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Journal articles on the topic 'Multicellular tumour spheroids'

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Author: Grafiati

Published: 4 June 2021

Last updated: 20 February 2023

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1

Molla, Annie, Morgane Couvet, and Jean-Luc Coll. "Unsuccessful mitosis in multicellular tumour spheroids." Oncotarget 8, no. 17 (February 24, 2017): 28769–84. http://dx.doi.org/10.18632/oncotarget.15673.

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2

Hargrave, P., P. W. Nicholson, D. T. Delpy, and M. Firbank. "Optical properties of multicellular tumour spheroids." Physics in Medicine and Biology 41, no. 6 (June 1, 1996): 1067–72. http://dx.doi.org/10.1088/0031-9155/41/6/010.

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3

SANTINI, M. T., G. RAINALDI, and P. L. INDOVINA. "Multicellular tumour spheroids in radiation biology." International Journal of Radiation Biology 75, no. 7 (January 1999): 787–99. http://dx.doi.org/10.1080/095530099139845.

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4

Jamieson, L. E., D. J. Harrison, and C. J. Campbell. "Chemical analysis of multicellular tumour spheroids." Analyst 140, no. 12 (2015): 3910–20. http://dx.doi.org/10.1039/c5an00524h.

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5

Sheth, Disha B., and Miklόs Gratzl. "Electrochemical mapping of oxygenation in the three-dimensional multicellular tumour hemi-spheroid." Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences 475, no. 2225 (May 2019): 20180647. http://dx.doi.org/10.1098/rspa.2018.0647.

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Blood capillaries deliver oxygen and nutrients to surrounding micro-regions of tissue and carry away metabolic waste. In normal tissue, capillaries are close enough to keep all the cells viable. In solid tumours, the capillary system is chaotic and typical inter-capillary distances are larger than in normal tissue. Therefore, hypoxic regions develop. Drug molecules may not reach these areas at concentrations above the lethal level. The combined effect of low drug concentrations and local hypoxia, often exacerbated by acidity, leads to therapy failure. To better understand the interplay between hypoxia and poor drug penetration, oxygenation needs to be assessed in different areas of inter-capillary tissue. The multicellular tumour spheroid is a well-established three-dimensional (3D) in vitro model of the capillary microenvironment. It is used to mimic nascent tumours and micro-metastases as well. In this work, we demonstrate for the first time that dynamic intra-spheroidal oxygen maps can be obtained at the 3D multicellular tumour hemi-spheroid (MCH) using a non-invasive microelectrode array. The same oxygen distributions exist inside the equivalent but less accessible full spheroid. The MCH makes high throughput—high content analysis of spheroids feasible and thus can assist studies on basic cancer biology, drug development and personalized medicine.

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6

Grimes, David Robert, Catherine Kelly, Katarzyna Bloch, and Mike Partridge. "A method for estimating the oxygen consumption rate in multicellular tumour spheroids." Journal of The Royal Society Interface 11, no. 92 (March 6, 2014): 20131124. http://dx.doi.org/10.1098/rsif.2013.1124.

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Hypoxia occurs when oxygen levels within a tissue drop below normal physiological levels. In tumours, hypoxia is associated with poor prognosis, increased likelihood of metastasis and resistance to therapy. Imaging techniques, for example, positron emission tomography, are increasingly used in the monitoring of tumour hypoxia and have the potential to help in the planning of radiotherapy. For this application, improved understanding of the link between image contrast and quantitative underlying oxygen distribution would be very useful. Mathematical models of tissue hypoxia and image formation can help understand this. Hypoxia is caused by an imbalance between vascular supply and tissue demand. While much work has been dedicated to the quantitative description of tumour vascular networks, consideration of tumour oxygen consumption is largely neglected. Oxidative respiration in standard two-dimensional cell culture has been widely studied. However, two-dimensional culture fails to capture the complexities of growing three-dimensional tissue which could impact on the oxygen usage. In this study, we build on previous descriptions of oxygen consumption and diffusion in three-dimensional tumour spheroids and present a method for estimating rates of oxygen consumption from spheroids, validated using stained spheroid sections. Methods for estimating the local partial pressure of oxygen, the diffusion limit and the extents of the necrotic core, hypoxic region and proliferating rim are also derived. These are validated using experimental data from DLD1 spheroids at different stages of growth. A relatively constant experimentally derived diffusion limit of 232 ± 22 μm and an O 2 consumption rate of 7.29 ± 1.4 × 10 −7 m 3 kg −1 s −1 for the spheroids studied was measured, in agreement with laboratory measurements.

