Abstract:
:Treatment with anti-cancer agents in most cases ultimately results in apoptotic cell death of the target tumor cells. Unfortunately, tumor cells can develop multidrug resistance, e.g., by a reduced propensity to engage in apoptosis by which they become insensitive to multiple chemotherapeutics. Ceramide. the central molecule in cellular sphingolipid metabolism, has been recognized as an important mediator of apoptosis. Moreover, an increased cellular capacity for ceramide glycosylation has been identified as a novel multidrug resistance mechanism. Indeed, virtually all multidrug resistant cell types exhibit a deviating sphingolipid composition, most typically an increased level of glucosylceramide. Thus, the enzyme glucosylceramide synthase, which converts ceramide into glucosylceramide, has emerged as a potential target to increase apoptosis and decrease drug resistance of tumor cells. In addition, several other steps in the pathways of sphingolipid metabolism arc altered in multidrug resistant cells, opening a perspective on additional sphingolipid metabolism enzymes as targets for anti-cancer therapy. In this article, we present an overview of the current understanding concerning drug resistance-related changes in sphingolipid metabolism and how interference with this metabolism can be exploited to over come multidrug resistance.
journal_name
Curr Drug Targetsjournal_title
Current drug targetsauthors
Kok JW,Sietsma Hdoi
10.2174/1389450043345452keywords:
subject
Has Abstractpub_date
2004-05-01 00:00:00pages
375-82issue
4eissn
1389-4501issn
1873-5592journal_volume
5pub_type
杂志文章,评审abstract::Cardiovascular diseases (CVD) are the leading cause of death, chronic illness and disability in Western countries. The most common cause of CVD derives from the harmful effects of acute myocardial ischemia and subsequent reperfusion injury. Cardioprotection against acute ischemia/ reperfusion injury is made possible b...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666150309115536
更新日期:2015-01-01 00:00:00
abstract::Osteoporosis causes bone loss, and makes bone to susceptible to fracture. The main cause of osteoporosis is estrogen deficiency. Estrogen, calcitonin, calcium, vitamin D and antioxidants can be used to prevent osteoporosis. For the treatment of osteoporosis, the potential biological activities of traditional medicines...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/13894501113149990205
更新日期:2013-12-01 00:00:00
abstract::Trypanosomes and Leishmaniae are the agents of several important parasitic diseases threatening hundreds of million human beings worldwide. As they diverged early in evolution, they display original molecular characteristics. These peculiarities are each defining putative specific targets for anti-parasitic drugs. Tra...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008786786064
更新日期:2008-11-01 00:00:00
abstract:AIMS:The aim of this study is to provide an overview of several emerging anti-diabetic molecules. BACKGROUND:Diabetes is a complex metabolic disorder involving the dysregulation of glucose homeostasis at various levels. Insulin, which is produced by β-pancreatic cells, is a chief regulator of glucose metabolism, regul...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450120666191031104653
更新日期:2020-01-01 00:00:00
abstract::The liver is essential for the control of glucose and lipid metabolism. Excessive accumulation of fat in the liver disturbs its function and leads to the development of fatty liver diseases. The nonalcoholic fatty liver disease (NAFLD) is a common type of fatty liver disease found in patients who have not consumed sig...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666150325231015
更新日期:2015-01-01 00:00:00
abstract::While breast cancer (BC) is commonest malignancy among female with highest death rate, male breast cancer (MBC) is very rare but exhibits highest cancer specific death in men and the incidences of MBCs are rising rapidly. Due to rarity of the disease, no detail information about biomarkers and drug targets available a...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945009787122842
更新日期:2009-01-01 00:00:00
abstract::Hypertension is usually associated with deficient nitric oxide (NO) bioavailability, and therefore stimulating NO activity is an important antihypertensive strategy. Recently, many studies have shown that both nitrite and nitrate anions are not simple products of NO metabolism and indeed may be reduced back to NO. Whi...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450119666180816120816
更新日期:2019-01-01 00:00:00
