The Experts below are selected from a list of 6672 Experts worldwide ranked by ideXlab platform
Bernard Ducommun - One of the best experts on this subject based on the ideXlab platform.
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abstract 2025 multicellular Tumor Spheroid 3d models to decipher cancer cell biology and to evaluate anticancer drugs
Cancer Research, 2014Co-Authors: Bernard Ducommun, Valérie LobjoisAbstract:MultiCellular Tumor Spheroid (MCTS) mimic the organization of a Tumor and is considered as an invaluable model to study cancer cell biology and for the preclinical development of new antiproliferative drugs. We will report how engineering of MCTS in association with new technological developments can be used to explore the regionalization and the effects of novel drugs. We will demonstrate the potential of these 3D models to study the kinetics aspects of the response on live Spheroids expressing fluorescent reporters and markers using light sheet microscopy (SPIM). We will also report the development of innovative microdevices dedicated to the study of the dynamics of MCTS formation and to the monitoring of mechanosensing and Tumor growth-induced mechanical stress. We will present our latest advances on the characterization of these processes and on the use of these assays for the identification of new original targets and compounds. Citation Format: Bernard Ducommun, Valerie Lobjois. Multicellular Tumor Spheroid 3D models to decipher cancer cell biology and to evaluate anticancer drugs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2025. doi:10.1158/1538-7445.AM2014-2025
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optical signature of multicellular Tumor Spheroid using index mismatch induced spherical aberrations
Proceedings of SPIE, 2014Co-Authors: Le G Corre, Bernard Ducommun, Pierre Weiss, Corinne LorenzoAbstract:The development of new cancer treatments and the early prediction of their therapeutic potential are often made difficult by the lack of predictive pharmacological models. The 3D multicellular Tumor Spheroid (MCTS) model offers a level of complexity that recapitulates the three-dimensional organization of a Tumor and appears to be fairly predictive of therapeutic efficiency. The use of Spheroids in large-scale automated screening was recently reported to link the power of a high throughput analysis to the predictability of a 3D cell model. The Spheroid has a radial symmetry; this simple geometry allows establishing a direct correlation between structure and function. The outmost layers of MCTS are composed of proliferating cells and form structurally uniform domain with an approximate thickness of 100 microns. The innermost layers are composed of quiescent cells. Finally, cells in the center of the Spheroid can form a necrotic core. This latest region is structurally heterogeneous and is poorly characterized. These features make the Spheroid a model of choice and a paradigm to study the optical properties of various epithelial tissues. In this study, we used an in-vitro optical technique for label-free characterization of multicellular systems based on the index- mismatch induced spherical aberrations. We achieve to monitor and characterize the optical properties of MCTS. This new and original approach might be of major interest for the development of innovative screening strategies dedicated to the identification of anticancer drugs.
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abstract 4404 multicellular Tumor Spheroid models to evaluate drugs targeting cell cycle checkpoints in 3d
Cancer Research, 2013Co-Authors: Bernard Ducommun, Jennifer Laurent, Céline Frongia, Odile Mondesert, Valérie Lobjois, Martine CazalesAbstract:MultiCellular Tumor Spheroid (MCTS) mimic the organization of a Tumor and is considered as an invaluable model to study cancer cell biology and to evaluate new antiproliferative drugs. We report how the characteristics of MCTS in association with new technological developments can be used to explore the regionalization, the dynamics of cell cycle checkpoints and the effects of anticancer drugs in 3D. Spheroids expressing fluorescent reporters were engineered and used to explore cell cycle distribution and regionalization during growth. In these models we monitored cell cycle arrest in response to checkpoint activation after growth factor starvation, DNA injury or treatment with chemotherapeutic agents. The kinetics and regionalized aspects of the response were investigated both on fixed sections and on live Spheroids using light sheet microscopy. All together, our data demonstrate the power of the combination of Spheroids made of genetically modified cells expressing cell cycle reporters with both classical antibody-based detection and the use of innovative 3D imaging strategy. This study paves the way for the investigation of the molecular aspects of checkpoint response in 3D models and the dynamic studies of the 3D response to novel antiproliferative agents. Citation Format: Bernard Ducommun, Valerie Lobjois, Jennifer Laurent, Celine Frongia, Odile Mondesert, Martine Cazales. Multicellular Tumor Spheroid models to evaluate drugs targeting cell cycle checkpoints in 3D. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4404. doi:10.1158/1538-7445.AM2013-4404
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Multicellular Tumor Spheroid models to explore cell cycle checkpoints in 3D
BMC Cancer, 2013Co-Authors: Jennifer Laurent, Céline Frongia, Martine Cazales, Odile Mondesert, Bernard Ducommun, Valérie LobjoisAbstract:Background MultiCellular Tumor Spheroid (MCTS) mimics the organization of a Tumor and is considered as an invaluable model to study cancer cell biology and to evaluate new antiproliferative drugs. Here we report how the characteristics of MCTS in association with new technological developments can be used to explore the regionalization and the activation of cell cycle checkpoints in 3D.
