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https://www.readbyqxmd.com/read/29150846/cancer-stem-cells-as-targets-for-immunotherapy
#1
REVIEW
Amy S Codd, Takayuki Kanaseki, Toshihiko Torigo, Zsuzsanna Tabi
Current cancer therapies target the bulk of the tumour, while a population of highly resistant tumour cells may be able to repopulate the tumour and metastasise to new sites. Cancer cells with such stem cell-like characteristics can be identified based on their phenotypic and/or functional features which may open up ways for their targeted elimination. In this review we discuss potential off-target effects of inhibiting cancer stem-cell self-renewal pathways on immune cells, and summarise some recent immunological studies specifically targeting cancer stem cells based on their unique antigen expression...
November 18, 2017: Immunology
https://www.readbyqxmd.com/read/29147753/defective-wnt-signaling-associates-with-bone-marrow-fibrosis-a-cross-sectional-cohort-study-in-a-family-with-wnt1-osteoporosis
#2
R E Mäkitie, R Niinimäki, S Kakko, T Honkanen, P E Kovanen, O Mäkitie
This study explores bone marrow function in patients with defective WNT1 signaling. Bone marrow samples showed increased reticulin and altered granulopoiesis while overall hematopoiesis was normal. Findings did not associate with severity of osteoporosis. These observations provide new insight into the role of WNT signaling in bone marrow homeostasis. INTRODUCTION: WNT signaling regulates bone homeostasis and survival and self-renewal of hematopoietic stem cells. Aberrant activation may lead to osteoporosis and bone marrow pathology...
November 16, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/29147018/enforced-gfi1-expression-impedes-human-and-murine-leukemic-cell-growth
#3
Judith M Hönes, Aniththa Thivakaran, Lacramioara Botezatu, Pradeep Patnana, Symone Vitoriano da Conceição Castro, Yahya S Al-Matary, Judith Schütte, Karen B I Fischer, Lothar Vassen, André Görgens, Ulrich Dührsen, Bernd Giebel, Cyrus Khandanpour
The differentiation of haematopoietic cells is regulated by a plethora of so-called transcription factors (TFs). Mutations in genes encoding TFs or graded reduction in their expression levels can induce the development of various malignant diseases such as acute myeloid leukaemia (AML). Growth Factor Independence 1 (GFI1) is a transcriptional repressor with key roles in haematopoiesis, including regulating self-renewal of haematopoietic stem cells (HSCs) as well as myeloid and lymphoid differentiation. Analysis of AML patients and different AML mouse models with reduced GFI1 gene expression levels revealed a direct link between low GFI1 protein level and accelerated AML development and inferior prognosis...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29144570/lncapc-drives-wnt-%C3%AE-catenin-activation-and-liver-tic-self-renewal-through-ezh2-mediated-apc-transcriptional-inhibition
#4
Xiaomin Fu, Jizhen Lin, Fujun Qin, Zihe Yang, Yuechao Ding, Yong Zhang, Lu Han, Xiaoyan Zhu, Qinxian Zhang
Liver tumor initiating cells (TICs), a small subset cells in tumor bulk, are responsible for liver tumor initiation, metastasis and relapse. However, the regulatory mechanism of liver TICs remains largely unknown. Here we found a long noncoding RNA lncAPC, locating near from APC locus, was highly expressed in liver cancer and liver TICs. LncAPC was required for liver TIC self-renewal. Silencing and overexpressing lncAPC showed impaired and enhanced sphere formation capacity of liver TICs, respectively. By recruiting EZH2 to APC promoter, LncAPC inhibits APC transcription and thus drives the activation of Wnt/β-catenin signaling...
