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https://www.readbyqxmd.com/read/29694896/high-dimensional-phenotyping-identifies-age-emergent-cells-in-human-mammary-epithelia
#1
Fanny A Pelissier Vatter, Denis Schapiro, Hang Chang, Alexander D Borowsky, Jonathan K Lee, Bahram Parvin, Martha R Stampfer, Mark A LaBarge, Bernd Bodenmiller, James B Lorens
Aging is associated with tissue-level changes in cellular composition that are correlated with increased susceptibility to disease. Aging human mammary tissue shows skewed progenitor cell potency, resulting in diminished tumor-suppressive cell types and the accumulation of defective epithelial progenitors. Quantitative characterization of these age-emergent human cell subpopulations is lacking, impeding our understanding of the relationship between age and cancer susceptibility. We conducted single-cell resolution proteomic phenotyping of healthy breast epithelia from 57 women, aged 16-91 years, using mass cytometry...
April 24, 2018: Cell Reports
https://www.readbyqxmd.com/read/29693155/assessing-stemness-and-proliferation-properties-of-the-newly-established-colon-cancer-stem-cell-line-csc480-and-novel-approaches-to-identify-dormant-cancer-cells
#2
Faisal Alowaidi, Saeed Mujahid Hashimi, Naif Alqurashi, Reem Alhulais, Saso Ivanovski, Bernadette Bellette, Adrian Meedenyia, Alfred Lam, Stephen Wood
To date two questions that remain unanswered regarding cancer are the following: i) how is it initiated, and ii) what is the role that cancer stem cells (CSCs) play in the disease process? Understanding the biology of CSCs and how they are generated is pivotal for the development of successful treatment regimens. To date, the lack of a representative cell model has prevented the successful identification and eradication of CSCs in vivo. The current methods of CSC identification are dependent on the protocol used to generate these cells, which has introduced variation and made the identification process more complicated...
April 23, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29688817/current-status-of-messenger-rna-delivery-systems
#3
Matthew G Stanton
Messenger RNA is emerging as a highly versatile biological construct for creation of impactful medicines. mRNA vaccines directed toward infectious disease and cancer are in clinical development with encouraging early reads on tolerability and efficacy. The use of mRNA to direct intense but transient expression of paracrine factors is finding utility in reprogramming progenitor cells for wound healing and cardiac regeneration and for stimulation of antitumor immune responses, at least preclinically as we await clinical results...
April 24, 2018: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/29682980/aging-and-senescence-associated-changes-of-mesenchymal-stromal-cells-in-myelodysplastic-syndromes
#4
Domenico Mattiucci, Giulia Maurizi, Pietro Leoni, Antonella Poloni
Hematopoietic stem and progenitor cells reside within the bone marrow (BM) microenvironment. By a well-balanced interplay between self-renewal and differentiation, they ensure a lifelong supply of mature blood cells. Physiologically, multiple different cell types contribute to the regulation of stem and progenitor cells in the BM microenvironment by cell-extrinsic and cell-intrinsic mechanisms. During the last decades, mesenchymal stromal cells (MSCs) have been identified as one of the main cellular components of the BM microenvironment holding an indispensable role for normal hematopoiesis...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29681544/dissecting-the-contributions-of-cooperating-gene-mutations-to-cancer-phenotypes-and-drug-responses-with-patient-derived-ipscs
#5
Chan-Jung Chang, Andriana G Kotini, Malgorzata Olszewska, Maria Georgomanoli, Julie Teruya-Feldstein, Henrik Sperber, Roberto Sanchez, Robert DeVita, Timothy J Martins, Omar Abdel-Wahab, Robert K Bradley, Eirini P Papapetrou
Connecting specific cancer genotypes with phenotypes and drug responses constitutes the central premise of precision oncology but is hindered by the genetic complexity and heterogeneity of primary cancer cells. Here, we use patient-derived induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 genome editing to dissect the individual contributions of two recurrent genetic lesions, the splicing factor SRSF2 P95L mutation and the chromosome 7q deletion, to the development of myeloid malignancy. Using a comprehensive panel of isogenic iPSCs-with none, one, or both genetic lesions-we characterize their relative phenotypic contributions and identify drug sensitivities specific to each one through a candidate drug approach and an unbiased large-scale small-molecule screen...
