The NP matrix can be added directly to the culture medium or separately via a culture insert. Direct contact between NP tissue and the cells may produce higher yield than the non-contact culture. The method is effective and reproducible and does not require additional growth factors and cytokines or cell sorting process. The generated NC-like cells displayed typical notochordal gene expression profile and functional differentiation ability to generate NP-like tissue in vitro. In particular, the generated NP-like tissue had a high GAGs: hydroxyproline ratio which is close to that of native NP tissue. The serine and tyrosine residues in this motif are necessary for the interaction, further more, a phosphorylation modification on the tyrosine residue slightly attenuates its affinity to the cten SH2 domain. The Grb7 protein family, identified through cDNA expression libraries encoding phosphotyrosine receptor targets, is an SH2 domain protein clan that recruits downstream molecules and participates in important cellular signaling pathways. Three members of this family are Grb7, Grb10 and Grb14. Grb7 participates in cell migration and angiogenesis, Grb10 is involved in cell metabolic control and development amplification and Grb14 has roles in cell metabolic regulation and proliferation. Indeed, CD4+ leukocytes have been implicated in MPTP induced DA cell death and increased neutrophil infiltration has been associated with selective nigral dopaminergic degeneration in PD. The SH2 domain of Grb7 family members displays a more permissive structure by having three more residues in the DE loop and five less residues in the CD loop. SH2 domains of Grb10c and Grb7 form dimers, whereas other SH2 domains are normally monosomatic. There are also dissimilarities in the SH2 domains of the three Grb7 family members. Grb10 and Grb14 have the most similar SH2 domain sequences, the SH2 domain of Grb10 shares approximately 90% similarity with that of Grb14. The SH2 domain of Grb7, but not that of Grb10 and Grb14, associates with b-turn peptides, which is similar to the SH2 domain of Grb2. SH2 domains promote rapid and reversible signaling transduction. If a nonphosphorylated Cinoxacin peptide has a higher affinity to the SH2 domain comparable to phosphorylated ligand, the interaction becomes independent of phosphorylation and signaling may not be rapidly attenuated. The nonphosphorylated G718 NATE peptide has been used to inhibit Grb7 protein functions. Mice injected with pancreatic cancer cells and treated with the G7-18NATE peptide have fewer peritoneal metastases compared to controls. Therapy-related myeloblastic leukemia, including 2-Thiouracil therapyrelated myelodysplasia,, constitutes approximately 10% of AML and has several characteristic features. As the incidence of cancers increases, so does that of t-AML. Nowadays, thanks to treatment intensification, the cure rate of primary neoplasia has increased but these very treatments are also implicated in severe therapy-related hematological consequences. Two different types of t-AML are to be distinguished. The first one is due to prior therapy with alkylating agents or radiotherapy. It occurs generally after a latency period of 5 to 7 years. This kind of t-AML is often preceded by a preleukemic period of myelodysplasia.