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  • 1
    Publication Date: 2013-10-11
    Description: Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant three-dimensional associations in the mouse bone marrow among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal bone marrow. These arterioles are ensheathed exclusively by rare NG2 (also known as CSPG4)(+) pericytes, distinct from sinusoid-associated leptin receptor (LEPR)(+) cells. Pharmacological or genetic activation of the HSC cell cycle alters the distribution of HSCs from NG2(+) periarteriolar niches to LEPR(+) perisinusoidal niches. Conditional depletion of NG2(+) cells induces HSC cycling and reduces functional long-term repopulating HSCs in the bone marrow. These results thus indicate that arteriolar niches are indispensable for maintaining HSC quiescence.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821873/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821873/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kunisaki, Yuya -- Bruns, Ingmar -- Scheiermann, Christoph -- Ahmed, Jalal -- Pinho, Sandra -- Zhang, Dachuan -- Mizoguchi, Toshihide -- Wei, Qiaozhi -- Lucas, Daniel -- Ito, Keisuke -- Mar, Jessica C -- Bergman, Aviv -- Frenette, Paul S -- HL069438/HL/NHLBI NIH HHS/ -- HL097700/HL/NHLBI NIH HHS/ -- R00 CA139009/CA/NCI NIH HHS/ -- R01 DK056638/DK/NIDDK NIH HHS/ -- R01 DK098263/DK/NIDDK NIH HHS/ -- R01 DK100689/DK/NIDDK NIH HHS/ -- R01 HL069438/HL/NHLBI NIH HHS/ -- R01 HL097700/HL/NHLBI NIH HHS/ -- R01 HL116340/HL/NHLBI NIH HHS/ -- T32 063754/PHS HHS/ -- England -- Nature. 2013 Oct 31;502(7473):637-43. doi: 10.1038/nature12612. Epub 2013 Oct 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA [2] Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24107994" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arterioles/*cytology ; Bone Marrow/blood supply ; Cell Division ; Cell Separation ; Female ; Flow Cytometry ; Hematopoietic Stem Cells/*cytology/metabolism ; Male ; Mesenchymal Stromal Cells/cytology ; Mice ; Mice, Inbred C57BL ; Nestin/metabolism ; *Stem Cell Niche
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-09-17
    Description: Blood polymorphonuclear neutrophils provide immune protection against pathogens, but may also promote tissue injury in inflammatory diseases. Although neutrophils are generally considered to be a relatively homogeneous population, evidence for heterogeneity is emerging. Under steady-state conditions, neutrophil heterogeneity may arise from ageing and replenishment by newly released neutrophils from the bone marrow. Aged neutrophils upregulate CXCR4, a receptor allowing their clearance in the bone marrow, with feedback inhibition of neutrophil production via the IL-17/G-CSF axis, and rhythmic modulation of the haematopoietic stem-cell niche. The aged subset also expresses low levels of L-selectin. Previous studies have suggested that in vitro-aged neutrophils exhibit impaired migration and reduced pro-inflammatory properties. Here, using in vivo ageing analyses in mice, we show that neutrophil pro-inflammatory activity correlates positively with their ageing whilst in circulation. Aged neutrophils represent an overly active subset exhibiting enhanced alphaMbeta2 integrin activation and neutrophil extracellular trap formation under inflammatory conditions. Neutrophil ageing is driven by the microbiota via Toll-like receptor and myeloid differentiation factor 88-mediated signalling pathways. Depletion of the microbiota significantly reduces the number of circulating aged neutrophils and dramatically improves the pathogenesis and inflammation-related organ damage in models of sickle-cell disease or endotoxin-induced septic shock. These results identify a role for the microbiota in regulating a disease-promoting neutrophil subset.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712631/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712631/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Dachuan -- Chen, Grace -- Manwani, Deepa -- Mortha, Arthur -- Xu, Chunliang -- Faith, Jeremiah J -- Burk, Robert D -- Kunisaki, Yuya -- Jang, Jung-Eun -- Scheiermann, Christoph -- Merad, Miriam -- Frenette, Paul S -- R01 CA154947/CA/NCI NIH HHS/ -- R01 CA173861/CA/NCI NIH HHS/ -- R01 CA190400/CA/NCI NIH HHS/ -- R01 DK056638/DK/NIDDK NIH HHS/ -- R01 HL069438/HL/NHLBI NIH HHS/ -- R01 HL116340/HL/NHLBI NIH HHS/ -- England -- Nature. 2015 Sep 24;525(7570):528-32. doi: 10.1038/nature15367. Epub 2015 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA. ; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. ; Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461, USA. ; Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA. ; The Immunology Institute, Mount Sinai School of Medicine, New York, New York 10029, USA. ; The Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, New York 10029, USA. ; Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26374999" target="_blank"〉PubMed〈/a〉
