NOS1 expression predicts melanoma-dependent immune dysfunction
Individuals with cancer often exhibit dysfunctional immune signaling in response to interferon (IFN) stimulation. Furthermore, recent evidence indicates that pSTAT-1 levels, which are indicative of IFN responsiveness, in circulating immune cells are predictive of clinical outcome in melanoma patients. In this issue of the Journal of Clinical Investigation, Qiuzhen Liu and colleagues at Southern Medical University, Guangzhou, China determined that melanoma cells have differing capacity to dampen IFN responses in peripheral blood mononuclear cells and that NOS1 expression is indicative of the inhibitory potential of a particular melanoma. In melanoma patient metastases there was an inverse relationship between NOS1 expression and patient response to adoptive T cell therapy. These findings establish a link between a melanoma specific factors and immune dysfunction and suggest that NOS1 expression can be used as a predictive biomarker in melanoma.
TITLE: Melanoma NOS1 expression promotes dysfunctional IFN signaling
AUTHOR CONTACT: Qiu-Zhen Liu Southern Medical University, Guangzhou, CHN Phone: 86.20.62789410; E-mail: liuqiuzhen@126.com
View this article at: http://www.jci.org/articles/view/69611
Murine model of glucocorticoid-induced glaucoma
Patients with inflammatory diseases, including allergy, asthma, and autoimmune disorders are often prescribed glucocorticoids; however, a subset of patients develop secondary glaucoma in response to treatment and must stop use of these beneficial steroid hormones. In this issue of the Journal of Clinical Investigation, Val Sheffield and colleagues at the University of Iowa developed a murine model of glucocorticoid-induced glaucoma in which topical administration of 0.1% dexamethasone to the eye produces clinical hallmarks of human disease, including a substantial increase in intraocular pressure (IOP), functional and structural loss of retinal ganglion cells, axonal degeneration, and ECM alterations within cells of the trabecular meshwork (TM). Evaluation of human TM cells revealed chronic ER stress in response to dexamethasone. Moreover, increased IOP in response to dexamethasone was prevented in animals lacking the ER stress-associated transcription factor CHOP or treated with the chemical chaperone sodium 4-phenylbutyrate. These results indicate that ER stress contributes to the etiology of glucocorticoid-induced glaucoma and suggest that reducing ER stress has therapeutic potential for relieving elevated IOP.
TITLE: Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma
AUTHOR CONTACT: Val C. Sheffield Dept. Of Pediatrics, Iowa City, IA, USA Phone: 319/335-6898 office; Fax: 319-335-7588; E-mail: val-sheffield@uiowa.edu
View this article at: http://www.jci.org/articles/view/69774
CELL BIOLOGY
TITLE: Ciliopathy proteins regulate paracrine signaling by modulating proteasomal degradation of mediators
AUTHOR CONTACT: Nicholas Katsanis Duke University Medical Center, Durham, NC, USA E-mail: katsanis@cellbio.duke.edu
View this article at: http://www.jci.org/articles/view/71898
HEMATOLOGY
TITLE: Platelet-derived S100 family member myeloid-related protein-14 regulates thrombosis
AUTHOR CONTACT: Daniel Simon Case Western Reserve University School of, Cleveland, OH, USA Phone: 216-844-8151; Fax: 216-983-3202; E-mail: Daniel.Simon@UHhospitals.org
View this article at: http://www.jci.org/articles/view/70966?key=5779faf807faaa6c6485
IMMUNOLOGY
TITLE: Hydroxycarboxylic acid receptor 2 mediates dimethyl fumarate's protective effect in EAE
AUTHOR CONTACT: Markus Schwaninger University of Luebeck, Luebeck, , DEU Phone: +49-451-5002681; E-mail: markus.schwaninger@pharma.uni-luebeck.de
View this article at: http://www.jci.org/articles/view/72151
TITLE: Laminins affect T cell trafficking and allograft fate
AUTHOR CONTACT: Bryna Burrell University of Maryland School of Medicine, Baltimore, MD, USA Phone: 410 706 8070; E-mail: brynaeburrell@yahoo.com
View this article at: http://www.jci.org/articles/view/73683
NEUROSCIENCE
TITLE: Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis
AUTHOR CONTACT: Heike Heuer Leibniz Institute for Age Research/Fritz Lipmann Institute, Jena, UNK, DEU Phone: 00493641656021; Fax: 00493641656335; E-mail: hheuer@fli-leibniz.de
View this article at: http://www.jci.org/articles/view/70324
ONCOLOGY
TITLE: Excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer
AUTHOR CONTACT: Robert J. Coffey Vanderbilt University Medical Center, Nashville, TN, USA Phone: 615 343-6228; Fax: 615-343-1591; E-mail: robert.coffey@vanderbilt.edu
View this article at: http://www.jci.org/articles/view/71103
TITLE: Senescence-associated SIN3B promotes inflammation and pancreatic cancer progression
AUTHOR CONTACT: Gregory David New York University School of Medicine, New York, NY, USA Phone: 212-263-7111; E-mail: Gregory.David@nyumc.org
View this article at: http://www.jci.org/articles/view/72619
VIROLOGY
TITLE: Cytomegalovirus pp65 limits dissemination but is dispensable for persistence
AUTHOR CONTACT: Klaus Frueh Oregon Health and Science University, Beaverton, OR, USA Phone: 503 418 2735; Fax: 503 418 2722; E-mail: fruehk@ohsu.edu
View this article at: http://www.jci.org/articles/view/67420
Journal
Journal of Clinical Investigation