Lysine demethylase LSD1 delivered via small extracellular vesicles promotes gastric cancer cell stemness.

Several studies have examined the functions of nucleic acids in small extracellular vesicles (sEVs). However, much less is known about the protein cargos of sEVs and their functions in recipient cells. This study demonstrates the presence of lysine-specific demethylase 1 (LSD1), which is the first identified histone demethylase, in the culture medium of gastric cancer cells. We show that sEVs derived from gastric cancer cells and the plasma of patients with gastric cancer harbor LSD1. The shuttling of LSD1-containing sEVs from donor cells to recipient gastric cancer cells promotes cancer cell stemness by positively regulating the expression of Nanog, OCT4, SOX2, and CD44. Additionally, sEV-delivered LSD1 suppresses oxaliplatin response of recipient cells in vitro and in vivo, whereas LSD1-depleted sEVs do not. Taken together, we demonstrate that LSD1-loaded sEVs can promote stemness and chemoresistance to oxaliplatin. These findings suggest that the LSD1 content of sEV could serve as a biomarker to predict oxaliplatin response in gastric cancer patients.

Autoantibodies to PAX5, PTCH1, and GNA11 as Serological Biomarkers in the Detection of Hepatocellular Carcinoma in Hispanic Americans.

Studies have demonstrated that autoantibodies to tumor-associated antigens (TAAs) may be used as efficient biomarkers with low-cost and highly sensitive characteristics. In this study, an enzyme-linked immunosorbent assay (ELISA) was conducted to analyze autoantibodies to paired box protein Pax-5 (PAX5), protein patched homolog 1 (PTCH1), and guanine nucleotide-binding protein subunit alpha-11 (GNA11) in sera from Hispanic Americans including hepatocellular carcinoma (HCC) patients, patients with liver cirrhosis (LC), patients with chronic hepatitis (CH), as well as normal controls. Meanwhile, 33 serial sera from eight HCC patients before and after diagnosis were used to explore the potential of these three autoantibodies as early biomarkers. In addition, an independent non-Hispanic cohort was used to evaluate the specificity of these three autoantibodies. In the Hispanic cohort, at the 95.0% specificity for healthy controls, 52.0%, 44.0%, and 44.0% of HCC patients showed significantly elevated levels of autoantibodies to PAX5, PTCH1, and GNA11, respectively. Among patients with LC, the frequencies for autoantibodies to PAX5, PTCH1, and GNA11 were 32.1%, 35.7%, and 25.0%, respectively. The area under the ROC curves (AUCs) of autoantibodies to PAX5, PTCH1, and GNA11 for identifying HCC from healthy controls were 0.908, 0.924, and 0.913, respectively. When these three autoantibodies were combined as a panel, the sensitivity could be improved to 68%. The prevalence of PAX5, PTCH1, and GNA11 autoantibodies has already occurred in 62.5%, 62.5%, or 75.0% of patients before clinical diagnosis, respectively. In the non-Hispanic cohort, autoantibodies to PTCH1 showed no significant difference; however, autoantibodies to PAX5, PTCH1, and GNA11 showed potential value as biomarkers for early detection of HCC in the Hispanic population and they may monitor the transition of patients with high-risk (LC, CH) to HCC. Using a panel of the three anti-TAA autoantibodies may enhance the detection of HCC.

Oridonin Induces Apoptosis in Esophageal Squamous Cell Carcinoma by Inhibiting Cytoskeletal Protein LASP1 and PDLIM1.

Esophageal squamous cell carcinoma is a severe malignancy for its high mortality and poor prognosis. Mainstay chemotherapies cause serious side effects for their ways of inducing cell death. Oridonin is the main bioactive constituent from natural plants that has anticancer ability and weak side effects. The proteomics method is efficient to understand the anticancer mechanism. However, proteins identified by proteomics aimed at understanding oridonin's anticancer mechanism is seldom overlapped by different groups. This study used proteomics based on two-dimensional electrophoresis sodium dodecyl sulfate-polyacrylamide gel electrophoresis (2-DE SDS-PAGE) integrated with mass spectrometry and Gene Set Enrichment Analysis (GSEA) to understand the anticancer mechanism of oridonin on esophageal squamous cell carcinoma (ESCC). The results showed that oridonin induced ESCC cell death via apoptosis by decreasing the protein expression of LASP1 and PDLIM1.