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multicellular Tumor Spheroid models to explore cell cycle checkpoints in 3d
BMC Cancer, 2013Co-Authors: Jennifer Laurent, Céline Frongia, Martine Cazales, Odile Mondesert, Bernard DucommunAbstract:MultiCellular Tumor Spheroid (MCTS) mimics the organization of a Tumor and is considered as an invaluable model to study cancer cell biology and to evaluate new antiproliferative drugs. Here we report how the characteristics of MCTS in association with new technological developments can be used to explore the regionalization and the activation of cell cycle checkpoints in 3D. Cell cycle and proliferation parameters were investigated in Capan-2 Spheroids by immunofluorescence staining, EdU incorporation and using cells engineered to express Fucci-red and -green reporters. We describe in details the changes in proliferation and cell cycle parameters during Spheroid growth and regionalization. We report the kinetics and regionalized aspects of cell cycle arrest in response to checkpoint activation induced by EGF starvation, lovastatin treatment and etoposide-induced DNA damage. Our data present the power and the limitation of Spheroids made of genetically modified cells to explore cell cycle checkpoints. This study paves the way for the investigation of molecular aspects and dynamic studies of the response to novel antiproliferative agents in 3D models.
Céline Frongia - One of the best experts on this subject based on the ideXlab platform.
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abstract 4404 multicellular Tumor Spheroid models to evaluate drugs targeting cell cycle checkpoints in 3d
Cancer Research, 2013Co-Authors: Bernard Ducommun, Jennifer Laurent, Céline Frongia, Odile Mondesert, Valérie Lobjois, Martine CazalesAbstract:MultiCellular Tumor Spheroid (MCTS) mimic the organization of a Tumor and is considered as an invaluable model to study cancer cell biology and to evaluate new antiproliferative drugs. We report how the characteristics of MCTS in association with new technological developments can be used to explore the regionalization, the dynamics of cell cycle checkpoints and the effects of anticancer drugs in 3D. Spheroids expressing fluorescent reporters were engineered and used to explore cell cycle distribution and regionalization during growth. In these models we monitored cell cycle arrest in response to checkpoint activation after growth factor starvation, DNA injury or treatment with chemotherapeutic agents. The kinetics and regionalized aspects of the response were investigated both on fixed sections and on live Spheroids using light sheet microscopy. All together, our data demonstrate the power of the combination of Spheroids made of genetically modified cells expressing cell cycle reporters with both classical antibody-based detection and the use of innovative 3D imaging strategy. This study paves the way for the investigation of the molecular aspects of checkpoint response in 3D models and the dynamic studies of the 3D response to novel antiproliferative agents. Citation Format: Bernard Ducommun, Valerie Lobjois, Jennifer Laurent, Celine Frongia, Odile Mondesert, Martine Cazales. Multicellular Tumor Spheroid models to evaluate drugs targeting cell cycle checkpoints in 3D. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4404. doi:10.1158/1538-7445.AM2013-4404
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Multicellular Tumor Spheroid models to explore cell cycle checkpoints in 3D
BMC Cancer, 2013Co-Authors: Jennifer Laurent, Céline Frongia, Martine Cazales, Odile Mondesert, Bernard Ducommun, Valérie LobjoisAbstract:Background MultiCellular Tumor Spheroid (MCTS) mimics the organization of a Tumor and is considered as an invaluable model to study cancer cell biology and to evaluate new antiproliferative drugs. Here we report how the characteristics of MCTS in association with new technological developments can be used to explore the regionalization and the activation of cell cycle checkpoints in 3D.
