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https://www.readbyqxmd.com/read/28210556/are-breast-cancer-stem-cells-the-key-to-resolving-clinical-issues-in-breast-cancer-therapy
#1
REVIEW
Hidetaka Shima, Akimitsu Yamada, Takashi Ishikawa, Itaru Endo
Despite the dramatic advances in breast cancer treatment over the past two decades, it is still the most common malignancies in women. One of the reasons patients succumb to breast cancer is treatment resistance leading to metastasis and recurrence. Recently, cancer stem cells (CSCs) have been suggested as a cause of metastasis and recurrence in several cancers because of their unique characteristics, including self-renewal, pluripotency, and high proliferative ability. Increasing evidence has implicated breast cancer stem cells (BCSCs) as essential for tumor development, progression, recurrence, and treatment resistance...
February 2017: Gland Surgery
https://www.readbyqxmd.com/read/28205531/wnt5a-is-a-crucial-regulator-of-neurogenesis-during-cerebellum-development
#2
Chandramohan Subashini, Sivadasan Bindu Dhanesh, Chih-Ming Chen, Paul Ann Riya, Vadakkath Meera, Thulasi Sheela Divya, Rejji Kuruvilla, Kerstin Buttler, Jackson James
The role of Wnt5a has been extensively explored in various aspects of development but its role in cerebellar development remains elusive. Here, for the first time we unravel the expression pattern and functional significance of Wnt5a in cerebellar development using Wnt5a(-/-) and Nestin-Cre mediated conditional knockout mouse models. We demonstrate that loss of Wnt5a results in cerebellar hypoplasia and depletion of GABAergic and glutamatergic neurons. Besides, Purkinje cells of the mutants displayed stunted, poorly branched dendritic arbors...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203140/tamoxifen-activation-of-cre-recombinase-has-no-persisting-effects-on-adult-neurogenesis-or-learning-and-anxiety
#3
Peter Rotheneichner, Pasquale Romanelli, Lara Bieler, Sebastian Pagitsch, Pia Zaunmair, Christina Kreutzer, Richard König, Julia Marschallinger, Ludwig Aigner, Sébastien Couillard-Després
Adult neurogenesis is a tightly regulated process continuously taking place in the central nervous system of most mammalian species. In neuroscience research, transgenic animals bearing the tamoxifen-inducible CreER(T2)-Lox system are widely used. In this study, we made use of a Nestin-CreER(T2)/R26R-YFP transgenic mouse model in which the CreER(T2) activates the expression of YFP in multipotent neural stem cells upon tamoxifen application. Humoral factors, such as the levels of estrogens, have been reported to affect the hippocampal neurogenesis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28193719/brain-specific-ablation-of-efr3a-promotes-adult-hippocampal-neurogenesis-via-the-brain-derived-neurotrophic-factor-pathway
#4
Qi Qian, Qiuji Liu, Dongming Zhou, Hongyu Pan, Zhiwei Liu, Fangping He, Suying Ji, Dongpi Wang, Wangxiao Bao, Xinyi Liu, Zhaoling Liu, Heng Zhang, Xiaoqin Zhang, Ling Zhang, Mingkai Wang, Ying Xu, Fude Huang, Benyan Lao, Binggui Sun
Efr3 is a newly identified plasma membrane protein and plays an important role in the phosphoinositide metabolism on the plasma membrane. However, although it is highly expressed in the brain, the functional significance of Efr3 in the brain is not clear. In the present study, we generated Efr3a(f/f) mice and then crossed them with Nestin-Cre mice to delete Efr3a, one of the Efr3 isoforms, specifically in the brain. We found that brain-specific ablation of Efr3a promoted adult hippocampal neurogenesis by increasing survival and maturation of newborn neurons without affecting their dendritic tree morphology...
February 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28193212/corticomedullary-mixed-tumour-resembling-a-small-adrenal-gland-involvement-of-cancer-stem-cells-case-report
#5
Lian Duan, Fang Fang, Wanlei Fu, Zhenqiang Fang, Hui Wang, Shicang Yu, Zili Tang, Zhenqi Liu, Hongting Zheng
BACKGROUND: Adrenal corticomedullary mixed tumours are very rare. Its mechanism is rarely reported. Here we report the first case of a corticomedullary mixed tumour resembling a "small adrenal gland" with distinct arrangement of the cortical and medullary layers. We further hypothesize regarding the tumorigenic mechanism of this tumour. CASE PRESENTATION: A 58-year man had been diagnosed with diabetes and hypertension for 3 years. His 24-h urine vanillylmandelic acid (VMA) levels were slightly elevated...