November 16, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29144448/regeneration-of-the-entire-human-epidermis-using-transgenic-stem-cells
#5
Tobias Hirsch, Tobias Rothoeft, Norbert Teig, Johann W Bauer, Graziella Pellegrini, Laura De Rosa, Davide Scaglione, Julia Reichelt, Alfred Klausegger, Daniela Kneisz, Oriana Romano, Alessia Secone Seconetti, Roberta Contin, Elena Enzo, Irena Jurman, Sonia Carulli, Frank Jacobsen, Thomas Luecke, Marcus Lehnhardt, Meike Fischer, Maximilian Kueckelhaus, Daniela Quaglino, Michele Morgante, Silvio Bicciato, Sergio Bondanza, Michele De Luca
Junctional epidermolysis bullosa (JEB) is a severe and often lethal genetic disease caused by mutations in genes encoding the basement membrane component laminin-332. Surviving patients with JEB develop chronic wounds to the skin and mucosa, which impair their quality of life and lead to skin cancer. Here we show that autologous transgenic keratinocyte cultures regenerated an entire, fully functional epidermis on a seven-year-old child suffering from a devastating, life-threatening form of JEB. The proviral integration pattern was maintained in vivo and epidermal renewal did not cause any clonal selection...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29143796/angelica-sinensis-polysaccharides-ameliorate-stress-induced-premature-senescence-of-hematopoietic-cell-via-protecting-bone-marrow-stromal-cells-from-oxidative-injuries-caused-by-5-fluorouracil
#6
Hanxianzhi Xiao, Lirong Xiong, Xiaoying Song, Pengwei Jin, Linbo Chen, Xiongbin Chen, Hui Yao, Yaping Wang, Lu Wang
Myelosuppression is the most common complication of chemotherapy. Decline of self-renewal capacity and stress-induced premature senescence (SIPS) of hematopoietic stem cells (HSCs) induced by chemotherapeutic agents may be the cause of long-term myelosuppression after chemotherapy. Whether the mechanism of SIPS of hematopoietic cells relates to chemotherapeutic injury occurred in hematopoietic microenvironment (HM) is still not well elucidated. This study explored the protective effect of Angelica sinensis polysaccharide (ASP), an acetone extract polysaccharide found as the major effective ingredients of a traditional Chinese medicinal herb named Chinese Angelica (Dong Quai), on oxidative damage of homo sapiens bone marrow/stroma cell line (HS-5) caused by 5-fluorouracil (5-FU), and the effect of ASP relieving oxidative stress in HM on SIPS of hematopoietic cells...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29143345/lin28a-enhances-in-vitro-osteoblastic-differentiation-of-human-periosteum-derived-cells
#7
Jin-Ho Park, Bong-Wook Park, Young-Hoon Kang, Sung-Hoon Byun, Sun-Chul Hwang, Deok Ryong Kim, Dong Kyun Woo, June-Ho Byun
Despite a capacity for proliferation and an ability to differentiate into multiple cell types, in long-term culture and with ageing, stem cells show a reduction in growth, display a decrease in differentiation potential, and enter senescence without evidence of transformation. The Lin28a gene encodes an RNA-binding protein that plays a role in regulating stem cell activity, including self-renewal and differentiation propensity. However, the effect of the Lin28a gene on cultured human osteoprecursor cells is poorly understood...
November 16, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29142785/role-of-cord-blood-and-bone-marrow-mesenchymal-stem-cells-in-recent-deep-burn-a-case-control-prospective-study
#8
Wael Abo-Elkheir, Fawzy Hamza, Ahmed M Elmofty, Atef Emam, Magdy Abdl-Moktader, Sameh Elsherefy, Hala Gabr
RATIONALE: Burn injuries represent one of the major worldwide public health problems causing more severe physiological stress than other traumas. Effective treatment of burn injuries is mandatory to prevent the numerous life-threatening complications and possible disabilities. Stem cells, a population of multipotent cells retaining the properties of self-renewal and differentiation, are the main player in tissue regeneration after major trauma. Thus, they are thought to play a key role in wound healing inducing efficient and physiological skin regeneration...
2017: American Journal of Stem Cells
https://www.readbyqxmd.com/read/29142594/micrornas-a-subpopulation-of-regulators-are-involved-in-breast-cancer-progression-through-regulating-breast-cancer-stem-cells
#9
Xuemei Fan, Wei Chen, Ziyi Fu, Lihua Zeng, Yongmei Yin, Hongyan Yuan
Cancer stem cells (CSCs; also known as tumor-initiating cells) are essential effectors of tumor progression due to their self-renewal capacity, differentiation potential, tumorigenic ability and resistance to chemotherapy, all of which contribute to cancer relapse, metastasis and a poor prognosis. Breast cancer stem cells (BCSCs) have been identified to be involved in the processes of BC initiation, growth and recurrence. MicroRNAs (miRNAs) are a class of non-coding small RNAs of 19-23 nucleotides in length that regulate gene expression at the post-transcriptional level through various mechanisms, and serve critical roles in cancer progression...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29141956/rapid-isolation-and-expansion-of-skin-derived-precursor-cells-from-human-primary-fibroblast-cultures
#10
Leithe Budel, Karima Djabali
Skin-derived precursor (SKP) cells have self-renewal and multipotent abilities and are found in the dermis. SKP cells have been isolated previously from pre-established dermal fibroblast cultures. In these procedures, long-term culture and low yield remain the crucial aspects requiring improvement. In this study, we exposed pre-established dermal fibroblasts to 30-min acid stress prior to isolating SKP cells (termed pH-SKP) and compared the yield to the previously published trypsin- and no-stress methods. Spheroid formation was confirmed and analyzed at days 3, 5 and 7...
