steven Chen, Mithat Gonen, J. Joshua Smith, Paul B. Romesser. Development of a translational tumoroid-organoid platform revealing tumor-specific radiosensitization in rectal cancer using matched patient-derived models. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A012.
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Truelsen, Sarah Line Bring, Nabi Mousavi, Haoche Wei, Lucy Harvey, Rikke Stausholm, Erik Spillum, Grith Hagel, et al. "The cancer angiogenesis co-culture assay: In vitro quantification of the angiogenic potential of tumoroids." PLOS ONE 16, no. 7 (July 7, 2021): e0253258. http://dx.doi.org/10.1371/journal.pone.0253258.
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The treatment response to anti-angiogenic agents varies among cancer patients and predictive biomarkers are needed to identify patients with resistant cancer or guide the choice of anti-angiogenic treatment. We present “the Cancer Angiogenesis Co-Culture (CACC) assay”, an in vitro Functional Precision Medicine assay which enables the study of tumouroid induced angiogenesis. This assay can quantify the ability of a patient-derived tumouroid to induce vascularization by measuring the induction of tube formation in a co-culture of vascular cells and tumoroids established from the primary colorectal tumour or a metastasis. Furthermore, the assay can quantify the sensitivity of patient-derived tumoroids to anti-angiogenic therapies. We observed that tube formation increased in a dose-dependent manner upon treatment with the pro-angiogenic factor vascular endothelial growth factor A (VEGF-A). When investigating the angiogenic potential of tumoroids from 12 patients we found that 9 tumoroid cultures induced a significant increase in tube formation compared to controls without tumoroids. In these 9 angiogenic tumoroid cultures the tube formation could be abolished by treatment with one or more of the investigated anti-angiogenic agents. The 3 non-angiogenic tumoroid cultures secreted VEGF-A but we observed no correlation between the amount of tube formation and tumoroid-secreted VEGF-A. Our data suggests that the CACC assay recapitulates the complexity of tumour angiogenesis, and when clinically verified, could prove a valuable tool to quantify sensitivity towards different anti-angiogenic agents.
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Yankaskas, Chris, Brittany Balhouse, Colin Paul, Pradip Shahi Thakuri, Shyanne Salen, Mark Kennedy, Matt Dallas, and David Kuninger. "Abstract 4251: Establishment of hormone-dependent endometrial tumoroids in a conditioned-medium free, serum-free medium." Cancer Research 84, no. 6_Supplement (March 22, 2024): 4251. http://dx.doi.org/10.1158/1538-7445.am2024-4251.
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Abstract Tumoroids, also known as cancer organoids, are self-assembled three-dimensional cultures of patient-derived tumor cells. Compared to traditional 2D cancer cell lines, tumoroids better maintain key characteristics of the original tumor including the genotype and transcriptome, which lead to better in vitro modeling of clinically relevant functional responses such as drug sensitivity. An under-studied aspect of tumoroid cultures has been their ability to recapitulate dependence on hormone signaling in vitro, with some reports indicating hormone dependence is lost over time in culture. To investigate this, we utilized Gibco™ OncoPro™ Tumoroid Culture Medium and defined tissue-specific supplements, FGF10 and beta-estradiol, that when added to the medium enabled the derivation of endometrial tumoroids from tumor resections. Derivation of tumoroid lines compatible with long-term growth depended on a variety of factors, including tissue quality and time from resection to culture initiation. Each of the 15 samples processed formed tumoroids when initially seeded into culture. 11/15 samples reformed tumoroids through multiple passages (typically 1-2 weeks per passage) over 1-3 months in culture. 7/15 samples met our high criteria for stable tumoroid line growth of >5 passages and reaching >5 cumulative population doublings (from initial number of cells seeded post-resection) in culture. Next-generation sequencing of the established tumoroids and the uncultured tumor material demonstrated a high degree of correlation (pearson’s r>0.9) of genomic mutations in a targeted panel; few differentially expressed genes were detected beyond down-regulation of immune-related genes, presumably because the medium is optimized for outgrowth of cancer epithelial cells, and immune cells do not persist during long-term culture. Endometrial tumoroids were capable of growing embedded in basement membrane extract (BME) or in suspension with dilute BME added and could be cryopreserved and recovered. Endometrial tumoroids retained gene expression levels (both presence and absence) of estrogen receptor and progesterone receptor for up to the 20 passages tested in vitro. A subset of the models was tested and showed increased growth rates in response to increased concentrations of beta-estradiol. Of those tested, 2/3 tumoroid cultures stopped growing within 1-2 weeks after removal of beta-estradiol from the medium, demonstrating dependence on this hormone for growth. Maintenance of hormone receptor expression and dependency should enable in vitro studies to understand the signaling mechanisms and potential ways to modulate them in the context of cancer. Overall, this method provides a toolset for studying endometrial cancer, particularly hormone dependency, and may be more broadly applicable to other gynecological or hormone dependent cancers. Citation Format: Chris Yankaskas, Brittany Balhouse, Colin Paul, Pradip Shahi Thakuri, Shyanne Salen, Mark Kennedy, Matt Dallas, David Kuninger. Establishment of hormone-dependent endometrial tumoroids in a conditioned-medium free, serum-free medium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4251.
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Kim, Sung Min, Yoo Ri Ko, Hye Seon Park, and Se Jin Jang. "Abstract 218: Deciphering tumoroid-CAF interactions through a spatially segregated coculture model." Cancer Research 84, no. 6_Supplement (March 22, 2024): 218. http://dx.doi.org/10.1158/1538-7445.am2024-218.
