Disease relevance of ALKYL-LYSOPHOSPHOLIPID

• In order to evaluate the specificity of alkyl-lysophospholipid-induced cell destruction, peripheral blood leukocytes from chronic myelogenous leukemia (CML) patients in chronic phase of the disease as well as in blastic crisis have been separated by density centrifugation [1].
• Reduction of epidermal growth factor binding in human breast cancer cell lines by an alkyl-lysophospholipid [2].
• Cytotoxicity of alkyl-lysophospholipid derivatives and low-alkyl-cleavage enzyme activities in rat brain tumor cells [3].
• Effect of alkyl-lysophospholipid on glioblastoma cell invasion into fetal rat brain tissue in vitro [4].
• We studied the effects of the alkyl-lysophospholipid, 1-octadecyl-2-methyl-sn-glycerol-3-phosphocholine (ALP), on human leukemia cells from 56 patients with various leukemias and on normal bone marrow progenitors in order to assess the application of ALP as an in vitro marrow-purging agent [5].

High impact information on ALKYL-LYSOPHOSPHOLIPID

• The human leukemia cell lines K562, HL60, and Raji and the mouse leukemia cell line L1210 showed a differential susceptibility to the action of the alkyl-lysophospholipid (ALP) 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) [6].
• The cytostatic-cytotoxic effect of the new thioether alkyl lysophospholipid analogue Ilmofosine (1-hexadecylthio-2-methoxymethyl-rac-glycero-3-phosphocholine, BM 41.440) on colony formation of 30 different spontaneous human tumors was investigated in vitro with the use of a methylcellulose monolayer assay [7].
• Autologous bone marrow transplantation in acute leukemia with marrow purged with alkyl-lysophospholipid [8].
• A spleen colony assay showed that ALP has some cytotoxic effect on normal hematopoietic stem cells [9].
• The demonstration of differential action of ALP on two cell lines should significantly simplify the investigation of the mechanism of the reported differential action of ET180CH3 on normal and leukemic cell membranes [10].

Chemical compound and disease context of ALKYL-LYSOPHOSPHOLIPID

• We investigated the effect of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3), an alkyl-lysophospholipid, on the uptake of estrogen, the secretion of transforming growth factor (TGF) alpha and the content of progesterone receptors (PRs) in the hormone-dependent breast cancer cell line, MCF-7 [11].
• Inhibition of estradiol uptake and transforming growth factor alpha secretion in human breast cancer cell line MCF-7 by an alkyl-lysophospholipid [11].
• PURPOSE: A Phase I trial was performed to determine the dose-limiting toxicity and maximum tolerated dose, and to describe the pharmacokinetics of the alkyl-lysophospholipid, ilmofosine, when administered as a weekly 2-h infusion in patients with solid tumors [12].

Biological context of ALKYL-LYSOPHOSPHOLIPID

• ALP eliminated clonogenicity in HL60 but not in K562 cultures; 3H-TdR uptake and cell numbers were depressed at low concentrations of ET180CH3 in HL60, but not K562 cultures [10].
• The PL-Ca-PK activity and the phosphatidylserine-Ca2+-stimulated phosphorylation of endogenous proteins from leukemic cells were inhibited by alkyl-lysophospholipid, which acted as a competitive inhibitor of the phospholipid cofactor of the enzyme [13].
• Perturbations of cellular acylation processes by the synthetic alkyl-lysophospholipid 1-O-octadecyl-2-O-methylglycero-3-phosphocholine do not correlate with inhibition of proliferation of MCF7 and T84 cell lines [14].
• The synthetic alkyl-lysophospholipid (ALP), 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine, is an antitumor agent that acts on cell membranes and can induce apoptosis [15].
• Synthesis of sulfur analogues of alkyl lysophospholipid and neoplastic cell growth inhibitory properties [16].

