Abstract：
:With the concept of precision medicine, combining multiple molecular-targeting therapies has brought new approaches to current cancer treatments. Malfunction of the tumor suppressor protein, p53 is a universal hallmark in human cancers. Under normal conditions, p53 is degraded through an ubiquitin-proteosome pathway regulated by its negative regulator, MDM2. In contrast, cellular stress such as DNA damage will activate p53 to carry out DNA repair, cell cycle arrest, and apoptosis. In this study, we focused on ovarian carcinoma with high EGFR and MDM2 overexpression rate. We assessed the effects of combined inhibition by MDM2 (JNJ-26854165) and EGFR (gefitinib) inhibitors on various ovarian cell lines to determine the importance of these two molecular targets on cell proliferation. We then used a proteomic strategy to investigate the relationship between MDM2 and EGFR inhibition to explore the underlying mechanisms of how their combined signaling blockades work together to exert cooperative inhibition. Our results demonstrated that all four cell lines were sensitive to both individual and combined, MDM2 and EGFR inhibition. The proteomic analysis also showed that gefitinib/JNJ-treated CAOV3 cells exhibited downregulation of proteins involved in nucleotide biosynthesis such as nucleoside diphosphate kinase B (NME2). In conclusion, our study showed that the combined treatment with JNJ and gefitinib exerted synergistic inhibition on cell proliferation, thereby suggesting the potential application of combining MDM2 inhibitors with EGFR inhibitors for enhancing efficacy in ovarian cancer treatment.
journal_name
Arch Biochem Biophysjournal_title
Archives of biochemistry and biophysicsauthors
Chang SJ,Liao EC,Yeo HY,Kuo WH,Chen HY,Tsai YT,Wei YS,Chen YJ,Wang YS,Li JM,Shih CC,Chan CH,Lai ZY,Chou HC,Chuang YJ,Chan HLdoi
10.1016/j.abb.2018.04.004subject
Has Abstractpub_date
2018-06-01 00:00:00pages
10-32eissn
0003-9861issn
1096-0384pii
S0003-9861(18)30104-8journal_volume
647pub_type
杂志文章abstract：:Arachidonate 12-lipoxygenase (12-LO) from porcine leukocytes was expressed in insect cells using a baculovirus expression vector. The recombinant 12-LO was expressed as an N-terminal fusion protein with a 31-amino acid polypeptide carrying a six-histidine tag and an enterokinase cleavage site. Maximal intracellular en...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1994.1302
更新日期：1994-07-01 00:00:00
abstract：:MicroRNA-342-3p (miR-342) has been shown to act as a tumor-suppressor in different cancer types. However, the role and therapeutic implications of miR-342 via modulation of Cofilin 1 (CFL1) has not been studied in any type of cancer. Given the importance of Cofilin signalling in breast, this study was undertaken to ex...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/j.abb.2020.108385
更新日期：2020-07-15 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/0003-9861(84)90556-3
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/0003-9861(88)90326-8
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/j.abb.2010.06.001
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1993.1190
更新日期：1993-04-01 00:00:00
abstract：:6-(Difluoromethyl)indole has been characterized and developed as a probe for the turnover of indole by the bifunctional enzyme, tryptophan synthase (alpha 2 beta 2). The neutral form of the indolyl species undergoes a slow and spontaneous hydrolysis to produce 6-formylindole with a rate constant (k1) of 0.0089 +/- 0.0...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/0003-9861(91)90068-t
更新日期：1991-05-01 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/0003-9861(84)90555-1
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章,评审
doi：10.1016/j.abb.2016.08.003
更新日期：2017-03-01 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/0003-9861(89)90391-3
更新日期：1989-12-01 00:00:00
abstract：:Active, wild-type v-Src and its kinase-dead double Y416F-K295N mutant were expressed in hamster fibroblasts. Expression of the active v-Src induced activation of endogenous c-Src and increased general protein-tyrosine phosphorylation in the infected cells. Expression of the kinase-dead mutant induced hypophosphorylati...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/j.abb.2006.09.011
更新日期：2006-11-15 00:00:00
abstract：:Reactive oxygen species like hydrogen peroxide (H2O2) have been shown to serve as messengers in the induction of NF-kappa B and, hence, in the activation and replication of human immunodeficiency virus type 1 (HIV-1) in human cells. Several antioxidant compounds and iron chelators have been shown to interfere with bot...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1995.1394
更新日期：1995-08-01 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章,评审
doi：10.1016/j.abb.2019.01.033
更新日期：2019-03-30 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1994.1291
更新日期：1994-07-01 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/0003-9861(92)90510-4
更新日期：1992-06-01 00:00:00
