Leukaemic cells

Numerous studies have demonstrated that degradation products of (3-carotene exhibit deleterious effects in cellular systems (Alija et al., 2004, 2006 Hurst et al., 2005 Salerno et al., 2005 Siems et al., 2003). A mixture of (3-carotene degradation products exerts pro-apoptotic effects and cytotoxicity to human neutrophils (Salerno et al., 2005 Siems et al., 2003), and enhances the geno-toxic effects of oxidative stress in primary rat hepatocytes (Alija et al., 2004, 2006), as well as dramatically reduces mitochondrial activity in a human leukaemic cell line, K562, and RPE 28 SV4 cell line derived from stably transformed fetal human retinal pigmented epithelial cells (Hurst et al., 2005). As a result of degradation or enzymatic cleavage of (3-carotene, retinoids are formed, which are powerful modulators of cell proliferation, differentiation, and apoptosis (Blomhoff and Blomhoff, 2006). 

In the U.S.A. various pyridazine analogues of naturally occurring pyrimidine nucleosides have been prepared [299, 300] for a review on this subject see [13]. Within this series, 3-deaza-6-azauridine (86) has been found to inhibit the growth of L-1210 mouse leukaemic cells with an ID50 value of a 7 X 10 5 M [299, 301], The inhibitory effect of this uridine isoster might be due to interference in pyrimidine biosynthesis [302],... 

G-CSF increases the number of progenitor cells in the bloodstream tenfold. It has been used in the treatment of patients with myelodysplastic syndromes (MDS 8.8) where it can increase neutrophil counts and sometimes improve neutrophil function in these patients. Because some leukaemic cells are able to proliferate rather than differentiate in response to G-CSF, this CSF may potentially induce a leukaemic transformation in these patients however, its combined use with cytotoxic agents such as cytosine arabinoside appears to decrease this possibility. No doubt clinical trials already underway will establish the optimal treatment regimen for G-CSF, so that the beneficial effects of this cytokine for the treatment and management of haematological disorders can be realised. 

ICAM-1 and -2 are constitutively expressed on endothelial cells ICAM-1 may be further up-regulated by exposure to cytokines. ICAM-3 has recently been described (its identity based on the unique specificity of a monoclonal antibody) and is a 124-kDa glycoprotein present on the surfaces of T cells, monocytes and neutrophils its expression may be up-regulated by stimulants such as mitogens. VCAM-1, which is expressed on the luminal surface of cytokine-exposed endothelial cells, binds T cells via VLA-4. It is also expressed on the surface of some leukaemic cell lines, on rheumatoid synovial cells and on some tumours.On the other hand, ICAM-1 is found on all endothelial surfaces, and its interaction with neutrophil integrins is the major mechanism that results in the stimulation of transendothelial migration. 

Yang, M., Nazhat, N. B., Jiang, X., Kelsey, S. M., Blake, D. R., Newland, A. C., and Morris, C. J., 1996, Adriamycin stimulates proliferation ofhuman lymphoblastic leukaemic cells via a mechanism of hydrogen peroxide (H2O2) production, Br. J. Hemeatol. 95 339-344. 

The haemoglobinization of human leukaemic cell lines by alkaloids demonstrated through in vitro means that these compounds are biologically very active. Alkaloids are therefore a promising botanical to be used in future applications. 

Kl. Kamihira, S., Yamada, Y., Hirakata, Y, Tsuruda, K., Sugahara, K., Tomonaga, M., Maeda, T, Tsukasaki, K., Atogami, S., and Kobayashi, N., Quantitative characterization and potential function of membrane Fas/APO-1 (CD95) receptors on leukaemic cells from chronic B and T lymphoid leukaemias. Br. J. Haematol. 99, 858—865 (1997). 

It destroys essential amino acid (asparagine) hence leukaemic cells are deprived of amino acid and leads to cell... 

Perillyl alcohol represents a novel small molecule that might be effective for treating leukaemia by inducing growth arrest and apoptosis in transformed cells [313], Blends of isoprenoids suppressed growth of murine melanoma and human leukaemic cells [265, 271],... 

Thurnher, M., Wagner, E., Clausen, H., et al. (1994). Carbohydrate receptor-mediated gene transfer to human T leukaemic cells. Glycobiology, 4, 429 -35. 

