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1.
Minh C. Nguyen Guang Huan Tu Kathryn E. Koprivnikar Melissa Gonzalez-Edick Karin U. Jooss Thomas C. Harding 《Cancer immunology, immunotherapy : CII》2010,59(9):1313-1323
A critical factor in clinical development of cancer immunotherapies is the identification of tumor-associated antigens that
may be related to immunotherapy potency. In this study, protein microarrays containing >8,000 human proteins were screened
with serum from prostate cancer patients (N = 13) before and after treatment with a granulocyte–macrophage colony-stimulating factor (GM-CSF)-secreting whole cell immunotherapy.
Thirty-three proteins were identified that displayed significantly elevated (P ≤ 0.05) signals in post-treatment samples, including three proteins that have previously been associated with prostate carcinogenesis,
galectin-8, T-cell alternative reading frame protein (TARP) and TNF-receptor-associated protein 1 (TRAP1). Expanded analysis
of antibody induction in metastatic, castration-resistant prostate cancer (mCRPC) patients (N = 92) from two phase 1/2 trials of prostate cancer immunotherapy, G-9803 and G-0010, indicated a significant (P = 0.03) association of TARP antibody induction and median survival time (MST). Antibody induction to TARP was also significantly
correlated (P = 0.036) with an increase in prostate-specific antigen doubling time (PSADT) in patients with a biochemical (PSA) recurrence
following prostatectomy or radiation therapy (N = 19) from in a previous phase 1/2 trial of prostate cancer immunotherapy, G-9802. RNA and protein encoding TARP and TRAP1
was up-regulated in prostate cancer tissue compared to matched normal controls. These preliminary findings suggest that antibody
induction to TARP may represent a possible biomarker for treatment response to GM-CSF secreting cellular immunotherapy in
prostate cancer patients and demonstrates the utility of using protein microarrays for the high-throughput screening of patient-derived
antibody responses. 相似文献
2.
l-Phenylalanyl-l-Glutamate-Stimulated, Chloride-Dependent Glutamate Binding Represents Glutamate Sequestration Mediated by an Exchange System 总被引:7,自引:6,他引:1
Markus Kessler Gene Petersen Hai Minh Vu Michel Baudry Gary Lynch 《Journal of neurochemistry》1987,48(4):1191-1200
Stimulation of glutamate binding by the dipeptide L-phenylalanyl-L-glutamate (Phe-Glu) was inhibited by the peptidase inhibitor bestatin, suggesting that the stimulation was caused by glutamate liberated from the dipeptide and not by the dipeptide itself. It further suggests that this form of glutamate binding should be reinterpreted as glutamate sequestration and that stimulation of binding both by dipeptides and after preincubation with high concentrations of glutamate is likely to be due to counterflow accumulation. Several other criteria indicate that most of glutamate binding stimulated by chloride represents glutamate sequestration: Binding is reduced when the osmolarity of the incubation medium is increased, when membranes incubated with [3H]glutamate are lysed before filtration, and when membranes are made permeable by transient exposure to saponin. Moreover, dissociation of bound glutamate after a 100-fold dilution of the incubation medium is accelerated about 50 times by the addition of glutamate to the dilution medium. This result would be anomalous if glutamate were bound to a receptor site; it suggests instead that glutamate is transported in and out of membrane vesicles by a transport system that preferentially mediates exchange between internal and external glutamate. Glutamate binding contains a component of glutamate sequestration even when measured in the absence of chloride. Sequestration is adequately abolished only after treating membranes with detergents; even extensive lysis, sonication, and freezing/thawing may be insufficient. 相似文献
3.
