Public Release:  JCI early table of contents for Oct. 25, 2013

Journal of Clinical Investigation

Ionizing radiation exposure promotes fusion oncogene formation

The accident at the Chernobyl nuclear power plant exposed hundreds of thousands of individuals to high levels of ionizing radiation. In the years immediately following the disaster, there was a sharp increase in the number of papillary thyroid cancers (PTC) in patients that were children at the time of the explosion. In this issue of the Journal of Clinical Investigation, James Fagin and colleagues at Memorial Sloan-Kettering Cancer Institute, examined tissues from Ukrainian PTC patients that were children at the time of the Chernobly catastrophe and identified their cancer-driving mutations. The authors found that the majority of patient tumors had chromosomal rearrangements that resulted in fusion oncogenes. Many of these fusion events promoted upregulation of MAPK signaling, which is a common cancer-associated pathway. In contrast, fusion oncogenes were less common in PCT tumors from patients from the same geographical region, but had not been exposed to radiation. In the accompanying commentary, Massimo Santoro and Francesca Carlomagno of the University of Naples discuss how this study provides new insight into how ionizing radiation exposure promotes cancer development.

TITLE: Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced thyroid cancers

AUTHOR CONTACT: James Fagin
Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Phone: 646 888 2136; Fax: 646 422 0675; E-mail: faginj@mskcc.org

View this article at: http://www.jci.org/articles/view/69766?key=cdfbc3f1c40d0fe25fc2

ACCOMPANYING COMMENTARY

TITLE: Oncogenic rearrangements driving ionizing radiation-associated human cancer

AUTHOR CONTACT: Massimo Santoro
University of Naples Federico II, Naples, , ITA
Phone: 39-081-7463037; Fax: ; E-mail: masantor@unina.it

View this article at: http://www.jci.org/articles/view/72725?key=14085f7fdfd084da5da8


Researchers track lethal prostate cancer to determine clonal origin

Prostate cancer has variable manifestations, ranging from relatively benign localized tumors to widespread life-threatening metastases. The origin of most prostate cancer metastases can be traced back to the primary tumor; therefore, understanding the mutations in the primary tumor that promote cancer spread is of great interest. In this issue of the Journal of Clinical Investigation, Srinivasan Yegnasubramanian and colleagues at Johns Hopkins University track the development of lethal prostate cancer in a patient. Using tissue samples taken throughout the progression of the cancer, the authors identified the origin of the lethal clone. Surprisingly, in this case the lethal clone originated from a small, low-grade foci in the primary tumor and not from the larger high-grade region of the tumor. In the accompanying commentary, Rose Brannon and Charles Sawyers of Memorial Sloan-Kettering Cancer Center discuss the importance of individual case studies and how a comprehensive database of such studies is needed to identify common patterns in cancer progression.

TITLE: Tracking the clonal origin of lethal prostate cancer

AUTHOR CONTACT: Michael C. Haffner
Johns Hopkins Medical Institutions, Baltimore, MD, USA
Phone: 4106142676; Fax: ; E-mail: michael.c.haffner@gmail.com

View this article at: http://www.jci.org/articles/view/70354?key=4f436390394081ee2a50

ACCOMPANYING COMMENTARY

TITLE: "N of 1" case reports in the era of whole-genome sequencing

AUTHOR CONTACT: Charles Sawyers
Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Phone: 646-888-2138; Fax: ; E-mail: sawyersc@mskcc.org

View this article at: http://www.jci.org/articles/view/70935?key=0fe6ce6bb3bf4e8a509a


Reduction of reactive oxygen species in diabetes-associated nephrology

Diabetes-associated complications, including retinopathy, neuropathy, and nephropathy are associated with increased glucose levels, but it is not understood how glucose drives these manifestations. There is evidence that cultured cells exposed to high levels of glucose produce reactive oxygen species (ROS); however it is unknown if ROS contributes directly to diabetes complications. In this issue of the Journal of Clinical Investigation, Kumar Sharma and colleagues at the University of California, San Diego determined that ROS production was actually reduced in kidneys of diabetic mice, and this decrease was associated with lowered activity of the major energy-sensing enzyme, AMPK. Furthermore, AMPK activity was also reduced in kidneys of diabetic patients. Treatment of diabetic mice with a compound that increased AMPK activity reduced kidney-associated symptoms, including fibrosis and albuminuria. In the companion commentary, Dwight Towler of the Sanford-Burnham Medical Institute discusses how this view of ROS in diabetes will require a new look at therapeutic approaches for relieving diabetes complications.

