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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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3.
Georg Steinhauser Johannes H. Sterba Karin Poljanc Max Bichler Karl Buchtela 《Journal of trace elements in medicine and biology》2006,20(3):119-153
In this study, 18 partly commercially available samples of rock salt from Austria, Germany, Pakistan, Poland, Switzerland, and Ukraine were investigated with respect to their content of trace elements using instrumental neutron activation analysis. Elements detected were Al, Ba, Br, Ca, Ce, Cl, Co, Cr, Cs, Eu, Fe, Hf, La, Mn, Na, Rb, Sb, Sc, Sm, Sr, Ta, Tb, Th, and Zn, some of them only in individual cases. An estimation of the bioavailability of these trace elements was performed by dissolving an equivalent of the sodium chloride samples in diluted hydrochloric acid (simulating stomach acid), filtering off the insoluble components, and analyzing the evaporated filtrate. It could be shown that in most cases bioactive trace elements like Fe can be found in rock salt in the form of almost insoluble compounds and are therefore not significantly bioavailable, whereas thorium, for example, was partly bioavailable in two cases. A significant contribution to the recommended daily intake of metal trace elements by using rock salt for nutrition can be excluded. 相似文献
4.
Metallothioneins: proteins in search of function 总被引:43,自引:0,他引:43
5.
Amanda McGrosky Carlo Meloro Ana Navarrete Sandra A. Heldstab Andrew C. Kitchener Karin Isler Marcus Clauss 《American journal of primatology》2019,81(8)
Although it is generally assumed that among mammals and within mammal groups, those species that rely on diets consisting of greater amounts of plant fiber have larger gastrointestinal tracts (GIT), statistical evidence for this simple claim is largely lacking. We compiled a dataset on the length of the small intestine, caecum, and colon in 42 strepsirrhine, platyrrhine, and catarrhine primate species, using specimens with known body mass (BM). We tested the scaling of intestine length with BM, and whether dietary proxies (percentage of leaves and a diet quality index) were significant covariates in these scaling relationships, using two sets of models: one that did not account for the phylogenetic structure of the data, and one that did. Intestine length mainly scaled geometrically at exponents that included 0.33 in the confidence interval; Strepsirrhini exhibited particularly long caeca, while those of Catarrhini were comparatively short. Diet proxies were only significant for the colon and the total large intestine (but not for the small intestine or the caecum), and only in conventional statistics (but not when accounting for phylogeny), indicating the pattern occurred across but not within clades. Compared to terrestrial Carnivora, primates have similar small intestine lengths, but longer large intestines. The data on intestine lengths presented here corroborate recent results on GIT complexity, suggesting that diet, as currently described, does not exhaustively explain GIT anatomy within primate clades. 相似文献
6.
Sam Mavandadi Steve Feng Frank Yu Stoyan Dimitrov Karin Nielsen-Saines William R. Prescott Aydogan Ozcan 《PloS one》2012,7(10)
We propose a methodology for digitally fusing diagnostic decisions made by multiple medical experts in order to improve accuracy of diagnosis. Toward this goal, we report an experimental study involving nine experts, where each one was given more than 8,000 digital microscopic images of individual human red blood cells and asked to identify malaria infected cells. The results of this experiment reveal that even highly trained medical experts are not always self-consistent in their diagnostic decisions and that there exists a fair level of disagreement among experts, even for binary decisions (i.e., infected vs. uninfected). To tackle this general medical diagnosis problem, we propose a probabilistic algorithm to fuse the decisions made by trained medical experts to robustly achieve higher levels of accuracy when compared to individual experts making such decisions. By modelling the decisions of experts as a three component mixture model and solving for the underlying parameters using the Expectation Maximisation algorithm, we demonstrate the efficacy of our approach which significantly improves the overall diagnostic accuracy of malaria infected cells. Additionally, we present a mathematical framework for performing ‘slide-level’ diagnosis by using individual ‘cell-level’ diagnosis data, shedding more light on the statistical rules that should govern the routine practice in examination of e.g., thin blood smear samples. This framework could be generalized for various other tele-pathology needs, and can be used by trained experts within an efficient tele-medicine platform. 相似文献
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8.
Peter M. Zygmunt Anna Ermund Pouya Movahed David A. Andersson Charlotte Simonsen Bo A. G. J?nsson Anders Blomgren Bryndis Birnir Stuart Bevan Alain Eschalier Christophe Mallet Ana Gomis Edward D. H?gest?tt 《PloS one》2013,8(12)
Phospholipase C-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate generates diacylglycerol, inositol 1,4,5-trisphosphate and protons, all of which can regulate TRPV1 activity via different mechanisms. Here we explored the possibility that the diacylglycerol metabolites 2-arachidonoylglycerol and 1-arachidonoylglycerol, and not metabolites of these monoacylglycerols, activate TRPV1 and contribute to this signaling cascade. 2-Arachidonoylglycerol and 1-arachidonoylglycerol activated native TRPV1 on vascular sensory nerve fibers and heterologously expressed TRPV1 in whole cells and inside-out membrane patches. The monoacylglycerol lipase inhibitors methylarachidonoyl-fluorophosphonate and JZL184 prevented the metabolism of deuterium-labeled 2-arachidonoylglycerol and deuterium-labeled 1-arachidonoylglycerol in arterial homogenates, and enhanced TRPV1-mediated vasodilator responses to both monoacylglycerols. In mesenteric arteries from TRPV1 knock-out mice, vasodilator responses to 2-arachidonoylglycerol were minor. Bradykinin and adenosine triphosphate, ligands of phospholipase C-coupled membrane receptors, increased the content of 2-arachidonoylglycerol in dorsal root ganglia. In HEK293 cells expressing the phospholipase C-coupled histamine H1 receptor, exposure to histamine stimulated the formation of 2-AG, and this effect was augmented in the presence of JZL184. These effects were prevented by the diacylglycerol lipase inhibitor tetrahydrolipstatin. Histamine induced large whole cell currents in HEK293 cells co-expressing TRPV1 and the histamine H1 receptor, and the TRPV1 antagonist capsazepine abolished these currents. JZL184 increased the histamine-induced currents and tetrahydrolipstatin prevented this effect. The calcineurin inhibitor ciclosporin and the endogenous “entourage” compound palmitoylethanolamide potentiated the vasodilator response to 2-arachidonoylglycerol, disclosing TRPV1 activation of this monoacylglycerol at nanomolar concentrations. Furthermore, intracerebroventricular injection of JZL184 produced TRPV1-dependent antinociception in the mouse formalin test. Our results show that intact 2-arachidonoylglycerol and 1-arachidonoylglycerol are endogenous TRPV1 activators, contributing to phospholipase C-dependent TRPV1 channel activation and TRPV1-mediated antinociceptive signaling in the brain. 相似文献
9.
Mutations in the conserved C-terminal sequence in thyroid hormone receptor dissociate hormone-dependent activation from interference with AP-1 activity. 总被引:4,自引:2,他引:2
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