Clinical utility of level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1

The prognostic and/or predictive value of the cancer biomarkers, urokinase-type plasminogen activator (uPA) and its inhibitor (plasminogen activator inhibitor [PAI]-1), determined by ELISA in tumor-tissue extracts, was demonstrated for several cancer types in numerous clinically relevant retrospective or prospective studies, including a multicenter breast cancer therapy trial (Chemo-N0). Consequently, for the first time ever for any cancer biomarker for breast cancer, uPA and PAI-1 have reached the highest level of evidence, level-of-evidence-1. At present, two other breast cancer therapy trials, NNBC-3 and Plan B, also incorporating uPA and PAI-1 as treatment-assignment tools are in effect. Furthermore, small synthetic molecules targeting uPA are currently in Phase II clinical trials in patients afflicted with advanced cancer of the ovary, breast or pancreas.

[1]  N. Brünner,et al.  Emerging biomarkers in breast cancer care. , 2010, Biomarkers in medicine.

[2]  N. Brünner,et al.  Characteristics of the level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1 , 2010, Expert review of molecular diagnostics.

[3]  V. Heinemann,et al.  Randomized phase II trial with an uPA inhibitor (WX-671) in patients with locally advanced nonmetastatic pancreatic cancer. , 2010 .

[4]  F. Cardoso,et al.  Phase II, two-arm, double-blind, multicenter, randomized study of the combination of oral WX-671 plus capecitabine versus capecitabine in first-line HER2-negative metastatic breast cancer (MBC). , 2010 .

[5]  D. Goldstein,et al.  Development of a nomogram to predict overall survival in patients with locally advanced or metastatic gastrointestinal stromal tumor receiving first-line treatment with imatinib. , 2010 .

[6]  J. Kjems,et al.  RNA aptamers as conformational probes and regulatory agents for plasminogen activator inhibitor-1. , 2010, Biochemistry.

[7]  V. Lazar,et al.  Cancer-related forecast biomarkers: a topic in focus of the Worldwide Innovative Network in Personalized Cancer Medicine (WIN). , 2010, Bioanalysis.

[8]  D. Neri,et al.  Isolation and characterization of an inhibitory human monoclonal antibody specific to the urokinase-type plasminogen activator, uPA. , 2010, Protein engineering, design & selection : PEDS.

[9]  Detlev Suckau,et al.  Classification of HER2 receptor status in breast cancer tissues by MALDI imaging mass spectrometry. , 2010, Journal of proteome research.

[10]  Nils Brünner,et al.  HER2, TOP2A, and TIMP-1 and responsiveness to adjuvant anthracycline-containing chemotherapy in high-risk breast cancer patients. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  A. Walf,et al.  Estrogen action: A historic perspective on the implications of considering alternative approaches , 2010, Physiology & Behavior.

[12]  Christopher R Kinsinger,et al.  Analytical validation of protein-based multiplex assays: a workshop report by the NCI-FDA interagency oncology task force on molecular diagnostics. , 2010, Clinical chemistry.

[13]  H. Taubert,et al.  Co-detection of members of the urokinase plasminogen activator system in tumour tissue and serum correlates with a poor prognosis for soft-tissue sarcoma patients , 2010, British Journal of Cancer.

[14]  Soonmyung Paik,et al.  Use of archived specimens in evaluation of prognostic and predictive biomarkers. , 2009, Journal of the National Cancer Institute.

[15]  Lily Yang,et al.  Multiplexed fluorescence imaging of tumor biomarkers in gene expression and protein levels for personalized and predictive medicine. , 2009, Current molecular medicine.

[16]  M. Langenskiöld,et al.  Differential Prognostic Impact of uPA and PAI-1 in Colon and Rectal Cancer , 2009, Tumor Biology.

[17]  P. Workman,et al.  Biomarker-Driven Early Clinical Trials in Oncology: A Paradigm Shift in Drug Development , 2009, Cancer journal.

[18]  R. Schilsky,et al.  Translating the cancer genome into clinically useful tools and strategies , 2009, Disease Models & Mechanisms.

[19]  R. Franco,et al.  Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis , 2009, Molecular Cancer Therapeutics.

[20]  P. Kafarski,et al.  Proteases as anti-cancer targets--molecular and biological basis for development of inhibitor-like drugs against cancer. , 2009, Anti-cancer agents in medicinal chemistry.

[21]  Richard S Houlston,et al.  Plasminogen activator inhibitor variants PAI-1 A15T and PAI-2 S413C influence lung cancer prognosis. , 2009, Lung cancer.

[22]  K. Patterson,et al.  Expression of urokinase plasminogen activator and its receptor in advanced epithelial ovarian cancer patients. , 2009, Gynecologic oncology.

[23]  Yaling Tang,et al.  RNAi targeting urokinase‐type plasminogen activator receptor inhibits metastasis and progression of oral squamous cell carcinoma in vivo , 2009, International journal of cancer.

[24]  Yong Li,et al.  Coexpression of invasive markers (uPA, CD44) and multiple drug-resistance proteins (MDR1, MRP2) is correlated with epithelial ovarian cancer progression , 2009, British Journal of Cancer.

[25]  J. Martínková,et al.  Challenges in cancer research and multifaceted approaches for cancer biomarker quest , 2009, FEBS Letters.

[26]  B. Sullenger,et al.  Antimetastatic potential of PAI-1-specific RNA aptamers. , 2009, Oligonucleotides.

