scholarly journals Development of Breast Cancer Spheroids to Evaluate Cytotoxic Response to an Anticancer Peptide

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1863
Author(s):  
Marco Cavaco ◽  
Patrícia Fraga ◽  
Javier Valle ◽  
David Andreu ◽  
Miguel A. R. B. Castanho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Development ◽  
Three Dimensional ◽  
3D Models ◽  
Cell Permeabilization ◽  
Anticancer Peptide ◽  
Cell Monolayers ◽  
Common Causes ◽  
Cancer Spheroids

Breast cancer (BC) is the most commonly diagnosed cancer in women and one of the most common causes of cancer-related deaths. Despite intense research efforts, BC treatment still remains challenging. Improved drug development strategies are needed for impactful benefit to patients. Current preclinical studies rely mostly on cell-based screenings, using two-dimensional (2D) cell monolayers that do not mimic in vivo tumors properly. Herein, we explored the development and characterization of three-dimensional (3D) models, named spheroids, of the most aggressive BC subtypes (triple-negative breast cancer-TNBC; and human-epidermal growth receptor-2-HER2+), using the liquid overlay technique with several selected cell lines. In these cell line-derived spheroids, we studied cell density, proliferation, ultrastructure, apoptosis, reactive oxygen species (ROS) production, and cell permeabilization (live/dead). The results showed a formation of compact and homogeneous spheroids on day 7 after seeding 2000 cells/well for MDA-MB-231 and 5000 cells/well for BT-20 and BT-474. Next, we compared the efficacy of a model anticancer peptide (ACP) in cell monolayers and spheroids. Overall, the results demonstrated spheroids to be less sensitive to treatment than cell monolayers, revealing the need for more robust models in drug development.

Prevascularized, Co-Culture Model for Breast Cancer Drug Development

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].

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

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.

scholarly journals Three-dimensional in vivo fluorescence diffuse optical tomography of breast cancer in humans

2007 ◽  
Vol 15 (11) ◽  
pp. 6696 ◽  
Author(s):  
Alper Corlu ◽  
Regine Choe ◽  
Turgut Durduran ◽  
Mark A. Rosen ◽  
Martin Schweiger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Optical Tomography ◽  
Three Dimensional ◽  
Diffuse Optical Tomography ◽  
In Vivo Fluorescence ◽  
Fluorescence Diffuse Optical Tomography

scholarly journals Porcine hepatocytes culture on biofunctionalized 3D inverted colloidal crystal scaffolds as an in vitro model for predicting drug hepatotoxicity

RSC Advances ◽  
2019 ◽  
Vol 9 (31) ◽  
pp. 17995-18007 ◽  
Author(s):  
Lingyan Wu ◽  
Gaia Ferracci ◽  
Yan Wang ◽  
Teng Fei Fan ◽  
Nam-Joon Cho ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Colloidal Crystal ◽  
Three Dimensional ◽  
Drug Induced ◽  
Attrition Rates ◽  
Common Causes ◽  
Vitro Model ◽  
Colloidal Crystal Scaffolds

As drug-induced hepatotoxicity represents one of the most common causes of drug failure, three-dimensional in vitro liver platforms represent a fantastic toolbox to predict drug toxicity and reduce in vivo studies and drug attrition rates.

scholarly journals lncMat2B regulated by severe hypoxia induces cisplatin resistance by increasing DNA damage repair and tumor-initiating population in breast cancer cells

2020 ◽  
Vol 41 (11) ◽  
pp. 1485-1497 ◽  
Author(s):  
Alfredo García-Venzor ◽  
Edna Ayerim Mandujano-Tinoco ◽  
Araceli Ruiz-Silvestre ◽  
José Manuel Sánchez ◽  
Floria Lizarraga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Ectopic Expression ◽  
Three Dimensional ◽  
Severe Hypoxia ◽  
Loss Of Function ◽  
Mcf 7

Abstract Multicellular tumor spheroids (MCTSs) constitute a three-dimensional culture system that recapitulates the in vivo tumor microenvironment. Tumor cells cultured as MCTSs present antineoplastic resistance due to the effect of microenvironmental signals acting upon them. In this work, we evaluated the biological function of a new microenvironment-regulated long non-coding RNA, lncMat2B, in breast cancer. In MCTSs, the expression of lncMat2B presented an increase and a zonal heterogeneity, as it was expressed principally in quiescent cells of hypoxic regions of the MCTSs. As expected, functional assays supported the role of severe hypoxia in the regulation of lncMat2B. Moreover, gain- and loss-of-function assays using a transcriptional silencing CRISPR/Cas9 system and gBlock revealed that lncMAT2B regulates the tumor-initiating phenotype. Interestingly, lncMat2B is overexpressed in a cisplatin-resistant MCF-7 cell line, and its ectopic expression in wild type MCF-7 cells increased survival to cisplatin exposure by reducing DNA damage and reactive oxygen species accumulation. lncMAT2B is a possible link between severe hypoxia, tumor-initiating phenotype and drug resistance in breast cancer cells.