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multicellular Tumor Spheroid models to explore cell cycle checkpoints in 3d
BMC Cancer, 2013Co-Authors: Jennifer Laurent, Céline Frongia, Martine Cazales, Odile Mondesert, Bernard DucommunAbstract:MultiCellular Tumor Spheroid (MCTS) mimics the organization of a Tumor and is considered as an invaluable model to study cancer cell biology and to evaluate new antiproliferative drugs. Here we report how the characteristics of MCTS in association with new technological developments can be used to explore the regionalization and the activation of cell cycle checkpoints in 3D. Cell cycle and proliferation parameters were investigated in Capan-2 Spheroids by immunofluorescence staining, EdU incorporation and using cells engineered to express Fucci-red and -green reporters. We describe in details the changes in proliferation and cell cycle parameters during Spheroid growth and regionalization. We report the kinetics and regionalized aspects of cell cycle arrest in response to checkpoint activation induced by EGF starvation, lovastatin treatment and etoposide-induced DNA damage. Our data present the power and the limitation of Spheroids made of genetically modified cells to explore cell cycle checkpoints. This study paves the way for the investigation of molecular aspects and dynamic studies of the response to novel antiproliferative agents in 3D models.
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multicellular Tumor Spheroid model to evaluate spatio temporal dynamics effect of chemotherapeutics application to the gemcitabine chk1 inhibitor combination in pancreatic cancer
BMC Cancer, 2012Co-Authors: Isabelle Dufau, Céline Frongia, Bernard Ducommun, Flavie Sicard, Laure Dedieu, Pierre Cordelier, Frederic Ausseil, Annie ValetteAbstract:Background The multicellular Tumor Spheroid (MCTS) is an in vitro model associating malignant-cell microenvironment and 3D organization as currently observed in avascular Tumors.
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multicellular Tumor Spheroid model to evaluate spatio temporal dynamics effect of chemotherapeutics application to the gemcitabine chk1 inhibitor combination in pancreatic cancer
BMC Cancer, 2012Co-Authors: Isabelle Dufau, Céline Frongia, Bernard Ducommun, Flavie Sicard, Laure Dedieu, Pierre Cordelier, Frederic Ausseil, Annie ValetteAbstract:The multicellular Tumor Spheroid (MCTS) is an in vitro model associating malignant-cell microenvironment and 3D organization as currently observed in avascular Tumors. In order to evaluate the relevance of this model for pre-clinical studies of drug combinations, we analyzed the effect of gemcitabine alone and in combination with the CHIR-124 CHK1 inhibitor in a Capan-2 pancreatic cell MCTS model. Compared to monolayer cultures, Capan-2 MCTS exhibited resistance to gemcitabine cytotoxic effect. This resistance was amplified in EGF-deprived quiescent Spheroid suggesting that quiescent cells are playing a role in gemcitabine multicellular resistance. After a prolonged incubation with gemcitabine, DNA damages and massive apoptosis were observed throughout the Spheroid while cell cycle arrest was restricted to the outer cell layer, indicating that gemcitabine-induced apoptosis is directly correlated to DNA damages. The combination of gemcitabine and CHIR-124 in this MCTS model, enhanced the sensitivity to the gemcitabine antiproliferative effect in correlation with an increase in DNA damage and apoptosis. These results demonstrate that our pancreatic MCTS model, suitable for both screening and imaging analysis, is a valuable advanced tool for evaluating the spatio-temporal effect of drugs and drug combinations in a chemoresistant and microenvironment-depending Tumor model.
Annie Valette - One of the best experts on this subject based on the ideXlab platform.
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multicellular Tumor Spheroid model to evaluate spatio temporal dynamics effect of chemotherapeutics application to the gemcitabine chk1 inhibitor combination in pancreatic cancer
BMC Cancer, 2012Co-Authors: Isabelle Dufau, Céline Frongia, Bernard Ducommun, Flavie Sicard, Laure Dedieu, Pierre Cordelier, Frederic Ausseil, Annie ValetteAbstract:Background The multicellular Tumor Spheroid (MCTS) is an in vitro model associating malignant-cell microenvironment and 3D organization as currently observed in avascular Tumors.
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multicellular Tumor Spheroid model to evaluate spatio temporal dynamics effect of chemotherapeutics application to the gemcitabine chk1 inhibitor combination in pancreatic cancer
BMC Cancer, 2012Co-Authors: Isabelle Dufau, Céline Frongia, Bernard Ducommun, Flavie Sicard, Laure Dedieu, Pierre Cordelier, Frederic Ausseil, Annie ValetteAbstract:The multicellular Tumor Spheroid (MCTS) is an in vitro model associating malignant-cell microenvironment and 3D organization as currently observed in avascular Tumors. In order to evaluate the relevance of this model for pre-clinical studies of drug combinations, we analyzed the effect of gemcitabine alone and in combination with the CHIR-124 CHK1 inhibitor in a Capan-2 pancreatic cell MCTS model. Compared to monolayer cultures, Capan-2 MCTS exhibited resistance to gemcitabine cytotoxic effect. This resistance was amplified in EGF-deprived quiescent Spheroid suggesting that quiescent cells are playing a role in gemcitabine multicellular resistance. After a prolonged incubation with gemcitabine, DNA damages and massive apoptosis were observed throughout the Spheroid while cell cycle arrest was restricted to the outer cell layer, indicating that gemcitabine-induced apoptosis is directly correlated to DNA damages. The combination of gemcitabine and CHIR-124 in this MCTS model, enhanced the sensitivity to the gemcitabine antiproliferative effect in correlation with an increase in DNA damage and apoptosis. These results demonstrate that our pancreatic MCTS model, suitable for both screening and imaging analysis, is a valuable advanced tool for evaluating the spatio-temporal effect of drugs and drug combinations in a chemoresistant and microenvironment-depending Tumor model.