[27]  M. Langenskiöld,et al.  uPA and PAI-1 in rectal cancer--relationship to radiotherapy and clinical outcome. , 2009, The Journal of surgical research.

[28]  C. Roehrborn,et al.  Predictive value of the differential expression of the urokinase plasminogen activation axis in radical prostatectomy patients. , 2009, European urology.

[29]  M. Olman,et al.  CXCL12-mediated induction of plasminogen activator inhibitor-1 expression in human CXCR4 positive astroglioma cells. , 2009, Biological & pharmaceutical bulletin.

[30]  S. Russell,et al.  Tumor and vascular targeting of a novel oncolytic measles virus retargeted against the urokinase receptor. , 2009, Cancer research.

[31]  K. Mortensen,et al.  A Novel Mode of Intervention with Serine Protease Activity , 2009, Journal of Biological Chemistry.

[32]  S. Sorrenti,et al.  The urokinase plasminogen activator system: a target for anti-cancer therapy. , 2009, Current cancer drug targets.

[33]  Mitch Dowsett,et al.  Emerging Biomarkers and New Understanding of Traditional Markers in Personalized Therapy for Breast Cancer , 2008, Clinical Cancer Research.

[34]  H. Nielsen,et al.  National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. , 2008, Clinical chemistry.

[35]  K. Almholt,et al.  Antibody-mediated Targeting of the Urokinase-type Plasminogen Activator Proteolytic Function Neutralizes Fibrinolysis in Vivo* , 2008, Journal of Biological Chemistry.

[36]  M. Duffy,et al.  A personalized approach to cancer treatment: how biomarkers can help. , 2008, Clinical chemistry.

[37]  L. Goldstein Experience in Phase I Trials and an Upcoming Phase II Study with uPA Inhibitors in Metastatic Breast Cancer , 2008, Breast Care.

[38]  H. Graefe,et al.  The Oral Serine Protease Inhibitor WX-671 – First Experience in Patients with Advanced Head and Neck Carcinoma , 2008, Breast Care.

[39]  N. Harbeck,et al.  Assessment of Urokinase-Type Plasminogen Activator and Its Inhibitor PAI-1 in Breast Cancer Tissue: Historical Aspects and Future Prospects , 2008, Breast Care.

[40]  N. Brünner,et al.  Plasminogen activator inhibitor 1 protects fibrosarcoma cells from etoposide-induced apoptosis through activation of the PI3K/Akt cell survival pathway. , 2008, Neoplasia.

[41]  K. Behbakht,et al.  A phase 2, randomized, double-blind, placebo-controlled trial of clinical activity and safety of subcutaneous A6 in women with asymptomatic CA125 progression after first-line chemotherapy of epithelial ovarian cancer. , 2008, Gynecologic oncology.

[42]  A. Gils,et al.  A Peptide Accelerating the Conversion of Plasminogen Activator Inhibitor-1 to an Inactive Latent State , 2008, Molecular Pharmacology.

[43]  Z. Hua,et al.  A hybrid protein comprising ATF domain of pro‐UK and VAS, an angiogenesis inhibitor, is a potent candidate for targeted cancer therapy , 2008, International journal of cancer.

[44]  L. Kiemeney,et al.  Components of the plasminogen activator system and their complexes in renal cell and bladder cancer: comparison between normal and matched cancerous tissues , 2008, BJU international.

[45]  B. Binder,et al.  The plasminogen activator inhibitor "paradox" in cancer. , 2008, Immunology letters.

[46]  Michael M Ling,et al.  New molecular assays for cancer diagnosis and targeted therapy. , 2008, Current opinion in molecular therapeutics.

[47]  Xian-wen Hu,et al.  Inhibition of tumor growth and metastasis by ATF-Fc, an engineered antibody targeting urokinase receptor , 2008, Cancer biology & therapy.

[48]  S. Sheng The feasibility of uPA/uPAR-targeting strategies in cancer treatment , 2008, Cancer biology & therapy.

[49]  M. Nangaku,et al.  Inhibition of Plasminogen Activator Inhibitor-1: Its Mechanism and Effectiveness on Coagulation and Fibrosis , 2008, Arteriosclerosis, thrombosis, and vascular biology.

[50]  H. Miyake,et al.  EXPRESSION OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR SYSTEM IN PROSTATE CANCER: CORRELATION WITH CLINICOPATHOLOGICAL OUTCOMES IN PATIENTS UNDERGOING RADICAL PROSTATECTOMY , 2008 .

[51]  C. Scarlett,et al.  Prognostic Significance of Growth Factors and the Urokinase-Type Plasminogen Activator System in Pancreatic Ductal Adenocarcinoma , 2008, Pancreas.

[52]  S. Baldus,et al.  Significant Down-Regulation of the Plasminogen Activator Inhibitor 1 mRNA in Pancreatic Cancer , 2008, Pancreas.

[53]  D. Hasenclever,et al.  Role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) for prognosis in endometrial cancer. , 2008, Gynecologic oncology.

[54]  A. Samii,et al.  Expression of matrix metalloproteinases-1, -2, and -9; tissue inhibitors of matrix metalloproteinases-1 and -2; cathepsin B; urokinase plasminogen activator; and plasminogen activator inhibitor, type I in skull base chordoma. , 2008, Human pathology.

[55]  J. Jass,et al.  Multimarker phenotype predicts adverse survival in patients with lymph node‐negative colorectal cancer , 2008, Cancer.

