Dr. Cornelis F M Sier, PhD - Leiden University Medical Center - Senior scientist

Dr. Cornelis F M Sier

PhD

Leiden University Medical Center

Senior scientist

Leiden | Netherlands

Main Specialties: Hematology & Oncology, Oncology, Orthopaedic Trauma

ORCID logohttps://orcid.org/0000-0002-4337-2758

Dr. Cornelis F M Sier, PhD - Leiden University Medical Center - Senior scientist

Dr. Cornelis F M Sier

PhD

Introduction

Primary Affiliation: Leiden University Medical Center - Leiden , Netherlands

Specialties:

Education

May 1989 - Dec 1993
Universiteit Leiden
PhD
Gastroenterology-Hepatology

Publications

171Publications

598Reads

175Profile Views

553PubMed Central Citations

ITGA5 inhibition in pancreatic stellate cells attenuates desmoplasia and potentiates efficacy of chemotherapy in pancreatic cancer

Science Advances

Abundant desmoplastic stroma is the hallmark for pancreatic ductal adenocarcinoma (PDAC), which not only aggravates the tumor growth but also prevents tumor penetration of chemotherapy, leading to treatment failure. There is an unmet clinical need to develop therapeutic solutions to the tumor penetration problem. In this study, we investigated the therapeutic potential of integrin α5 (ITGA5) receptor in the PDAC stroma. ITGA5 was overexpressed in the tumor stroma from PDAC patient samples, and overexpression was inversely correlated with overall survival. In vitro, knockdown of ITGA5 inhibited differentiation of human pancreatic stellate cells (hPSCs) and reduced desmoplasia in vivo. Our novel peptidomimetic AV3 against ITGA5 inhibited hPSC activation and enhanced the antitumor effect of gemcitabine in a 3D heterospheroid model. In vivo, AV3 showed a strong reduction of desmoplasia, leading to decompression of blood vasculature, enhanced tumor perfusion, and thereby the efficacy of gemcitabine in co-injection and patient-derived xenograft tumor models.

http://dx.doi.org/10.1126/sciadv.aax2770

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October 2019
3 Reads

ITGA5 inhibition in pancreatic stellate cells attenuates desmoplasia and potentiates efficacy of chemotherapy in pancreatic cancer.

Sci Adv 2019 09 4;5(9):eaax2770. Epub 2019 Sep 4.

Department of Biomaterials, Science and Technology, Section: Targeted Therapeutics, Faculty of Science and Technology, University of Twente, Enschede, Netherlands.

Abundant desmoplastic stroma is the hallmark for pancreatic ductal adenocarcinoma (PDAC), which not only aggravates the tumor growth but also prevents tumor penetration of chemotherapy, leading to treatment failure. There is an unmet clinical need to develop therapeutic solutions to the tumor penetration problem. In this study, we investigated the therapeutic potential of integrin ?5 (ITGA5) receptor in the PDAC stroma. ITGA5 was overexpressed in the tumor stroma from PDAC patient samples, and overexpression was inversely correlated with overall survival. In vitro, knockdown of ITGA5 inhibited differentiation of human pancreatic stellate cells (hPSCs) and reduced desmoplasia in vivo. Our novel peptidomimetic AV3 against ITGA5 inhibited hPSC activation and enhanced the antitumor effect of gemcitabine in a 3D heterospheroid model. In vivo, AV3 showed a strong reduction of desmoplasia, leading to decompression of blood vasculature, enhanced tumor perfusion, and thereby the efficacy of gemcitabine in co-injection and patient-derived xenograft tumor models.

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http://dx.doi.org/10.1126/sciadv.aax2770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726450PMC
September 2019
2 Reads

Fluorescence-guided tumor detection with a novel anti-EpCAM targeted antibody fragment: Preclinical validation.

Surg Oncol 2019 Mar 23;28:1-8. Epub 2018 Oct 23.

