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Paul Reid, Puthenparampil Wilson, Yanrui Li, Loredana G Marcu, Alexander H Staudacher, Michael P Brown, Eva Bezak
INTRODUCTION: Some head and neck squamous cell carcinomas (HNSCC) have a distinct aetiology, which depends on the presence of oncogenic human papilloma virus (HPV). Also, HNSCC contains cancer stem cells (CSCs) that have greater radioresistance and capacity to change replication dynamics in response to irradiation compared to non-clonogenic cells. Since there is limited data on CSCs in HNSCC as a function of HPV status, better understanding of their radiobiology may enable improved treatment outcome...
2017: PloS One
Hongshuang Qin, Chuanqi Zhao, Yuhuan Sun, Jinsong Ren, Xiaogang Qu
Cancer stem cells (CSCs) are responsible for drug resistance, metastasis and recurrence of cancers. However, there is still no clinically approved drug that can effectively eradicate CSCs. Thus, it is crucial and important to develop specific CSC-targeting agents. Chiral molecular recognition of DNA plays an important role in rational drug design. Among them, poly-morphic telomeric G-quadruplex DNA has received much attention due to its significant roles in telomerase activity and chromosome stability. Herein, we find that one enantiomer of zinc-finger-like chiral metallohelices, [Ni2L3]4+-P, a telomeric G-quadruplex-targeting ligand, can preferentially reduce cell growth in breast CSCs compared to the bulk cancer cells...
October 13, 2017: Journal of the American Chemical Society
Aparna Jayachandran, Ritu Shrestha, Bijay Dhungel, I-Tao Huang, Marianna Yumi Kawashima Vasconcelos, Brian J Morrison, Charmaine A Ramlogan-Steel, Jason C Steel
AIM: To establish a model to enrich and characterize stem-like cells from murine normal liver and hepatocellular carcinoma (HCC) cell lines and to further investigate stem-like cell association with epithelial-to-mesenchymal transition (EMT). METHODS: In this study, we utilized a stem cell conditioned serum-free medium to enrich stem-like cells from mouse HCC and normal liver cell lines, Hepa 1-6 and AML12, respectively. We isolated the 3-dimensional spheres and assessed their stemness characteristics by evaluating the RNA levels of stemness genes and a cell surface stem cell marker by quantitative reverse transcriptase-PCR (qRT-PCR)...
September 26, 2017: World Journal of Stem Cells
Shan Peng, Cheng Wu, Wei Sun, Dongbo Liu, Min Luo, Beibei Su, Linli Zhang, Qi Mei, Guoqing Hu
BACKGROUND: Cancer stem cell (CSC)-like phenotype, which has been proven to play a critical role in invasion and metastasis of many kinds of cancers, has also been reported to be associated with epithelial-mesenchymal transition. Snail, a potent repressor of E-cadherin expression, was found to have a function to regulate the aforementioned processes. METHODS: In the current study, expression of putative CSCs biomarkers and the ratio of CSC-like CNE2 (cancer cell line) in total CNE2 were measured, and CSC-like characteristics were analyzed with tumor-sphere self-renewal and colony-forming assays...
October 12, 2017: Head & Neck
Francesca Pistollato, Ruben Calderón Iglesias, Roberto Ruiz, Silvia Aparicio, Jorge Crespo, Luis Dzul Lopez, Francesca Giampieri, Maurizio Battino
Among gynaecological cancers, ovarian cancer represents the leading cause of death in women. Current treatment for ovarian cancer entails surgery followed by combined chemotherapy with platinum and taxane, which are associated, particularly cisplatin, with severe side effects. While this treatment approach appears to be initially effective in a high number of patients, nearly 70% of them suffer a relapse within a few months after initial treatment. Therefore, more effective and better-tolerated treatment options are clearly needed...
October 7, 2017: Cancer Letters
Carol O'Callaghan, Athanassios Vassilopoulos
Sirtuins are stress-responsive proteins that direct various post-translational modifications (PTMs) and as a result, are considered to be master regulators of several cellular processes. They are known to both extend lifespan and regulate spontaneous tumor development. As both aging and cancer are associated with altered stem cell function, the possibility that the involvement of sirtuins in these events is mediated by their roles in stem cells is worthy of investigation. Research to date suggests that the individual sirtuin family members can differentially regulate embryonic, hematopoietic as well as other adult stem cells in a tissue- and cell type-specific context...