    Keywords: Anemia, Sickle Cell/blood/microbiology/pathology ; Animals ; Cell Aging/*immunology ; Disease Models, Animal ; Erythrocytes, Abnormal/pathology ; Inflammation/immunology/pathology ; Macrophage-1 Antigen/metabolism ; Male ; Mice ; Microbiota/*immunology ; Myeloid Differentiation Factor 88/metabolism ; Neutrophils/*cytology/*immunology ; Shock, Septic/immunology/microbiology/pathology ; Signal Transduction ; Toll-Like Receptors/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2015-12-05
    Description: Whereas the cellular basis of the hematopoietic stem cell (HSC) niche in the bone marrow has been characterized, the nature of the fetal liver niche is not yet elucidated. We show that Nestin(+)NG2(+) pericytes associate with portal vessels, forming a niche promoting HSC expansion. Nestin(+)NG2(+) cells and HSCs scale during development with the fractal branching patterns of portal vessels, tributaries of the umbilical vein. After closure of the umbilical inlet at birth, portal vessels undergo a transition from Neuropilin-1(+)Ephrin-B2(+) artery to EphB4(+) vein phenotype, associated with a loss of periportal Nestin(+)NG2(+) cells and emigration of HSCs away from portal vessels. These data support a model in which HSCs are titrated against a periportal vascular niche with a fractal-like organization enabled by placental circulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706788/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706788/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Khan, Jalal A -- Mendelson, Avital -- Kunisaki, Yuya -- Birbrair, Alexander -- Kou, Yan -- Arnal-Estape, Anna -- Pinho, Sandra -- Ciero, Paul -- Nakahara, Fumio -- Ma'ayan, Avi -- Bergman, Aviv -- Merad, Miriam -- Frenette, Paul S -- CA164468/CA/NCI NIH HHS/ -- DA033788/DA/NIDA NIH HHS/ -- DK056638/DK/NIDDK NIH HHS/ -- F30 943257/PHS HHS/ -- F32 HL123224/HL/NHLBI NIH HHS/ -- HL069438/HL/NHLBI NIH HHS/ -- HL097700/HL/NHLBI NIH HHS/ -- R01 CA173861/CA/NCI NIH HHS/ -- R01 CA190400/CA/NCI NIH HHS/ -- R01 DA033788/DA/NIDA NIH HHS/ -- R01 DK056638/DK/NIDDK NIH HHS/ -- R01 HL069438/HL/NHLBI NIH HHS/ -- R01 HL116340/HL/NHLBI NIH HHS/ -- R01GM098316/GM/NIGMS NIH HHS/ -- T32 063754/PHS HHS/ -- U54 HL127624/HL/NHLBI NIH HHS/ -- U54CA189201/CA/NCI NIH HHS/ -- U54HL127624/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2016 Jan 8;351(6269):176-80. doi: 10.1126/science.aad0084. Epub 2015 Dec 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research. Albert Einstein College of Medicine, Bronx, NY, USA. Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ; Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research. Albert Einstein College of Medicine, Bronx, NY, USA. Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA. ; Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ; Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research. Albert Einstein College of Medicine, Bronx, NY, USA. ; Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY, USA. ; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ; Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research. Albert Einstein College of Medicine, Bronx, NY, USA. Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA. paul.frenette@einstein.yu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26634440" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens/analysis ; Ephrin-B2/analysis ; Female ; Hematopoietic Stem Cells/*physiology ; Liver/blood supply/*embryology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Nestin/analysis ; Neuropilin-1/analysis ; Placental Circulation ; Portal System/chemistry/*embryology ; Pregnancy ; Proteoglycans/analysis ; Receptor, EphB4/analysis ; Stem Cell Niche/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2018-10-02
    Description: Background/Aim: The aim of this phase I/II study was to determine the safety, and efficacy of combination of neoadjuvant chemotherapy (NAC) with biweekly docetaxel, cisplatin, and S-1 (DCS) in stage III gastric cancer patients. Patients and Methods: In the phase I study, S1 was administered at doses of 80 mg/day to 120 mg/day depending on the body surface area and docetaxel was administered at 20 mg/m 2 , whereas cisplatin was initially administered at 25 mg/m 2 and was escalated by 5 mg/m 2 up to 50 mg/m 2 . In the phase II study, safety and therapeutic efficacy of DCS were evaluated using the recommended dose of cisplatin. Results: In phase I, 21 patients were enrolled. In level II, perforation of gastric cancer occurred in one case although no dose limiting toxicities (DLTs) were noted in level III-VI. Recommended dose for cisplatin was 50 mg/m 2 /day. In phase II, among 47 patients, 14 experienced grade 3/4 adverse events. Clinically, response rate was 66.7% and disease control rate was 97.9%. The curative (R0) resection rate was 95.7%. Pathological response rate was 53.3%. Three-year overall survival and relapse-free survival rates were 78.5% and 65.3%, respectively. Conclusion: Biweekly DCS as NAC was efficient, safe, and acceptable; however, long-term survival should be evaluated to confirm the efficacy of biweekly DCS for stage III gastric cancer patients.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
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  • 5
    ISSN: 0305-0491
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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