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81.
Although the epidermal growth factor receptor (EGFR), also known as HER1, has been studied for over a decade, it continues to be a molecule of great interest and focus of investigators for development of targeted therapies. The marketed monoclonal antibody cetuximab binds to HER1, and thus might serve as the basis for creation of imaging or therapies that target this receptor. The potential of cetuximab as a vehicle for the delivery of α-particle radiation was investigated in an intraperitoneal tumor mouse model. The effective working dose of 10 μCi of 212Pb-cetuximab was determined from a dose (10–50 μCi) escalation study. Toxicity, as indicated by the lack of animal weight loss, was not evident at the 10 μCi dose of 212Pb-cetuximab. A subsequent study demonstrated 212Pb-cetuximab had a therapeutic efficacy similar to that of 212Pb-trastuzumab (p = 0.588). Gemcitabine given 24 h prior to 212Pb-cetuximab increased the median survival from 174 d to 283 d, but carboplatin suppressed the effectiveness of 212Pb-cetuximab. Notably, concurrent treatment of tumor-bearing mice with 212Pb-labeled cetuximab and trastuzumab provided therapeutic benefit that was greater than either antibody alone. In conclusion, cetuximab proved to be an effective vehicle for targeting HER1-expressing tumors with α-radiation for the treatment of disseminated intraperitoneal disease. These studies provide further evidence that the multimodality therapy regimens may have greater efficacy and benefit in the treatment of cancer patients. 相似文献
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Hexokinase is the first enzyme in the glycolytic pathway catalyzing the reaction in which glucose is phosphorylated into glucose-6-phosphate. Mammals possess 4 isoforms of hexokinase; HK2 (hexokinase 2) is the predominant form in insulin-sensitive tissues such as adipocytes, as well as skeletal and cardiac muscle. In addition to its function in glucose metabolism, HK2 is associated with cardiomyocyte protection against mitochondrial-mediated apoptotic cell death; whether or not HK2 played a role in cardioprotective autophagy was yet to be discovered. However, in a recent study highlighted by a punctum in this issue of Autophagy, Roberts et al. addressed this possibility, uncovering a direct link between HK2, TORC1, and autophagy regulation. 相似文献
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Volatile chemicals in the environment provide ethologically important information to many animals. However, how animals learn to use this information is only beginning to be understood. This review highlights recent experimental advances elucidating olfactory learning in rodents, ranging from adaptations to the environment to task-dependent refinement and multisensory associations. The broad range of phenomena, mechanisms, and brain areas involved demonstrate the complex and multifaceted nature of olfactory learning. 相似文献
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The melanocyte-stimulating hormone receptor (MC1-R) is a central regulator of mammalian coat colour, encoded by the extension locus. In cattle, the dominant extension allele ED is associated with the production of black pigment in coloured areas. Genotyping of the MC1-R gene in a bull with mosaic expression of red vs. black pigment verified the existence of the ED allele, in spite of the fact that the majority of the animal is red coloured. No further mutations were found within the ED variant of the MC1-R gene, which was inherited from a completely red mother (genotype ED/e). 相似文献
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