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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Resveratrol Reverses Cigarette Smoke-Induced Urocystic Epithelial–Mesenchymal Transition via Suppression of STAT3 Phosphorylation in SV-HUC-1-Immortalized Human Urothelial Cells

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          Abstract

          Purpose

          Bladder cancer is a malignant tumor of the urinary tract, and cigarette smoke (CS) is closely related to tumorigenesis. Resveratrol, a plant-derived bioactive nutrient, possesses multiple anticancer effects. However, the mechanism of CS-induced tumorigenesis is still not clear. The role of resveratrol in CS-meditated bladder cancer development has not been reported.

          Methods

          MTT assay showed the toxicity of cigarette smoke extract (CSE) on the cell viability of SV-HUC-1 cells. Western blotting detected the expression levels of related proteins. Transwell migration or invasion assay evaluated the capacity of cell migration or invasion after treatment. Wound-healing assay revealed the effect of cell migratory capacity. The cell cycle was detected by flow cytometry.

          Results

          Our study demonstrated that CSE-triggered epithelial–mesenchymal transition (EMT) in SV-HUC-1-immortalized human urothelial cells via the STAT3/TWIST1 pathway. Furthermore, the results showed resveratrol effectively inhibited STAT3 phosphorylation, thus reversed EMT triggered by CSE. Meanwhile, the cell proliferation was also suppressed.

          Conclusion

          In conclusion, inhibition of the STAT3 in CSE-induced EMT on bladder cancer may be a promising cancer treatment target for suppression by resveratrol.

          Most cited references28

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          Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics?

          Rui-Mei Feng, Yi-Nan Zong, Su-Mei Cao … (2019)
          Cancer is the leading cause of death in China and depicting the cancer pattern of China would provide basic knowhows on how to tackle it more effectively. In this study we have reviewed several reports of cancer burden, including the Global cancer statistics 2018 and Cancer statistics in China, 2015, along with the GLOBCAN 2018 online database, to investigate the differences of cancer patterns between China, the United States (USA) and the United Kingdom (UK). An estimated 4.3 million new cancer cases and 2.9 million new cancer deaths occurred in China in 2018. Compared to the USA and UK, China has lower cancer incidence but a 30% and 40% higher cancer mortality than the UK and USA, among which 36.4% of the cancer-related deaths were from the digestive tract cancers (stomach, liver, and esophagus cancer) and have relatively poorer prognoses. In comparison, the digestive cancer deaths only took up ≤ 5% of the total cancer deaths in either USA or UK. Other reasons for the higher mortality in China may be the low rate of early-stage cancers at diagnosis and non-uniformed clinical cancer treatment strategies performed by different regions. China is undergoing the cancer transition stage where the cancer spectrum is changing from developing country to developed country, with a rapidly increase cancer burden of colorectal, prostate, female breast cancers in addition to a high occurrence of infection-related and digestive cancers. The incidence of westernized lifestyle-related cancers in China (i.e. colorectal cancer, prostate, bladder cancer) has risen but the incidence of the digestive cancers has decreased from 2000 to 2011. An estimated 40% of the risk factors can be attributed to environmental and lifestyle factors either in China or other developed countries. Tobacco smoking is the single most important carcinogenic risk factor in China, contributing to ~ 24.5% of cancers in males. Chronic infection is another important preventable cancer contributor which is responsible for ~ 17% of cancers. Comprehensive prevention and control strategies in China should include effective tobacco-control policy, recommendations for healthier lifestyles, along with enlarging the coverage of effective screening, educating, and vaccination programs to better sensitize greater awareness control to the general public.
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            Macrophage-secreted IL-8 induces epithelial-mesenchymal transition in hepatocellular carcinoma cells by activating the JAK2/STAT3/Snail pathway.

