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      Identification of Gastric Cancer Biomarkers Using 1H Nuclear Magnetic Resonance Spectrometry

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      Author(s): 1 , 2 , 1 , *
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      Publication date (Electronic):
      Journal: PLoS ONE
      Publisher: Public Library of Science

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          Abstract

          Existing gastric cancer diagnosing methods were invasive, hence, a reliable non-invasive gastric cancer diagnosing method is needed. As a starting point, we used 1H NMR for identifying gastric cancer biomarkers using a panel of gastric cancer spheroids and normal gastric spheroids. We were able to identify 8 chemical shift biomarkers for gastric cancer spheroids. Our data suggests that the cancerous and non-cancerous spheroids significantly differ in the lipid composition and energy metabolism. These results encourage the translation of these biomarkers into in-vivo gastric cancer detection methodology using MRI-MS.

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          From cells to organs: building polarized tissue.

          David M Bryant, Keith E. Mostov (2008)
          How do animal cells assemble into tissues and organs? A diverse array of tissue structures and shapes can be formed by organizing groups of cells into different polarized arrangements and by coordinating their polarity in space and time. Conserved design principles underlying this diversity are emerging from studies of model organisms and tissues. We discuss how conserved polarity complexes, signalling networks, transcription factors, membrane-trafficking pathways, mechanisms for forming lumens in tubes and other hollow structures, and transitions between different types of polarity, such as between epithelial and mesenchymal cells, are used in similar and iterative manners to build all tissues.
          Article 0 comments Cited 243 times – based on 0 reviews     Review now
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            Cell plasticity and heterogeneity in cancer.

            Nemanja D Marjanovic, Robert Weinberg, Christine L Chaffer (2013)
            Heterogeneity within a given cancer arises from diverse cell types recruited to the tumor and from genetic and/or epigenetic differences amongst the cancer cells themselves. These factors conspire to create a disease with various phenotypes. There are 2 established models of cancer development and progression to metastatic disease. These are the clonal evolution and cancer stem cell models. The clonal evolution theory suggests that successive mutations accumulating in a given cell generate clonal outgrowths that thrive in response to microenvironmental selection pressures, dictating the phenotype of the tumor. The alternative cancer stem cell (CSC) model suggests that cancer cells with similar genetic backgrounds can be hierarchically organized according to their tumorigenic potential. Accordingly, CSCs reside at the apex of the hierarchy and are thought to possess the majority of a cancer's tumor-initiating and metastatic ability. A defining feature of this model is its apparent unidirectional nature, whereby CSCs undergo symmetric division to replenish the CSC pool and irreversible asymmetric division to generate daughter cells (non-CSCs) with low tumorigenic potential. However, evolving evidence supports a new model of tumorigenicity, in which considerable plasticity exists between the non-CSC and CSC compartments, such that non-CSCs can reacquire a CSC phenotype. These findings suggest that some tumors may adhere to a plastic CSC model, in which bidirectional conversions are common and essential components of tumorigenicity. Accumulating evidence surrounding the plasticity of cancer cells, in particular, suggests that aggressive CSCs can be created de novo within a tumor. Given the current focus on therapeutic targeting of CSCs, we discuss the implications of non-CSC-to-CSC conversions on the development of future therapies. © 2012 American Association for Clinical Chemistry
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              A three-dimensional microenvironment alters protein expression and chemosensitivity of epithelial ovarian cancer cells in vitro.

