American Association for Cancer Research

December 1, 2008 Cancer Research Highlights

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Selected Articles from the December 1, 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 December 1 issue of Cancer Research.


TC21 and Tamoxifen Treatment Outcome 

Rokavec et al.

Page 9799

Growing evidence suggests that cross-talk between estrogen receptor and growth factor signal transduction pathways contributes
to tamoxifen resistance. Rokavec and colleagues provide the first evidence for the relevance of TC21, a member of the Ras superfamily of GTP-binding proteins, in tamoxifen resistance. The authors provide functional and patient-based data that support the notion that the promoter polymorphism TC21 −582 C>T improves the prediction of treatment outcome in breast cancer. 
 

ERα in Cervical Carcinogenesis

Chung et al.

Page 9928

The majority of cervical cancers are associated with certain human papilloma viruses (HPV). However, HPV infection alone is not sufficient for the development of cervical cancer. Compelling evidence for estrogen’s role in this cancer comes from studies in HPV transgenic mice. Chung and colleagues show that estrogen’s contribution to cervical cancer in the K13E7 HPV transgenic mouse model is wholly dependent upon estrogen receptor alpha (ERα). This finding raises the prospect that human cervical cancer could be responsive to drugs that interfere with ERα function.


SPINT2 Inhibits the Growth of Medulloblastoma

Kongkham et al.

Page 9945

Kongkham et al.To identify novel genes involved in medulloblastoma pathogenesis, Kongkham and colleagues used a genome-wide epigenetic screen and identified the HGF/MET signaling inhibitor SPINT2 as a putative tumor suppressor silenced by promoter methylation. Hemizygous loss of SPINT2 and gains of the HGF and MET loci were identified by SNP array. SPINT2 expression was reduced and MET expression increased in 73.2% and 45.5% of tumors, respectively, and promoter methylation was seen in 34.3%. SPINT2 re-expression reduced proliferation, anchorage-independent growth, cell motility, and increased survival in a xenograft model. These data support the role of SPINT2 as a tumor suppressor gene and further implicate the HGF/MET pathway in medulloblastoma pathogenesis.


Sung et al.Standish and colleagues used Doppler optical coherence tomography (DOCT), the optical analog of high-resolution ultrasound imaging, to measure changes in microvascular blood flow during photodynamic therapy (PDT) in Dunning rat prostate tumors. A strong inverse relationship was found between the rate of PDT-induced blood flow shutdown during light administration and the resulting percent of local tumor necrosis at 24 h posttreatment. This suggests a potential role for minimally-invasive interstitial DOCT in monitoring local tumor response during PDT, with the possibility of on-line monitoring for optimizing treatment parameters in individual patients. 


Tumor-Stroma Interactions in the Prostate

Sung et al.

Page 9996

Tumor-microenvironment interactions are crucial in oncogenesis and cancer progression. Sung and colleagues use a 3-dimensional coculture system to show that human bone stromal cells undergo permanent cytogenetic and gene expression changes when cocultured with prostate cancer cells and that these changes are mediated by reactive oxygen species. The evolved stromal cells are highly inductive of human prostate cancer growth in mice, and express increased levels of extracellular matrix (versican and tenascin) and chemokine (BDNF, CCL5, CXCL5 and CXCL16) genes which are validated in clinical specimens. These results, combined with previous observations, suggest coevolution of cancer and stromal cells, which could ultimately accelerate cancer growth and metastasis. 


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