February 13, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/28191756/aberrant-transforming-growth-factor-%C3%AE-activation-recruits-mesenchymal-stem-cells-during-prostatic-hyperplasia
#6
Long Wang, Liang Xie, Francis Tintani, Hui Xie, Changjun Li, Zhuang Cui, Mei Wan, Xiongbing Zu, Lin Qi, Xu Cao
Benign prostatic hyperplasia (BPH) is the overgrowth of prostate tissues with high prevalence in older men. BPH pathogenesis is not completely understood, but it is believed to be a result of de novo overgrowth of prostatic stroma. In this study, we show that aberrant activation of transforming growth factor-β (TGF-β) mobilizes mesenchymal/stromal stem cells (MSCs) in circulating blood, which are recruited for the prostatic stromal hyperplasia. Elevated levels of active TGF-β were observed in both a phenylephrine-induced prostatic hyperplasia mouse model and human BPH tissues...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28181105/protein-kinase-ck2-is-important-for-the-function-of-glioblastoma-brain-tumor-initiating-cells
#7
Amber L Rowse, Sara A Gibson, Gordon P Meares, Rajani Rajbhandari, Susan E Nozell, Kory J Dees, Anita B Hjelmeland, Braden C McFarland, Etty N Benveniste
Protein kinase CK2 is a ubiquitously expressed serine/threonine kinase composed of two catalytic subunits (α) and/or (α') and two regulatory (β) subunits. The expression and kinase activity of CK2 is elevated in many different cancers, including glioblastoma (GBM). Brain tumor initiating cells (BTICs) are a subset of cells that are highly tumorigenic and promote the resistance of GBM to current therapies. We previously reported that CK2 activity promotes prosurvival signaling in GBM. In this study, the role of CK2 signaling in BTIC function was examined...
February 8, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28180061/kinase-suppressor-of-ras-2-ksr2-expression-in-the-brain-regulates-energy-balance-and-glucose-homeostasis
#8
Lili Guo, Diane L Costanzo-Garvey, Deandra R Smith, Beth K Neilsen, Richard G MacDonald, Robert E Lewis
OBJECTIVE: Kinase Suppressor of Ras 2 (KSR2) is a molecular scaffold coordinating Raf/MEK/ERK signaling that is expressed at high levels in the brain. KSR2 disruption in humans and mice causes obesity and insulin resistance. Understanding the anatomical location and mechanism of KSR2 function should lead to a better understanding of physiological regulation over energy balance. METHODS: Mice bearing floxed alleles of KSR2 (KSR2(fl/fl)) were crossed with mice expressing the Cre recombinase expressed by the Nestin promoter (Nes-Cre) to produce Nes-CreKSR2(fl/fl) mice...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28173861/laminin-differentially-regulates-the-stemness-of-type-i-and-type-ii-pericytes
#9
Jyoti Gautam, Abhijit Nirwane, Yao Yao
BACKGROUND: Laminin, a major basement membrane component that has direct contact with pericytes under physiological conditions, actively regulates the proliferation and differentiation/fate determination of pericytes. Recently, two types of pericytes (type I and type II) with different molecular markers and functions have been identified in skeletal muscles. Whether laminin differentially regulates the proliferation and differentiation of these two subpopulations remains unclear. METHODS: Wild-type and pericytic laminin-deficient mice under Nestin-GFP background were used to determine if laminin differentially regulates the proliferation and differentiation of type I and type II pericytes...
February 7, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28173797/tumour-associated-glial-host-cells-display-a-stem-like-phenotype-with-a-distinct-gene-expression-profile-and-promote-growth-of-gbm-xenografts
#10
Lina Leiss, Ercan Mutlu, Anne Øyan, Tao Yan, Oleg Tsinkalovsky, Linda Sleire, Kjell Petersen, Mohummad Aminur Rahman, Mireille Johannessen, Sidhartha S Mitra, Hege K Jacobsen, Krishna M Talasila, Hrvoje Miletic, Inge Jonassen, Xingang Li, Nicolaas H Brons, Karl-Henning Kalland, Jian Wang, Per Øyvind Enger
BACKGROUND: Little is known about the role of glial host cells in brain tumours. However, supporting stromal cells have been shown to foster tumour growth in other cancers. METHODS: We isolated stromal cells from patient-derived glioblastoma (GBM) xenografts established in GFP-NOD/scid mice. With simultaneous removal of CD11b(+) immune and CD31(+) endothelial cells by fluorescence activated cell sorting (FACS), we obtained a population of tumour-associated glial cells, TAGs, expressing markers of terminally differentiaed glial cell types or glial progenitors...