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Abstract In the context of lung cancers, cancer-associated fibroblast (CAF) plays a pivotal role as a key component of the tumor microenvironment (TME), affecting tumor growth, invasion, metastasis, immune modulation, and drug resistance. Despite the recognized impact of CAFs, the precise interaction between the CAF and tumor cell remains elusive. Previous studies have reported that CAFs stimulate tumor cell growth both in vitro and in vivo. However, our tumoroid models reveal an intriguing phenomenon where CAFs inhibit tumoroids growth within Matrigel. This led us to hypothesize that paracrine signaling might be the primary mode of interaction between CAFs and tumor cells. To unravel the intricacies of this interaction, we developed an innovative coculture method. Using hydrophobic barrier, we segregated the coculture of nine sets of CAFs and tumoroids within a single well, preventing CAFs from infiltrating the tumoroid culture area. This setup enabled interaction solely through paracrine signaling. Surprisingly, cocultured tumoroids exhibited no significant differences compared to individually cultured tumoroids. Conversely, cocultured CAFs displayed a remarkable increase in growth compared to their individually cultured counterparts. This suggests that tumoroids influence CAF growth, while CAFs do not significantly impact tumoroid growth. Furthermore, in three coculture sets, tumor cells within the Matrigel migrated towards the CAF culture area, indicating that CAFs induce tumor cell metastasis. Immunofluorescence staining confirmed this metastatic phenomenon. To identify the paracrine factors influencing CAFs and tumoroids, we employed RNA-sequencing, single-cell RNA-sequencing, and proteomic analysis of culture soup. Proteomic analysis revealed a substantial increase in proteins and signaling pathways related to the extracellular matrix in cocultures compared to single cultures. Our findings suggest that tumor cells recruit CAFs, promoting CAF growth to establish and fortify their TME, ultimately leading to drug resistance, metastasis, and immune modulation Citation Format: Sung Min Kim, Yoo Ri Ko, Hye Seon Park, Se Jin Jang. Deciphering tumoroid-CAF interactions through a spatially segregated coculture model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 218.
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Taha, Eman, Chiharu Sogawa, Yuka Okusha, Hotaka Kawai, May Oo, Abdellatif Elseoudi, Yanyin Lu, et al. "Knockout of MMP3 Weakens Solid Tumor Organoids and Cancer Extracellular Vesicles." Cancers 12, no. 5 (May 16, 2020): 1260. http://dx.doi.org/10.3390/cancers12051260.
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The tumor organoid (tumoroid) model in three-dimensional (3D) culture systems has been developed to reflect more closely the in vivo tumors than 2D-cultured tumor cells. Notably, extracellular vesicles (EVs) are efficiently collectible from the culture supernatant of gel-free tumoroids. Matrix metalloproteinase (MMP) 3 is a multi-functional factor playing crucial roles in tumor progression. However, roles of MMP3 within tumor growth and EVs have not unveiled. Here, we investigated the protumorigenic roles of MMP3 on integrities of tumoroids and EVs. We generated MMP3-knockout (KO) cells using the CRISPR/Cas9 system from rapidly metastatic LuM1 tumor cells. Moreover, we established fluorescent cell lines with palmitoylation signal-fused fluorescent proteins (tdTomato and enhanced GFP). Then we confirmed the exchange of EVs between cellular populations and tumoroids. LuM1-tumoroids released large EVs (200–1000 nm) and small EVs (50–200 nm) while the knockout of MMP3 resulted in the additional release of broken EVs from tumoroids. The loss of MMP3 led to a significant reduction in tumoroid size and the development of the necrotic area within tumoroids. MMP3 and CD9 (a category-1 EV marker tetraspanin protein) were significantly down-regulated in MMP3-KO cells and their EV fraction. Moreover, CD63, another member of the tetraspanin family, was significantly reduced only in the EVs fractions of the MMP3-KO cells compared to their counterpart. These weakened phenotypes of MMP3-KO were markedly rescued by the addition of MMP3-rich EVs or conditioned medium (CM) collected from LuM1-tumoroids, which caused a dramatic rise in the expression of MMP3, CD9, and Ki-67 (a marker of proliferating cells) in the MMP3-null/CD9-low tumoroids. Notably, MMP3 enriched in tumoroids-derived EVs and CM deeply penetrated recipient MMP3-KO tumoroids, resulting in a remarkable enlargement of solid tumoroids, while MMP3-null EVs did not. These data demonstrate that EVs can mediate molecular transfer of MMP3, resulting in increasing the proliferation and tumorigenesis, indicating crucial roles of MMP3 in tumor progression.
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Paul, Colin, Anthony Chatman, Amber Bullock, Xiaoyu Jenny Yang, Garrett Wong, Brittany Balhouse, Chris Yankaskas, Erik Willems, Matt Dallas, and David Kuninger. "Abstract 2047: Scale up and scale down approaches for screening of 3D patient-derived cell models." Cancer Research 84, no. 6_Supplement (March 22, 2024): 2047. http://dx.doi.org/10.1158/1538-7445.am2024-2047.
