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Open Access Research article

Daily administration of low molecular weight heparin increases Hepatocyte Growth Factor serum levels in gynaecological patients: pharmacokinetic parameters and clinical implications

Anna Surbone1, Luca Fuso1*, Roberto Passera3, Annamaria Ferrero1, Cristiana Marchese2, Cosimo Martino4, Annalisa Luchin2, Maria Flavia Di Renzo4 and Paolo Zola1

Author Affiliations

1 Unit of Gynecologic Oncology, Department of Gynecology and Obstetrics of the University of Torino at Azienda Ospedaliera Ordine Mauriziano, Largo Turati 62, Turin, Italy

2 Clinical Chemistry Laboratory, Azienda Ospedaliera Ordine Mauriziano, Turin, Italy

3 Nuclear Medicine Unit, University of Torino at San Giovanni Battista Hospital, Turin, Italy

4 Department of Oncological Sciences of the University of Torino, Institute for Cancer Research ant treatment Candiolo, Turin, Italy

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BMC Research Notes 2012, 5:517  doi:10.1186/1756-0500-5-517

Published: 23 September 2012

Abstract

Background

Hepatocyte Growth Factor (HGF) enhances cytotoxicity of paclitaxel (PTX) and cisplatin (CDDP) in human ovarian cancer cells. Because of potential pitfalls of HGF exogenous administration, we investigated whether HGF serum concentration might be alternatively raised in vivo by administering low molecular weight heparin (LMWH).

Methods

The main HGF pharmacokinetic parameters were evaluated following acute and chronic LMWH treatment. First, women, operated on for gynaecological tumors, were treated with a single dose of calcium nadroparin and studied for 12 hours. Next, women operated on for benign or malignant gynaecological tumors were treated daily with calcic nadroparin for one month. Subsequently, the biological activity of the measured HGF serum levels was tested in assays of ovarian cancer cell sensitization to drugs.

Results

In the short-term treated group, median HGF AUCss, Cmax and Caverage were about four-fold that of the control group, whereas Cmin was three-fold. In the patients treated chronically median HGF serum levels rose about six-fold in the first week, and decreased but remained significantly higher after one month. The pharmacokinetic of nadroparin-dependent HGF increase were similar in the two groups. The HGF concentrations measured after both acute and chronic treatment were found to be effective in sensitising ovarian cancer cells to chemotherapeutics.

Conclusions

This study raises the possibility of using LMWH to increase HGF serum concentration and to take advantage of its biological activities. In particular, nadroparin might be used as a chemo-potentiating agent in epithelial cell ovarian carcinoma through its action on HGF serum concentration.

Trial registration

ClinicalTrials.gov ID: NCT01523652

Keywords:
HGF; LMWH; Pharmacokinetics; Nadroparin; Epithelial ovarian cancer