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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
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In human hepatoma cell line Hep3B/T2, the human heat-shock-inducible gene hsp70 could be induced by insulin. The dose-dependent insulin effect correlates very well with the dissociation constant of the insulin receptor, indicating that the insulin effect is mediated by the insulin receptor. The expression of hsp70 gene was neither significantly induced by growth factors of epidermal and platelet-derived growth factors, nor by tumor promoter, calcium ionophore, cAMP, and glucocorticoids. These results indicate that the induction of expression of hsp70 gene by insulin is very specific and not cell cycle-related. Furthermore, the insulin-induced expression of hsp70 gene is transient, occurring specifically from 4 to 8 h after insulin addition. 相似文献
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Y H Gulcan N Duman A Kumral B Sa?olLebe S Kavuk?u D Er?al M Celilo?lu H Ozkan 《Genetic counseling (Geneva, Switzerland)》2001,12(3):263-267
Cerebrohepatorenal malformation is a rare familial disorder characterized by typical renal lesions combined with Dandy-Walker malformation, and congenital hepatic fibrosis. In this case report, a male premie with the diagnosis of cerebrorenal syndrome or so called Goldston syndrome is presented. Besides the rarity of this syndrome, this case is the second reported patient diagnosed prenatally. 相似文献
8.
Carbonic Anhydrase and the Uptake of Inorganic Carbon by Synechococcus sp. (UTEX-2380) 总被引:10,自引:7,他引:3 下载免费PDF全文
We report the changes in the concentrations and 18O contents of extracellular CO2 and HCO3− in suspensions of Synechococcus sp. (UTEX 2380) using membrane inlet mass spectrometry. This marine cyanobacterium is known to have an active uptake mechanism for inorganic carbon. Measuring 18O exchange between CO2 and water, we have found the intracellular carbonic anhydrase activity to be equivalent to 20 times the uncatalyzed CO2 hydration rate in different samples of cells that were grown on bubbled air (low-CO2 conditions). This activity was only weakly inhibited by ethoxzolamide with an I50 near 7 to 10 micromolar in lysed cell suspensions. We have shown that even with CO2-starved cells there is considerable generation of CO2 from intracellular stores, a factor that can cause errors in measurement of net CO2 uptake unless accounted for. It was demonstrated that use of 13C-labeled inorganic carbon outside the cell can correct for such errors in mass spectrometric measurement. Oxygen-18 depletion experiments show that in the light, CO2 readily passes across the cell membrane to the sites of intracellular carbonic anhydrase. Although HCO3− was readily taken up by the cells, these experiments shown that there is no significant efflux of HCO3− from Synechococcus. 相似文献
9.
Three hemorrhagic toxins with proteolytic activity were isolated from the venom of Crotalus ruber ruber (red rattlesnake). Molecular weights of HT-1, HT-2, and HT-3 were 60,000, 25,000, and 25,500, respectively. Although HT-3 was a basic protein, HT-1 and HT-2 were slightly acidic proteins. Total amino acid residues were 482,207, and 221 for HT-1, HT-2, and HT-3, respectively. Protease activity of all the toxins was inhibited in the presence of EDTA or o-phenanthroline, suggesting that the toxins are metalloproteins. Analyses for various metals by inductively coupled plasma-atomic emission spectrometry indicated that sodium, potassium, zinc, and calcium atoms were present in significant quantities. With all three toxins, there was roughly 1 mol of zinc to 1 mol of protein; the results for calcium were not consistent. All three hemorrhagic toxins degraded the A alpha chain of fibrinogen, while HT-1 also degraded the B beta chain. Although fibrinogen was degraded by the three toxins, no clots were observed, indicating that the proteolytic specificities of the three toxins were different from those of thrombin. The hemorrhagic toxins increased creatine kinase activity in mice serum, indicating muscle damage, which was substantiated by histological examination. 相似文献
10.
Enzymatic transformation of PGH2 to PGF2 alpha catalyzed by glutathione S-transferases 总被引:2,自引:0,他引:2
J R Burgess H Yang M Chang M K Rao C P Tu C C Reddy 《Biochemical and biophysical research communications》1987,142(2):441-447
Glutathione S-transferases (GSTs) purified from both rat liver cytosol and microsomes catalyzed the direct reduction of PGH2 to PGF2 alpha. As much as 40% of the substrate was transformed into a prostanoid whose Rf value corresponded to that of PGF2 alpha. The identification of the reaction product as PGF2 alpha was confirmed by TLC and reverse-phase HPLC as well as by mass spectral analysis. In the absence of GSTs, PGH2 was found to be primarily converted to PGE2 and PGD2. Also, PGF2 alpha formation was completely abolished by decylglutathione, a potent inhibitor of both peroxidase and transferase activity associated with GSTs. These results indicate that the direct reduction of endoperoxide moiety of PGH2 to form PGF2 alpha is an enzymatic process. Interestingly, selenium-dependent glutathione peroxidase (Se-GSH-Px) showed very little PGF2 alpha formation from PGH2. However, this enzyme was very active in the reduction of PGG2 to PGH2. In contrast, GSTs were very poor in the conversion of PGG2 to PGH2. Therefore, it is possible that the relative tissue distribution of Se-GSH-Px and GSTs might play an important role in the tissue specific synthesis of PGF2 alpha. 相似文献