Abstract:
:Innate immune mechanisms respond rapidly to bacterial infection. A key cellular component of the innate immune response is the neutrophil, whose cytoplasmic granules contain a variety of antimicrobial proteins and peptides. Among these is the bactericidal/permeability-increasing protein (BPI), a cationic 55 kDa protein whose selective anti-infective action against Gram-negative bacteria is based on its high (nM) affinity for lipopolysaccharide (LPS, or "endotoxin"). Binding of BPI to Gram-negative bacteria results in growth inhibition, serves as an opsonin that enhances phagocytosis of bacteria and inhibits bacteria-induced inflammatory responses by blocking the interaction of LPS with host pro-inflammatory pathways. Expression of BPI appears to be developmentally regulated as human newborns apparently have lower neutrophil BPI levels than adults. BPI expression has also recently been demonstrated in human epithelial cells where it appears to be inducible by endogenous anti-inflammatory lipids (lipoxins). BPI's potent anti-endotoxic activity against a broad range of Gram-negative bacterial pathogens is manifest in biological fluids and renders it an attractive template for pharmaceutical development. Indeed, rBPI(21), an active recombinant protein derived from human BPI, has proven safe in Phase I human trials, shown promise in Phase II trials and has recently completed a Phase III trial for severe meningococcaemia with apparent benefit. Identification and evaluation of additional disease entities characterised by Gram-negative bacteraemia and/or endotoxaemia as possible targets for BPI therapy continues.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Levy Odoi
10.1517/13543784.11.2.159subject
Has Abstractpub_date
2002-02-01 00:00:00pages
159-67issue
2eissn
1354-3784issn
1744-7658journal_volume
11pub_type
杂志文章,评审abstract::IL-5 is the predominant cytokine associated with antigen-induced eosinophilic inflammation in the lung. The activation of Th-2 cells leads to the production of IL-5. The pro-eosinophilic effects of IL-5 include: (1) enhanced replication and differentiation of eosinophilic myelocytes; (2) enhanced degranulation of eosi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.3.491
更新日期:2000-03-01 00:00:00
abstract:INTRODUCTION:the search for effective inhibitors to multiple infectious agents including influenza, smallpox and hemorrhagic fever viruses is an area of active research as many of these agents pose dramatic health and economic challenges to the human population. Many of these infectious agents are not only endemic thre...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2011.547852
更新日期:2011-02-01 00:00:00
abstract:INTRODUCTION:In asthma, most commonly, 'conventional' anti-inflammatory medications represented by inhaled corticosteroids and leukotriene inhibitors are effective. In some patients however additional inhibition of the airways inflammation is necessary. Such compounds might be molecules inhibiting specifically certain ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1227319
更新日期:2016-10-01 00:00:00
abstract::Cyclin-dependent protein kinases (CDKs) are key regulators of the cell division cycle, whose various checkpoints proliferating cells must traverse. Since CDK deregulation, either through direct or indirect means, is found in most cancer cells, pharmacological CDK inhibition has become an attractive strategy towards me...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.6.955
更新日期:2003-06-01 00:00:00
abstract:BACKGROUND:With 170 million people infected worldwide and an inadequate current standard of care, hepatitis C virus (HCV) infection represents a major unmet medical need. Multiple companies are working on the discovery and development of specific HCV antiviral drugs, including inhibitors of HCV polymerase, protease and...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.3.303
更新日期:2008-03-01 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
abstract:IMPORTANCE OF THE FIELD:Hepatitis C virus (HCV) is the main agent of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma in the western world. It affects more than 170 million people worldwide. HCV treatment, based on the combination of Peg-interferon and ribavirin, is effective in about 50% of treated pati...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903501505
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Multiple myeloma (MM) remains an incurable malignancy indicating a need for continued investigation of novel therapies. Recent studies have highlighted the role of cyclin-dependent kinases (CDK) in the pathogenesis of MM. PD0332991 (Palbociclib) is an orally bioavailable, highly selective inhibitor of the ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.993753
更新日期:2015-02-01 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::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:Recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) has a dismal prognosis. With the emergence of monoclonal antibodies and tyrosine kinase inhibitors (TKI) targeting the epidermal growth factor receptor (EGFR), several drugs were developed and tested in HNSCC. To date, the monoclonal...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1177022
更新日期:2016-06-01 00:00:00
abstract::Prinomastat (formerly AG3340, Agouron Pharmaceuticals, Inc.) is a potent, selective oral inhibitor of matrix metalloproteinase-2, -9, -13 and -14. This peculiar selectivity should represent an advantage for prinomastat in terms of efficacy/tolerability. The drug has been shown to inhibit tumour growth and angiogenesis...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.9.2159
更新日期:2000-09-01 00:00:00
abstract:INTRODUCTION:Aurora kinases are key regulators of mitosis and inhibition of Aurora kinase activity is a rational therapeutic strategy in the treatment of solid tumors and hematological malignancies. AREAS COVERED:This paper will provide an updated summary of preclinical and clinical experience with ENMD-2076 in hemato...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.668882
更新日期:2012-05-01 00:00:00
