Abstract:
:The extracellular signal-regulated kinase (ERK) pathway is a major determinant in the control of diverse cellular processes such as proliferation, survival, and motility. This pathway is often upregulated in human cancers and as such represents an attractive target for mechanism-based approaches to cancer treatment. However, specific blockade of the ERK pathway alone induces mostly cytostatic rather than proapoptotic effects, resulting in limited therapeutic efficacy. Blockade of the constitutively activated ERK pathway by an ERK kinase (MEK) inhibitor sensitizes tumor cells to apoptotic cell death induced by several cytotoxic anticancer agents including microtubule-destabilizing agents and histone deacetylase inhibitors, not only in vitro but also in tumor zenografts in vivo. Thus, low concentrations of these anticancer drugs that by themselves show little cytotoxicity effectively kill tumor cells in which the ERK pathway is constitutively activated when co-administrated with a MEK inhibitor. The combination of a cytostatic signaling pathway inhibitor (MEK inhibitors) and conventional anticancer drugs (microtubule-destabilizing agents or histone deacetylase inhibitors) provides an excellent basis for the development of safer anticancer chemotherapies with enhanced efficacy through lowering the required dose of the latter cytotoxic drugs.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Kohno M,Tanimura S,Ozaki Kdoi
10.1248/bpb.34.1781subject
Has Abstractpub_date
2011-01-01 00:00:00pages
1781-4issue
12eissn
0918-6158issn
1347-5215pii
JST.JSTAGE/bpb/34.1781journal_volume
34pub_type
杂志文章,评审abstract::Diosgenyl saponins are the most abundant steroid saponins, and exert a large variety of biological functions. In a previous report, we showed that dioscin was able to induce cytotoxicity and apoptosis in human myeloblast leukemia HL-60 cells. This study further investigated the action mechanisms underlying this effect...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.27.1059
更新日期:2004-07-01 00:00:00
abstract::Human parvovirus B19 is a clinically important pathogen in both children and adults. In adults, it frequently causes acute and chronic arthritis, which may be related to persistent infection. The effect of the capsid of human parvovirus B19 on monocytes, which are thought to be responsible for the first line of defens...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.30.2027
更新日期:2007-11-01 00:00:00
abstract::Bupleuri Radix (Chai-hu in Chinese and Saiko in Japanese) is one of the most important traditional Chinese crude drugs for treating hepatitis malaria and intermittent fever. B. kaoi is one of the Bupleurum spp. families locally found in Taiwan. The effects of saponin-enriched fraction (SEF) from Bupleurum Kaoi in huma...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.27.1112
更新日期:2004-07-01 00:00:00
abstract::A bacterium isolated as the contaminant of a batch of commercial benzalkonium chloride (BAC) solution (10% (w/v)) stored in a loosely capped bottle in the Department of Pharmacy Shinshu University Hospital was identified as Pseudomonas fluorescens belonging to biotype G of Stanier, et al. The strain was highly resista...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.19.873
更新日期:1996-06-01 00:00:00
abstract::We determined the binding affinity of tamsulosin, a selective α(1)-adrenoceptor antagonist, for human α(1)-adrenoceptor subtypes in comparison with those of other α(1)-adrenoceptor antagonists including silodosin, prazosin, 5-methylurapidil, terazosin, alfuzosin, nafopidil, urapidil and BMY7378. The association and di...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.35.72
更新日期:2012-01-01 00:00:00
abstract::Markedly inhibitory effects of Ca(2+) on the growth of human tumor cells were attained through the induction of apoptosis in vitro. On the other hand, a good correlation between the growth inhibition effects of Ca(2+) and the amounts of phosphatidylserines (PS) in the cell membranes (plasma membranes) was obtained. Fu...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.34.439
更新日期:2011-01-01 00:00:00
abstract::Checkpoint kinase 1 (Chk1) plays important roles in genotoxic stress-induced cell cycle checkpoint and in normal cell cycle progression. Here, we show that Chk1 is cleaved in the treatment of apoptotic dose of etoposide (ETP) or cisplatin (CIS) but not of viable dose in HeLa S3 cells. The cleavage of Chk1 was complete...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.30.359
更新日期:2007-02-01 00:00:00
abstract::The purpose of this study was to develop a method for the measurement of the cell kinetics of spleen lymphocytes using the ROSA 26 transgenic mouse ubiquitously expressing beta-galactosidase (beta-gal). Spleen lymphocytes were isolated from ROSA 26 mice and intravenously inoculated into C57BL/6 mice under normal condi...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.25.1378
更新日期:2002-10-01 00:00:00
abstract::Cannabinoids are the active ingredients in marijuana, which is among the most widely used addictive drugs despite the well-documented harmfulness related to its abuse. The mechanism underlying cannabinoid addiction remains unclear, which is attributed partially to the difficulty in behavioral testing of high-dose cann...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b15-00834
更新日期:2016-05-01 00:00:00
abstract::The purpose of this study was to evaluate the accuracy of the recommended theophylline therapeutic range in the treatment of acute airway obstruction. Twenty seven patients (20 to 64 years) with acute asthma attack were given aminophylline intravenously to obtain a theophylline concentration between 10 and 20 microgra...