April 17, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29679075/apkc%C3%AE-dependent-repression-of-yap-is-necessary-for-functional-restoration-of-irradiated-salivary-glands-with-igf-1
#6
Alejandro M Chibly, Wen Yu Wong, Maricela Pier, Hongqiang Cheng, Yongxin Mu, Ju Chen, Sourav Ghosh, Kirsten H Limesand
Xerostomia and salivary hypofunction often result as a consequence of radiation therapy for head and neck cancers, which are diagnosed in roughly 60,000 individuals every year in the U.S. Due to the lack of effective treatments for radiation-induced salivary hypofunction, stem cell-based therapies have been suggested to regenerate the irradiated salivary glands. Pharmacologically, restoration of salivary gland function has been accomplished in mice by administering IGF-1 shortly after radiation treatment, but it is not known if salivary stem and progenitor cells play a role...
April 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29677215/tracking-the-fate-of-adoptively-transferred-myeloid-derived-suppressor-cells-in-the-primary-breast-tumor-microenvironment
#7
Jaclyn Sceneay, Christoph M Griessinger, Sabrina H L Hoffmann, Shu Wen Wen, Christina S F Wong, Sophie Krumeich, Manfred Kneilling, Bernd J Pichler, Andreas Möller
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid progenitor cells that are expanded in cancer and act as potent suppressors of the anti-tumor immune response. MDSCs consist of two major subsets, namely monocytic (M-) MDSCs and granulocytic (G-) MDSCs that differ with respect to their phenotype, morphology and mechanisms of suppression. Here, we cultured bone marrow cells with IL-6 and GM-CSF in vitro to generate a population of bone marrow MDSCs (BM-MDSCs) similar to G-MDSCs from tumor-bearing mice in regards to phenotype, morphology and suppressive-function...
2018: PloS One
https://www.readbyqxmd.com/read/29674122/4-fluorobenzaldehyde-limonene-based-thiosemicarbazone-induces-apoptosis-in-pc-3-human-prostate-cancer-cells
#8
Bruna Dos Santos Rodrigues, Renato Ivan de Ávila, Polyana Lopes Benfica, Ludmila Pires Bringel, Cecília Maria Alves de Oliveira, Fábio Vandresen, Cleuza Conceição da Silva, Marize Campos Valadares
AIMS: This study evaluated parameters of toxicity and antiproliferative effects of (+)-N(1)-4-fluorobenzaldehyde-N(4)-{1-methyl-1-[(1R)-4-methylcyclohexene-3-il]-ethyl}-thiossemicarbazone (4-FTSC) in PC-3 adenocarcinoma prostate cells. MAIN METHODS: Cytotoxicity of 4-FTSC in PC-3 cells was evaluated using MTT assay. Morphology examination of PC-3 cells treated with 4-FTSC was also performed as well as the cell death mechanisms induced were investigated using flow cytometry...
April 16, 2018: Life Sciences
https://www.readbyqxmd.com/read/29668670/exosomes-released-by-gastric-cancer-cells-induce-transition-of-pericytes-into-cancer-associated-fibroblasts
#9
Xiaofei Ning, Hongran Zhang, Cong Wang, Xiuqi Song
BACKGROUND Cancer-associated fibroblasts (CAFs) are functionally and structurally essential for tumor progression. There are 3 main origins of CAFs: mesenchymal stem cells (MSCs), epithelial-to-mesenchymal (EMT) transition cells, and tissue-resident cells. Pericytes retain characteristics of progenitor cells and can differentiate into other cells under normal physiological conditions and into myofibroblasts under pathological conditions. Exosomes play an important role in intercellular communication by transferring membrane components and nucleic acids between different cells...
April 18, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29663717/salivary-gland-stem-cells-a-review-of-development-regeneration-and-cancer
#10
REVIEW
Elaine Emmerson, Sarah M Knox
Salivary glands are responsible for maintaining the health of the oral cavity and are routinely damaged by therapeutic radiation for head and neck cancer as well as by autoimmune diseases such as Sjögren's syndrome. Regenerative approaches based on the reactivation of endogenous stem cells or the transplant of exogenous stem cells hold substantial promise in restoring the structure and function of these organs to improve patient quality of life. However, these approaches have been hampered by a lack of knowledge on the identity of salivary stem cell populations and their regulators...
