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      Targeting circulating tumor cells to prevent metastases

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          Abstract

          Circulating tumor cells (CTCs) are cancer cells that detach from the primary tumor, enter the bloodstream or body fluids, and spread to other body parts, leading to metastasis. Their presence and characteristics have been linked to cancer progression and poor prognosis in different types of cancer. Analyzing CTCs can offer valuable information about tumors’ genetic and molecular diversity, which is crucial for personalized therapy. Epithelial-mesenchymal transition (EMT) and the reverse process, mesenchymal-epithelial transition (MET), play a significant role in generating and disseminating CTCs. Certain proteins, such as EpCAM, vimentin, CD44, and TGM2, are vital in regulating EMT and MET and could be potential targets for therapies to prevent metastasis and serve as detection markers. Several devices, methods, and protocols have been developed for detecting CTCs with various applications. CTCs interact with different components of the tumor microenvironment. The interactions between CTCs and tumor-associated macrophages promote local inflammation and allow the cancer cells to evade the immune system, facilitating their attachment and invasion of distant metastatic sites. Consequently, targeting and eliminating CTCs hold promise in preventing metastasis and improving patient outcomes. Various approaches are being explored to reduce the volume of CTCs. By investigating and discussing targeted therapies, new insights can be gained into their potential effectiveness in inhibiting the spread of CTCs and thereby reducing metastasis. The development of such treatments offers great potential for enhancing patient outcomes and halting disease progression.

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          Most cited references152

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          Macrophage plasticity, polarization, and function in health and disease.

          Macrophages are heterogeneous and their phenotype and functions are regulated by the surrounding micro-environment. Macrophages commonly exist in two distinct subsets: 1) Classically activated or M1 macrophages, which are pro-inflammatory and polarized by lipopolysaccharide (LPS) either alone or in association with Th1 cytokines such as IFN-γ, GM-CSF, and produce pro-inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, IL-12, IL-23, and TNF-α; and 2) Alternatively activated or M2 macrophages, which are anti-inflammatory and immunoregulatory and polarized by Th2 cytokines such as IL-4 and IL-13 and produce anti-inflammatory cytokines such as IL-10 and TGF-β. M1 and M2 macrophages have different functions and transcriptional profiles. They have unique abilities by destroying pathogens or repair the inflammation-associated injury. It is known that M1/M2 macrophage balance polarization governs the fate of an organ in inflammation or injury. When the infection or inflammation is severe enough to affect an organ, macrophages first exhibit the M1 phenotype to release TNF-α, IL-1β, IL-12, and IL-23 against the stimulus. But, if M1 phase continues, it can cause tissue damage. Therefore, M2 macrophages secrete high amounts of IL-10 and TGF-β to suppress the inflammation, contribute to tissue repair, remodeling, vasculogenesis, and retain homeostasis. In this review, we first discuss the basic biology of macrophages including origin, differentiation and activation, tissue distribution, plasticity and polarization, migration, antigen presentation capacity, cytokine and chemokine production, metabolism, and involvement of microRNAs in macrophage polarization and function. Secondly, we discuss the protective and pathogenic role of the macrophage subsets in normal and pathological pregnancy, anti-microbial defense, anti-tumor immunity, metabolic disease and obesity, asthma and allergy, atherosclerosis, fibrosis, wound healing, and autoimmunity.
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            The basics of epithelial-mesenchymal transition.

            The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.
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              Macrophage activation and polarization: nomenclature and experimental guidelines.

              Description of macrophage activation is currently contentious and confusing. Like the biblical Tower of Babel, macrophage activation encompasses a panoply of descriptors used in different ways. The lack of consensus on how to define macrophage activation in experiments in vitro and in vivo impedes progress in multiple ways, including the fact that many researchers still consider there to be only two types of activated macrophages, often termed M1 and M2. Here, we describe a set of standards encompassing three principles-the source of macrophages, definition of the activators, and a consensus collection of markers to describe macrophage activation-with the goal of unifying experimental standards for diverse experimental scenarios. Collectively, we propose a common framework for macrophage-activation nomenclature. Copyright © 2014 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                karolgostomczyk.research@gmail.com
                Journal
                Hum Cell
                Hum Cell
                Human Cell
                Springer Nature Singapore (Singapore )
                0914-7470
                1749-0774
                24 October 2023
                24 October 2023
                2024
                : 37
                : 1
                : 101-120
                Affiliations
                [1 ]GRID grid.5374.5, ISNI 0000 0001 0943 6490, Department of Obstetrics, Gynaecology and Oncology, Chair of Pathomorphology and Clinical Placentology, Collegium Medicum in Bydgoszcz, , Nicolaus Copernicus University, ; Torun, Poland
                [2 ]University Hospital No. 2 Im. Dr Jan Biziel, Ujejskiego 75, 85-168 Bydgoszcz, Poland
                [3 ]Department of Tumor Pathology and Pathomorphology, Oncology Centre, Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Poland
                [4 ]University of Baghdad, Al-Kindy College of Medicine, ( https://ror.org/007f1da21) Baghdad, Iraq
                [5 ]Mayo Hospital, ( https://ror.org/046jyn221) Lahore, Pakistan
                [6 ]Kasturba Medical College, ( https://ror.org/05hg48t65) Manipal, India
                [7 ]Universidad del Norte Santo Tomás de Aquino, ( https://ror.org/0198n3j25) San Miquel de Tucuman, Argentina
                [8 ]American University of Integrative Sciences, Cole Bay, Saint Martin, Barbados
                [9 ]Bukovinian State Medical University, ( https://ror.org/0562ytb14) Chernivtsi, Ukraine
                [10 ]Chair of Pathology, Dr Jan Biziel Memorial University Hospital No. 2, Bydgoszcz, Poland
                Author information
                http://orcid.org/0000-0002-1956-7598
                Article
                992
                10.1007/s13577-023-00992-6
                10764589
                37874534
                73c17930-69af-438e-98a3-3b525681498d
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 September 2023
                : 3 October 2023
                Categories
                Review Article
                Custom metadata
                © Japan Human Cell Society 2024

                Cell biology
                ctcs,tams,targeted therapies,detection,metastases,cancer
                Cell biology
                ctcs, tams, targeted therapies, detection, metastases, cancer

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