October 10, 2017: Aging Cell
Nga Yi Tsang, Wai I Chik, Lai Pan Sze, Siu Wai Tsang, Hongjie Zhang
Cancer is a leading cause of mortality in the world and metastasis is to blame. Invasion is the initial step of metastasis. Therapies targeting epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and signal transducer and activator of transcription 3 (STAT3) signaling pathways can reduce stemness of cancer cells and thus inhibit cancer invasion. A large number of anti-cancer naphthoquinones (NQs) can target cancer invasion by acting on EMT, CSCs and STAT3 signaling. Furano-naphthoquinones (FNQs) belong to a class of NQ derivatives commonly characterized by a naphthoquinone fused with a furano ring...
October 6, 2017: Current Medicinal Chemistry
Jiankai Wang, Wenjuan Wang, Hongyi Cai, Binbin Du, Lijuan Zhang, Wen Ma, Yongguo Hu, Shifang Feng, Guoying Miao
With regards to colon cancer, resistance to 5‑fluorouracil (5‑FU)‑based chemotherapy and cancer stem cells (CSCs) are considered important factors underlying therapy failure. Metastasis‑associated colon cancer 1 (MACC1) has been associated with poor prognosis and the promotion of metastasis within several types of cancer. However, the biological behavior of MACC1 in chemoresistance and CSC‑like properties remains unclear. In the present study, various methods including gene knockdown, gene overexpression, western blotting, quantitative polymerase chain reaction and MTT assay, have been adopted...
October 4, 2017: Molecular Medicine Reports
Yanyan Miao, Haixia Zhang, Yubin Pan, Jian Ren, Miaoman Ye, Fangfang Xia, Rui Huang, Zhuoheng Lin, Shuai Jiang, Ya Zhang, Zhou Songyang, Yan Zhang
Cancer stem cells (CSCs) are believed to have a critical role in tumorigenesis, metastasis, therapeutic resistance or recurrence. Therefore, strategies designed to specifically target and eliminate CSCs have become one of the most promising and desirable ways for tumor treatment. Osteosarcoma stem cells (OSCs), the CSCs in osteosarcoma (OS), are critically associated with OS progression. Here, we show that single-walled carbon nanotubes (SWCNTs), including unmodified SWCNT (SWCNT-Raw) and SWCNT-COOH, have the ability to specifically inhibit the process of TGFβ1-induced OS cells dedifferentiation, prevent the stem cell phenotypes acquisition in OS cells and reduce the OSC viability under conditions which mimic the OS microenvironment...
September 26, 2017: Biomaterials
Martina Intartaglia, Rosalaura Sabetta, Monica Gargiulo, Giovanna Roncador, Federica Zito Marino, Renato Franco
Cancer stem cells (CSCs) are rare immortal cells within a tumor that can self-renew and drive tumorigenesis. CSCs play a pivotal role in the tumor development, progression and relapse, as well as in the resistance of anticancer therapy. Different tools could help in the analysis of CSCs, especially Immunohistochemistry (IHC) represents a useful technique able to identify several specific CSC markers. The main aims of this chapter are the description of the explain immunohistochemical methods used in the characterization of CSCs...
2018: Methods in Molecular Biology
Vivian Petersen Wagner, Manoela Domingues Martins, Rogerio Moraes Castilho
Chromatin decondensation is a key mechanism that guarantees gene transcription and repair of the genome, regulated mainly by the acetylation of histones. Emerging evidence has pointed out to histones as a new controlling mechanism of stem cell maintenance and fate. In this chapter, we will focus on the methods used to enrich tumor cell lines for cancer stem cells, and in the methods to identify the status of the histone acetylation in cancer cells and stem cells using immunofluorescence, invasion, and adhesion assays and identification of nuclear size...
2018: Methods in Molecular Biology
Maria Laura De Angelis, Ruggero De Maria, Marta Baiocchi
Banks of genetically characterized cancer stem cells (CSCs) isolated from individual patients and grown as spheroids offer an invaluable approach to identify genetic determinants of drug resistance versus sensitivity, and to study new stem cell-directed therapies. Here, we describe our standardized procedure for in vitro drug screening on colorectal CSCs, taking irinotecan as an example.
2018: Methods in Molecular Biology
Manuela Porru, Luca Pompili, Carla Caruso, Carlo Leonetti
The identification of experimental models that recapitulate human cancers designed to predict patient clinical response to therapies is a major break in oncology. Cancer stem cells (CSCs) represent a small tumor cell population responsible for drug resistance, where their effective killing may lead to identifying better treatment options. While the CSCs hypothesis highlights the need for a specific tumor target, patient-derived xenografts (PDXs) should also be considered for drug development as they better represent tumor heterogeneity and the environment in which a tumor develops...
