JCI online ahead of print table of contents for Feb. 24, 2014

February 24, 2014

Clinical trial assesses anti-FGF23 for treating X-linked hypophosphatemia

X-linked hypophosphatemia (XLH) is a heritable form of rickets that results from mutations in the gene encoding the phosphate regulating endopeptidase (PHEX). Unlike diet-associated forms of rickets, XLH cannot be ameliorated by vitamin D ingestion. XLH patients have increased serum levels of FGF23, which decreases both inorganic phosphate (Pi) and the activated form of vitamin D. In this issue of the Journal of Clinical Investigation, Thomas Carpenter and colleagues at Yale University evaluated the effectiveness and safety of an anti-FGF23 antibody (KRN23) in a small cohort of XLH patients. A single dose of KRN23 administered intravenously (i.v.) or subcutaneously (s.c.) improved renal phosphate reabsorption, and increased serum Pi and activated vitamin D concentrations, and s.c. administration provided benefit for a longer duration than i.v. dosing. These findings, along with a favorable safety profile, indicate that KRN23 should be further evaluated for use in XLH patients.

TITLE:
Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia

AUTHOR CONTACT:
Thomas Carpenter
Dept. Of Pediatrics (Endocrinology), New Haven, CT, USA
Phone: 203-785-6526; Fax: 203-737-4290; E-mail: thomas.carpenter@yale.edu

View this article at: http://www.jci.org/articles/view/72829




Altered glycosylation patterns protect tumors from NK cells

Compared to other diseased cells, malignant tumor cells often exhibit modified surface glycosylation patterns, potentially altering recognition by host immune cells. Natural killer (NK) cells are sentinels of cancer immunosurveillanc system and express multiple receptors that allow for discrimination between healthy and malignant cells. In this issue of the , Stephan von Gunten and colleagues at the University of Bern determined that ligands of the inhibitory sialic acid-binding lectins Siglec-7 and Siglec-9 are expressed on the surface of multiple tumor cell types, and that expression of these ligands protects tumor cells from NK cell responses. Evaluation of NK cells in healthy donors revealed the presence of a Siglec-9-expressing cytotoxic NK cell population with enhanced chemotactic potential. Interestingly, the Siglec-9-expressing NK cell population was reduced in peripheral blood from patients with colon adenocarcinoma and malignant melanoma. These data suggest that targeting Siglec-7 and Siglec-9 ligands may enhance NK cell-based cancer therapies.

TITLE:
Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent tumor immunosurveillance

AUTHOR CONTACT:
Stephan von Gunten
University of Bern, Bern, CHE
Phone: +41 31 632 32 98; Fax: +41 31 632 49 92; E-mail: stephan.vongunten@pki.unibe.ch

View this article at: http://www.jci.org/articles/view/65899




ALSO IN THIS ISSUE:

IMMUNOLOGY

TITLE:
IL-7 receptor blockade following T cell depletion promotes long-term allograft survival

AUTHOR CONTACT:
Hoa-Le Mai
INSERM, Nantes, FRA
Phone: 33240087410; Fax: 33240087411; E-mail: Le.Hoa-Mai@univ-nantes.fr

View this article at: http://www.jci.org/articles/view/66287

TITLE:
Pegylated IFN-α regulates hepatic gene expression through transient Jak/STAT activation

AUTHOR CONTACT:
Markus Heim
University Hospital Basel, Basel, , CHE
Phone: 011 41 61 265 33 62; E-mail: markus.heim@unibas.ch

View this article at: http://www.jci.org/articles/view/70408

MICROBIOLOGY

TITLE
Soluble TNFRp75 regulates host protective immunity against Mycobacterium tuberculosis

AUTHOR CONTACT:
Muazzam Jacobs
University of Cape Town, Cape Town, , ZAF
Phone: +27214066078; E-mail: muazzam.jacobs@uct.ac.za

View this article at: http://www.jci.org/articles/view/45005

NEUROSCIENCE

TITLE:
Familial Alzheimer's disease-associated presenilin-1 alters cerebellar activity and calcium homeostasis

AUTHOR CONTACT:
Markus Glatzel
Center for Diagnostic, University Medical Center Hamburg-Eppendorf, Hamburg, DEU
Phone: ++49-40-7410-57583; E-mail: m.glatzel@uke.de

View this article at: http://www.jci.org/articles/view/66407

ONCOLOGY

TITLE:
Hematopoiesis and RAS-driven myeloid leukemia differentially require PI3K isoform p110α

AUTHOR CONTACT:
Kira Gritsman
Dana Farber Cancer Institute, Boston, MA, USA
Phone: 617-459-7585; Fax: 617-632-4770; E-mail: kgritsman@partners.org

View this article at: http://www.jci.org/articles/view/69927

TITLE:
Oncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma

AUTHOR CONTACT:
David Carbone
The Ohio State University Medical Center, Columbus, OH
Phone: 617-632-4786; E-mail: david.carbone@osumc.edu

View this article at: http://www.jci.org/articles/view/72763
-end-


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