Anatomical context of ALKYL-LYSOPHOSPHOLIPID

• Both leukemic and solid tumor cells took up this alkyl-lysophospholipid and expressed the two putative edelfosine targets, namely cell surface Fas death receptor (also known as APO-1 or CD95) and endoplasmic reticulum CTP: phosphocholine cytidylyltransferase [17].
• Noncytotoxic alkyl-lysophospholipid treatment increases sensitivity of leukemic K562 cells to lysis by natural killer (NK) cells [18].
• Oral administration of dodecylglycerol, inflammatory product of cancerous tissues, and the alkyl lysophospholipid derivative, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3-choline), greatly activated mouse peritoneal macrophages [19].
• Chemopurging of peripheral blood-derived progenitor cells by alkyl-lysophospholipid and its effect on haematopoietic rescue after high-dose therapy [20].
• In contrast, 3T3 fibroblasts were resistant to the alkyl-lysophospholipid [21].

Associations of ALKYL-LYSOPHOSPHOLIPID with other chemical compounds

• Akt is strongly inhibited by perifosine, an orally active alkyl-lysophospholipid currently being evaluated as an anti-cancer agent in phase 1 and 2 clinical trials [22].
• Alkyl lysophospholipid analogs II and cholesterol form liposomes with high encapsulation efficiency and low permeability for entrapped substances [23].
• The antineoplastic activity of two ether lipid derivatives, the alkyl-lysophospholipid derivative (ALP) ET-18-OCH3 and the ether-linked lipoidal amine CP-46,665 was tested in a human tumor clonogenic assay (HTCA) in vitro [24].
• Maximal in vitro potency was obtained with 1-O-octadecyl-2-O-(2-pyrimidinyl)-3-O-[2-(2-trimethylammonioethoxy )ethyl] glycerol (1g; IC50 values for both HL-60 and KB were 0.32 microgram/ml, indicating a higher activity than alkyl-lysophospholipid, ET18-OMe) [25].
• Leukemia cells in primary culture from most, but not all, patients underwent morphological, cytochemical and biochemical changes after treatment with inducers of differentiation such as 12-O-tetradecanoylphorbol-13-acetate (TPA), retinoic acid, actinomycin D, aclarubicin, and alkyl lysophospholipid [26].

Gene context of ALKYL-LYSOPHOSPHOLIPID

• The effects of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3), an alkyl lysophospholipid derivative, on the binding of epidermal growth factor (EGF) to human breast cancer cell lines (MCF-7, ZR-75-1, and BT-20), the human epidermoid cancer cell line (A431), and the rat fibroblast cell line (NIH3T3) were investigated [2].
• Alkyl-lysophospholipid resistance in multidrug-resistant Leishmania tropica and chemosensitization by a novel P-glycoprotein-like transporter modulator [27].
• Analogues of the synthetic antitumor phospholipid ALP (1-octadecyl-2-methyl-sn-glycero-3-phosphocholine; alkyl lysophospholipid) in which the 1-ether oxygen atom has been removed have been prepared and evaluated for in vitro and in vivo anticancer activity [28].
• Taken together, these data suggest that combination purging with alkyl-lysophospholipid and MC540-mediated PDT may provide a simple, versatile, and effective means of eliminating large numbers of leukemia cells from autologous bone marrow grafts without causing excessive damage to normal hematopoietic stem cells [29].
• Twenty-two alkyl lysophospholipid analogs were chemically synthesized, and their antitumor activity against mouse experimental tumors (Sarcoma 180, MM46, P388) was examined [30].

Analytical, diagnostic and therapeutic context of ALKYL-LYSOPHOSPHOLIPID

• After treatment with alkyl lysophospholipid, glycopeptides proteolytically derived from normal and malignant cells displayed a shift in the size distribution profiles obtained by gel filtration [31].
• The gas chromatographic determination of 1-O-octadecyl-2-O-methyl-DL-glycero-3-phosphorylcholine (Et-18-OMe), an anti-invasive alkyl lysophospholipid, in cell culture media is described [32].
• The cytotoxicity of alkyl-lysophospholipid on clonogenic leukemia cells and on normal bone marrow progenitor cells is highly, but differentially, increased by cryopreservation [33].
• The objective of this study was to perform, in a preclinical purging model, an initial assessment of the safety and efficacy of a two-step purging procedure that combined Merocyanine 540-mediated photodynamic therapy (MC540-PDT) with a brief exposure to the alkyl-lysophospholipid, Edelfosine [34].

References