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7

Chignola, R., A. Schenetti, E. Chiesa, R. Foroni, S. Sartpris, A. Brendolan, G. Tridente, G. Andrighetto, and D. Liberati. "Oscillating growth patterns of multicellular tumour spheroids." Cell Proliferation 32, no. 1 (February 1999): 39–48. http://dx.doi.org/10.1046/j.1365-2184.1999.3210039.x.

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8

McMillan, Kay S., Anthony G. McCluskey, Annette Sorensen, Marie Boyd, and Michele Zagnoni. "Emulsion technologies for multicellular tumour spheroid radiation assays." Analyst 141, no. 1 (2016): 100–110. http://dx.doi.org/10.1039/c5an01382h.

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9

St-Georges-Robillard, Amélie, Maxime Cahuzac, Benjamin Péant, Hubert Fleury, Muhammad Abdul Lateef, Alexis Ricard, Alexandre Sauriol, Frédéric Leblond, Anne-Marie Mes-Masson, and Thomas Gervais. "Long-term fluorescence hyperspectral imaging of on-chip treated co-culture tumour spheroids to follow clonal evolution." Integrative Biology 11, no. 4 (April 1, 2019): 130–41. http://dx.doi.org/10.1093/intbio/zyz012.

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Abstract Multicellular tumour spheroids are an ideal in vitro tumour model to study clonal heterogeneity and drug resistance in cancer research because different cell types can be mixed at will. However, measuring the individual response of each cell population over time is challenging: current methods are either destructive, such as flow cytometry, or cannot image throughout a spheroid, such as confocal microscopy. Our group previously developed a wide-field fluorescence hyperspectral imaging system to study spheroids formed and cultured in microfluidic chips. In the present study, two subclones of a single parental ovarian cancer cell line transfected to express different fluorophores were produced and co-culture spheroids were formed on-chip using ratios forming highly asymmetric subpopulations. We performed a 3D proliferation assay on each cell population forming the spheroids that matched the 2D growth behaviour. Response assays to PARP inhibitors and platinum-based drugs were also performed to follow the clonal evolution of mixed populations. Our experiments show that hyperspectral imaging can detect spheroid response before observing a decrease in spheroid diameter. Hyperspectral imaging and microfluidic-based spheroid assays provide a versatile solution to study clonal heterogeneity, able to measure response in subpopulations presenting as little as 10% of the initial spheroid.

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10

Kerr, David J., Thomas E. Wheldon, Sharyn Hydns, and Stanley B. Kaye. "Cytotoxic drug penetration studies in multicellular tumour spheroids." Xenobiotica 18, no. 6 (January 1988): 641–48. http://dx.doi.org/10.3109/00498258809041702.

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11

Liu, Tianqing, Ivan Kempson, Martin de Jonge, Daryl L. Howard, and Benjamin Thierry. "Quantitative synchrotron X-ray fluorescence study of the penetration of transferrin-conjugated gold nanoparticles inside model tumour tissues." Nanoscale 6, no. 16 (2014): 9774–82. http://dx.doi.org/10.1039/c4nr02100b.

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12

Guirado, D., M. Aranda, M. Ortiz, J. A. Mesa, L. I. Zamora, E. Amaya, M. Villalobos, and A. M. Lallena. "Low-dose radiation hyper-radiosensitivity in multicellular tumour spheroids." British Journal of Radiology 85, no. 1018 (October 2012): 1398–406. http://dx.doi.org/10.1259/bjr/33201506.

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13

Grimes, D. R., and M. Partridge. "PO-0953: Modelling oxygen distribution in multicellular tumour spheroids." Radiotherapy and Oncology 111 (2014): S128. http://dx.doi.org/10.1016/s0167-8140(15)31071-9.

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14

Heredia-Soto, Victoria, Andrés Redondo, José Juan Pozo Kreilinger, Virginia Martínez-Marín, Alberto Berjón, and Marta Mendiola. "3D Culture Modelling: An Emerging Approach for Translational Cancer Research in Sarcomas." Current Medicinal Chemistry 27, no. 29 (September 2, 2020): 4778–88. http://dx.doi.org/10.2174/0929867326666191212162102.