journal_title:Biological & pharmaceutical bulletin
pub_type: 临床试验,杂志文章
doi:10.1248/bpb.19.710
更新日期:1996-05-01 00:00:00
abstract::To determine the mechanism involved, the incorporation rate (ICR) of drugs into hair was compared to melanin affinity, lipophilicity and membrane permeability. The following 20 drugs were tested; amphetamine, methamphetamine, p-hydroxyamphetamine, p-hydroxymethamphetamine, cocaine, benzoylecgonine, ecgonine methyl est...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.18.1223
更新日期:1995-09-01 00:00:00
abstract::Methylripariochromene A (MRC) was isolated from the leaves of Orthosiphon aristatus (Lamiaceae) and subjected to the examination of several pharmacological actions related to antihypertensive activity. The following four findings were revealed from the present study: 1) MRC caused a continuous decrease in systolic blo...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.22.1083
更新日期:1999-10-01 00:00:00
abstract::The antiproliferative constituents in the MeOH extracts of the aerial parts of Lippia dulcis Trev. and Lippia canescens Kunth (Verbenaceae) were investigated. Activity-guided chemical investigation of the MeOH extracts resulted in the isolation of the three bisabolane-type sesquiterpenes [(+)-hernandulcin (1), (-)-epi...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.25.920
更新日期:2002-07-01 00:00:00
abstract::Despite the relatively high prevalence of migraine or headache, the pathophysiological mechanisms triggering headache-associated peripheral hypersensitivities, are unknown. Since nitric oxide (NO) is well known as a causative factor in the pathogenesis of migraine or migraine-associated hypersensitivities, a mouse mod...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b17-00589
更新日期:2018-02-01 00:00:00
abstract::Upon stimulation, endothelial cells release various factors to regulate the vascular tone. In particular, vasorelaxing factors, called endothelium-derived relaxing factors (EDRFs), are altered in the production and/or release, as well as their signaling every vessel and under pathophysiological states, including cardi...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b19-00177
更新日期:2019-01-01 00:00:00
abstract::Cinobufagin isolated from traditional Chinese herbs has antitumour, anaesthetic, analgesic and anti-inflammatory effects. Recently, the antitumour activity of cinobufagin has attracted increasing attention from researchers. However, the anticancer activity of this drug on esophageal cancer cells and the precise mechan...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b19-00174
更新日期:2019-01-01 00:00:00
abstract::The effects of gamma-oryzanol, a drug mainly used for the treatment of hyperlipidaemia, on several cytochrome P450 (CYP) specific reactions in human liver microsomes were investigated to predict drug interactions with gamma-oryzanol in vivo from in vitro data. The following eight CYP catalytic reactions were used in t...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.27.1151
更新日期:2004-07-01 00:00:00
abstract::Salt-sensitive hypertension induces renal injury via decreased blood flow in the renal artery (RA), and ion channel dysfunction in RA myocytes (RAMs) may be involved in the higher renal vascular resistance. We examined the effects of several voltage-gated K+ (KV) channel blockers on the resting tension in endothelium-...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b17-00289
更新日期:2017-01-01 00:00:00
abstract::Nine compounds, including six phenylethanoid glycosides: acteoside (1); bioside (2); echinacoside (3); poliumoside (4); phenylethyl glycoside (5); salidroside (6) and three flavonoids; linarin (7); apigenin (8); isorhoifolin (9), were isolated from the flowers of Buddleja officinalis MAXIM. (Buddlejaceae). Chemical st...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.32.1952
更新日期:2009-12-01 00:00:00
abstract::The inhibitory activity of 40 stilbene oligomers isolated from six plant species against topoisomerase II was evaluated, of which nine compounds showed a potent inhibitory effect, stronger than daunorubicin, a topoisomerase II inhibitor, used as an anti-cancer drug. The specificity of active stilbene oligomers on topo...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.29.1504