November 15, 2017: Biology Open
https://www.readbyqxmd.com/read/29141947/aging-of-hematopoietic-stem-cells
#11
Gerald de Haan, Seka Lazare
Hematopoietic stem cells (HSCs) ensure a balanced production of all blood cells throughout life. As they age, HSCs gradually lose their self-renewal and regenerative potential, while the occurrence of cellular derailment strongly increases. Here we review our current understanding of the molecular mechanisms that contribute to HSC aging. We argue that most of the causes that underlie HSC aging result from cell-intrinsic pathways, and reflect on which aspects of the aging process may be reversible. As many hematological pathologies are strongly age-associated, strategies to intervene in aspects of the stem cell aging process may have significant clinical relevance...
November 15, 2017: Blood
https://www.readbyqxmd.com/read/29141553/epigenetic-regulation-of-gene-expression-in-epithelial-stem-cells-fate
#12
Hongyu Li, Dixin Cui, Si Wu, Xin Xu, Ling Ye, Xuedong Zhou, Mian Wan, Liwei Zheng
BACKGROUND: Epithelial tissues have the ability to self-renew throughout animal's life due to the presence of the epithelial stem cells. Except for complicated genes regulation, the fate of epithelial stem cells is also regulated by the epigenetics, including DNA methylation, histone modification and microRNAs, which are emerging as vital elements of epigenetic regulation for epithelial stem cells self-renewal and differentiation. However, the mechanisms underlying these are still poorly understood...
November 15, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29139178/notch1-and-notch2-coordinately-regulate-stem-cell-function-in-the-quiescent-and-activated-states-of-muscle-satellite-cells
#13
Shin Fujimaki, Daiki Seko, Yasuo Kitajima, Kiyoshi Yoshioka, Yoshifumi Tsuchiya, Shinya Masuda, Yusuke Ono
Satellite cells, the muscle tissue stem cells, express three Notch receptors (Notch1-3). The function of Notch1 and Notch2 in satellite cells has to date not been fully evaluated. We investigated the role of Notch1 and Notch2 in myogenic progression in adult skeletal muscle using tamoxifen-inducible satellite cell-specific conditional knockout mice for Notch1 (N1-scKO), Notch2 (N2-scKO), and Notch1/Notch2 (scDKO). In the quiescent state, the number of satellite cells was slightly reduced in N2-scKO, but not significantly in N1-scKO, and almost completely depleted in scDKO mice...
November 15, 2017: Stem Cells
https://www.readbyqxmd.com/read/29139089/cancer-stem-cells-in-head-and-neck-carcinomas-identification-and-possible-therapeutic-implications
#14
Elize Wolmarans, Sonja C Boy, Sulette Nel, Anne E Mercier, Michael Sean Pepper
The recurrence and/or lack of response of certain tumors to radio- and chemotherapy has been attributed to a small subpopulation of cells termed cancer stem cells (CSCs). CSCs have been identified in many tumors (including solid and hematological tumors). CSCs are characterized by their capacity for self-renewal, their ability to introduce heterogeneity within a tumor mass and its metastases, genomic instability, and their insensitivity to both radiation and chemotherapy. The latter highlights the clinical importance of studying this subpopulation since their resistance to traditional treatments may lead to metastatic disease and/or tumor relapse...
November 15, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29138851/nrp1-positive-lung-cancer-cells-possess-tumor-initiating-properties
#15
Luis E Jimenez-Hernandez, Karla Vazquez-Santillan, Rosario Castro-Oropeza, Gustavo Martinez-Ruiz, Laura Muñoz-Galindo, Carolina Gonzalez-Torres, Carlo C Cortes-Gonzalez, Georgina Victoria-Acosta, Jorge Melendez-Zajgla, Vilma Maldonado
Tumor-initiating cells possess the capacity for self-renewal and to create heterogeneous cell lineages within a tumor. Therefore, the identification and isolation of cancer stem cells is an essential step in the analysis of their biology. The aim of the present study was to determine whether the cell surface protein neuropilin 1 (NRP1) can be used as a biomarker of stem-like cells in lung cancer tumors. For this purpose, NRP1-negative (NRP1-) and NRP1-positive (NRP1+) cell subpopulations from two lung cancer cell lines were sorted by flow cytometry...