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Sarcomas are tumours of mesenchymal origin, which can arise in bone or soft tissues. They are rare but frequently quite aggressive and with a poor outcome. New approaches are needed to characterise these tumours and their resistance mechanisms to current therapies, responsible for tumour recurrence and treatment failure. This review is focused on the potential of three-dimensional (3D) in vitro models, including multicellular tumour spheroids (MCTS) and organoids, and the latest data about their utility for the study on important properties for tumour development. The use of spheroids as a particularly valuable alternative for compound high throughput screening (HTS) in different areas of cancer biology is also discussed, which enables the identification of new therapeutic opportunities in commonly resistant tumours.

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15

Kelly, Suainibhe, Maria H. Byrne, Susan J. Quinn, and Jeremy C. Simpson. "Multiparametric nanoparticle-induced toxicity readouts with single cell resolution in HepG2 multicellular tumour spheroids." Nanoscale 13, no. 41 (2021): 17615–28. http://dx.doi.org/10.1039/d1nr04460e.

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16

Luján, Emmanuel, Daniela Soto, María S. Rosito, Alejandro Soba, Liliana N. Guerra, Juan C. Calvo, Guillermo Marshall, and Cecilia Suárez. "Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported byin vitrostudies." Integrative Biology 10, no. 5 (2018): 325–34. http://dx.doi.org/10.1039/c8ib00049b.

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17

Hallou, Adrien, Joel Jennings, and Alexandre J. Kabla. "Tumour heterogeneity promotes collective invasion and cancer metastatic dissemination." Royal Society Open Science 4, no. 8 (August 2017): 161007. http://dx.doi.org/10.1098/rsos.161007.

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Heterogeneity within tumour cell populations is commonly observed in most cancers. However, its impact on metastatic dissemination, one of the primary determinants of the disease prognosis, remains poorly understood. Working with a simplified numerical model of tumour spheroids, we investigated the impact of mechanical heterogeneity on the onset of tumour invasion into surrounding tissues. Our work establishes a positive link between tumour heterogeneity and metastatic dissemination, and recapitulates a number of invasion patterns identified in vivo , such as multicellular finger-like protrusions. Two complementary mechanisms are at play in heterogeneous tumours. A small proportion of stronger cells are able to initiate and lead the escape of cells, while collective effects in the bulk of the tumour provide the coordination required to sustain the invasive process through multicellular streaming. This suggests that the multicellular dynamics observed during metastasis is a generic feature of mechanically heterogeneous cell populations and might rely on a limited and generic set of attributes.

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18

Stenberg, Vilde Yuli, Roy Hartvig Larsen, Li-Wei Ma, Qian Peng, Petras Juzenas, Øyvind Sverre Bruland, and Asta Juzeniene. "Evaluation of the PSMA-Binding Ligand 212Pb-NG001 in Multicellular Tumour Spheroid and Mouse Models of Prostate Cancer." International Journal of Molecular Sciences 22, no. 9 (May 1, 2021): 4815. http://dx.doi.org/10.3390/ijms22094815.

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Radioligand therapy targeting the prostate-specific membrane antigen (PSMA) is rapidly evolving as a promising treatment for metastatic castration-resistant prostate cancer. The PSMA-targeting ligand p-SCN-Bn-TCMC-PSMA (NG001) labelled with 212Pb efficiently targets PSMA-positive cells in vitro and in vivo. The aim of this preclinical study was to evaluate the therapeutic potential of 212Pb-NG001 in multicellular tumour spheroid and mouse models of prostate cancer. The cytotoxic effect of 212Pb-NG001 was tested in human prostate C4-2 spheroids. Biodistribution at various time points and therapeutic effects of different activities of the radioligand were investigated in male athymic nude mice bearing C4-2 tumours, while long-term toxicity was studied in immunocompetent BALB/c mice. The radioligand induced a selective cytotoxic effect in spheroids at activity concentrations of 3–10 kBq/mL. In mice, the radioligand accumulated rapidly in tumours and was retained over 24 h, while it rapidly cleared from nontargeted tissues. Treatment with 0.25, 0.30 or 0.40 MBq of 212Pb-NG001 significantly inhibited tumour growth and improved median survival with therapeutic indexes of 1.5, 2.3 and 2.7, respectively. In BALB/c mice, no signs of long-term radiation toxicity were observed at activities of 0.05 and 0.33 MBq. The obtained results warrant clinical studies to evaluate the biodistribution, therapeutic efficacy and toxicity of 212Pb-NG001.