Valérie Lobjois - One of the best experts on this subject based on the ideXlab platform.
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abstract 2025 multicellular Tumor Spheroid 3d models to decipher cancer cell biology and to evaluate anticancer drugs
Cancer Research, 2014Co-Authors: Bernard Ducommun, Valérie LobjoisAbstract:MultiCellular Tumor Spheroid (MCTS) mimic the organization of a Tumor and is considered as an invaluable model to study cancer cell biology and for the preclinical development of new antiproliferative drugs. We will report how engineering of MCTS in association with new technological developments can be used to explore the regionalization and the effects of novel drugs. We will demonstrate the potential of these 3D models to study the kinetics aspects of the response on live Spheroids expressing fluorescent reporters and markers using light sheet microscopy (SPIM). We will also report the development of innovative microdevices dedicated to the study of the dynamics of MCTS formation and to the monitoring of mechanosensing and Tumor growth-induced mechanical stress. We will present our latest advances on the characterization of these processes and on the use of these assays for the identification of new original targets and compounds. Citation Format: Bernard Ducommun, Valerie Lobjois. Multicellular Tumor Spheroid 3D models to decipher cancer cell biology and to evaluate anticancer drugs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2025. doi:10.1158/1538-7445.AM2014-2025
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abstract 4404 multicellular Tumor Spheroid models to evaluate drugs targeting cell cycle checkpoints in 3d
Cancer Research, 2013Co-Authors: Bernard Ducommun, Jennifer Laurent, Céline Frongia, Odile Mondesert, Valérie Lobjois, Martine CazalesAbstract:MultiCellular Tumor Spheroid (MCTS) mimic the organization of a Tumor and is considered as an invaluable model to study cancer cell biology and to evaluate new antiproliferative drugs. We report how the characteristics of MCTS in association with new technological developments can be used to explore the regionalization, the dynamics of cell cycle checkpoints and the effects of anticancer drugs in 3D. Spheroids expressing fluorescent reporters were engineered and used to explore cell cycle distribution and regionalization during growth. In these models we monitored cell cycle arrest in response to checkpoint activation after growth factor starvation, DNA injury or treatment with chemotherapeutic agents. The kinetics and regionalized aspects of the response were investigated both on fixed sections and on live Spheroids using light sheet microscopy. All together, our data demonstrate the power of the combination of Spheroids made of genetically modified cells expressing cell cycle reporters with both classical antibody-based detection and the use of innovative 3D imaging strategy. This study paves the way for the investigation of the molecular aspects of checkpoint response in 3D models and the dynamic studies of the 3D response to novel antiproliferative agents. Citation Format: Bernard Ducommun, Valerie Lobjois, Jennifer Laurent, Celine Frongia, Odile Mondesert, Martine Cazales. Multicellular Tumor Spheroid models to evaluate drugs targeting cell cycle checkpoints in 3D. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4404. doi:10.1158/1538-7445.AM2013-4404
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Multicellular Tumor Spheroid models to explore cell cycle checkpoints in 3D
BMC Cancer, 2013Co-Authors: Jennifer Laurent, Céline Frongia, Martine Cazales, Odile Mondesert, Bernard Ducommun, Valérie LobjoisAbstract:Background MultiCellular Tumor Spheroid (MCTS) mimics the organization of a Tumor and is considered as an invaluable model to study cancer cell biology and to evaluate new antiproliferative drugs. Here we report how the characteristics of MCTS in association with new technological developments can be used to explore the regionalization and the activation of cell cycle checkpoints in 3D.
Suzanne A Eccles - One of the best experts on this subject based on the ideXlab platform.
