Clinical trial evaluates ex vivo cultured cord blood
Umbilical cord blood (UCB) is a rich source of hematopoietic stem and progenitor cells (HSPCs) that can be used for bone marrow transplantation; however, UCB transplantation is hampered by low numbers of HSPCs per donation, which delays engraftment and immune reconstitution. In this issue of the Journal of Clinical Investigation, Mitchell Horwitz and colleagues at Duke University Medical Center conducted a phase I clinical trial to test the long term engraftment capability of UCB HSPCs that were expanded ex vivo for 21 days in the presence of nicotinamide and then combined with the non-cultured T cell fraction of the UCB (NiCord). Eleven adults with hematological malignancies received 1 unit of NiCord and a second unit of un-manipulated UCB following myeloablative bone marrow conditioning. Eight patients exhibited complete or partial engraftment of the NiCord unit and achieved earlier hematopoietic recovery compared to historical controls. These results indicate that further clinical study of NiCord is warranted.
TITLE: Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment
AUTHOR CONTACT:
Mitchell Horwitz
Duke University Medical Center, Durham, NC, USA
Phone: 919-668-1045; E-mail: mitchell.horwitz@duke.edu
View this article at: http://www.jci.org/articles/view/74556
Murine model of Ewing's sarcoma reveals tumor origins
Ewing's sarcoma is a rare pediatric bone tumor that results from a genetic translocation that results in an EWS-ETS fusion. The tumor can have both mesodermal and ectodermal features, making it difficult to determine the cellular origin. In this issue of the Journal of Clinical Investigation, Takuro Nakamura and colleagues at the Japanese Foundation for Cancer Research developed a murine model of Ewing's sarcoma by introducing EWS-ETS fusion genes into a late gestational cell fraction enriched for osteochondrogenic progenitors from the embryonic superficial zone (eSZ) of the long bones The model tumors shared a gene expression profile with human Ewing's sarcoma and both murine and human tumors exhibited upregulated of WNT/β-catenin and EGF signaling. Finally, inhibitors of the WNT/β-catenin pathway attenuated murine tumor growth. This model provides a tool to evaluate potential therapies for treatment of this rare disease.
TITLE: Ewing's sarcoma precursors are highly enriched in embryonic osteochondrogenic progenitors
AUTHOR CONTACT:
Takuro Nakamura
The Cancer Institute, Tokyo, JPN
Phone: 81-3-3570-0462; Fax: 81-3-3570-0463; E-mail: takuro-ind@umin.net
View this article at: http://www.jci.org/articles/view/72399
ALSO IN THIS ISSUE
AGING
TITLE: Phosphatase WIP1 regulates adult neurogenesis and WNT signaling during aging
AUTHOR CONTACT:
Dmitry Bulavin
Institute Of Molecular And Cellular Biology, Singapore, SGP
Phone: 65-65869589; E-mail: dvbulavin@imcb.a-star.edu.sg
View this article at: http://www.jci.org/articles/view/73015
BONE BIOLOGY
TITLE: Vitamin B12–dependent taurine synthesis regulates growth and bone mass
AUTHOR CONTACT:
Vijay Yadav
Wellcome Trust Sanger Institute, Cambridge, GBR
Phone: +44-01223-496948; E-mail: vy1@sanger.ac.uk
View this article at: http://www.jci.org/articles/view/72606
GENETICS
TITLE: Hypomorphic PCNA mutation underlies a human DNA repair disorder
AUTHOR CONTACT:
Andrew Crosby
University of Exeter Medical School, Exeter, GBR
Phone: +44 (0)1392 408302; E-mail: a.h.crosby@exeter.ac.uk
View this article at: http://www.jci.org/articles/view/74593
IMMUNOLOGY
TITLE: Characterization of pandemic influenza immune memory signature after vaccination or infection
AUTHOR CONTACT:
Behazine Combadiere
INSERM UMR 1135, Paris, , FRA
Phone: +33140779888; Fax: +33140779734; E-mail: behazine.combadiere@upmc.fr
View this article at: http://www.jci.org/articles/view/74565
TITLE: Immune activation alters cellular and humoral responses to yellow fever 17D vaccine
AUTHOR CONTACT:
Lydie Trautmann
Vaccine and Gene Therapy Institute-Florida, Port Saint Lucie, FL, USA
Phone: 772-345-5671; Fax: 772-345-0625; E-mail: ltrautmann@vgtifl.org
View this article at: http://www.jci.org/articles/view/75429?key=57f03b2ed420ac53701b
NEUROSCIENCE
TITLE: Missense dopamine transporter mutations associate with adult parkinsonism and ADHD
AUTHOR CONTACT:
Ulrik Gether
University of Copenhagen, DK-2200 Copenhagen N, Denmark
Phone: 45.2384.0089; Fax: 45.3532.7610; E-mail: gether@sund.ku.dk.
View this article at: http://www.jci.org/articles/view/73778
ONCOLOGY
TITLE: CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor resistance
AUTHOR CONTACT:
Giuseppe Giaccone
Georgetown University, Washington, DC, USA
Phone: 202.687.7072; Fax: 202.687.0313; E-mail:gg496@georgetown.edu
Or
Yisong Wang
Georgetown University, Washington, DC, USA
Phone: 202.687.4738; Fax: 202.687.0313; E-mail:yw350@georgetown.edu
View this article at: http://www.jci.org/articles/view/73048
TITLE: MicroRNA-205 signaling regulates mammary stem cell fate and tumorigenesis
AUTHOR CONTACT:
Chun-Ju (Alice) Chang
Purdue University, West Lafayette, USA
Phone: 7654942648; E-mail: chunjuchang@purdue.edu
View this article at: http://www.jci.org/articles/view/73351
Journal
Journal of Clinical Investigation