Mucin concentration contributes to a sticky situation in cystic fibrosis
Patients with cystic fibrosis (CF) accumulate thick, sticky mucus in the lungs that clogs the airways and leads to life-threatening lung infections. It has recently been proposed that differing concentrations of mucin with in mucus layers of the CF lung contribute to decreased mucus clearance; however, it has been challenging to accurately access mucin concentration. In this issue of the Journal of Clinical Investigation, Mehmet Kesimer and colleagues at the University of North Carolina applied size exclusion chromatography/differential refractometry techniques to measure the mucin concentration in sputum from normal and CF airways. Mucin concentrations and partial osmotic pressure were greater in CF secretions compared to normal secretions. Importantly, increased mucin concentration and partial osmotic pressure promoted mucus stasis, thereby contributing to lung infection and inflammation in CF.
TITLE: Cystic fibrosis airway secretions exhibit mucin hyperconcentration and increased osmotic pressure
The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Phone: 9198432577; E-mail: firstname.lastname@example.org
View this article at: http://www.jci.org/articles/view/73469
Engineered aptimer targets malignant and tumor-associated T cells
The transcription factor STAT3 mediates tumor survival, proliferation, invasion, and immunosuppression, and is persistently activated in tumor cells and tumor-associated immune cells. In T cells, STAT3 activation impairs anti-tumor responses, while inhibition or loss of STAT3 promotes anti-tumor responses. In this issue of the Journal of Clinical Investigation, Hua Yu and colleagues at the Beckman Research Institute developed an aptamer-based strategy to deliver STAT3 siRNA and inhibit STAT3 in tumor cells and tumor-associated immune cells. An aptamer that binds the cell surface receptor cytotoxic T lymphocyte-associated antigen-4 (CTLA), an inhibitor of the T cell anti-tumor response, was attached to STAT3 siRNA (CTLA4apt-STAT3 siRNA), allowing for targeted delivery to tumor-associated T cells, Tregs or malignant T cells. Local or systemic administration of CTLA4apt STAT3 siRNA in different murine tumor models decreased STAT3 expression in CTLA4-expressing T cells, reduced tumor-associated Tregs, and decreased tumor growth and metastasis. Importantly, CTLA4apt STAT3 siRNA inhibited tumor growth and promoted tumor cell apoptosis in mice bearing human T cell lymphoma.
TITLE: CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells
Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
Phone: 626-471-7238; Fax: 626-256-8708; E-mail: email@example.com
View this article at: http://www.jci.org/articles/view/73174
ALSO IN THIS ISSUE:
TITLE: NOTCH inhibits osteoblast formation in inflammatory arthritis via noncanonical NF-κB
University of Rochester Medical Center, Rochester, NY, USA
Phone: 585.273.4090; Fax: 585.756.4468; E-mail: Lianping_xing@urmc.rochester.edu.
View this article at: http://www.jci.org/articles/view/68901
TITLE: Myosin Vb uncoupling from RAB8A and RAB11A elicits microvillus inclusion disease
Vanderbilt University School of Medicine, Nashville, TN, USA
Phone: 615-936-3726; Fax: 615-343-1591; E-mail: firstname.lastname@example.org
University of Arizona College of Medicine, Phoenix, AZ, USA
Phone: 602.933.0940; Fax: 602.933.0373; E-mail: email@example.com.
View this article at: http://www.jci.org/articles/view/71651
Biliary repair and carcinogenesis are mediated by IL-33–dependent cholangiocyte proliferation
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
Phone: 5136363008; Fax: 5136365581; E-mail: firstname.lastname@example.org
View this article at: http://www.jci.org/articles/view/73742
TITLE: Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals
National Institutes of Health, Bethesda, MD, USA
Phone: 301-402-4559; Fax: 301-480-0643; E-mail: email@example.com
View this article at: http://www.jci.org/articles/view/74351?key=97bbd7f61e344de76f06
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