Leukemia derived growth factor

The way to create a serum-free culture is to adapt the cells to the serum-free medium. In our laboratory, we tried to adapt a human lymphoblastoid cell line, Namalwa, from a medium containing 10% serum to serum-free. We were able to adapt Namalwa cell to a ITPSG serum-free medium which contained insulin, transferrin, sodium pyruvate, selenious acid and galactose in RPMI-1640. In the case of cell adaptation for production of autocrine growth factor, we were able to grow the cell line in serum- and protein-free media as well as in K5 62-K1 (T1) which produces an autocrine growth factor, LGF-1 (leukemia derived growth factor-1). 

Imatinib (STI571) is an inhibitor of the tyrosine kinase domain of the Bcr-Abl oncoprotein and prevents the phosphorylation of the kinase substrate by ATP. It is indicated for the treatment of chronic myelogenous leukemia (CML), a pluripotent hematopoietic stem cell disorder characterized by the t(9 22) Philadelphia chromosomal translocation. This translocation results in the Bcr-Abl fusion protein, the causative agent in CML, and is present in up to 95% of patients with this disease. This agent inhibits other activated receptor tyrosine kinases for platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF), and c-kit. 

Pantazis, P., Sariban, E., Kufe, D. and Antoniades, H.N. (1986). Induction of c-sis gene expression and synthesis of platelet derived growth factor in human myeloid leukemia... 

Imatinib is a protein-tyrosine-kinase inhibitor. Imatinib inhibits proliferation and induces apoptosis in BCR-ABL positive cell lines as well as fresh leukemic cells from Philadelphia chromosome-positive (Ph-r) chronic myeloid leukemia (CML). Imatinib inhibits tumor growth of BCR-ABL transfected murine myeloid cells and BCR-ABL positive leukemia lines derived from CML patients in blast crisis. It also inhibits the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, and inhibits PDGF- and SCF-mediated cellular events. It is indicated in the treatment of newly diagnosed adult patients with Ph-t CML in chronic phase patients with Ph-t CML in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha treatment children with Ph-t chronic phase CML whose disease has recurred after stem cell transplant or who are resistant to interferon-alpha therapy and treatment of gastrointestinal stromal tumors (GIST). 

Typically, cancer cells have accumulated a number of mutations in genes that code for proteins that are involved in signaling pathways, or in the cell cycle. These mutant proteins either are locked into a permanently active form or have lost the ability to carry out their normal regulatory functions. An example involves the platelet-derived growth factor receptor that in some human leukemias is locked into a permanently active state because of a chromosomal translocation. This mutation affects the N terminus of the receptor that is replaced by that of a transcription factor called Tel. 

Platelet-derived growth factor, 1450 Platydesma, 734 Pleiospermium, 764 P388 leukemia, 982, 988, 996 Plinia cerrocampanensis, 2986 Plocamiaceae, 2891 Plocamiales, 2891 Plocamium... 

The BBB is known to transport several cytokines in the blood-to-brain direction. For example, the BBB transports the IL-l s, IL-6, and TNF by three separate transport systems. Additionally, nerve growth factor, brain derived neurotrophic factor, interferons, neurotrophins, and leukemia inhibitory factor (Poduslo and Curran, 1996 Pan et al., 1997b Pan et al., 1998b Pan et al., 1998a) are also transported across the BBB. In some cases, the same gene which gives rise to a cytokine s receptor also produces the cytokine s transporter, whereas in other cases the receptor and transporter are immunologic ally distinct proteins (Banks and Kastin, 1992 Pan and Kastin,... 

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