Daily administration of low molecular weight heparin increases Hepatocyte Growth Factor serum levels in gynaecological patients

Pharmacokinetic parameters and clinical implications

Anna Surbone, Luca Fuso, Roberto Passera, Annamaria Ferrero, Cristiana Marchese, Cosimo Martino, Annalisa Luchin, Maria Flavia Di Renzo, Paolo Zola

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 12hours. 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, C max 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. Clinical Trials.gov ID: NCT01523652.

Original languageEnglish
Article number517
JournalBMC Research Notes
Volume5
DOIs
Publication statusPublished - 2012

Fingerprint

Pharmacokinetics
Hepatocyte Growth Factor
Low Molecular Weight Heparin
Nadroparin
Serum
Ovarian Neoplasms
Cells
Bioactivity
Tumors
Cytotoxicity
Paclitaxel
Cisplatin
Assays
Neoplasms
Epithelial Cells
Clinical Trials
Carcinoma

Keywords

  • Epithelial ovarian cancer
  • HGF
  • LMWH
  • Nadroparin
  • Pharmacokinetics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Daily administration of low molecular weight heparin increases Hepatocyte Growth Factor serum levels in gynaecological patients : Pharmacokinetic parameters and clinical implications. / Surbone, Anna; Fuso, Luca; Passera, Roberto; Ferrero, Annamaria; Marchese, Cristiana; Martino, Cosimo; Luchin, Annalisa; Di Renzo, Maria Flavia; Zola, Paolo.

In: BMC Research Notes, Vol. 5, 517, 2012.

Research output: Contribution to journalArticle

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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 12hours. 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, C max 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. Clinical Trials.gov ID: NCT01523652.",
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T1 - Daily administration of low molecular weight heparin increases Hepatocyte Growth Factor serum levels in gynaecological patients

T2 - Pharmacokinetic parameters and clinical implications

AU - Surbone, Anna

AU - Fuso, Luca

AU - Passera, Roberto

AU - Ferrero, Annamaria

AU - Marchese, Cristiana

AU - Martino, Cosimo

AU - Luchin, Annalisa

AU - Di Renzo, Maria Flavia

AU - Zola, Paolo

PY - 2012

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N2 - 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 12hours. 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, C max 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. Clinical Trials.gov ID: NCT01523652.

AB - 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 12hours. 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, C max 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. Clinical Trials.gov ID: NCT01523652.

KW - Epithelial ovarian cancer

KW - HGF

KW - LMWH

KW - Nadroparin

KW - Pharmacokinetics

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