Abstract:
:The interaction between the urokinase receptor (uPAR) and its ligand urokinase (uPA) mediates phenomena such as tissue remodelling, chemotaxis, tumour invasion, dissemination, proliferation, and angiogenesis. The broad-spectrum of biological processes that the uPA/uPAR interaction plays a role in has led researchers to speculate that this interaction may be a useful molecular target for therapeutic intervention in several pathological conditions, particularly in the prevention and inhibition of the dissemination of cancer cells. In syngeneic and xenograft murine tumour models, in which metastasis is driven by the uPA/uPAR interaction, inhibition of primary tumour growth, metastasis and angiogenesis has been shown with several proteins acting as uPAR antagonists. Immunohistochemistry, in conjunction with prognostic studies, has implicated the uPA/uPAR interaction in the dissemination of tumours, such as malignant melanoma, colon cancer, non-small cell lung cancer (NSCLC) and stomach cancer, as well as breast and ovarian carcinomas. A potential inhibitor of the uPA/uPAR interaction should result in a significant increase in the disease-free interval and survival time following resection of the primary tumour in a clinical Minimal Residual Disease (MRD) setting. Low molecular weight uPAR antagonists should be orally active, and have few side-effects, excellent bioavailability, favourable pharmacokinetic properties and a long half-life. Furthermore, these compounds should be able to inhibit the dissemination of cancer cells without the need for targeted drug and vector delivery.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Weidle UH,König Bdoi
10.1517/13543784.7.3.391subject
Has Abstractpub_date
1998-03-01 00:00:00pages
391-403issue
3eissn
1354-3784issn
1744-7658journal_volume
7pub_type
杂志文章abstract:INTRODUCTION:Current treatment for polycythemia vera (PV) is limited and primarily targets thrombosis risk. Agents targeting distinct mechanisms of action within myeloproliferation are undergoing clinical evaluation to optimize efficacy, improve tolerance and augment long term disease complications. AREA COVERED:This ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2020.1782886
更新日期:2020-08-01 00:00:00
abstract::In order to improve therapy and increase the quality of life for diabetic patients, it has been of significant interest to develop rapid-acting insulin preparations that mimic the physiological meal-time profile of insulin more closely than soluble human insulin. Insulin aspart (B28Asp human insulin) is a novel rapid-...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.8.9.1431
更新日期:1999-09-01 00:00:00
abstract::Background: We aimed to estimate population-based trends in the prevalence of coexisting type 2 diabetes (T2D) and suspected nonalcoholic fatty liver disease (NAFLD) and pioglitazone use among U.S. adults.Research design and methods: We conducted a cross-sectional analysis of the National Health and Nutrition Examinat...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2020.1704731
更新日期:2020-02-01 00:00:00
abstract::Neuroimmunophilin ligands are a class of compounds that hold great promise for the treatment of nerve injuries and neurological disease. In contrast to neurotrophins (e.g., nerve growth factor), these compounds readily cross the blood-brain barrier, being orally effective in a variety of animal models of ischaemia, tr...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.10.2331
更新日期:2000-10-01 00:00:00
abstract:BACKGROUND:Age-related macular degeneration (AMD) affects > 14 million individuals worldwide. Although 90% of patients with AMD have the dry form, neovascular AMD accounts for the vast majority of patients who develop legal blindness. Until recently, few treatment options existed for treatment of neovascular AMD. The a...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903201684
更新日期:2009-10-01 00:00:00
abstract::Hepatitis C virus is the most common chronic, blood-bourne infection, affecting 170 million people worldwide, approximately 3% of the global population. Of those infected with hepatitis C virus, 50 - 85% will develop chronic hepatitis C. Although hepatitis C is primarily a disease of the liver, a diagnosis is currentl...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.4.515
更新日期:2002-04-01 00:00:00
abstract::Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are secreted by the heart and play important roles in the compensation of congestive heart failure with their vasodilating, natriuretic, antiproliferative, lusitropic and neurohumoral-modulating properties. Based on these beneficial properties, exog...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.13.6.643
更新日期:2004-06-01 00:00:00
abstract:INTRODUCTION:Although the combination of an anti-CD20 monoclonal antibody and chemotherapy has widely improved survival of patients with B-cell lymphoma, the disease still relapses. A better understanding of the biology of lymphomas has highlighted the role of the cell of origin in response to treatment and outcome. Le...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1208170
更新日期:2016-09-01 00:00:00
abstract::The beneficial effect of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in primary prevention of coronary artery disease in those with hypercholesterolaemia and in secondary prevention in those with established coronary vascular disease are now well known. A growing body of eviden...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.10.10.1847