更新日期:2006-07-01 00:00:00
abstract::PhiC31 integrase has the potential to achieve long-term transgene expression because of site-specific and unidirectional recombination. In this study, plasmid DNA (pDNA) encoding Gaussia luciferase (Gluc) cDNA was constructed and the optimal condition for long-term gene expression using phiC31 integrase in mouse liver...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b12-00083
更新日期:2012-01-01 00:00:00
abstract::Although distigmine is known to sometimes cause severe adverse drug reactions (ADRs), such as cholinergic crisis, there are limited data on the risk factors for these ADRs. In this study, we defined a serum cholinesterase (sChE) cutoff level for early detection of ADRs to distigmine and sought to identify risk factors...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b20-00216
更新日期:2020-01-01 00:00:00
abstract::Our previous study using apoptosis analysis suggested that Ca(2+) release through inositol 1,4,5-trisphosphate (IP3) receptors and the subsequent Ca(2+) influx through store-operated channels (SOCs) constitute a triggering signal for H2O2-induced β-cell apoptosis. In the present study, we further examined the obligato...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b15-00396
更新日期:2015-01-01 00:00:00
abstract::A previous study showed that macelignan extracted from Myristica fragrans has anti-inflammatory properties using hippocampal neuronal and primary microglial cells. Subsequently, a study using animals with chronic lipopolysaccharide (LPS) infusion into the brain showed that oral treatments of macelignan reduced the hip...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.32.1085
更新日期:2009-06-01 00:00:00
abstract::Recently, a silent polymorphism of C3435T of the MDR1 gene, encoding the multidrug resistant transporter MDR1/P-glycoprotein, has been found to be associated with susceptibility to ulcerative colitis (UC), but this remains controversial. This study was conducted to find a possible reason for the discrepancies, and it ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.29.324
更新日期:2006-02-01 00:00:00
abstract::Cisplatin-induced nephrotoxicity is related to an increase in lipid peroxidation and oxygen free radicals in a kidney. In the present study, we investigated the effect of the dietary antioxidants, capsaicin (Cap), against cisplatin-induced lipid peroxidation and nephrotoxicity in rats. Nephrotoxicity induced by treatm...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.28.1635
更新日期:2005-09-01 00:00:00
abstract::The surface topology of ligands on liposomes is an important factor in active targeting in drug delivery systems. Accurately evaluating the density of anchors and bioactive functional ligands on a liposomal surface is critical for ensuring the efficient delivery of liposomes. For evaluating surface ligand density, it ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b16-00462
更新日期:2016-01-01 00:00:00
abstract::A fungus of Pestalotiopsis species produced an extracellular, water-soluble polysaccharide (PS-N). PS-N exhibited significant hypoglycemic activity in streptozotocin-induced diabetic mice following intraperitoneal administration and had an effect on oral glucose tolerance in normal mice following oral administration. ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.20.118
更新日期:1997-02-01 00:00:00
abstract::The purpose of this research is improvement of therapeutic treatment for periodontitis by using lipophilic and/or hydrophilic zinc materials. The sample suspension injections were prepared from zinc octanate (C8Zn), zinc stearate (C18Zn), zinc sulfate hepta-hydrate (ZnSO4) and tricalcium phosphate (ZnTCP) containing 6...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b12-00218
更新日期:2012-01-01 00:00:00
abstract::Studies were performed to characterize the opioid receptors in guinea pig brain using the radiolabeled opioid antagonists, [3H]naloxone and [3H]diprenorphine and the kappa-agonist [3H]U-69593. The binding of [3H]U-69593 to guinea pig cerebellar membranes was reduced by NaCl, guanyl-5'yl-imidodiphosphate (GppNHp) and N...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.16.921
更新日期:1993-09-01 00:00:00