Discovery of vanoxerine dihydrochloride as a CDK2/4/6 triple-inhibitor for the treatment of human hepatocellular carcinoma.

BACKGROUND: Cyclin-dependent kinases 2/4/6 (CDK2/4/6) play critical roles in cell cycle progression, and their deregulations are hallmarks of hepatocellular carcinoma (HCC). METHODS: We used the combination of computational and experimental approaches to discover a CDK2/4/6 triple-inhibitor from FDA approved small-molecule drugs for the treatment of HCC. RESULTS: We identified vanoxerine dihydrochloride as a new CDK2/4/6 inhibitor, and a strong cytotoxicdrugin human HCC QGY7703 and Huh7 cells (IC50: 3.79 µM for QGY7703and 4.04 µM for Huh7 cells). In QGY7703 and Huh7 cells, vanoxerine dihydrochloride treatment caused G1-arrest, induced apoptosis, and reduced the expressions of CDK2/4/6, cyclin D/E, retinoblastoma protein (Rb), as well as the phosphorylation of CDK2/4/6 and Rb. Drug combination study indicated that vanoxerine dihydrochloride and 5-Fu produced synergistic cytotoxicity in vitro in Huh7 cells. Finally, in vivo study in BALB/C nude mice subcutaneously xenografted with Huh7 cells, vanoxerine dihydrochloride (40 mg/kg, i.p.) injection for 21 days produced significant anti-tumor activity (p < 0.05), which was comparable to that achieved by 5-Fu (10 mg/kg, i.p.), with the combination treatment resulted in synergistic effect. Immunohistochemistry staining of the tumor tissues also revealed significantly reduced expressions of Rb and CDK2/4/6in vanoxerinedihydrochloride treatment group. CONCLUSIONS: The present study isthe first report identifying a new CDK2/4/6 triple inhibitor vanoxerine dihydrochloride, and demonstrated that this drug represents a novel therapeutic strategy for HCC treatment.

Design and exploration of 5-nitro-3-trinitromethyl-1H-1,2,4-triazole and its derivatives as energetic materials.

According to the fact that 5-nitro-3-trinitromethyl-1H-1,2,4 triazole (NTNMT) is a successful, good explosive, energetic groups such as -CH3, -NH2, -NHNO2, -NO2, -ONO2, -NF2, -CN, -NC, -N3 groups were introduced into NTNMT and their oxygen balance was at about zero. The energetic properties, detonation performance, and sensitivity were studied at the B3LYP/6-31G** level of density functional theory to seek for possible high energy density compounds. The effects of substituent groups on heat of formation (HOF), density ρ, detonation velocity D, detonation pressure P, detonation energy Q, and sensitivity (evaluated using oxygen balance OB, the nitro group charges -QNO2, and bond dissociation energies BDE were studied and discussed. The order of contribution of the substituent groups to ρ, D, and P was -NF2 > -ONO2 > -NO2 > -NHNO2 > -N3 > -NH2 > -NC > -CN > -CH3; while to HOF is -N3 > -NC > -CN > -NO2 > -NF2 > -ONO2 > -NH2 > -NHNO2 > -CH3. The trigger bonds in the pyrolysis process for NTNMT derivatives may be N-NO2, N-NH2, N-NHNO2, C-NO2, or O-NO2 varying with the attachment of different substituents. Results show that NTNMT-NHNO2, -NH2, -CN, and -NC derivatives have high detonation performance and good stability. In a word, the oxygen balance at about zero strategy in this work offers new routes for the improvement in properties and stabilities of energetic materials. In the present paper, several 5-nitro-3-trinitromethyl-1H-1,2,4 triazole (NTNMT) derivatives were designed. Their energetic properties, detonation performance, and sensitivity were studied at the B3LYP/6-31G** level of density functional theory (DFT) to seek for possible high energy density compounds (HEDCs). The different substituents have some changes in the influence on heat of formation (HOF), density ρ, detonation velocity D, detonation pressure P, detonation energy Q, and sensitivity. In a word, the oxygen balance at about zero strategy in this work offers new routes for the improvement in properties and stabilities of energetic materials.

