Goal treatment, a pattern of expression of Was similar to the pairs of p53 TOV21G in vitro. For example, the increased expression of gemcitabine therapy CLSPN 2 times and Wee1 inhibitor downregulation of the expression quarter compared to gemcitabine single sample. We measure the degree of phosphorylated CDC2 in xenograft tumor samples from the WiDr by Western blot. NPI-2358 Profile gene expression signature resembles Wee1 CDC2 phosphorylated when the correlation coefficient between phosphorylated and calculated CDC2 mRNA expression of each gene in the signature Wee1 gene. This correlation supports the concept that The function of each gene in the cell cycle inhibition with signature Wee1 G2 S and / or its control points Connected.
With respect to GDC-0449 the anti-tumor activity, statistically significant improvement of the effectiveness of gemcitabine was observed when co with more than 0.5 mg / kg / h of MK treated 1775th Nally To term to best That Selected Hlten genes a signature real Wee1 inhibition independently On the kind of the inhibition of mRNA expression of the five genes in cells with siRNA were for Wee1 in vitro WiDr treated examined. Twenty-four hours following gemcitabine treatment siRNA to Wee1 was added to the cells and the expression of the candidate signature is transferred analyzed. In line with the results of the study Wee1 inhibitor significant down-regulation of mRNA expression was obtained observed when Wee1 has been associated with siRNA to silence. Discussion A number of reports have demonstrated the utility of protein biomarkers for target engagement of anti-cancer tumors.
Some protein markers Wee1 inhibitor in pr Clinical trial confinement, Lich CDC2 phosphorylated histone H3 have been reported. Assays of protein markers are generally not quantitative and require large amounts of e biopsy specimens in clinical trials. The same applies to protein markers inhibitor Wee1. The development of the Wee1 gene signature as a biomarker based on mRNA expression offers several advantages over protein markers. The Wee1 gene signature provides data, as measured by quantitative RT-PCR. This makes It makes the world researchers accurately correlate the Ver Changes in gene expression signature Wee1 and antitumor activity of the inhibitor of Wee1. Wee1 gene signature is also better than conventional markers such as phosphorylated IHC CDC2 regarding the required amount of sample.
To measure CDC2 phosphorylated in cancer, several slices of formalin-fixed paraffin-embedded tissue for total CDC2, phosphorylated CDC2 and best confirmation test Required. In contrast, a wafer is sufficient for a plurality of repeated measurements of the signature Wee1 expression. As technology quantification and amplification of mRNA can rapidly, m, a further reduction of the required samples Be possible to analyze the signature Wee1 gene. To assess the participation of specific objectives Wee1 inhibitor, it is preferable to measure PD biomarkers in tumors. However, the M Dependent possibility of tumor biopsy Dependent. Of the type of tumor It is relatively easy to obtain tumor biopsies of skin cancer are biopsies of lung cancer or pancreatic cancer is quite difficult.