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https://www.readbyqxmd.com/read/29238067/alternative-nhej-pathway-proteins-as-components-of-mycn-oncogenic-activity-in-human-neural-crest-stem-cell-differentiation-implications-for-neuroblastoma-initiation
#1
Erika A Newman, Sahiti Chukkapalli, Daniela Bashllari, Tina T Thomas, Raelene A Van Noord, Elizabeth R Lawlor, Mark J Hoenerhoff, Anthony W Opipari, Valerie P Opipari
Neuroblastoma is a cancer of neural crest stem cell (NCSC) lineage. Signaling pathways that regulate NCSC differentiation have been implicated in neuroblastoma tumorigenesis. This is exemplified by MYCN oncogene targets that balance proliferation, differentiation, and cell death similarly in normal NCSC and in high-risk neuroblastoma. Our previous work discovered a survival mechanism by which MYCN-amplified neuroblastoma circumvents cell death by upregulating components of the error-prone non-canonical alternative nonhomologous end-joining (alt-NHEJ) DNA repair pathway...
December 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29233928/integrated-molecular-characterization-of-the-lethal-pediatric-cancer-pancreatoblastoma
#2
Tomoya Isobe, Masafumi Seki, Kenichi Yoshida, Masahiro Sekiguchi, Yusuke Shiozawa, Yuichi Shiraishi, Shunsuke Kimura, Misa Yoshida, Yoshikage Inoue, Akira Yokoyama, Nobuyuki Kakiuchi, Hiromichi Suzuki, Keisuke Kataoka, Yusuke Sato, Tomoko Kawai, Kenichi Chiba, Hiroko Tanaka, Teppei Shimamura, Motohiro Kato, Akihiro Iguchi, Asahito Hama, Tomoaki Taguchi, Masaharu Akiyama, Junya Fujimura, Akiko Inoue, Tsuyoshi Ito, Takao Deguchi, Chikako Kiyotani, Tomoko Iehara, Hajime Hosoi, Akira Oka, Masashi Sanada, Yukichi Tanaka, Kenichiro Hata, Satoru Miyano, Seishi Ogawa, Junko Takita
Pancreatoblastoma (PBL) is a rare pediatric pancreatic malignancy for which the molecular pathogenesis is not understood. In this study, we report the findings of an integrated multi-omics study of whole exome and RNA sequencing as well as genome-wide copy number and methylation analyses of 10 PBL cases. The PBL genome was characterized by a high frequency of aberrant activation of the Wnt signaling pathway, either via somatic mutations of CTNNB1 (90%) and copy-neutral loss of heterozygosity (CN-LOH) of APC (10%)...
December 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/29233553/breast-cancers-activate-stromal-fibroblast-induced-suppression-of%C3%A2-progenitors-in-adjacent-normal-tissue
#3
Sumanta Chatterjee, Pratima Basak, Edward Buchel, Janice Safneck, Leigh C Murphy, Michael Mowat, Sam K Kung, Peter Eirew, Connie J Eaves, Afshin Raouf
Human breast cancer cells are known to activate adjacent "normal-like" cells to enhance their own growth, but the cellular and molecular mechanisms involved are poorly understood. We now show by both phenotypic and functional measurements that normal human mammary progenitor cells are significantly under-represented in the mammary epithelium of patients' tumor-adjacent tissue (TAT). Interestingly, fibroblasts isolated from TAT samples showed a reduced ability to support normal EGF-stimulated mammary progenitor cell proliferation in vitro via their increased secretion of transforming growth factor β...
December 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29232628/epithelial-plasticity-in-the-mammary-gland
#4
REVIEW
Lindsey Seldin, Armelle Le Guelte, Ian G Macara
Many epithelial tissues rely on multipotent stem cells for the proper development and maintenance of their diverse cell lineages. Nevertheless, the identification of multipotent stem cell populations within the mammary gland has been a point of contention over the past decade. In this review, we provide a critical overview of the various lineage-tracing studies performed to address this issue and conclude that although multipotent stem cells exist in the embryonic mammary placode, the postnatal mammary gland instead contains distinct unipotent progenitor populations that contribute to stage-specific development and homeostasis...