abstract::Bacterial respiratory infections are the main reason of morbidity and mortality among cystic fibrosis (CF) patients. In early childhood, the respiratory infections are due to Staphylococcus aureus and Haemophilus influenzae. In older CF patients, pathogenic Gram-negative bacteria like Achromobacter xylosoxidans, Burkh...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160208145934
更新日期:2017-01-01 00:00:00
abstract::Histone deacetylases are a class of enzymes that play important roles in post translational modifications of histones by deacetylating the lysine residues as well as interacting with various non-histone proteins. This type of enzymes is closely related to oncogenesis and has been proved to be attractive targets for de...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666140306152642
更新日期:2014-06-01 00:00:00
abstract::Thromboembolic diseases such as deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI) and ischemic strokes are mainly responsible for people's morbidity and mortality and have severely affected the people's quality of life all over the world. According to WHO statistics, an average of 17 mill...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666150518095533
更新日期:2015-01-01 00:00:00
abstract::Stroke is one of the leading causes of death and disability worldwide. Because stroke is a multifactorial disease with a short therapeutic window many clinical stroke trials have failed and the only currently approved therapy is thrombolysis. MicroRNAs (miRNA) are endogenously expressed noncoding short single-stranded...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945013804806424
更新日期:2013-01-01 00:00:00
abstract::Thrombomodulin (TM) is a type 1 membrane bound glycoprotein that has a C-type lectin domain at its Nterminus, 6 copies of the epidermal growth factor-like (EGF) motif and serine/threonine rich domain carrying a glycosoaminoglycan external to the membrane. TM binds thrombin changing thrombin's substrate specificity fro...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945012799424606
更新日期:2012-03-01 00:00:00
abstract::Multifunctional rational drug design of protein tyrosine kinases inhibitors allows a potent drug to be utilized to treat more than one disease for greater patient benefits. Many protein tyrosine kinases (PTK), including Janus kinase 3 (JAK3) and Bruton's tyrosine kinase (BTK), have been identified as potential drug ta...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006776054997
更新日期:2006-03-01 00:00:00
abstract::Baculoviruses have adapted novel tactics to transcribe their genes during the late stages of replication. These include a DNA-directed RNA polymerase which is evolutionarily divergent from cellular polymerases. The viral RNA polymerase is a multisubunit and multifunctional RNA polymerase that has the ability to recogn...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945007782151324
更新日期:2007-10-01 00:00:00
abstract::The HIV-1 transactivator Tat protein plays a key role in AIDS pathogenesis. Besides the Tat role as activator of HIV-1 transcription, it exerts several important functions on infected and uninfected cells. In fact, HIV-1 Tat is released by infected cells and is taken up by neighboring cells. In this way it regulates e...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666150825110658
更新日期:2016-01-01 00:00:00
abstract::Breast Cancer (BC) is the most common cancer among women and the second cause of female death for cancer. When the tumor is not correctly eradicated, there is a high relapse risk and incidence of metastasis. Breast Cancer Stem Cells (BCSCs) are responsible for initiating tumors and are resistant to current anticancer ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450120666181122113300
更新日期:2019-01-01 00:00:00
abstract::Inflammation is a risk factor for cancer development in several tissues. In the colorectum, inflammatory bowel disease (ulcerative colitis and Crohn's disease) is a longstanding inflammatory disease with increased risk for colorectal cancer (CRC). Several molecular events involving in chronic inflammatory process cont...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945012804545452
更新日期:2012-12-01 00:00:00
abstract::Aldose reductase (AR) enzymatically transforms cytosolic glucose into sorbitol, a molecule that poorly penetrates cell membranes and is sometimes slowly metabolized. Hyperglycemia can cause intracellular accumulation of sorbitol and its metabolite, fructose, which can create osmotic swelling and cell dysfunction. Driv...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008783431781
更新日期:2008-01-01 00:00:00
abstract::Stroke is one of the major causes of mortality and disability in adults in industrialized countries. Despite numerous preclinical studies and clinical trials in the field of cerebral ischemia, no pharmacological agent has been validated in the treatment of acute ischemic, except thrombolysis. Cerebral ischemia is not ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450111314070005