abstract::Venous and arterial thromboembolism are a major cause for morbidity and mortality. The list of established drugs for the prevention of thrombus formation and embolisation includes heparins, hirudin and derivatives, aspirin, ADP and glycoprotein IIb/IIIa receptor antagonists, as well as vitamin K antagonists. Several l...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.5.781
更新日期:2003-05-01 00:00:00
abstract:INTRODUCTION:The ubiquitin-proteasome system (UPS) is responsible for the degradation of misfolded or damaged proteins, regulating inflammatory processes and cell cycle progression. The aim of this article is to summarize the currently available data regarding the possible utility of proteasome inhibitors (PIs) in the ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2013.840287
更新日期:2014-01-01 00:00:00
abstract::Urinary tract infections (UTIs) are one of the most common reasons people seek medical attention. There are > 50% of women who will have at least one UTI during their lifetime and most of these will require a physician visit and antibiotic treatment. The high prevalence continues to the in-patient setting where genito...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.5.519
更新日期:2006-05-01 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: Advanced melanoma historically had a very poor outcome but targeted therapies and immune checkpoint inhibitors (IC) have changed the course of the disease and made durable responses possible. However, most patients will develop progressive disease, so further strategies to overcome treatment resistance a...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2020.1769066
更新日期:2020-07-01 00:00:00
abstract::Phytoestrogens, such as the soya isoflavones genistein and daidzein, are currently being extensively investigated through both molecular, preclinical and clinical studies to determine their potential health benefits. Phytoestrogens may protect against chronic diseases such as hormone-dependent cancer (e.g., breast and...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.8.1829
更新日期:2000-08-01 00:00:00
abstract::Preclinical and clinical evidence support the effectiveness of neurotrophins in Alzheimer's disease (AD) and neurodegenerative diseases. Delivery of neurotrophins to target sites in the brain remains a major obstacle for their use in humans. Development of orally active agents that mimic the effects of nerve growth fa...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.10.1413
更新日期:1997-10-01 00:00:00
abstract:INTRODUCTION:Obesity is a major health threat in the Western world because of its high incidence and prevalence, and its association with metabolic and cardiovascular disease as well as cancer. The reduction of food intake in obese patients can be achieved only transiently (generally for no longer than 6 months), in th...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2011.630660
更新日期:2011-12-01 00:00:00
abstract::Clinical trials showing the benefits of reducing the effects of TNF- alpha in rheumatoid arthritis have highlighted the key role of the cytokine TNF- alpha in this inflammatory condition. A new approach to reducing the effects of TNF- alpha is to decrease its synthesis by inhibiting TNF- alpha converting enzyme with G...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.11.7.1003
更新日期:2002-07-01 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::Carvedilol is a beta-blocker with ancillary properties. Pilot clinical studies with carvedilol, added to the standard therapy of digoxin, diuretics and ACE inhibitors, showed beneficial effects in mild, moderate and severe heart failure. Patients consistently showed improvement in LV ejection fraction and NYHA functio...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.10.5.971
更新日期:2001-05-01 00:00:00
abstract::All of the glucose-lowering agents available today for the treatment of diabetes resulted from the in vivo antidiabetic drug discovery approach. This is not surprising given the limited understanding of the biochemical basis of diabetes. With new developments in the elucidation of the biochemistry and physiology of di...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.6.987
更新日期:1998-06-01 00:00:00
abstract:INTRODUCTION:Signal transducer and activator of transcription 3 (STAT3) controls a key signaling pathway in the development of many malignant diseases. Several genetic studies have proven its central role in the regulation of apoptosis, proliferation, angiogenesis and immune responses making it an attractive target for...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2011.601739
更新日期:2011-09-01 00:00:00
abstract::The failure of drug candidates in clinical development remains a critical issue for the pharmaceutical and biotechnology industries. This article documents those oncology drugs discontinued in 2008 and briefly reviews reasons for termination of development. Source information was derived from a search of the Pharmapro...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543780903151806
更新日期:2009-11-01 00:00:00
abstract:INTRODUCTION:The addition of monoclonal antibody (mAb) epidermal growth factor receptor (EGFR) inhibitors to classic chemotherapy doublet backbones has improved survival of metastatic colorectal cancer (mCRC). However, the role of triple-drug chemotherapy regimens in combination with an anti-EGFR mAb inhibitor is not y...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2019.1599860
更新日期:2019-05-01 00:00:00
abstract:INTRODUCTION:Aberrant regulation of platelet-derived growth factors (PDGFs) and their receptors (PDGFR) has been shown to be involved in many solid tumors, including breast cancer. PDGFR-α and PDGFR-β expressions were documented in breast cancer and are correlated with tumor aggressiveness and metastasis. Preclinical e...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.895323
更新日期:2014-05-01 00:00:00
abstract::Therapeutic angiogenesis has yielded promising results in animal models, including the demonstration of newly created blood vessels, increased perfusion and functional benefits. On the other hand, clinical studies using similar methods of angiogenesis have so far been disappointing. The possibility that endothelial dy...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.1.37
更新日期:2005-01-01 00:00:00