Publications by authors named "Jacques Eduardo Nör"

12 Publications

  • Page 1 of 1

Expression of Cancer Stem Cell Biomarkers in Human Head and Neck Carcinomas: a Systematic Review.

Stem Cell Rev Rep 2018 Dec;14(6):769-784

Department of Morphological Sciences, Health Sciences Center, Federal University of Santa Catarina, Trindade, Florianópolis, Santa Catarina, Brazil.

Malignant neoplasms may be composed of several cell groups, including cancer stem cells (CSC). These cells have been related with the capacity of metastasis, relapse and resistance to multiple drugs during chemotherapy. This study aims to identify CSC biomarkers and their expression pattern in human head and neck carcinomas. This study was conducted following the PRISMA checklist. The search for articles was carried out in five databases (PubMed, Scopus, Web of Science, Lilacs and Scielo). The articles found were selected in two phases: 1) reading the titles and / or abstract and 2) reading the full text. At the end, the selected articles were evaluated by QUADAS-2. Most studies evaluated oral neoplastic tissues and, as a control, samples of normal local mucosa. All studies performed immunohistochemistry as a method of immunolocalization and some also applied immunofluorescence. The most commonly used biomarker was CD44. However, other such as Sox2, Oct4, Nestin, Nanog, BMI1, ALDH1, CD133 and CD166 were also found. Several biomarkers were (ALDH1, Sox2, Oct4, ABCB5, AGR2 and TAZ) correlated with clinical characteristics of the tumor, such as staging, tumor size and lymph node metastasis. These data reinforce the CSC theory and favor the use of these biomarkers as possible determinants of prognosis.
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http://dx.doi.org/10.1007/s12015-018-9839-4DOI Listing
December 2018

A mathematical model for IL-6-mediated, stem cell driven tumor growth and targeted treatment.

PLoS Comput Biol 2018 01 19;14(1):e1005920. Epub 2018 Jan 19.

Department of Mathematics, University of Michigan, Ann Arbor, Michigan, United States of America.

Targeting key regulators of the cancer stem cell phenotype to overcome their critical influence on tumor growth is a promising new strategy for cancer treatment. Here we present a modeling framework that operates at both the cellular and molecular levels, for investigating IL-6 mediated, cancer stem cell driven tumor growth and targeted treatment with anti-IL6 antibodies. Our immediate goal is to quantify the influence of IL-6 on cancer stem cell self-renewal and survival, and to characterize the subsequent impact on tumor growth dynamics. By including the molecular details of IL-6 binding, we are able to quantify the temporal changes in fractional occupancies of bound receptors and their influence on tumor volume. There is a strong correlation between the model output and experimental data for primary tumor xenografts. We also used the model to predict tumor response to administration of the humanized IL-6R monoclonal antibody, tocilizumab (TCZ), and we found that as little as 1mg/kg of TCZ administered weekly for 7 weeks is sufficient to result in tumor reduction and a sustained deceleration of tumor growth.
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http://dx.doi.org/10.1371/journal.pcbi.1005920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5792033PMC
January 2018

Immunohistochemical Expression of TGF-β1 and Osteonectin in engineered and Ca(OH)2-repaired human pulp tissues.

Braz Oral Res 2016 Oct 10;30(1):e93. Epub 2016 Oct 10.

Universidade Federal de Pelotas, School of Dentistry,Post Graduation Program in Dentistry, Pelotas, Brazil.

