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      Assessing the Racial and Ethnic Disparities in Breast Cancer Mortality in the United States

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          Abstract

          Breast cancer is the second leading cause of cancer related deaths among women aged 40–55 in the United States and currently affects more than one in ten women worldwide. It is also one of the most diagnosed cancers in women both in wealthy and poor countries. Fortunately, the mortality rate from breast cancer has decreased in recent years due to increased emphasis on early detection and more effective treatments in White population. Although the mortality rates have declined in some ethnic populations, the overall cancer incidence among African American and Hispanic populations has continued to grow. The goal of the present review article was to highlight similarities and differences in breast cancer morbidity and mortality rates primarily among African American women compared to White women in the United States. To reach our goal, we conducted a search of articles in journals with a primary focus on minority health, and authors who had published articles on racial/ethnic disparity related to breast cancer patients. A systematic search of original research was conducted using MEDLINE, PUBMED and Google Scholar databases. We found that racial/ethnic disparities in breast cancer may be attributed to a large number of clinical and non-clinical risk factors including lack of medical coverage, barriers to early detection and screening, more advanced stage of disease at diagnosis among minorities, and unequal access to improvements in cancer treatment. Many African American women have frequent unknown or unstaged breast cancers than White women. These risk factors may explain the differences in breast cancer treatment and survival rate between African American women and White women. New strategies and approaches are needed to promote breast cancer prevention, improve survival rate, reduce breast cancer mortality, and ultimately improve the health outcomes of racial/ethnic minorities.

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          Broad targeting of resistance to apoptosis in cancer

          Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer.
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            Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer.

            TP53 mutation occurs in 50-75% of human pancreatic ductal adenocarcinomas (PDAC) following an initiating activating mutation in the KRAS gene. These p53 mutations frequently result in expression of a stable protein, p53(R175H), rather than complete loss of protein expression. In this study we elucidate the functions of mutant p53 (Trp53(R172H)), compared to knockout p53 (Trp53(fl)), in a mouse model of PDAC. First we find that although Kras(G12D) is one of the major oncogenic drivers of PDAC, most Kras(G12D)-expressing pancreatic cells are selectively lost from the tissue, and those that remain form premalignant lesions. Loss, or mutation, of Trp53 allows retention of the Kras(G12D)-expressing cells and drives rapid progression of these premalignant lesions to PDAC. This progression is consistent with failed growth arrest and/or senescence of premalignant lesions, since a mutant of p53, p53(R172P), which can still induce p21 and cell cycle arrest, is resistant to PDAC formation. Second, we find that despite similar kinetics of primary tumor formation, mutant p53(R172H), as compared with genetic loss of p53, specifically promotes metastasis. Moreover, only mutant p53(R172H)-expressing tumor cells exhibit invasive activity in an in vitro assay. Importantly, in human PDAC, p53 accumulation significantly correlates with lymph node metastasis. In summary, by using 'knock-in' mutations of Trp53 we have identified two critical acquired functions of a stably expressed mutant form of p53 that drive PDAC; first, an escape from Kras(G12D)-induced senescence/growth arrest and second, the promotion of metastasis.
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              The effect of patient race and socio-economic status on physicians' perceptions of patients

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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                05 May 2017
                May 2017
                : 14
                : 5
                : 486
                Affiliations
                [1 ]Natural Chemotherapeutics Research Laboratory, Research Centers in Minority Institutio (RCMI)-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, 1400 Lynch Street, Box 18750, Jackson, MS 39217, USA; paul.b.tchounwou@ 123456jsums.edu (P.B.T.); gomezfonseca@ 123456gmail.com (D.D.F.)
                [2 ]Center of Excellence in Minority Health and Health Disparities, School of Public Health, Jackson State University, Jackson Medical Mall-Thad Cochran Center, 350 West Woodrow Wilson Avenue, Jackson, MS 39213, USA; marinelle.payton@ 123456jsums.edu
                [3 ]Department of Genetics, LSU Health Sciences Center, School of Medicine, 533 Bolivar Street, Room 657, New Orleans, LA 70112, USA; lmiele@ 123456lsuhsc.edu
                [4 ]Lancaster Environment Centre, Lancaster University, Bailrigg, Lancaster LA1 4YW, UK; leroy.lowe@ 123456gettingtoknowcancer.org
                [5 ]Department of Civil and Environmental Engineering, College of Science, Engineering and Technology, Jackson State University, 1400 Lynch Street, Box 18750, Jackson, MS 39217, USA; richard.a.alo@ 123456jsums.edu
                Author notes
                [* ]Correspondence: clement.yedjou@ 123456jsums.edu ; Tel.: +1-601-979-0215; Fax: +1-601-979-5853
                Article
                ijerph-14-00486
                10.3390/ijerph14050486
                5451937
                28475137
                71493337-625d-4c42-b10d-60c03096398d
                © 2017 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
                : 28 December 2016
                : 26 April 2017
                Categories
                Review

                Public health
                breast cancer,racial disparity,health disparity,african american
                Public health
                breast cancer, racial disparity, health disparity, african american

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