April 16, 2018: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/29660313/the-convergent-roles-of-cd271-p75-in-neural-crest-derived-melanoma-plasticity
#11
Jennifer C Kasemeier-Kulesa, Paul M Kulesa
The embryonic microenvironment is an important source of signals that promote multipotent cells to adopt a specific fate and direct cells along distinct migratory pathways. Yet, the ability of the embryonic microenvironment to retain multipotent progenitors or reprogram de-differentiated cells is less clear. Mistakes in cell differentiation or migration often result in developmental defects and tumorigenesis, including aggressive cancers that share many characteristics with embryonic progenitor cells. This is a striking feature of the vertebrate neural crest, a multipotent and highly migratory cell population first identified by Wilhelm His (His, 1868) with the potential to metamorphose into aggressive melanoma cancer...
April 13, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29659011/immune-system-augmentation-via-humanization-using-stem-progenitor-cells-and-bioengineering-in-a-breast-cancer-model-study
#12
Abbas Shafiee, Jacqui A McGovern, Christoph A Lahr, Christoph Meinert, Davide Moi, Ferdinand Wagner, Marietta Landgraf, Elena De-Juan-Pardo, Roberta Mazzieri, Dietmar W Hutmacher
Despite significant advances, most current in vivo models fail to fully recapitulate the biological processes that occur in humans. Here we aimed to develop an advanced humanized model with features of an organ bone by providing different bone tissue cellular compartments including pre-osteoblasts, mesenchymal stem/stromal (MSCs), endothelial and hematopoietic cells in an engineered microenvironment. The bone compartment was generated by culturing the human MSCs, umbilical vein endothelial cells with gelatin methacryloyl hydrogels in the centre of a melt-electrospun polycaprolactone tubular scaffolds which were seeded with human pre-osteoblasts...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29655982/polyprenylated-polycyclic-acylphloroglucinol-angiogenesis-inhibitor-from-garcinia-multiflora
#13
Lin-Yang Cheng, Chun-Lin Chen, Yueh-Hsiung Kuo, Tsung-Hsien Chang, I-Wei Lin, Shih-Wei Wang, Mei-Ing Chung, Jih-Jung Chen
A new polyprenylated polycyclic acylphloroglucinol, garcimultiflorone K (1), has been isolated from the stems of Garcinia multiflora, together with two known compounds, garcimultiflorone A (2) and garcimultiflorone B (3). The structure of new compound 1 was determined through spectroscopic methods including 1D and 2D NMR and MS analyses. The anti-angiogenic and anti-cancer effects of compounds 1-3 were evaluated in human endothelial progenitor cells (EPCs) and cancer cells. Of these, garcimultiflorone K (1) displayed the most potent anti-angiogenic property by suppressing cell growth and tube formation of EPCs...
April 6, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29650953/hsp27-is-a-partner-of-jak2-stat5-and-a-potential-therapeutic-target-in-myelofibrosis
#14
Margaux Sevin, Lucia Kubovcakova, Nicolas Pernet, Sébastien Causse, Franck Vitte, Jean Luc Villeval, Catherine Lacout, Marine Cordonnier, Fernando Rodrigues-Lima, Gaétan Chanteloup, Matthieu Mosca, Marie-Lorraine Chrétien, Jean Noël Bastie, Sylvain Audia, Paul Sagot, Selim Ramla, Laurent Martin, Martin Gleave, Valérie Mezger, Radek Skoda, Isabelle Plo, Carmen Garrido, François Girodon, Aurélie de Thonel
Heat shock protein 27 (HSP27/HSPB1) is a stress-inducible chaperone that facilitates cancer development by its proliferative and anti-apoptotic functions. The OGX-427 antisense oligonucleotide against HSP27 has been reported to be beneficial against idiopathic pulmonary fibrosis. Here we show that OGX-427 is effective in two murine models of thrombopoietin- and JAKV617F-induced myelofibrosis. OGX-427 limits disease progression and is associated with a reduction in spleen weight, in megakaryocyte expansion and, for the JAKV617F model, in fibrosis...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29648645/does-human-endometrial-lgr5-gene-expression-suggest-the-existence-of-another-hormonally-regulated-epithelial-stem-cell-niche
#15
N Tempest, A M Baker, N A Wright, D K Hapangama
STUDY QUESTION: Is human endometrial leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) gene expression limited to the postulated epithelial stem cell niche, stratum basalis glands, and is it hormonally regulated? SUMMARY ANSWER: LGR5 expressing cells are not limited to the postulated stem cell niche but LGR5 expression is hormonally regulated. WHAT IS KNOWN ALREADY: The human endometrium is a highly regenerative tissue; however, endometrial epithelial stem cell markers are yet to be confirmed...
