Abstract：
:Inhibition of angiogenesis is becoming one promising, alternative approach to stop tumor from growth and spreading to distant organs. TNP-470, an analog of fumagillin, possesses potent anti-angiogenic effects with minimal toxicity in animal tumor models and is now in the phase III of human cancer trial. Although TNP-470 induced endothelial cell cycle arrest at G1 phase via p53 and p21(Cip1), the underlying mechanism of the cytostatic effect of TNP-470 on endothelial cells remains limited. We have found that TNP-470 did not only induce p53 and p21(Cip1) but also cyclin D1 in the basic fibroblast growth factors (bFGF)-treated endothelial cells. The TNP-470-mediated increase of cyclin D1 protein was due to the enhanced expression of mRNA. The induced cyclin D1 formed a complex with cyclin-dependent kinase4 (CDK4) and p21(Cip1). The ability of cyclin D1-associated CDK4 to phosphorylate retinoblastoma (Rb) protein was, however, reduced in the same cells. TNP-470 also significantly increased senescence-associated-beta-galactosidase activity (SA-gal), hallmark of cells undergoing senescence. Interestingly, the effect of increased cyclin D1 protein mimicked by overexpression of cyclin D1 increased the sensitivity of human umbilical vein endothelial cells (HUVECs) to TNP-470. In summary, the cytostatic effect of TNP-470 on endothelial cells is in part mediated by induction of senescence and cyclin D1 is a key molecule participating in this event.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Lien WH,Chen CK,Lai LY,Chen YH,Wu MP,Wu LWdoi
10.1016/j.bcp.2004.05.020subject
Has Abstractpub_date
2004-08-15 00:00:00pages
729-38issue
4eissn
0006-2952issn
1873-2968pii
S0006295204003314journal_volume
68pub_type
杂志文章abstract：:A cyclic nucleotide phosphodiesterase from guinea-pig heart is activated by calmodulin in the presence of calcium ions. Activation was measured over a range of calmodulin concentrations, and is antagonised by several tricyclic psychotropic drugs including trifluoperazine, imipramine, chlorpromazine and amitriptyline. ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90192-7
更新日期：1982-02-01 00:00:00
abstract：:Interferon and interferon inducers are well known to depress the cytochrome P450-dependent hepatic mixed-function oxidase system and cause a decrease in the capacity of the liver to metabolize drugs and xenobiotics. In this study we have shown that the interferon-mediated changes in an induced form of hepatic cytochro...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90458-u
更新日期：1992-08-04 00:00:00
abstract：:Lipophilicity of camptothecins derivatives has been reported to improve the stability of the lactone ring and to favor rapid uptake and intracellular accumulation. Recently, a novel series of lipophilic camptothecins substituted at position 7 was developed, and gimatecan (ST1481) was selected for clinical development ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2003.10.034
更新日期：2004-03-15 00:00:00
abstract：:Adipogenesis plays a central role in obesity development. The processes of adipogenesis include migration, adhesion, proliferation and survival of preadipocytes and differentiation to mature adipocytes. Many of these biological functions are related to integrins. Here, we found that snake venom-derived arginine-glycin...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.07.035
更新日期：2005-11-15 00:00:00
abstract：:A series of cytotoxic propenal (3-oxoprop-1-enyl) derivatives of pyrimidine bases and deoxynucleosides was evaluated for their ability to block thymidylate synthesis in intact and permeabilized murine leukemia L1210 cells. Several were potent inhibitors of this process, likely contributing to their cytotoxicity. The I...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90732-k
更新日期：1991-07-05 00:00:00
abstract：:A major problem in the treatment of cancer is cellular resistance to cytotoxic drugs. In tumor cells in vitro, the development of multidrug resistance is usually accompanied by increased expression of drug transporters, either P-glycoprotein (P-gp) or multidrug resistance-associated protein (MRP(1)). Both proteins bel...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00453-6
更新日期：2000-11-15 00:00:00
abstract：:Thermodynamic parameters DeltaG degrees , DeltaH degrees and DeltaS degrees of the binding equilibrium of 12 ligands (six agonists and six antagonists) to the A(2B) adenosine receptor subtype have been determined by affinity measurements carried out on HEK 293 cells stably transfected with human A(2B) adenosine recept...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.09.003