更新日期:2013-06-01 00:00:00
abstract::Aberrant activation of receptor-tyrosine kinase c-Met/HGF pathway is shown to be associated with cell proliferation, invasion, metastasis and poor-prognosis in several tumor types, including upper gastrointestinal-malignancies. The interaction of c-Met with multiple signalling-pathways involved in tumorigenic-properti...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666141107105456
更新日期:2014-01-01 00:00:00
abstract::Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, most cases are on an advanced and inoperable stage, with limited therapeutic options. Existing therapies have shown to be insufficient and novel strategies are urgently necessary. New advances in understanding the disease a...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666140528151649
更新日期:2015-01-01 00:00:00
abstract::Tachykinins (TKs) and their receptors (NK1, NK2 and NK3), which are diffusely expressed in the human gastrointestinal tract, represent an endogenous modulator system regulating enteric secretomotor functions, inflammatory and immune responses, and visceral hypersensitivity, mainly during pathological gut diseases. Pat...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006778019354
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND:Osteosarcoma is considered the most frequent primary bone malignancy. Lung metastasis is the leading cause of death and the most consistent factor for predicting negative patient outcome in osteosarcoma. Third-generation nitrogen-containing bisphosphonates, such as zoledronic acid, have been shown to reduce ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1573399811666150615145409
更新日期:2018-01-01 00:00:00
abstract::In this review we focus on the impact of genetic admixture on pharmacogenomics in the American continent, where five centuries of intermarriage between Amerindians, European and Africans, resulted in the extensive population heterogeneity observed nowadays. We compare two alternative views of human genomic variation, ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006779025392
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND:The mitochondria may very well determine the final commitment of the cell to death, particularly in times of energy stress. Cancer chemotherapeutics such as the anthracycline doxorubicin perturb mitochondrial structure and function in tumour cells, as evidenced in osteosarcoma, for which doxorubicin is used ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666150416115852
更新日期:2018-01-01 00:00:00
abstract::The fibrinolytic system consists of a balance between rates of plasminogen activation and fibrin degradation, both of which are finely regulated by spatio-temporal mechanisms. Three distinct inhibitors of the fibrinolytic system that differently regulate these two steps are plasminogen activator inhibitor type-1 (PAI-...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450120666190715102510
更新日期:2019-01-01 00:00:00
abstract::Pain is a complex multidimensional concept that facilitates the initiation of the signaling cascade in response to any noxious stimuli. Action potential generation in the peripheral nociceptor terminal and its transmission through various types of nociceptors corresponding to mechanical, chemical or thermal stimuli le...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450120666190131114244
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Gabapentin and pregabalin inhibit Ca(2+) currents via high-voltage-activated channels containing the alpha2delta-1 subunit, reducing neurotransmitter release and attenuating the postsynaptic excitability. They are antiepileptic drugs successfully used also for the chronic pain treatment. A large number of cl...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945009788982513
更新日期:2009-08-01 00:00:00
abstract::Diabetes is reaching epidemic proportions worldwide. Many dietary compounds have been found to exert health beneficial effects against different pathologies including diabetes. Most bioactive compounds have been identified in fruits and vegetables and their mechanisms of action explored both in vitro and in vivo. In p...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666151001105230
更新日期:2017-01-01 00:00:00
abstract::Advancing age presents a major challenge for the elderly population in terms of quality of life. The risk of cognitive impairment, motor in-coordination, and behavioral inconsistency due to neuronal damage is relatively higher in aging individuals of society. The brain, through its structural and functional integrity,...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121999201209202247
更新日期:2020-12-09 00:00:00