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Abstract 3D cell culture is becoming more prevalent as scientists work to better model human physiology using in vitro systems. However, differences in handling 3D cell cultures compared to traditional 2D cell lines have limited adoption of 3D techniques in compound and cell therapy screening experiments. To facilitate use of patient-derived 3D tumoroid models, we developed protocols for both scale up and scale down of these models in Gibco™ OncoPro™ Tumoroid Culture Medium. OncoPro Tumoroid Culture Medium is a serum-free, conditioned medium-free culture medium designed to promote the growth of patient-derived 3D cancer models (tumoroids, cancer organoids). OncoPro medium is compatible with a suspension culture approach for easier handling compared to traditional embedded culture formats. We studied the growth of tumoroids in different flask sizes during suspension culture to optimize scale up for downstream assays. Tumoroid growth rates and morphologies were consistent across non-tissue culture treated flask sizes, and viable cell yield increased with surface area during scale up. In some cases, as many as 100 × 106 dissociated tumoroid cells can be recovered from a single Nunc™ TripleFlask™ after a week of growth. After scaling up, tumoroids were dissociated and seeded in multiwell plates to test multiple screening conditions (compound identity, compound concentration) in parallel. Dissociated cells were seeded in 96-well plates using both manual and automated liquid handling (Tecan Fluent 780). Due to the tendency of 3D cell models to aggregate and fall out of solution, initial seeding in a 96-well flat bottom plate resulted in high well-to-well variability. Optimization of cell seeding protocols led to standard deviations in tumoroid metabolic activity, number, and size that were comparable to manual seeding, with a coefficient of variation of less than 3% between wells for multiple tumoroid lines when automation was implemented. Generally, variability in cell seeding was lower when using the optimized, automated cell seeding protocol compared to manual methods. After seeding, cells were grown for three days to form tumoroids prior to the addition of compounds. At this time point, there was low well-to-well variability in tumoroid metabolic activity (CV<2%). Compounds and reagents to analyze cell health could also be added using automated liquid handling prior to analysis on plate readers or high-content imaging platforms. Citation Format: Colin Paul, Anthony Chatman, Amber Bullock, Xiaoyu Jenny Yang, Garrett Wong, Brittany Balhouse, Chris Yankaskas, Erik Willems, Matt Dallas, David Kuninger. Scale up and scale down approaches for screening of 3D patient-derived cell models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2047.
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Sogawa, Chiharu, Takanori Eguchi, Yuri Namba, Yuka Okusha, Eriko Aoyama, Kazumi Ohyama, and Kuniaki Okamoto. "Gel-Free 3D Tumoroids with Stem Cell Properties Modeling Drug Resistance to Cisplatin and Imatinib in Metastatic Colorectal Cancer." Cells 10, no. 2 (February 6, 2021): 344. http://dx.doi.org/10.3390/cells10020344.
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Researchers have developed several three-dimensional (3D) culture systems, including spheroids, organoids, and tumoroids with increased properties of cancer stem cells (CSCs), also called cancer-initiating cells (CICs). Drug resistance is a crucial issue involving recurrence in cancer patients. Many studies on anti-cancer drugs have been reported using 2D culture systems, whereas 3D cultured tumoroids have many advantages for assessing drug sensitivity and resistance. Here, we aimed to investigate whether Cisplatin (a DNA crosslinker), Imatinib (a multiple tyrosine kinase inhibitor), and 5-Fluorouracil (5-FU: an antimetabolite) alter the tumoroid growth of metastatic colorectal cancer (mCRC). Gene expression signatures of highly metastatic aggregative CRC (LuM1 cells) vs. low-metastatic, non-aggregative CRC (Colon26 and NM11 cells) were analyzed using microarray. To establish a 3D culture-based multiplexing reporter assay system, LuM1 was stably transfected with the Mmp9 promoter-driven ZsGreen fluorescence reporter gene, which was designated as LuM1/m9 cells and cultured in NanoCulture Plate®, a gel-free 3D culture device. LuM1 cells highly expressed mRNA encoding ABCG2 (a drug resistance pump, i.e., CSC/CIC marker), other CSC/CIC markers (DLL1, EpCAM, podoplanin, STAT3/5), pluripotent stem cell markers (Sox4/7, N-myc, GATA3, Nanog), and metastatic markers (MMPs, Integrins, EGFR), compared to the other two cell types. Hoechst efflux stem cell-like side population was increased in LuM1 (7.8%) compared with Colon26 (2.9%), both of which were markedly reduced by verapamil treatment, an ABCG2 inhibitor. Smaller cell aggregates of LuM1 were more sensitive to Cisplatin (at 10 μM), whereas larger tumoroids with increased ABCG2 expression were insensitive. Notably, Cisplatin (2 μM) and Imatinib (10 μM) at low concentrations significantly promoted tumoroid formation (cell aggregation) and increased Mmp9 promoter activity in mCRC LuM1/m9, while not cytotoxic to them. On the other hand, 5-FU significantly inhibited tumoroid growth, although not completely. Thus, drug resistance in cancer with increased stem cell properties was modeled using the gel-free 3D cultured tumoroid system. The tumoroid culture is useful and easily accessible for the assessment of drug sensitivity and resistance.
Dissertations / Theses on the topic "Tumoroïde"
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Burgy, Mickaël. "Intérêt pronostic et thérapeutique de l'axe miR-30a/e-3p -Cav1 dans les carcinomes épidermoïdes de la tête et du cou." Electronic Thesis or Diss., Strasbourg, 2025. http://www.theses.fr/2025STRAJ002.
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Le pronostic péjoratif des carcinomes épidermoïdes de la tête et du cou (CETEC) tient en partie aux mécanismes encore non élucidés de résistances aux thérapies actuelles. De plus l’absence de biomarqueurs complique le développement de stratégies thérapeutiques reposant actuellement sur le stade de la maladie excluant les caractéristiques biologiques tumorales. Dans ce projet de recherche translationnelle, nous avons identifié la cavéoline-1 (Cav1) et les miR-30a/e-3p comme des biomarqueurs pronostiques de la survie et de la récidive tumorale. Nous avons validé l’implication de l’axe CAV1/EREG/YAP dans la résistance au Cetuximab et à la radiothérapie. Nous avons également identifié miR-30a/e-3p à la fois comme des régulateurs de la voie du TGF-β via la répression de TGFBR1 et BMPR2 à l‘origine d’une diminution de l’agressivité tumorale, et également comme des immunomodulateurs favorisant l’activité phagocytaire des macrophages envers les cellules tumorales. Enfin nous avons pu développer un modèle de tumoroïdes issus de pièces opératoires de patients atteints de CETEC ayant permis de valider certains de nos résultats et destiné à un projet de recherche de drug-testingThe poor prognosis of head and neck squamous cell carcinomas (HNSCC) patients is partly attributed to resistance mechanisms against current therapies, which remain poorly understood. Furthermore, the absence of biomarkers complicates the development of therapeutic strategies currently based on disease staging, excluding the tumor's biological characteristics. In this translational research project, we identified caveolin-1 (Cav1) and miR-30a/e-3p as prognostic biomarkers for survival and recurrence. We validated the involvement of the CAV1/EREG/YAP axis in the resistance to Cetuximab and radiotherapy. We also identified miR-30a/e-3p both as regulators of the TGF-β pathway through the repression of TGFBR1 and BMPR2 leading to reduced tumor cell aggressiveness and as immunomodulators promoting the phagocytic activities of macrophages towards tumor cells. Finally, we developed a tumoroid model derived from resected tissue of HNSCC patients which confirmed several of our results and will be used in a drug-testing research project
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Guschmann, Michael. "Zum Einfluss angiogener Wachstumsfaktoren auf tumoröse Gefässerkrankungen der Plazenta." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=968960243.