[56]  J. Nesland,et al.  FAP-α and uPA Show Different Expression Patterns in Premalignant and Malignant Esophageal Lesions , 2008, Ultrastructural pathology.

[57]  N. Brünner,et al.  TIMP-1 as a tumor marker in breast cancer – An update , 2008, Acta oncologica.

[58]  K. Hemminki,et al.  Polymorphisms in the genes of the urokinase plasminogen activation system in relation to colorectal cancer. , 2007, Annals of oncology : official journal of the European Society for Medical Oncology.

[59]  E. Baker,et al.  Plasminogen activator system in oral squamous cell carcinoma. , 2007, The British journal of oral & maxillofacial surgery.

[60]  R. Bast,et al.  American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[61]  K. Iguchi,et al.  Pamidronate down-regulates urokinase-type plasminogen activator expression in PC-3 prostate cancer cells. , 2007, Anticancer research.

[62]  Elena P Moiseeva,et al.  Extended treatment with physiologic concentrations of dietary phytochemicals results in altered gene expression, reduced growth, and apoptosis of cancer cells , 2007, Molecular Cancer Therapeutics.

[63]  M. Stack,et al.  Urinary-type plasminogen activator (uPA) and its receptor (uPAR) in squamous cell carcinoma of the oral cavity. , 2007, The Biochemical journal.

[64]  B. Lebleu,et al.  Inhibition of PAI-1 expression in breast cancer carcinoma cells by siRNA at nanomolar range. , 2007, Biochimie.

[65]  E. Pignotti,et al.  Altered expression of urokinase-type plasminogen activator and plasminogen activator inhibitor in high-risk soft tissue sarcomas. , 2007, Histology and histopathology.

[66]  P. Andreasen PAI-1 - a potential therapeutic target in cancer. , 2007, Current drug targets.

[67]  C. Sotiriou,et al.  Taking gene-expression profiling to the clinic: when will molecular signatures become relevant to patient care? , 2007, Nature Reviews Cancer.

[68]  Ermina Iljazović,et al.  Monitoring of chemotherapy successfulness of platina/taxol chemotherapy protocol by using determination of serum urokinase plasminogen activator (uPA) and soluble urokinase plasminogen activator receptor (suPAR) in patients with ovarian carcinoma FIGO II and III stage. , 2007, Bosnian journal of basic medical sciences.

[69]  J. Overgaard,et al.  Urokinase plasminogen activator and plasminogen activator inhibitor type-1 in nonsmall-cell lung cancer: relation to prognosis and angiogenesis. , 2007, Lung cancer.

[70]  S. Leppla,et al.  Systematic urokinase-activated anthrax toxin therapy produces regressions of subcutaneous human non-small cell lung tumor in athymic nude mice. , 2007, Cancer research.

[71]  J. Foekens,et al.  Prognostic value of plasminogen activator inhibitor‐1 in head and neck squamous cell carcinoma , 2007, Head & neck.

[72]  Kay Dickersin,et al.  Shaping the future of biomarker research in breast cancer to ensure clinical relevance , 2007, Nature Reviews Cancer.

[73]  Mei Zhao,et al.  [Expression and clinical significance of uPA and PAI-1 in epithelial ovarian cancer]. , 2007, Ai zheng = Aizheng = Chinese journal of cancer.

[74]  C. Roehrborn,et al.  Association of the circulating levels of the urokinase system of plasminogen activation with the presence of prostate cancer and invasion, progression, and metastasis. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[75]  J. Wang,et al.  Inhibition of urokinase plasminogen activator with a novel enzyme inhibitor, wxc-340, ameliorates endotoxin and surgery-accelerated growth of murine metastases , 2007, British Journal of Cancer.

[76]  H. Allgayer,et al.  Tumor-Associated Proteolytic Factors uPA and PAI-1: Critical Appraisal of Their Clinical Relevance in Breast Cancer and Their Integration into Decision-Support Algorithms , 2007, Critical reviews in clinical laboratory sciences.

[77]  Jiahong Dong,et al.  Interaction between Cancer Cells and Stromal Fibroblasts Is Required for Activation of the uPAR-uPA-MMP-2 Cascade in Pancreatic Cancer Metastasis , 2006, Clinical Cancer Research.

[78]  G. De Petro,et al.  RNA Interference against Urokinase in Hepatocellular Carcinoma Xenografts in Nude Mice , 2006, Tumor Biology.

[79]  D. Lawrence,et al.  Effect of pharmacologic plasminogen activator inhibitor‐1 inhibition on cell motility and tumor angiogenesis , 2006, Journal of thrombosis and haemostasis : JTH.

[80]  S. Chu,et al.  Black rice anthocyanins inhibit cancer cells invasion via repressions of MMPs and u-PA expression. , 2006, Chemico-biological interactions.

[81]  R. Herbst,et al.  Antimetastatic activity of insulin-like growth factor binding protein-3 in lung cancer is mediated by insulin-like growth factor–independent urokinase-type plasminogen activator inhibition , 2006, Molecular Cancer Therapeutics.

[82]  Yong Li,et al.  Evaluation of urokinase plasminogen activator and its receptor in different grades of human prostate cancer. , 2006, Human pathology.

[83]  B. Peng,et al.  [Expression and clinical significance of coagulate and fibrolysis factors in tissue and plasma from hepatocellular carcinoma patients]. , 2006, Ai zheng = Aizheng = Chinese journal of cancer.

