排序方式: 共有69条查询结果,搜索用时 31 毫秒
1.
2.
Xiangdan Wang Valerie Quarmby Carl Ng Anan Chuntharapai Theresa Shek Charles Eigenbrot Robert F. Kelley Steven Shia Krista M McCutcheon John Lowe Cecilia Leddy Kyle Coachman Gary Cain Felix Chu Isidro Hotzel Mauricio Maia Eric Wakshull Jihong Yang 《MABS-AUSTIN》2013,5(4):540-554
Pharmacokinetic (PK) and immunohistochemistry (IHC) assays are essential to the evaluation of the safety and efficacy of therapeutic monoclonal antibodies (mAb) during drug development. These methods require reagents with a high degree of specificity because low concentrations of therapeutic antibody need to be detected in samples containing high concentrations of endogenous human immunoglobulins. Current assay reagent generation practices are labor-intensive and time-consuming. Moreover, these practices are molecule-specific and so only support one assay for one program at a time. Here, we describe a strategy to generate a unique assay reagent, 10C4, that preferentially recognizes a panel of recombinant human mAbs over endogenous human immunoglobulins. This “panel-specific” feature enables the reagent to be used in PK and IHC assays for multiple structurally-related therapeutic mAbs. Characterization revealed that the 10C4 epitope is conformational, extensive and mainly composed of non-CDR residues. Most key contact residues were conserved among structurally-related therapeutic mAbs, but the combination of these residues exists at low prevalence in endogenous human immunoglobulins. Interestingly, an indirect contact residue on the heavy chain of the therapeutic appears to play a critical role in determining whether or not it can bind to 10C4, but has no affect on target binding. This may allow us to improve the binding of therapeutic mAbs to 10C4 for assay development in the future. Here, for the first time, we present a strategy to develop a panel-specific reagent that can expedite the development of multiple clinical assays for structurally-related therapeutic mAbs. 相似文献
3.
Background
The main goal of this study is to examine the distributions of illness conditions and resulting medical expenditures and their associated factors. To achieve this goal, an in-house survey was conducted in August of 2012 in rural Beijing, the capital city of China.Results
The survey was conducted in Nanjianchang and Beijianchang, which are two villages 20 KM away from Miyun, a satellite city of Beijing. Data was collected on 346 households, which included 834 members. Variables measured included household characteristics, household head characteristics, illness conditions, and medical expenditures. Illness conditions and corresponding expenditure were measured for inpatient treatment, outpatient treatment, and self-treatment separately. Multivariate analysis suggested that the presence of inpatient treatment was associated with household head characteristics including age, gender, and education. The presence of a high level of outpatient treatment was associated with household head characteristics including gender and education. The presence of a high level of self-treatment was significantly associated with household size. In the analysis of overall out-of-pocket (OOP) medical expenditure, only age of household head was borderline significant. In the analysis of OOP inpatient expenditure, age and gender of household head were borderline significant. The OOP outpatient expenditure was associated with household size, presence of members older than 60, household head''s gender, marital status, and occupation. The OOP self-treatment expenditure was not associated with any household characteristic.Conclusions
For the surveyed households, medical expenditure made up a considerable proportion of the total consumption. This study suggested that the presence of illness conditions and resulting OOP medical expenditure were associated with certain household and household head characteristics. Such results may help identify the subgroup that is the most affected by illness conditions. As this study collected recent data on inpatient, outpatient, and self-treatment separately, it may provide a useful complement to the existing studies. 相似文献4.
5.
Hakimelahi GH Shia KS Pasdar M Hakimelahi S Khalafi-Nezhad A Soltani MN Mei NW Mei HC Saboury AA Rezaei-Tavirani M Moosavi-Movahedi AA 《Bioorganic & medicinal chemistry》2002,10(9):2927-2932
A novel cephalosporin derivative of monohydroguaiaretic acid (cephem-M(3)N, 7) was synthesized and found to possess anticancer activity against human leukemia (K562), breast carcinoma (MCF7), human lung cancer (A549), human colon cancer (Colo205) and pancreatic cancer cells (Capan2 and MiaPaCa2). A tumor targeting fusion protein (dsFv3-beta-lactamase) was also used in conjunction with cephem-based M(3)N 7 and its potency toward K562, MCF7, A549, Colo205, Capan2, and MiaPaCa2 was found to approach that of the free M(3)N (4). In the presence of dsFv3-beta-lactamase, tumor cells were found to be much more susceptible to conjugate 7 than normal human embryonic lung (HEL) cells and normal fibroblasts (Hef522). These notions provide a new approach to the use of nordihydroguaiaretic acid (NDGA) and its derivatives for antitumor therapy. 相似文献
6.
7.
8.
