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      In Search of Effective Anticancer Agents—Novel Sugar Esters Based on Polyhydroxyalkanoate Monomers

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          Abstract

          Cancer is one of the deadliest illness globally. Searching for new solutions in cancer treatments is essential because commonly used mixed, targeted and personalized therapies are sometimes not sufficient or are too expensive for common patients. Sugar fatty acid esters (SFAEs) are already well-known as promising candidates for an alternative medical tool. The manuscript brings the reader closer to methods of obtaining various SFAEs using combined biological, chemical and enzymatic methods. It presents how modification of SFAE’s hydrophobic chains can influence their cytotoxicity against human skin melanoma and prostate cancer cell lines. The compound’s cytotoxicity was determined by an MTT assay, which followed an assessment of SFAEs’ potential metastatic properties in concentrations below IC 50 values. Despite relatively high IC 50 values (63.3–1737.6 μM) of the newly synthesized SFAE, they can compete with other sugar esters already described in the literature. The chosen bioactives caused low polymerization of microtubules and the depolymerization of actin filaments in nontoxic levels, which suggest an apoptotic rather than metastatic process. Altogether, cancer cells showed no propensity for metastasis after treating them with SFAE. They confirmed that lactose-based compounds seem the most promising surfactants among tested sugar esters. This manuscript creates a benchmark for creation of novel anticancer agents based on 3-hydroxylated fatty acids of bacterial origin.

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          Cancer treatment and survivorship statistics, 2019

          The number of cancer survivors continues to increase in the United States because of the growth and aging of the population as well as advances in early detection and treatment. To assist the public health community in better serving these individuals, the American Cancer Society and the National Cancer Institute collaborate every 3 years to estimate cancer prevalence in the United States using incidence and survival data from the Surveillance, Epidemiology, and End Results cancer registries; vital statistics from the Centers for Disease Control and Prevention's National Center for Health Statistics; and population projections from the US Census Bureau. Current treatment patterns based on information in the National Cancer Data Base are presented for the most prevalent cancer types. Cancer-related and treatment-related short-term, long-term, and late health effects are also briefly described. More than 16.9 million Americans (8.1 million males and 8.8 million females) with a history of cancer were alive on January 1, 2019; this number is projected to reach more than 22.1 million by January 1, 2030 based on the growth and aging of the population alone. The 3 most prevalent cancers in 2019 are prostate (3,650,030), colon and rectum (776,120), and melanoma of the skin (684,470) among males, and breast (3,861,520), uterine corpus (807,860), and colon and rectum (768,650) among females. More than one-half (56%) of survivors were diagnosed within the past 10 years, and almost two-thirds (64%) are aged 65 years or older. People with a history of cancer have unique medical and psychosocial needs that require proactive assessment and management by follow-up care providers. Although there are growing numbers of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based resources are needed to optimize care.
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            Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018

            Europe contains 9% of the world population but has a 25% share of the global cancer burden. Up-to-date cancer statistics in Europe are key to cancer planning. Cancer incidence and mortality estimates for 25 major cancers are presented for the 40 countries in the four United Nations-defined areas of Europe and for Europe and the European Union (EU-28) for 2018.
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              Vimentin contributes to epithelial-mesenchymal transition cancer cell mechanics by mediating cytoskeletal organization and focal adhesion maturation

              Modulations of cytoskeletal organization and focal adhesion turnover correlate to tumorigenesis and epithelial-mesenchymal transition (EMT), the latter process accompanied by the loss of epithelial markers and the gain of mesenchymal markers (e.g., vimentin). Clinical microarray results demonstrated that increased levels of vimentin mRNA after chemotherapy correlated to a poor prognosis of breast cancer patients. We hypothesized that vimentin mediated the reorganization of cytoskeletons to maintain the mechanical integrity in EMT cancer cells. By using knockdown strategy, the results showed reduced cell proliferation, impaired wound healing, loss of directional migration, and increased large membrane extension in MDA-MB 231 cells. Vimentin depletion also induced reorganization of cytoskeletons and reduced focal adhesions, which resulted in impaired mechanical strength because of reduced cell stiffness and contractile force. In addition, overexpressing vimentin in MCF7 cells increased cell stiffness, elevated cell motility and directional migration, reoriented microtubule polarity, and increased EMT phenotypes due to the increased β1-integrin and the loss of junction protein E-cadherin. The EMT-related transcription factor slug was also mediated by vimentin. The current study demonstrated that vimentin serves as a regulator to maintain intracellular mechanical homeostasis by mediating cytoskeleton architecture and the balance of cell force generation in EMT cancer cells.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                05 July 2021
                July 2021
                : 22
                : 13
                : 7238
                Affiliations
                [1 ]Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Niezapominajek 8, 30-239 Kraków, Poland; wojciech.snoch@ 123456ikifp.edu.pl (W.S.); tomasz.witko@ 123456ikifp.edu.pl (T.W.); ewelina.jarek@ 123456ikifp.edu.pl (E.J.)
                [2 ]Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland; dawid.wnuk@ 123456uj.edu.pl
                [3 ]Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland; staron@ 123456if-pan.krakow.pl (J.S.); bojarski@ 123456if-pan.krakow.pl (A.J.B.)
                [4 ]Instituto de Catalisis y Petroleoquimica, CSIC (Spanish National Research Council), Calle de Marie Curie, 2, 28049 Madrid, Spain; fplou@ 123456icp.csic.es
                Author notes
                [* ]Correspondence: maciej.guzik@ 123456ikifp.edu.pl ; Tel.: +48-12-6395-159
                Author information
                https://orcid.org/0000-0003-1039-1458
                https://orcid.org/0000-0002-1451-0306
                https://orcid.org/0000-0003-1417-6333
                https://orcid.org/0000-0002-1491-4458
                https://orcid.org/0000-0003-0831-893X
                https://orcid.org/0000-0001-7999-6645
                Article
                ijms-22-07238
                10.3390/ijms22137238
                8268987
                34281292
                dd56db27-db5e-4cb9-93a4-12cb1e32fd8e
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 28 May 2021
                : 29 June 2021
                Categories
                Article

                Molecular biology
                anticancer agents,sugar esters,polyhydroxyalkanoates,fluorination,chemical modifications,melanoma,prostate cancer

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