abstract：:The cationic protein, lysozyme, is present in cartilage but its precise role in this tissue has not yet been established. This study shows that two major and structurally similar glycosaminoglycans (GAGs) of cartilage, i.e., chondroitin sulfate (CS) and hyaluronan (HA) interact with lysozyme at salt concentrations up ...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1994.1134
更新日期：1994-04-01 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章,评审
doi：10.1016/j.abb.2010.04.006
更新日期：2010-09-01 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1999.1402
更新日期：1999-10-15 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/s0003-9861(02)00283-7
更新日期：2002-08-15 00:00:00
abstract：:Glycosaminoglycan (GAG)-protein interactions regulate a myriad of physiologic and pathologic processes, yet an understanding of how these molecules interact is lacking. The role of the pattern and spacing of basic amino acids (arginine (R) and lysine (K)) in heparin binding sites was investigated using peptide analogs...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1997.0147
更新日期：1997-07-01 00:00:00
abstract：:An adenosine-sensitive (Ados) mutant of baby hamster kidney (BHK) cells, ara-S10d, when treated with a toxic concentration of adenosine (Ado), displayed a substantial elevation of S-adenosylhomocysteine (SAH), S-adenosylmethionine (SAM), and methylthioadenosine (MTA). Wild-type BHK cells treated with the same concentr...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/0003-9861(86)90329-2
更新日期：1986-05-01 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/0003-9861(86)90587-4
更新日期：1986-06-01 00:00:00
abstract：:Adenylate kinase (Adk) that catalyses the synthesis of ADP from ATP and AMP has also been shown to perform an ATP dependent phosphorylation of ribo- and deoxynucleoside diphosphates to their corresponding nucleoside triphosphate; ATP+(d)NDP<-->ADP+(d)NTP. This reaction, suggested to occur by the transfer of the gamma-...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/j.abb.2005.10.003
更新日期：2005-12-15 00:00:00
abstract：:The effect of glutathione (GSH) on the superoxide-sensitive [4Fe-4S]-containing aconitase of Escherichia coli was explored. A mutant deficient in GSH biosynthesis, designated gshA, grew slower in a defined medium than did the parental strain and this effect was more pronounced when succinate was supplied as the carbon...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1993.1120
更新日期：1993-02-15 00:00:00
abstract：:Nucleotide-free kinesin motor domains from several kinesin families convert reversibly to a refractory conformation that cannot rapidly rebind ADP. In the absence of glycerol, the refractory conformation of Drosophila kinesin motor domains is favored by 50-fold with conversion of the active to the refractory species a...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/j.abb.2016.08.019
更新日期：2016-10-15 00:00:00
abstract：:Short, strong (low barrier) hydrogen bonds occur when the pK values of the atoms sharing the proton are similar. The overall distance is 2.5 A or less, the deuterium fractionation factor is less than 0.5, the proton NMR chemical shift can approach 20 ppm, and deuterium or tritium substitution causes an up-field change...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章,评审
doi：10.1006/abbi.2000.2011
更新日期：2000-10-01 00:00:00
abstract：:While prior studies focusing on male mice suggest a role for sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x; DKO) on hepatic phytol metabolism, its role in females is unresolved. This issue was addressed using female and male wild-type (WT) and DKO mice fed a phytoestrogen-free diet without or with 0.5...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/j.abb.2017.10.011
更新日期：2017-12-01 00:00:00
abstract：:Human promatrilysin (matrix metalloproteinase-7) has been produced in Escherichia coli as an N-terminal fusion protein with ubiquitin. The insoluble product was solubilized, refolded, and activated with amino-phenylmercuric acetate. Activation of the fusion protein demonstrated kinetics and intermediates that were ver...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1995.9929
更新日期：1995-12-01 00:00:00
abstract：:The kinetics and thermodynamics of Ulex europeas agglutinin 1-H-antigenic determinant was studied by monitoring the binding of the lectin to H-antigenic fucolipid incorporated in liposomes tethered to the sensor surface by surface plasmon resonance. The second-order rate constants for the interactions are several orde...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1999.1594
更新日期：2000-02-01 00:00:00
abstract：:Drought is one of the most serious factors affecting crop yields in the world. Macleaya cordata (Willd.) is a draught-tolerant medicinal plant that has been proposed as a pioneer crop to be cultivated in arid areas. However, the exact molecular mechanisms through which M. cordata responds to draught stress remain elus...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/j.abb.2020.108300
更新日期：2020-05-15 00:00:00