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Alexander, Frank. "RTEMIS: Real-Time Tumoroid and Environment Monitoring Using Impedance Spectroscopy and pH Sensing." Scholar Commons, 2014. https://scholarcommons.usf.edu/etd/5168.
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This research utilizes Electrical Impedance Spectroscopy, a technique classically used for electrochemical analysis and material characterization, as the basis for a non-destructive, label-free assay platform for three dimensional (3D) cellular spheroids. In this work, a linear array of microelectrodes is optimized to rapidly respond to changes located within a 3D multicellular model. In addition, this technique is coupled with an on chip micro-pH sensor for monitoring the environment around the cells. Finally, the responses of both impedance and pH are correlated with physical changes within the cellular model. The impedance analysis system realized through this work provides a foundation for the development of high-throughput drug screening systems that utilize multiple parallel sensing modalities including pH and impedance sensing in order to quickly assess the efficacy of specific drug candidates.
The slow development of new drugs is mainly attributed to poor predictability of current chemosensitivity and resistivity assays, as well as genetic differences between the animal models used for tests and humans. In addition, monolayer cultures used in early experimentation are fundamentally different from the complex structure of organs in vivo. This requires the study of smaller 3D models (spheroids) that more efficiently replicate the conditions within the body.
The main objective of this research was to develop a microfluidic system on a chip that is capable of deducing viability and morphology of 3D tumor spheroids by monitoring both the impedance of the cellular model and the pH of their local environment. This would provide a fast and reliable method for screening pharmaceutical compounds in a high-throughput system.
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Tourbez, Arthur. "Développement et caractérisation d'organoïdes de tumeurs cérébrales pédiatriques utilisés en recherche fondamentale et translationnelle." Electronic Thesis or Diss., Lyon 1, 2023. https://n2t.net/ark:/47881/m6416x50.
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Les gliomes de haut grade pédiatriques (pHGG) et les épendymomes de la fosse postérieure de type A (EPN-PFA) représentent l'un des plus grands défis de la neuro-oncologie pédiatrique. Leur singularité se manifeste par une remarquable hétérogénéité inter- et intra-tumorale qui complique le développement de stratégies thérapeutiques efficaces. Afin d'améliorer les perspectives cliniques pour les patients atteints de ces cancers, il est impératif de disposer de modèles pré-cliniques capables de refléter fidèlement les principales caractéristiques de leurs tumeurs d'origine. Au cours de mon doctorat, j'ai élaboré un protocole pour la création et la conservation de tumoroïdes pHGG (pHGG_O) et de tumoroïdes de EPN-PFA (EPN-PFA_O). Ces modèles peuvent être cultivés plusieurs mois/années. De plus, des analyses histologiques et moléculaires approfondies ont permis de montrer que ces modèles préservent l'hétérogénéité inter- et intra-tumorale de leur tumeur d'origine, et ce même après plusieurs passages en culture et cryopréservation. J'ai également démontré que ces modèles peuvent servir à l'évaluation de la réponse aux traitements qui reste comparable à celle observée chez les patients. De plus, ces modèles ont révélé leur potentiel pré-clinique (1) en permettant d'identifier l'ONC201, un inhibiteur de DRD2, comme un agent thérapeutique d'intérêt pour les tumeurs H3K27 nonaltérées, et (2) en contribuant à élaborer des stratégies de combinaison visant à amplifier la réponse thérapeutique à l'ONC201. Ces modèles sont donc des outils pré-cliniques robustes et puissants, en particulier pour l'appréciation des profils de réponses aux traitements et la recherche de nouvelles combinaisons de médicaments efficacesPediatric high-grade gliomas (pHGG) and posterior fossa type A ependymomas (EPN-PFA) remain one of the biggest challenges in pediatric oncology. They exhibit vast inter- and intra-tumoral heterogeneity, complicating the development of effective therapeutic strategies. Then to improve their clinical outcome, we absolutely need pre-clinical models that recapitulate key features of their corresponding parental tumors. During my PhD, I developed an optimized protocol for the establishment and biobanking of pHGG organoids (pHGG_O) and EPN-PFA organoids (EPN-PFA_O). These models can be grown long-term and comprehensive histological and molecular analyses showed that they recapitulate inter- and intra-tumoral heterogeneity of their parental tumor even after several passages and cryopreservation as 3D cultures. I further showed that they can be employed to test responses to standard of care therapy as well as new therapeutic options, including drugs from clinical trials as they accurately capture the clinical phenotypes of their respective parental tumors. Moreover, these models led to the identification of the DRD2 inhibitor ONC201 as an unexpected potential therapeutic agent for H3K27M non-altered pediatric brain tumors and helped identify combination strategies to increase the therapeutic response to ONC201. Thus, those models are positioned to support powerful and innovative preclinical studies, particularly those related to personalized assessments of treatment response profiles and identification of novel efficient drug combinations
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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 poumonDespite 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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Mastrogiovanni, Gianmarco. "Establishment of new human and mouse liver cancer models and their use to uncover the role of RNF43 and ZNRF3 in liver homeostasis and repair." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/273341.