Immunodiagnostic Biomarkers for Hepatocellular Carcinoma (HCC): The First Step in Detection and Treatment.

Hepatocellular carcinoma (HCC) exerts huge effects on the health burden of the world because of its high mortality and poor prognosis. HCC is often clinically detected late in patients. If HCC could be detected and treated earlier, the survival rate of patients will be greatly improved. Therefore, identifying specific biomarkers is urgent and important for HCC. The liver is also recognized as an immune organ. The occurrence of HCC is related to exacerbation of immune tolerance and/or immunosurveillance escape. The host immune system plays an important role in the recognition and targeting of tumor cells in cancer immunotherapy, as can be seen from the clinical success of immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cells. Thus, there is a pressing medical need to discover immunodiagnostic biomarkers specific to HCC for understanding the pathological mechanisms of HCC, especially for immunotherapy targets. We have reviewed the existing literature to summarize the immunodiagnostic markers of HCC, including autoantibodies against tumor-associated antigens (TAAs) and exosomes, to provide new insights into HCC and early detection of this deadly cancer.

iTRAQ-based quantitative analysis reveals the mechanism underlying the changes in physiological activity in a glutamate racemase mutant strain of Streptococcus mutans UA159.

Streptococcus mutans UA159 is responsible for human dental caries with robust cariogenic potential. Our previous study noted that a glutamate racemase (MurI) mutant strain (designated S. mutans FW1718), with the hereditary background of UA159, displayed alterations of morphogenesis, attenuated stress tolerance, and weakened biofilm-forming capabilities, accompanying with unclear mechanisms. In this study, we applied isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics to characterize the proteome profiles of the murI mutant strain vs. the wild-type strain in chemically defined media to elucidate the mechanisms by which S. mutans copes with MurI deficiency. Whole-cell proteins of S. mutans FW1718 and UA159 were assessed by iTRAQ-coupled LC-ESI-MS/MS. Furthermore, differentially expressed proteins (DEPs) were identified by Mascot, Gene Ontology (GO) annotation, Cluster of Orthologous Groups of proteins (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Finally, a protein-protein interaction (PPI) network was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Among 1173 total bacterial proteins identified, 112 DEPs exhibited altered expression patterns in S. mutans UA159 with or without the murI mutation. The ΔmurI cells displayed an increase in the relative expression of 93 proteins (fold change ≥ 1.2, p < 0.05) and a decrease in 29 proteins (fold change ≤ 0.833, p < 0.05) compared with the wild-type cells. PPI analysis revealed a complex network of DEPs containing 191 edges and 122 nodes. The DEPs significantly upregulated after murI knockout had roles in diverse functional processes spanning cell-wall biosynthesis, energy production, and DNA replication and repair. We identified distinct variations and diverse modulators caused by murI mutation in the proteome of S. mutans, indicating that the modification of cell membrane structure, redistribution of energy metabolism and enhanced nucleic acid machinery contributed to the S. mutans response to specific environmental contexts.

Influence of exogenous acid protease in broiler chickens fed corn-soybean meal-based diets.

This study was conducted to determine the influence of exogenous acid protease (EAP) on growth performance, blood profiles, excreta noxious gas emissions, ileum digesta viscosity and apparent ileal digestibility in broilers. A total of 600 1-d-old broilers with average initial body weight of 47.0 ± 0.2 g were used in a 5-week feeding trial. The broilers were randomly allotted to 1 of 4 treatments with 10 replicate pens per treatment and 15 birds per cage. Dietary treatments consisted of: CON, basal diets; EAP1, CON + 2,700 exogenous acid protease unite (APU)/kg; EAP2, CON + 5,400 APU/kg; EAP3, CON + 8,100 APU/kg. The body weight gain (BWG) had a linear improvement when chicks fed 8,100 AP/kg diets from d 18 to 35 and overall (p < .05). Lower feed conversion ratio (FCR) was obtained in broilers fed 5,400 APU/kg and 8,100 APU/kg as compared with the CON during overall (p < .05). Birds fed diets supplemented with EAP diet led to a linear increase in the ileal digestibility of crude protein, energy and amino acids (lysine, methionine, cystine, threonine, isoleucine, leucine, histidine and tryptophan) compared with CON group (p < .05). In conclusion, based on our results, we suggest that supplementation with EAP diet was effective in improving growth performance through increasing ileal digestibility of some nutrients (crude protein, energy and amino acids) in broilers.

