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      Effects of combination therapy of docetaxel with selenium on the human breast cancer cell lines MDA-MB-231 and MCF-7

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          Abstract

          Purpose

          The anticancer property and cytoprotective role of selenium in chemotherapy have been reported. However, the combination effects of selenium on chemotherapy for advanced breast cancer have not yet been clearly defined. The purpose of this study was to investigate the combined effects of selenium on chemotherapy using docetaxel on breast cancer cell lines.

          Methods

          Under adherent culture conditions, two breast cancer cell lines, MDA-MB-231 and MCF-7, were treated with docetaxel at 500pM and selenium at 100nM, 1µM, or 10µM. Changes in cell growth, cell cycle duration, and degree of apoptosis after 72 hours in each treated group were evaluated.

          Results

          In the MDA-MB-231 cells, the combination therapy group (docetaxel at 500pM plus selenium at 10µM) showed a significantly decreased percentage of cell growth (15% vs. 28%; P = 0.004), a significantly increased percentage of late apoptosis (63% vs. 26%; P = 0.001), and an increased cell cycle arrest in the G2/M phase (P = 0.001) compared with the solitary docetaxel therapy group. Isobologram analysis demonstrated the synergistic effect of the combination therapy in the MDA-MB-231 cells. However, in the MCF-7 cells, no significant differences in the percentage of cell growth apoptosis, the percentage of apoptosis, and the pattern of cell cycle arrest were noted between the combination therapy groups and the solitary docetaxel therapy group.

          Conclusion

          Our in vitro study indicated that the combination of selenium with docetaxel inhibits cell proliferation through apoptosis and cell arrest in the G2/M phase in MDA-MB-231 breast cancer cells.

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          Most cited references28

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          Taxol suppresses dynamics of individual microtubules in living human tumor cells.

          Microtubules are intrinsically dynamic polymers, and their dynamics play a crucial role in mitotic spindle assembly, the mitotic checkpoint, and chromosome movement. We hypothesized that, in living cells, suppression of microtubule dynamics is responsible for the ability of taxol to inhibit mitotic progression and cell proliferation. Using quantitative fluorescence video microscopy, we examined the effects of taxol (30-100 nM) on the dynamics of individual microtubules in two living human tumor cell lines: Caov-3 ovarian adenocarcinoma cells and A-498 kidney carcinoma cells. Taxol accumulated more in Caov-3 cells than in A-498 cells. At equivalent intracellular taxol concentrations, dynamic instability was inhibited similarly in the two cell lines. Microtubule shortening rates were inhibited in Caov-3 cells and in A-498 cells by 32 and 26%, growing rates were inhibited by 24 and 18%, and dynamicity was inhibited by 31 and 63%, respectively. All mitotic spindles were abnormal, and many interphase cells became multinucleate (Caov-3, 30%; A-498, 58%). Taxol blocked cell cycle progress at the metaphase/anaphase transition and inhibited cell proliferation. The results indicate that suppression of microtubule dynamics by taxol deleteriously affects the ability of cancer cells to properly assemble a mitotic spindle, pass the metaphase/anaphase checkpoint, and produce progeny.
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            Review of selenium toxicity in the aquatic food chain.

            In many environmental contaminant situations selenium has become the primary element of concern because of its bioaccumulative nature in food webs. Initial concerns about selenium were related to fish kills at Belews Lake, NC, Martin Lake, TX, and Kesterson Reservoir, CA, and to bird deformities at Kesterson Reservoir. Additional concerns were identified under the National Irrigation Water Quality Program at Salton Sea, CA, Kendrick, WY, Stewart Lake, UT, and Grand Valley and Uncompahgre Valley, CO. Recent studies have raised concerns about selenium impacts on aquatic resources in Southeastern Idaho and British Columbia. The growing discomfort among the scientific community with a waterborne criterion has lead the US Environment Protection Agency to consider a tissue-based criterion for selenium. Some aquatic ecosystems have been slow to recover from selenium contamination episodes. In recent years, non-governmental researchers have been proposing relatively high selenium thresholds in diet and tissue relative to those proposed by governmental researchers. This difference in opinions is due in part to the selection of datasets and caveats in selecting scientific literature. In spite of the growing selenium literature, there are needs for additional research on neglected organisms. This review also discusses the interaction of selenium with other elements, inconsistent effects of selenium on survival and growth of fish, and differences in depuration rates and sensitivity among species. Copryright 2004 Elsevier B.V.
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              Arm edema in breast cancer patients.

              The improvement in the life expectancy of women with breast cancer raises important questions about how to improve the quality of life for women sustaining complications of breast cancer treatment. In particular, attention to common problems, such as arm edema, is of critical importance. We reviewed published breast cancer guidelines and literature identified via MEDLINE(R) searches in an effort to summarize the research literature pertinent to management of breast cancer-related arm edema, including incidence, prevalence, and timing; risk factors; morbidity; prevention; diagnosis; and efficacy of nonpharmacologic and pharmacologic interventions. We found that arm edema is a common complication of breast cancer therapy that can result in substantial functional impairment and psychological morbidity. The risk of arm edema increases when axillary dissection and axillary radiation therapy are used. Recommendations for preventive measures, such as avoidance of trauma, are available, but these measures have not been well studied. Nonpharmacologic treatments, such as massage and exercise, have been shown to be effective therapies for lymphedema, but the effect of pharmacologic interventions remains uncertain. Comparing results across studies is complicated by the fact that the definitions of interventions and measures of outcomes and risk stratification vary substantially among studies. As arm edema becomes more prevalent with the increasing survival of breast cancer patients, further research is needed to evaluate the efficacy of preventive strategies and therapeutic interventions.
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                Author and article information

                Journal
                Ann Surg Treat Res
                Ann Surg Treat Res
                ASTR
                Annals of Surgical Treatment and Research
                The Korean Surgical Society
                2288-6575
                2288-6796
                February 2015
                27 January 2015
                : 88
                : 2
                : 55-62
                Affiliations
                Department of Emergency Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
                [1 ]Department of Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
                [2 ]Department of Surgery, Konkuk University Chungju Hospital, Chungju, Korea.
                [3 ]Department of Emergency Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
                [4 ]Department of Emergency Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea.
                Author notes
                Corresponding Author: Kyoung Sik Park. Department of Surgery, Konkuk University Medical Centre, Konkuk University School of Medicine, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-729, Korea. Tel: +82-2-2030-7697, Fax: +82-2-2030-7346, kspark@ 123456kuh.ac.kr
                Article
                10.4174/astr.2015.88.2.55
                4325646
                25692115
                fe7f9973-e1d9-481c-9e27-9524d7632670
                Copyright © 2015, the Korean Surgical Society

                Annals of Surgical Treatment and Research is an Open Access Journal. All articles are distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 June 2014
                : 06 September 2014
                : 25 September 2014
                Funding
                Funded by: Konkuk University
                Categories
                Original Article

                breast neoplasms,selenium,docetaxel,combination drug therapy

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