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Primary liver cancer (PLC) is the second most common cause of cancer death worldwide, preceded only by lung cancer. Current models for PLC either fail to fully recapitulate tumour histology and architecture or are expensive, time consuming and do not allow for personalised drug testing. During the first part of my PhD, I have collaborated with Dr. Laura Broutier in order to established a new 3D in vitro model system for liver cancer. Based on the current knowledge on organoid cultures, we have managed to establish a system to grow primary human liver cancer cells long-term (Broutier et al., in press). Interestingly, the tumour-derived organoids (tumoroids) recapitulate the original tumour histology and genetic alterations and are also able to generate tumours in an in vivo xenograft mouse model after long-term expansion. Furthermore, we have shown that tumoroids can also be successfully used for drug testing, suggesting their use to devise new targeted therapy as well as personalised treatment strategies. Current models to investigate the role of genes in cancer rely mostly on animal studies, which can be very time consuming and cost demanding, especially if resulting in negative outcomes. To overcome this issue, I have set up a protocol for introducing mutations in healthy human liver organoids using the CRISPR-Cas9 technology. Interestingly, after mutating TP53, RNF43 and ZNRF3 either alone or in combination, human organoids undergo genetic alterations and phenotypic changes that partially resemble the ones observed in tumoroids. This data suggests that this system could be used as a screening platform to study gene function before using animal models. In the last part, I have further explored the role of RNF43 and ZNRF3 (R&Z) - two newly identified WNT pathway negative regulators mutated in many cancer types - in the liver using an in vivo mouse model. Interestingly, conditional deletion of R&Z specifically in adult mouse hepatocytes results metabolic changes that eventually lead to extensive liver damage. However, when the liver is challenged to regenerate in a chronic damage model, R&Z mutated livers fail to fully repair and show presence of multiple regenerative nodules. Later, livers develop either focal nodular hyperplasia and/or early hepatocellular carcinoma. These data suggest that R&Z have an important role in both liver metabolic homeostasis and liver regeneration and that their alteration can eventually lead to cancer formation.
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Dolivet, Enora. "Ιntérêt des surnageants de cultures des οrganοïdes dérivés de tumeurs οvariennes pοur l'identificatiοnde miRΝA circulants prédictifs de la répοnses aux thérapies innοvantes." Electronic Thesis or Diss., Normandie, 2025. http://www.theses.fr/2025NORMC402.
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En 2023, le cancer épithélial de l’ovaire est une maladie rare, représentant la 5ème cause de mortalité par cancer chez la femme en France. En complément de nouvelles thérapies, le développement de biomarqueurs fiables capable de prédire la réponse aux traitements conventionnels et innovants, facilement transposables en clinique, représente également un enjeu majeur pour améliorer sa prise en charge. Dans ce contexte, les miARNs cellulaires et circulants constituent un champ d’investigation prometteur. L’identification de miARNs dans des modèles d’organoïdes dérivés de tumeurs de patientes (ou tumoroïdes) dont la réponse ex vivo à un traitement d’intérêt serait connue permettrait de s’affranchir des difficultés liées à la mise en place d’une collection d’échantillons biologiques mais surtout de la nécessité que ce traitement soit déjà utilisé en clinique. Il serait alors possible d’identifier un ou des miARNs prédictifs de la réponse à une molécule dès son développement. La première étape de ce travail, consistant en l’étude de l’expression de six miARNs d’intérêt (miR-21-5p, miR-200a 3p, miR-200b-3p, miR-622, miR-484, miR-642a-5p) dans 14 lignées de tumoroïdes ovariens, a permis de démontrer la faisabilité de leur dosage dans la fraction cellulaire et extracellulaire (surnageant de culture) de tumoroïdes, mais également toute la complexité pour définir une méthodologie robuste. Afin de contrôler la variabilité de l’expression des miARNs au sein des réplicas de culture d’une même lignée, nos résultats ont montré l’intérêt d’utiliser une normalisation commune basée sur la moyenne géométrique de deux miARNs endogènes (miR-16-5p et miR-191-5p) pour la fraction cellulaire et extracellulaire des tumoroïdes et d’utiliser au minimum huit réplicas de culture. Fort de ce constat, une corrélation de l’expression de ces six miARNs d’intérêt est observée entre les deux compartiments des tumoroïdes mais également entre la fraction cellulaire des tumoroïdes et les tumeurs congelées, et entre le surnageant de culture et les échantillons de sérum, appariés. Par ailleurs, bien que les variations d’expression des six miARNs d’intérêt n’ont pas montré de différence significative entre les lignées classées sensibles et résistantes au carboplatine, le miR-622 semblait plus exprimé dans les lignées résistantes de manière cohérente avec les résultats décrits chez les patientes. En résumé ces résultats posent les bases de l’utilisation des tumoroïdes comme nouvelle approche permettant l’identification de miARNs prédictifs de réponse à un traitement dans les cancers de l’ovaireIn 2023, Epithelial Ovarian Cancer is a rare disease, representing the 5th leading cause of cancer mortality in women in France. In addition to new therapies, the development of reliable biomarkers capable of predicting response to conventional and innovative treatments, which can be easily transferred to the clinic, also represents a main challenge for improving its management. In this context, cellular and circulating miRNAs represent a promising field of investigation. The identification of miRNAs in Patient-derived tumor organoids (PDTO or tumoroids) whose ex vivo response to a treatment of interest is known would make it possible to avoid the issues associated with setting up a collection of biological samples, and above all the need for the treatment to already be in clinical use. It would then be possible to identify one or additional miRNAs predictive of the response to a molecule as soon as it is developed. The first stage of this work, consisting in the study of the expression of six miRNAs of interest (miR-21-5p, miR-200a 3p, miR-200b-3p, miR-622, miR-484, miR-642a-5p) in 14 ovarian PDTO lines, demonstrated the feasibility of their quantification in the cellular and extracellular fraction (culture supernatant) of tumoroids, but also the complexity of defining a robust methodology. To control the variability of miRNA expression within culture replicas of the same line, our results demonstrated the relevance of using a common normalization based on the geometric mean of two endogenous miRNAs (miR 16-5p and miR-191-5p) for the cellular and extracellular fraction of PDTO, and of using a minimum of eight culture replicas. Based on these observations, a correlation in the expression of these six miRNAs of interest was observed between the two tumoroid compartments, but also between the tumoroid cell fraction and frozen tumors, and between culture supernatant and serum samples, matched. Furthermore, although the variations in expression of the six miRNAs of interest showed no significant difference between PDTO lines classified as sensitive and resistant to carboplatin, miR-622 appeared to be more highly expressed in PDTO resistant lines, according to the results described in the patients. In summary, these results open future opportunities for the use of tumoroids as a new approach to identifying miRNAs predictive of response to treatment in ovarian carcinoma
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Jehl, Aude. "Cavéoline-1 prédictive de la métastase et de la rechute locorégionale des cancers des voies aérodigestives supérieures." Thesis, Strasbourg, 2022. http://www.theses.fr/2022STRAJ070.
