Abstract:
:Liver targeted therapy is designed to deliver a substance preferentially to the organ in order to increase the accumulation, improve the therapeutic effect and reduce toxicity to other organs. The aim of selective targeting is to deliver a substance to a specific cell type in the liver. A variety of vehicles have been designed and further modified for selective targeting of therapeutics to the liver. The targeting properties and strategies of commonly used agents, such as liposomes, microspheres and recombinant chylomicrons, are discussed. Viral and non-viral vectors, such as cationic liposomes, reconstituted chylomicron remnants, adenoviruses, adeno-associated viruses, retroviruses, and SV-40, are currently being evaluated for the delivery of DNA to the liver. New developments in improving the targeting efficiency of the available vectors while avoiding their disadvantages have made their use in clinical trials of various genetic disorders possible. For viral hepatitis, antisense and ribozyme techniques are being employed with selective targeting approaches. A commonly employed current strategy for targeting hepatocellular carcinoma cells is to make the tumour cells convert non-toxic 'prodrugs' to toxic metabolites in situ, achieving a high concentration of the toxic product in the local milieu, while avoiding systemic toxicity. Although gene therapy itself is in its infancy, some encouraging results have been developed in studies of familial hypercholesterolaemia, haemophilia, alpha1-antitrypsin deficiency and Crigler-Najjar syndrome. The potential strengths as well as the problems with these studies are discussed.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Wu J,Wu GY,Zern MAdoi
10.1517/13543784.7.11.1795subject
Has Abstractpub_date
1998-11-01 00:00:00pages
1795-817issue
11eissn
1354-3784issn
1744-7658journal_volume
7pub_type
杂志文章abstract:INTRODUCTION:About 185,000,000 people worldwide are chronically infected with hepatitis C virus (HCV). Currently, the most successful HCV infection antiviral therapies reduce the chance of progression towards the advanced phases of the hepatopathy (liver cirrhosis, hepatocellular carcinoma and death). Recently, however...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1059820
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Therapeutic options for mycosis fungoides and Sézary syndrome include a variety of immunomodulatory, epigenetic, and cytotoxic options; however, none has been demonstrated to be efficacious for all patients, or to deliver deep and durable responses to the majority of patients. In this review, we examine th...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1498081
更新日期:2018-08-01 00:00:00
abstract:INTRODUCTION:Dysregulation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is central to the pathophysiology of myeloproliferative neoplasms (MPN). Small molecule inhibitors of JAK family members are currently under investigation for the treatment of MPN. Of these, ruxolitinib ha...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2013.774373
更新日期:2013-06-01 00:00:00
abstract::Novel classes of antibiotics that are useful against resistant bacteria are a major need in human medicine. Cationic antimicrobial peptides are utilised as nature's antibiotics, being produced constitutively or in response to infection in virtually every type of organism from plants and insects to man. Thus, these pep...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.2.167
更新日期:1998-02-01 00:00:00
abstract::Atherothrombosis, or thrombus formation, at the site of a disrupted atherosclerotic plaque is the common pathophysiology related to myocardial infarction, ischaemic stroke and peripheral arterial disease. A growing body of evidence demonstrates an important role for vascular inflammation in the pathophysiology of athe...
journal_title:Expert opinion on investigational drugs
pub_type: 社论
doi:10.1517/13543784.13.5.457
更新日期:2004-05-01 00:00:00
abstract:INTRODUCTION:Psychostimulants are first-line treatments for attention-deficit/hyperactivity disorder (ADHD), but their tolerability profiles and individual response variability fuel a continuing search for alternative medications. The observation that nicotinic agents improve cognition has led pharmaceutical companies ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.934806
更新日期:2014-08-01 00:00:00
abstract:INTRODUCTION:Circadian rhythm is a natural endogenous process occurring roughly every 24 hours. Circadian rhythm dysfunction is involved in diabetic retinopathy (DR) pathogenesis. Interestingly, there are investigational drugs that exhibit potential in the treatment of DR by targeting circadian rhythm dysfunction. ARE...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2020.1842872
更新日期:2020-12-01 00:00:00
abstract::Heat shock proteins are vital to cell survival under conditions of stress. They bind client proteins to assist in protein stabilization, translocation of polypeptides across cell membranes and recovery of proteins from aggregates. Heat shock protein inhibitors are a diverse group of novel agents that have been demonst...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903158934
更新日期:2009-09-01 00:00:00
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:Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease that can lead to permanent disability and deformity. Despite current treatment modalities, many patients are still unable to reach remission. Interleukin-1 receptor-associated kinase 4 (IRAK-4) inhibitors are novel agents designed to s...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2020.1752660
更新日期:2020-05-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Several studies have demonstrated the high prevalence of hypertension and the crucial role of the association between endothelial function and hypertension. Thus, in depth investigation of the pathophysiological mechanisms linking endothelial dysfunction and hypertension, as well as evaluation o...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2010.522989
更新日期:2010-11-01 00:00:00
abstract::Histone deacetylase (HDAC) inhibitors are a new class of targeted anticancer agents. Several HDAC inhibitors are in clinical trials and have shown significant activity against a spectrum of both haematological and solid tumours at doses that are well tolerated by patients. HDACs and histone acetyltransferases can, by ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.12.1497
