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https://www.readbyqxmd.com/read/28346882/determination-of-prodrug-treosulfan-and-its-biologically-active-monoepoxide-in-rat-plasma-liver-lungs-kidneys-muscle-and-brain-by-hplc-esi-ms-ms-method
#1
Michał Romański, Anna Kasprzyk, Artur Teżyk, Agnieszka Widerowska, Czesław Żaba, Franciszek Główka
A prodrug treosulfan (TREO) is currently investigated in clinical trials for conditioning prior to hematopoietic stem cell transplantation. Bioanalysis of TREO and its active derivatives, monoepoxide (S,S-EBDM) and diepoxide, in plasma and urine underlay the pharmacokinetic studies of these compounds but cannot explain an organ pharmacological action or toxicity. Recently, distribution of TREO and S,S-EBDM into brain, cerebrospinal fluid, and aqueous humor of the eye has been investigated in animal models and the obtained results presented clinical relevance...
March 18, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28346802/metabolome-profiling-of-partial-and-fully-reprogrammed-induced-pluripotent-stem-cells
#2
Soon-Jung Park, Sang A Lee, Nutan Prasain, Daekyeong Bae, Hyunsu Kang, Taewon Ha, Jong Soo Kim, Ki-Sung Hong, Charlie Mantel, Sung-Hwan Moon, Hal E Broxmeyer, Man Ryul Lee
Acquisition of proper metabolomic fate is required to convert somatic cells toward fully reprogrammed pluripotent stem cells. The majority of induced pluripotent stem cells (iPSCs) are partially reprogrammed and have a transcriptome different from that of the pluripotent stem cells. The metabolomic profile and mitochondrial metabolic functions required to achieve full reprogramming of somatic cells to iPSC status have not yet been elucidated. Clarification of the metabolites underlying reprogramming mechanisms should enable further optimization to enhance the efficiency of obtaining fully reprogrammed iPSCs...
March 27, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28346798/priming-adipose-stem-cells-with-tumor-necrosis-factor-alpha-preconditioning-potentiates-their-exosome-efficacy-for-bone-regeneration
#3
ZuFu Lu, YongJuan Chen, Colin Dunstan, Seyediman Roohani-Esfahani, Hala Zreiqat
Mesenchymal stem cells (MSCs) have been widely used for tissue repair and regeneration. However, the inherent drawbacks, including limited cell survival after cell transplantation, have hindered direct MSC transplantation for tissue repair and regeneration. The aim of this study was to investigate if exosomes isolated from MSCs can promote the proliferation and differentiation of human primary osteoblastic cells (HOBs) and be potentially used for bone tissue regeneration. We showed that adipose tissue-derived MSC (ASC)-derived exosomes (ASC-EXO) were able to promote the proliferation and osteogenic differentiation in HOBs; and the trophic effects of ASC-EXO on HOBs were further harnessed when ASCs were preconditioned with tumor necrosis factor-alpha (TNF-α) for 3 days, which mimics the acute inflammatory phase upon bone injury...
March 23, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28346797/substituted-borosilicate-glasses-with-improved-osteogenic-capacity-for-bone-tissue-engineering
#4
João S Fernandes, Piergiorgio Gentile, Aileen Crawford, Ricardo A Pires, Paul V Hatton, Rui L Reis
Borosilicate bioactive glasses (BBGs) have shown the capacity to promote higher formation of new bone when compared with silicate bioactive glasses. Herein, we assessed the capacity of BBGs to induce osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) as a function of their substituted divalent cations (Mg(2+), Ca(2+), Sr(2+)). To this purpose, we synthesized BBG particles by melt quenching. The cell viability, proliferation, and morphology (i.e., PrestoBlue(®), PicoGreen(®), and DAPI and Phalloidin stainings, respectively), as well as protein expression (i...
March 27, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28346796/harnessing-external-cues-development-and-evaluation-of-an-in-vitro-culture-system-for-osteochondral-tissue-engineering
#5
Deborah L Dorcemus, Eve O George, Caroline N Dealy, Syam P Nukavarapu
Over the last decade, engineered structures have been developed for osteochondral (OC) tissue regeneration. While the optimal structure design is yet to be determined, these scaffolds require in vitro evaluation before clinical use. However, the means by which complex scaffolds, such as OC scaffolds, can be tested are limited. Taking advantage of a mesenchymal stem cell's (MSC's) ability to respond to its surrounding we harness external cues, such as the cell's mechanical environment and delivered factors, to create an in vitro culture system for OC tissue engineering with a single cell source on a gradient yet integrated scaffold system...
