Cornelis FM Sier

Publications (76) View all

• Article: Circulating bone morphogenetic protein levels and delayed fracture healing.

  Laurens J van Baardewijk, Jacob van der Ende, Suzanne Lissenberg-Thunnissen, Loes M Romijn, Lukas J A C Hawinkels, Cornelis F M Sier, Inger B Schipper
  [show abstract] [hide abstract]
  ABSTRACT: OBJECTIVE: Despite adequate treatment 5-30 % of bone fracture patients experience delayed union. During normal fracture union, bone morphogenetic proteins (BMPs) induce healing through a sequential cascade of events. Improved fracture healing after BMP-2 or -7 supplementation in patients with impaired fracture union suggests a deficiency of one or more of these factors. We postulated that low levels of circulating BMPs may result in delayed bone healing. The aim of this study was to quantify differences in levels of circulating BMP-2, -4, -6, -7, and -9 in patients that have demonstrated normal or delayed fracture healing. PATIENTS AND METHODS: Blood samples were collected from an unselected cohort of 65 patients that had been treated for a diaphyseal tibia or femur fracture. Patients were divided into a group with fracture healing within nine months after injury and a group with delayed fracture union. BMP plasma concentrations were quantified using ELISAs and compared between these two groups. RESULTS: Circulating plasma levels of BMP-2, -4, -6, and -7 did not differ between 34 patients with normal fracture healing and 31 patients with delayed fracture healing. Also the median BMP-9 plasma levels were not statistically different between the two groups of patients. However, the distribution in the patients with normal union showed a wider range (72-2496 pg/ml) compared with the delayed union group (120-816 pg/ml). CONCLUSION: In general, circulating BMP concentrations are not statistically different between patients who demonstrated normal or delayed fracture healing. High circulating BMP-9 levels seem to be associated with faster fracture healing, but are apparently not decisive.
  International Orthopaedics 12/2012; · 2.03 Impact Factor
• Article: Reply to the letter to the editor: Could the use of bone morphogenetic proteins in fracture healing do more harm than good to our patients?

  Cornelis F M Sier, Suzanne N Lissenberg-Thunnissen, David J J De Gorter, Inger B Schipper
  International Orthopaedics 12/2011; 36(3):685. · 2.03 Impact Factor
• Article: Clinical applications of the urokinase receptor (uPAR) for cancer patients.

  Martin C Boonstra, Hein W Verspaget, Sjam Ganesh, Frank J G M Kubben, Alexander L Vahrmeijer, Cornelis J H van de Velde, Peter J K Kuppen, Paul H A Quax, Cornelis F M Sier
  [show abstract] [hide abstract]
  ABSTRACT: Since decades the urokinase plasminogen activator (uPA) system has been associated with the invasion of malignant cells. The receptor of urokinase (uPAR) is one of the key players in this proteolytic cascade, because it focuses uPA's proteolytic activity to the cell surface and in addition functions as a signaling receptor. uPAR is highly expressed in virtually all human cancers, suggesting possible clinical applications as diagnostic marker, predictive tool of survival or clinical response, and as a target for therapy and imaging. This review summarizes the possibilities of uPAR in clinical applications for cancer patients.
  Current pharmaceutical design 06/2011; 17(19):1890-910. · 4.41 Impact Factor
• Source

  Available from: Inger B Schipper

  Article: Use and efficacy of bone morphogenetic proteins in fracture healing.

  Suzanne N Lissenberg-Thunnissen, David J J de Gorter, Cornelis F M Sier, Inger B Schipper
  [show abstract] [hide abstract]
  ABSTRACT: This review evaluates the application of bone morphogenetic proteins (BMPs) in delayed bone repair, aiming at a broad audience from clinicians to scientists. Next to an overview of the role of the different BMPs, their antagonists and their current applications, special attention is focused on new scientific developments improving the effects of BMP-based therapy for bone repair. Publication searches in PubMed and Embase revealed 850 relevant articles on the criteria 'BMP' AND 'bone repair' (as of May 2011). The abstracts were carefully reviewed and papers were selected according to the content. The resulting publications showed that BMP-2 and BMP-7 are clearly the most extensively evaluated BMPs, in general with positive results on bone healing, comparable to the use of unspecific preparations such as autologous bone grafts or platelet-rich plasma. Although the efficacy of BMPs as stimulators of bone repair has been demonstrated in model systems and clinical studies, the use of BMPs to enhance fracture healing in the clinical setting is still controversial. Issues such as when, where and how much of which BMP is the most effective and profitable to use still have to be elucidated. But optimisation of the BMP products used in combination with cheaper production methods will inevitably stimulate the clinical use of BMPs for bone fracture healing in the near future.
  International Orthopaedics 06/2011; 35(9):1271-80. · 2.03 Impact Factor
• Article: Matrix metalloproteinase-14 (MT1-MMP)-mediated endoglin shedding inhibits tumor angiogenesis.

  Lukas J A C Hawinkels, Patricia Kuiper, Eliza Wiercinska, Hein W Verspaget, Zhen Liu, Evangelia Pardali, Cornelis F M Sier, Peter ten Dijke
  [show abstract] [hide abstract]
  ABSTRACT: Endoglin is a transforming growth factor-beta coreceptor with a crucial role in angiogenesis. A soluble form of endoglin is present in the circulation, but the role of soluble endoglin (sEndoglin) is poorly understood. In addition, the endoglin shedding mechanism is not known. Therefore, we examined the role of sEndoglin in tumor angiogenesis and the mechanism by which the extracellular domain of endoglin is released from the membrane.In colorectal cancer specimens, we observed high endothelial endoglin protein expression, accompanied with slightly lower sEndoglin levels in the circulation, compared with healthy controls. In vitro analysis using endothelial sprouting assays revealed that sEndoglin reduced spontaneous and vascular endothelial growth factor-induced endothelial sprouting. Human umbilical vascular endothelial cells were found to secrete high levels of sEndoglin. Endoglin shedding was inhibited by matrix metalloproteinase (MMP) inhibitors and MMP-14 short hairpin RNA, indicating MMP-14 as the major endoglin shedding protease. Coexpression of endoglin and membrane-bound MMP-14 led to a strong increase in sEndoglin levels. Endoglin shedding required a direct interaction between endoglin and membrane-localized MMP-14. Using cleavage site mutants, we determined that MMP-14 cleaved endoglin at a site in close proximity to the transmembrane domain. Taken together, this study shows that MMP-14 mediates endoglin shedding, which may regulate the angiogenic potential of endothelial cells in the (colorectal) tumor microenvironment.
  Cancer Research 05/2010; 70(10):4141-50. · 7.86 Impact Factor