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19

Marušić, M., Ž. Bajzer, J. P. Freyer, and S. Vuk-Pavlović. "Analysis of growth of multicellular tumour spheroids by mathematical models." Cell Proliferation 27, no. 2 (February 1994): 73–94. http://dx.doi.org/10.1111/j.1365-2184.1994.tb01407.x.

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20

Schaller, Gernot, and Michael Meyer-Hermann. "Continuum versus discrete model: a comparison for multicellular tumour spheroids." Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 364, no. 1843 (April 18, 2006): 1443–64. http://dx.doi.org/10.1098/rsta.2006.1780.

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We study multicellular tumour spheroids with a continuum model based on partial differential equations (PDEs). The model includes viable and necrotic cell densities, as well as oxygen and glucose concentrations. Viable cells consume nutrients and become necrotic below critical nutrient concentrations. Proliferation of viable cells is contact-inhibited if the total cellular density locally exceeds volume carrying capacity. The model is discussed under the assumption of spherical symmetry. Unknown model parameters are determined by simultaneously fitting the cell number to several experimental growth curves for different nutrient concentrations. The outcome of the PDE model is compared with an analogous off-lattice agent-based model for tumour growth. It turns out that the numerically more efficient PDE model suffices to explain the macroscopic growth data. As in the agent-based model, we find that the experimental growth curves are only reproduced when a necrotic core develops. However, evaluation of morphometric properties yields differences between the models and the experiment.

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21

Tindall, Marcus J., Louise Dyson, Kieran Smallbone, and Philip K. Maini. "Modelling acidosis and the cell cycle in multicellular tumour spheroids." Journal of Theoretical Biology 298 (April 2012): 107–15. http://dx.doi.org/10.1016/j.jtbi.2011.11.009.

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22

Griffon, G., C. Marchal, J. L. Merlin, S. Marchal, R. M. Parache, and P. Bey. "Radiosensitivity of multicellular tumour spheroids obtained from human ovarian cancers." European Journal of Cancer 31, no. 1 (January 1995): 85–91. http://dx.doi.org/10.1016/0959-8049(94)00377-h.

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23

Timmins, Nicholas, Stefanie Dietmair, and Lars Nielsen. "Hanging-drop multicellular spheroids as a model of tumour angiogenesis." Angiogenesis 7, no. 2 (2004): 97–103. http://dx.doi.org/10.1007/s10456-004-8911-7.

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24

Han, Seokgyu, Sein Kim, Zhenzhong Chen, Hwa Kyoung Shin, Seo-Yeon Lee, Hyo Eun Moon, Sun Ha Paek, and Sungsu Park. "3D Bioprinted Vascularized Tumour for Drug Testing." International Journal of Molecular Sciences 21, no. 8 (April 23, 2020): 2993. http://dx.doi.org/10.3390/ijms21082993.

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An in vitro screening system for anti-cancer drugs cannot exactly reflect the efficacy of drugs in vivo, without mimicking the tumour microenvironment (TME), which comprises cancer cells interacting with blood vessels and fibroblasts. Additionally, the tumour size should be controlled to obtain reliable and quantitative drug responses. Herein, we report a bioprinting method for recapitulating the TME with a controllable spheroid size. The TME was constructed by printing a blood vessel layer consisting of fibroblasts and endothelial cells in gelatine, alginate, and fibrinogen, followed by seeding multicellular tumour spheroids (MCTSs) of glioblastoma cells (U87 MG) onto the blood vessel layer. Under MCTSs, sprouts of blood vessels were generated and surrounding MCTSs thereby increasing the spheroid size. The combined treatment involving the anti-cancer drug temozolomide (TMZ) and the angiogenic inhibitor sunitinib was more effective than TMZ alone for MCTSs surrounded by blood vessels, which indicates the feasibility of the TME for in vitro testing of drug efficacy. These results suggest that the bioprinted vascularized tumour is highly useful for understanding tumour biology, as well as for in vitro drug testing.

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25

Barathova, Monika, Katarina Grossmannova, Petra Belvoncikova, Veronika Kubasova, Veronika Simko, Rudolf Skubla, Lucia Csaderova, and Jaromir Pastorek. "Impairment of Hypoxia-Induced CA IX by Beta-Blocker Propranolol—Impact on Progression and Metastatic Potential of Colorectal Cancer Cells." International Journal of Molecular Sciences 21, no. 22 (November 19, 2020): 8760. http://dx.doi.org/10.3390/ijms21228760.