March 24, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28346794/comparative-study-of-xenobiotic-free-media-for-the-cultivation-of-human-limbal-epithelial-stem-progenitor-cells
#6
Sheyla González, Luxia Chen, Sophie X Deng
The culture of human limbal epithelial stem/progenitor cells (LSCs) in the presence of animal components poses the risk of cross-species contamination in clinical applications. We quantitatively compared different xenobiotic-free culture media for the cultivation of human LSCs. LSCs were cultured from 2 × 2 mm limbal tissue explants on denuded human amniotic membrane with different xenobiotic-free culture media: CnT-Prime (CnT-PR) supplemented with 0%, 1%, 5%, and 10% human serum (HS), embryonic stem cell medium (ESCM) alone or in combination with the standard supplemented hormonal epithelium medium (SHEM, control) at a 1:1 dilution ratio, and modified SHEM (mSHEM), in which cholera toxin and dimethyl sulfoxide (DMSO) were removed, isoproterenol was added, and the epidermal growth factor concentration was reduced...
March 24, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28346781/metabolism-of-ibuprofen-by-phragmites-australis-uptake-and-phytodegradation
#7
Yujie He, Alette A M Langenhoff, Nora B Sutton, Huub H M Rijnaarts, Marco H Blokland, Feiran Chen, Christian Huber, Peter Schröder
This study explores ibuprofen (IBP) uptake and transformation in the wetland plant species Phragmites australis and the underlying mechanisms. We grew P. australis in perlite under greenhouse conditions and treated plants with 60 µg/l of IBP. Roots and rhizomes (RR), stems and leaves (SL), and liquid samples were collected during 21 days of exposure. Results show that P. australis can take up, translocate, and degrade IBP. IBP was completely removed from the liquid medium after 21 days with a half-life of 2...
March 27, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28346544/epigenetic-silencing-of-v-d-j-recombination-is-a-major-determinant-for-selective-differentiation-of-mucosal-associated-invariant-t-cells-from-induced-pluripotent-stem-cells
#8
Yutaka Saito, Chie Sugimoto, Toutai Mituyama, Hiroshi Wakao
Mucosal-associated invariant T cells (MAITs) are innate-like T cells that play a pivotal role in the host defense against infectious diseases, and are also implicated in autoimmune diseases, metabolic diseases, and cancer. Recent studies have shown that induced pluripotent stem cells (iPSCs) derived from MAITs selectively redifferentiate into MAITs without altering their antigen specificity. Such a selective differentiation is a prerequisite for the use of MAITs in cell therapy and/or regenerative medicine...
2017: PloS One
https://www.readbyqxmd.com/read/28346462/wnt-tcf1-pathway-restricts-embryonic-stem-cell-cycle-through-activation-of-the-ink4-arf-locus
#9
Anchel De Jaime-Soguero, Francesco Aulicino, Gokhan Ertaylan, Anna Griego, Aniello Cerrato, Aravind Tallam, Antonio Del Sol, Maria Pia Cosma, Frederic Lluis
Understanding the mechanisms regulating cell cycle, proliferation and potency of pluripotent stem cells guarantees their safe use in the clinic. Embryonic stem cells (ESCs) present a fast cell cycle with a short G1 phase. This is due to the lack of expression of cell cycle inhibitors, which ultimately determines naïve pluripotency by holding back differentiation. The canonical Wnt/β-catenin pathway controls mESC pluripotency via the Wnt-effector Tcf3. However, if the activity of the Wnt/β-catenin controls the cell cycle of mESCs remains unknown...
March 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28346452/purine-synthesis-promotes-maintenance-of-brain-tumor-initiating-cells-in-glioma
#10
Xiuxing Wang, Kailin Yang, Qi Xie, Qiulian Wu, Stephen C Mack, Yu Shi, Leo J Y Kim, Briana C Prager, William A Flavahan, Xiaojing Liu, Meromit Singer, Christopher G Hubert, Tyler E Miller, Wenchao Zhou, Zhi Huang, Xiaoguang Fang, Aviv Regev, Mario L Suvà, Tae Hyun Hwang, Jason W Locasale, Shideng Bao, Jeremy N Rich
Brain tumor initiating cells (BTICs), also known as cancer stem cells, hijack high-affinity glucose uptake active normally in neurons to maintain energy demands. Here we link metabolic dysregulation in human BTICs to a nexus between MYC and de novo purine synthesis, mediating glucose-sustained anabolic metabolism. Inhibiting purine synthesis abrogated BTIC growth, self-renewal and in vivo tumor formation by depleting intracellular pools of purine nucleotides, supporting purine synthesis as a potential therapeutic point of fragility...
