American Association for Cancer Research

October 15, 2008 Cancer Research Highlights

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Selected Articles from the October 15, 2008 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 October 15 issue of Cancer Research.


Naturally Occurring HPV16 Integration Sites

Dall et al.

Page 8249

Cervical carcinoma is caused by persistent infection with high-risk human papillomavirus (HR-HPV). Using the W12 cervical carcinogenesis model, Dall and colleagues isolated clones of HPV16-infected keratinocytes in the absence of the competitive pressures that underlie cell selection in mixed populations. The authors found a profile of integration patterns similar to those seen in carcinomas, supporting the view that particular genomic regions show increased susceptibility to integration, rather than conferring a selective benefit. The data also suggest that integration can occur at any time during HPV infection, providing biological support to the importance of viral persistence in cervical carcinogenesis. 
 

Fetal Cell Microchimerism in Papillary Thyroid Cancer

Cirello et al.

Page 8482

Cirello et al.Fetal cells enter the maternal circulation during pregnancy and can persist in the maternal blood or tissues for decades, creating a physiological microchimerism. Cirello and colleagues studied the role of microchimerism in thyroid cancer. Persistent fetal male cells were detected in approximately half of the papillary thyroid cancers studied, and the total number of microchimeric cells was significantly higher in neoplastic tissues than in controlateral normal sections. Male cells were positive for the CD45 leukocytic antigen and negative for MHC II, indicating that they might be committed to destroy tumor cells, while microchimeric cells positive for tissue repair–associated thyroglobulin were found either in neoplastic and normal surrounding tissues. This is the first report suggestive of a protective role of microchimerism in thyroid cancer.


Murine and Human B-Cell Lymphoma Expression Profiling

Mori et al.

Page 8525

The Eμ-myc transgenic mouse model has been used as a model for the study of B-cell lymphoma and, like most cancer models initiated by a defined genetic alteration, the development of lymphomas involves the acquisition of multiple mutations that can serve as a model for the heterogeneity of human cancer. Mori and colleagues identified gene expression signatures associated with the activation of various cell signaling pathways and found several forms of B-cell lymphoma in the Eμ-myc mice. This study provides insight into the complexity of the oncogenic process and a novel strategy for dissecting the heterogeneity of B-cell lymphoma.


MicroRNAs (miRNA) are recently identified gene regulators that are at abnormal levels and implicated in virtually all types of cancer. Because miRNAs each regulate hundreds of mRNAs simultaneously, the potential for cellular transformation resulting from dysfunction of a single miRNA is high and the role of miRNA single nucleotide polymorphisms (SNP) in disease is just being defined. Chin and colleagues report on a SNP in a miRNA binding site of the human oncogene (KRAS) that increases the risk for developing non–small cell lung cancer. While the role of miRNAs in cancer has quickly become realized, the potential of SNPs that disrupt miRNA binding as predictors of cancer risk is a new and likely extremely fruitful direction of future study. 


Hyperpolarized 13C MRI of Prostate Cancer Biomarkers

Albers et al.

Page 8607

Albers et al.Hyperpolarization is a powerful new technique that provides an unprecedented increase in the signal-to-noise for in-vivo 13C magnetic resonance spectroscopic imaging (MRSI). Using this technique, Albers and colleagues determined if hyperpolarized [1-13C]pyruvate and its metabolic products could improve the detection and characterization of prostate cancer aggressiveness. They found that the level of hyperpolarized lactate that evolved from injected [1-13C]pyruvate increased with prostate tumor pathologic grade in transgenic mice. The lactate levels demonstrated minimal overlap between low-grade tumors and normal prostates and no overlap between low- and high-grade tumors. Thus, hyperpolarized lactate has great potential to become a new biomarker capable of improving prostate cancer detection and characterization of aggressiveness in patients. 


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