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Ce projet de recherche translationnelle sur les cancers des voies aérodigestives supérieures (VADS) a permis d’identifier la cavéoline-1 (Cav1) comme un biomarqueur pronostique de l’évolution d’une tumeur primitive des VADS. En effet, une surexpression de cette protéine favorise une rechute locorégionale alors qu’un déficit de Cav1 engage la tumeur vers un processus métastatique. De plus, nous avons mis en évidence l’implication de l’axe Cav1 / EREG / YAP dans la résistance au traitement (cétuximab et radiothérapie). Enfin, nous avons identifié l’épireguline (EREG) comme la protéine clé de la résistance au cétuximab. Ainsi, un déficit d’EREG sensibilise les cellules au cétuximab par activation de la ferroptose et l’association de cette thérapie ciblée à la molécule de RSL3 ou à la metformine restreint drastiquement la survie cellulaire en accentuant cette mort cellulaire programmée. Ces derniers résultats ont pu être confirmés grâce à un modèle 3D complexe récapitulant l’hétérogénéité intra- et inter-tumorale, à savoir le modèle tumoroïde établi à partir de pièces opératoires de patients atteints d’un cancer des VADSThis translational research project on head and neck cancers has identified caveolin-1 (Cav1) as a prognostic biomarker for the evolution of a primary tumor of these cancers. Indeed, an overexpression of this protein favors a locoregional relapse whereas a deficiency of Cav1 engages the tumor towards a metastatic process. Moreover, we have highlighted the involvement of the Cav1 / EREG / YAP axis in the resistance to treatment (cetuximab and radiotherapy). Finally, we identified epiregulin (EREG) as the key protein in cetuximab resistance. Thus, a deficiency of EREG sensitizes cells to cetuximab by activation of ferroptosis and the association of this target therapy with the RSL3 molecule or metformin drastically restricts cell survival by accentuating this programmed cell death. These last results could be confirmed thanks to a complex 3D model recapitulating the intra- and inter-tumoral heterogeneity, namely the tumoroid model established from surgical parts of patients with head and neck cancer
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Thorel, Lucie. "Utilisatiοn de tests fοnctiοnnels pοur la prédictiοn de la répοnse des cancers οvariens à la chimiοthérapie cοnventiοnnelle et aux inhibiteurs de ΡARΡ : intérêt des οrganοides tumοraux." Electronic Thesis or Diss., Normandie, 2024. http://www.theses.fr/2024NORMC416.
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Les cancers ovariens constituent la deuxième cause de décès par cancers gynécologiques dans le monde, principalement en raison d'un diagnostic tardif associé au développement de résistances à la chimiothérapie. Environ la moitié de ces cancers présentent des altérations dans la recombinaison homologue (RH), ce qui les rend sensibles aux inhibiteurs des protéines PARP (PARPi), impliquées dans la réparation de l'ADN. Cependant, identifier les patientes répondeuses à la chimiothérapie et sélectionner celles éligibles aux PARPi demeure un défi pour les cliniciens. Dans ce contexte, l'utilisation de tumoroïdes pour des tests fonctionnels prédictifs représente une approche prometteuse pour orienter les choix thérapeutiques en première ligne et au-delà. L'objectif de cette thèse est d'étudier la faisabilité de tests fonctionnels basés sur des tumoroïdes afin d'évaluer leur applicabilité potentielle en médecine de précision. L’établissement d'un panel de tumoroïdes issus de divers sous-types histologiques ovariens a permis de démontrer que ces modèles récapitulent les caractéristiques histologiques et moléculaires de leurs tumeurs d'origine. Suite aux test fonctionnels d’exposition directe des tumoroïdes à des traitements de 1ère et 2nde ligne, nous avons pu montrer que ces modèles présentent des réponses hétérogènes aux traitements et notamment que les modèles tumoroïdes identifiés par le test prédictif comme sensibles au carboplatine provenaient principalement de patientes répondeuses. Parallèlement, nous avons étudié les résultats d'un test fonctionnel évaluant le statut RH, le test RECAP et avons démontré que ce test était complémentaire à la méthode actuelle de détermination du statut RH, qui repose sur des techniques de séquençage NGS. Bien que des investigations à plus grande échelle soient nécessaires pour confirmer le potentiel des tumoroïdes, ces résultats fournissent des arguments supplémentaires en faveur de l'utilisation des tumoroïdes ovariens dans un contexte de médecine de précisionOvarian cancers are the second leading cause of death from gynecological cancers worldwide, primarily due to late diagnosis combined with the development of resistance to chemotherapy. Approximately half of these cancers exhibit alterations in homologous recombination (HR), making them sensitive to PARP protein inhibitors (PARPi), which are involved in DNA repair. However, identifying patients who respond to chemotherapy and selecting those eligible for PARPi remains a challenge for clinicians. In this context, the use of patient-derived tumor organoids (PDTO) for predictive functional testing represents a promising approach to guide therapeutic choices in first-line treatment and beyond. The aim of this thesis is to study the feasibility of functional tests based on PDTO to evaluate their potential applicability in precision medicine. Establishing a panel of PDTO derived from various ovarian histological subtypes has demonstrated that these models