Further observations on the folate-binding factor in some leukemic cells

Rothenberg, Sheldon P.; DaCosta, Maria

doi:10.1172/jci106542

Cited by 54 publications

(14 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is in accordance with other published work on the charac teristics of FABP in the serum in folate deficiency [6], pregnancy [1], and some cases of chronic myeloid leukaemia [4]. No significant macromolecular peak was found in normal subjects.…”

Section: Discussionsupporting

confidence: 93%

A Study of Folic-Acid-Binding Protein in Normal Subjects

Gorst¹,

Courtis²,

Delamore³

1977

Acta Haematol

View full text Add to dashboard Cite

6 normal females were found to have a high level of folic-acid-binding protein (FABP) in their sera (mean level 345 pg/ml). Lysates of their various leucocytes were assayed and FABP found exclusively in the polymorph fraction. The sera and lysates were fractionated by Sephadex G-200 gel column chromatography and the molecular weight of the FABP appeared to be approximately 40,000. A hitherto unreported inhibitory effect of heparin on folate binding was noticed. Studies have been performed on folic-acid-binding protein (FABP) in various pathological states, but the levels found in normal people are usually considered too low to permit investigation. In an earlier study [3], 6 normal females were found to have levels in excess of 300 pg/ml whilst the mean level of 94 controls was 76 pg/ml. Sera and leucocyte lysates from these people have been used to estimate the molecular weight of FABP in normal people.

show abstract

Section: Discussionsupporting

confidence: 93%

A Study of Folic-Acid-Binding Protein in Normal Subjects

Gorst¹,

Courtis²,

Delamore³

1977

Acta Haematol

View full text Add to dashboard Cite

show abstract

“…The presence of a folate-binding pro tein in granulocytes was first demonstrat ed in patients with chronic myelogenous leukemia [1] and subsequently in women who were pregnant or taking oral contra ceptives [2]. We have recently reported great interindividual variations in the fo late-binding activity of leukocytes from normal subjects of both sexes [3,4].…”

Section: Introductionmentioning

confidence: 99%

High-Affinity Folate Binding in Leukocyte Lysate from Normal Subjects: Effect of Concentration of Binding Protein, Temperature and pH

Holm¹,

Hansen²,

Lyngbye³

1983

Acta Haematol

View full text Add to dashboard Cite

Folate binding in lysate prepared from leukocytes containing large amounts of the folate-binding protein was studied in equilibrium dialysis experiments (pH 7.4, 37 °C). Binding displayed positive cooperativity, and the binding affinity increased with decreasing concentration of binding protein (affinity constants in the range of 5 × 10⁹1/mol to 7 × 10¹⁰l/mol). Both phenomena could be interpreted in terms of ligand binding to a polymerizing system where the affinity of ligand for the oligomer is greater than its affinity for the polymer prevailing at high concentrations of the binding protein. Binding affinity was decreased at a low temperature (7 °C) and particularly at pH 5.0 where positive cooperativity also disappeared. The binder (M_r∼25,000–30,000) eluted in the front effluent after DEAE-Sepharose® CL-6B chromatography of the lysate at pH 6.3.

show abstract

“…For instance, receptor-mediated endocytosis has been used to increase the uptake of synthetic ODNs and other foreign molecules such as proteins complexed to specific ligands (Wu & Wu, 1987, 1988Cotten et al, 1990;Leamon & Low, 1991;Citro et al, 1992;Manfredini et al, 1993). Since the receptors for some growth factors, vitamins and hormones are overexpressed in rapidly dividing tumour cells (Rothemberg & Da Costa, 1971;Asok et al, 1981;Sclhub & Franklin, 1984; Lacey et al, 1989), the ligands of these receptors can be exploited to selectively introduce therapeutic compounds into the cells. The use of modified ligands for specific cell-surface receptors as carriers of oncogene-targeted antisense ODNs represents a potentially useful therapy to be used alone or in combination with antineoplastic drugs.…”

mentioning

confidence: 99%

Inhibition of leukaemia cell proliferation by folic acid–polylysine-mediated introduction of c-myb antisense oligodeoxynucleotides into HL-60 cells

Citro¹,

Szczylik²,

Ginobbi³

et al. 1994

Br J Cancer

View full text Add to dashboard Cite

Summary The inhibitory effect of c-myb antisense oligodeoxynucleotides (ODNs) conjugated to folic acid (FA) on HL-60 cell proliferation was examined. Folic acid was covalently linked to a polylysine chain and purified by gel chromatography. Sterile FA-polylysine was complexed with c-myb sense and antisense. Exposure of HL-60 cells to the FA-polylysine-c-myb antisense ODN complex resulted in a down-regulation of c-myb expression and a greater inhibition of proliferation than that obtained using free ODNs. Moreover, FA-polylysine conjugate alone or complexed to c-myb sense ODN was not toxic to cells. The antigenic properties and uptake of the vitamin were not affected by the polylysine chain. These data suggest that this strategy is potentially useful for the selective delivery of anti-oncogene-targeted ODNs into cancer cells.Antisense oligodeoxynucleotides (ODNs) have proven useful for selective inhibition of gene expression (Holt et al., 1988; Szczylik et al, 1991). However, their rate of cellular uptake appears to be quite slow, and consequently attempts have been made to enhance their stability and their delivery into cells. For instance, receptor-mediated endocytosis has been used to increase the uptake of synthetic ODNs and other foreign molecules such as proteins complexed to specific ligands (Wu & Wu, 1987, 1988Cotten et al., 1990;Leamon & Low, 1991;Citro et al., 1992;Manfredini et al., 1993). Since the receptors for some growth factors, vitamins and hormones are overexpressed in rapidly dividing tumour cells (Rothemberg & Da Costa, 1971;Asok et al., 1981;Sclhub & Franklin, 1984; Lacey et al., 1989), the ligands of these receptors can be exploited to selectively introduce therapeutic compounds into the cells. The use of modified ligands for specific cell-surface receptors as carriers of oncogene-targeted antisense ODNs represents a potentially useful therapy to be used alone or in combination with antineoplastic drugs.We have previously reported that a c-myb antisensetransferrin-polylysine complex produces an enhanced uptake into HL-60 cells, resulting in an increased biological effect. Recently, we have also observed that a polylysine chain covalently linked to compounds such as insulin, folic acid, retinoic acid, oestrone and testosterone can be used for specific interactions with nucleic acids in physiological ionic conditions (G. Citro, unpublished observation). The presented study describes the efficacy of folic acid receptor-targeted c-myb antisense in the HL-60 cell line. The effect of the complexed phosphodiester (PO) ODNs was compared with that of phosphorothioate (PS) ODN antisense given alone.With doses of 20 and 30 fig mlVl, we found that PS c-myb antisense actively inhibited the rate of the cell proliferation while free PO c-myb antisense had no effect. However, when free PO c-myb antisense ODNs were complexed to FApolylysine, their inhibitory effect on the cell proliferation was even greater than that obtained using the free PS oligos. Furthermore, whereas recent research has indicated there...

show abstract

Further observations on the folate-binding factor in some leukemic cells

Cited by 54 publications

References 18 publications

A Study of Folic-Acid-Binding Protein in Normal Subjects

A Study of Folic-Acid-Binding Protein in Normal Subjects

High-Affinity Folate Binding in Leukocyte Lysate from Normal Subjects: Effect of Concentration of Binding Protein, Temperature and pH

Inhibition of leukaemia cell proliferation by folic acid–polylysine-mediated introduction of c-myb antisense oligodeoxynucleotides into HL-60 cells

Contact Info

Product

Resources

About