              Lucineh Cristina Parsanian, Kate Lawrenson, Y. Lin … (2013)
              For many cancers, there is a real need for more effective therapies. Although many drugs show promising results in vitro, most fail to translate into an in vivo model system, and only ∼5% show anti-tumor activity in clinical trials. It remains a significant challenge to accurately replicate in vitro the complex in vivo microenvironment in which cancers thrive, but this will be key to increasing the success of translating novel therapies into clinical practice. Three-dimensional (3D) cell culture models may better mimic primary tumors in vivo than traditional two-dimensional (2D) cultures. Therefore, we established and characterized 3D in vitro models of 31 epithelial ovarian cancer (EOC) cell lines, compared their biological and molecular features with 2D cultures and primary tumors, and tested their efficacy as models for evaluating chemoresponse. When cultured in 3D using polyhydroxoethylamethacrylate-coated plastics, EOC lines formed multicellular aggregates that could be classified as 'large dense', 'large loose', and 'small', based on size, light permeability, and proportion of cells incorporated into the complex structures. Features of histological differentiation characteristic of primary tumors that were not present in 2D cultures were restored in 3D. For many cell lines, the transition from a 2D to 3D microenvironment induced changes in the expression of several biomarkers relevant to disease. Generally, EOC cell lines proliferated more slowly and were more chemoresistant in 3D compared with 2D culture. In summary, 3D models of EOCs better reflect the histological, biological, and molecular features of primary tumors than the same cells cultured using traditional 2D techniques; 3D in vitro models also exhibit different sensitivities to chemotherapeutic agents compared with 2D models, which may have a significant impact on the success of drug testing pipelines for EOC. These findings could also impact in vitro modeling approaches and drug development strategies for other solid tumor types.
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                Author and article information

                Contributors
                Andrea Motta: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 9 September 2016
                Publication date Collection: 2016
                Volume: 11
                Issue: 9
                Electronic Location Identifier: e0162222
                Affiliations
                [1 ]Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore
                [2 ]Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), Singapore
                National Research Council of Italy, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: GKR.

                • Data curation: GKR.

                • Formal analysis: GKR.

                • Funding acquisition: CHY.

                • Investigation: GKR.

                • Methodology: GKR.

                • Project administration: CHY.

                • Supervision: CHY WPY.

                • Visualization: GKR.

                • Writing – original draft: GKR.

                • Writing – review & editing: CHY WPY.

                Author information
                http://orcid.org/0000-0001-5365-4348
                Article
                Publisher ID: PONE-D-16-26791
                DOI: 10.1371/journal.pone.0162222
                PMC ID: 5017672
                PubMed ID: 27611679
                SO-VID: 3e280f25-23b9-4045-8850-32ec5a3dc6fd
                Copyright © © 2016 Ramachandran et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 4 July 2016
                Date accepted : 18 August 2016
                Page count
                Figures: 5, Tables: 1, Pages: 15
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100001459, Ministry of Education - Singapore;
                Award ID: R397-000-143-133
                Award Recipient :
                This research is funded by the MOE Academic research fund (AcRF) Tier-1 grant (R397-000-143-133) awarded to YCH at National University of Singapore, Singapore. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Oncology
                Subject: Cancers and Neoplasms
                Subject: Gastrointestinal Tumors
                Subject: Gastric Cancer
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Biomarkers
                Subject: Research and analysis methods
                Subject: Spectrum analysis techniques
                Subject: NMR spectroscopy
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Diagnostic Radiology
                Subject: Magnetic Resonance Imaging
                Subject: Magnetic Resonance Spectroscopy
                Subject: Research and Analysis Methods
                Subject: Imaging Techniques
                Subject: Diagnostic Radiology
                Subject: Magnetic Resonance Imaging
                Subject: Magnetic Resonance Spectroscopy
                Subject: Medicine and Health Sciences
                Subject: Radiology and Imaging
                Subject: Diagnostic Radiology
                Subject: Magnetic Resonance Imaging
                Subject: Magnetic Resonance Spectroscopy
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Cancer Detection and Diagnosis
                Subject: Medicine and Health Sciences
                Subject: Oncology
                Subject: Cancer Detection and Diagnosis
                Subject: Physical Sciences
                Subject: Chemistry
                Subject: Chemical Compounds
                Subject: Organic Compounds
                Subject: Vitamins
                Subject: B Vitamins
                Subject: Cholines
                Subject: Physical Sciences
                Subject: Chemistry
                Subject: Organic Chemistry
                Subject: Organic Compounds
                Subject: Vitamins
                Subject: B Vitamins
                Subject: Cholines
                Subject: Physical Sciences
                Subject: Physics
                Subject: Condensed Matter Physics
                Subject: Magnetism
                Subject: Nuclear Magnetic Resonance
                Subject: Physical Sciences
                Subject: Physics
                Subject: Condensed Matter Physics
                Subject: Magnetism
                Subject: Magnetic Resonance
                Custom metadata
                Data Availability All relevant data are within the paper.

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