The aim of the present study was to evaluate the expression of transforming growth factor-β1 (TGF-β1) and osteonectin (ON) in pulp-like tissues developed by tissue engineering and to compare it with the expression of these proteins in pulps treated with Ca(OH)2 therapy. Tooth slices were obtained from non-carious human third molars under sterile procedures. The residual periodontal and pulp soft tissues were removed. Empty pulp spaces of the tooth slice were filled with sodium chloride particles (250-425 µm). PLLA solubilized in 5% chloroform was applied over the salt particles. The tooth slice/scaffold (TS/S) set was stored overnight and then rinsed thoroughly to wash out the salt. Scaffolds were previously sterilized with ethanol (100-70°) and washed with phosphate-buffered saline (PBS). TS/S was treated with 10% EDTA and seeded with dental pulp stem cells (DPSC). Then, TS/S was implanted into the dorsum of immunodeficient mice for 28 days. Human third molars previously treated with Ca(OH)2 for 90 days were also evaluated. Samples were prepared and submitted to histological and immunohistochemical (with anti-TGF-β1, 1:100 and anti-ON, 1:350) analyses. After 28 days, TS/S showed morphological characteristics similar to those observed in dental pulp treated with Ca(OH)2. Ca(OH)2-treated pulps showed the usual repaired pulp characteristics. In TS/S, newly formed tissues and pre-dentin was colored, which elucidated the expression of TGF-β1 and ON. Immunohistochemistry staining of Ca(OH)2-treated pulps showed the same expression patterns. The extracellular matrix displayed a fibrillar pattern under both conditions. Regenerative events in the pulp seem to follow a similar pattern of TGF-β1 and ON expression as the repair processes.
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http://dx.doi.org/10.1590/1807-3107BOR-2016.vol30.0093DOI Listing
October 2016

Influence of poly-L-lactic acid scaffold's pore size on the proliferation and differentiation of dental pulp stem cells.

Braz Dent J 2015 Mar-Apr;26(2):93-8. Epub 2015 Apr 1.

Post-Graduate Program in Dentistry, Dental School, UFPel - Federal University of Pelotas, Pelotas, RS, Brazil.

The aim of this study was to evaluate the influence of the poly-L-lactic acid (PLLA)-based scaffold's pore size on the proliferation and differentiation of dental pulp stem cells (DPSCs). The scaffolds were prepared in pulp chambers of 1-mm-thick tooth slices from third molars using salt crystals (150-250 µm or 251-450 µm) as porogen. DPSC (1x105 cells) were seeded in the scaffolds with different pore sizes, and cultured in 24-well plates. The cell proliferation was evaluated using the WST-1 assay after 3-21 days. Furthermore, RT-PCR was used to assess the differentiation of the DPSCs into odontoblasts, using markers of odontoblastic differentiation (DSPP, DSP-1 and MEPE). RNA from human odontoblasts was used as control. Cell proliferation rate was similar in both scaffolds except at the 14th day period, in which the cells seeded in the scaffolds with larger pores showed higher proliferation (p<0.05). After 21 days DPSCs seeded in both evaluated scaffolds were able of expressing odontoblastic markers DMP-1, DSPP and MEPE. In summary, both scaffolds tested in this study allowed the proliferation and differentiation of DPSCs into odontoblast-like cells.
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http://dx.doi.org/10.1590/0103-6440201300032DOI Listing
December 2016

Tumor angiogenesis and lymphangiogenesis: tumor/endothelial crosstalk and cellular/microenvironmental signaling mechanisms.

Life Sci 2013 Feb 21;92(2):101-7. Epub 2012 Nov 21.

Nucleus of Cellular and Tecidual Biology (NCTBio), Department of Oral Pathology, School of Dentistry, Federal University of Pelotas, Brazil.

Tumor angiogenesis and lymphangiogenesis are key features of tumor progression and metastasis. The role of tumor cells-derived factors in the promotion of associated angiogenesis and lymphangiogenesis is much studied and, no doubt, very important for the understanding of cancer progression. This review aims to present and discuss the work done on the pro-angiogenic and lymphangiogenic cellular interactions within the tumor microenvironment and the signaling pathways that regulate this crosstalk. Such multifactor studies are critical for the development of future therapeutic approaches for cancer because they take into account the complexities of cellular interactions within the tumor microenvironment.
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http://dx.doi.org/10.1016/j.lfs.2012.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740377PMC
February 2013

Nano-/microfiber scaffold for tissue engineering: physical and biological properties.

J Biomed Mater Res A 2012 Nov 19;100(11):3051-8. Epub 2012 Jun 19.

Department of Operative Dentistry School of Dentistry, Federal University of Pelotas, Pelotas, RS, Brazil.

