THE CREATING OF THREE-DIMENSIONAL CELLULAR MODELS TO SOLVE THEORETICAL AND PRACTICAL PROBLEMS OF MODERN ONCOLOGY

A tumor is a multicomponent, spatially difficult organi-zated system, which is characterized by individual characteristics for each patient. In vitro cell model creating that is close in structure and properties to the natural tumor system will promotes to solving such practical and theoretical problems of modern oncology as identifying the biological patterns of tumor growth, the behavior of cells of the immune system, testing potential antitumor drugs, determining the effectiveness of methods chemo-, radio-, photodynamic, targeted and immunotherapy. Such model can be three-dimensional cellular structures - spheroids (tumoroids). The review presents data about the features of three-dimensional cell modeling, the characteristics of existing 3D models and their application in experimental and clinical studies.

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Three-dimensional cell culture systems as an in vitro platform for cancer and stem cell modeling

World Journal of Stem Cells ◽

10.4252/wjsc.v11.i12.1065 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1065-1083 ◽

Cited By ~ 25

Author(s):

Nipha Chaicharoenaudomrung ◽

Phongsakorn Kunhorm ◽

Parinya Noisa

Keyword(s):

Cell Culture ◽

Stem Cell ◽

Three Dimensional ◽

Culture Systems ◽

Cell Culture Systems ◽

Cell Modeling ◽

Dimensional Cell

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The Revolutionary Roads to Study Cell–Cell Interactions in 3D In Vitro Pancreatic Cancer Models

Cancers ◽

10.3390/cancers13040930 ◽

2021 ◽

Vol 13 (4) ◽

pp. 930

Author(s):

Donatella Delle Cave ◽

Riccardo Rizzo ◽

Bruno Sainz ◽

Giuseppe Gigli ◽

Loretta L. del Mercato ◽

...

Keyword(s):

Pancreatic Cancer ◽

Therapeutic Response ◽

Three Dimensional ◽

Cellular Models ◽

Common Cancer ◽

Cancer Models ◽

Anti Cancer ◽

Tumor Environment

Pancreatic cancer, the fourth most common cancer worldwide, shows a highly unsuccessful therapeutic response. In the last 10 years, neither important advancements nor new therapeutic strategies have significantly impacted patient survival, highlighting the need to pursue new avenues for drug development discovery and design. Advanced cellular models, resembling as much as possible the original in vivo tumor environment, may be more successful in predicting the efficacy of future anti-cancer candidates in clinical trials. In this review, we discuss novel bioengineered platforms for anticancer drug discovery in pancreatic cancer, from traditional two-dimensional models to innovative three-dimensional ones.

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Prevascularized, Co-Culture Model for Breast Cancer Drug Development

ASME 2012 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2012-80409 ◽

2012 ◽

Author(s):

Lauren Marshall ◽

Isabel Löwstedt ◽

Paul Gatenholm ◽

Joel Berry

Keyword(s):

Breast Cancer ◽

Drug Development ◽

Three Dimensional ◽

Human Tumor ◽

3D Models ◽

Cancer Drug ◽

Cancer Therapies ◽

Anti Cancer

The objective of this study was to create 3D engineered tissue models to accelerate identification of safe and efficacious breast cancer drug therapies. It is expected that this platform will dramatically reduce the time and costs associated with development and regulatory approval of anti-cancer therapies, currently a multi-billion dollar endeavor [1]. Existing two-dimensional (2D) in vitro and in vivo animal studies required for identification of effective cancer therapies account for much of the high costs of anti-cancer medications and health insurance premiums borne by patients, many of whom cannot afford it. An emerging paradigm in pharmaceutical drug development is the use of three-dimensional (3D) cell/biomaterial models that will accurately screen novel therapeutic compounds, repurpose existing compounds and terminate ineffective ones. In particular, identification of effective chemotherapies for breast cancer are anticipated to occur more quickly in 3D in vitro models than 2D in vitro environments and in vivo animal models, neither of which accurately mimic natural human tumor environments [2]. Moreover, these 3D models can be multi-cellular and designed with extracellular matrix (ECM) function and mechanical properties similar to that of natural in vivo cancer environments [3].

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The Role of Pre-Clinical 3-Dimensional Models of Osteosarcoma

International Journal of Molecular Sciences ◽

10.3390/ijms21155499 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5499

Author(s):

Hannah L. Smith ◽

Stephen A. Beers ◽

Juliet C. Gray ◽

Janos M. Kanczler

Keyword(s):

Three Dimensional ◽

Chorioallantoic Membrane ◽

3D Models ◽

In Ovo ◽

Future Directions ◽

3 Dimensional ◽

In Vivo Animal Models

Treatment for osteosarcoma (OS) has been largely unchanged for several decades, with typical therapies being a mixture of chemotherapy and surgery. Although therapeutic targets and products against cancer are being continually developed, only a limited number have proved therapeutically active in OS. Thus, the understanding of the OS microenvironment and its interactions are becoming more important in developing new therapies. Three-dimensional (3D) models are important tools in increasing our understanding of complex mechanisms and interactions, such as in OS. In this review, in vivo animal models, in vitro 3D models and in ovo chorioallantoic membrane (CAM) models, are evaluated and discussed as to their contribution in understanding the progressive nature of OS, and cancer research. We aim to provide insight and prospective future directions into the potential translation of 3D models in OS.

