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“A series of tandem duplications of an ancestral cathepsin L gene has given rise to a family of eight placenta-specific cathepsins in mice. These genes are differentially regulated both spatially and temporally and thus each can perform unique placental functions. Analysis of

the function and expression of these genes is yielding new insights into gene regulation and proteolytic processes in placenta, and may dissect critical placental roles of the single human functional ortholog, cathepsin L. (C) 2008 Elsevier Ltd. All rights reserved.”
“Although several drugs have been designed in the last few years to target specific BIX 01294 inhibitor key pathways and functions in colorectal cancer (CRC), the backbone of CRC treatment is still made up of compounds which rely on DNA damage to accomplish their role. DNA damage response (DDR) and checkpoint pathways are intertwined signaling networks that arrest cell cycle, recognize and repair genetic mistakes which arise during DNA replication and transcription, as well as through the exposure to chemical and physical agents that interact with nucleic acids. The good but highly variable

activity of DNA damaging agents in the treatment of CRC suggests that Selleck NU7026 intrinsic alterations in DDR pathways and cell cycle checkpoints may contribute differentially to the way cancer cells react to DNA damage. In the present review, our aim is to depict the recent advances in understanding the molecular basis of the activity of DNA damaging agents used for the treatment of CRC. We focus on the known and potential drug targets that are part of these complex and intertwined pathways. We describe the potential role of the checkpoints in CRC, and how their pharmacological manipulation could lead to chemopotentiation or synergism with currently used drugs.

Novel therapeutic agents playing a role in DDR and checkpoint inhibition are assessed. We discuss the possible rationale for combining PARP inhibition β-Nicotinamide with DNA damaging agents, and we address the link between DDR and EGFR pathways in CRC.”
“The efficacy of one-stage artificial dermis and skin grafting was tested in a nude rat model. Reconstruction with artificial dermis is usually a two-stage procedure with 2to 3-week intermission. If one-stage use of artificial dermis and split-thickness skin grafting are effective, the overall burden on patients and the medical cost will markedly decrease. The graft take rate, contraction rate, tissue elasticity, histology, morphometric analysis of the dermal thickness, fibroblast counting, immunohistochemistry of a-smooth muscle actin, matrix metalloproteinase-2, CD31, and F4/ 80, as well as gelatin zymography, real-time reverse transcriptase polymerase chain reaction for matrix metalloproteinase-2, and electron microscopy, were investigated from day 3 to 3 months postoperatively.