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The coexistence of cancer and other concomitant diseases is very frequent and has substantial implications for treatment decisions and outcomes. Beta-blockers, agents that block the beta-adrenergic receptors, have been related also to cancers. In the model of multicellular spheroids formed by colorectal cancer cells we described a crosstalk between beta-blockade by propranolol and tumour microenvironment. Non-selective beta-blocker propranolol decreased ability of tumour cells to adapt to hypoxia by reducing levels of HIF1α and carbonic anhydrase IX in 3D spheroids. We indicated a double action of propranolol in the tumour microenvironment by inhibiting the stability of HIF1α, thus mediating decrease of CA IX expression and, at the same time, by its possible effect on CA IX activity by decreasing the activity of protein kinase A (PKA). Moreover, the inhibition of β-adrenoreceptors by propranolol enhanced apoptosis, decreased number of mitochondria and lowered the amount of proteins involved in oxidative phosphorylation (V-ATP5A, IV-COX2, III-UQCRC2, II-SDHB, I-NDUFB8). Propranolol reduced metastatic potential, viability and proliferation of colorectal cancer cells cultivated in multicellular spheroids. To choose the right treatment strategy, it is extremely important to know how the treatment of concomitant diseases affects the superior microenvironment that is directly related to the efficiency of anti-cancer therapy

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26

Gliozzi, A. S., C. Guiot, R. Chignola, and P. P. Delsanto. "Oscillations in growth of multicellular tumour spheroids: a revisited quantitative analysis." Cell Proliferation 43, no. 4 (June 29, 2010): 344–53. http://dx.doi.org/10.1111/j.1365-2184.2010.00683.x.

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27

Ter Haar, G., J. Walling, P. Loverock, and S. Townsend. "The Effect of Combined Heat and Ultrasound on Multicellular Tumour Spheroids." International Journal of Radiation Biology 53, no. 5 (January 1988): 813–27. http://dx.doi.org/10.1080/09553008814551151.

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28

KUNZ‐SCHUGHART, LEONI A., MARINA KREUTZ, and RUTH KNUECHEL. "Multicellular spheroids: a three‐dimensionalin vitroculture system to study tumour biology." International Journal of Experimental Pathology 79, no. 1 (February 1998): 1–23. http://dx.doi.org/10.1046/j.1365-2613.1998.00051.x.

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29

Tindall, M. J., and C. P. Please. "Modelling the Cell Cycle and Cell Movement in Multicellular Tumour Spheroids." Bulletin of Mathematical Biology 69, no. 4 (March 20, 2007): 1147–65. http://dx.doi.org/10.1007/s11538-006-9110-z.

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30

BYRNE, H. M., and M. A. J. CHAPLAIN. "Free boundary value problems associated with the growth and development of multicellular spheroids." European Journal of Applied Mathematics 8, no. 6 (December 1997): 639–58. http://dx.doi.org/10.1017/s0956792597003264.

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In this paper a generalized model for the growth of avascular tumours is presented. The formulation leads naturally to the incorporation of free boundaries which define the outer tumour surface explicitly and various inner surfaces implicitly. A combination of numerical simulations, asymptotic analysis and perturbation techniques is used to study the model and yields results, which agree well with experimentally-observed phenomena.

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31

Gonçalves, Inês G., and Jose Manuel Garcia-Aznar. "Extracellular matrix density regulates the formation of tumour spheroids through cell migration." PLOS Computational Biology 17, no. 2 (February 26, 2021): e1008764. http://dx.doi.org/10.1371/journal.pcbi.1008764.

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In this work, we show how the mechanical properties of the cellular microenvironment modulate the growth of tumour spheroids. Based on the composition of the extracellular matrix, its stiffness and architecture can significantly vary, subsequently influencing cell movement and tumour growth. However, it is still unclear exactly how both of these processes are regulated by the matrix composition. Here, we present a centre-based computational model that describes how collagen density, which modulates the steric hindrance properties of the matrix, governs individual cell migration and, consequently, leads to the formation of multicellular clusters of varying size. The model was calibrated using previously published experimental data, replicating a set of experiments in which cells were seeded in collagen matrices of different collagen densities, hence producing distinct mechanical properties. At an initial stage, we tracked individual cell trajectories and speeds. Subsequently, the formation of multicellular clusters was also analysed by quantifying their size. Overall, the results showed that our model could accurately replicate what was previously seen experimentally. Specifically, we showed that cells seeded in matrices with low collagen density tended to migrate more. Accordingly, cells strayed away from their original cluster and thus promoted the formation of small structures. In contrast, we also showed that high collagen densities hindered cell migration and produced multicellular clusters with increased volume. In conclusion, this model not only establishes a relation between matrix density and individual cell migration but also showcases how migration, or its inhibition, modulates tumour growth.

