Abstract：
:Although the interaction between FUra and DP in HCT 116 cells is fairly complex, data from other investigators indicate that in cell lines in which inhibition of TS is growth limiting at relatively low concentrations of fluoropyrimidines, DP appears to augment the cytotoxicity of FUra and FdUrd by blocking the salvage of dThd (Miller et al., 1987; Schwartz et al., 1987). The previous in vitro data regarding the ability of DP to modulate the toxicity of fluoropyrimidines was obtained in exponentially growing cells. An additional observation that warrants consideration is a report that the inhibition of nucleoside incorporation by DP changed as a function of time in culture (Zhen et al., 1986). Hepatoma 3924A cells in lag and log phase were highly sensitive to DP with IC50 values for dThd incorporation of 0.2 and 0.32 microM, respectively. In contrast, stationary phase cells were insensitive to DP (IC50 = 38.9 microM). Amphotericin B, an antifungal agent which perturbs cell membranes, restored the sensitivity to DP in stationary cells. Several investigators have presented information on the effect of DP on fluoropyrimidines in normal tissues. Lee and Park (1987) examined the effect of DP on FUra and MTX toxicity in a soft-agar cloning assay against two human cancer cell lines and on pooled normal human bone marrow (CFU-C). DP (1 microM) potentiated the action of both MTX (0.1 microM) and FUra (5 microM) on Hep-2 (epidermoid carcinoma), MCF-7 (breast carcinoma) and CFU-C in medium supplemented with either non-dialyzed or dialyzed serum. Woodcock et al. (1987) incubated gallbladder mucosa, obtained from patients undergoing elective surgery for cholelithiasis, with control medium or varying concentrations of DP for 1 hr, and then exposed the mucosal cells to 2.5 microCi [3H]-FdUrd (2.5 microM). After 1 hr, the uptake of FdUrd into the tissue was inhibited to 49% and 42% of control by 0.1 microM and 1 microM, respectively.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Grem JL,Fischer PHdoi
10.1016/0163-7258(89)90084-3subject
Has Abstractpub_date
1989-01-01 00:00:00pages
349-71issue
3eissn
0163-7258issn
1879-016Xpii
0163-7258(89)90084-3journal_volume
40pub_type
杂志文章,评审abstract：:Atrial fibrillation (AF) is a growing clinical problem associated with increased morbidity and mortality. Development of safe and effective pharmacological treatments for AF is one of the greatest unmet medical needs facing our society. In spite of significant progress in non-pharmacological AF treatments (largely due...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.08.002
更新日期：2011-12-01 00:00:00
abstract：:RSV infection of the lower respiratory tract in infants is the leading cause of pediatric hospitalizations and second to malaria in causing infant deaths worldwide. RSV also causes substantial morbidity in immunocompromised and elderly populations. The only available therapeutic is a prophylactic drug called Palivizum...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107712
更新日期：2020-10-27 00:00:00
abstract：:The tumor microenvironment is increasingly recognized as a major factor influencing the success of therapeutic treatments and has become a key focus for cancer research. The progressive growth of a tumor results in an inability of normal tissue blood vessels to oxygenate and provide sufficient nutritional support to t...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.06.006
更新日期：2015-09-01 00:00:00
abstract：:The coronavirus disease 2019 (COVID-19) pandemic is caused by a newly emerged coronavirus (CoV) called Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). COVID-19 patients with cardiovascular disease (CVD) comorbidities have significantly increased morbidity and mortality. The use of angiotensin-converting ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107628
更新日期：2020-11-01 00:00:00
abstract：:Pokeweed antiviral protein (PAP) is a ribosome-inactivating protein (RIP) that inactivates ribosomes by the removal of a single adenine from ribosomal RNA. The studies summarized in our review concern the nature and application of this novel therapeutic agent. We describe how researchers continue to elucidate the stru...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90053-3
更新日期：1992-01-01 00:00:00
abstract：:There is clear evidence that CB(2), historically referred to as the peripheral cannabinoid receptor, mediates many of the immune modulatory effects of cannabinoids. However, cannabinoid receptors cannot be classified simply as central or peripheral since CB(2) has been shown to play a role in the central nervous syste...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.12.004
更新日期：2013-03-01 00:00:00