LncRNA LINC01305 silencing inhibits cell epithelial-mesenchymal transition in cervical cancer by inhibiting TNXB-mediated PI3K/Akt signalling pathway.

Cervical cancer (CC) remains one of the leading malignancies afflicting females worldwide, with its aetiology associated with long-term papillomavirus infection. Recent studies have shifted their focus and research attention to the relationship between long non-coding RNAs (lncRNAs) and CC therapeutic. Thus, the aim of the current study was to investigate the underlying mechanism of lncRNA LINC01305 on the cell invasion, migration and epithelial-mesenchymal transition (EMT) of CC cells via modulation of the PI3K/Akt signalling pathway by targeting tenascin-X B (TNXB). The expressions of LINC01305, TNXB, MMP2, MMP9, E-cadherin, vimentin, PI3K, Akt, p-PI3K, p-Akt and TNXB were detected in this study. After which, the cell invasion and migration abilities of the CC cells were determined respectively. Bioinformatics and the application of a dual luciferase reporter gene assay provided verification indicating that TNXB is the target gene of lncRNA LINC01305. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis methods revealed that the expressions of MMP2, MMP9, vimentin, PI3K, Akt, p-PI3K and p-Akt were decreased following the down-regulation of LncRNA LINC01305 or overexpression of TNXB. LncRNA LINC01305 silencing or TNXB overexpression was noted to decrease the migration and invasion of SiHa cells. Taken together, the key findings of the current study present evidence suggesting that lncRNA LINC01305 silencing suppresses EMT, invasion and migration via repressing the PI3K/Akt signalling pathway by means of targeting TNXB in CC cells, which ultimately provides novel insight and identification of potential therapeutic targets for CC.

Coffee consumption and risk of pancreatic cancer: a systematic review and dose-response meta-analysis.

The association between coffee consumption and pancreatic cancer risk has been extensively studied; however, there is no consistent conclusion. Therefore, this meta-analysis study sought to evaluate dose-response relationship between them. A search was conducted using the PubMed and Web of Science databases. Thirteen high-quality cohort studies were identified, involving in 959,992 study participants and 3831 pancreatic cancer cases. Comparing the highest with lowest categories of coffee intake, the pooled relative risk (RR) was 1.08 (95% CI 0.94-1.25). For dose-response analysis, no evidence of a nonlinear dose-response association between coffee consumption and pancreatic cancer (p for nonlinearity =0.171) was found. The risk of pancreatic cancer was increased by 5.87% (RR =1.06, 95% CI 1.05-1.07) with the increment of one cup/day. Coffee consumption was identified to be related with the increasing risk of pancreatic cancer in a dose-response manner. Nevertheless, further mechanistic studies are needed to clarify the concerned issues.

Effects of dietary supplemental phytoncide instead of zinc oxide on growth performance, nutrient digestibility, blood profiles, and faecal microflora in growing pigs.

This study was aimed to evaluate the effect of phytoncide (PTC) instead of zinc oxide on growth performance, blood profile, nutrient digestibility and faecal microflora in growing pigs. A total of 120 growing pigs [(Landrace × Yorkshire) × Duroc] with initial body weight 24.48 ± 1.62 kg were randomly assigned to four dietary treatments for a 6 weeks feeding trials, the treatments as follow: CON (base diet)，ZO (CON + 0.03% Zinc Oxide), PTC1 (CON + 0.5% PTC), PTC2 (CON + 1.0% PTC). Compared to basal diet, during weeks 1-3, 3-6, and overall experimental period, the ADG of growing pigs fed phytoncide diet trend to be increased, and fed ZO diet was significantly increased (p < 0.05). During weeks 3-6 and overall experiment period, pigs fed the ZO diet showed improvement in feed intake compared to pigs fed basal diet as a trend. Compared with basal diet, the pigs receiving phytoncide diet significantly increased the digestibility of DM and reduced the concentration of aspartate transaminase in pigs receiving 1.0% phytoncide diet. These results suggested that dietary supplement of phytoncide, Korean pine extract, could be used as an alternative to zinc oxide by decreasing detoxify to soil and plants without influencing the performance of growing pigs. Further study is needed to determine the systemic estimation of the dose of phytoncide.

