subject:(Multicellular aggregates)

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1. Gontran, Emilie. Elaboration d'un nouvel hydrogel pour l'étude in vitro des gliomes et modélisation mathématique de leur origine : Development of a New Hydrogel for in Vitro Gliomas Study and Mathematical Modeling of their Origin.

Degree: Docteur es, Physique, 2017, Université Paris-Saclay (ComUE)

URL: http://www.theses.fr/2017SACLS416

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Les gliomes sont des tumeurs qui seforment par prolifération anormale de cellules dansle tissu cérébral. La dangerosité de ces tumeursréside dans le fait que la… (more)

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Les gliomes sont des tumeurs qui seforment par prolifération anormale de cellules dansle tissu cérébral. La dangerosité de ces tumeursréside dans le fait que la plupart des gliomes sontinvasifs : les cellules tumorales migrent dans le tissusain autour de la tumeur. Ces cellules tumoralesisolées provoquent des récidives quasi systématiquesaprès traitement (chirurgie, chimiothérapie,radiothérapie), rendant ces tumeurs incurablesactuellement et conduisant au décès du patient. Il estimportant d'associer des études fondamentales pourmieux comprendre leur évolution dès l'origine et desétudes plus appliquées en développant de nouveauxsubstrats pour reproduire in vitro leur évolution. Lescellules progénitrices des oligodendrocytes (OPC)représentent la plus grande population de cellules enprolifération et la plus largement distribuée dans lecerveau adulte, ce qui en fait un suspect idéal del’origine des gliomes. A partir de donnéesexpérimentales de la littérature sur la dynamique invivo de ces cellules, un modèle mathématiquereproduisant cette dynamique dans un tissu sain a étédéveloppé.Ce modèle montre également que les OPC pourraientêtre à l’origine de toutes les formes de gliomerencontrées aussi bien de bas grade que de hautgrade. Par ailleurs, l’approche expérimentale utiliséevisait à développer un substrat de culture cellulaireadapté à l’étude des gliomes in vitro. Ainsi, unhydrogel biocompatible, minimaliste et contrôlable aété élaboré. Celui-ci mime l’élasticité de la matriceextracellulaire (MEC) cérébrale avec une rigidité del’ordre de 200 Pa et l’effet adhésif des molécules dela MEC impliqué dans l’adhésion et la proliférationdes cellules tumorales. Grâce à ses propriétés,l’hydrogel favorise la survie de près de 90% desmodèles cellulaires de gliome utilisés dans notreétude et supporte la croissance en trois dimensionsd’agrégats multicellulaires semblables à lamorphologie de micro-tumeurs in vivo. Le modèled’hydrogel est donc validé pour favoriser la viabilitéet la prolifération cellulaires. Les perspectives detravail futures porteront sur l'optimisation de sacomposition pour mimer de manière encore plusréaliste la croissance tumorale in vivo.

Gliomas are brain tumors arising fromanomalous cell proliferation into the brain tissue.The hazard of these tumors resides in their invasiveability : tumor cells migrate into the healthy tissuesurrounding the tumor. These isolated cells causequasi systematic recurrences after treatment(surgery, chemotherapy, radiotherapy) making thesetumors currently incurable and leading to patientdeath. Hence, it is important to associatefundamental studies for better understanding of theirevolution from their origin with more appliedstudies developing new substrates for reproducingtheir evolution in vitro. Oligodendrocyte progenitorcells (OPC) are the most widely spread proliferatingpopulation in the adult brain, which makes them themain suspect of causing gliomas origin. Fromexperimental data in the literature about in vivodynamic of OPC, a mathematical model that depictsthis dynamic into…

Advisors/Committee Members: Badoual, Mathilde (thesis director), Seksek, Olivier (thesis director).

Subjects/Keywords: Gliomes; Cellules progénitrices des oligodendrocytes; Modélisation; Hydrogel; Prolifération cellulaire; Agrégats multicellulaires; Gliomas; Oligodendrocyte precursor cells; Modeling; Hydrogel; Cell proliferation; Multicellular aggregates

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gontran, E. (2017). Elaboration d'un nouvel hydrogel pour l'étude in vitro des gliomes et modélisation mathématique de leur origine : Development of a New Hydrogel for in Vitro Gliomas Study and Mathematical Modeling of their Origin. (Doctoral Dissertation). Université Paris-Saclay (ComUE). Retrieved from http://www.theses.fr/2017SACLS416

Chicago Manual of Style (16^th Edition):

Gontran, Emilie. “Elaboration d'un nouvel hydrogel pour l'étude in vitro des gliomes et modélisation mathématique de leur origine : Development of a New Hydrogel for in Vitro Gliomas Study and Mathematical Modeling of their Origin.” 2017. Doctoral Dissertation, Université Paris-Saclay (ComUE). Accessed January 17, 2021. http://www.theses.fr/2017SACLS416.