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32

Müllner, Markus, Kylie Yang, Amandeep Kaur, and Elizabeth J. New. "Aspect-ratio-dependent interaction of molecular polymer brushes and multicellular tumour spheroids." Polymer Chemistry 9, no. 25 (2018): 3461–65. http://dx.doi.org/10.1039/c8py00703a.

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Molecular polymer brushes allow for independent tailoring of nanoparticle design parameters. Brush particles with altered shape and aspect ratio revealed that particle shape effects may be decoupled from surface chemistry to achieve higher tumour spheroid interaction and penetration.

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33

Guirado, D., M. Aranda, M. Vilches, M. Villalobos, and A. M. Lallena. "Dose dependence of the growth rate of multicellular tumour spheroids after irradiation." British Journal of Radiology 76, no. 902 (February 2003): 109–16. http://dx.doi.org/10.1259/bjr/30772617.

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34

Casciari, J. J., S. V. Sotirchos, and R. M. Sutherland. "Mathematical modelling of microenvironment and growth in EMT6/Ro multicellular tumour spheroids." Cell Proliferation 25, no. 1 (January 1992): 1–22. http://dx.doi.org/10.1111/j.1365-2184.1992.tb01433.x.

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35

Chignola, R., R. Foroni, A. Franceschi, M. Pasti, C. Candiani, C. Anselmi, G. Fracasso, G. Tridente, and M. Colombatti. "Heterogeneous response of individual multicellular tumour spheroids to immunotoxins and ricin toxin." British Journal of Cancer 72, no. 3 (September 1995): 607–14. http://dx.doi.org/10.1038/bjc.1995.381.

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36

Al Balushi, Noora, Mitchell Boyd-Moss, Rasika M. Samarasinghe, Aaqil Rifai, Stephanie J. Franks, Kate Firipis, Benjamin M. Long, et al. "Self-Assembled Peptide Habitats to Model Tumor Metastasis." Gels 8, no. 6 (May 25, 2022): 332. http://dx.doi.org/10.3390/gels8060332.

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Metastatic tumours are complex ecosystems; a community of multiple cell types, including cancerous cells, fibroblasts, and immune cells that exist within a supportive and specific microenvironment. The interplay of these cells, together with tissue specific chemical, structural and temporal signals within a three-dimensional (3D) habitat, direct tumour cell behavior, a subtlety that can be easily lost in 2D tissue culture. Here, we investigate a significantly improved tool, consisting of a novel matrix of functionally programmed peptide sequences, self-assembled into a scaffold to enable the growth and the migration of multicellular lung tumour spheroids, as proof-of-concept. This 3D functional model aims to mimic the biological, chemical, and contextual cues of an in vivo tumor more closely than a typically used, unstructured hydrogel, allowing spatial and temporal activity modelling. This approach shows promise as a cancer model, enhancing current understandings of how tumours progress and spread over time within their microenvironment.

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37

Ho, Vincent H. B., Nigel K. H. Slater, and Rongjun Chen. "pH-responsive endosomolytic pseudo-peptides for drug delivery to multicellular spheroids tumour models." Biomaterials 32, no. 11 (April 2011): 2953–58. http://dx.doi.org/10.1016/j.biomaterials.2011.01.010.

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38

Karolak, Aleksandra, Dmitry A. Markov, Lisa J. McCawley, and Katarzyna A. Rejniak. "Towards personalized computational oncology: from spatial models of tumour spheroids, to organoids, to tissues." Journal of The Royal Society Interface 15, no. 138 (January 2018): 20170703. http://dx.doi.org/10.1098/rsif.2017.0703.

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A main goal of mathematical and computational oncology is to develop quantitative tools to determine the most effective therapies for each individual patient. This involves predicting the right drug to be administered at the right time and at the right dose. Such an approach is known as precision medicine. Mathematical modelling can play an invaluable role in the development of such therapeutic strategies, since it allows for relatively fast, efficient and inexpensive simulations of a large number of treatment schedules in order to find the most effective. This review is a survey of mathematical models that explicitly take into account the spatial architecture of three-dimensional tumours and address tumour development, progression and response to treatments. In particular, we discuss models of epithelial acini, multicellular spheroids, normal and tumour spheroids and organoids, and multi-component tissues. Our intent is to showcase how these in silico models can be applied to patient-specific data to assess which therapeutic strategies will be the most efficient. We also present the concept of virtual clinical trials that integrate standard-of-care patient data, medical imaging, organ-on-chip experiments and computational models to determine personalized medical treatment strategies.