[84]  F. S. Ambesi-Impiombato,et al.  Differential expression of the components of the plasminogen activating system in human thyroid tumour derived cell lines and papillary carcinomas. , 2006, European journal of cancer.

[85]  S. Leppla,et al.  A urokinase-activated recombinant anthrax toxin is selectively cytotoxic to many human tumor cell types , 2006, Molecular Cancer Therapeutics.

[86]  S. Burdach,et al.  Identification and classification of differentially expressed genes in non-small cell lung cancer by expression profiling on a global human 59.620-element oligonucleotide array. , 2006, Oncology reports.

[87]  S. Baldus,et al.  Is the Urokinase-type Plasminogen Activator System a Reliable Prognostic Factor in Gastric Cancer? , 2006, The International journal of biological markers.

[88]  Y. Kodera,et al.  Plasminogen activator inhibitor‐1 as a potential marker for the malignancy of gastric cancer , 2006, Cancer science.

[89]  S. Chu,et al.  Mulberry anthocyanins, cyanidin 3-rutinoside and cyanidin 3-glucoside, exhibited an inhibitory effect on the migration and invasion of a human lung cancer cell line. , 2006, Cancer letters.

[90]  C. Gondi,et al.  siRNA-mediated simultaneous downregulation of uPA and its receptor inhibits angiogenesis and invasiveness triggering apoptosis in breast cancer cells. , 2006, International journal of oncology.

[91]  C. Denkert,et al.  Overexpression of the plasminogen activator inhibitor type-1 in epithelial ovarian cancer. , 2006, Anticancer research.

[92]  H. Allgayer,et al.  Urokinase system expression in gastric carcinoma , 2006, Cancer.

[93]  C. Marras,et al.  Production and post-surgical modification of VEGF, tPA and PAI-1 in patients with glioma , 2006, Cancer biology & therapy.

[94]  N. Brünner,et al.  The complex between urokinase (uPA) and its type-1 inhibitor (PAI-1) in pulmonary adenocarcinoma: relation to prognosis. , 2006, Lung cancer.

[95]  P. Kristjansen,et al.  Antitumor efficacy of a urokinase activation–dependent anthrax toxin , 2006, Molecular Cancer Therapeutics.

[96]  J. Kucab,et al.  Celecoxib Inhibits Urokinase-Type Plasminogen Activator (uPA) Production in MDA-MB-231 Breast Cancer Cells , 2005, Breast Cancer Research and Treatment.

[97]  M. Kralik,et al.  Urokinase-type plasminogen activator and its inhibitor in thyroid neoplasms: a cytosol study , 2005, Wiener klinische Wochenschrift.

[98]  N. Brünner,et al.  A6, a urokinase plasminogen activator (uPA)-derived peptide in patients with advanced gynecologic cancer: a phase I trial. , 2005, Gynecologic oncology.

[99]  S. Loening,et al.  Differential gene expression of urokinase-type plasminogen activator and its receptor in human renal cell carcinoma. , 2005, Oncology reports.

[100]  H. Elokdah,et al.  Evaluation of PAI-039 [{1-Benzyl-5-[4-(trifluoromethoxy)phenyl]-1H-indol-3-yl}(oxo)acetic Acid], a Novel Plasminogen Activator Inhibitor-1 Inhibitor, in a Canine Model of Coronary Artery Thrombosis , 2005, Journal of Pharmacology and Experimental Therapeutics.

[101]  K. Ohba,et al.  Expression of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and plasminogen activator inhibitors in patients with renal cell carcinoma: correlation with tumor associated macrophage and prognosis. , 2005, The Journal of urology.

[102]  N. Brünner,et al.  Measurement of plasminogen activator system components in plasma and tumor tissue extracts obtained from patients with breast cancer: an EORTC Receptor and Biomarker Group collaboration. , 2005, Oncology reports.

[103]  Kyung-Hee Lee,et al.  Expression of E-cadherin and uPA and their association with the prognosis of pancreatic cancer. , 2005, Japanese journal of clinical oncology.

[104]  P. Dettmar,et al.  Tumour-associated urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in normal and neoplastic tissues of patients with squamous cell cancer of the oral cavity - clinical relevance and prognostic value. , 2005, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[105]  R. Ball,et al.  Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues , 2005, British Journal of Cancer.

[106]  Yung-Sheng Huang,et al.  Green Tea Polyphenols Modulate Secretion of Urokinase Plasminogen Activator (uPA) and Inhibit Invasive Behavior of Breast Cancer Cells , 2005, Nutrition and cancer.

[107]  J. Foekens,et al.  Suppression of rat breast cancer metastasis and reduction of primary tumour growth by the small synthetic urokinase inhibitor WX-UK1 , 2005, Thrombosis and Haemostasis.

[108]  Soonmyung Paik,et al.  Gene expression profiling of breast cancer: a new tumor marker. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[109]  N. Brünner,et al.  Expression of urokinase plasminogen activator, its receptor and type‐1 inhibitor in malignant and benign prostate tissue , 2005, International journal of cancer.

[110]  G. Fleuren,et al.  Prognostic relevance of TGF‐β1 and PAI‐1 in cervical cancer , 2004 .

[111]  Q. Chu,et al.  Overexpression of Urinary Plasminogen Activator (uPA) Protein and mRNA in Thyroid Carcinogenesis , 2004, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

[112]  V. Slivova,et al.  Soy isoflavones suppress invasiveness of breast cancer cells by the inhibition of NF-kappaB/AP-1-dependent and -independent pathways. , 2004, International journal of oncology.