abstract：:The physiological role of K+ channel opening by endogenous substances (e.g., neurotransmitters and hormones) is a recognised inhibitory mechanism. Thus, the identification of novel synthetic molecules that 'directly' open K+ channels has led to a new direction in the pharmacology of ion channels. The existence of many...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(96)00003-4
更新日期：1996-01-01 00:00:00
abstract：:Sphingolipid metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate (S1P), play many important roles in cellular activities. Ceramide and sphingosine inhibit cell proliferation and induce cell apoptosis while S1P has the opposite effect. Maintaining a metabolic balance of sphingolipids is essential for...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.10.011
更新日期：2019-03-01 00:00:00
abstract：:Granulocytes are defined as the population of granulated white blood cells (eosinophils, neutrophils, and basophils). These cells are involved in inflammation and contribute to the pathogenesis of allergic and inflammatory diseases. Inflammation is induced by the release of mediators from granulocytes recruited to or ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.03.008
更新日期：2005-09-01 00:00:00
abstract：:Administration of antidepressant drugs to rodents appears to decrease 5-HT2 receptor function while transmission through postsynaptic 5-HT1 receptor synapses may be enhanced. Antidepressant drugs also alter 5-HT mechanisms in humans; some of these changes are congruent with effects noted in animal studies. Thus certai...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(90)90033-x
更新日期：1990-01-01 00:00:00
abstract：:Exacerbations of asthma are the main cause of asthma morbidity. They induce acute respiratory failure, and sometimes death. Two immunological signals acting in synergy are necessary for inducing asthma exacerbations. The first, triggered by allergens and/or unknown agents leads to the chronic Th2 inflammation characte...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.03.010
更新日期：2011-07-01 00:00:00
abstract：:Adipocyte hyperplasia occurs by the proliferation and differentiation of adipocyte precursor cells or preadipocytes. Although the process of commitment to the adipocyte lineage is poorly understood, a great deal of information has accumulated about the processes and regulatory mechanisms involved in preadipocyte diffe...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(94)90018-3
更新日期：1994-01-01 00:00:00
abstract：:The pharmaceutical industry offers the world's population alleviation and cure from a variety of medical conditions, while also contributing to the economic performance of many countries. The potential importance of these characteristics have made the industry an area of intense debate, criticism and praise. This revi...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(95)00002-x
更新日期：1995-05-01 00:00:00
abstract：:Macrovascular complications of diabetes, including diabetic cardiovascular disease (CVD), occur through a number of hyperglycaemia-induced mechanisms that include generation of oxidative stress, accumulation of advanced glycation end-products (AGE) and activation of protein kinase C (PKC). Cardiac oxidative stress is ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.11.013
更新日期：2017-04-01 00:00:00
abstract：:Cell proliferation is an essential mechanism for growth, development and regeneration of eukaryotic organisms; however, it is also the cause of one of the most devastating diseases of our era: cancer. Given the relevance of the processes in which cell proliferation is involved, its regulation is of paramount importanc...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2013.01.011
更新日期：2013-05-01 00:00:00
abstract：:Decades of research have established that the biological functions of thyrotropin-releasing hormone (TRH) extend far beyond its role as a regulator of the hypothalamic-pituitary-thyroid axis. Gary et al. [Gary, K.A., Sevarino, K.A., Yarbrough, G.G., Prange, A.J. Jr., Winokur, A. (2003). The thyrotropin-releasing hormo...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.09.004
更新日期：2009-01-01 00:00:00
abstract：:The widespread coronavirus SARS-CoV-2 has already infected over 4 million people worldwide, with a death toll over 280,000. Current treatment of COVID-19 patients relies mainly on antiviral drugs lopinavir/ritonavir, arbidol, and remdesivir, the anti-malarial drugs hydroxychloroquine and chloroquine, and traditional C...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107587
更新日期：2020-09-01 00:00:00
abstract：:Thoracic aortic aneurysms (TAAs) are a potential life-threatening disease with limited pharmacological treatment options. Current treatment options are aimed at lowering aortic hemodynamic stress, predominantly with β-adrenoceptor blockers. Increasing evidence supports a role for the renin-angiotensin system (RAS) in ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.04.002
更新日期：2011-07-01 00:00:00
