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View the Table of Contents for the March 15 issue of Cancer Research.
Estrada et al. Page 3078
Tumors of similar histological appearance often differ in aggressiveness and therapeutic response. Current methods to identify high-risk patients and predict response to therapy are limited. Estrada et al. used an orthotopic organ culture model of bladder cancer together with quantum-dot–based fluorescent imaging approaches to obtain quantitative measurements of tumor cell behavior. With this approach, distinct phenotypes were assigned to two metastatic bladder cancer cell lines based on different patterns of invasiveness into the bladder wall. This assay system, EViTAS (ex vivo tumor assay system), is amenable to behavioral profiling of human cancer.
Xie et al. Page 3188
Brain metastasis is a major cause of morbidity and mortality in patients with melanoma. The molecular changes that lead to brain metastasis remain poorly understood. Xie et al. developed a model to study human melanoma brain metastasis and found that Stat3 activity is increased in human brain–metastatic melanoma cells. The expression of activated Stat3 is also increased in human brain metastasis specimens when compared with that in the primary melanoma specimens. Increased Stat3 activation enhances brain metastasis, whereas blockade of Stat3 activation suppresses brain metastasis of human melanoma cells in animal models. Furthermore, the results indicate that Stat3 activation plays an important role in dysregulated expression of bFGF, VEGF, and MMP-2 and, hence, angiogenesis and invasion of melanoma cells. Stat3 activation also contributes to brain metastasis of melanoma, which may make it a new potential target for therapy of human melanoma brain metastases.
Page 3264
Global inhibition of transcription is an effective approach against certain tumors, which depend on labile antiapoptotic proteins for their survival. Radhakrishnan and Gartel report the identification of a novel transcriptional inhibitor, ARC, and show that it down-regulates the antiapoptotic gene survivin in several tumor cell lines. Remarkably, ARC induces apoptosis in human tumor and transformed cells, but not in normal cells, and possesses strong antiangiogenic activity in vitro. Although ARC promotes accumulation of p53, ARCinduced apoptosis in tumor cells is p53-independent, suggesting that it may be useful for treatment of tumors with functionally inactive p53. All of these properties make ARC an attractive candidate for anticancer drug development.
Page 3338
A sensitive screening approach for lung cancer could markedly reduce the mortality for this disease. A nested, casecontrol study of incident lung cancer cases from a high-risk cohort was conducted to evaluate promoter methylation of genes in sputum. Six of 14 genes were associated with a >50% increased lung cancer risk. Importantly, the concomitant methylation of three or more of these genes was associated with a 6.5-fold increased risk and a sensitivity and specificity of 64%. This study shows the promise of promoter hypermethylation of a panel of genes as a molecular marker for identifying people at high risk for cancer incidence.