Anti-SRC

Table 6. Primary anti-SRC and anti-ChRC response with lymphocytes depleted of SRC...

Antibody Response Reference anti-SRC anti-ChRC... 

X lO" spleen cells from normal mice per ml) Anti-SRC Anti-BRC ... 

A number of experiments have been reported by Bell and Dray (1969, 1970, 1971a, b, 1972, 1973) in which the authors describe conversion of non-immune rabbit spleen cells by RNA from immunized rabbit to produce IgM and IgG of donor light chain allotype. Furthermore, spleen cells from non-immunized rabbits were converted to antibody-forming cells by incubation with RNA extracts of lymph node cells obtained from rabbits immunized with SRC. If the RNA was extracted from lymph nodes of rabbits immunized 5 days previously, IgM anti-SRC antibody-forming cells were produced, while if the donor of RNA was immunized 18 to 24 days previously, IgG anti-SRC antibody-forming cells were detected in the converted spleen cells. 

Though a large number of small molecule inhibitors against a variety of tyrosine kinases are being developed, the most advanced drugs can be roughly classified as (i) Bcr-Abl/Src family kinase inhibitors, (ii) ErbB inhibitors and (iii) broad spectrum TfCIs with an anti-angiogenic component. 

AP23451 administration to mice inoculated with MDA-231 breast cancer cells effectively prevents metastasis-induced osteolysis similar to bisphosphonate zoledronic (Zometa ). However, it also significantly reduces the volirme of tumor cells inside the bone marrow cavities of the mice as opposed to a lack of inhibitory effect on tirmor cell volume in mice treated with zoledronic acid. AP23588 is also a bone-targeted Src kinase inhibitor which has been determined to possess both anti-resorptive and anabohc properties in vitro with respect to reducing osteoclast activity and stimulating osteoblast activity, respectively. 

While no in vivo activity has been reported in an Abl-dependent CML model, AZD0530 was active in a xenograft model using Src-transformed NIH 3T3 cells and in an orthotopic model of pancreatic cancer, two Src-dependent models. The results of a Phase I trial in normal volunteers have been disclosed and AZD0530 was tolerated when administered at doses of up to 250 mg [156,157]. While it appears that the initial efficacy trial for AZD0530 will be as an anti-invasive agent for the treatment of metastatic bone disease, this compound probably also has potential for use in CML. 

Loss of the p53 tumor suppressor gene has been shown to impede the anti-leukemic response to BCR-ABLl inhibition (43). Another mechanism for resistance that is independent of BCR-ABLl and that has been demonstrated in vitro is over-expression of SRC-related kinases such as LYN (44). It appears that kinases from the SRC family mediate signaling of BCR-ABLL This has been demonstrated in vitro with the use of SRC kinase inhibitors and SRC mutants that are kinase defective (45,46,47). 

Abu-Ghazaleh, R., Kabir, J., Jia, H., Lobo, M., and Zachary, I. 2001. Src mediates stimulation by vascular endothelial growth factor of the phosphorylation of focal adhesion kinase at tyrosine 861, and migration and anti-apoptosis in endothelial cells. Biochem. J. 360 255-264. 

Src-homology 2 domain of Grb2 Enzyme I of the bacterial phosphoenolpyruvate-sugar phosphotransferase system Taq DNA polymerase Human insulin Apolipoprotein A-l Mouse anti-DNA antibody Phosphatase-1 a-Bungarotoxin Toxic shock syndrome toxin-1 Mouse organs... 

Anti Solvent Deashed SRC Wyoming Subb1tum1nous Coal Kentucky High Vol. Bit. Coal ... 

Analysis Pressure Filtered Deashed SRC Cricital Solvent Deashed SRC Anti-Solvent Deashed SRC... 

Burkhardt, A. L., Bmnswick, M., Bolen, J. B., and Mond, J. J. (1991). Anti-immunoglobulin Stimulation of B Lymphocytes Activates src-Related Protein-Tyrosine Kinases. Proc Natl Acad Sci USA 88 7410. 

L.l. Plotkin, T. Bellido, Bisphosphonate-induced, hemichannel-mediated, anti-apoptosis through the Src/ ERK pathway a gap junction-independent action of conncxin43, Cell Commun Adhes 8, 377-382 (2001). 

---