scholarly journals Highly multiplexed molecular and cellular mapping of breast cancer tissue in three dimensions using mass tomography

2020 ◽  
Author(s):  
Raúl Catena ◽  
Alaz Özcan ◽  
Laura Kütt ◽  
Alex Plüss ◽  
Peter Schraml ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Three Dimensional ◽  
Three Dimensions ◽  
Cellular Heterogeneity ◽  
Cancer Tissue ◽  
Tissue Architecture ◽  
Tissue Microenvironment ◽  
Tissue Organization ◽  
Holistic Understanding ◽  
Cancer Sample

ABSTRACTA holistic understanding of tissue and organ structures and their functions requires the detection of molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) makes possible the detection of up to 40 antigens and specific nucleic acids simultaneously using metal-tagged antibodies or nucleic acid probes, respectively, but has so far been restricted to two-dimensional imaging. To enable use of IMC for 3D tissue analyses, we developed mass tomography, which combines quasi deformation-free serial sectioning with novel computational methods. We utilized mass tomography to analyze a breast cancer sample. The resulting 3D representation reveals spatial and cellular heterogeneity, preferential cell-to-cell interactions, detailed tissue-architecture motifs, and the unique microenvironment of a micro-invasion, where micro-metastases clonality is examined, showing that cells arising from the same invasive area, displaying very distinct phenotypes, are all able to produce initial invasive lesions. Mass tomography will provide invaluable insights into the tissue microenvironment, cellular neighborhoods, and tissue organization.

Evaluation of photodynamic therapy efficiency using an in vitro three-dimensional microfluidic breast cancer tissue model

Lab on a Chip ◽  
2015 ◽  
Vol 15 (3) ◽  
pp. 735-744 ◽  
Author(s):  
Yamin Yang ◽  
Xiaochuan Yang ◽  
Jin Zou ◽  
Chao Jia ◽  
Yue Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gold Nanoparticles ◽  
Photodynamic Therapy ◽  
Three Dimensional ◽  
Therapeutic Agents ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Tissue Model

A microfluidic-based in vitro three-dimensional (3D) breast cancer tissue model was established for determining the efficiency of photodynamic therapy (PDT) with therapeutic agents (photosensitizer and gold nanoparticles) under various irradiation conditions.

Determining tamoxifen sensitivity using primary breast cancer tissue in collagen-based three-dimensional culture

Biomaterials ◽  
2012 ◽  
Vol 33 (3) ◽  
pp. 907-915 ◽  
Author(s):  
Alexander D. Leeper ◽  
Joanne Farrell ◽  
Linda J. Williams ◽  
Jeremy S. Thomas ◽  
J. Michael Dixon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Three Dimensional ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Three Dimensional Culture ◽  
Primary Breast Cancer Tissue ◽  
Tamoxifen Sensitivity

scholarly journals Exploration and analysis of molecularly annotated, 3D models of breast cancer at single-cell resolution using virtual reality

2021 ◽  
Author(s):  
Dario Bressan ◽  
Claire M Mulvey ◽  
Fatime Qosaj ◽  
Robert Becker ◽  
Flaminia Grimaldi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Virtual Reality ◽  
Cancer Biology ◽  
Time Series Data ◽  
Three Dimensional ◽  
3D Models ◽  
Three Dimensions ◽  
Series Data ◽  
Spatially Resolved ◽  
Molecular Features

A set of increasingly powerful approaches are enabling spatially resolved measurements of growing numbers of molecular features in biological samples. While important insights can be derived from the two-dimensional data that many of these technologies generate, it is clear that extending these approaches into the third and fourth dimensions will magnify their impact. Realizing biological insights from datasets where thousands to millions of cells are annotated with tens to hundreds of parameters in space will require the development of new computational and visualization strategies. Here, we describe Theia, a virtual reality-based platform, which enables exploration and analysis of either volumetric or segmented, molecularly-annotated, three-dimensional datasets, with the option to extend the analysis to time-series data. We also describe our pipeline for generating annotated 3D models of breast cancer and supply several datasets to enable users to explore the utility of Theia for understanding cancer biology in three dimensions.

scholarly journals Unravelling the Encapsulation of DNA and Other Biomolecules in HAp Microcalcifications of Human Breast Cancer Tissues by Raman Imaging

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2658
Author(s):  
Monica Marro ◽  
Anna Maria Rodríguez-Rivero ◽  
Cuauhtémoc Araujo-Andrade ◽  
Maria Teresa Fernández-Figueras ◽  
Laia Pérez-Roca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammography Screening ◽  
Human Breast Cancer ◽  
Biochemical Analysis ◽  
Three Dimensional ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Human Breast ◽  
Cancer Tissues