December 9, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29229583/integrative-genomic-analysis-of-coincident-cancer-foci-implicates-ctnnb1-and-pten-alterations-in-ductal-prostate-cancer
#5
Marc Gillard, Justin Lack, Andrea Pontier, Divya Gandla, David Hatcher, Adam G Sowalsky, Jose Rodriguez-Nieves, Donald Vander Griend, Gladell Paner, David VanderWeele
BACKGROUND: Ductal adenocarcinoma of the prostate is an aggressive subtype, with high rates of biochemical recurrence and overall poor prognosis. It is frequently found coincident with conventional acinar adenocarcinoma. The genomic features driving evolution to its ductal histology and the biology associated with its poor prognosis remain unknown. OBJECTIVE: To characterize genomic features distinguishing ductal adenocarcinoma from coincident acinar adenocarcinoma foci from the same patient...
December 8, 2017: European Urology Focus
https://www.readbyqxmd.com/read/29225342/differentiation-dynamics-of-mammary-epithelial-cells-revealed-by-single-cell-rna%C3%A2-sequencing
#6
Karsten Bach, Sara Pensa, Marta Grzelak, James Hadfield, David J Adams, John C Marioni, Walid T Khaled
Characterising the hierarchy of mammary epithelial cells (MECs) and how they are regulated during adult development is important for understanding how breast cancer arises. Here we report the use of single-cell RNA sequencing to determine the gene expression profile of MECs across four developmental stages; nulliparous, mid gestation, lactation and post involution. Our analysis of 23,184 cells identifies 15 clusters, few of which could be fully characterised by a single marker gene. We argue instead that the epithelial cells-especially in the luminal compartment-should rather be conceptualised as being part of a continuous spectrum of differentiation...
December 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29223442/exosomes-derived-from-imatinib-resistant-chronic-myeloid-leukemia-cells-mediate-a-horizontal-transfer-of-drug-resistant-trait-by-delivering-mir-365
#7
Qing-Hua Min, Xiao-Zhong Wang, Jing Zhang, Qing-Gen Chen, Shu-Qi Li, Xiao-Qing Liu, Jing Li, Jing Liu, Wei-Ming Yang, Yu-Huan Jiang, Yan-Mei Xu, Jin Lin, Qiu-Fang Gao, Fan Sun, Lei Zhang, Bo Huang
Chronic myeloid leukemia (CML) is a malignant disorder of hematopoietic stem/progenitor cells. Majority of patients can be effectively treated with tyrosine kinase inhibitors (TKIs) such as imatinib, but a portion of patients will develop drug resistance. Accumulated evidences have identified exosomes in cancer as promoters of tumor progression. Herein, we found that exosomes derived from imatinib resistant CML cells can be internalized into sensitive CML cells and confer drug-resistance traits. We also demonstrated a significant higher level of miR-365 in exosomes derived from drug-resistant CML cells compared with those from sensitive ones using microarray and qRT-PCR...
December 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29220692/plag-alleviates-chemotherapy-induced-thrombocytopenia-via-promotion-of-megakaryocyte-erythrocyte-progenitor-differentiation-in-mice
#8
Ha-Reum Lee, Nina Yoo, Jinseon Jeong, Ki-Young Sohn, Sun Young Yoon, Jae Wha Kim
Previously, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol, acetylated diglyceride) was reported to have an effect on the proliferation of hematopoietic stem cells (HSCs) or to contribute to the prevention of chemotherapy-induced neutropenia. In this study, we examined the role of PLAG in the differentiation of bone marrow cells from HSCs into progenitor cells in mice. After 15days, the lineage-negative cells, especially megakaryocyte/erythrocyte progenitors (MEP), were significantly increased in mice that received daily PLAG administration compared to those in the untreated mice...
October 10, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/29212818/the-histone-demethylase-kdm5a-is-required-for-the-repression-of-astrocytogenesis-and-regulated-by-the-translational-machinery-in-neural-progenitor-cells
#9
Sun-Young Kong, Woosuk Kim, Ha-Rim Lee, Hyun-Jung Kim
Histone demethylases are known to play important roles in the determination of the fate of stem cells and in cancer progression. In this study, we show that the lysine 4 of histone H3 (H3K4), lysine-specific demethylase 5A (KDM5A) is essential for the repression of astrocyte differentiation in neural progenitor cells (NPCs), and its expression is regulated by translational machinery. Knockdown of KDM5A in NPCs increased astrocytogenesis, and conversely, KDM5A overexpression reduced the transcriptional activity of the Gfap promoter...