Effect of dietary supplemental medium chain fatty acids instead of antibiotics on the growth performance, digestibility and blood profiles in growing pigs.

Antibiotics have great functions in farm animal. However, the harm of antibiotics can't be ignored. The effects of medium-chain fatty acids (MCFAs) supplementation to basal diet instead of antibiotics (CSP, Chlortetracycline, sulphonamide dimethazine and procaine penicillin, 1:1:1) on growth performance, nutrient digestibility and blood profile in growing pigs were studied. A total of 140 growing pigs (Landrace × Yorkshire × Duroc) with an average body weight of 27.84 ± 0.42 kg were allotted to four treatments of seven replicates/treatment and five pigs/replicate. The four experimental diets included: CON (basal diet, non-antibiotic, negative control); CSP (CON + CSP 0.1%, positive control); M1 (CON + MCFA 0.15%) and M2 (CON + MCFA 0.3%). After 5 weeks, the fresh faecal and blood samples were collected from rectum and jugular vein respectively. The average daily gain (ADG) was significantly improved for pigs fed 0.3% MCFAs in relation to basal diet. Meanwhile, CSP supplementation had comparable effect on ADG. The lymphocyte percentage and IgG concentration were higher in blood of pigs-fed MCFAs in relation to that of CON and CSP treatment while white blood cell and red blood cell were not affected. In relation to basal diet and CSP treatment, the digestibility of dry matter, nitrogen and gross energy (E) were unaffected with MCFAs supplementation. In conclusion, MCFAs improved growth performance on body weight gain and immune profile. Addition 0.3% MCFAs into the diet indicated that its partial positive effect as an alternative to antibiotic.

Effect of supplementation with brewer's yeast hydrolysate on growth performance, nutrients digestibility, blood profiles and meat quality in growing to finishing pigs.

Objective: This study was aimed to investigate the effects of brewer's yeast hydrolysate (YH) on growth performance, nutrients digestibility, blood profiles and meat quality of growing pigs. Methods: A total of 200 growing pigs [(Landrace × Yorkshire) × Duroc] (initial BW, 25.31 ± 1.29 kg) were allotted to 5 treatments as follow: CON: basic diet, and YH treatment: CON + 0.05%, 0.1%, 0.5%, and 1.0% of YH, respectively. Results: On wk11, 16 and overall phase, pigs fed YH diet showed linear improvement in average daily body gain (ADG) and G/F (p<0.05). The pigs received YH linearly increased the digestibility of dry matter (DM), nitrogen (N), and energy (E) on wk 11 and 16. The concentration of serum urea nitrogen(SUN) was linearly increased in YH treatments on wk 16. Meanwhile, the carcass weight, back fat and lean muscle percentage of pigs received YH diet have no significant change. Besides, no difference was observed in creatinine and total protein in the blood among treatment (p > 0.05). Conclusion: The pigs fed graded YH diet could improve the growth performance and nutrients digestibility of growing pigs, meanwhile, the yeast hydr olysate could increase the serum urea nitrogen in the growing pigs.

Long Noncoding RNA HOST2 Promotes Epithelial-Mesenchymal Transition, Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating the JAK2-STAT3 Signaling Pathway.

