Where Man And Docetaxel E7080 Collide

The inducing effects would lower their intestinal absorption and so improve rst pass clearance of Docetaxel CYP3A4 and/or P gp substrates. In future research other danshen preparations containing a larger information of cryptotanshinone and tanshinone IIA should be evaluated for their ability to induce in vivo CYP3A4 and P gp.

Use of CYP3A substrates with Docetaxel concurrent danshen tablet use may call for caution, depending on the drugs exposure response relationship. Dose adjustment of CYP3A substrates may be necessary in patients receiving concomitant therapy with danshen preparations containing lipophilic components. The CIS/suppressors of cytokine signaling family of proteins is one of the major mechanisms for regulations of cytokine signaling. The rst member of the family discovered is CIS, cytokine inducible SH2 protein. This molecule was identied by subtraction as an immediate early gene induced by erythropoietin. CIS is found to be a negativefeedback regulator of the STAT5 pathway, binding to the phosphorylated tyrosine residues of cytokine receptors through the SH2 domain, thereby masking STAT5 docking sites.

The SOCS proteins and CIS protein comprise a family of intracellular proteins. There are eight CIS/SOCS family proteins: CIS, SOCS1, SOCS2, SOCS3, SOCS4, SOCS5, SOCS6, and SOCS7, each of which has a central SH2 domain, an amino terminal domain of variable length and sequence, and a carboxy terminal 40 amino acid module known as the SOCS box. In addition, NSCLC both SOCS1 and SOCS3 can inhibit JAK tyrosine kinase activity directly through their kinase inhibitory region. KIR has been proposed to function as a pseudosubstrate that is essential for the suppression of cytokine signals. The SH2 domain of SOCS3 does not have a high afnity to the activation loop of JAKs yet the KIR of SOCS3 has a higher afnity to the kinase domain of JAK2 than that of SOCS1.

Although SOCS proteins inhibit growth factor responses, tyrosine phosphorylation of SOCS3 can ensure cell survival and proliferation through the Ras pathway. The SOCS box is also found in other miscellaneous proteins.