December 6, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29212456/helicobacter-induced-gastric-inflammation-alters-the-properties-of-gastric-tissue-stem-progenitor-cells
#10
Wataru Shibata, Soichiro Sue, Sachiko Tsumura, Yasuaki Ishii, Takeshi Sato, Eri Kameta, Makoto Sugimori, Hiroaki Yamada, Hiroaki Kaneko, Tomohiko Sasaki, Tomohiro Ishii, Toshihide Tamura, Masaaki Kondo, Shin Maeda
BACKGROUND: Although Helicobacter-induced gastric inflammation is the major predisposing factor for gastric carcinogenesis, the precise mechanism by which chronic gastritis causes gastric cancer remains unclear. Intestinal and spasmolytic polypeptide-expressing metaplasia (SPEM) is considered as precancerous lesions, changes in epithelial tissue stem/progenitor cells after chronic inflammation has not been clarified yet. In this study, we utilized three-dimensional gastric epithelial cell culture systems that could form organoids, mimicking gastric epithelial layer, and characterized the changes in epithelial cells after chronic Helicobacter felis infection...
December 6, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/29212046/hematopoietic-defects-in-response-to-reduced-arhgap21
#11
Juliana Xavier-Ferrucio, Lauremília Ricon, Karla Vieira, Ana Leda Longhini, Mariana Lazarini, Carolina Louzão Bigarella, Gilberto Franchi, Diane S Krause, Sara T O Saad
Arhgap21 is a member of the Rho GTPase activating protein (RhoGAP) family, which function as negative regulators of Rho GTPases. Arhgap21 has been implicated in adhesion and migration of cancer cells. However, the role of Arhgap21 has never been investigated in hematopoietic cells. Herein, we evaluated functional aspects of hematopoietic stem and progenitor cells (HSPC) using a haploinsufficient (Arhgap21+/-) mouse. Our results show that Arhgap21+/- mice have an increased frequency of phenotypic HSC, impaired ability to form progenitor colonies in vitro and decreased hematopoietic engraftment in vivo, along with a decrease in LSK cell frequency during serial bone marrow transplantation...
November 23, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29211494/exhaustion-of-airway-basal-progenitor-cells-in-early-and-established-copd
#12
Moumita Ghosh, York E Miller, Ichiro Nakachi, Jennifer B Kwon, Anna E Barón, Alexandra E Brantley, Daniel T Merrick, Wilbur A Franklin, Robert L Keith, R William Vandivier
RATIONALE: Up to 40% of smokers develop chronic obstructive pulmonary disease (COPD) over a period that spans decades. Despite the importance of COPD, much remains to be learned about susceptibility and pathogenesis, especially during early, pre-diagnostic stages of disease. Airway basal progenitor cells are crucial for lung health and resilience, because of their ability to repair injured airways. In COPD, the normal airway epithelium is replaced with increased basal and secretory (mucous) cells and decreased ciliated cells, suggesting that progenitors are impaired...
December 6, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29202481/bone-marrow-drives-central-nervous-system-regeneration-after-radiation-injury
#13
Jorg Dietrich, Ninib Baryawno, Naema Nayyar, Yannis K Valtis, Betty Yang, Ina Ly, Antoine Besnard, Nicolas Severe, Karin U Gustafsson, Ovidiu C Andronesi, Tracy T Batchelor, Amar Sahay, David T Scadden
Nervous system injury is a frequent result of cancer therapy involving cranial irradiation, leaving patients with marked memory and other neurobehavioral disabilities. Here, we report an unanticipated link between bone marrow and brain in the setting of radiation injury. Specifically, we demonstrate that bone marrow-derived monocytes and macrophages are essential for structural and functional repair mechanisms, including regeneration of cerebral white matter and improvement in neurocognitive function. Using a granulocyte-colony stimulating factor (G-CSF) receptor knockout mouse model in combination with bone marrow cell transplantation, MRI, and neurocognitive functional assessments, we demonstrate that bone marrow-derived G-CSF-responsive cells home to the injured brain and are critical for altering neural progenitor cells and brain repair...
December 4, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29187227/obesity-reversibly-depletes-the-basal-cell-population-and-enhances-mammary-epithelial-cell-estrogen-receptor-alpha-expression-and-progenitor-activity
#14
Tamara Chamberlin, Joseph V D'Amato, Lisa M Arendt
BACKGROUND: Obesity is correlated with an increased risk for developing postmenopausal breast cancer. Since obesity rates continue to rise worldwide, it is important to understand how the obese microenvironment influences normal mammary tissue to increase breast cancer risk. We hypothesized that obesity increases the proportion of luminal progenitor cells, which are thought to be the cells of origin for the most common types of breast cancer, potentially leading to an increased risk for breast cancer...