MLA Handbook (7^th Edition):

Vancouver:

Gontran E. Elaboration d'un nouvel hydrogel pour l'étude in vitro des gliomes et modélisation mathématique de leur origine : Development of a New Hydrogel for in Vitro Gliomas Study and Mathematical Modeling of their Origin. [Internet] [Doctoral dissertation]. Université Paris-Saclay (ComUE); 2017. [cited 2021 Jan 17]. Available from: http://www.theses.fr/2017SACLS416.

Council of Science Editors:

Gontran E. Elaboration d'un nouvel hydrogel pour l'étude in vitro des gliomes et modélisation mathématique de leur origine : Development of a New Hydrogel for in Vitro Gliomas Study and Mathematical Modeling of their Origin. [Doctoral Dissertation]. Université Paris-Saclay (ComUE); 2017. Available from: http://www.theses.fr/2017SACLS416

Virginia Tech

2. Jack, Graham Dillon. Endogenous Stress Signaling within Human Multicellular Aggregates (Spheroids).

Degree: PhD, Biochemistry, 2006, Virginia Tech

URL: http://hdl.handle.net/10919/28407

► A wide variety of adherent mammalian cells can be induced into a reversible state of metabolic arrest (quiescence) by conversion to non-adherent multicellular aggregates. These… (more)

▼ A wide variety of adherent mammalian cells can be induced into a reversible state of metabolic arrest (quiescence) by conversion to non-adherent multicellular aggregates. These "spheroids" can be maintained at room temperature under oxygen- and nutrient-deprived conditions for extended periods of time (weeks) as well as converted back to viable proliferating monolayers. Herein it is shown that HEK293 spheroid arrest and recovery requires the co-activation of both NF-kB and JNK, and chemical inhibition of either NF-κB nuclear translocation or JNK phosphorylation leads to cell death. Cytokine profiling within the aggregates during the arrest and recovery process is suggestive that a cyclical cascade was in operation, leading to endogenous cytokine production of TNF-Alpha, IL-1Beta, and IL-8, thereby propagating the cellular stress signal within cells as well as throughout the aggregate. Cytokines exist <i>in vivo</i> as mixtures, yet tissue culture studies delineating how cells respond to these molecules are often performed using individual effectors added exogenously. Are the results obtained in these studies true representations of physiological responses? As HEK293 multicellular aggregates (spheroids) survive long term arrest by endogenous cytokine (TNF-α and IL-1β) and chemokine (IL-8) signaling, adherent monolayer cells were evaluated for their ability to provide a "spheroid signal response" when exposed to TNF-α, IL-1β and IL-8 individually, and in combination, at concentrations observed in the aggregates. The spheroid signal transduction response was only observed when all three cytokines were present, demonstrating that signal transduction cascade mechanisms are cytokine-profile dependent. To determine if similar processes were involved in the arrest and recovery of multicellular aggregates derived from other cell types, the responses of primary human foreskin fibroblasts (HFF-2) and a glioblastoma cell line (T98G) were characterized, utilizing the procedures developed in the HEK293 study. Both the T98G and HFF-2 cell lines entered and exited from the long term arrest utilizing an autocrine response. However, while the carcinoma cell line was dependent upon NF-κB for survival, its signaling partner was Gadd45α and signaling occurred through the p38 pathway. Primary fibroblast arrest and recovery proceeded through the p38 pathway as well, but was independent of NF-κB. Thus, three different cell types and transformation states (HEK293, HFF-2, and T98G) provided three different routes to survival, all with cyclical cytokine production and signaling. These routes cannot be measured or modulated effectively in adherent monolayers. Multicellular aggregates provide higher ordered systems that can be used to describe signaling pathways within a cell, highlighting the role of autocrine responses and the synergistic relationships between cytokines and neighboring cells. Advisors/Committee Members: Helm, Richard Frederick (committeechair), Potts, Malcolm (committee member), Hess, John L. (committee member), Bevan, David R. (committee member), McDowell, John M. (committee member).

Subjects/Keywords: Human Cells; NF-kB; survival; cytokines; Multicellular aggregates; JNK

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jack, G. D. (2006). Endogenous Stress Signaling within Human Multicellular Aggregates (Spheroids). (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/28407

Chicago Manual of Style (16^th Edition):

Jack, Graham Dillon. “Endogenous Stress Signaling within Human Multicellular Aggregates (Spheroids).” 2006. Doctoral Dissertation, Virginia Tech. Accessed January 17, 2021. http://hdl.handle.net/10919/28407.