BACKGROUND/AIMS: This study aims to examine the effect of long noncoding RNA HOST2 (LncRNA HOST2) on epithelial-mesenchymal transition (EMT), proliferation, invasion and migration of hepatocellular carcinoma (HCC) cells via activation of the JAK2-STAT3 signaling pathway. METHODS: HCC and para-cancerous tissues were collected from 136 HCC patients. Immunohistochemistry was used to detect the expression of JAK2 and STAT3. HCC SMMC7721 cells were grouped into blank, negative control (NC), HOST2 mimic and HOST2 inhibitor groups. The mRNA and protein expression levels of HOST2, JAK2, STAT3, E-cadherin, vimentin, Snail, Slug, Twist and Zeb1 in tissues and cells were determined by reverse transcription -quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. An MTT assay, scratch test and Transwell assay were applied to measure cell proliferation, migration and invasion, respectively. RESULTS: The levels of JAK2, STAT3 and vimentin were higher in HCC tissues, while the expression of E-cadherin was lower in HCC tissues compared with para-cancerous tissues. The silencing of HOST2 significantly decreased cell proliferation, migration and invasion, reduced the levels of HOST2, JAK2, STAT3 and vimentin, and elevated the expression of E-cadherin. HOST2 silencing also decreased the levels of Snail, Slug and Twist but increased the level of Zeb1 protein, while the opposite findings were observed in the HOST2 mimic group. CONCLUSION: These results reveal a possible mechanism in HCC in which LncRNA HOST2 may increase EMT and enhance proliferation, invasion and metastasis of HCC cells via activation of the JAK2-STAT3 signaling pathway.

Early detection of hepatocellular carcinoma using autoantibody profiles from a panel of tumor-associated antigens.

BACKGROUND: Multiple antigen miniarrays used for detecting autoantibodies to tumor-associated antigens (TAAs) can be a useful approach for cancer detection and diagnosis. We here address a very specific question: might there be autoimmune responses to TAAs which precede clinical detection of hepatocellular carcinoma (HCC) in HBV and HCV chronic liver disease patients under continuous medical surveillance, and if so, could these anti-TAAs be added to the armamentarium of diagnostic tests? METHODS: We here examine the utility of a panel of 12 TAAs for the diagnosis of hepatocellular carcinoma (HCC). We derived a predictive rule for the presence of HCC based on the panel, from a cohort comprising 160 HCC patients and 90 normals. We then applied this rule to sequential anti-TAA data from a cohort of 17 HCC patients, from whom this information was available prior to diagnosis. RESULTS: The predictors (autoantibodies to HCC1, P16, P53, P90, and survivin) indicated the presence of HCC prior to diagnosis in 16 of the 17 patients, at a median lead time of 0.75 year. CONCLUSIONS: We believe these findings warrant further study of anti-TAA profiles as biomarkers for primary or early diagnosis of HCC.

Immunoseroproteomic Profiling in African American Men with Prostate Cancer: Evidence for an Autoantibody Response to Glycolysis and Plasminogen-Associated Proteins.

African American (AA) men suffer from a disproportionately high incidence and mortality of prostate cancer (PCa) compared with other racial/ethnic groups. Despite these disparities, African American men are underrepresented in clinical trials and in studies on PCa biology and biomarker discovery. We used immunoseroproteomics to profile antitumor autoantibody responses in AA and European American (EA) men with PCa, and explored differences in these responses. This minimally invasive approach detects autoantibodies to tumor-associated antigens that could serve as clinical biomarkers and immunotherapeutic agents. Sera from AA and EA men with PCa were probed by immunoblotting against PC3 cell proteins, with AA sera showing stronger immunoreactivity. Mass spectrometry analysis of immunoreactive protein spots revealed that several AA sera contained autoantibodies to a number of proteins associated with both the glycolysis and plasminogen pathways, particularly to alpha-enolase (ENO1). The proteomic data is deposited in ProteomeXchange with identifier PXD003968. Analysis of sera from 340 racially diverse men by enzyme-linked immunosorbent assays (ELISA) showed higher frequency of anti-ENO1 autoantibodies in PCa sera compared with control sera. We observed differences between AA-PCa and EA-PCa patients in their immunoreactivity against ENO1. Although EA-PCa sera reacted with higher frequency against purified ENO1 in ELISA and recognized by immunoblotting the endogenous cellular ENO1 across a panel of prostate cell lines, AA-PCa sera reacted weakly against this protein by ELISA but recognized it by immunoblotting preferentially in metastatic cell lines. These race-related differences in immunoreactivity to ENO1 could not be accounted by differential autoantibody recognition of phosphoepitopes within this antigen. Proteomic analysis revealed differences in the posttranslational modification profiles of ENO1 variants differentially recognized by AA-PCa and EA-PCa sera. These intriguing results suggest the possibility of race-related differences in the antitumor autoantibody response in PCa, and have implications for defining novel biological determinants of PCa health disparities.