November 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29138837/vegf-secreted-by-mesenchymal-stem-cells-mediates-the-differentiation-of-endothelial-progenitor-cells-into-endothelial-cells-via-paracrine-mechanisms
#16
Quanhu Ge, Hongwei Zhang, Jixue Hou, Longfei Wan, Wenzhe Cheng, Xiaoyi Wang, Dan Dong, Congzhe Chen, Jie Xia, Jun Guo, Xueling Chen, Xiangwei Wu
Stem cell therapy is a promising treatment strategy for ischemic diseases. Mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) adhere to each other in the bone marrow cavity and in in vitro cultures. We have previously demonstrated that the adhesion between MSCs and EPCs is critical for MSC self‑renewal and their multi‑differentiation into osteoblasts and chondrocytes. In the present study, the influence of the indirect communication between EPCs and MSCs on the endothelial differentiation potential of EPCs was investigated, and the molecular mechanisms underlying MSC‑mediated EPC differentiation were explored...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138802/in-vitro-investigation-of-the-mechanism-underlying-the-effect-of-ginsenoside-on-the-proliferation-and-differentiation-of-neural-stem-cells-subjected-to-oxygen-glucose-deprivation-reperfusion
#17
Jian Gao, Huajing Bai, Qiang Li, Jian Li, Feng Wan, Mo Tian, Yuanyuan Li, Yilun Song, Jianping Zhang, Yinchu Si
The present study comprised a series of experiments to investigate the mechanism underlying the effect of ginsenoside on the self-renewal, proliferation and differentiation of neural stem cells (NSCs) undergoing oxygen-glucose deprivation/reperfusion (OGD/R) in vitro. The NSCs, which were isolated from the hippocampus of embryonic day 17 embryo rats, were subjected to OGD/R to establish an in vitro model of brain ischemia-reperfusion, following which different doses of ginsenoside were administered to the model...
November 13, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29138265/targeted-delivery-of-stat-3-modulator-to-breast-cancer-stem-like-cells-down-regulates-a-series-of-stem-ness-genes
#18
Santosh K Misra, Arun De, Dipanjan Pan
Cancer stem cells are known to be controlled by pathways that are dormant in normal adult cells, e.g. PTEN, which is a negative regulator of transcription factor STAT3. STAT3 regulates genes that are involved in stem cell self-renewal and thus represents a novel therapeutic target of enormous clinical significance. Studies on breast cancer stem cells (BCSCs) have been also significantly correlated with STATs. We describe here for the first time a novel strategy to selectively target CSCs and to induce downregulation of STAT3 downstream target genes reducing expression of series of 'stem-ness genes' in treated tumors...
November 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29137597/reduction-of-pluripotent-gene-expression-in-murine-embryonic-stem-cells-exposed-to-mechanical-loading-or-cyclo-rgd-peptide
#19
Olesja Hazenbiller, Neil A Duncan, Roman J Krawetz
BACKGROUND: Self-renewal and differentiation of embryonic stem cells (ESCs) is directed by biological and/or physical cues that regulate multiple signaling cascades. We have previously shown that mESCs seeded in a type I collagen matrix demonstrate a loss of pluripotent marker expression and differentiate towards an osteogenic lineage. In this study, we examined if this effect was mediated in part through Arginylglycylaspartic acid (RGD) dependent integrin activity and/or mechano-transduction...
November 14, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/29137267/tumacrophage-macrophages-transformed-into-tumor-stem-like-cells-by-virulent-genetic-material-from-tumor-cells
#20
Yizhuang Zhang, Na Zhou, Xiuyan Yu, Xuehui Zhang, Shanxin Li, Zhen Lei, Ruobi Hu, Hui Li, Yiqing Mao, Xi Wang, Jinshu Zhang, Yuan Li, Hongyan Guo, David M Irwin, Gang Niu, Huanran Tan
Tumor-associated macrophages are regarded as tumor-enhancers as they have key roles in the subversion of adaptive immunity and in inflammatory circuits that promote tumor progression. Here, we show that cancer cells can subvert macrophages yielding cells that have gained pro-tumor functions. When macrophages isolated from mice or humans are co-cultured with dead cancer cell line cells, induced to undergo apoptosis to mimic chemotherapy, up-regulation of pro-tumor gene expression was identified. Phagocytosis of apoptotic cancer cells by macrophages resulted in their transformation into tumor stem (initiating)-like cells, as indicated by the expression of epithelial markers (e...
October 10, 2017: Oncotarget
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