[113]  N. Harbeck,et al.  Cathepsin B, plasminogenactivator-inhibitor (PAI-1) and plasminogenactivator-receptor (uPAR) are prognostic factors for patients with non-small cell lung cancer. , 2004, Anticancer research.

[114]  A. Mondino,et al.  uPA and uPAR in fibrinolysis, immunity and pathology. , 2004, Trends in immunology.

[115]  Y. Kodera,et al.  Plasminogen Activator Inhibitor-1 as a Potential Marker for the Malignancy of Esophageal Squamous Cell Carcinoma , 2004, Clinical Cancer Research.

[116]  M. Fernö,et al.  High tumor tissue concentration of urokinase plasminogen activator receptor is associated with good prognosis in patients with ovarian cancer , 2003, International journal of cancer.

[117]  Makoto Ohnishi,et al.  Identification of potential biomarkers of lymph node metastasis in oral squamous cell carcinoma by cDNA microarray analysis , 2003, International journal of cancer.

[118]  Manfred Schmitt,et al.  Tumor Markers , 2003, Molecular & Cellular Proteomics.

[119]  D. Waisman,et al.  Exploitation of Astrocytes by Glioma Cells to Facilitate Invasiveness: A Mechanism Involving Matrix Metalloproteinase-2 and the Urokinase-Type Plasminogen Activator–Plasmin Cascade , 2003, The Journal of Neuroscience.

[120]  Y. Fujiuchi,et al.  Clinical significance of expression of urokinase-type plasminogen activator in patients with prostate cancer. , 2003, Anticancer research.

[121]  I. Bartenjev,et al.  Urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 and type 2 in stage I malignant melanoma. , 2003, Oncology reports.

[122]  T. Wheeler,et al.  Association of plasma urokinase-type plasminogen activator and its receptor with clinical outcome in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder. , 2003, Urology.

[123]  P. Russell,et al.  Quantitative expression of protein markers of plasminogen activation system in prognosis of colorectal cancer , 2003, Journal of surgical oncology.

[124]  N. Brünner,et al.  Tumor Tissue Concentrations of the Proteinase Inhibitors Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and Plasminogen Activator Inhibitor Type 1 (PAI-1) Are Complementary in Determining Prognosis in Primary Breast Cancer * , 2003, Molecular & Cellular Proteomics.

[125]  M. Watson,et al.  Plasminogen activator inhibitor-1 gene polymorphism and colorectal cancer risk and prognosis. , 2003, Cancer letters.

[126]  Megumi Baba,et al.  Urokinase‐type plasminogen activator expression correlates with tumor angiogenesis and poor outcome in gastric cancer , 2003, Cancer science.

[127]  P. Carmeliet,et al.  uPAR: a versatile signalling orchestrator , 2002, Nature Reviews Molecular Cell Biology.

[128]  Y. Takai,et al.  Significance of plasminogen-activation system in the formation of macroscopic types and invasion in esophageal carcinoma. , 2002, Anticancer research.

[129]  A. Scorilas,et al.  Significance of Urokinase-Type Plasminogen Activator and Plasminogen Activator Inhibitor-1 (PAI-1) Expression in Human Colorectal Carcinomas , 2002, Tumor Biology.

[130]  J. Foekens,et al.  Enhanced benefit from adjuvant chemotherapy in breast cancer patients classified high-risk according to urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (n = 3424). , 2002, Cancer research.

[131]  S. Pippig,et al.  Clinical relevance of urokinase‐type plasminogen activator and its inhibitor type 1 (PAI‐1) in squamous cell carcinoma of the uterine cervix , 2002, The Australian & New Zealand journal of obstetrics & gynaecology.

[132]  G. Steineck,et al.  Expression of UPA and UPAR is associated with the clinical course of urinary bladder neoplasms , 2002, International journal of cancer.

[133]  Jacqueline Palmari,et al.  PAI-1 and EGFR expression in adult glioma tumors: toward a molecular prognostic classification. , 2002, International journal of radiation oncology, biology, physics.

[134]  S. Kidson,et al.  The active fraction of plasmatic plasminogen activator inhibitor type 1 as a possible indicator of increased risk for metastatic melanoma. , 2002, Cancer detection and prevention.

[135]  Xin-da Zhou Recurrence and metastasis of hepatocellular carcinoma: progress and prospects. , 2002, Hepatobiliary & pancreatic diseases international : HBPD INT.

[136]  N. Brünner,et al.  Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients. , 2002, Journal of the National Cancer Institute.

[137]  N. Brünner,et al.  Urokinase plasminogen activator and its inhibitor, PAI-1, in association with progression-free survival in early stage endometrial cancer. , 2001, European journal of cancer.

[138]  M. Schmitt,et al.  The uPA/uPA receptor system as a target for tumor therapy. , 2001, Drug news & perspectives.

[139]  E. Gershtein,et al.  Plasminogen Activators and Their Inhibitor in Bone Tumors and Tumor-Like Damages , 2001, Bulletin of Experimental Biology and Medicine.

[140]  E. Gershtein,et al.  Tissue- and Urokinase-Type Plasminogen Activators and Type 1 Plasminogen Activator Inhibitor in Melanomas and Benign Skin Pigment Neoplasms , 2001, Bulletin of Experimental Biology and Medicine.

[141]  H. Friess,et al.  Serine proteinase activation in esophageal cancer. , 2001, Anticancer research.