MLA Handbook (7^th Edition):

Jack, Graham Dillon. “Endogenous Stress Signaling within Human Multicellular Aggregates (Spheroids).” 2006. Web. 17 Jan 2021.

Vancouver:

Jack GD. Endogenous Stress Signaling within Human Multicellular Aggregates (Spheroids). [Internet] [Doctoral dissertation]. Virginia Tech; 2006. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10919/28407.

Council of Science Editors:

Jack GD. Endogenous Stress Signaling within Human Multicellular Aggregates (Spheroids). [Doctoral Dissertation]. Virginia Tech; 2006. Available from: http://hdl.handle.net/10919/28407

3. Brunel, Benjamin. Mesure des déplacements cellulaires dans les tissus non transparents : une application de la diffusion dynamique de la lumière : Measuring cell displacements inside non-transparent tissues : an application of dynamic light scattering.

Degree: Docteur es, Physique pour les sciences du vivant, 2018, Université Grenoble Alpes (ComUE)

URL: http://www.theses.fr/2018GREAY047

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Lorsqu'une tumeur grossit, elle exerce une pression sur les tissus environnants et est comprimée en retour. Des expériences sur un modèle de tumeur in vitro,… (more)

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Lorsqu'une tumeur grossit, elle exerce une pression sur les tissus environnants et est comprimée en retour. Des expériences sur un modèle de tumeur in vitro, appelé sphéroïde, ont montré que cette pression influence largement le devenir du tissu cancéreux, notamment en freinant sa croissance, mais aussi en le rendant plus invasif. Pour mieux comprendre ce dernier effet, nous avons cherché à étudier le comportement migratoire des cellules à l'intérieur d'un sphéroïde sous pression. Observer l'intérieur d'un sphéroïde pose cependant un problème technique car les méthodes usuelles d'imagerie ne sont pas utilisables dans des tissus épais (> 100 μm). L'imagerie classique étant limitée en profondeur à cause de la diffusion de la lumière, nous nous sommes tournés vers une méthode qui utilise justement celle-ci : la diffusion dynamique de lumière ou DLS (Dynamic Light Scattering). Nous avons développé son application à la migration cellulaire, afin d'obtenir la distribution des déplacements relatifs des cellules au cours du temps. Cette mesure est faite sans utiliser de marqueurs spécifiques et est applicable à des sphéroïdes allant jusqu'à 400 μm de diamètre. Nous avons ainsi mis en évidence une organisation radiale du sphéroïde en termes de mobilité, avec des cellules rapides en surface et plus lentes au centre. Nous avons aussi montré qu'en appliquant une contrainte au sphéroïde, la vitesse moyenne diminue jusqu'à être réduite de moitié pour des pressions supérieures à 15kPa. Une autre équipe a mesuré par ailleurs une augmentation de la vitesse des cellules en surface suite à une compression, ce qui indique que l'organisation radiale se retrouve dans la réponse à la pression. Nous avons montré que cette sensibilité à la pression est une propriété qui émerge de l'organisation 3D du tissu, dans laquelle la matrice extracellulaire joue un rôle primordial. Enfin, pour explorer les possibilités qu'offre notre technique, nous l'avons appliquée à une autre question : comment la migration des macrophages est-elle affectée par les signaux provenant de cellules apoptotiques ? Les résultats ont montré que les cellules apoptotiques précoces augmentent la vitesse des macrophages tandis que les cellules apoptotiques tardives la réduisent. D'un cas à l'autre, la longueur de persistance du mouvement est conservée.

As a tumor grows, it exerts a mechanical pressure on its surrounding tissue and is compressed back as a reaction. Recent experiments on an in vitro tumor model, called spheroid, have shown that this pressure is crucial for the fate of the cancerous tissue. In particular, the pressure slows down its growth, but makes it more invasive. To further understand the latter effect, we decided to study the migration of cells inside spheroids under pressure. However, imaging the inside of a spheroid is technically challenging as usual microscopy methods do not work on thick tissues (> 100 μm). Standard imaging methods are limited in terms of depth penetration because of light scattering. For this reason, we decided to take advantage…

Advisors/Committee Members: Cappello, Giovanni (thesis director).