November 29, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29181122/oxidative-stress-and-cellular-response-to-doxorubicin-a-common-factor-in-the-complex-milieu-of-anthracycline-cardiotoxicity
#15
REVIEW
Donato Cappetta, Antonella De Angelis, Luigi Sapio, Lucia Prezioso, Michela Illiano, Federico Quaini, Francesco Rossi, Liberato Berrino, Silvio Naviglio, Konrad Urbanek
The production of reactive species is a core of the redox cycling profile of anthracyclines. However, these molecular characteristics can be viewed as a double-edged sword acting not only on neoplastic cells but also on multiple cellular targets throughout the body. This phenomenon translates into anthracycline cardiotoxicity that is a serious problem in the growing population of paediatric and adult cancer survivors. Therefore, better understanding of cellular processes that operate within but also go beyond cardiomyocytes is a necessary step to develop more effective tools for the prevention and treatment of progressive and often severe cardiomyopathy experienced by otherwise successfully treated oncologic patients...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29181082/sox10-mitf-pathway-activity-in-melanoma-cells
#16
Karol B Tudrej, Edyta Czepielewska, Małgorzata Kozłowska-Wojciechowska
Melanoma is one of the most dangerous and lethal skin cancers, with a considerable metastatic potential and drug resistance. It involves a malignant transformation of melanocytes. The exact course of events in which melanocytes become melanoma cells remains unclear. Nevertheless, this process is said to be dependent on the occurrence of cells with the phenotype of progenitor cells - cells characterized by expression of proteins such as nestin, CD-133 or CD-271. The development of these cells and their survival were found to be potentially dependent on the neural crest stem cell transcription factor SOX10...
October 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29181066/stem-cell-factor-in-the-serum-of-patients-with-esophageal-cancer-in-relation-to-its-histological-types
#17
Marta Łukaszewicz-Zając, Barbara Mroczko, Mirosław Kozłowski, Maciej Szmitkowski
Introduction: Hematopoietic growth factors (HGFs), such as stem cell factor (SCF), may stimulate proliferation and differentiation of hematopoietic progenitor cells. Stem cell factor is also able to affect the growth of malignant tumors, including esophageal cancer (EC). The prognosis of EC patients' survival is still unfavorable. Thus, novel biomarkers are necessary to improve the diagnosis and prognosis of EC patients. The aim of this study was to determine the serum SCF concentrations in EC patients in relation to its histological types and compare these levels with the classical tumor marker - carcinoembryonic antigen (CEA)...
October 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29177909/stem-cells-and-progenitors-in-human-peripheral-blood-get-activated-by-extremely-active-resveratrol-xar%C3%A2
#18
Vinaykumar Tripathi, Sagar Chhabria, Vaibhav Jadhav, Deepa Bhartiya, Ashish Tripathi
Resveratrol generated enormous interest as it improved functions of multiple organs and could delay aging in animal models. However, basic mechanism of action was not understood and due to poor bioavailability, it has failed to enter the market. A highly active nano-formulation of resveratrol (XAR™) with enhanced bioavailability is now available. Present study was undertaken to evaluate its effects on stem cells biology in the human peripheral blood. Twelve healthy participants were enrolled of which five received XAR™, five were age-matched placebo controls and two were 76 and 85 years old...
November 24, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29177029/tumorigenesis-as-a-process-of-gradual-loss-of-original-cell-identity-and-gain-of-properties-of-neural-precursor-progenitor-cells
#19
REVIEW
Ying Cao
Cancer is a complex disease without a unified explanation for its cause so far. Our recent work demonstrates that cancer cells share similar regulatory networks and characteristics with embryonic neural cells. Based on the study, I will address the relationship between tumor and neural cells in more details. I collected the evidence from various aspects of cancer development in many other studies, and integrated the information from studies on cancer cell properties, cell fate specification during embryonic development and evolution...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29175091/phosphoprotein-dige-profiles-reflects-blast-differentiation-cytogenetic-risk-stratification-flt3-npm1-mutations-and-therapy-response-in-acute-myeloid-leukaemia
#20
Rakel Brendsdal Forthun, Elise Aasebø, Josef Daniel Rasinger, Siv Lise Bedringaas, Frode Berven, Frode Selheim, Øystein Bruserud, Bjørn Tore Gjertsen
Acute myeloid leukaemia (AML) is an aggressive blood cancer characterized by a distinct block in differentiation of myeloid progenitors, recurrent chromosomal translocations and gene mutations of which >50% involve signal transduction through dysregulated kinases and phosphatases. In search for novel protein biomarkers for disease stratification we investigated the phosphoproteome in leukaemic cells from 62 AML patients at time of diagnosis using immobilized metal-affinity chromatography, protein separation by two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry before validation by selected reaction monitoring (SRM)...
November 21, 2017: Journal of Proteomics
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