Leiden University Medical Centre, Department of Surgery, Leiden, the Netherlands. Electronic address:

Tumor-specific fluorescent imaging agents are moving towards the clinic, supporting surgeons with real-time intraoperative feedback about tumor locations. The epithelial cell adhesion molecule (EpCAM) is considered as one of the most promising tumor-specific proteins due its high overexpression on epithelial-derived cancers. This study describes the development and evaluation of EpCAM-F800, a novel fluorescent anti-EpCAM antibody fragment, for intraoperative tumor imaging. Fab production, conjugation to the fluorophore IRDye 800CW, and binding capacities were determined and validated using HPLC, spectrophotometry and cell-based assays. In vivo, dose escalation-, blocking-, pharmacokinetic- and biodistribution studies (using both fluorescence and radioactivity) were performed, next to imaging of clinically relevant orthotopic xenografts for breast and colorectal cancer. EpCAM-F800 targets EpCAM with high specificity in vitro, which was validated using in vivo blocking experiments with a 10x higher dose of unlabeled Fab. The optimal dose range for fluorescence tumor detection in mice was 1-5?nmol (52-260??g), which corresponds to a human equivalent dose of 0.2-0.8?mg/kg. Biodistribution showed high accumulation of EpCAM-F800 in tumors and metabolizing organs. Breast and colorectal tumors could clearly be visualized within 8?h post-injection and up to 96?h, while the agent already showed homogenous tumor distribution within 4?h. The blood half-life was 4.5?h. This study describes the development and evaluation of a novel EpCAM-targeting agent and the feasibility to visualize breast and colorectal tumors by fluorescence imaging during resections. EpCAM-F800 will be translated for clinical use, considering its abundance in a broad range of tumor types.

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http://dx.doi.org/10.1016/j.suronc.2018.10.004DOI Listing
March 2019
27 Reads
3.270 Impact Factor

Increased expression of cancer-associated fibroblast markers at the invasive front and its association with tumor-stroma ratio in colorectal cancer.

BMC Cancer 2019 Mar 29;19(1):284. Epub 2019 Mar 29.

Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, the Netherlands.

Background: The tumor microenvironment has a critical role in regulating cancer cell behavior. Tumors with high stromal content are associated with poor patient outcome. The tumor-stroma ratio (TSR) identifies colorectal cancers (CRC) with poor patient prognosis based on hematoxylin & eosin stained sections. The desmoplastic reaction consists to a great extent of cancer-associated fibroblasts (CAFs) of which different subtypes are known. The aim of this study is to investigate and quantify CAFs present in the tumor stroma of CRC stratified by the TSR to possibly add prognostic significance to the TSR.

Methods: The expression of established CAF markers was compared between stroma-low and stroma-high tumors using transcriptomic data of 71 stage I - III CRC. Based on literature, fibroblast and stromal markers were selected to perform multiplex immunofluorescent staining on formalin fixed, paraffin-embedded tumor sections of patients diagnosed with stage III colon cancer. Antibodies against the following markers were used: ?SMA, PDGFR -?, FAP, FSP1 and the stromal markers CD45 and CD31 as reference. The markers were subsequently quantified in the stroma using the Vectra imaging microscope.

Results: The transcriptomic data showed that all CAF markers except one were higher expressed in stroma-high compared to stroma-low tumors. Histologically, stroma-high tumors showed a decreased number of FSP1/CD45 cells and a trend of an increased expression of FAP compared to stroma-low tumors. FAP was higher expressed at the invasive part compared to the tumor center in both stroma-high and stroma-low tumors.

Conclusions: The increased expression of FAP at the invasive part and in stroma-high tumors might contribute to the invasive behavior of cancer cells. Future functional experiments should investigate the contribution of FAP to cancer cell invasion. Combining the quantity of the stroma as defined by the TSR with the activity level of CAFs using the expression of FAP may result in an expanded stroma-based tool for patient stratification.

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http://dx.doi.org/10.1186/s12885-019-5462-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440123PMC
March 2019
2 Reads
3.362 Impact Factor

Fluorescence- and multispectral optoacoustic imaging for an optimized detection of deeply located tumors in an orthotopic mouse model of pancreatic carcinoma.

Int J Cancer 2018 05 19;142(10):2118-2129. Epub 2018 Jan 19.

Institute of Interventional and Diagnostic Radiology, University Medical Center Göttingen, Göttingen, Lower Saxony, Germany.