Microcalcifications are detected through mammography screening and, depending on their morphology and distribution (BI-RADS classification), they can be considered one of the first indicators of suspicious cancer lesions. However, the formation of hydroxyapatite (HAp) calcifications and their relationship with malignancy remains unknown. In this work, we report the most detailed three-dimensional biochemical analysis of breast cancer microcalcifications to date, combining 3D Raman spectroscopy imaging and advanced multivariate analysis in order to investigate in depth the molecular composition of HAp calcifications found in 26 breast cancer tissue biopsies. We demonstrate that DNA has been naturally adsorbed and encapsulated inside HAp microcalcifications. Furthermore, we also show the encapsulation of other relevant biomolecules in HAp calcifications, such as lipids, proteins, cytochrome C and polysaccharides. The demonstration of natural DNA biomineralization, particularly in the tumor microenvironment, represents an unprecedented advance in the field, as it can pave the way to understanding the role of HAp in malignant tissues.

scholarly journals Constructing and Visualizing Cancer Genomic Maps in 3D Spatial Context by Phenotype-based High-throughput Laser-aided Isolation and Sequencing (PHLI-seq)

2018 ◽  
Author(s):  
Sungsik Kim ◽  
Amos Chungwon Lee ◽  
Han-Byoel Lee ◽  
Jinhyun Kim ◽  
Yushin Jung ◽  
...  
Keyword(s):  
High Resolution ◽  
High Throughput ◽  
Cancer Biology ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Genomic Analysis ◽  
Three Dimensions ◽  
Cancer Tissue ◽  
Tumour Mass ◽  
Spatially Resolved

A spatially resolved analysis of the heterogeneous cancer genome, in which the data are connected to the three-dimensional space of a tumour, is crucial to understand cancer biology and the clinical impact of cancer heterogeneity on patients. However, despite recent progress in spatially resolved transcriptomics, spatial mapping of genomic data in a high-throughput and high-resolution manner has been challenging due to current technical limitations. Here, we describe a novel approach, phenotype-based high-throughput laser-aided isolation and sequencing (PHLI-seq), which enables high-throughput isolation of a single-cell or a small number of cells and their genome-wide sequence analysis to construct genomic maps within cancer tissue in relation to the phenotypes of the cells. By applying PHLI-seq, we reveal the heterogeneity of breast cancer tissues at a high resolution and map the genomic landscape of the cells to their corresponding spatial locations and phenotypes in the tumour mass. Additionally, with different staining modalities, the genotypes of the cells can be connected to corresponding phenotypic information of the tissue. Together with the spatially resolved genomic analysis, we can infer the histories of heterogeneous cancer cells in two or three dimensions, providing significant insight into cancer biology and precision medicine.

scholarly journals Three-dimensional imaging mass cytometry for highly multiplexed molecular and cellular mapping of tissues and the tumor microenvironment

Nature Cancer ◽  
2021 ◽  
Author(s):  
Laura Kuett ◽  
Raúl Catena ◽  
Alaz Özcan ◽  
Alex Plüss ◽  
H. R. Ali ◽  
...  
Keyword(s):  
Simultaneous Detection ◽  
Three Dimensional ◽  
3D Models ◽  
Two Dimensions ◽  
Mass Cytometry ◽  
3D Space ◽  
Tissue Organization ◽  
Holistic Understanding ◽  
Cellular Microenvironments ◽  
And Function

AbstractA holistic understanding of tissue and organ structure and function requires the detection of molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous detection of up to 40 antigens and transcripts using metal-tagged antibodies but has so far been restricted to two-dimensional imaging. Here we report the development of 3D IMC for multiplexed 3D tissue analysis at single-cell resolution and demonstrate the utility of the technology by analysis of human breast cancer samples. The resulting 3D models reveal cellular and microenvironmental heterogeneity and cell-level tissue organization not detectable in two dimensions. 3D IMC will prove powerful in the study of phenomena occurring in 3D space such as tumor cell invasion and is expected to provide invaluable insights into cellular microenvironments and tissue architecture.

scholarly journals The complex three-dimensional organization of epithelial tissues

Development ◽  
2021 ◽  
Vol 148 (1) ◽  
pp. dev195669
Author(s):  
Pedro Gómez-Gálvez ◽  
Pablo Vicente-Munuera ◽  
Samira Anbari ◽  
Javier Buceta ◽  
Luis M. Escudero
Keyword(s):  
Three Dimensional ◽  
Complex Problem ◽  
Three Dimensions ◽  
Cellular Organization ◽  
Dimensional Representation ◽  
Epithelial Tissues ◽  
Tissue Organization ◽  
Realistic Approach ◽  
Organization Problem ◽  
Cell Shapes

ABSTRACTUnderstanding the cellular organization of tissues is key to developmental biology. In order to deal with this complex problem, researchers have taken advantage of reductionist approaches to reveal fundamental morphogenetic mechanisms and quantitative laws. For epithelia, their two-dimensional representation as polygonal tessellations has proved successful for understanding tissue organization. Yet, epithelial tissues bend and fold to shape organs in three dimensions. In this context, epithelial cells are too often simplified as prismatic blocks with a limited plasticity. However, there is increasing evidence that a realistic approach, even from a reductionist perspective, must include apico-basal intercalations (i.e. scutoidal cell shapes) for explaining epithelial organization convincingly. Here, we present an historical perspective about the tissue organization problem. Specifically, we analyze past and recent breakthroughs, and discuss how and why simplified, but realistic, in silico models require scutoidal features to address key morphogenetic events.

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