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      High aldehyde dehydrogenase activity identifies cancer stem cells in human cervical cancer

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          Abstract

          High aldehyde dehydrogenase (ALDH) activity characterizes a subpopulation of cells with cancer stem cell (CSC) properties in several malignancies. To clarify whether ALDH can be used as a marker of cervical cancer stem cells (CCSCs), ALDH high and ALDH low cells were sorted from 4 cervical cancer cell lines and 5 primary tumor xenografts and examined for CSC characteristics. Here, we demonstrate that cervical cancer cells with high ALDH activity fulfill the functional criteria for CSCs: (1) ALDH high cells, unlike ALDH low cells, are highly tumorigenic in vivo; (2) ALDH high cells can give rise to both ALDH high and ALDH low cells in vitro and i n vivo, thereby establishing a cellular hierarchy; and (3) ALDH high cells have enhanced self-renewal and differentiation potentials. Additionally, ALDH high cervical cancer cells are more resistant to cisplatin treatment than ALDH low cells. Finally, expression of the stem cell self-renewal-associated transcription factors OCT4, NANOG, KLF4 and BMI1 is elevated in ALDH high cervical cancer cells. Taken together, our data indicated that high ALDH activity may represent both a functional marker for CCSCs and a target for novel cervical cancer therapies.

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          Most cited references 34

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          Global cancer statistics

           A. JEMAL,  F BRAY,  MM Center (2011)
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            Identification of pancreatic cancer stem cells.

            Emerging evidence has suggested that the capability of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. Although data have been provided to support this theory in human blood, brain, and breast cancers, the identity of pancreatic cancer stem cells has not been determined. Using a xenograft model in which primary human pancreatic adenocarcinomas were grown in immunocompromised mice, we identified a highly tumorigenic subpopulation of pancreatic cancer cells expressing the cell surface markers CD44, CD24, and epithelial-specific antigen (ESA). Pancreatic cancer cells with the CD44(+)CD24(+)ESA(+) phenotype (0.2-0.8% of pancreatic cancer cells) had a 100-fold increased tumorigenic potential compared with nontumorigenic cancer cells, with 50% of animals injected with as few as 100 CD44(+)CD24(+)ESA(+) cells forming tumors that were histologically indistinguishable from the human tumors from which they originated. The enhanced ability of CD44(+)CD24(+)ESA(+) pancreatic cancer cells to form tumors was confirmed in an orthotopic pancreatic tail injection model. The CD44(+)CD24(+)ESA(+) pancreatic cancer cells showed the stem cell properties of self-renewal, the ability to produce differentiated progeny, and increased expression of the developmental signaling molecule sonic hedgehog. Identification of pancreatic cancer stem cells and further elucidation of the signaling pathways that regulate their growth and survival may provide novel therapeutic approaches to treat pancreatic cancer, which is notoriously resistant to standard chemotherapy and radiation.
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              The causal relation between human papillomavirus and cervical cancer.

               F Bosch,  A Lorincz,  N Muñoz (2002)
              The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                December 2013
                25 November 2013
                : 4
                : 12
                : 2462-2475
                Affiliations
                1 Department of Reproductive Medicine, The First Affiliated Hospital of the Medical College, Xi'an Jiaotong University, Xi'an, The People's Republic of China
                2 Section of Cancer Stem Cell Research, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of the People's Republic of China, Xi'an, The People's Republic of China
                Author notes
                Correspondence to: Peng-Sheng Zheng, zpsheng@ 123456mail.xjtu.edu.cn
                Article
                3926841
                24318570
                Copyright: © 2013 Liu and Zheng

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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                Research Paper

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