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This Week in BMC Cancer: Oct 31, 2011


In BMC Cancer this week, researchers in Kansas and Oklahoma describe the development and characterization of a novel C-terminal inhibitor of heat shock protein 90 in prostate cancer cells. Hsp90 has been shown to be over-expressed in a number of cancers, the authors write. For this study, the team used PC3-MM2 and LNCaP-LN3 prostate cancer cell lines to test an Hsp90 inhibitor, KU174. The compound exhibits "robust anti-proliferative and cytotoxic activity along with client protein degradation and disruption of Hsp90 native complexes without induction of a [heat shock response]," a toxic effect of certain Hsp inhibitors, the team says. In addition, the compound demonstrated direct binding to the Hsp90 protein and Hsp90 complexes in the cancer cells, suggesting it has potential as a prostate cancer therapeutic.

Also in BMC Cancer this week, researchers in South Korea classify subtypes of breast cancer using protein and lipid MALDI profiles. The team analyzed 34 pairs of frozen, resected breast cancer and adjacent normal tissue samples using MALDI mass spec analysis, and were able to distinguish cancer from adjacent normal tissue using protein and lipid profiles with 94.1 percent median accuracy. "Luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles," the team writes. "Discriminatory proteins and lipids were useful for classifying tumors according to their intrinsic subtype with median prediction accuracies of 80 percent to 81.3 percent in random test sets."

Finally in BMC Cancer, researchers in Germany report their activation of the human immune system using chemotherapeutic agents combined with the oncolytic parvovirus H-1. Parvovirus H-1 infects and lyses human tumor cells, the team says. For this study, they used human ex vivo models to evaluate the biological and immunological effects of H-1PV-induced tumor cell lysis alone or with chemotherapy in human melanoma cells, and found that the H-1PV-infected cells showed a clear reduction in cell viability of more than 50 percent. The effect was further enhanced when the parvovirus was combined with chemotherapeutic agents. "In our human models, chemotherapeutic or targeted agents did not only interfere with the pronounced immunomodulatory properties of H-1PV, but also reinforced drug-induced tumor cell killing," the authors write. "H-1PV combined with cisplatin, vincristine or sunitinib induced effective immunostimulation via a pronounced DC maturation, better cytokine release and cytotoxic T-cell activation compared with agents alone. Thus, the clinical assessment of H-1PV oncolytic tumor therapy not only alone but also in combination strategies is warranted."

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