Alginate hydrogel (AH) has intrinsic physical and biological limitations that hinder its broader application in tissue engineering. We hypothesized that the inclusion of nanofibers in the hydrogel and the use of a biotemplate that mimics nature would enhance the translational potential of alginate hydrogels. In this study, we have shown a method to obtain nano-/microfibers of titanium (nfTD) and hydroxyapatite (nfHY) using cotton as a biotemplate. These fibers were incorporated in the alginate hydrogel and the mechanical characteristics and biological response to these reinforced materials were evaluated. We observed that these nanofibers resembled the structure of natural collagen and did not mediate cell toxicity. The incorporation of nfTD or nfHY to the AH has not increased the viscosity of the hydrogel. Therefore, this is a feasible method to produce a scaffold with improved physical characteristics, while at the same time generating an enhanced environment for cell adhesion and proliferation.
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http://dx.doi.org/10.1002/jbm.a.34242DOI Listing
November 2012

Tissue engineering: from research to dental clinics.

Dent Mater 2012 Apr 10;28(4):341-8. Epub 2012 Jan 10.

Post-graduate Program in Dentistry, Dental School, University of Passo Fundo, Passo Fundo, RS, Brazil.

Unlabelled: Tissue engineering is an interdisciplinary field that combines the principles of engineering, material and biological sciences toward the development of therapeutic strategies and biological substitutes that restore, maintain, replace or improve biological functions. The association of biomaterials, stem cells, growth and differentiation factors has yielded the development of new treatment opportunities in most of the biomedical areas, including Dentistry. The objective of this paper is to present the principles underlying tissue engineering and the current scenario, the challenges and the perspectives of this area in Dentistry.

Significance: The growth of tissue engineering as a research field has provided a novel set of therapeutic strategies for biomedical applications. Indeed, tissue engineering may lead to new strategies for the clinical management of patients with dental and craniofacial needs in the future.
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http://dx.doi.org/10.1016/j.dental.2011.11.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727423PMC
April 2012

Pulp tissue from primary teeth: new source of stem cells.

J Appl Oral Sci 2011 May-Jun;19(3):189-94

Department of Community Dentistry and Pediatric Dentistry, Dental School, Federal University of Bahia, Salvador, BA, Brazil.

SHED (stem cells from human exfoliated deciduous teeth) represent a population of postnatal stem cells capable of extensive proliferation and multipotential differentiation. Primary teeth may be an ideal source of postnatal stem cells to regenerate tooth structures and bone, and possibly to treat neural tissue injury or degenerative diseases. SHED are highly proliferative cells derived from an accessible tissue source, and therefore hold potential for providing enough cells for clinical applications. In this review, we describe the current knowledge about dental pulp stem cells and discuss tissue engineering approaches that use SHED to replace irreversibly inflamed or necrotic pulps with a healthy and functionally competent tissue that is capable of forming new dentin.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234327PMC
http://dx.doi.org/10.1590/s1678-77572011000300002DOI Listing
November 2011

Dental pulp tissue engineering.

Braz Dent J 2011 ;22(1):3-13

Graduate Program in Dentistry, Federal University of Pelotas, RS, Brazil.

Dental pulp is a highly specialized mesenchymal tissue that has a limited regeneration capacity due to anatomical arrangement and post-mitotic nature of odontoblastic cells. Entire pulp amputation followed by pulp space disinfection and filling with an artificial material cause loss of a significant amount of dentin leaving as life-lasting sequelae a non-vital and weakened tooth. However, regenerative endodontics is an emerging field of modern tissue engineering that has demonstrated promising results using stem cells associated with scaffolds and responsive molecules. Thereby, this article reviews the most recent endeavors to regenerate pulp tissue based on tissue engineering principles and provides insightful information to readers about the different aspects involved in tissue engineering. Here, we speculate that the search for the ideal combination of cells, scaffolds, and morphogenic factors for dental pulp tissue engineering may be extended over future years and result in significant advances in other areas of dental and craniofacial research. The findings collected in this literature review show that we are now at a stage in which engineering a complex tissue, such as the dental pulp, is no longer an unachievable goal and the next decade will certainly be an exciting time for dental and craniofacial research.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736569PMC
http://dx.doi.org/10.1590/s0103-64402011000100001DOI Listing
August 2011

Quantification of endothelial cell-targeted anti-Bcl-2 therapy and its suppression of tumor growth and vascularization.

Mol Cancer Ther 2009 Oct 6;8(10):2926-36. Epub 2009 Oct 6.

