News Release

JCI online early table of contents: April 1, 2009

Peer-Reviewed Publication

JCI Journals

EDITOR'S PICK: Active component of marijuana has anticancer effects

Guillermo Velasco and colleagues, at Complutense University, Spain, have provided evidence that suggests that cannabinoids such as the main active component of marijuana (THC) have anticancer effects on human brain cancer cells.

In the study, THC was found to induce the death of various human brain cancer cell lines and primary cultured human brain cancer cells by a process known as autophagy. Consistent with the in vitro data, administration of THC to mice with human tumors decreased tumor growth and induced the tumor cells to undergo autophagy. As analysis of tumors from two patients with recurrent glioblastoma multiforme (a highly aggressive brain tumor) receiving intracranial THC administration showed signs of autophagy, the authors suggest that cannabinoid administration may provide a new approach to targeting human cancers.

TITLE: Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells

AUTHOR CONTACT:
Guillermo Velasco
Complutense University, Madrid, Spain.
Phone: 34-913944668; Fax: 34-913944672; E-mail: gvd@bbm1.ucm.es.

View the PDF of this article at: https://www.the-jci.org/article.php?id=37948


EDITOR'S PICK: Lithium protects brain cells during cranial radiation

Cranial radiation therapy to treat brain cancer can result in various long-term neurological side effects, particularly in children. Lithium has protective properties in the brain that make it a potential therapy for reducing these side effects; however, little is known about the mechanisms by which it protects nerves. In a new study, Fen Xia and colleagues, at Vanderbilt University Medical Center, Nashville, present results, generated in irradiated mice, that lithium protects nerves in the region of the brain known as the hippocampus by promoting DNA repair. Specifically, a decreased number of double-strand DNA breaks were observed in lithium-treated, irradiated mice and brain cells compared to controls. This decrease was associated with increased markers for the nonhomologous end-joining DNA repair pathway. When this pathway was blocked in mice, lithium provided substantially less protection to the hippocampal nerve cells. The authors therefore conclude that lithium should be considered as a possible treatment to reduce the long-term neurological side effects of cranial radiation therapy, particularly in children, and that targeted therapies to enhance DNA repair may provide an avenue for future therapeutic development.

TITLE: Lithium-mediated protection of hippocampal cells involves enhancement of DNA-PK–dependent repair in mice

AUTHOR CONTACT:
Fen Xia
Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Phone: (615) 322-2555; Fax: (615) 343-0161; E-mail: fen.xia@vanderbilt.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=34051


IMMUNOLOGY: Girls lacking the protein ITK at risk from fatal viral infection

One of the most common viruses to infect humans is EBV. Although most people show no or few signs of infection, some develop glandular fever and boys with mutations in either one of two genes on the X-chromosome (SAP and XIAP) develop a fatal lymphoproliferative disease. Arndt Borkhardt and colleagues, at Heinrich Heine University, Germany, have now identified two girls from a consanguineous Turkish family who died after becoming infected with EBV and developing a lymphoproliferative disorder clinically resembling that observed in EBV-infected boys deficient for SAP or XIAP. Detailed analysis revealed that the girls had a mutation in both copies of their ITK gene that rendered them deficient in ITK protein. The authors therefore suggest that ITK deficiency should be considered as a cause of EBV-associated lymphoproliferative disorders by those diagnosing and treating patients.

TITLE: Girls homozygous for an IL-2–inducible T cell kinase mutation that leads to protein deficiency develop fatal EBV-associated lymphoproliferation

AUTHOR CONTACT:
Arndt Borkhardt
Heinrich Heine University, Düsseldorf, Germany.
Phone: 49-211-811-7680; Fax: 49-211-811-7607; E-mail: arndt.borkhardt@med.uni-duesseldorf.de.

View the PDF of this article at: https://www.the-jci.org/article.php?id=37901


NEUROBIOLOGY: Nerve disorder following critical illness can be rapidly reversible

Individuals who are critically ill often suffer weakness as a result of either muscle or nerve disorders, which are known as myopathies and neuropathies, respectively. By prospectively following patients during the acute phase of critical illness and early recovery and assessing nerve conduction, Mark Rich and colleagues, at Wright State University, Dayton, have identified a rapidly reversible neuropathy that is caused by reduced nerve excitability. This neuropathy is distinct from the neuropathy caused by nerve cell degeneration, which takes a long time to recover from. Follow up experiments in rats indicated that the reduced nerve excitability underlying acute, rapidly reversible neuropathy was caused by inactivation of sodium channels. These data led the authors to suggest that some individuals develop a neuropathy during the acute phase of a critical illness that is caused by an acquired sodium channelopathy.

TITLE: Inactivation of sodium channels underlies reversible neuropathy during critical illness in humans and rats

AUTHOR CONTACT:
Mark M. Rich
Wright State University, Dayton, Ohio, USA.
Phone: (937) 775-2234; Fax: (937) 775-3009; E-mail: mark.rich@wright.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=36570


NEPHROLOGY: A mouse model of the kidney disease focal and segmental glomerulosclerosis

Focal and segmental glomerulosclerosis (FSGS) is a common kidney condition that causes kidney damage in children and adolescents and kidney failure in adults. Although it has been proposed that T cell immune responses contribute to the development of some cases of FSGS, it is unclear exactly how. But now, a team of researchers, at the University of Chicago, Chicago, has developed a new mouse model of FSGS in which disease is caused by T cells lacking the protein DAF.

The team, led by Richard Quigg and Lihua Bao, administered to BALB/c mice, antibodies that bind kidney cells known as podocytes. Mice that lacked DAF developed the hallmark features of FSGS, whereas normal mice did not. Using a series of elegant experiments, they further showed that DAF-deficient T cells elicit the immune response that leads to disease, leading them to conclude that DAF acts as a brake to prevent T cells from attacking podocytes.

TITLE: Focal and segmental glomerulosclerosis induced in mice lacking decay-accelerating factor in T cells

AUTHOR CONTACT:
Lihua Bao
University of Chicago, Chicago, Illinois, USA.
Phone: (773) 834-7480; Fax: (773) 702-5818; E-mail: lbao@medicine.bsd.uchicago.edu.

Richard J. Quigg
University of Chicago, Chicago, Illinois, USA.
Phone: (773) 702-0757; Fax: (773) 702-4816; E-mail: rquigg@medicine.bsd.uchicago.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=36000

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