Green cybrids with a new nucleus-chloroplast combination cannot be selected after protoplast fusion in the intersubfamilial Nicotiana-Solanum combination. As an approach to overcome the supposed plastomegenome incompatibility, a partial plastome transfer by genetic recombination has been considered. After fusions of protoplasts of a light-sensitive Nicotiana tabacum (tobacco) plastome mutant and lethally irradiated protoplasts of wild-type Solanum tuberosum (potato), a single green colony was recovered among 2.5×104 colonies. The regenerated plants had tobacco-like (although abnormal) morphology, but were normally green, and sensitive to tentoxin, demonstrating chloroplast markers of the potato parent. Restriction enzyme analysis of the chloroplast DNA (cpDNA) revealed recombinant, nonparental patterns. A comparison with physical maps of the parental cpDNA demonstrated the presence of a considerable part of the potato plastome flanked by tobacco-specific regions. This potacco plastome proved to be stable in backcross and backfusion experiments, and normally functional in the presence solely of N. tabacum nucleus. 相似文献
4.
Human esterase D gene: complete cDNA sequence,genomic structure,and application in the genetic diagnosis of human retinoblastoma 总被引:4,自引:2,他引:2
Lih-Jiuan S. Young Eva Y. -H. P. Lee Hoang To Robert Bookstein Jin-Yuh Shew Larry A. Donoso Theodore Sery Michael Giblin Jerry A. Shields Wen-Hwa Lee 《Human genetics》1988,79(2):137-141
Summary The gene encoding human esterase D (EsD), a member of the nonspecific esterase family, is a useful genetic marker for retinoblastoma (RB) and Wilson's disease. Previously we identified a cDNA clone from this gene and determined its chromosomal location. In this report, we present the complete cDNA sequence of the human EsD gene. A long open reading frame encoded a predicted protein of 282 amino acids with molecular weight of 30 kD. A computer-assisted search of a protein sequence data base revealed homology with two other esterases, acetylcholinesterase of Torpedo and esterase-6 of Drosophila. Homologous region were centered around presumptive active sites, suggesting that the catalytic domains of the esterases are conserved during evolution. Three genomic clones of this gene were also isolated and characterized by restriction mapping. At least ten exons were distributed over a 35-kb (kilobase pair) region; each exon contained an average of 100 basepairs (bp). A polymorphic site for Apa I, located within an intron of the esterase D gene, can be used to identify chromosome 13 carrying defective RB alleles within retinoblastoma families. 相似文献
5.
6.
Hiep Nguyen Duc 《Mathematical biosciences》1985,74(1):23-35
A stochastic model of the evolution of mutant subpopulations from stem cells in a human tumor system is derived. From the model, the growth of mutants (both stem cell mutants and overall mutants) due to mutation of tumor stem cells during growth is explored in detail. This allows one to relate the mutant stem cell and overall tumor mutant cell population sizes. The relation of these average sizes is derived for large tumor size and confirms the result of the model due to MacKillop et al. [4], which is based on three tumor cell subpopulations: stem, transitional, and end cells. Furthermore, the results of the stem cell statistics obtained are the same as those obtained from the filtered Poisson process approach [2]. 相似文献
7.
Neurophysiology of geniculate ganglion (facial nerve) taste systems: species comparisons 总被引:2,自引:2,他引:0
Boudreau James C.; Sivakumar Latha; Do Ly Thi; White Thomas D.; Oravec Joseph; Hoang Nga Kieu 《Chemical senses》1985,10(1):89-127
On the basis of various measures taken from geniculate gangliontaste neurons in four species, it was concluded that withineach species the neurons could be subdivided into distinct functionalgroups. In this report, the neural groups of different specieswere directly compared. Units from all four species were studiedwith a common test series of solutions in addition to otherstimuli. Since these stimuli were presented at the same concentrationsto all species, direct quantitative comparisons across specieswere possible for a wide range of chemical compounds. In addition,the neural groups were compared with respect to spontaneousand evoked activity measures, latency to electrical stimulation,and receptive field characteristics. These neurophysiologicaldata suggest a basic model of four distinct subgroups: acidunits, salt units, amino acid units, and X units. 相似文献
8.