February 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28169963/glial-differentiation-of-human-inferior-turbinate-derived-stem-cells-a-new-source-of-cells-for-nerve-repair
#11
Yang Li, Ying Sheng, JianMin Liang, XiaoYong Ren, Yan Cheng
Schwann cell (SC) transplantation as a cell-based therapy can enhance peripheral and central nerve repair experimentally, but it is limited by donor site morbidity for clinical application. We investigated whether human turbinate-derived mesenchymal stem cells (hTMSCs) isolated from discarded inferior turbinate during surgery can differentiate into functional SC-like cells. hTMSCs expressed mesenchymal cell surface markers CD29, CD44, CD90, and CD105 and did not express neural crest markers P75 and Nestin. After monolayer culture in predifferentiation medium and transdifferentiation medium with a mixture of glial growth factors and chemical regents for 14 days, the differentiated hTMSCs exhibited a spindle-like morphology similar to that of SCs...
February 4, 2017: Neuroreport
https://www.readbyqxmd.com/read/28159699/drugs-targeting-intermediate-filaments-can-improve-neurosupportive-properties-of-astrocytes
#12
Yolanda de Pablo, Meng Chen, Elin Möllerström, Marcela Pekna, Milos Pekny
In response to central nervous system (CNS) injury, astrocytes upregulate intermediate filament (nanofilament) proteins GFAP and vimentin. Whereas the intermediate filament upregulation in astrocytes is important for neuroprotection in the acute phase of injury, it might inhibit the regenerative processes later on. Thus, timely modulation of the astrocyte intermediate filaments was proposed as a strategy to promote brain repair. We used clomipramine, epoxomicin and withaferin A, drugs reported to decrease the expression of GFAP, and assessed their effect on neurosupportive properties and resilience of astrocytes to oxygen and glucose deprivation (OGD)...
January 31, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28158247/neuroprotective-effects-of-dexmedetomidine-against-hyperoxia-induced-injury-in-the-developing-rat-brain
#13
Stefanie Endesfelder, Hanan Makki, Clarissa von Haefen, Claudia D Spies, Christoph Bührer, Marco Sifringer
Dexmedetomidine (DEX) is a highly selective agonist of α2-receptors with sedative, anxiolytic, and analgesic properties. Neuroprotective effects of dexmedetomidine have been reported in various brain injury models. In the present study, we investigated the effects of dexmedetomidine on hippocampal neurogenesis, specifically the proliferation capacity and maturation of neurons and neuronal plasticity following the induction of hyperoxia in neonatal rats. Six-day old sex-matched Wistar rats were exposed to 80% oxygen or room air for 24 h and treated with 1, 5 or 10 μg/kg of dexmedetomidine or normal saline...
2017: PloS One
https://www.readbyqxmd.com/read/28157712/the-interference-of-notch1-target-hes1-affects-cell-growth-differentiation-and-invasiveness-of-glioblastoma-stem-cells-through-modulation-of-multiple-oncogenic-targets
#14
Carlo Cenciarelli, Hany E Marei, Manuela Zonfrillo, Patrizia Casalbore, Armando Felsani, Stefano Giannetti, Gianluca Trevisi, Asma Althani, Annunziato Mangiola
The invasive and lethal nature of Glioblastoma multiforme (GBM) necessitates the continuous identification of molecular targets and search of efficacious therapies to inhibit GBM growth. The GBM resistance to chemotherapy and radiation it is attributed to the existence of a rare fraction of cancer stem cells (CSC) that we have identified within the tumor core and in peritumor tissue of GBM. Since Notch1 pathway is a potential therapeutic target in brain cancer, earlier we highlighted that pharmacological inhibition of Notch1 signalling by γ-secretase inhibitor-X (GSI-X), reduced cell growth of some c-CSC than to their respective p-CSC, but produced negligible effects on cell cycle distribution, apoptosis and cell invasion...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28150227/apobec1-promotes-neurotoxicity-induced-dedifferentiation-of-m%C3%A3-ller-glial-cells
#15
Jian Xiao, Xue Li, Lan Chen, Xin Han, Wei Zhao, Lianlian Li, Jie-Guang Chen
Retinal Müller glial cells in mammals acquire stem and progenitor cell properties after neurotoxic treatment. However, the molecular mechanisms underlying proliferation and dedifferentiation of adult Müller cells in the mammalian retina were unclear. In this study, treatments with N-methyl-D-aspartate (NMDA) plus epidermal growth factor (EGF) led to the proliferation of Müller cells and expression of stem cell markers including Nanog and Nestin in the retina. The increased mRNA for Nanog and Nestin were coincident with reduced methylation of a Nanog promoter and a Nestin enhancer specific in the neural stem cells, respectively...