April 10, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29644711/outlining-involvement-of-stem-cell-program-in-regulation-of-o6-methylguanine-dna-methyltransferase-and-development-of-temozolomide-resistance-in-glioblastoma-an-editorial-highlight-for-transcriptional-control-of-o-6-methylguanine-dna-methyltransferase-expression
#16
EDITORIAL
Anastasia Chumakova, Justin D Lathia
Glioblastoma is a malignant brain tumor that inevitably develops resistance to standard of care drug temozolomide (TMZ) due to a population of cells called cancer stem cells (CSCs). These cells utilize progenitor cell signaling programs and develop robust DNA repair machinery. In this editorial highlight we focus on stem cell regulation of TMZ resistance and discuss findings of Happold et al. () that outline direct transcriptional regulation of DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) in glioblastoma CSCs through NFkB activation...
March 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29644495/does-the-mouse-mammary-gland-arise-from-unipotent-or-multipotent-mammary-stem-progenitor-cells
#17
REVIEW
Gilbert H Smith, Daniel Medina
The presence of long-lived lineage restricted progenitor and multipotent progenitor cells in adult mouse mammary gland for cancer development is compelling. Mammary cancers are phenotypically diverse This might be explained by transformation of long-lived, lineage-limited progenitor subpopulations. Mammary multipotent epithelial stem cells and their environmental niches must be considered, since their niche(s), once empty might be occupied by lineage-limited progenitors that are proximal. The existence of premalignant mammary populationst that manifest characteristics of lineage limitation argues strongly for this proposition...
April 11, 2018: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/29642644/wnt-signaling-in-thyroid-homeostasis-and-carcinogenesis
#18
REVIEW
Kim A Ely, Lindsay A Bischoff, Vivian L Weiss
The Wnt pathway is essential for stem cell maintenance, but little is known about its role in thyroid hormone signaling and thyroid stem cell survival and maintenance. In addition, the role of Wnt signaling in thyroid cancer progenitor cells is also unclear. Here, we present emerging evidence for the role of Wnt signaling in somatic thyroid stem cell and thyroid cancer stem cell function. An improved understanding of the role of Wnt signaling in thyroid physiology and carcinogenesis is essential for improving both thyroid disease diagnostics and therapeutics...
April 10, 2018: Genes
https://www.readbyqxmd.com/read/29642503/migration-invasion-of-malignant-gliomas-and-implications-for-therapeutic-treatment
#19
REVIEW
Ching-Ann Liu, Chia-Yu Chang, Kuo-Wei Hsueh, Hong-Lin Su, Tzyy-Wen Chiou, Shinn-Zong Lin, Horng-Jyh Harn
Malignant tumors of the central nervous system (CNS) are among cancers with the poorest prognosis, indicated by their association with tumors of high-level morbidity and mortality. Gliomas, the most common primary CNS tumors that arise from neuroglial stem or progenitor cells, have estimated annual incidence of 6.6 per 100,000 individuals in the USA, and 3.5 per 100,000 individuals in Taiwan. Tumor invasion and metastasis are the major contributors to the deaths in cancer patients. Therapeutic goals including cancer stem cells (CSC), phenotypic shifts, EZH2/AXL/TGF-β axis activation, miRNAs and exosomes are relevant to GBM metastasis to develop novel targeted therapeutics for GBM and other brain cancers...
April 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29628445/the-telomerase-inhibitor-azt-enhances-differentiation-and-prevents-overgrowth-of-human-pluripotent-stem-cell-derived-neural-progenitors
#20
Yao Hu, Kai-Heng Fang, Lu-Ping Shen, Shi-Ying Cao, Fang Yuan, Yuwen Su, Min Xu, Yaoyu Chen, Yan Liu
Human pluripotent stem cell (hPSC)-based cell-replacement therapy has emerged as a promising approach for addressing numerous neurological diseases. However, hPSC transplantation has the potential to cause human cell overgrowth and cancer, which represents a major obstacle to implementing hPSC-based therapies. Inhibition of the overgrowth of transplanted cells could help reduce the risk for hPSC transplantation-induced tumorigenesis. In this study, we report that the telomerase inhibitor azidothymidine (3'-azido-3'-deoxythymidine, AZT) enhances the differentiation of cortical neurons and significantly suppresses the proliferation of hPSC-derived cortical progenitors...
April 8, 2018: Journal of Biological Chemistry
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