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
Many studies have examined the association between the FABP2 (rs1799883) Ala54Thr gene polymorphism and type 2 diabetes mellitus risk (T2DM) in various populations, but their results have been inconsistent. To assess this relationship more precisely, A HuGE review and meta‐analysis were performed. The PubMed and CNKI database was searched for case‐control studies published up to April 2014. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 13 studies, comprising 2020 T2DM cases and 2910 controls were included. Overall, for the Thr carriers (Ala/Thr and Thr/Thr) versus the wild‐type homozygotes (Ala/Ala), the pooled OR was 1.18 (95% CI = 1.04–1.34, P = 0.062 for heterogeneity), for Thr/Thr versus Ala/Ala the pooled OR was 1.17 (95% CI = 1.05–1.41 P = 0.087 for heterogeneity). In the stratified analysis by ethnicity, the significantly risks were found among Asians but not Caucasians. This meta‐analysis suggests that the FABP2 (rs1799883) Ala54Thr polymorphisms are associated with increased susceptibility to T2DM risk among Asians but not Caucasians. 相似文献
Caveolin induces membrane curvature and drives the formation of caveolae that participate in many crucial cell functions such as endocytosis. The central portion of caveolin-1 contains two helices (H1 and H2) connected by a three-residue break with both N- and C-termini exposed to the cytoplasm. Although a U-shaped configuration is assumed based on its inaccessibility by extracellular matrix probes, caveolin structure in a bilayer remains elusive. This work aims to characterize the structure and dynamics of caveolin-1 (D82–S136; Cav182–136) in a DMPC bilayer using NMR, fluorescence emission measurements, and molecular dynamics simulations. The secondary structure of Cav182–136 from NMR chemical shift indexing analysis serves as a guideline for generating initial structural models. Fifty independent molecular dynamics simulations (100 ns each) are performed to identify its favorable conformation and orientation in the bilayer. A representative configuration was chosen from these multiple simulations and simulated for 1 μs to further explore its stability and dynamics. The results of these simulations mirror those from the tryptophan fluorescence measurements (i.e., Cav182–136 insertion depth in the bilayer), corroborate that Cav182–136 inserts in the membrane with U-shaped conformations, and show that the angle between H1 and H2 ranges from 35 to 69°, and the tilt angle of Cav182–136 is 27 ± 6°. The simulations also reveal that specific faces of H1 and H2 prefer to interact with each other and with lipid molecules, and these interactions stabilize the U-shaped conformation. 相似文献
Four species of icefishes were sampled in the Yellow River estuary of the Bohai Sea from April 1984 to April 1985 and from February 1988 to June 1989. Morphological analysis showed that they belonged to three subfamilies of Salangidae: one species from Protosalangicae, Protosalanx chinensis ; two species from Salanginae, Salanx ariakensis and Salanx prognathus ; and one species, Neosalanx andersoni , from Salangichthyinae, a new subfamily. External morphological characteristics, population composition, growth, maturity, food habits, longevity, fecundity, abundance and distribution of these icefishes are described. Based on these analyses, a clear outline of taxonomy, zoogeography aod biology of icefishes in the Yellow River estuary of the Bohai Sea was established. 相似文献
This study aims to explore the protective effects of Picroside III, an active ingredient of Picrorhiza scrophulariiflora, on the intestinal epithelial barrier in tumor necrosis factor-α (TNF-α) induced Caco-2 cells and dextran sulfate sodium (DSS) induced colitis in mice. Results show that Picroside III significantly alleviated clinical signs of colitis including body weight loss, disease activity index increase, colon shortening, and colon tissue damage. It also increased claudin-3, ZO-1 and occludin expressions and decreased claudin-2 expression in the colon tissues of mice with colitis. In vitro, Picroside III also significantly promoted wound healing, decreased the permeability of cell monolayer, upregulated the expressions of claudin-3, ZO-1 and occludin and downregulated the expression of claudin-2 in TNF-α treated Caco-2 cells. Mechanism studies show that Picroside III significantly promoted AMP-activated protein kinase (AMPK) phosphorylation in vitro and in vivo, and blockade with AMPK could significantly attenuate the upregulation of Picroside III in ZO-1 and occludin expressions and the downregulation of claudin-2 expression in TNF-α treated Caco-2 cells. In conclusion, this study demonstrates that Picroside III attenuated DSS-induced colitis by promoting colonic mucosal wound healing and epithelial barrier function recovery via the activation of AMPK. 相似文献
Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising.
Methods
Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes.
Results
An integrated diagnostic model called “Combined method” was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.
The glucosyl transferase gene (gtr) from bacteriophage phage X (SfX) caused partial conversion of serotype Y (group antigen 3, 4) to X (group antigen 7, 8) when introduced into a candidate vaccine strain of Shigella flexneri serotype Y (SFL124). The gtr gene caused conversion of O-antigens but did not eliminate the adsorption of the corresponding phage SfX. The hybrid strain expressing both group antigens 7, 8 and 3, 4 showed 75% protection when immunized guinea pigs were challenged with a wild-type S. flexneri serotype X strain. No protection was observed against serotype Y challenge, although group antigen 3, 4 was detected in the LPS of the hybrid strain. This suggests the importance of O-antigen immunity in the host defense against shigellosis. 相似文献