A crucial point for the management of pancreatic ductal adenocarcinoma (PDAC) is the decrease of R1 resections. Our aim was to evaluate the combination of multispectral optoacoustic tomography (MSOT) with fluorescence guided surgery (FGS) for diagnosis and perioperative detection of tumor nodules and resection margins in a xenotransplant mouse model of human pancreatic cancer. The peptide cRGD, conjugated with the near infrared fluorescent (NIRF) dye IRDye800CW and with a trans-cyclooctene (TCO) tag for future click chemistry (cRGD-800CW-TCO), was applied to PDAC bearing immunodeficient nude mice; 27 days after orthotopic transplantation of human AsPC-1 cells into the head of the pancreas, mice were injected with cRGD-800CW-TCO and imaged with fluorescence- and optoacoustic devices before and 2, 6 and 24 hr after injection, before they were sacrificed and dissected with a guidance of FGS imaging system. Fluorescence imaging of cRGD-800CW-TCO allowed detection of the tumor area but without information about the depth, whereas MSOT allowed high resolution 3 D identification of the tumor area, in particular of small tumor nodules. Highly sensitive delineation of tumor burden was achieved during FGS in all mice. Imaging of whole-mouse cryosections, histopathological analysis and NIRF microscopy confirmed the localization of cRGD-800CW-TCO within the tumor tissue. In principle, all imaging modalities applied here were able to detect PDAC in vivo. However, the combination of MSOT and FGS provided detailed spatial information of the signal and achieved a complete overview of the distribution and localization of cRGD-800CW-TCO within the tumor before and during surgical intervention.

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http://doi.wiley.com/10.1002/ijc.31236
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http://dx.doi.org/10.1002/ijc.31236DOI Listing
May 2018
24 Reads
5.085 Impact Factor

uPAR directed-imaging of head-and-neck cancer.

Oncotarget 2017 03;8(13):20519-20520

Leiden University Medical Center, Department of Surgery, Albinusdreef, Leiden, The Netherlands.

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http://dx.doi.org/10.18632/oncotarget.16240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400521PMC
March 2017
7 Reads
1 Citation
6.360 Impact Factor

Evaluation of EphA2 and EphB4 as Targets for Image-Guided Colorectal Cancer Surgery.

Int J Mol Sci 2017 Feb 3;18(2). Epub 2017 Feb 3.

Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.

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http://dx.doi.org/10.3390/ijms18020307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343843PMC
February 2017
25 Reads
2 Citations
2.862 Impact Factor

Selecting Targets for Tumor Imaging: An Overview of Cancer-Associated Membrane Proteins.

Biomark Cancer 2016 27;8:119-133. Epub 2016 Sep 27.

Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.; Antibodies for Research Applications BV, Gouda, the Netherlands.

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http://dx.doi.org/10.4137/BIC.S38542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040425PMC
September 2016
22 Reads
7 Citations

Identification of cell-surface markers for detecting breast cancer cells in ovarian tissue.

Peters IT, Hilders CG, Sier CF, Vahrmeijer AL, Smit VT, Baptist Trimbos J, Kuppen PJ, Archives of gynecology and obstetrics, 2016, vol. 294, no. 2, pp. 385-393, 2016

http://europepmc.org/abstract/med/26946151

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August 2016
3 Reads

Endoglin targeting inhibits tumor angiogenesis and metastatic spread in breast cancer.

Paauwe M, Heijkants RC, Oudt CH, van Pelt GW, Cui C, Theuer CP, Hardwick JC, Sier CF, Hawinkels LJ, Oncogene, 2016, vol. 35, no. 31, pp. 4069-4079, 2016

http://europepmc.org/abstract/med/26804178

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August 2016
5 Reads

Identification of cell-surface markers for detecting breast cancer cells in ovarian tissue.

Arch Gynecol Obstet 2016 08 5;294(2):385-93. Epub 2016 Mar 5.

Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.

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http://dx.doi.org/10.1007/s00404-016-4036-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937067PMC
August 2016
8 Reads
4 Citations
1.280 Impact Factor

Stromal Targets for Fluorescent-Guided Oncologic Surgery.

Front Oncol 2015 20;5:254. Epub 2015 Nov 20.

Department of Surgery, Leiden University Medical Center , Leiden , Netherlands ; Antibodies for Research Applications BV , Gouda , Netherlands.

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http://dx.doi.org/10.3389/fonc.2015.00254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653299PMC
December 2015
45 Reads
4 Citations

Preclinical evaluation of a novel CEA-targeting near-infrared fluorescent tracer delineating colorectal and pancreatic tumors.

Boonstra MC, Tolner B, Schaafsma BE, Boogerd LS, Prevoo HA, Bhavsar G, Kuppen PJ, Sier CF, Bonsing BA, Frangioni JV, van de Velde CJ, Chester KA, Vahrmeijer AL, International journal of cancer, 2015, vol. 137, no. 8, pp. 1910-1920, 2015

http://europepmc.org/abstract/med/25895046

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October 2015
5 Reads

uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery.