Evaluation of serum autoantibodies against tumor-associated antigens as biomarkers in lung cancer.

We evaluated autoantibodies against nine tumor-associated antigens, including p62, p16, Koc, p53, Cyclin B1, Cyclin E, Survivin, HCC1, and RalA as serological markers in lung cancer. Enzyme-linked immunosorbent assay (ELISA) was used to detect autoantibodies in sera from 50 lung cancer patients and 42 normal controls. Then, four tumor-associated antigens of higher values were selected and validated in sera from validation group. Western blot and serum absorption test were used to confirm positive findings from ELISA. When cutoff values were set as mean optical density values plus 3 standard deviation of normal controls, the positive rate of autoantibodies against four tumor-associated antigens (Survivin, Cyclin B1, HCC1, and p53) reached 32%, 20%, 22%, and 18%, with area under the curve values of 0.653, 0.767, 0.622, and 0.623 in sera from 50 lung cancer, respectively (all p < 0.05). Results from the validation group confirmed the results. When lung cancer patients were divided by their clinicopathological characteristics into different subgroups, we have found that serum anti-Cyclin B1 and anti-HCC1 autoantibodies increased in stages 1, 2, and 3 lung cancer; anti-Survivin autoantibodies increased in stages 2 and 3 lung cancer; and anti-p53 autoantibody only increased in stage 1 when compared with their corresponding levels in controls (all p < 0.05). Serum anti-Cyclin B1 and anti-Survivin autoantibodies increased with disease histological grade 2 and 3 (both p < 0.05). And higher serum level of anti-p53 autoantibodies is positively associated with tumor size. Parallel utilization of these four anti-tumor-associated antigens (any positive) can increase sensitivity to 65.0% at 100% specificity with area under the curve of 0.908 ( p < 0.001) in lung cancer detection in validation group. Our results suggest that autoantibodies against these four tumor-associated antigens have higher values in lung cancer detection, and serum anti-Cyclin-B1 has the potential to serve as novel non-invasive biomarkers in early-stage lung cancer.

Serum autoantibodies against a panel of 15 tumor-associated antigens in the detection of ovarian cancer.

In this study, enzyme-linked immunosorbent assay has been used to examine the frequencies of serum autoantibodies against two candidate tumor-associated antigens intensively selected from the Human Protein Atlas database, in combination with 13 tumor-associated antigens available from our lab in sera from 44 OC patients and 50 normal healthy controls. Conventional evaluation (mean + 3SD as the cutoff value to determine a positive reactivity), receiver operating characteristic curve analyses, and classification tree analysis were further used to evaluate the diagnostic performance of autoantibodies against these tumor-associated antigens (anti-tumor-associated antigens) in ovarian cancer. For single anti-tumor-associated antigen, when the cutoff values were set as mean + 3SD of normal healthy controls, NPM1, MDM2, PLAT, p53, and c-Myc could achieve sensitivity higher than 20% at 98% specificity. Combinational utilization of autoantibodies against MDM2, PLAT, NPM1, 14-3-3 Zeta, p53, and RalA achieved the optimal diagnostic performance with 72.7% sensitivity at 96% specificity. Receiver operating characteristic curve analysis showed that the area under the receiver operating characteristic curves of autoantibodies against c-Myc, NPM1, MDM2, p16, p53, and 14-3-3 Zeta were greater than 0.80. This indicated that these tumor-associated antigens held high potential to serve as diagnostic biomarkers in ovarian cancer detection. Decision tree analysis indicated that anti-c-Myc held high potential in the detection of ovarian cancer. Further studies are warranted to validate the diagnostic performance of these anti-tumor-associated antigens with high area under the receiver operating characteristic curve, including autoantibodies against c-Myc, MDM2, PLAT, NPM1, 14-3-3 Zeta, p53, and RalA.