            Xiu-Tao Fu, Zhi Dai, In-Kang Song … (2015)
            Macrophages are a major component of the leukocyte infiltrate of tumors and play a pivotal role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanisms by which macrophages promote HCC invasion are poorly understood. The present study was undertaken to investigate the relationship between macrophages and epithelial-mesenchymal transition (EMT) of HCC. Double-staining immunohistochemistry was used to observe the association between macrophages and EMT markers in clinical HCC samples and it showed that EMT primarily occurred at the edge of the tumor nest, in which infiltrating macrophages were always observed. This indicated that CD68 which is a marker of macrophages, was correlated with EMT marker levels. In addition, after being cultured with macrophages for 24 h, the ability of HCC cells to migrate and invade increased, Snail and N-Cadherin expression was upregulated, and E-Cadherin was downregulated. An antibody array assay was applied to analyze the supernatant of these cultures and it demonstrated IL-8 increased significantly in the macrophage co-culture system. Finally, the role of macrophage-derived IL-8 in the invasion of HCC cells was assayed, and downstream signaling pathways were also investigated. We found that IL-8: i) may induce EMT and promote HCC cell migration and invasion and ii) is associated with the JAK2/STAT3/Snail signaling pathway. Taking together, these findings revealed that macrophages that have infiltrated tumors may induce epithelial-mesenchymal transition of HCC cells via the IL-8 activated JAK2/STAT3/Snail pathway. Thus, this may offer a potential target for developing new HCC therapies.
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              Resveratrol for breast cancer prevention and therapy: Preclinical evidence and molecular mechanisms.

              Dona Sinha, Nivedita Sarkar, Jaydip Biswas … (2016)
              Globally, breast cancer is the most frequently diagnosed cancer among women. The major unresolved problems with metastatic breast cancer is recurrence after receiving objective response to chemotherapy, drug-induced side effects of first line chemotherapy and delayed response to second line of treatment. Unfortunately, very few options are available as third line treatment. It is clear that under such circumstances there is an urgent need for new and effective drugs. Phytochemicals are among the most promising chemopreventive treatment options for the management of cancer. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a non-flavonoid polyphenol present in several dietary sources, including grapes, berries, soy beans, pomegranate and peanuts, has been shown to possess a wide range of health benefits through its effect on a plethora of molecular targets.The present review encompasses the role of resveratrol and its natural/synthetic analogue in the light of their efficacy against tumor cell proliferation, metastasis, epigenetic alterations and for induction of apoptosis as well as sensitization toward chemotherapeutic drugs in various in vitro and in vivo models of breast cancer. The roles of resveratrol as a phytoestrogen, an aromatase inhibitor and in stem cell therapy as well as adjuvent treatment are also discussed. This review explores the full potential of resveratrol in breast cancer prevention and treatment with current limitations, challenges and future directions of research.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Onco Targets Ther
                Journal ID (iso-abbrev): Onco Targets Ther
                Journal ID (publisher-id): OTT
                Journal ID (pmc): ott
                Title: OncoTargets and therapy
                Publisher: Dove
                ISSN (Electronic): 1178-6930
                Publication date (Electronic): 26 November 2019
                Publication date Collection: 2019
                Volume: 12
                Pages: 10227-10237
                Affiliations
                [1 ]Department of Urology, The Second Affiliated Hospital of Anhui Medical University , Hefei 230032, People’s Republic of China
                Author notes
                Correspondence: Dexin Yu Department of Urology, The Second Affiliated Hospital of Anhui Medical University , Hefei230032, People’s Republic of ChinaTel +86 137 0569 0883Fax +86 551 6386 9522 Email yudx_urology@126.com
                Article
                Publisher ID: 226580
                DOI: 10.2147/OTT.S226580
                PMC ID: 6884977
                PubMed ID: 32063715
                SO-VID: 8fd66181-9182-4a3d-8479-fe727beb0bb5
                Copyright © © 2019 Sun et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 09 August 2019
                Date accepted : 06 November 2019
                Page count
                Figures: 5, References: 39, Pages: 11
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: bladder cancer,cigarette smoke,resveratrol,stat3/twist1
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: bladder cancer, cigarette smoke, resveratrol, stat3/twist1

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