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This Week in Clinical Cancer Research: Jul 19, 2012


In Clinical Cancer Research this week, researchers in Brazil and Germany report their investigation of tumor-associated macrophages in pediatric classical Hodgkin lymphoma. The team analyzed the number of macrophages and dendritic cells in the tumor microenvironment of 100 cases of pediatric Hodgkin lymphoma and found that 44.8 percent of them were positive for Epstein-Barr virus. They also found that patients 10 years or younger had more CD14+ cells. "In comparison with nodular sclerosis, mixed cellularity was characterized by higher numbers of CD14+ and CD163+ cells," the authors write. "EBV+ cases exhibited higher numbers of CD14+, CD68+, and CD163+ cells." CD68+ cells didn't seem to have an effect on patient outcomes, but the team did observe worse progression-free survival in patients with a high numbers of CD163+ cells. "Our results suggest that macrophage composition in pediatric cHL is distinct from adults," the team adds. "Functional status of macrophages and their value as prognostic indicators in pediatric cHL may depend on EBV status."

Also in Clinical Cancer Research, researchers at Vanderbilt University Medical Center report that gastric cancer patients' resistance to tumor necrosis factor-related apoptosis inducing ligand, or TRAIL, therapy is mediated by the phosphoprotein DARPP-32. Using in vitro cell models, the team explored both stable expression and knock-down of DARPP-32 in gastric cancer cells. They write that stably expressed DARPP-32 enhanced cell survival and suppressed TRAIL-induced cytochrome c release and activation of caspase-3,-8, and -9. In addition, they found that knocking down DARPP-32 sensitized resistant cells to TRAIL-induced apoptosis. "DARPP-32 induced BCL-xL expression through activation of Src/STAT3 signaling, and treatment with the Src-specific inhibitor PP1 abrogated DARPP-32–dependent BCL-xL upregulation and cell survival," the authors write. "This suggests that upregulation of BCL-xL could play a possible role in blocking the mitochondria intrinsic apoptosis pathway, whereas the DARPP-32 effect on the NF-κB/FLIP(S) axis could serve as an additional negative feedback loop that blocks TRAIL-induced activation of caspase-8."

Finally in Clinical Cancer Research, researchers at the University of Texas MD Anderson Cancer Center investigate the value of SNPs in microRNA-related genes as predictors of clinical outcomes in colorectal cancer. The team genotyped 41 SNPs in 26 microRNA-related genes in 1,097 colorectal cancer patients and found that mir608: rs4919510 was associated with increased risk for recurrence and death in patients with stage III disease. The researchers also found that mir219-1:rs213210 was consistently associated with death. "In combined analysis of these two SNPs, patients carrying the variant genotypes at both sites exhibited a 5.6-fold increased risk of death," the authors write.

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