更新日期:2001-10-01 00:00:00
abstract:INTRODUCTION:Sepsis with Bacillus anthracis infection has a very high mortality rate despite appropriate antibiotic and supportive therapies. Over the past 15 years, recent outbreaks in the US and in Europe, coupled with anthrax's bioterrorism weapon potential, have stimulated efforts to develop adjunctive therapies to...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1041587
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Today, propofol or 2,6-diisopropylphenol is the anesthetic mainly used for monitored anesthetic care sedation and during intravenous anesthesia. The formulation, a lipid macroemulsion, shows several disadvantages. Therefore, during the past years considerable scientific effort has been undertaken to find eit...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903193063
更新日期:2009-10-01 00:00:00
abstract::The eating disorders anorexia nervosa, bulimia nervosa and binge eating disorder are common, significant public health problems which are treated with nutritional, psychotherapeutic and pharmacological interventions. A number of drugs (mostly antidepressant drugs) are currently used in their treatment to some benefit,...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.3.491
更新日期:2003-03-01 00:00:00
abstract:INTRODUCTION:Myocardial fibrosis is a remarkably dynamic process mediated by different molecular pathways that represent potential targets of novel therapeutic interventions. Transforming Growth Factor-beta (TGF-β), connective Tissue Growth Factor (cTGF) and Galectin-3 (Gal-3) represent the most promising targets on wh...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2021.1868432
更新日期:2021-01-04 00:00:00
abstract::Diminished efficacy in terms of clinical relapses and lesion load on magnetic resonance images for patients developing neutralising antibodies (NAbs) to recombinant IFN-beta may be found in multiple sclerosis. NAbs become detectable over the first few years of therapy, disappearing during the treatment course in some ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.7.1153
更新日期:2003-07-01 00:00:00
abstract::Biologically-based skin substitutes have developed as commercial products over the last 5 years. The first generation includes the collagen-based synthetic device, Integra, and Alloderm, which is based on devitalised and cross-linked human dermis. These are used as dermal replacements for third degree burns. Within th...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.5.803
更新日期:1998-05-01 00:00:00
abstract::Celiac disease is an autoimmune condition affecting genetically susceptible individuals. It is produced by the ingestion of gluten contained in wheat, rye, barley, and related products. The only treatment currently available is strict adherence to a gluten-free diet for life. This requirement for dietary compliance is...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903369333
更新日期:2009-12-01 00:00:00
abstract:INTRODUCTION:Minimal change disease (MCD) and Focal and segmental glomerulosclerosis (FSGS) are two of the major causes of nephrotic syndrome (NS) in children and adults. According to KDIGO (Kidney Disease: Improving Global Outcomes) guidelines, the treatment of adult primary MCD and FSGS should be based on immunosuppr...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1540587
更新日期:2018-11-01 00:00:00
abstract::TNP-470, an analogue of fumagillin, has been shown to inhibit angiogenesis in vitro and in vivo. In 1992, TNP-470 entered clinical development for cancer as an anti-angiogenic agent. It is currently in Phase I/II trials in Kaposi's sarcoma, renal cell carcinoma, brain cancer, breast cancer, cervical cancer and prostat...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.6.1383
更新日期:2000-06-01 00:00:00
abstract:INTRODUCTION:The highly divergent histological heterogeneities, aggressive invasion and extremely poor response to treatment make glioblastoma (GBM) one of the most lethal and difficult cancers in humans. Among key elements driving its behavior is epidermal growth factor receptor (EGFR), however, neither traditional th...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2013.806484
更新日期:2013-08-01 00:00:00
abstract:BACKGROUND:Potent new drugs against multidrug-resistant Gram-negative bacteria, namely Pseudomonas aeruginosa and Acinetobacter spp. and pan-drug-resistant Klebsiella pneumoniae, which constitute an increasing medical threat, are almost absent from the future pharmaceutical pipeline. OBJECTIVE:This drug evaluation foc...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.5.749
更新日期:2008-05-01 00:00:00
abstract::PDE3 cyclic nucleotide phosphodiesterases are important in cyclic AMP (cAMP) and possibly cyclic GMP-mediated signalling in cardiac and vascular smooth muscle myocytes. Drugs that inhibit these enzymes have inotropic and vasodilatory actions that have proven useful in the short-term treatment of contractile failure an...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.11.1529
更新日期:2002-11-01 00:00:00
abstract::The topics discussed at this conference covered many aspects of the pathogenesis, epidemiology, diagnosis and treatment of rheumatic diseases, from the search of new therapeutic targets and evaluation of new diagnostic techniques to preclinical and clinical development of novel therapies. This contribution focuses pri...