Subjects/Keywords: Diffusion dynamique de lumière; Motilité cellulaire; Agrégats multicellulaires; Cancer; Speckle; Mécanique des tissus; Dynamic Light Scattering; Cell motility; Multicellular aggregates; Cancer; Speckle; Mechanical properties of tissues; 530

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Brunel, B. (2018). Mesure des déplacements cellulaires dans les tissus non transparents : une application de la diffusion dynamique de la lumière : Measuring cell displacements inside non-transparent tissues : an application of dynamic light scattering. (Doctoral Dissertation). Université Grenoble Alpes (ComUE). Retrieved from http://www.theses.fr/2018GREAY047

Chicago Manual of Style (16^th Edition):

Brunel, Benjamin. “Mesure des déplacements cellulaires dans les tissus non transparents : une application de la diffusion dynamique de la lumière : Measuring cell displacements inside non-transparent tissues : an application of dynamic light scattering.” 2018. Doctoral Dissertation, Université Grenoble Alpes (ComUE). Accessed January 17, 2021. http://www.theses.fr/2018GREAY047.

MLA Handbook (7^th Edition):

Vancouver:

Brunel B. Mesure des déplacements cellulaires dans les tissus non transparents : une application de la diffusion dynamique de la lumière : Measuring cell displacements inside non-transparent tissues : an application of dynamic light scattering. [Internet] [Doctoral dissertation]. Université Grenoble Alpes (ComUE); 2018. [cited 2021 Jan 17]. Available from: http://www.theses.fr/2018GREAY047.

Council of Science Editors:

Brunel B. Mesure des déplacements cellulaires dans les tissus non transparents : une application de la diffusion dynamique de la lumière : Measuring cell displacements inside non-transparent tissues : an application of dynamic light scattering. [Doctoral Dissertation]. Université Grenoble Alpes (ComUE); 2018. Available from: http://www.theses.fr/2018GREAY047

4. Desjardins, Mark. Role of Versican in Epithelial Ovarian Carcinoma.

Degree: 2013, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/9704

► Epithelial ovarian carcinoma (EOC) is a leading cause of death from gynecologic malignancies, and the fifth leading cause of death in women. The extracellular matrix… (more)

▼ Epithelial ovarian carcinoma (EOC) is a leading cause of death from gynecologic malignancies, and the fifth leading cause of death in women. The extracellular matrix plays a key role in regulating cellular activities such as proliferation, adhesion, differentiation, and migration. Development of ovarian carcinoma can lead to the alteration of ECM components such as Versican (VCAN). Increased levels of versican have been found in primary epithelial ovarian tumors in pathology studies assessing the role of versican in EOC. The aim of this study was to elaborate the exact role that versican expression in migration and adhesion. Additionally, we sought to identify how versican expression affects multicellular aggregrates (spheroids) properties such as size, formation, and disaggregation. The importance of these multicellular aggregates has come to researchers attention as they have proven to be more resistant to traditional therapy than single cells. We have studied the expression of versican in cell lines expressing high levels of versican as well as lower levels of versican using QRT-PCR. The effect of versican on cellular migration was determined by performing the scratch wound healing assay, and monitoring wound closure over a 24 hour period. These results were corroborated using the modified boyden chamber method. Furthermore, silencing of versican expression in Skov-3, Dov-13, OVCA-429, and OVCA-433 cell lines using siRNA and shRNA resulted in an overall decrease in both single cell adhesion as well as multicellular adhesion on ECM components and on the LP-3 mesothelial monolayer. Additionally, the down-regulation of versican expression in Skov-3 and Dov-13 cell lines significantly inhibited their ability to disaggregate on the mesothelial monolayer and ECM components. We hypothesize that taken all together this data indicates that versican modulates EOC metastasis by increasing cellular adhesion, migration, spheroid formation, and multicellular disaggregation. Advisors/Committee Members: Barbolina, Maria (advisor), Tonetti, Debra (committee member), Swanson, Steven (committee member).

Subjects/Keywords: EOC; epithelial ovarian carcinoma; spheroids; multicellular aggregates; versican; VCAN; spheroid disaggregation

…suggested that the formation of multicellular aggregates known as spheroids may play a huge role… …disseminate off the surface of the ovary they can exist as single cells or multicellular aggregates… …Carcinoma Metastatic Progression. Adapted from: Multicellular spheroids in ovarian cancer…

10 more images…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Desjardins, M. (2013). Role of Versican in Epithelial Ovarian Carcinoma. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/9704

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Desjardins, Mark. “Role of Versican in Epithelial Ovarian Carcinoma.” 2013. Thesis, University of Illinois – Chicago. Accessed January 17, 2021. http://hdl.handle.net/10027/9704.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Desjardins, Mark. “Role of Versican in Epithelial Ovarian Carcinoma.” 2013. Web. 17 Jan 2021.

Vancouver:

Desjardins M. Role of Versican in Epithelial Ovarian Carcinoma. [Internet] [Thesis]. University of Illinois – Chicago; 2013. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10027/9704.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Desjardins M. Role of Versican in Epithelial Ovarian Carcinoma. [Thesis]. University of Illinois – Chicago; 2013. Available from: http://hdl.handle.net/10027/9704

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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