Boonstra MC, van Driel PB, van Willigen DM, Stammes MA, Prevoo HA, Tummers QR, Mazar AP, Beekman FJ, Kuppen PJ, van de Velde CJ, Löwik CW, Frangioni JV, van Leeuwen FW, Sier CF, Vahrmeijer AL, Oncotarget, 2015, vol. 6, no. 16, pp. 14260-14273, 2015

http://europepmc.org/abstract/med/25895028

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July 2015
5 Reads

Expression of uPAR in tumor-associated stromal cells is associated with colorectal cancer patient prognosis: a TMA study.

BMC Cancer 2014 Apr 17;14:269. Epub 2014 Apr 17.

Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands.

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http://dx.doi.org/10.1186/1471-2407-14-269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997436PMC
April 2014
23 Reads
13 Citations
3.362 Impact Factor

Circulating bone morphogenetic protein levels and delayed fracture healing.

Int Orthop 2013 Mar 28;37(3):523-7. Epub 2012 Dec 28.

Department of Surgery-Traumatology, Leiden University Medical Center, PO Box 9600, 2300, Leiden, The Netherlands.

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http://dx.doi.org/10.1007/s00264-012-1750-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580113PMC
March 2013
7 Reads
5 Citations
2.020 Impact Factor

Displaced midshaft fractures of the clavicle: non-operative treatment versus plate fixation (Sleutel-TRIAL). A multicentre randomised controlled trial.

Stegeman SA, de Jong M, Sier CF, Krijnen P, Duijff JW, van Thiel TP, de Rijcke PA, Soesman NM, Hagenaars T, Boekhoudt FD, de Vries MR, Roukema GR, Tanka AF, van den Bremer J, van der Meulen HG, Bronkhorst MW, van Dijkman BA, van Zutphen SW, Vos DI, Schep NW, BMC musculoskeletal disorders, 2011, vol.

http://europepmc.org/abstract/med/21864352

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2011
4 Reads

Clinical applications of the urokinase receptor (uPAR) for cancer patients.

Boonstra MC, Verspaget HW, Ganesh S, Kubben FJ, Vahrmeijer AL, van de Velde CJ, Kuppen PJ, Quax PH, Sier CF, Current pharmaceutical design, 2011, vol. 17, no. 19, pp. 1890-1910, 2011

http://europepmc.org/abstract/med/21711239

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2011
5 Reads

Implant removal associated complications in children with limb fractures due to trauma.

Gorter EA, Vos DI, Sier CF, Schipper IB, European journal of trauma and emergency surgery : official publication of the European Trauma Society, 2011, vol. 37, no. 6, pp. 623-627, 2011

http://europepmc.org/abstract/med/22207879

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2011
5 Reads

Clinical applications of the urokinase receptor (uPAR) for cancer patients.

Curr Pharm Des 2011 ;17(19):1890-910

Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.

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http://dx.doi.org/10.2174/138161211796718233DOI Listing
December 2011
6 Reads
20 Citations
3.452 Impact Factor

Use and efficacy of bone morphogenetic proteins in fracture healing.

Lissenberg-Thunnissen SN, de Gorter DJ, Sier CF, Schipper IB, International orthopaedics, 2011, vol. 35, no. 9, pp. 1271-1280, 2011

http://europepmc.org/abstract/med/21698428

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October 2011
3 Reads

Use and efficacy of bone morphogenetic proteins in fracture healing.

Int Orthop 2011 Sep 23;35(9):1271-80. Epub 2011 Jun 23.

Department of Surgery-Traumatology, Leiden University Medical Center, Leiden, The Netherlands.

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http://dx.doi.org/10.1007/s00264-011-1301-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3167450PMC
September 2011
2 Reads
53 Citations
2.020 Impact Factor

Single-nucleotide polymorphisms of matrix metalloproteinases and their inhibitors in gastrointestinal cancer.

Langers AM, Verspaget HW, Hommes DW, Sier CF, World journal of gastrointestinal oncology, 2011, vol. 3, no. 6, pp. 79-98, 2011

http://europepmc.org/abstract/med/21731908

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July 2011
2 Reads

[The midshaft clavicular fracture].