journal_title:Expert opinion on investigational drugs
pub_type:
doi:10.1517/13543784.12.10.1713
更新日期:2003-10-01 00:00:00
abstract::Targeting cellular proliferation persists as a mainstay of cancer therapeutic strategy. Although microtubule-targeting drugs (such as taxanes and vinca alkaloids) have been used successfully in the clinic to treat a variety of cancers, they carry substantial liabilities that have spurred drug companies to aggressively...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.11.1411
更新日期:2006-11-01 00:00:00
abstract::In addition to a variety of other novel agents, interest in histone deacetylase inhibitors (HDACIs) as antineoplastic drugs has recently accelerated and increasing numbers of these compounds have entered clinical trials in humans. HDACIs represent a prototype of molecularly targeted agents that perturb signal transduc...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.13.1.21
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Armodafinil is a wake-promoting agent developed by Cephalon that was approved in mid-2007 for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea and shift work disorder. It is the R-enantiomer of the compound modafinil. Like modafinil, the mechanism of action for armoda...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.4.565
更新日期:2008-04-01 00:00:00
abstract::Two methods of using tumour located enzymes have been described. These are antibody directed enzyme prodrug therapy (ADEPT) and macromolecule directed enzyme prodrug therapy (MDEPT), where the tumour located enzyme converts a non-toxic prodrug into a cytotoxic drug at tumour sites. The alternative use of tumour locate...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.8.2.161
更新日期:1999-02-01 00:00:00
abstract:INTRODUCTION:Although significant advances have been made in the treatment of advanced renal cell carcinoma (RCC), patients still develop resistance to standard therapies and require the administration of subsequent lines of treatment. New therapeutic approaches are thus imperative to improve the prognosis for patients...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1427731
更新日期:2018-02-01 00:00:00
abstract::Atopic dermatitis (AD) is a common inflammatory disease involving the skin and often other organs and systems, mainly respiratory. A definitive general consensus on the AD pathogenesis has not yet been established, however several lines of evidence suggest that T-cells play a crucial role in priming AD early-stage les...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.10.1.49
更新日期:2001-01-01 00:00:00
abstract::There are several reasons to believe that agents that augment cAMP-mediated signalling in cardiac myocytes should have beneficial effects in patients with heart failure. However, clinical trials of first-generation cyclic nucleotide phosphodiesterase (PDE3) inhibitors, which raise cAMP content by blocking its hydrolys...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.5.963
更新日期:2000-05-01 00:00:00
abstract::Improving the tumour selectivity of cytotoxic drugs through conjugation to tumour-reactive monoclonal antibodies may lead to novel, more potent agents for cancer therapy. The maytansinoid drugs are 100- to 1000-fold more cytotoxic in vitro than current clinical anticancer drugs. We recently demonstrated that conjugati...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.2.169
更新日期:1997-02-01 00:00:00