recapitulate the histological and molecular characteristics of their tumors of origin. Following direct exposure functional tests of the tumor organoids to first- and second-line treatments, we showed that these models exhibit heterogeneous responses to treatments, and particularly that PDTO identified by the predictive test as sensitive to carboplatin mainly originated from responding patients. Additionally, we investigated the results of a functional test assessing HR status, the RECAP test, and demonstrated that this test is complementary to the current method for determining HR status, which relies on NGS sequencing techniques. Although larger-scale investigations are needed to confirm the potential of tumor organoids, these results provide further support for the use of ovarian tumor organoids in the context of precision medicine
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Perréard, Marion. "Dévelοppement, caractérisatiοn et utilisatiοn de mοdèles d'οrganοïdes issus de tumeurs VADS pοur la prédictiοn de la répοnse aux traitements et le dévelοppement de stratégies innοvantes." Electronic Thesis or Diss., Normandie, 2025. http://www.theses.fr/2025NORMC405.
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Les carcinomes épidermoïdes (CE) des voies aéro-digestives supérieures (VADS) sont le 5ème cancer en France, et son pronostic est sombre avec une survie à 5 ans tous stades confondus de l’ordre de 40%. Les stratégies thérapeutiques reposent sur des associations des traitements (chirurgie, radiothérapie, chimiothérapie à base de platine) avec une lourde toxicité pour les patients. La résistance aux traitements est également une problématique majeure. Ces éléments soulignent l’importance d’une médecine personnalisée pour améliorer la prise en charge des patients atteints d’un CE des VADS et augmenter l’efficacité des traitements tout en réduisant le risque de toxicité de la prise en charge globale. Dans ce contexte, l’utilisation de tests fonctionnels sur des modèles ex vivo, comme les tumoroïdes, pourrait être une solution pour répondre à ces problématiques. Les objectifs de cette thèse étaient d’établir des lignées de tumoroïdes des CE des VADS, de vérifier leur pertinence en comparant leurs caractéristiques histologiques et moléculaires avec les tumeurs d’origine, de les exposer à des thérapies conventionnelles pour étudier la corrélation avec la réponse clinique du patient et de les exposer à des thérapies innovantes pour explorer de nouvelles possibilités thérapeutiques. Nous avons établi 24 lignées de tumoroïdes de CE des VADS à long terme avec une amélioration des conditions de culture permettant d’atteindre un taux d’établissement de 26%. Les tumoroïdes avaient les même les caractéristiques histologiques de CE que les tumeurs appariées et avaient une expression des marqueurs tumoraux comparable. La réponse des tumoroïdes au cisplatine et à la radiothérapie a pu être évaluée et la réponse au cisplatine était corrélée au pronostic du patient. Les tumoroïdes ont été exposé à des thérapies innovantes, notamment des ions carbone, permettant de montrer l’intérêt de ces modèles dans l’étude des particules lourdes et la meilleure efficacité biologique des ions carbone par rapport aux rayons X. Notre travail a donc permis de consolider les arguments en faveur de l’utilisation des tumoroïdes de VADS comme modèle pertinent en cancérologie, que ce sont à des fins de recherche préclinique ou à des fins de médecine personnaliséeHead and Neck Squamous Cell Carcinoma (HNSCC) is the 5th most common cancer in France, and has a poor prognosis with a 5-year survival rate for all stages combined around 40%. Therapeutic strategies are based on combinations of treatments (surgery, radiotherapy, platinum-based chemotherapy), with high toxicity for patients. Resistance to treatment is also a major problem. These factors underline the importance of personalized medicine in improving the management of patients with HNSCC, by increasing the efficiency of treatments while reducing the risk of toxicity. In this context, the use of functional tests on ex vivo models, such as patient-derived tumor organoids (PDTO), could be a solution to address these issues. The aims of this thesis were to establish HNSCC PDTO lines, validate their relevance by comparing their histological and molecular characteristics with the original tumors, expose them to conventional therapies to study correlation with patient clinical response, and expose them to innovative therapies to explore new therapeutic possibilities. We established 24 long-term HNSCC PDTO lines achieving a success rate of establishment of 26%. The PDTO had the same histological features of SCC as the matched tumors and had matched tumor marker expression. The response of PDTO to cisplatin and radiotherapy had been assessed, and response to cisplatin correlated with patient prognosis. The PDTO were exposed to innovative therapies, in particular carbon ions, demonstrating the interest of these models in the study of heavy particles and the greater biological efficacy of carbon ions over X-rays. Our work has thus consolidated the arguments in favor of using HNSCC PDTO as a relevant model in oncology, whether for preclinical research or personalized medicine
Book chapters on the topic "Tumoroïde"
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Wu, Peng V., and Roel Nusse. "3D Culture of Primary Patient-Derived Hepatoblastoma Tumoroids." In Methods in Molecular Biology, 259–67. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2557-6_19.