Frankfurt Institute for Advanced Studies, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.

Proapoptotic and antiapoptotic proteins in the Bcl family are key regulators of programmed cell death. It is the interaction between these molecules that determines cellular response to apoptotic signals, making them attractive targets for therapeutic intervention. In recent experiments designed to study tumor angiogenesis, Bcl-2 upregulation in endothelial cells was shown to be a critical mediator of vascular development. In this article, we develop a mathematical model that explicitly incorporates the response of endothelial cells to variations in proapoptotic and antiapoptotic proteins in the Bcl family, as well as the administration of specific antiangiogenic therapies targeted against Bcl-2. The model is validated by comparing its predictions to in vitro experimental data that reports microvessel density prior to and following the administration of 0.05 to 5.0 micromol/L of BL193, a promising small molecule inhibitor of Bcl-2. Numerical simulations of in vivo treatment of tumors predict the existence of a threshold for the amount of therapy required for successful treatment and quantify how this threshold varies with the stage of tumor growth. Furthermore, the model shows how rapidly the least effective dosage of BL193 decreases if an even moderately better inhibitor of Bcl-2 is used and predicts that increasing cell wall permeability of endothelial cells to BL193 does not significantly affect this threshold. A critical challenge of experimental therapeutics for cancer is to decide which drugs are the best candidates for clinical trials. These results underscore the potential of mathematical modeling to guide the development of novel antiangiogenic therapies and to direct drug design.
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http://dx.doi.org/10.1158/1535-7163.MCT-08-1223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776748PMC
October 2009

Stem cells: therapeutic potential in dentistry.

J Contemp Dent Pract 2009 Jul 1;10(4):90-6. Epub 2009 Jul 1.

School of Dentistry, Federal University of Pelotas, Pelotas, RS, Brazil.

Aim: The aim of this paper is to present a review and discussion of the current status of stem cell research with regard to tooth generation.

Background: Stem cells have been isolated from the pulp tissue of both deciduous and permanent teeth as well as from the periodontal ligament. Dental pulp stem cells demonstrate the capacity to form a dentin pulp-like complex in immunocompromised mice. A tooth-like structure was successfully formed, using a heterogeneous mixture of dental enamel epithelium, pulp mesenchymal cells, and scaffolds.

Conclusion: The scientific community understands the need for more investigations to completely understand the conditions that would best favor the creation of a tooth substitute. Recent gains in the understanding of the molecular regulation of tooth morphogenesis, stem cell biology, and biotechnology offers the opportunity to realize this goal.

Clinical Significance: These findings, combined with the recent progress in stem cell research and tissue engineering, might allow the development of alternatives for current materials and therapies used to treat tooth tissue loss (e.g., enamel, dentin, pulp), reconstruct dentoalveolar and craniofacial bone defects, and eventually replace an entire tooth.
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July 2009

Vascular endothelial growth factor and its relationship with the dental pulp.

J Endod 2007 May 23;33(5):524-30. Epub 2007 Mar 23.

School of Dentistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.

The dental pulp is a loose connective tissue located within rigid dentinal walls. Therefore, when subjected to a stimulus, the pulpal tissue has little expansion capacity. The defense mechanisms of this tissue include the formation of tertiary dentin as well as the production of signaling molecules that help in the repair. The dentin matrix is rich in growth factors (GFs) that, when diluted and diffused into the pulp tissue, aid the healing process of the dentinopulpar complex. The angiogenic GFs participate in this event. Vascular endothelial growth factor (VEGF), a potent mitogen for endothelial cells, promotes endothelial cell survival and angiogenesis. Among its receptors, VEGFR-2 seems to be the most intimately associated with mitogenic activities, cell migration, vascular permeability, and survival of endothelial cells. This literature review addresses the cell-signaling process that occurs in response to a pulp stimulus up to its transduction in the target cell, describing the VEGF, as well as its characteristics and receptors. The reported studies have correlated the expression of VEGF and its potential functions that may have an impact on several dental specialties, thus indicating that further clinical investigations should be conducted in order to translate the results obtained until this moment primarily in laboratory experiments.
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http://dx.doi.org/10.1016/j.joen.2007.01.003DOI Listing
May 2007