Tissue biomarkers for prostate cancer radiation therapy.

Prostate cancer is the most common cancer and second leading cause of cancer deaths among men in the United States. Most men have localized disease diagnosed following an elevated serum prostate specific antigen test for cancer screening purposes. Standard treatment options consist of surgery or definitive radiation therapy directed by clinical factors that are organized into risk stratification groups. Current clinical risk stratification systems are still insufficient to differentiate lethal from indolent disease. Similarly, a subset of men in poor risk groups need to be identified for more aggressive treatment and enrollment into clinical trials. Furthermore, these clinical tools are very limited in revealing information about the biologic pathways driving these different disease phenotypes and do not offer insights for novel treatments which are needed in men with poor-risk disease. We believe molecular biomarkers may serve to bridge these inadequacies of traditional clinical factors opening the door for personalized treatment approaches that would allow tailoring of treatment options to maximize therapeutic outcome. We review the current state of prognostic and predictive tissue-based molecular biomarkers which can be used to direct localized prostate cancer treatment decisions, specifically those implicated with definitive and salvage radiation therapy.

Dlxin-1, a member of MAGE family, inhibits cell proliferation, invasion and tumorigenicity of glioma stem cells.

We have previously reported the presence of Dlxin-1, a member of the melanoma antigen gene (MAGE) family, in the brain and showed its function as a cell cycle arrest protein, suggesting that Dlxin-1 may have anti-proliferative functions in rapidly growing tumors. Using the cancer stem cell hypothesis, which attributes the initiation and progression of brain tumors to the cancer-initiating stem cells, we have investigated the role of Dlxin-1 in the glioma stem cells propagated by us as a cell culture system comprising of HNGC-2 cells. Our studies provide evidence about the role of Dlxin-1 as an anti-tumorigenic protein in the highly chemo-resistant glioma stem cells. Next, we show that these anti-proliferative effects are manifested by Dlxin-1 through down regulation of the activities of MMP-2 and MMP-9, and through interaction of Dlxin-1 with its target protein P311 that is involved in glioma cell invasion. In summary, we establish the roles for Dlxin-1, one as an anti-tumorigenic and anti-invasive protein in high-grade gliomas and the other as an inducer of differentiation of glioma stem cells. These two attributes, in conjunction, result in conversion of the drug-resistant brain tumor stem cells to the tumor-attenuated cells that may now be more amenable to effective therapeutic targeting.