Influence of droloxifene on plasma levels of insulin-like growth factor (IGF)-I, pro-IGF-IIE, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-3 in breast cancer patients

1996 ◽  
Vol 57 (3-4) ◽  
pp. 167-171 ◽  
Author(s):  
Svein I. Helle ◽  
Gun B. Anker ◽  
Michael Tally ◽  
Kerstin Hall ◽  
Per E. Lønning
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Patients ◽  
Plasma Levels ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Breast Cancer Patients ◽  
Factor Binding ◽  
Igf I ◽  
Igfbp 3

Significant Changes in Circulating Plasma Levels of IGF1 and IGFBP3 after Conventional or Dose-Intensified Adjuvant Treatment of Breast Cancer Patients with one to three Positive Lymph Nodes

2007 ◽  
Vol 22 (3) ◽  
pp. 186-193 ◽  
Author(s):  
S. Kümmel ◽  
H. Eggemann ◽  
D. Lüftner ◽  
N. Gebauer ◽  
H. Bühler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Adjuvant Chemotherapy ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Plasma Levels ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Breast Cancer Patients ◽  
Positive Lymph Nodes

The insulin-like growth factor 1 (IGF1) and its binding protein IGFBP3 (insulin-like growth factor binding protein 3) play a pivotal role during the growth and development of tissues. The purpose of this study was to evaluate the influence of anthracycline- and taxane-containing adjuvant chemotherapy in breast cancer patients on the circulating plasma levels of IGF1 and its main binding protein, IGFBP3. This investigation was part of a prospective randomized phase III study in which breast cancer patients were treated with either conventional or dose-intensified adjuvant chemotherapy. The factors were quantified in the plasma of 151 patients with a commercially available sandwich enzyme immunoassay. Before therapy, both parameters were within the normal range in most patients (n=145 and n=144). After therapy, both factors had increased significantly by 29% (IGF1) and 19% (IGFBP3), with the highest increase being observed in the dose-intensified group. Correlations with patient and tumor characteristics revealed a relatively higher increase in both parameters in premenopausal patients, patients with lower-grade tumors, more positive lymph nodes, larger tumor volume, and positive hormone receptor status. No correlation was found with the HER2 expression of the tumors.

Radioimmunoassay of insulin-like growth factor-binding protein-6 in human serum and other body fluids

1992 ◽  
Vol 134 (1) ◽  
pp. 133-139 ◽  
Author(s):  
R. C. Baxter ◽  
H. Saunders
Keyword(s):  
Cerebrospinal Fluid ◽  
Growth Factor ◽  
Human Serum ◽  
Follicular Fluid ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Igf I ◽  
The Mean ◽  
Igfbp 3

ABSTRACT A radioimmunoassay has been established for the insulin-like growth factor-binding protein, IGFBP-6, isolated from a human transformed fibroblast cell-line. The binding proteins IGFBP-I and IGFBP-3 did not cross-react, but both IGF-I and IGF-II markedly inhibited IGFBP-6 tracer binding to antiserum. This inhibition, greater for IGF-II than for IGF-I, was fully reversed by the addition of IGFBP-3 to sequester the IGFs. After fractionation of human serum and follicular fluid samples by gel chromatography, interference in the radioimmunoassay by fractions corresponding to the 150 kDa IGF-IGFBP complex could be eliminated by IGFBP-3. The equivalent fractions from cerebrospinal fluid and amniotic fluid fractionation did not interfere in the assay. The mean IGFBP-6 level in adult human serum was 0·221 ±0·110 mg/l, with values significantly higher in men than women, and slightly decreased in pregnancy. Similar values were seen in umbilical cord serum and in amniotic and follicular fluid samples, while the mean level in cerebrospinal fluid was slightly lower, 0·152±0·049 mg/l. This assay will facilitate studies on the regulation of IGFBP-6 production, and its role as an IGF carrier. Journal of Endocrinology (1992) 134, 133–139

Altered serum levels of insulin-like growth-factor binding proteins in breast cancer patients

1998 ◽  
Vol 5 (2) ◽  
pp. 194-201 ◽  
Author(s):  
Eng-Hen Ng ◽  
Chen-Yang Ji ◽  
Puay-Hoon Tan ◽  
Valerie Lin ◽  
Khee-Chee Soo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Patients ◽  
Binding Proteins ◽  
Serum Levels ◽  
Insulin Like Growth Factor ◽  
Breast Cancer Patients ◽  
Factor Binding ◽  
Altered Serum

The ovine pancreatic protein which binds insulin-like growth factor binding protein-3 is procarboxypeptidase A

1996 ◽  
Vol 150 (1) ◽  
pp. 51-56 ◽  
Author(s):  
P J Fowke ◽  
S C Hodgkinson
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Binding Protein ◽  
Binding Activity ◽  
Insulin Like Growth Factor ◽  
Surface Binding ◽  
Factor Binding ◽  
Amino Terminal ◽  
Igf I ◽  
Igfbp 3