March 27, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28346436/detailed-comparison-of-retroviral-vectors-and-promoter-configurations-for-stable-and-high-transgene-expression-in-human-induced-pluripotent-stem-cells
#11
D Hoffmann, J W Schott, F K Geis, L Lange, F-J Müller, D Lenz, D Zychlinski, D Steinemann, M Morgan, T Moritz, A Schambach
Correction of patient-specific induced pluripotent stem cells (iPSC) upon gene delivery through retroviral vectors offers new treatment perspectives for monogenetic diseases. Gene-modified iPSC clones can be screened for safe integration sites and differentiated into transplantable cells of interest. However, the current bottleneck is epigenetic vector silencing. In order to identify the most suitable retroviral expression system in iPSC, we systematically compared vectors from different retroviral genera, different promoters and their combination with ubiquitous chromatin opening elements (UCOE), and several envelope pseudotypes...
March 27, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28346424/skp2-deficiency-restricts-the-progression-and-stem-cell-features-of-castration-resistant-prostate-cancer-by-destabilizing-twist
#12
D Ruan, J He, C-F Li, H-J Lee, J Liu, H-K Lin, C-H Chan
Castration-resistant prostate cancer (CRPC) remains a major clinical challenge because of the lack of effective targeted therapy for its treatment. The mechanism underlying how CRPC gains resistance toward hormone depletion and other forms of chemotherapy is poorly understood. Research on understanding the factors that drive these processes is desperately needed to generate new therapies to cure the disease. Here, we discovered a fundamental role of S-phase protein kinase 2 (Skp2) in the formation and progression of CRPC...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346423/mob1-yap1-taz-nkx2-1-axis-controls-bronchioalveolar-cell-differentiation-adhesion-and-tumour-formation
#13
K Otsubo, H Goto, M Nishio, K Kawamura, S Yanagi, W Nishie, T Sasaki, T Maehama, H Nishina, K Mimori, T Nakano, H Shimizu, T W Mak, K Nakao, Y Nakanishi, A Suzuki
Mps One Binder Kinase Activator (MOB)1A/1B are core components of the Hippo pathway. These proteins, which coactivate LArge Tumour Suppressor homologue kinases, are also tumour suppressors. To investigate MOB1A/B's roles in normal physiology and lung cancer, we generated doxycycline (Dox)-inducible, bronchioalveolar epithelium-specific, null mutations of MOB1A/B in mice (SPC-rtTA/(tetO)7-Cre/Mob1a(flox/flox)/Mob1b(-/-); termed luMob1DKO mice). Most mutants (70%) receiving Dox in utero (luMob1DKO (E6.5-18.5) mice) died of hypoxia within 1 h post-birth...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346418/first-experience-of-hematopoietic-stem-cell-transplantation-treatment-of-shwachman-diamond-syndrome-using-unaffected-hla-matched-sibling-donor-produced-through-preimplantation-hla-typing
#14
A A Isaev, R V Deev, A Kuliev, I L Plaxa, N V Stancheva, A S Borovkova, I V Potapov, E A Pomerantseva, A G Chogovadze, K Y Boyarsky, A E Semenenko, A V Mikhailov, K G Shevchenko, A V Prikhodko, S Rechitsky, O V Paina, I M Barchatov, L S Zubarovskaya, O Verlinsky, I Y Bozo, B V Afanasyev
The only proven cure for Shwachman-Diamond syndrome (SDS) bone marrow failure is allogeneic hematopoietic stem cell transplantation (HSCT). However HSCT with donors other than HLA-identical siblings is associated with high mortality and unfavorable prognosis. This paper presents the first experience of HSCT treatment of SDS using an unaffected HLA-identical sibling produced through preimplantation genetic diagnosis (PGD). The patient was a 6-year-old blood transfusion-dependent SDS baby girl with secondary myelodysplastic syndrome, for whom no HLA-identical donor was available...
March 27, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28346415/haplo-cord-transplantation-compared-to-haploidentical-transplantation-with-post-transplant-cyclophosphamide-in-patients-with-aml
#15
M Kwon, G Bautista, P Balsalobre, I Sánchez-Ortega, P Montesinos, A Bermúdez, A de Laiglesia, P Herrera, C Martin, K Humala, A Zabalza, M Torres, L Bento, L L Corral, I Heras, D Serrano, I Buño, J Anguita, C Regidor, R Duarte, R Cabrera, J Gayoso, J L Diez-Martin
For patients with AML, the best alternative donor remains to be defined. We analyze outcomes of patients who underwent myeloablative umbilical cord blood or haploidentical hemopoietic stem cell transplantation (HSCT) in Spain. Fifty-one patients underwent single umbilical cord blood transplantation supported by a third party donor (Haplo-Cord) between 1999 and 2012, and 36 patients received an haploidentical HSCT with post-transplant cyclophosphamide (PTCY-haplo) between 2012 and 2014 in GETH centers. The Haplo-Cord cohort included a higher proportion of patients with high disease risk index and use of TBI in the conditioning regimen, and hematopoietic cell transplantation-age Comorbidity Age Index was higher in PTCY-haplo patients...