Chung TL Hsiao HH Yeh YY Shia HL Chen YL Liang PH Wang AH Khoo KH Shoei-Lung Li S 《The Journal of biological chemistry》2004,279(38):39653-39662
Protein sumoylation by small ubiquitin-like modifier (SUMO) proteins is an important post-translational regulatory modification. A role in the control of chromosome dynamics was first suggested when SUMO was identified as high-copy suppressor of the centromere protein CENP-C mutants. CENP-C itself contains a consensus sumoylation sequence motif that partially overlaps with its DNA binding and centromere localization domain. To ascertain whether CENP-C can be sumoylated, tandem mass spectrometry (MS) based strategy was developed for high sensitivity identification and sequencing of sumoylated isopeptides present among in-gel-digested tryptic peptides of SDS-PAGE fractionated target proteins. Without a predisposition to searching for the expected isopeptides based on calculated molecular mass and relying instead on the characteristic MS/MS fragmentation pattern to identify sumolylation, we demonstrate that several other lysine residues located not within the perfect consensus sumoylation motif psiKXE/D, where psi represents a large hydrophobic amino acid, and X represents any amino acid, can be sumolylated with a reconstituted in vitro system containing only the SUMO proteins, E1-activating enzyme and E2-conjugating enzyme (Ubc9). In all cases, target sites that can be sumoylated by SUMO-2 were shown to be equally susceptible to SUMO-1 attachments which include specific sites on SUMO-2 itself, Ubc9, and the recombinant CENP-C fragments. Two non-consensus sites on one of the CENP-C fragments were found to be sumoylated in addition to the predicted site on the other fragment. The developed methodologies should facilitate future studies in delineating the dynamics and substrate specificities of SUMO-1/2/3 modifications and the respective roles of E3 ligases in the process. 相似文献
9.
Cheng‐Wei Lin Shing‐Chuan Shen Chih‐Chiang Chien Liang‐Yo Yang Lin‐Ting Shia Yen‐Chou Chen 《Journal of cellular physiology》2010,225(2):472-481
An increase in MMP‐9 gene expression and enzyme activity with stimulating the migration of GBM8401 glioma cells via wound healing assay by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) was detected in glioblastoma cells GBM8401. TPA‐induced translocation of protein kinase C (PKC)α from the cytosol to membranes, and migration of GBM8401 elicited by TPA was suppressed by adding the PKCα inhibitors, GF109203X and H7. Activation of extracellular signal‐regulated kinase (ERK) and c‐Jun‐N‐terminal kinase (JNK) by TPA was identified, and TPA‐induced migration and MMP‐9 activity was significantly blocked by ERK inhibitor PD98059 and U0126, but not JNK inhibitor SP600125. Activation of NF‐κB protein p65 nuclear translocation and IκBα protein phosphorylation with increased NF‐κB‐directed luciferase activity by TPA were observed, and these were blocked by the PD98059 and IkB inhibitor BAY117082 accompanied by reducing migration and MMP‐9 activity induced by TPA in GBM8401 cells. Transfection of GBM8401 cells with PKCα siRNA specifically reduced PKCα protein expression with blocking TPA‐induced MMP‐9 activation and migration. Additionally, suppression of TPA‐induced PKCα/ERK/NK‐κB activation, migration, and MMP‐9 activation by flavonoids including kaempferol (Kae; 3,5,7,4′‐tetrahydroxyflavone), luteolin (Lut; 5,7,3′4′‐tetrahydroxyflavone), and wogonin (Wog; 5,7‐dihydroxy‐8‐methoxyflavone) was demonstrated, and structure–activity relationship (SAR) studies showed that hydroxyl (OH) groups at C4′ and C8 are critical for flavonoids' action against MMP‐9 enzyme activation and migration/invasion of glioblastoma cells elicited by TPA. Application of flavonoids to prevent the migration/invasion of glioblastoma cells through blocking PKCα/ERK/NF‐κB activation is first demonstrated herein. J. Cell. Physiol. 225: 472–481, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
10.
Synthesis and anticancer evaluation of vitamin K(3) analogues 总被引:3,自引:0,他引:3
Novel vitamin K(3) analogues were synthesized and evaluated for their anticancer activity. Compound 6, 9, 10, 11, 14, and (+/-)15 demonstrated a strong inhibitory activity against the tumor cells of A-549, Hep G2, MCF7, MES-SA, MES-SA/Dx5, MKN45, SW-480, and TW-039. Compound (+/-)15 displayed potent tumor cell cytotoxicity, and compound 14 selectively affected MCF7, even though it did not influence normal cells Detroit551 and WI-38. Compound (+/-)15 inhibited MES-SA and MES-SA/Dx5, and this specific result shows that compound (+/-)15 may become a good anticancer drug candidate. 相似文献