February 2, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28148846/tumor-homing-cytotoxic-human-induced-neural-stem-cells-for-cancer-therapy
#16
Juli R Bagó, Onyi Okolie, Raluca Dumitru, Matthew G Ewend, Joel S Parker, Ryan Vander Werff, T Michael Underhill, Ralf S Schmid, C Ryan Miller, Shawn D Hingtgen
Engineered neural stem cells (NSCs) are a promising approach to treating glioblastoma (GBM). The ideal NSC drug carrier for clinical use should be easily isolated and autologous to avoid immune rejection. We transdifferentiated (TD) human fibroblasts into tumor-homing early-stage induced NSCs (h-iNSC(TE)), engineered them to express optical reporters and different therapeutic gene products, and assessed the tumor-homing migration and therapeutic efficacy of cytotoxic h-iNSC(TE) in patient-derived GBM models of surgical and nonsurgical disease...
February 1, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28148530/usp40-gene-knockdown-disrupts-glomerular-permeability-in-zebrafish
#17
Hisashi Takagi, Yukino Nishibori, Kan Katayama, Tomohisa Katada, Shohei Takahashi, Zentaro Kiuchi, Shin-Ichiro Takahashi, Hiroyasu Kamei, Hayato Kawakami, Yoshihiro Akimoto, Akihiko Kudo, Katsuhiko Asanuma, Hiromu Takematsu, Kunimasa Yan
Unbiased transcriptome profiling and functional genomics approaches have identified ubiquitin specific protease 40 (USP40) as a highly specific glomerular transcript. This gene product remains uncharacterized, and its biological function is completely unknown. Here, we showed that mouse and rat glomeruli exhibit specific expression of the USP40 protein, which migrated at 150 kDa and was exclusively localized in the podocyte cytoplasm of the adult kidney. Double-labeling immunofluorescence staining and confocal microscopy analysis of fetal and neonate kidney samples revealed that USP40 was also expressed in the vasculature, including in glomerular endothelial cells at the premature stage...
February 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28145507/transplanted-mir-219-overexpressing-oligodendrocyte-precursor-cells-promoted-remyelination-and-improved-functional-recovery-in-a-chronic-demyelinated-model
#18
Hong-Bin Fan, Li-Xia Chen, Xue-Bin Qu, Chuan-Lu Ren, Xiu-Xiang Wu, Fu-Xing Dong, Bao-Le Zhang, Dian-Shuai Gao, Rui-Qin Yao
Oligodendrocyte precursor cells (OPCs) have the ability to repair demyelinated lesions by maturing into myelin-producing oligodendrocytes. Recent evidence suggests that miR-219 helps regulate the differentiation of OPCs into oligodendrocytes. We performed oligodendrocyte differentiation studies using miR-219-overexpressing mouse embryonic stem cells (miR219-mESCs). The self-renewal and multiple differentiation properties of miR219-mESCs were analyzed by the expression of the stage-specific cell markers Nanog, Oct4, nestin, musashi1, GFAP, Tuj1 and O4...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28138519/single-cell-analysis-reveals-a-nestin-tendon-stem-progenitor-cell-population-with-strong-tenogenic-potentiality
#19
Zi Yin, Jia-Jie Hu, Long Yang, Ze-Feng Zheng, Cheng-Rui An, Bing-Bing Wu, Can Zhang, Wei-Liang Shen, Huan-Huan Liu, Jia-Lin Chen, Boon Chin Heng, Guo-Ji Guo, Xiao Chen, Hong-Wei Ouyang
The repair of injured tendons remains a formidable clinical challenge because of our limited understanding of tendon stem cells and the regulation of tenogenesis. With single-cell analysis to characterize the gene expression profiles of individual cells isolated from tendon tissue, a subpopulation of nestin(+) tendon stem/progenitor cells (TSPCs) was identified within the tendon cell population. Using Gene Expression Omnibus datasets and immunofluorescence assays, we found that nestin expression was activated at specific stages of tendon development...
November 2016: Science Advances
https://www.readbyqxmd.com/read/28131784/attenuation-of-subchondral-bone-abnormal-changes-in-osteoarthritis-by-inhibition-of-sdf-1-signaling
#20
Y Chen, S Lin, Y Sun, J Guo, Y Lu, C W Suen, J Zhang, Z Zha, K W Ho, X Pan, G Li
BACKGROUND: Current conservative treatments for osteoarthritis (OA) are largely symptoms control therapies. Further understanding on the pathological mechanisms of OA is crucial for new pharmacological intervention. OBJECTIVE: In this study, we investigated the role of Stromal cell-derived factor-1(SDF-1) in regulating subchondral bone changes during the progression of OA. METHODS: Clinical samples of different stages of OA severity were analyzed by histology staining, micro-CT, enzyme-linked immunosorbent assay (ELISA) and western blotting, to compare SDF-1 level in subchondral bone...
January 25, 2017: Osteoarthritis and Cartilage
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