Abstract Insulin-like growth factor binding protein-3 (IGFBP-3) is known to modulate the actions of insulin-like growth factors (IGF)-I and -II at the level of the cell. Proposed mechanisms include association of IGFBP-3 with cell surface proteoglycan, with cell surface binding proteins, proteolysis and/or internalization of IGFBP-3. In previous studies we have characterized a protein of 40 kDa in extracts of ovine pancreas and muscle which binds IGFBP-3 on ligand blot analyses. This paper reports the identity of the pancreatic species as procarboxypeptidase A (peptidyl-l-amino acid hydrolase, E.C. 3.4.17.1; proCPA). Identity was established by amino terminal sequence analysis, binding studies with pure bovine carboxypeptidase A (CPA) and observations that the binding activity was present in pancreatic secretions consistent with the role of proCPA as a secretory zymogen. The binding activity was inhibited by unlabelled IGFBP-3 at high doses (10 μg/ml) and reduced but not abolished by preincubation of 125I-IGFBP-3 with excess IGF-I. Digestion of 125I-IGFBP-3 with mature CPA produced a 26 kDa product. Modification of IGFBP-3 by CPA or binding to proCPA may provide a mechanism for modulation of IGFBP activity and hence IGF action. Journal of Endocrinology (1996) 150, 51–56

Long-term treatment of Laron type dwarfs with insulin-like growth factor-1 increases serum insulin-like growth factor-binding protein-3 in the absence of growth hormone activity

1993 ◽  
Vol 128 (2) ◽  
pp. 144-149 ◽  
Author(s):  
Hannah Kanety ◽  
Avraham Karasik ◽  
Beatrice Klinger ◽  
Aviva Silbergeld ◽  
Zvi Laron
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Binding Protein ◽  
Serum Insulin ◽  
Continuous Treatment ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Long Term Treatment ◽  
Igf I ◽  
Igfbp 3

Insulin-like growth factor binding protein-3 (IGFBP-3) is the major carrier of insulin-like growth factor I (IGF-1) in serum, and its production is growth hormone (GH) dependent. It is unclear whether in humans IGFBP-3 production is directly regulated by GH or mediated via IGF-I. We addressed this question in six patients with Laron-type dwarfism, a syndrome characterized by the absence of GH receptor activity (LTD), who were chronically treated with recombinant IGF-I. Analysis of the electrophoretic profiles of serum IGFBPs in these patients by Western ligand blotting revealed an extremely low IGFBP-3 level. A striking progressive increase in serum IGFBP-3 was observed with continuous treatment, despite the absence of GH action. In LTD children, serum IGFBP-3 increased up to 19-fold after six months of therapy and equalled levels observed in controls, whereas in adult LTD patients the increase was smaller. A rise in serum levels of 34, 30 and 24 kDa BPs (presumably IGFBP-2, -1 and -4, respectively was also noted with chronic IGF-I therapy. This proof of GH-independent induction of IGFBP-3 by IGF-1 may be a major advantage in the therapeutic use of biosynthetic IGF-I in several types of short stature children.

scholarly journals Targeting Insulin-Like Growth Factor Binding Protein-3 Signaling in Triple-Negative Breast Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Kamila A. Marzec ◽  
Robert C. Baxter ◽  
Janet L. Martin
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Breast Cancers ◽  
Novel Therapy ◽  
Factor Binding ◽  
Igfbp 3

Insulin-like growth factor binding protein-3 (IGFBP-3) is a key regulatory molecule of the IGF axis and can function in a tissue-specific way as both a tumor suppressor and promoter. Triple-negative breast cancer (TNBC) has high tumor expression of IGFBP-3 associated with markers of poor prognosis and, although accounting for 15–20% of all breast cancers, is responsible for disproportionate rates of morbidity and mortality. Because they lack estrogen and progesterone receptors and overexpression of HER2, TNBC are resistant to treatments that target these molecules, making the development of new therapies an important goal. In addition to frequent high expression of IGFBP-3, these tumors also express EGFR highly, but targeting EGFR signaling alone in TNBC has been of little success. Identification of a functional growth-stimulatory interaction between EGFR and IGFBP-3 signaling prompted investigation into cotargeting these pathways as a novel therapy for TNBC. This involves inhibition of both EGFR kinase activity and a mediator of IGFBP-3’s stimulatory bioactivity, sphingosine kinase-1 (SphK1), and has shown promise in a preclinical setting. Functional interaction between EGFR and IGFBP-3 may also promote chemoresistance in TNBC, and delineating the mechanisms involved may identify additional targets for development of therapies in cancers that express both IGFBP-3 and EGFR.

Sign in / Sign up

Export Citation Format

Share Document