JCI table of contents: April 22, 2008

TITLE: Human and simian immunodeficiency viruses deregulate early hematopoiesis through a Nef/PPAR-gamma/STAT5 signaling pathway in macaques

AUTHOR CONTACT:
Stéphane Prost
Institute of Emerging Disease and Innovative Therapies, CEA, Fontenay-aux-Roses, France.
Phone: 33-1-46-54-94-69; Fax: 33-1-46-54-77-26; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=33037

ACCOMPANYING COMMENTARY
TITLE: Is Nef the elusive cause of HIV-associated hematopoietic dysfunction?

AUTHOR CONTACT:
Frank Kirchhoff
University of Ulm, Ulm, Germany.
Phone: 49-731-50065109; Fax: 49-731-50065131; E-mail: .

Guido Silvestri
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: (215) 573-5363; Fax: (215) 573-5366; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=35487

ONCOLOGY: Downfall of some tumor cells is their reliance on just one of three cyclin D proteins

Unlike normal cells, which have three cyclin D proteins that can each cover for the others, the cells of many types of cancer, especially blood cancers such as multiple myeloma, express only one cyclin D protein. This has led to the suggestion that targeting individual cyclin D proteins might provide a good approach to treating individuals with cancers characterized by a reliance on just one cyclin D protein. Evidence to support this idea has now been generated in preclinical models by Keith Stewart and colleagues, at the Mayo Clinic in Scottsdale, Arizona.

In the study, a large number of chemicals were screened for their ability to inhibit the expression of the CCND2 gene, which is the gene that carries the information for making the cyclin D2 protein. During the screen, a chemical from plants known as kinetin riboside was shown to inhibit expression of both the CCND2 gene and the CCND1 gene. Further analysis revealed that the chemical inhibited the expression of both cyclin D1 and cyclin D2 in cells from individuals with multiple myeloma and myeloma cell lines, causing the cells to stop growing and to die. The chemical also prevented myeloma cell lines from growing when transplanted into mice. The authors have therefore suggested that these data provide a good rationale for further exploration of the ability of kinetin riboside and other drugs that target cyclin D1 and/or cyclin D2 to benefit individuals with cancers characterized by a reliance on either cyclin D1 or cyclin D2, such as many individuals with multiple myeloma.

TITLE: Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity

AUTHOR CONTACT:
A. Keith Stewart
Mayo Clinic, Scottsdale, Arizona, USA.
Phone: (480) 301 4411; Fax: (480) 301 8387; E-mail: .