abstract：:Integrins are heterodimeric cell surface receptors, which principally mediate the interaction between cells and their extracellular microenvironments. Because of their pivotal roles in cancer proliferation, survival, invasion and metastasis, integrins have been recognized as promising targets for cancer treatment. As ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2013.05.007
更新日期：2013-10-01 00:00:00
abstract：:Enzymes of the UDP-glucuronosyltransferase (UGT) superfamily contribute to the elimination of drugs from almost all therapeutic classes. Awareness of the importance of glucuronidation as a drug clearance mechanism along with increased knowledge of the enzymology of drug and chemical metabolism has stimulated interest ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107689
更新日期：2021-02-01 00:00:00
abstract：:Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptors family. PPARs are a family of 3 ligand-activated transcription factors: PPARalpha (NR1C1), PPARbeta/delta (NUC1; NR1C2), and PPARgamma (NR1C3). PPARalpha, -beta/delta, and -gamma are encoded by different genes but show sub...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.08.007
更新日期：2006-06-01 00:00:00
abstract：:The aim of the present paper was to present an overview of the current status of the methods used to predict the magnitude of pharmacokinetic drug-drug interactions (DDIs) which are caused by apparent changes in cytochrome P450 (CYP) activity with an emphasis on a method using in vivo information. In addition, more th...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.10.011
更新日期：2010-02-01 00:00:00
abstract：:Thioredoxin 1 (Trx 1) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys- that is ubiquitously present in the human body. Trx 1 is a defensive protein induced by various stresses and has anti-oxidative, anti-apoptotic and anti-inflammatory effects. The anti-oxidative effect of Trx 1 is m...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.04.004
更新日期：2010-09-01 00:00:00
abstract：:During the past decade, it has become evident that dopamine plays an important role in the regulation of renal function and blood pressure. Dopamine exerts its actions via a class of cell-surface receptors coupled to G-proteins that belong to the rhodopsin family. Dopamine receptors have been classified into two famil...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(98)00027-8
更新日期：1998-11-01 00:00:00
abstract：:Primaquine is the only antimalarial drug available to clinicians for the treatment of relapsing forms of malaria. Primaquine development and usage dates back to the 1940s and has been administered to millions of individuals to treat and eliminate malaria infections. Primaquine therapy is not without disadvantages, how...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.03.011
更新日期：2016-05-01 00:00:00
abstract：:Recent epidemiologic studies have shown that aerobic exercise, one of lifestyle modifications, reduces cardiovascular morbidity and mortality in the general population. However, the mechanisms underlying the anti-atherogenic and anti-hypertensive effects of exercise remain unclear. Hypertension is associated with alte...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2004.02.003
更新日期：2004-04-01 00:00:00
abstract：:Drug resistance of Plasmodium falciparum is not a recent phenomenon, but it became a major problem when the parasite became resistant to chloroquine, the cheapest and initially the most effective antimalarial compound that could be used for treatment and suppression. In some areas this problem is compounded by resista...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(91)90074-v
更新日期：1991-01-01 00:00:00
abstract：:Tumor progression and metastasis are complex processes involving intricate interplay among multiple gene products. Astrocyte elevated gene (AEG)-1 was cloned as an human immunodeficiency virus (HIV)-1-inducible and tumor necrosis factor-alpha (TNF-alpha)-inducible transcript in primary human fetal astrocytes (PHFA) by...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.01.010
更新日期：2007-05-01 00:00:00
abstract：:Increasing evidence of a critical role played by the bronchial epithelium in airway homeostasis is opening new therapeutic avenues. Its unique situation at the interface with the environment suggests that the subtle regulation orchestrated by the epithelium between tolerance and specific immune response might be impai...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2013.07.008
更新日期：2013-12-01 00:00:00
abstract：:In the 1980s, Bowery and colleagues discovered the presence of a novel, bicuculline-resistant and baclofen-sensitive type of GABA receptor on peripheral nerve terminals, the GABA(B) receptor. Since this pioneering work, GABA(B) receptors have been identified in the Central Nervous System (CNS), where they provide an i...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.06.004
更新日期：2011-11-01 00:00:00