Ned Tijdschr Geneeskd 2010 ;154:A2367

Leids Universitair Medisch Centrum, afd. Heelkunde, The Netherlands.

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December 2010
3 Reads
1 Citation

Matrix metalloproteinase-14 (MT1-MMP)-mediated endoglin shedding inhibits tumor angiogenesis.

Cancer Res 2010 May 27;70(10):4141-50. Epub 2010 Apr 27.

Departmentsof Molecular Cell Biology, Centre for Biomedical Genetics, Gastroenterology-Hepatology, and Surgery, Leiden University Medical Center, Leiden, the Netherlands.

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http://dx.doi.org/10.1158/0008-5472.CAN-09-4466DOI Listing
May 2010
4 Reads
65 Citations
9.330 Impact Factor

5-Aminosalicylic acid inhibits TGF-beta1 signalling in colorectal cancer cells.

Cancer Lett 2010 Jan 21;287(1):82-90. Epub 2009 Jun 21.

Department of Gastroenterology-Hepatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.

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http://dx.doi.org/10.1016/j.canlet.2009.05.033DOI Listing
January 2010
1 Read
7 Citations
5.621 Impact Factor

Active TGF-beta1 correlates with myofibroblasts and malignancy in the colorectal adenoma-carcinoma sequence.

Cancer Sci 2009 Apr;100(4):663-70

Leiden University Medical Center, Department of Gastroenterology-Hepatology, Leiden, The Netherlands.

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http://dx.doi.org/10.1111/j.1349-7006.2009.01100.xDOI Listing
April 2009
2 Reads
12 Citations

Matrix metalloproteinases and their tissue inhibitors as prognostic indicators for diagnostic and surgical recurrence in Crohn's disease.

Inflamm Bowel Dis 2009 Jan;15(1):84-92

LUMC, Department of Gastroenterology-Hepatology, Leiden, The Netherlands.

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http://dx.doi.org/10.1002/ibd.20581DOI Listing
January 2009
6 Reads
5 Citations
4.464 Impact Factor

VEGF release by MMP-9 mediated heparan sulphate cleavage induces colorectal cancer angiogenesis.

Eur J Cancer 2008 Sep 6;44(13):1904-13. Epub 2008 Aug 6.

Department of Gastroenterology-Hepatology, Leiden University Medical Centre, P.O. Box 9600, 2300 RC Leiden, The Netherlands.

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http://dx.doi.org/10.1016/j.ejca.2008.06.031DOI Listing
September 2008
6 Reads
63 Citations
5.420 Impact Factor

Endothelium specific matrilysin (MMP-7) expression in human cancers.

Matrix Biol 2008 Apr 26;27(3):267-71. Epub 2007 Oct 26.

Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

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http://dx.doi.org/10.1016/j.matbio.2007.10.006DOI Listing
April 2008
9 Reads
3 Citations
5.074 Impact Factor

Efficient degradation-aided selection of protease inhibitors by phage display.

Biochem Biophys Res Commun 2007 Dec 15;364(3):549-55. Epub 2007 Oct 15.

Leiden/Amsterdam Centre for Drug Research, Division of Biopharmaceutics, Leiden, The Netherlands.

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http://dx.doi.org/10.1016/j.bbrc.2007.10.032DOI Listing
December 2007
16 Reads
2 Citations
2.300 Impact Factor

Eradication of Helicobacter pylori infection favourably affects altered gastric mucosal MMP-9 levels.

Kubben FJ, Sier CF, Schram MT, Witte AM, Veenendaal RA, van Duijn W, Verheijen JH, Hanemaaijer R, Lamers CB, Verspaget HW, Helicobacter, 2007, vol. 12, no. 5, pp. 498-504, 2007

http://europepmc.org/abstract/med/17760717

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October 2007
3 Reads

Eradication of Helicobacter pylori infection favourably affects altered gastric mucosal MMP-9 levels.

Helicobacter 2007 Oct;12(5):498-504

Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.

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http://dx.doi.org/10.1111/j.1523-5378.2007.00527.xDOI Listing
October 2007
3 Reads
7 Citations
4.110 Impact Factor

Clinical evidence for a protective role of lipocalin-2 against MMP-9 autodegradation and the impact for gastric cancer.

Eur J Cancer 2007 Aug 2;43(12):1869-76. Epub 2007 Jul 2.