[142]  N. Harbeck,et al.  Interference with the urokinase plasminogen activator system: a promising therapy concept for solid tumours , 2001, Expert opinion on biological therapy.

[143]  C. Sweep,et al.  Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1. , 2001, Journal of the National Cancer Institute.

[144]  A. Kulig,et al.  Plasminogen activator inhibitor 1 (PAI-1) levels and gene promoter polymorphisms in subjects with colorectal cancer. , 2001, Journal of experimental & clinical cancer research : CR.

[145]  R. Kimmig,et al.  Association of urokinase-type plasminogen activator and its inhibitor with disease progression and prognosis in ovarian cancer. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[146]  H.-B. Tang,et al.  Invasion and metastasis of hepatocellular carcinoma in relation to urokinase-type plasminogen activator, its receptor and inhibitor , 2000, Journal of Cancer Research and Clinical Oncology.

[147]  K. Preissner,et al.  Urokinase receptor: a molecular organizer in cellular communication. , 2000, Current opinion in cell biology.

[148]  K. Shirouzu,et al.  Significance of coexpression of urokinase-type plasminogen activator, and matrix metalloproteinase 3 (stromelysin) and 9 (gelatinase B) in colorectal carcinoma. , 2000, The Journal of surgical research.

[149]  D. Doering,et al.  Clinical relevance of urokinase-type plasminogen activator, its receptor and inhibitor type 1 in ovarian cancer. , 2000, International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.

[150]  P. Strojan,et al.  Urokinase-type plasminogen activator, plasminogen activator inhibitor type 1 and cathepsin D: analysis of their prognostic significance in squamous cell carcinoma of the head and neck. , 2000, Anticancer research.

[151]  T. Morii,et al.  Prognostic relevance of urokinase type plasminogen activator, its receptor and inhibitors in chondrosarcoma. , 2000, Anticancer research.

[152]  D. Tavian,et al.  u‐PA and c‐MET mRNA expression is co‐ordinately enhanced while hepatocyte growth factor mRNA is down‐regulated in human hepatocellular carcinoma , 2000, International journal of cancer.

[153]  R. Ippoliti,et al.  Endocytosis of a chimera between human pro‐urokinase and the plant toxin saporin: an unusual internalization mechanism , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[154]  H. Allgayer,et al.  c-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[155]  J. Rui,et al.  Expression of urokinase‐type plasminogen activator, urokinase‐type plasminogen activator receptor, and plasminogen activator inhibitor‐1 and ‐2 in hepatocellular carcinoma , 2000, Pathology international.

[156]  P. Declerck,et al.  Plasminogen activator inhibitor 1 may promote tumour growth through inhibition of apoptosis , 2000, British Journal of Cancer.

[157]  J. Rui,et al.  Clinical significance of urokinase‐type plasminogen activator activity in hepatocellular carcinoma , 2000, Journal of gastroenterology and hepatology.

[158]  A. Krüger,et al.  The urokinase plasminogen activator system as a novel target for tumour therapy , 2000 .

[159]  Matthias Thewes,et al.  The urokinase plasminogen activator system in angiosarcoma, Kaposi's sarcoma, granuloma pyogenicum, and angioma: an immunohistochemical study , 2000, International journal of dermatology.

[160]  J. Foekens,et al.  The urokinase-type plasminogen activator system in resected non-small-cell lung cancer. Rotterdam Oncology Thoracic Study Group. , 2000, Annals of oncology : official journal of the European Society for Medical Oncology.

[161]  T. Tani,et al.  Cellular distribution and clinical value of urokinase-type plasminogen activator, its receptor, and plasminogen activator inhibitor-2 in esophageal squamous cell carcinoma. , 2000, The American journal of pathology.

[162]  C. Yuan,et al.  Diagnostic and prognostic values of plasma levels of fibrinolytic markers in ovarian cancer. , 1999, Gynecologic oncology.

[163]  Z. Tulassay,et al.  The role of cysteine and serine proteases in colorectal carcinoma , 1999, Cancer.

[164]  A. Bergenheim,et al.  Expression of the proteolytic factors, tPA and uPA, PAI-1 and VEGF during malignant glioma progression , 1999, International Journal of Developmental Neuroscience.

[165]  M. Volm,et al.  Relationship of urokinase and urokinase receptor in non-small cell lung cancer to proliferation, angiogenesis, metastasis and patient survival. , 1999, Oncology reports.

[166]  H. Höfler,et al.  Prognostic significance of urokinase (uPA) and its inhibitor PAI-1 for survival in advanced ovarian carcinoma stage FIGO IIIc , 1999, British Journal of Cancer.

[167]  C. Sweep,et al.  Comparison of immunohistochemistry with immunoassay (ELISA) for the detection of components of the plasminogen activation system in human tumour tissue , 1999, British Journal of Cancer.

[168]  M. Carcangiu,et al.  Plasminogen activator inhibitor‐1 is an independent poor prognostic factor for survival in advanced stage epithelial ovarian cancer patients , 1998, International journal of cancer.

[169]  M. Skobe,et al.  Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization , 1998, Nature Medicine.

[170]  H. Nekarda,et al.  Strong prognostic impact of tumor-associated urokinase-type plasminogen activator in completely resected adenocarcinoma of the esophagus. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[171]  P. Strojan,et al.  Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) in tissue and serum of head and neck squamous cell carcinoma patients. , 1998, European journal of cancer.

