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This Week in Clinical Cancer Research: Oct 7, 2011


In Clinical Cancer Research this week, a team of US researchers writes that cyclin-dependent kinase 5 is amplified and over-expressed in pancreatic cancer. The team analyzed the expression of CDK5 and its activators, p35 and p39, during the progression of pancreatic cancer. The team observed amplification of CDK5, and either p35 or p39 in 67 percent of the human pancreatic ductal adenocarcinoma cell lines it studied. In addition, the team says, inhibition of CDK5 kinase activity significantly decreased the migration and invasion of pancreatic cancer cells in vitro. The increased CDK5 activity was also observed in human pancreatic nestin-expressing cells expressing a mutant form of K-Ras. "These results suggest that mutant K-Ras acts in concert with CDK5 and its activators to increase malignant progression, migration, and invasion of pancreatic cancer cells," the authors write.

Also in Clinical Cancer Research this week, researchers in Canada write that recombinant human erythropoietin given in combination with chemotherapy can increase breast cancer metastasis. Erythropoiesis-stimulating agents are used to treat cancer-related anemia, the authors write. The team treated breast cancer cell lines with recombinant human erythropoietin, and screened for the expression of its receptors. They observed a large variation in receptor expression across the cell lines. In vitro, the erythropoietin had a protective effect on radiation-treated cells. But the erythropoietin alone or in combination with chemotherapy in a mouse model of breast cancer increased lung metastases compared to mice treated with chemotherapy alone. "These studies may begin to uncover the underlying functional explanation for the observed EPO-related adverse events and decreased survival in ESA-treated metastatic breast cancer patients undergoing chemotherapy," the team says.

Finally in Clinical Cancer Research this week, researchers at the National Cancer Institute observe that adoptive transfer of autologous natural killer cells does not mediate tumor regression. Adoptive transfer of tumor-infiltrating lymphocytes can mediate regression of metastatic melanoma, but since many patients are ineligible for this treatment, adoptively transferred autologous natural killer cells are used instead, the authors write. The team treated eight patients with metastatic melanoma or renal cell carcinoma with adoptively transferred in vitro activated autologous natural killer cells, however, and found that although they persisted in the peripheral circulation, they could not mediate antibody-dependent cell-mediated cytotoxicity. This suggests, the authors write, "that coupling adoptive natural killer cell transfer with monoclonal antibody administration deserves evaluation."

The Scan

LINE-1 Linked to Premature Aging Conditions

Researchers report in Science Translational Medicine that the accumulation of LINE-1 RNA contributes to premature aging conditions and that symptoms can be improved by targeting them.

Team Presents Cattle Genotype-Tissue Expression Atlas

Using RNA sequences representing thousands of cattle samples, researchers looked at relationships between cattle genotype and tissue expression in Nature Genetics.

Researchers Map Recombination in Khoe-San Population

With whole-genome sequences for dozens of individuals from the Nama population, researchers saw in Genome Biology fine-scale recombination patterns that clustered outside of other populations.

Myotonic Dystrophy Repeat Detected in Family Genome Sequencing Analysis

While sequencing individuals from a multi-generation family, researchers identified a myotonic dystrophy type 2-related short tandem repeat in the European Journal of Human Genetics.