Department of Gastroenterology - Hepatology, Leiden University Medical Centre, P.O. Box 9600, 2300 RC Leiden, The Netherlands.

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http://dx.doi.org/10.1016/j.ejca.2007.05.013DOI Listing
August 2007
5 Reads
41 Citations
5.420 Impact Factor

Determination of matrilysin activity in gastrointestinal neoplasia.

Hawinkels LJ, Verspaget HW, van den Berg M, Hanemaaijer R, Sier CF, European journal of clinical investigation, 2007, vol. 37, no. 7, pp. 598-599, 2007

http://europepmc.org/abstract/med/17576214

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July 2007
5 Reads

EMMPRIN-induced MMP-2 activation cascade in human cervical squamous cell carcinoma.

Int J Cancer 2006 Jun;118(12):2991-8

Department of Pathology, Leiden University Medical Center, The Netherlands.

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http://dx.doi.org/10.1002/ijc.21778DOI Listing
June 2006
28 Reads
10 Citations
5.085 Impact Factor

Cross-linking tumor cells with effector cells via CD55 with a bispecific mAb induces beta-glucan-dependent CR3-dependent cellular cytotoxicity.

Eur J Immunol 2006 Apr;36(4):977-84

Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

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http://dx.doi.org/10.1002/eji.200535653DOI Listing
April 2006
1 Read
2 Citations
4.034 Impact Factor

Beta-glucan enhanced killing of renal cell carcinoma micrometastases by monoclonal antibody G250 directed complement activation.

Int J Cancer 2004 May;109(6):900-8

Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

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http://dx.doi.org/10.1002/ijc.20029DOI Listing
May 2004
2 Reads
6 Citations
5.085 Impact Factor

Metabolism of tumour-derived urokinase receptor and receptor fragments in cancer patients and xenografted mice.

Thromb Haemost 2004 Feb;91(2):403-11

Department of Molecular Biology and Functional Genomics and FIRC Institute of Molecular Oncology, San Raffaele Scientific Institute and Hospital, Milan, Italy.

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http://dx.doi.org/10.1160/TH03-06-0351DOI Listing
February 2004
14 Reads
7 Citations
4.984 Impact Factor

Urinary levels of urokinase-type plasminogen activator and its receptor in the detection of bladder carcinoma.

Cancer 2003 Nov;98(9):1995; author reply 1996

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http://dx.doi.org/10.1002/cncr.11751DOI Listing
November 2003
1 Read
4.890 Impact Factor

Plasminogen activators in multiple sclerosis lesions: implications for the inflammatory response and axonal damage.

Gveric D, Hanemaaijer R, Newcombe J, van Lent NA, Sier CF, Cuzner ML, Brain : a journal of neurology, 2001, vol. 124, no. Pt 10, pp. 1978-1988, 2001

http://europepmc.org/abstract/med/11571216

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October 2001
4 Reads

PAI-1 inhibits urokinase-induced chemotaxis by internalizing the urokinase receptor.

Degryse B, Sier CF, Resnati M, Conese M, Blasi F, FEBS letters, 2001, vol. 505, no. 2, pp. 249-254, 2001

http://europepmc.org/abstract/med/11566185

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October 2001
5 Reads

Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection.

Blood 2000 Dec;96(13):4091-5

Department of Molecular Pathology and Medicine, Molecular Genetics Unit, DIBIT, San Raffaele Scientific Institute, Milan, Italy.

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December 2000
1 Read
41 Citations
10.452 Impact Factor

Soluble urokinase receptor levels correlate with number of circulating tumor cells in acute myeloid leukemia and decrease rapidly during chemotherapy.

Cancer Res 2000 Dec;60(24):7126-32

Haartman Institute, University of Helsinki, Finland.

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December 2000
2 Reads
16 Citations
9.330 Impact Factor

Enhanced urinary gelatinase activities (matrix metalloproteinases 2 and 9) are associated with early-stage bladder carcinoma: a comparison with clinically used tumor markers.

Clin Cancer Res 2000 Jun;6(6):2333-40

Department of Molecular Pathology and Medicine DIBIT, San Raffaele Scientific Institute, Milan, Italy.

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June 2000
2 Reads
14 Citations
8.722 Impact Factor

MMP-9 activity in urine from patients with various tumors, as measured by a novel MMP activity assay using modified urokinase as a substrate.