Doan Minh Sang Ik Ho Na Dr. Duong Tien Anh Do Thi Mai Dung Nguyen Thi Thu Hang Nguyen T. Phuong-Anh Assoc. Prof. Dr. Pham-The Hai Assoc. Prof. Dr. Dao Thi Kim Oanh Dr. Truong Thanh Tung Soo Jung Lee Joo Hee Kwon Prof. Dr. Jong Soon Kang Prof. Dr. Sang-Bae Han Assoc. Prof. Dr. Dinh Thi Thanh Hai Prof. Dr. Nguyen-Hai Nam 《化学与生物多样性》2023,20(5):e202201030
Herein, we report the design, synthesis and evaluation of novel (E)-3-(3-oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides ( 4 a – i , 7 a – g ) targeting histone deacetylases. Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC-3, prostate; NCI−H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a – i bearing the alkyl substituents seemed to be less potent than the benzyl-containing compounds 7 a – g in all biological assays. Compounds 7 e – f were found to be the most active HDAC inhibitors with IC50 of 1.498±0.020 μM and 1.794±0.159 μM, respectively. In terms of cytotoxicity and anticancer assay, 7 e and 7 f also showed good activity with IC50 values in the micromolar range. In addition, the cell cycle and apoptosis of SW620 were affected by compound 7 f in almost a similar manner to that of reference compound SAHA. Docking assays were carried out for analysis the binding mode and selectivity of this compound toward 8 HDAC isoforms. Overall, our data confirmed that the inhibition of HDAC plays a pivotal role in their anticancer activity. 相似文献
9.
Summary Using a combinatorial peptide library method, we identified YIYGSFK as an efficient and specific peptide substrate for pp60c-src protein tyrosine kinase (PTK) [Lam et al., Int. J. Pept. Protein Res., 45 (1995) 587]. Employing YIYGSFK as a template, we synthesized and evaluated a series of pseudosubstrate-based inhibitors for pp60c-src. We found that the efficiency of a given inhibitor was highly dependent on the specific tyrosine analog used at the phosphorylation site of the substrate. One of these pseudosubstrate inhibitors, YI(2-Nal)GSFK, selectively inhibited the kinase activity of pp60c-src, with a Ki of 24 M. This peptide inhibitor exhibited selectivity for pp60c-src as compared to other PTKs tested, such as c-Abl and Bcr-Abl. Our results suggest that selective inhibitors for a specific PTK can be developed when the structure of a specific and efficient small peptide substrate for this PTK can be used as a template for structure modification.Abbreviations 1-Nal
l-1-naphthylalanine
- 2-Nal
l-2-naphthylalanine
- BOP
benzotriazolyl-N-oxy-tris(dimethylamino)-phosphonium hexafluorophosphate
- BSA
bovine serum albumin
- cAPK
cyclic AMP-dependent protein kinase
- DIEA
diisopropylethylamine
- EGFR
epidermal growth factor receptor
- Fmoc
fluorenylmethoxycarbonyl
- HOBt
1-hydroxybenzotriazole
- MES
2-[N-morpholino]ethanesulfonic acid
- PBS
phosphate-buffered salts
- pCl
l-p-chlorophenylalanine
- pF
l-p-fluorophenylalanine
- PTK
protein tyrosine kinase
- TLC
thin-layer chromatography 相似文献
10.
When flax seedlings are decapitated above cotyledons and three days later one of the two cotyledons is removed then the remaining
cotyledon stimulates in four to five days growth of its axillary bud. It has been found that content of endogenous cytokinins
was higher in the stimulated bud as compared with the other one already 12 h after the cotyledon removal.
Flax seedlings decapitated under cotyledons regenerate adventitious buds on thy hypocotyl stump during 5–6 days. The endogenous
fytohormonal preparation of this regeneration was investigated in the 20 mm apical part of the hypocotyl stump. Decrease in
auxin and increase in gibberellins was already found during the first day after decapitation while the level of cytokinins
increased as late as three days after the apex removal. 相似文献