March 27, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28346393/choerosponins-a-and-b-two-new-cytotoxic-bridged-ring-ketones-and-the-determination-of-their-absolute-configurations
#16
Chang-Wei Li, Bing Han, Bing Cai, Cheng-Bin Cui
Bioactivity-directed fractionation of antitumor compounds from the stem barks of Choerospondias axillaries (Roxb.) Burtt et Hill (Anacardiaceae) afforded two new cytotoxic bridged-ring ketones, choerosponins A (1) and B (2), and their structures were elucidated by spectroscopic methods; their stereochemistry was determined by NOE difference experiments, CD spectra and the modified Mosher's method. Compound 1 has a rare dioxatricyclo skeleton. Flow cytometry and SRB methods were employed to evaluate the antitumor activity of the two compounds against tsFT210, HCT-15, HeLa, A2780 and MCF-7 cell lines, and both of them showed strong cytotoxicity...
March 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28346367/transplantation-of-menstrual-blood-derived-mesenchymal-stem-cells-promotes-the-repair-of-lps-induced-acute-lung-injury
#17
Bingyu Xiang, Lu Chen, Xiaojun Wang, Yongjia Zhao, Yanling Wang, Charlie Xiang
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high morbidity and mortality. Menstrual blood-derived stem cells (MenSCs) have been shown to be good therapeutic tools in diseases such as ovarian failure and cardiac fibrosis. However, relevant studies of MenSCs in ALI have not yet proceeded. We hypothesized that MenSC could attenuate the inflammation in lipopolysaccharide (LPS)-induced ALI and promote the repair of damaged lung. ALI model was induced by LPS in C57 mice, and saline or MenSCs were administered via tail vein after four hours...
March 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28346229/clinical-efficacy-of-gene-modified-stem-cells-in-adenosine-deaminase-deficient-immunodeficiency
#18
Kit L Shaw, Elizabeth Garabedian, Suparna Mishra, Provaboti Barman, Alejandra Davila, Denise Carbonaro, Sally Shupien, Christopher Silvin, Sabine Geiger, Barbara Nowicki, E Monika Smogorzewska, Berkley Brown, Xiaoyan Wang, Satiro de Oliveira, Yeong Choi, Alan Ikeda, Dayna Terrazas, Pei-Yu Fu, Allen Yu, Beatriz Campo Fernandez, Aaron R Cooper, Barbara Engel, Greg Podsakoff, Arumugam Balamurugan, Stacie Anderson, Linda Muul, G Jayashree Jagadeesh, Neena Kapoor, John Tse, Theodore B Moore, Ken Purdy, Radha Rishi, Kathey Mohan, Suzanne Skoda-Smith, David Buchbinder, Roshini S Abraham, Andrew Scharenberg, Otto O Yang, Kenneth Cornetta, David Gjertson, Michael Hershfield, Rob Sokolic, Fabio Candotti, Donald B Kohn
BACKGROUND: Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase-deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. METHODS: Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28346106/isolation-and-characterization-of-a-distinct-subpopulation-from-the-wm115-cell-line-that-resembles-in-vitro-properties-of-melanoma-cancer-stem-cells
#19
Sonia G Escobar, Mark H Chin, Mark L Sandberg, Han Xu
Despite key advances in cancer therapies, malignant tumors, such as melanoma, continue to be one of the leading causes of mortality. Recent debate on whether cancer can originate from a tumor-initiating subpopulation has permeated oncology and stem cell research. It has been well established that primary and immortalized tumor cells consist of heterogeneous cell populations. The profound effect of tumor heterogeneity on tumor growth and drug resistance remains elusive, but it is highly likely that subpopulations of cancer cells have different capabilities of self-renewal and drug resistance...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346100/robotic-mammosphere-assay-for-high-throughput-screening-in-triple-negative-breast-cancer
#20
P A Fitzpatrick, N Akrap, E M V Söderberg, H Harrison, G J Thomson, G Landberg
In order to identify novel treatment principles specifically affecting cancer stem cells in triple-negative breast cancer, we have developed a high-throughput screening method based on the mammosphere and anoikis resistance assays allowing us to screen compounds using a functional readout. The assay was validated against manual protocols and through the use of positive controls, such as the response to hypoxia and treatment with the known cancer stem cell-targeting compound salinomycin. Manual and robotic procedures were compared and produced similar results in cell handling, cell cultures, and counting techniques, with no statistically significant difference produced from either method...
February 1, 2017: SLAS Discov
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