更新日期:2005-12-01 00:00:00
abstract::Sitagliptin is a once-daily, orally active, competitive and fully reversible inhibitor of dipeptidyl peptidase 4, the enzyme that is responsible for the rapid degradation of the incretin hormone glucagon-like peptide-1. It is the first in this new class of antihyperglycaemic agents to gain regulatory approval for the ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.4.533
更新日期:2007-04-01 00:00:00
abstract::Gossypol has received significant attention as a result of its potential therapeutic application as a male antifertility agent. Furthermore, recent research examining the biological activity of gossypol has revealed a number of other promising lines of enquiry. These have focused on the antitumour, antiviral and antio...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.11.1419
更新日期:2005-11-01 00:00:00
abstract::Neural cell transplantation is an emerging therapy that may provide an effective treatment for neurodegenerative disorders. The most extensive work with neural transplants has been carried out for Parkinson's and Huntington's diseases. However, intensive efforts are also being made for the treatment of other neurologi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.4.527
更新日期:1998-04-01 00:00:00
abstract::The introduction of HIV-1 protease inhibitors in 1995 ushered in the era of highly active antiretroviral therapy. For the first time, inhibition of two key enzymes responsible for HIV replication, reverse transcriptase and protease, was possible. The combination of two nucleoside reverse transcriptase inhibitors with ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.9.1295
更新日期:2002-09-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Antiangiogenic strategies are affording considerable interest and have become a major milestone in therapeutics of various adult cancers. However, progress has been slow to expand such therapies to patients with pediatric solid malignancies. AREAS COVERED IN THIS REVIEW:This review discusses th...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2010.487654
更新日期:2010-07-01 00:00:00
abstract:INTRODUCTION:Since the discovery of the activating V617F mutation in Janus kinase 2 (JAK2), a number of pharmacologic inhibitors of JAK2 have entered clinical trials for patients with myelofibrosis. However, ruxolitinib, approved in 2011, remains the only one currently available for treatment of myelofibrosis, with man...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1323871
更新日期:2017-06-01 00:00:00
abstract::This paper gives an overview of the available pharmacological and clinical data of a new class of anticancer drugs which act by binding DNA in the minor groove, comprising cyclopropylpyrrolo-indole (CC-1065) derivatives and Distamycin derivatives. The emphasis of this review is placed on the distinctive mode of action...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.7.875
更新日期:1997-07-01 00:00:00
abstract::Despite advances in supportive care, septic shock remains a major cause of morbidity and mortality. With the identification of the systemic inflammatory response as a major component in the pathogenesis of the septic shock syndrome, much of the recent work has focused on modulating this response. This includes antiend...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.2.139
更新日期:2003-02-01 00:00:00
abstract::Cholesterol can promote inflammation by its ability to stimulate the production of reactive oxygen species that result in the formation of pro-inflammatory oxidised phospholipids. High-density lipoproteins (HDLs) are part of the innate immune response and can be either pro- or anti-inflammatory independently of plasma...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.1.13
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:IL-6 is a key cytokine in the pathogenesis of rheumatoid arthritis (RA). The clinical efficacy of tocilizumab (TCZ), a humanized anti-IL6-receptor mAb, confirmed the value of IL-6 blockade in this disease. A number of new anti-IL-6 biologics are currently in Phase I - III of clinical development for RA. A...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.912276
更新日期:2014-07-01 00:00:00
abstract:INTRODUCTION:The purpose of this article is to highlight novel therapies that are being used in scleroderma (SSc). Therapeutic interventions in SSc generally target at least one of three ongoing biological processes characteristic of the disease: vasculopathy, autoimmunity and tissue fibrosis. Treatment decisions in SS...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.848852
更新日期:2014-02-01 00:00:00
abstract::Human cytomegalovirus (HCMV) is the most common viral opportunistic infection in patients suffering with acquired immunodeficiency virus (AIDS). HCMV is a systemic infection that may infect several sites in the body, including the retina, gastrointestinal tract, lungs, liver, and central nervous system. Retinitis is t...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.9.1157
更新日期:1997-09-01 00:00:00
abstract::Recently there have been considerable advances made in the treatment of multiple sclerosis. For the first time since its initial clinical description in the 1800s, there are now available several medications which unequivocally exert favourable clinical effects through the lowering of the biological activity of the hu...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.4.655
更新日期:2000-04-01 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:INTRODUCTION:Frontline chemotherapy is successful against chronic lymphocytic leukemia (CLL), but results in untoward toxicity. Further, prognostic factors, cytogenetic anomalies, and compensatory cellular signaling lead to therapy resistance or disease relapse. Therefore, for the past few years, development of targete...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1312338
更新日期:2017-05-01 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: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:INTRODUCTION:Ewing sarcoma family tumors (ESFT) are a group of aggressive diseases, characterized histologically by small, round, blue cells and genetically by translocation involving EWS and ETS partner genes. The current treatment of localized Ewing sarcoma (ES) requires a multi-disciplinary approach, including multi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2016.1168398
更新日期:2016-06-01 00:00:00