scholarly journals Akt1 governs breast cancer progression in vivo

2007 ◽  
Vol 104 (18) ◽  
pp. 7438-7443 ◽  
Author(s):  
Xiaoming Ju ◽  
Sanjay Katiyar ◽  
Chenguang Wang ◽  
Manran Liu ◽  
Xuanmao Jiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Lung Metastases ◽  
Three Dimensional ◽  
Mammary Tumorigenesis ◽  
Mammary Epithelial ◽  
Serine Threonine Kinase ◽  
Epithelial Tumor ◽  
Induced Changes

The serine threonine kinase Akt1 has been implicated in the control of cellular metabolism, survival and growth. Here, disruption of the ubiquitously expressed member of the Akt family of genes, Akt1, in the mouse demonstrates a requirement for Akt1 in ErbB2-induced mammary tumorigenesis. Akt1 deficiency delayed tumor growth and reduced lung metastases, correlating with a reduction in phosphorylation of the Akt1 target, tuberous sclerosis 2 (TSC2) at Ser-939. Akt1-deficient mammary epithelial tumor cells (MEC) were reduced in size and proliferative capacity, with reduced cyclin D1 and p27KIP1 abundance. Akt1 deficiency abrogated the oncogene-induced changes in polarization of MEC in three-dimensional culture and reverted oncogene-induced relocalization of the phosphorylated ezrin–radixin–moesin proteins. Akt1 increased MEC migration across an endothelial cell barrier, enhancing the persistence of migratory directionality. An unbiased proteomic analysis demonstrated Akt1 mediated MEC migration through paracrine signaling via induction of expression and secretion of CXCL16 and MIP1γ. Akt1 governs MEC polarity, migratory directionality and breast cancer onset induced by ErbB2 in vivo.

scholarly journals In Vitro Tissue Microarrays for Quick and Efficient Spheroid Characterization

2017 ◽  
Vol 23 (2) ◽  
pp. 211-217 ◽  
Author(s):  
D. P. Ivanov ◽  
A. M. Grabowska
Keyword(s):  
Single Cells ◽  
Three Dimensional ◽  
Tissue Microarrays ◽  
3D Models ◽  
Morphological Examination ◽  
Protein Targets ◽  
Cell Monolayers ◽  
Her 2 ◽  
Models Of Disease

Three-dimensional (3D) in vitro microphysiological cultures, such as spheroids and organoids, promise increased patient relevance and therapeutic predictivity compared with reductionist cell monolayers. However, high-throughput characterization techniques for 3D models are currently limited to simplistic live/dead assays. By sectioning and staining in vitro microtissues, researchers can examine their structure; detect DNA, RNA, and protein targets; and visualize them at the level of single cells. The morphological examination and immunochemistry staining for in vitro cultures has historically been done in a laborious manner involving testing one set of cultures at a time. We have developed a technology to rapidly screen spheroid phenotype and protein expression by arranging 66 spheroids in a gel array for paraffin embedding, sectioning, and immunohistochemsitry. The process is quick, mostly automatable, and uses 11 times less reagents than conventional techniques. Here we showcase the capabilities of the technique in an array made up of 11 different cell lines stained in conventional hematoxylin and eosin (H&E) staining, as well as immunohistochemistry staining for estrogen (ER), progesterone (PR), and human epidermal growth factor (Her-2) receptors, and TP53. This new methodology can be used in optimizing stem cell–based models of disease and development, for tissue engineering, safety screening, and efficacy screens in cancer research.

scholarly journals Novel Image Analysis Approach Quantifies Morphological Characteristics of 3D Breast Culture Acini with Varying Metastatic Potentials

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Lindsey McKeen Polizzotti ◽  
Basak Oztan ◽  
Chris S. Bjornsson ◽  
Katherine R. Shubert ◽  
Bülent Yener ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Image Analysis ◽  
Three Dimensional ◽  
Morphological Characteristics ◽  
Tissue Samples ◽  
Metastatic Cascade ◽  
Automated Grading

Prognosis of breast cancer is primarily predicted by the histological grading of the tumor, where pathologists manually evaluate microscopic characteristics of the tissue. This labor intensive process suffers from intra- and inter-observer variations; thus, computer-aided systems that accomplish this assessment automatically are in high demand. We address this by developing an image analysis framework for the automated grading of breast cancer inin vitrothree-dimensional breast epithelial acini through the characterization of acinar structure morphology. A set of statistically significant features for the characterization of acini morphology are exploited for the automated grading of six (MCF10 series) cell line cultures mimicking three grades of breast cancer along the metastatic cascade. In addition to capturing both expected and visually differentiable changes, we quantify subtle differences that pose a challenge to assess through microscopic inspection. Our method achieves 89.0% accuracy in grading the acinar structures as nonmalignant, noninvasive carcinoma, and invasive carcinoma grades. We further demonstrate that the proposed methodology can be successfully applied for the grading ofin vivotissue samples albeit with additional constraints. These results indicate that the proposed features can be used to describe the relationship between the acini morphology and cellular function along the metastatic cascade.

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