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three dimensional 3d Tumor Spheroid invasion assay
Journal of Visualized Experiments, 2015Co-Authors: Maria Vinci, Carol Box, Suzanne A EcclesAbstract:Invasion of surrounding normal tissues is generally considered to be a key hallmark of malignant (as opposed to benign) Tumors. For some cancers in particular (e.g., brain Tumors such as glioblastoma multiforme and squamous cell carcinoma of the head and neck – SCCHN) it is a cause of severe morbidity and can be life-threatening even in the absence of distant metastases. In addition, cancers which have relapsed following treatment unfortunately often present with a more aggressive phenotype. Therefore, there is an opportunity to target the process of invasion to provide novel therapies that could be complementary to standard anti-proliferative agents. Until now, this strategy has been hampered by the lack of robust, reproducible assays suitable for a detailed analysis of invasion and for drug screening. Here we provide a simple micro-plate method (based on uniform, self-assembling 3D Tumor Spheroids) which has great potential for such studies. We exemplify the assay platform using a human glioblastoma cell line and also an SCCHN model where the development of resistance against targeted epidermal growth factor receptor (EGFR) inhibitors is associated with enhanced matrix-invasive potential. We also provide two alternative methods of semi-automated quantification: one using an imaging cytometer and a second which simply requires standard microscopy and image capture with digital image analysis.
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Tumor Spheroid based migration assays for evaluation of therapeutic agents
Methods of Molecular Biology, 2013Co-Authors: Maria Vinci, Carol Box, Miriam Zimmermann, Suzanne A EcclesAbstract:Cell migration is a key hallmark of malignant cells that contributes to the progression of cancers from a primary, localized mass to an invasive and/or metastatic phenotype. Traditional methods for the evaluation of Tumor cell migration in vitro generally employ two-dimensional (2D), homogeneous cultures that do not take into account Tumor heterogeneity, three-dimensional (3D) cell-cell contacts between Tumor and/or host cells or interactions with extracellular matrix proteins. Here we describe a 3D Tumor Spheroid-based migration assay which more accurately reflects the solid Tumor microenvironment and can accommodate both extracellular matrix and host cell interactions. It is a rapid and highly reproducible 96-well plate-based technique and we demonstrate its utility for the evaluation of therapeutic agents/drugs with anti-migratory properties.
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advances in establishment and analysis of three dimensional Tumor Spheroid based functional assays for target validation and drug evaluation
BMC Biology, 2012Co-Authors: Maria Vinci, Miriam Zimmermann, Sharon Gowan, Frances E Boxall, Lisa Patterson, William Court, Cara Lomas, Marta Mendiola, David Hardisson, Suzanne A EcclesAbstract:There is overwhelming evidence that in vitro three-dimensional Tumor cell cultures more accurately reflect the complex in vivo microenvironment than simple two-dimensional cell monolayers, not least with respect to gene expression profiles, signaling pathway activity and drug sensitivity. However, most currently available three-dimensional techniques are time consuming and/or lack reproducibility; thus standardized and rapid protocols are urgently needed. To address this requirement, we have developed a versatile toolkit of reproducible three-dimensional Tumor Spheroid models for dynamic, automated, quantitative imaging and analysis that are compatible with routine high-throughput preclinical studies. Not only do these microplate methods measure three-dimensional Tumor growth, but they have also been significantly enhanced to facilitate a range of functional assays exemplifying additional key hallmarks of cancer, namely cell motility and matrix invasion. Moreover, mutual tissue invasion and angiogenesis is accommodated by coculturing Tumor Spheroids with murine embryoid bodies within which angiogenic differentiation occurs. Highly malignant human Tumor cells were selected to exemplify therapeutic effects of three specific molecularly-targeted agents: PI-103 (phosphatidylinositol-3-kinase (PI3K)-mammalian target of rapamycin (mTOR) inhibitor), 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) (heat shock protein 90 (HSP90) inhibitor) and CCT130234 (in-house phospholipase C (PLC)γ inhibitor). Fully automated analysis using a Celigo cytometer was validated for Tumor Spheroid growth and invasion against standard image analysis techniques, with excellent reproducibility and significantly increased throughput. In addition, we discovered key differential sensitivities to targeted agents between two-dimensional and three-dimensional cultures, and also demonstrated enhanced potency of some agents against cell migration/invasion compared with proliferation, suggesting their preferential utility in metastatic disease. We have established and validated a suite of highly reproducible Tumor microplate three-dimensional functional assays to enhance the biological relevance of early preclinical cancer studies. We believe these assays will increase the translational predictive value of in vitro drug evaluation studies and reduce the need for in vivo studies by more effective triaging of compounds.