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Contraction-related stimuli regulate GLUT4 traffic in C2C12-GLUT4myc skeletal muscle cells

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00773.2009 ◽

2010 ◽

Vol 298 (5) ◽

pp. E1058-E1071 ◽

Cited By ~ 37

Author(s):

Wenyan Niu ◽

Philip J. Bilan ◽

Shuhei Ishikura ◽

Jonathan D. Schertzer ◽

Ariel Contreras-Ferrat ◽

...

Keyword(s):

Skeletal Muscle ◽

Cell Surface ◽

Glucose Uptake ◽

Nicotinic Acetylcholine Receptors ◽

Cell Model ◽

Cytosolic Calcium ◽

Atpase Inhibitor ◽

Cellular Models ◽

Compound C

Muscle contraction stimulates glucose uptake acutely to increase energy supply, but suitable cellular models that faithfully reproduce this complex phenomenon are lacking. To this end, we have developed a cellular model of contracting C2C12 myotubes overexpressing GLUT4 with an exofacial myc-epitope tag (GLUT4 myc) and explored stimulation of GLUT4 traffic by physiologically relevant agents. Carbachol (an acetylcholine receptor agonist) induced a gain in cell surface GLUT4 myc that was mediated by nicotinic acetylcholine receptors. Carbachol also activated AMPK, and this response was sensitive to the contractile myosin ATPase inhibitor N-benzyl- p-toluenesulfonamide. The gain in surface GLUT4 myc elicited by carbachol or by the AMPK activator 5-amino-4-carboxamide-1 β-ribose was sensitive to chemical inhibition of AMPK activity by compound C and partially reduced by siRNA-mediated knockdown of AMPK catalytic subunits or LKB1. In addition, the carbachol-induced gain in cell surface GLUT4 myc was partially sensitive to chelation of intracellular calcium with BAPTA-AM. However, the carbachol-induced gain in cell surface GLUT4 myc was not sensitive to the CaMKK inhibitor STO-609 despite expression of both isoforms of this enzyme and a rise in cytosolic calcium by carbachol. Therefore, separate AMPK- and calcium-dependent signals contribute to mobilizing GLUT4 in response to carbachol, providing an in vitro cell model that recapitulates the two major signals whereby acute contraction regulates glucose uptake in skeletal muscle. This system will be ideal to further analyze the underlying molecular events of contraction-regulated GLUT4 traffic.

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Advanced in vitro management of three-dimensional cell cultures and explanted tissue

Cytotherapy ◽

10.1016/s1465324921005156 ◽

2021 ◽

Vol 23 (5) ◽

pp. S145

Author(s):

S. Kress ◽

D. Egger ◽

C. Kasper

Keyword(s):

Cell Cultures ◽

Three Dimensional ◽

Dimensional Cell

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A three-dimensional cell biology model of human hepatocellular carcinoma in vitro

Tumor Biology ◽

10.1007/s13277-010-0140-7 ◽

2010 ◽

Vol 32 (3) ◽

pp. 469-479 ◽

Cited By ~ 15

Author(s):

Jianhua Tang ◽

Jiefeng Cui ◽

Rongxin Chen ◽

Kun Guo ◽

Xiaonan Kang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Biology ◽

Three Dimensional ◽

Human Hepatocellular Carcinoma ◽

Dimensional Cell

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An optimised GAS-pharyngeal cell biofilm model

Scientific Reports ◽

10.1038/s41598-021-87377-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Heema K. N. Vyas ◽

Jason D. McArthur ◽

Martina L. Sanderson-Smith

Keyword(s):

Crystal Violet ◽

Biofilm Formation ◽

Cell Model ◽

Matrix Material ◽

Three Dimensional ◽

Growth Period ◽

Optimal Growth ◽

Abiotic Surfaces

AbstractGroup A Streptococcus (GAS) causes 700 million infections and accounts for half a million deaths per year. Biofilm formation has been implicated in both pharyngeal and dermal GAS infections. In vitro, plate-based assays have shown that several GAS M-types form biofilms, and multiple GAS virulence factors have been linked to biofilm formation. Although the contributions of these plate-based studies have been valuable, most have failed to mimic the host environment, with many studies utilising abiotic surfaces. GAS is a human specific pathogen, and colonisation and subsequent biofilm formation is likely facilitated by distinct interactions with host tissue surfaces. As such, a host cell-GAS model has been optimised to support and grow GAS biofilms of a variety of GAS M-types. Improvements and adjustments to the crystal violet biofilm biomass assay have also been tailored to reproducibly detect delicate GAS biofilms. We propose 72 h as an optimal growth period for yielding detectable biofilm biomass. GAS biofilms formed are robust and durable, and can be reproducibly assessed via staining/washing intensive assays such as crystal violet with the aid of methanol fixation prior to staining. Lastly, SEM imaging of GAS biofilms formed by this model revealed GAS cocci chains arranged into three-dimensional aggregated structures with EPS matrix material. Taken together, we outline an efficacious GAS biofilm pharyngeal cell model that can support long-term GAS biofilm formation, with biofilms formed closely resembling those seen in vivo.

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