We initiated the treatment of mice with EtPhCbl to explore whether this would lead to a Cbl- deficient state. Our results show that the Cbl-deficient state is likely to be caused by a combination of Cbl depletion and tissue accumulation of EtPhCbl. At the end of the experiment, the mice treated with EtPhCbl showed an increase in MMA and tHcy of 3.4 and 1.5, respectively, when compared to control animals. The increase in MMA and tHcy is considerably higher than observed in other models of Cbl deficiency such as total gastrectomy, nutritional deprivation of Cbl or treatment with cobinamide. At the same time, the increase in MMA is much lower than in transgenic mice with a none-functioning Ado-Cbl dependent enzyme. MMA in the knockout mice is up to 500 ��l/L at 8 weeks of age. These observations suggest that our model creates a more profound state of Cbl deficiency than previously reported models. Simultaneously, our results indicate the presence of a considerable residual enzyme activity, even in animals where the total amount of Cbl in the liver is reduced to one third of that in the control animals and where more than half of the total Cbl present occurs as EtPhCbl. In conclusion, we have shown that prolonged treatment of mice with the new Cbl derivative, EtPhCbl, induces a more severe Cbl deficiency than previous experimental models aimed at establishing Cbl deficiency. Surprisingly, Cbl deficiency was associated with cellular depletion of endogenous Cbl apparently caused by binding of EtPhCbl to TC at the expense of endogenous Cbl combined with an impaired cellular uptake of EtPhCbl. This observation points to the fact that binding of a Cbl derivative to TC does not necessarily predict cellular accumulation of the derivative. We suggest the use of animal models, such as ours, in order to explore the potential pharmacological benefits of new Cbl derivatives. A clinical useful derivative must enter the cells without impairing the transport of endogenous Cbl. Generally, breast cancers with LN+ER/AbMole Diatrizoic acid PR-Her2+ status phonotype are practically considered at high risk for recurrence. However, no report on the accurately recurrent rate of LN +ER/PR-Her2+ status breast cancer has been found. Our current limited data showed that the recurrent rate of LN +ER/PR-Her2+ status breast cancer was about 43.3% and the recurrent rate of LN-ER/PR+Her2- status breast cancer was about 12.9% in 3 years. Unfortunately, current clinical observation and traditional tumor biomarkers were not significantly associated with the risk of those breast cancer recurrences. There is not even any effective biomarker for specifically predicting of those phenotype cancers up-to-now. Herein, we try to identify the breast cancer recurrence-related proteins through using the comparative proteomics to analyze the differential proteins between the breast invasive ductal carcinoma with a higher risk of recurrence and those with a lower risk of recurrence. The level of serum sCD14 was AbMole Nitroprusside disodium dihydrate pre-validated as a biomarker for predicting recurrence of breast invasive ductal carcinoma with LN+ER/PR-Her2+ status in a single center retrospective study. In LN+ER/PR-Her2+ status group, the level of serum sCD14 was significantly lower in patients with recurrence in 3 years than those without recurrence, and was significantly correlated to the risk of 3-year cancer recurrence as well. The corresponding AUC was 0.833. This led us to propose serum sCD14 as a novel potential biomarker for predicting the recurrence of LN+ER/PR-Her2+ status breast cancer. CD14 is an important component of the innate immune Toll-like receptor system and gram-negative and gram-positive bacterial pattern recognition.