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39

Manoto, Sello, Nicolette Houreld, and Heidi Abrahamse. "Resistance of Lung Cancer Cells Grown as Multicellular Tumour Spheroids to Zinc Sulfophthalocyanine Photosensitization." International Journal of Molecular Sciences 16, no. 12 (May 5, 2015): 10185–200. http://dx.doi.org/10.3390/ijms160510185.

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40

Sauer, H., V. Pütz, K. Fischer, J. Hescheler, and M. Wartenberg. "Increased doxorubicin uptake and toxicity in multicellular tumour spheroids treated with DC electrical fields." British Journal of Cancer 80, no. 8 (May 28, 1999): 1204–13. http://dx.doi.org/10.1038/sj.bjc.6690487.

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41

Wheldon, T. E., A. Livingstone, L. Wilson, J. O'Donoghue, and A. Gregor. "The radiosensitivity of human neuroblastoma cells estimated from regrowth curves of multicellular tumour spheroids." British Journal of Radiology 58, no. 691 (July 1985): 661–64. http://dx.doi.org/10.1259/0007-1285-58-691-661.

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Zacharaki, Evangelia I., Georgios S. Stamatakos, Konstantina S. Nikita, and Nikolaos K. Uzunoglu. "Simulating growth dynamics and radiation response of avascular tumour spheroids—model validation in the case of an EMT6/Ro multicellular spheroid." Computer Methods and Programs in Biomedicine 76, no. 3 (December 2004): 193–206. http://dx.doi.org/10.1016/j.cmpb.2004.07.003.

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Li, Xia, Manpreet Sambi, Alexandria DeCarlo, Sergey V. Burov, Roman Akasov, Elena Markvicheva, Cecile Malardier-Jugroot, and Myron R. Szewczuk. "Functionalized Folic Acid-Conjugated Amphiphilic Alternating Copolymer Actively Targets 3D Multicellular Tumour Spheroids and Delivers the Hydrophobic Drug to the Inner Core." Nanomaterials 8, no. 8 (August 2, 2018): 588. http://dx.doi.org/10.3390/nano8080588.

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Engineering of a “smart” drug delivery system to specifically target tumour cells has been at the forefront of cancer research, having been engineered for safer, more efficient and effective use of chemotherapy for the treatment of cancer. However, selective targeting and choosing the right cancer surface biomarker are critical for a targeted treatment to work. Currently, the available delivery systems use a two-dimensional monolayer of cancer cells to test the efficacy of the drug delivery system, but designing a “smart” drug delivery system to be specific for a tumour in vivo and to penetrate the inner core remains a major design challenge. These challenges can be overcome by using a study model that integrates the three-dimensional aspect of a tumour in a culture system. Here, we tested the efficacy of a functionalized folic acid-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) to specifically target and penetrate the inner core of three-dimensional avascular human pancreatic and breast tumour spheroids in culture. The copolymer was quantitatively analyzed for its hydrophobic drug encapsulation efficiency using three different chemical drug structures with different molecular weights. Their release profiles and tumour targeting properties at various concentrations and pH environments were also characterized. Using the anticancer drug curcumin and two standard clinical chemotherapeutic hydrophobic drugs, paclitaxel and 5-fluorouracil, we tested the ability of FA-DABA-SMA nanoparticles to encapsulate the differently sized drugs and deliver them to kill monolayer pancreatic cancer cells using the WST-1 cell proliferation assay. The findings of this study revealed that the functionalized folic acid-conjugated amphiphilic alternating copolymer shows unique properties as an active “smart” tumor-targeting drug delivery system with the ability to internalize hydrophobic drugs and release the chemotherapeutics for effective killing of cancer cells. The novelty of the study is the first to demonstrate a functionalized “smart” drug delivery system encapsulated with a hydrophobic drug effectively targeting and penetrating the inner core of pancreatic and breast cancer spheroids and reducing their volumes in a dose- and time-dependent manner.

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Pham, Kara, Hermann B. Frieboes, Vittorio Cristini, and John Lowengrub. "Predictions of tumour morphological stability and evaluation against experimental observations." Journal of The Royal Society Interface 8, no. 54 (June 2, 2010): 16–29. http://dx.doi.org/10.1098/rsif.2010.0194.