Effectiveness and safety of single-port versus multi-port laparoscopic surgery for treating liver diseases: a meta-analysis.

OBJECTIVE: To compare the effectiveness and safety of single-port versus multi-port laparoscopic surgery for treating liver diseases. METHODS: Several databases were systematically searched for randomized controlled trials, cohort studies, and case-control studies on the use of single-port versus multi-port laparoscopic surgery to treat liver diseases from their inception until March 24, 2016. The primary outcomes were the operative time, volume of intraoperative blood loss, rate of postoperative complications, median length of postoperative stay, recovery time of gastrointestinal function, volume of postoperative drainage, and postoperative drainage time. The study-specific effect sizes and their 95 % confidence interval were all combined to calculate the pooled value by using a random-effects model. RESULTS: A total of nine studies were included, which involved 277 patients. The total and subgroup data were combined by meta-analysis. This meta-analysis showed that single-port and multi-port laparoscopic liver surgery for treating liver diseases did not differ in terms of operative time (P = 0.48), rate of postoperative complications (P = 0.56), median length of postoperative stay (P = 0.80), and recovery time of gastrointestinal function (P = 0.54). For liver diseases, the single-port group exhibited a lower volume of intraoperative blood loss than that presented by the multi-port group (P = 0.0006). In the hepatic resection subgroup, a lower volume of intraoperative blood loss was noted in the single-port group (P < 0.0001). By contrast, in the hepatic cyst subgroup, the single-port group showed a higher volume of intraoperative blood loss (P = 0.02) but a shorter median length of postoperative stay (P = 0.02). The findings of the potential subgroup analysis in these outcomes were consistent with the total data. CONCLUSION: Compared with multi-port laparoscopic surgery, the single-port method showed comparable effectiveness and safety for the treatment of liver diseases in terms of current evidence.

Using Serological Proteome Analysis to Identify Serum Anti-Nucleophosmin 1 Autoantibody as a Potential Biomarker in European-American and African-American Patients With Prostate Cancer.

BACKGROUND: The prostate-specific antigen (PSA) testing has been widely implemented for the early detection and management of prostate cancer (PCa). However, the lack of specificity has led to overdiagnosis, resulting in many possibly unnecessary biopsies and overtreatment. Therefore, novel serological biomarkers with high sensitivity and specificity are of vital importance needed to complement PSA testing in the early diagnosis and effective management of PCa. This is particularly critical in the context of PCa health disparities, where early detection and management could help reduce the disproportionately high PCa mortality observed in African-American men. Previous studies have demonstrated that sera from patients with PCa contain autoantibodies that react with tumor-associated antigens (TAAs). METHODS: The serological proteome analysis (SERPA) approach was used to identify tumor-associated antigens (TAAs) of PCa. In evaluation study, the level of anti-NPM1 antibody was examined in sera from test cohort, validation cohort, as well as European-American (EA) and African-American (AA) men with PCa by using immunoassay. RESULTS: Nucleophosmin 1 (NPM1) as a 33 kDa TAA in PCa was identified and characterized by SERPA approach. Anti-NPM1 antibody level in PCa was higher than in benign prostatic hyperplasia (BPH) patients and healthy individuals. Receiver operating characteristic (ROC) curve analysis showed similar high diagnostic value for PCa in the test cohort (area under the curve (AUC):0.860) and validation cohort (AUC: 0.822) to differentiate from normal individuals and BPH. Interestingly, AUC values were significantly higher for AA PCa patients. When considering concurrent serum measurements of anti-NPM1 antibody and PSA, 97.1% PCa patients at early stage were identified correctly, while 69.2% BPH patients who had elevated PSA levels were found to be anti-NPM1 negative. Additionally, anti-NPM1 antibody levels in PCa patients at early stage significantly increased after surgery treatment. CONCLUSION: This intriguing data suggested that NPM1 can elicit autoantibody response in PCa and might be a potential biomarker for the immunodiagnosis and prognosis of PCa, and for supplementing PSA testing in distinguishing PCa from BPH. Prostate 76:1375-1386, 2016. © 2016 Wiley Periodicals, Inc.