Barancik, M., et al. 1994. Reversal effects of several Ca(2+)-entry blockers, neuroleptics and local anaesthetics on P-glycoprotein-mediated vincristine resistance of L1210/VCR mouse leukaemic cell line. Drugs Exp Clin Res 20 13. 

Up-regulation of annexin 2 has also been implicated in pro-B cell acute lymphoblastic leukaemia ALL (Matsunaga et al., 2004). This occurs as a result of a different translocation t(17 19)(q22 pl3) and the expression of the fusion protein E2A-HLF is also associated with poor prognosis, hypercalcemia and haemorrhagic complications. Expression of E2A-HLF was sufficient to induce annexin 2 overexpression in leukaemic cell lines. 

Lanza F, Castoldi GL, Castagnari B, Todd RF, III, Moretti S, Spisani S, et al. Expression and functional role of urokinase-type plasminogen activator receptor in normal and acute leukaemic cells. Br J Haematol 1998 103(1) 110-123. 

Eluates can be analyzed with an on-line radiodetector or can be collected in fractions (0.5 mL) and quantitated by 3-scintillation counting. Eluted peaks are compared to retention times for standards prepared from commercial [3H] phosphoinositides and [32P]-labeled D-3-phosphoinositides prepared as described in Subheading 3.2. An example of a typical HPLC separation of the water soluble deacylation products from [32P]Pi- labeled leukaemic cell line is shown in Fig. 2. 

Gallo, R.C., Young, S.S., Ting, R.C. RNA-dependent DNA polymerase of human acute leukaemic cells. Nature 228, 927 (1970)... 

Circadian rhythms exist in cell metabolism and proliferation and those of leukaemic cells differ from normal leucocytes. Evidence is increasing that the time of day at which therapy is administered does iirfluence the outcome for example, maintenance chemotherapy of some leukaemias is more effective if given in the evening (chronomodulation). 

Cytotoxicity Issues. In-vivo hemolysis has been observed with parenteral administration of all of the parent CDs. In-vitro studies with human erythrocytes have demonstrated that the damaging effect of the CDs is in the order p-CD > ot-CD > y-CD. This cellular destruction has also been observed in studies with human skin fibroblasts and intestinal cells, P388 murine leukaemic cells, E. coli bacterial cells, and immortalized human corneal epithelial cells.f " Mechanistic studies suggest that CDs extract either cholesterol (p-CD and y-CD) or phospholipids (a-CD) from the cell membrane causing small pores which allow leakage and eventually lead to cell lysis. 

Figure 4.4.4 shows a typical Percoll gradient for isolation of apoptotic cells from a human promyelocytic leukaemic cell culture (HL-60). 

IB-MECA is an adenosine derivative, active as a (PI purinoceptor) ADENOSINE RECEPTOR AGONIST selective at the As-subtypc. It is used as a tool in adenosine receptor studies. It is reported to show cerebral antiischaemic activity in an animal model also induces apoptosis in a human leukaemic cell line. 

Campos, L., Guyotat, D., Archimbaud, E., Calmard-Oriol, P., Tsuruo, T Troncy, J., Treille, D., and Fiere, D. (1992) Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukaemic cells. Blood 79, 473-176. 

Chapman, R. S., Chresta, C. M Herberg, A. A., Beere, H. M., Heer, S., Whetton, A. D Hickman, J. A., and Dive, C. (1995) Further characterisation of the in situ terminal deoxynucleotidyl transferase (TdT) assay for the flow cytometric analysis of apoptosis in drag resistant and drug sensitive leukaemic cells. Cytometry 20,245-256. 

Hegewisch-Becker, S., Faltz, C., and Hossfeld, D. K. (1996) Prolongation of medium exchange is associated with a decrease in function but not expression of the P-glycoprotein pump in leukaemic cells. Eur. J. Haematol. 56,12-22. 

Lemoli RM, Fogli M, Fortuna A, et al. Interleukin-11 (IL-11) acts as a synergistic factor for the proliferation of human myeloid leukaemic cells. Br J Haematol 1995 91 319-26. 

Siddiqui, R.A., Jenski, L.J., Harvey, K.A., Wiesehan, J.D., Stillwell, W., and Zaloga, G.P. 2003. Cell-cycle arrest in Jurkat leukaemic cells A possible role for docosahexaenoic acid. Biochem. J. 371, 621-629. 

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