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The hallmark of malignant tumours is their spread into neighbouring tissue and metastasis to distant organs, which can lead to life threatening consequences. One of the defining characteristics of aggressive tumours is an unstable morphology, including the formation of invasive fingers and protrusions observed both in vitro and in vivo . In spite of extensive biological, clinical and modelling study and research at physical scales ranging from the molecular to the tissue, the driving dynamics of tumour invasiveness are not completely understood, partly because it is challenging to observe and study cancer as a multi-scale system. Mathematical modelling has been applied to provide further insights into these complex invasive and metastatic behaviours. Modelling a solid tumour as an incompressible fluid, we consider three possible constitutive relations to describe tumour growth, namely Darcy's law, Stokes' law and the combined Darcy–Stokes law. We study the tumour morphological stability described by each model and evaluate the consistency between theoretical model predictions and experimental data from in vitro three-dimensional multicellular tumour spheroids. The analysis reveals that the Stokes model is the most consistent with the experimental observations, and that it predicts our experimental tumour growth is marginally stable. We further show that it is feasible to extract parameter values from a limited set of data and create a self-consistent modelling framework that can be extended to the multi-scale study of cancer.

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Laderoute, KR, BJ Murphy, SM Short, TD Grant, AM Knapp, and RM Sutherland. "Enhancement of transforming growth factor-α synthesis in multicellular tumour spheroids of A431 squamous carcinoma cells." British Journal of Cancer 65, no. 2 (February 1992): 157–62. http://dx.doi.org/10.1038/bjc.1992.34.

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Bradford, R., J. L. Darling, N. Sier, and D. G. T. Thomas. "The VM model of glioma: Preparation of multicellular tumour spheroids (MTS) and their response to chemotherapy." Journal of Neuro-Oncology 9, no. 2 (October 1990): 105–14. http://dx.doi.org/10.1007/bf02427830.

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Mao, Xinjian, Sarah McManaway, Jagdish K. Jaiswal, Priyanka B. Patel, William R. Wilson, Kevin O. Hicks, and Gib Bogle. "An agent-based model for drug-radiation interactions in the tumour microenvironment: Hypoxia-activated prodrug SN30000 in multicellular tumour spheroids." PLOS Computational Biology 14, no. 10 (October 24, 2018): e1006469. http://dx.doi.org/10.1371/journal.pcbi.1006469.

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De Santis, Ilaria, Ervin Tasnadi, Peter Horvath, Alessandro Bevilacqua, and Filippo Piccinini. "Open-Source Tools for Volume Estimation of 3D Multicellular Aggregates." Applied Sciences 9, no. 8 (April 18, 2019): 1616. http://dx.doi.org/10.3390/app9081616.

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The volume is one of the most relevant features that define the treatment of an in vivo tumour. When using cancer 3D in vitro models in pre-clinical studies, it becomes important to evaluate the macroscopic effects of drugs and radiotherapy treatments. Depending on the nature of the 3D in vitro model used, different open-source solutions can be used for measuring the volume by starting from microscope-acquired images. In this work, we introduced several open-source tools today available for estimating the volume of 3D multicellular aggregates (e.g., spheroids, organoids), also giving hints for defining the “best software” by analysing characteristics of 3D in vitro models and limits of the tools. Finally, using several cancer organoids imaged by a fluorescent microscope, we compared volume estimations obtained with different tools, besides presenting a new version of the Reconstruction and Visualization from Multiple Sections (ReViMS version 2.0) tool. This work aims to be the reference for researchers interested in estimating the volume of 3D multicellular aggregates through an open-source tool.

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Kwok, T. T., and P. R. Twentyman. "The relationship between tumour geometry and the response of tumour cells to cytotoxic drugs — Anin vitro study using EMT6 multicellular spheroids." International Journal of Cancer 35, no. 5 (May 15, 1985): 675–82. http://dx.doi.org/10.1002/ijc.2910350517.

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Rofstad, Einar K., Anne Wahl, Catharina de L. Davies, and Tor Brustad. "Growth Characteristics of Human Melanoma Multicellular Spheroids In Liquid-Overlay Culture: Comparisons With the Parent Tumour Xenografts." Cell Proliferation 19, no. 2 (March 1986): 205–16. http://dx.doi.org/10.1111/j.1365-2184.1986.tb00731.x.

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