Myeloid

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

Enzymes Degrading Macromolecules. Enzymes that degrade macromolecules such as membrane polysaccharides, stmctural and functional proteins, or nucleic acids, have all shown oncolytic activity. Treatment strategies include the treatment of inoperable tumors with pepsin (1) antitumor activity of carboxypeptidase (44) cytotoxicity of ribonudease (45—47) oncolytic activity of neuraminidase (48—52) therapy with neuraminidase of patients with acute myeloid leukemia (53) antitumor activity of proteases (54) and hyaluronidase treatment in the management of human soHd tumors (55). 

Mark-, medullary, markant, a. striking, remarkable, markartig, a. marrow-like, myeloid, medullary pith-like. 

Busulfan was used for the treatment of chronic myeloid leukemia and polycytemia vera. 

Moore J, Seiter K, Kolitz J et al (2006) A Phase II study of Bcl-2 antisense (oblimersen sodium) combined with gemtuzumab ozogamicin in older patients with acute myeloid leukemia in first relapse. Leuk Res 30(7) 777-783... 

Inhibition of hematopoietic growth factors Imatinib (Glivec ) is applied to treat chronic myeloid leukemia in Philadelphia-chromosome positive patients. In these patients, translocation of parts of chromosomes 9 and 22 results in the expression of a fusion protein with increased tyrosine kinase activity, called Bcr-Abl. Imatinib is a small Mw inhibitor selective for the tyrosine kinase activity of Bcr-Abl. Thereby, it inhibits the Bcr-Abl induced cell cycle progression and the uncontrolled proliferation of tumor cells. 

Expression (Mouse) Tissues lungs, Cells myeloid leukocytes, neutrophils, T-cells, macrophages, mast cells, eosinophils Tissues lung, skin, small intestine Cells macrophages, fibroblasts, leukocytes Tissues lung, skin, brain, small intestine, spleen Cells macrophages, fibroblasts, endothelial cells, leukocytes... 

A particularly active area of research concerns the elucidation of the mechanisms of refractoriness or resistance to anti-VEGF therapy. Tumor cell-intrinsic or treatment-induced expression of angiogenic factors may be implicated Very recent studies have provided evidence that, at least is some murine models, refractor-inessm to anti-VEGF therapy is related to the ability of the tumor to recruit CDllb+Grl+ myeloid cells, which promote angiogenesis [5]. It remains to be established whether these findings also apply to human tumors. 

Shojaei F, Wu X, Malik AK et al (2007) Tumor refrectoriness to anti-VEGF treatment is mediated by CDllb+ Grl+ myeloid cells. Nat Biotechnol 8 911-920... 

Included among other differentiating cell lines which have been established in culture, is the human promyelocytic cell line HL-60, which differentiates into more mature myeloid cells upon treatment with retinoic acid and prostaglandin E] (PGEi). Friend erythroleukemia cells differentiate into hemoglobin-producing cells when treated with either dimethyl sulfoxide, or hexamethylene bis-acetamide. 

Seggewiss R, Pittaluga S, Adler RL, Guenaga FJ, Ferguson C, Pilz I, Ryu B, Sorrentino BP, Young WS, Donahue RE, von Kalle C, Nienhuis AW, Dunbar CE (2006) Acute myeloid leukemia associated with retroviral gene transfer to hematopoietic progenitor cells of a rhesus macaque. Blood 107 3865-3867... 

Rapozzi V., Burm B.E.A., CoGOi S., Van DER Marel G.A., Van Boom J.H., Quad-RiFOGLio F., XoDO L. E. Antiproliferative effect in chronic myeloid leukaemia cells by antisense peptide nucleic acids. Nucleic Acids Res. 2002 30 3712-3721. 

Lanzavecchia A Specialization and complementar- 57 ity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells. Eur J Immunol 2001 31 3388-3393. 

Raponi M, Belly RT, Karp JE, Lancet JE, Atkins D, Wang Y. Microarray analysis reveals genetic pathways modulated by tipifarnib in acute myeloid leukemia. BMC Cancer 2004 4 56. 

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