Hanemaaijer R, Sier CF, Visser H, Scholte L, van Lent N, Toet K, Hoekman K, Verheijen JH, Annals of the New York Academy of Sciences, 1999, vol. 878, pp. 141-149, 1999

http://europepmc.org/abstract/med/10415726

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July 1999
6 Reads

Presence of urokinase-type plasminogen activator receptor in urine of cancer patients and its possible clinical relevance.

Lab Invest 1999 Jun;79(6):717-22

Department of Molecular Pathology and Medicine, DIBIT, San Raffaele Vita-Salute University, Milan, Italy.

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June 1999
15 Citations
3.680 Impact Factor

Superoxide dismutases in relation to the overall survival of colorectal cancer patients.

Janssen AM, Bosman CB, Sier CF, Griffioen G, Kubben FJ, Lamers CB, van Krieken JH, van de Velde CJ, Verspaget HW, British journal of cancer, 1998, vol. 78, no. 8, pp. 1051-1057, 1998

http://europepmc.org/abstract/med/9792149

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October 1998
4 Reads

High performance density gradient electrophoresis of subcellular organelles, protein complexes and proteins.

Tulp A, Verwoerd D, Benham A, Jalink K, Sier C, Neefjes J, Electrophoresis, 1998, vol. 19, no. 7, pp. 1171-1178, 1998

http://europepmc.org/abstract/med/9662180

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July 1998
2 Reads

The level of urokinase-type plasminogen activator receptor is increased in serum of ovarian cancer patients.

Cancer Res 1998 May;58(9):1843-9

Department of Biology and Biotechnology, San Raffaele Scientific Institute, Milan, Italy.

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May 1998
1 Read
29 Citations
9.330 Impact Factor

Tissue levels of matrix metalloproteinases MMP-2 and MMP-9 are related to the overall survival of patients with gastric carcinoma.

Sier CF, Kubben FJ, Ganesh S, Heerding MM, Griffioen G, Hanemaaijer R, van Krieken JH, Lamers CB, Verspaget HW, British journal of cancer, 1996, vol. 74, no. 3, pp. 413-417, 1996

http://europepmc.org/abstract/med/8695357

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August 1996
4 Reads

Gastric mucosal plasminogen activators in Helicobacter pylori infection.

Götz JM, Vergouwe Y, Verspaget HW, Biemond I, Sier CF, Lamers CB, Veenendaal RA, Digestive diseases and sciences, 1996, vol. 41, no. 8, pp. 1577-1582, 1996

http://europepmc.org/abstract/med/8769282

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August 1996
4 Reads

Correlation of glutathione S-transferases with overall survival in patients with gastric carcinoma.

Int J Oncol 1996 Aug;9(2):357-63

UNIV NIJMEGEN HOSP,DEPT MED ONCOL,NL-6500 HB NIJMEGEN,NETHERLANDS. LEIDEN UNIV HOSP,DEPT GASTROENTEROL & HEPATOL,LEIDEN,NETHERLANDS.

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http://dx.doi.org/10.3892/ijo.9.2.357DOI Listing
August 1996
1 Citation
3.025 Impact Factor

Prognostic value of the plasminogen activation system in patients with gastric carcinoma.

Ganesh S, Sier CF, Heerding MM, van Krieken JH, Griffioen G, Welvaart K, van de Velde CJ, Verheijen JH, Lamers CB, Verspaget HW, Cancer, 1996, vol. 77, no. 6, pp. 1035-1043, 1996

http://europepmc.org/abstract/med/8635120

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March 1996
5 Reads

Glutathione S-transferase pi in colorectal tumors is predictive for overall survival.

Cancer Res 1995 Jun;55(12):2696-702

Department of Gastroenterology, St. Radboud University Hospital, Nijmegen, The Netherlands.

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June 1995
6 Citations
9.330 Impact Factor

Increased urokinase receptor levels in human gastrointestinal neoplasia and related liver metastases.

Invasion Metastasis 1993 ;13(6):277-88

Department of Gastroenterology and Hepatology, University Hospital, Leiden, The Netherlands.

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March 1995
1 Read
5 Citations

Plasminogen activators and inhibitor type 1 in neoplastic colonic tissue from patients with familial adenomatous polyposis.

Sier CF, Vloedgraven HJ, Griffioen G, Ganesh S, Nagengast FM, Lamers CB, Verspaget HW, British journal of cancer, 1995, vol. 71, no. 2, pp. 393-396, 1995

http://europepmc.org/abstract/med/7841059

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March 1995
5 Reads

Tetranectin expression in human colonic neoplasia.