2018: Methods in Molecular Biology
Hui Wang, Anna M Paczulla, Martina Konantz, Claudia Lengerke
Cancer stem cells (CSCs) are a subpopulation of cells within cancer tissues that are thought to mediate tumor initiation. CSCs are furthermore considered the cause of tumor progression and recurrence after conventional therapies, based on their enhanced therapy resistance properties. A method commonly used to assess CSC potential in vitro is the so-called tumor spheres assay in which cells are plated under non-adherent culture conditions in serum-free medium supplemented with growth factors. Tumor spheres assays have been used in cancer research as an intermediate in vitro cell culture model to be explored before performing more laborious in vivo tumor xenograft assays...
2018: Methods in Molecular Biology
Pooja Mehta, Caymen Novak, Shreya Raghavan, Maria Ward, Geeta Mehta
Cancer stem cells (CSC) are a vital component to the progression and reoccurrence of cancers, making them a primary target of study for both fundamental understanding of cancer biology and the development of effective and targeted treatments. CSCs reside in a complex 3D microenvironment, and the 3D spheroids are an indispensable tool in tumor biology due to their 3D structure and replication of the tumor microenvironment. Within this chapter the methodology for CSC isolation, suspension culture in hanging drop model, and characterization assays for CSC are described...
2018: Methods in Molecular Biology
Luigi Mele, Davide Liccardo, Virginia Tirino
The aldehyde dehydrogenase (ALDH) is a polymorphic enzyme responsible for the oxidation of aldehydes to carboxylic acids. In this chapter, it is described the role of ALDH in the identification of cancer stem cells (CSCs), having been shown that stem cells express high levels of ALDH. Here, we present a method called ALDEFLUOR assay used for the identification, evaluation, and isolation of normal, cancer stem and progenitor cells.
2018: Methods in Molecular Biology
Liang Wang, Xiangsheng Zuo, Keping Xie, Daoyan Wei
Solid tumors are composed of mutually interacting cancer cells and tumor microenvironment. Many environmental components, such as extracellular matrix (ECM), mesenchymal stem cells, endothelial and immune cells, and various growth factors and cytokines, provide signals, either stimulatory or inhibitory, to cancer cells and determine their fates. Meanwhile, cancer cells can also educate surrounding cells or tissues to undergo changes that are in favorable of tumor progression. CD44, as a transmembrane receptor for hyaluronic acid (HA) and many other ECM components and a coreceptor for growth factors and cytokines, is a critical cell surface molecule that can sense, integrate, and transduce cellular microenvironmental signals to membrane-associated cytoskeletal proteins or to cell nucleus to regulate a variety of gene expressions that govern cell behaviors...
2018: Methods in Molecular Biology
David Bakhshinyan, Ashley A Adile, Maleeha A Qazi, Mohini Singh, Michelle M Kameda-Smith, Nick Yelle, Chirayu Chokshi, Chitra Venugopal, Shiela K Singh
The Cancer Stem Cell (CSC) hypothesis postulates the existence of a small population of cancer cells with intrinsic properties allowing for resistance to conventional radiochemotherapy regiments and increased metastatic potential. Clinically, the aggressive nature of CSCs has been shown to correlate with increased tumor recurrence, metastatic spread, and overall poor patient outcome across multiple cancer subtypes. Traditionally, isolation of CSCs has been achieved through utilization of cell surface markers, while the functional differences between CSCs and remaining tumor cells have been described through proliferation, differentiation, and limiting dilution assays...
2018: Methods in Molecular Biology
Ying Wang, Yanli Xia, Dong Kuang, Yaqi Duan, Guoping Wang
AIMS: Previous studies have shown that stem cell factor (SCF) induces the migration of cardiac stem cells (CSCs) and helps to repair myocardial infarctions. Earlier studies on the migration mechanism only focused on the activation of kinases; here, we aimed to explore the functional role of protein phosphatase 2A (PP2A) in SCF-induced CSC migration. MAIN METHODS: CSCs were treated with SCF, PP2A enzymatic activity was measured, the phosphorylation levels of PP2A, p38 MAPK and cofilin were evaluated using western blot...
October 3, 2017: Life Sciences
Eduard Batlle, Hans Clevers
The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their identification and eradication has not been as obvious as was initially hoped. Recently developed lineage-tracing and cell-ablation strategies have provided insights into CSC plasticity, quiescence, renewal, and therapeutic response...
October 6, 2017: Nature Medicine
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