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Afify, Said M., and Masaharu Seno. "In Vitro Tumoroid Model Using Cancer Stem Cells." In Methods in Cancer Stem Cell Biology, 233–43. Singapore: Springer Nature Singapore, 2023. http://dx.doi.org/10.1007/978-981-99-1331-2_20.
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Kark, U., M. Kiechle-Schwarz, H. G. Meerpohl, and H. P. Zahradnik. "Biologische Effekte einer intraperitonealen TNF-Applikation. Kein Hinweis für Stimulation von Tumoroder Fibroblastenwachstum." In Gynäkologie und Geburtshilfe 1992, 1089–91. Berlin, Heidelberg: Springer Berlin Heidelberg, 1993. http://dx.doi.org/10.1007/978-3-642-77857-5_428.
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Burkhard, Kathleen M., and Geeta Mehta. "Multicellular Tumoroids for Investigating Cancer Stem-Like Cells in the Heterogeneous Tumor Microenvironment." In Methods in Molecular Biology, 99–122. New York, NY: Springer US, 2024. http://dx.doi.org/10.1007/978-1-0716-3730-2_8.
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Movia, Dania, and Adriele Prina-Mello. "A Method for Culturing 3D Tumoroids of Lung Adenocarcinoma Cells at the Air–Liquid Interface." In Methods in Molecular Biology, 173–78. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-3056-3_9.
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Yousefpour Marzbali, Mahsa, and Nima Rezaei. "The Role of Tumoroids in Cancer Research." In Interdisciplinary Cancer Research. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/16833_2022_112.
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Rijal, Girdhari. "Dynamic Fibroblasts Turn a Tumoroid to a Tumor." In Advanced Concepts in Medicine and Medical Research Vol. 11, 48–73. B P International, 2023. http://dx.doi.org/10.9734/bpi/acmmr/v11/6914b.
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Ferreira, Bárbara, Joana Peixoto, and Jorge Lima. "Application and Relevance of Organoid/Tumoroid Models in the Context of Pediatric Solid Tumors." In Reference Module in Biomedical Sciences. Elsevier, 2023. http://dx.doi.org/10.1016/b978-0-443-15717-2.00011-1.
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Mierke, Claudia Tanja. "A survey of biophysical techniques used for the mechanical characterization of cell spheroids, organoids, and tumoroids." In Physics of Cancer, Volume 4 (Second Edition), 4–1. IOP Publishing, 2023. http://dx.doi.org/10.1088/978-0-7503-4003-8ch4.
Full textConference papers on the topic "Tumoroïde"
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Dhanushkodi, Nisha R., Abhinit Nagar, Jared Ehrhart, Arnat Balabiyev, Jessica Linkous, Savannah Richardson, Michelle Ataya, et al. "253 Harnessing tumoroids to advance CAR-T cell therapies." In SITC 39th Annual Meeting (SITC 2024) Abstracts, A291. BMJ Publishing Group Ltd, 2024. http://dx.doi.org/10.1136/jitc-2024-sitc2024.0253.
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Müller, S. "Personalisierte Onkologie mithilfe von Tumoroiden als 3D Modelle von Weichgewebssarkomen." In Viszeralmedizin 2023 77. Jahrestagung der DGVS mit Sektion Endoskopie Herbsttagung der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie mit den Arbeitsgemeinschaften der DGAV und Jahrestagung der CACP. Georg Thieme Verlag, 2023. http://dx.doi.org/10.1055/s-0043-1771948.
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Balabiyev, Arnat, Abhinit Nagar, Jared Ehrhart, Nisha R. Dhanushkodi, Jessica Linkous, Savannah Richardson, Michelle Ataya, et al. "816 Predictive modeling of immune-related adverse events using tumoroids." In SITC 39th Annual Meeting (SITC 2024) Abstracts, A923. BMJ Publishing Group Ltd, 2024. http://dx.doi.org/10.1136/jitc-2024-sitc2024.0816.
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Finnberg, Niklas K., Prashanth Gokare, Avital Lev, Alexander W. MacFarlane, Kerry S. Campbell, Karen Kaputa, Jeffrey Farma, Luigi Grasso, Nicholas C. Nicolaides, and Wafik El-Deiry. "Abstract 3990: Use of 3D tumoroid systems to define immune and cytotoxic therapeutic responses based on tumoroid and tissue slice culture molecular signatures." 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.am2017-3990.
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Xie, Chao, Gabriel Jobin, Hector Mendez-Gomez, Chong Zhao, Dingpeng Zhang, John A. Ligon, and Elias Sayour. "1416 A patients-derived glioblastoma tumoroids model to study individual response to chemo-radiation." In SITC 39th Annual Meeting (SITC 2024) Abstracts, A1583. BMJ Publishing Group Ltd, 2024. http://dx.doi.org/10.1136/jitc-2024-sitc2024.1416.
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Reinhardt, J., A. Kühnle, V. Nischalke, S. Brosch, L. Hirschwald, C. Esch, S. Rensen, et al. "Etablierung eines neuen Tumoroid-on-a-Chip Modells bei Pankreaskarzinom und Cholangiozellulärem Karzinom." In Viszeralmedizin 2023 77. Jahrestagung der DGVS mit Sektion Endoskopie Herbsttagung der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie mit den Arbeitsgemeinschaften der DGAV und Jahrestagung der CACP. Georg Thieme Verlag, 2023. http://dx.doi.org/10.1055/s-0043-1771904.
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Rosanò, Laura, Judith Pape, Umber Cheema, Marilena Loizidou, and Anna Bagnato. "Abstract 49: ET-1 receptor blockade in engineered 3D high-grade serous ovarian cancer tumoroids." 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.sabcs18-49.
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Rosanò, Laura, Judith Pape, Umber Cheema, Marilena Loizidou, and Anna Bagnato. "Abstract 49: ET-1 receptor blockade in engineered 3D high-grade serous ovarian cancer tumoroids." 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.am2019-49.
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