February 1 Cancer Research Highlights

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Selected Articles from the February 1, 2007 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the February 1 issue of Cancer Research.

Liver Tumors Linked to Metabolic Regulation

Farnesoid X receptor (FXR, NR1H4) is a member of the nuclear hormone receptor superfamily, which plays an essential role in regulating bile acid, lipid, and glucose homeostasis. Yang et al. have described a novel function of the bile acid receptor FXR in preventing liver carcinogenesis. In aging FXR mutant mice between 13–15 months of age, both male and female FXR^-/- mice spontaneously developed liver tumors; however, no other tumors were developed after 15 months of age. In contrast, no liver tumors were observed in wild-type mice of the same age. The authors’ results suggest an intriguing link between metabolic regulation and hepatocarcinogenesis.

Prostaglandins Inhibit Intestinal Tumors

Experiments 20–30 years ago suggested that PGD2 may suppress tumors, but a role for PGD2 biosynthetic enzymes in tumor development had not been studied. Park et al. demonstrated that knockout of the hematopoietic prostaglandin D synthase (H-Pgds) gene in Apc^Min/+ mice led to roughly 50% more intestinal adenomas. Conversely, Apc^Min/+ mice with transgenic human H-PGDS tended to have 80% fewer adenomas. H-Pgds occurred mainly in stromal macrophages and monocytes of the gut mucosa. The results support an interpretation that H-Pgds had an inhibitory effect on tumor growth. Routing of prostaglandin production away from protumorigenic PGE₂ or inhibition of growth signals by PGD₂ metabolites are possible mechanisms. 

Nanoparticles Tracked in Tumors of Live Mice

Quantitative investigation of the dynamics of delivery in vivo is crucial in order to develop an effective drug delivery system. Tada et al. reported that single particles of quantum dots conjugated with anti-HER2 antibody could be tracked in tumors of living mice through a dorsal skin fold chamber using a high speed confocal microscopy system. The specific delivery of the drug from the vessels within the tumor to the perinuclear region of the tumor cells was recorded. This tracking method and the quantitative analysis is a powerful tool for developing an improved drug delivery system in the tumor microenvironment.

FasL Improves Adoptive T Cell Transfer

One strategy for improving adoptive therapy is preconditioning host immune environment by depleting CD4⁺CD25⁺ regulatory T cells (Treg) suppressive to antitumor responses. Given that Treg increase, or selectively accumulate, within tumors and are sensitive to FasL-mediated apoptosis, Chen et al. tested the hypothesis that inducing apoptosis of intratumoral Treg using FasL may improve adoptive T-cell therapy. The authors showed that FasL applied intratumorally via protein transfer decreased intratumoral Treg via inducing apoptosis in these cells. Their study demonstrated that using FasL to predeplete intratumoral Treg provides a useful means for optimizing adoptive therapy.

Peptide Vaccines Fight Spontaneous Breast Tumors

BALB-neuT transgenic mice expressing the neu oncogene in breast tissues develop spontaneous tumors at a relatively young age. Nava-Parada et al. showed that vaccination using a synthetic peptide (p66) representing a cytotoxic T lymphocyte epitope together with a Toll-like receptor ligand adjuvant (CpG) induced a strong immune response that prevented or delayed the development of breast tumors. The effectiveness of the vaccine against the spontaneous tumors was enhanced by concurrent treatment with anti-CD25 antibodies (aCD25), which blocked the suppressor activity of T regulatory cells. Antitumor vaccine efficacy was accompanied by the generation of T-cell responses to additional epitopes.