TITLE: AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function

AUTHOR CONTACT: Kumar Sharma
UCSD, La Jolla, CA, USA
Phone: 858-822-0870; Fax: 858-822-7483; E-mail: kusharma@ucsd.edu

View this article at: http://www.jci.org/articles/view/66218?key=5fad8f958699794ef103

ACCOMPANYING COMMENTARY

TITLE: Mitochondrial ROS deficiency and diabetic complications: AMP[K]-lifying the adaptation to hyperglycemia

AUTHOR CONTACT: Dwight Towler
Sanford-Burnham Medical Research Institute, orlando, , USA
Phone: 407-745-2079; E-mail: dtowler@sanfordburnham.org

View this article at: http://www.jci.org/articles/view/72326?key=dcdae15a08a5b61c4555


Synthetic vitamin D receptor ligands reduce murine kidney fibrosis

Vitamin D deficiency has been associated with kidney disease including fibrosis. Some studies have even suggested that treatment with vitamin D or vitamin D analogs can reduce renal fibrosis; however, the pathways targeted by vitamin D therapy are not completely understood. In this issue of the Journal of Clinical Investigation, Junn Yanagisawa and colleagues at the University of Tsukuba found that vitamin D binding to its receptor inhibited the TGF-β/SMAD signaling pathway and prevented renal fibrosis in mice. The authors then generated a synthetic ligand of the vitamin D receptor that, like vitamin D, reduced renal fibrosis; however, unlike vitamin D, this synthetic ligand did not promote hypercalcemia. In the accompanying commentary Joseph Bonventre suggests that synthetic ligands of the vitamin D receptor should be further studied as therapeutics for patients with fibrotic diseases.

TITLE: A nonclassical vitamin D receptor pathway suppresses renal fibrosis

AUTHOR CONTACT: Junn Yanagisawa
University of Tsukuba, Tsukuba, , JPN
Phone: 81-29-853-7320; E-mail: junny@agbi.tsukuba.ac.jp

View this article at: http://www.jci.org/articles/view/67804?key=e9b75812c32074994393

ACCOMPANYING COMMENTARY

TITLE: Antifibrotic vitamin D analogs

AUTHOR CONTACT: Joseph V. Bonventre
Brigham and Women's Hospital, Boston, MA, USA
Phone: 617-525-5966; Fax: 617-525-5965; E-mail: joseph_bonventre@hms.harvard.edu

View this article at: http://www.jci.org/articles/view/72748?key=c9aa266738ffedbb76ab


Itch maintains regulatory T cell stability

Regulatory T cells (Tregs) function to suppress immune responses of other cells, and their dysfunction has been associated with development of immune disorders. Recent studies suggest that Tregs maintain plasticity even after differentiation, and can be influenced to change their regulatory profile. In this issue of the Journal of Clinical Investigation, Yun-Cai Liu and colleagues at the La Jolla Institute for Allergy and Immunology identified the E3 ubiquitin ligase Itch as a regulator of Tregs stability. The authors found that in the absence of Itch, Tregs took on a Th2 phenotype, which promoted the development of severe antigen-induced airway inflammation, skin lesion formation and other inflammatory characteristics in mice. In a companion commentary, WanJun Chen of the National Institutes of Health discusses the implications of this study on our understanding of allergy and asthma development.

TITLE: Itch expression by Treg cells controls Th2 inflammatory responses

AUTHOR CONTACT: Yun-Cai Liu
La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA
Phone: 858-752-6810; Fax: 858-752-6985; E-mail: yuncail@liai.org

View this article at: http://www.jci.org/articles/view/69355?key=34db86acfb334e362aa5

ACCOMPANYING COMMENTARY

TITLE: Regulatory T cells use "Itch" to control asthma

AUTHOR CONTACT: Wanjun Chen
Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD, USA
Phone: 301-435-7168; Fax: 301-4021064; E-mail: wchen@dir.nidcr.nih.gov

View this article at: http://www.jci.org/articles/view/72477?key=1155af77c3a6e661aeb8


ALSO IN THIS ISSUE

TITLE: Essential amino acid supplementation in patients following total knee arthroplasty

AUTHOR CONTACT: Hans Dreyer
University of Oregon, Eugene, OR, USA
Phone: 541-346-5775; E-mail: hcdreyer@uoregon.edu

View this article at: http://www.jci.org/articles/view/70160?key=48ce954b6c56505ca64d

TITLE: Developmental and tumoral vascularization is regulated by G protein-coupled receptor kinase 2

AUTHOR CONTACT: Petronila Penela
Centro de Biologia Molecular "Severo Ochoa", Madrid, , ESP
Phone: 34-91-1964640; E-mail: ppenela@cbm.uam.es

View this article at: http://www.jci.org/articles/view/67333?key=605468cd5840ccf93d9f

TITLE: Human iPS cell-derived alveolar epithelium repopulates lung extracellular matrix

AUTHOR CONTACT: Mahboobe Ghaedi
Yale University, New Haven, CT, USA
Phone: 475 227 9071; Fax: (203) 737-1484; E-mail: mahboobe.ghaedi@yale.edu

View this article at: http://www.jci.org/articles/view/68793?key=39bc1cc716812428ac32

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