[172]  A. Copeta,et al.  Expression of urokinase-type plasminogen activator (u-PA), u-PA receptor, and tissue-type PA messenger RNAs in human hepatocellular carcinoma. , 1998, Cancer research.

[173]  M. Duffy,et al.  Urokinase-type plasminogen activator in colorectal cancer: relationship with clinicopathological features and patient outcome. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[174]  Z. Tulassay,et al.  Urokinase-type plasminogen activator receptor in gastric cancer: tissue expression and prognostic role , 1997, Clinical & Experimental Metastasis.

[175]  H. Höfler,et al.  Clinical Impact of the Plasminogen Activation System in Tumor Invasion and Metastasis: Prognostic Relevance and Target for Therapy , 1997, Thrombosis and Haemostasis.

[176]  J. Roh,et al.  High level of urokinase‐type plasminogen activator is a new prognostic marker in patients with gastric carcinoma , 1997, Cancer.

[177]  J. Foekens,et al.  Expression of urokinase‐type plasminogen activator (uPA) and its inhibitor PAI‐1 in benign, borderline, malignant primary and metastatic ovarian tumors , 1996, International journal of cancer.

[178]  H. Satoh,et al.  The effect of TNP-470 on cell proliferation and urokinase-type plasminogen activator and its inhibitor in human lung cancer cell lines. , 1996, Journal of experimental therapeutics & oncology.

[179]  M. Ray,et al.  Changes in plasminogen activator inhibitor-1 levels in non-small cell lung cancer. , 1996, Bollettino della Societa italiana di biologia sperimentale.

[180]  R. Bast,et al.  Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers. , 1996, Journal of the National Cancer Institute.

[181]  M. Fernö,et al.  Urokinase‐plasminogen‐activator levels and prognosis in 69 soft‐tissue sarcomas , 1996, International journal of cancer.

[182]  K. Ulm,et al.  Clinical relevance of urokinase plasminogen activator, its receptor, and its inhibitor in patients with renal cell carcinoma , 1996, Cancer.

[183]  R. Hartung,et al.  Prognostic value of urokinase plasminogen activator and plasminogen activator inhibitor-1 in renal cell cancer. , 1996, The Journal of urology.

[184]  H. Allgayer,et al.  The prognostic impact of the urokinase-type plasminogen activator system is associated with tumour differentiation in gastric cancer. , 1996, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[185]  H. Höfler,et al.  Primary tumor and metastasis in ovarian cancer differ in their content of urokinase-type plasminogen activator, its receptor, and inhibitors types 1 and 2. , 1995, Cancer research.

[186]  H. Allgayer,et al.  Tumor-associated proteolysis and prognosis: new functional risk factors in gastric cancer defined by the urokinase-type plasminogen activator system. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[187]  E. Hedley‐Whyte,et al.  Prognostic role of urokinase-type plasminogen activator in human gliomas. , 1995, The American journal of pathology.

[188]  R. Gertz,et al.  The significance of urokinase‐type plasminogen activator, its inhibitors, and its receptor in ascites of patients with epithelial ovarian cancer , 1995, Cancer.

[189]  P. Quax,et al.  Components of the plasminogen activation system in uveal melanoma—a clinico‐pathological study , 1995, The Journal of pathology.

[190]  H. Kobayashi,et al.  Impact of urokinase-type plasminogen activator and its inhibitor type 1 on prognosis in cervical cancer of the uterus. , 1994, Cancer research.

[191]  P. Dettmar,et al.  Urokinase (uPA) and PAI-1 predict survival in advanced ovarian cancer patients (FIGO III) after radical surgery and platinum-based chemotherapy. , 1994, Gynecologic oncology.

[192]  S. Blasius,et al.  Plasminogen activators and their inhibitor in osteosarcomas and other bone tumors. , 1994, Zentralblatt fur Pathologie.

[193]  N. Brünner,et al.  Prognostic impact of urokinase, urokinase receptor, and type 1 plasminogen activator inhibitor in squamous and large cell lung cancer tissue. , 1994, Cancer research.

[194]  K. Becker,et al.  Prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in completely resected gastric cancer. , 1994, Cancer research.

[195]  J. Bruner,et al.  Immunohistochemical Localization of Plasminogen Activator Inhibitor Type 1 in Human Brain Tumors , 1994, Journal of neuropathology and experimental neurology.

[196]  S. Brem,et al.  Elevated levels of urokinase-type plasminogen activator and plasminogen activator inhibitor type-1 in malignant human brain tumors. , 1994, Cancer research.

[197]  J. Thompson,et al.  Fibrinolytic activity of ascites caused by alcoholic cirrhosis and peritoneal malignancy. , 1993, Gut.

[198]  K. Sugimachi,et al.  Immunohistochemical evidence of urokinase-type plasminogen activator in primary and metastatic tumors of pulmonary adenocarcinoma. , 1991, Cancer research.

[199]  F. Jänicke,et al.  Clinical Relevance of the Urokinase-Type and Tissue-Type Plasminogen Activators and of Their Type 1 Inhibitor in Breast Cancer , 1991, Seminars in thrombosis and hemostasis.

[200]  M. Schmitt,et al.  UROKINASE-TYPE PLASMINOGEN ACTIVATOR ANTIGEN AND EARLY RELAPSE IN BREAST CANCER , 1989, The Lancet.

[201]  K. Huber,et al.  Plasminogen activators and plasminogen activator inhibitor in malignant and non‐malignant ascitic fluid , 1988, European journal of clinical investigation.