Verspaget HW, Clemmensen I, Ganesh S, Christensen L, Sier CF, Griffioen G, Lamers CB, Histopathology, 1994, vol. 25, no. 5, pp. 463-467, 1994

http://europepmc.org/abstract/med/7868087

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December 1994
4 Reads

Inactive urokinase and increased levels of its inhibitor type 1 in colorectal cancer liver metastasis.

Sier CF, Vloedgraven HJ, Ganesh S, Griffioen G, Quax PH, Verheijen JH, Dooijewaard G, Welvaart K, van de Velde CJ, Lamers CB, Gastroenterology, 1994, vol. 107, no. 5, pp. 1449-1456, 1994

http://europepmc.org/abstract/med/7926508

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December 1994
6 Reads

Glutathione S-transferases in liver metastases of colorectal cancer. A comparison with normal liver and primary carcinomas.

Mulder TP, Roelofs HM, Peters WH, Wagenmans MJ, Sier CF, Verspaget HW, Carcinogenesis, 1994, vol. 15, no. 10, pp. 2149-2153, 1994

http://europepmc.org/abstract/med/7955047

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October 1994
6 Reads

Urokinase receptor and colorectal cancer survival.

Ganesh S, Sier CF, Heerding MM, Griffioen G, Lamers CB, Verspaget HW, Lancet (London, England), 1994, vol. 344, no. 8919, pp. 401-402, 1994

http://europepmc.org/abstract/med/7914317

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August 1994
6 Reads

Prognostic relevance of plasminogen activators and their inhibitors in colorectal cancer.

Cancer Res 1994 Aug;54(15):4065-71

Department of Gastroenterology and Hepatology, University Hospital Leiden, The Netherlands.

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August 1994
1 Read
24 Citations
9.330 Impact Factor

Plasminogen activators in normal tissue and carcinomas of the human oesophagus and stomach.

Sier CF, Verspaget HW, Griffioen G, Ganesh S, Vloedgraven HJ, Lamers CB, Gut, 1993, vol. 34, no. 1, pp. 80-85, 1993

http://europepmc.org/abstract/med/8432457

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January 1993
6 Reads

Association of aneuploidy in index adenomas with metachronous colorectal adenoma development and a comparison.

Griffioen G, Cornelisse CJ, Verspaget HW, Sier CF, Eulderink F, Bosman FT, Lamers CB, Cancer, 1992, vol. 70, no. 8, pp. 2035-2043, 1992

http://europepmc.org/abstract/med/1394033

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October 1992
5 Reads

Imbalance of plasminogen activators and their inhibitors in human colorectal neoplasia. Implications of urokinase in colorectal carcinogenesis.

Gastroenterology 1991 Dec;101(6):1522-8

Department of Gastroenterology and Hepatology, University Hospital, Leiden, The Netherlands.

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http://dx.doi.org/10.1016/0016-5085(91)90387-zDOI Listing
December 1991
2 Reads
14 Citations
16.720 Impact Factor

Comparative evaluation of carcinoembryonic antigen, secretory component, and mucins in index and metachronous adenomas of the colorectum.

Gastroenterology 1991 Oct;101(4):919-26

Department of Gastroenterology and Hepatology, University Hospital, Leiden, The Netherlands.

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http://dx.doi.org/10.1016/0016-5085(91)90716-xDOI Listing
October 1991
1 Citation
16.720 Impact Factor

Immunolocalization of urokinase-type plasminogen activator in adenomas and carcinomas of the colorectum.

Sier CF, Fellbaum C, Verspaget HW, Schmitt M, Griffioen G, Graeff H, Hôfler H, Lamers CB, Histopathology, 1991, vol. 19, no. 3, pp. 231-237, 1991

http://europepmc.org/abstract/med/1916697

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October 1991
5 Reads

Top co-authors

Alexander L Vahrmeijer
Alexander L Vahrmeijer

Leiden University Medical Center

15
Martin C Boonstra
Martin C Boonstra

Leiden University Medical Center

10
Hein W Verspaget
Hein W Verspaget

Leiden University Medical Center

9
Roeland Hanemaaijer
Roeland Hanemaaijer

Leiden University Medical Center

4
Inger B Schipper
Inger B Schipper

Leiden University Medical Center

4