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      Phytochemicals in Skin Cancer Prevention and Treatment: An Updated Review

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          Abstract

          Skin is the largest human organ, our protection against various environmental assaults and noxious agents. Accumulation of these stress events may lead to the formation of skin cancers, including both melanoma and non-melanoma skin cancers. Although modern targeted therapies have ameliorated the management of cutaneous malignancies, a safer, more affordable, and more effective strategy for chemoprevention and treatment is clearly needed for the improvement of skin cancer care. Phytochemicals are biologically active compounds derived from plants and herbal products. These agents appear to be beneficial in the battle against cancer as they exert anti-carcinogenic effects and are widely available, highly tolerated, and cost-effective. Evidence has indicated that the anti-carcinogenic properties of phytochemicals are due to their anti-oxidative, anti-inflammatory, anti-proliferative, and anti-angiogenic effects. In this review, we discuss the preventive potential, therapeutic effects, bioavailability, and structure–activity relationship of these selected phytochemicals for the management of skin cancers. The knowledge compiled here will provide clues for future investigations on novel oncostatic phytochemicals and additional anti-skin cancer mechanisms.

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          Distribution and Biological Activities of the Flavonoid Luteolin

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            Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B.

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              Role of angiogenesis in human tumor dormancy: animal models of the angiogenic switch.

              Tumor progression depends on sequential events, including a switch to the angiogenic phenotype (i.e., initial recruitment of blood vessels). Failure of a microscopic tumor to complete one or more early steps in this process may lead to delayed clinical manifestation of the cancer. Microscopic human cancers can remain in an asymptomatic, non-detectable, and occult state for the life of a person. Clinical and experimental evidence suggest that human tumors can persist for long periods of time as microscopic lesions that are in a state of dormancy (i.e., not expanding in tumor mass). Because it is well established that tumor growth beyond the size of 1-2 mm is angiogenesis-dependent, we hypothesized that presentation of large tumors is attributed to a switch to the angiogenic phenotype in otherwise microscopic, dormant tumors. Although clinically important, the biology of human tumor dormancy is poorly understood. The development of animal models which recapitulate the clinically observed timing and proportion of dormant tumors which switch to the angiogenic phenotype are reviewed here. The contributing molecular mechanisms involved in the angiogenic switch and different strategies for isolation of both angiogenic and non-angiogenic tumor cell populations from otherwise heterogeneous human tumor cell lines or surgical specimens are also summarized. Several imaging techniques have been utilized for the qualitative and quantitative detection of microscopic tumors in mice and their strengths and limitations are discussed. The animal models employed here permitted further studies of the angiogenic switch. These models also allowed development of an angiogenesis-based panel of blood and urine biomarkers that can be quantified and used to detect microscopic tumors before or during the angiogenic switch. If the information obtained from these animal models is translatable to the clinic, it may be possible in the future to liberate the management of cancer from a dependency on anatomical site years before it becomes symptomatic and detectable.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                22 March 2018
                April 2018
                : 19
                : 4
                : 941
                Affiliations
                [1 ]Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taipei, and Keelung 105, Taiwan; charlene870811@ 123456gmail.com (C.Y.N.); hsi.k.yen@ 123456gmail.com (H.Y.); ssu1@ 123456cgmh.org.tw (S.-C.S.)
                [2 ]Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei, and Keelung 105, Taiwan
                [3 ]School of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
                [4 ]Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan 333, Taiwan
                [5 ]Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
                [6 ]Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung 204, Taiwan
                Author notes
                [* ]Correspondence: ivyhsiao@ 123456gmail.com ; Tel.: +886-3-328-1200-2509
                [†]

                These authors contributed equally to this work.

                Article
                ijms-19-00941
                10.3390/ijms19040941
                5979545
                29565284
                496291cb-236b-481b-b00d-dd027d7dc7b9
                © 2018 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 ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 24 January 2018
                : 20 March 2018
                Categories
                Review

                Molecular biology
                phytomedicine,skin cancer,chemoprevention
                Molecular biology
                phytomedicine, skin cancer, chemoprevention

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