更新日期：2008-01-15 00:00:00
abstract：:It has been reported that chelerythrine chloride, a benzophenanthridine alkaloid, with a wide variety of biologic effects stimulates the phosphorylation of an approximately 20 kDa protein present in the mitochondrial fraction of the rat retina. It has also been shown previously that both the serine and threonine resid...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00202-x
更新日期：1996-07-26 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2012.03.022
更新日期：2012-07-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90575-2
更新日期：1987-12-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90153-8
更新日期：1994-09-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00483-8
更新日期：1998-02-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90665-x
更新日期：1988-12-01 00:00:00
abstract：:Sublines of K562 human leukemia cells were selected for resistance (30- to 80-fold) to etoposide by continuous exposure to 0.5 microM VP-16. Two etoposide-resistant cell lines, K/VP.5 and K/VP.5-1, showed a 5-fold reduction in levels of topoisomerase II alpha protein compared with K562 cells. Northern analysis indicat...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90643-b
更新日期：1993-12-03 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90485-0
更新日期：1987-06-15 00:00:00
abstract：:Nitrogen dioxide (NO2), an environmental oxidant pollutant, is known to peroxidize membrane lipids of lung cells. We evaluated the ability of NO2 to alter the surface membrane fluidity, lipid composition, and insulin receptor binding of porcine pulmonary artery endothelial cells in culture. After 3- to 24-hr exposure ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90011-1
更新日期：1988-04-15 00:00:00
abstract：:The effect of chronic hypoxia (10.5% O2 for 8-9 days) on acetaminophen metabolism was studied in vivo or in isolated cell or microsomal systems. Results from in vivo studies with oral administration of acetaminophen showed that in hypoxic rats, the plasma appearance of the drug was delayed and the plasma half-life was...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90285-d
更新日期：1991-08-08 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.04.012
更新日期：2018-08-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90268-2
更新日期：1993-03-09 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90432-2
更新日期：1989-09-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90097-1
更新日期：1982-10-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90242-9
更新日期：1984-02-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2017.03.003
更新日期：2017-05-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90074-6
更新日期：1983-09-15 00:00:00
abstract：:Tamoxifen (Tam) is a selective estrogen receptor modulator (SERM) that remains one of the major drugs used in the hormonotherapy of breast cancer (BC). In addition to its SERM activity, we recently showed that the oxidative metabolism of cholesterol plays a role in its anticancer pharmacology. We established that thes...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2013.02.031
更新日期：2013-07-01 00:00:00
abstract：:Human immunodeficiency virus type 1 (HIV-1) gene expression is modulated by some virus-encoded proteins, possibly acting at multiple levels of control, which are also known to be involved in the regulation of gene expression in uninfected cells (transcriptional, post-transcriptional, nucleocytoplasmic transport, and t...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90078-0
更新日期：1988-10-15 00:00:00
abstract：:Multidrug resistance in tumor cells is often associated with the presence of an approximately 170 kDa plasma membrane glycoprotein (Pgp) that acts as a drug-efflux pump and decreases intracellular antitumor drug concentration. We measured the uptake of seven anthracyclines (daunorubicin, doxorubicin, 4'-epi-doxorubici...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00042-1
更新日期：1996-05-17 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90386-2
更新日期：1986-09-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00284-1
更新日期：1999-12-15 00:00:00
abstract：:Interleukin (IL)-22 plays protective roles in infections and in inflammatory diseases that have been linked to its meditation of innate immunity via multiple mechanisms. IL-22 binds specifically to its heterodimeric receptor, which is expressed on a variety of epithelial tissues. UTTR1147A is a recombinant fusion prot...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.03.031
更新日期：2018-06-01 00:00:00