[202]  T. Nakajima,et al.  [Prognostic factors in gastric cancer]. , 1988, Gan to kagaku ryoho. Cancer & chemotherapy.

[203]  M. Duffy,et al.  Urokinase‐plasminogen activator, a marker for aggressive breast carcinomas. Preliminary report , 1988, Cancer.

[204]  M. Duffy,et al.  Multiple forms of plasminogen activator in human breast tumors. , 1985, Cancer research.

[205]  L. Terracciano,et al.  Urokinase-type plasminogen activator is a marker of aggressive phenotype and an independent prognostic factor in mismatch repair-proficient colorectal cancer. , 2010, Human pathology.

[206]  Robert B Livingston,et al.  Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. , 2010, The Lancet. Oncology.

[207]  C. Gondi,et al.  Therapeutic potential of siRNA-mediated targeting of urokinase plasminogen activator, its receptor, and matrix metalloproteinases. , 2009, Methods in molecular biology.

[208]  P. Andreasen,et al.  Biochemical properties of plasminogen activator inhibitor-1. , 2009, Frontiers in bioscience.

[209]  T. Verbeuren,et al.  S35225 is a direct inhibitor of Plasminogen Activator Inhibitor type-1 activity in the blood. , 2008, Thrombosis research.

[210]  Y. Iwadate,et al.  High serum level of plasminogen activator inhibitor-1 predicts histological grade of intracerebral gliomas. , 2008, Anticancer research.

[211]  D. Gingras,et al.  Anthocyanidins inhibit migration of glioblastoma cells: Structure‐activity relationship and involvement of the plasminolytic system , 2007, Journal of cellular biochemistry.

[212]  J. S. Rao,et al.  Prognostic significance of proteolytic enzymes in human brain tumors , 2005, Journal of Neuro-Oncology.

[213]  E. Żekanowska,et al.  [Plasminogen activator inhibitor type 1 (PAI-1) in blood and tissue extracts of patients with non-small cell lung cancer]. , 2004, Pneumonologia i alergologia polska.

[214]  T. Terao,et al.  A soybean Kunitz trypsin inhibitor suppresses ovarian cancer cell invasion by blocking urokinase upregulation , 2004, Clinical & Experimental Metastasis.

[215]  A. El‐kott,et al.  Immunohistochemical expressions of uPA and its receptor uPAR and their prognostic significant in urinary bladder carcinoma , 2004, International Urology and Nephrology.

[216]  A. Kulig,et al.  Plasminogen activator inhibitor 1 (PAI-1) 1334G/A genetic polymorphism in colorectal cancer. , 2003, Acta biochimica Polonica.

[217]  J. Haerting,et al.  Gene-expression signatures in breast cancer. , 2003, The New England journal of medicine.

[218]  T. Lah,et al.  Proteases in brain tumour progression , 2003, Acta Neurochirurgica.

[219]  C. Sweep,et al.  Clinical value of components of the plasminogen activation system in ovarian cyst fluid. , 2002, Anticancer research.

[220]  D. Doering,et al.  Clinical relevance of urokinase-type plasminogen activator, its receptor, and its inhibitor type 1 in endometrial cancer. , 2001, Gynecologic oncology.

[221]  C. Marth,et al.  Predictive value of uPA, PAI-1, HER-2 and VEGF in the serum of ovarian cancer patients. , 2000, Anticancer research.

[222]  H. Strittmatter,et al.  Urokinase and Plasminogen Activator-Inhibitor (PAI-1) Status in Primary Ovarian Carcinomas and Ovarian Metastases Compared to Benign Ovarian Tumors as A Function of Histopathological Parameters , 1999, Clinical chemistry and laboratory medicine.

[223]  T. Kubota,et al.  Production of Urokinase-Type Plasminogen Activator (u-PA) and Plasminogen Activator Inhibitor-1 (PAI-1) in Human Brain Tumours , 1998, Acta Neurochirurgica.

[224]  K. Nakanishi,et al.  Urokinase-type plasminogen activator, its inhibitor, and its receptor in patients with upper urinary tract carcinoma. , 1998, Cancer.

[225]  K. Nakagawa,et al.  Immunohistochemical localization of a urokinase-type plasminogen activator system in squamous cell carcinoma of the oral cavity: association with mode of invasion and lymph node metastasis. , 1998, Oral oncology.

[226]  B. Czerniak,et al.  Expression of plasminogen activators and plasminogen activator inhibitor 1 in dedifferentiated chondrosarcoma , 1997, Cancer.

[227]  H. Friess,et al.  Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma. , 1997, British Journal of Cancer.

[228]  C. V. D. van de Velde,et al.  Contribution of plasminogen activators and their inhibitors to the survival prognosis of patients with Dukes' stage B and C colorectal cancer. , 1997, British Journal of Cancer.

[229]  J. Fiorica,et al.  Urokinase plasminogen activator in ovarian cancer. , 1996, European journal of gynaecological oncology.

[230]  Y. Asada,et al.  Prognostic value of urokinase-type plasminogen activator in patients with superficial bladder cancer. , 1996, Urology.

[231]  P. Mckeever,et al.  Plasminogen activators and inhibitors in gliomas: an immunohistochemical study. , 1994, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[232]  N. Brünner,et al.  Urokinase and plasminogen activator inhibitor type 1 in pulmonary adenocarcinoma. , 1994, Cancer research.

[233]  R. Johnson Letter: Primary non-function in cadaver kidney transplants. , 1975, Lancet.