Tumor-specific neoantigens have attracted much attention since they can be used as biomarkers to predict therapeutic effects of immune checkpoint blockade therapy and as potential targets for cancer immunotherapy. In this study, we developed a comprehensive tumor-specific neoantigen database (TSNAdb v1.0), based on pan-cancer immunogenomic analyses of somatic mutation data and human leukocyte antigen (HLA) allele information for 16 tumor types with 7748 tumor samples from The Cancer Genome Atlas (TCGA) and The Cancer Immunome Atlas (TCIA). We predicted binding affinities between mutant/wild-type peptides and HLA class I molecules by NetMHCpan v2.8/v4.0, and presented detailed information of 3,707,562/1,146,961 potential neoantigens generated by somatic mutations of all tumor samples. Moreover, we employed recurrent mutations in combination with highly frequent HLA alleles to predict potential shared neoantigens across tumor patients, which would facilitate the discovery of putative targets for neoantigen-based cancer immunotherapy. TSNAdb is freely available at http://biopharm.zju.edu.cn/tsnadb.
Antigens, Neoplasm ; metabolism ; Data Analysis ; Databases, Genetic ; Humans ; Immunotherapy ; Mutation ; genetics ; Neoplasms ; genetics ; immunology ; Tumor Suppressor Protein p53 ; genetics ; Urinary Bladder Neoplasms ; genetics

OBJECTIVE: This paper applied a transcriptomic approach to investigate the mechanisms of adriamycin (ADR) in treating proliferative vitreoretinopathy (PVR) using ARPE-19 cells. METHODS: The growth inhibitory effects of ADR on ARPE-19 cells were assessed by sulforhodamine B (SRB) assay and propidium iodide (PI) staining using flow cytometry. The differentially expressed genes between ADR-treated ARPE-19 cells and normal ARPE-19 cells and the signaling pathways involved were investigated by microarray analysis. Mitochondrial function was detected by JC-1 staining using flow cytometry and the Bcl-2/Bax protein family. The phosphorylated histone H2AX (γ-H2AX), phosphorylated checkpoint kinase 1 (p-CHK1), and phosphorylated checkpoint kinase 2 (p-CHK2) were assessed to detect DNA damage and repair. RESULTS: ADR could significantly inhibit ARPE-19 cell proliferation and induce caspase-dependent apoptosis in vitro. In total, 4479 differentially expressed genes were found, and gene ontology items and the p53 signaling pathway were enriched. A protein-protein interaction analysis indicated that the TP53 protein molecules regulated by ADR were related to DNA damage and oxidative stress. ADR reduced mitochondrial membrane potential and the Bcl-2/Bax ratio. p53-knockdown restored the activation of c-caspase-3 activity induced by ADR by regulating Bax expression, and it inhibited ADR-induced ARPE-19 cell apoptosis. Finally, the levels of the γ-H2AX, p-CHK1, and p-CHK2 proteins were up-regulated after ADR exposure. CONCLUSIONS The mechanism of ARPE-19 cell death induced by ADR may be caspase-dependent apoptosis, and it may be regulated by the p53-dependent mitochondrial dysfunction, activating the p53 signaling pathway through DNA damage.
Apoptosis ; Caspases/metabolism* ; Cell Proliferation ; Cell Survival/drug effects* ; Doxorubicin/pharmacology* ; Flow Cytometry ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Membrane Potential, Mitochondrial ; Oligonucleotide Array Sequence Analysis ; Oxidative Stress/drug effects* ; Phosphorylation ; Propidium/chemistry* ; RNA, Small Interfering/metabolism* ; Retinal Pigment Epithelium/metabolism* ; Rhodamines/chemistry* ; Signal Transduction/drug effects* ; Transcriptome ; Tumor Suppressor Protein p53/metabolism* ; Vitreoretinopathy, Proliferative/drug therapy*

Royal jelly (RJ) from honeybee has been widely used as a health promotion supplement. The major royal jelly proteins (MRJPs) have been identified as the functional component of RJ. However, the question of whether MRJPs have anti-senescence activity for human cells remains. Human embryonic lung fibroblast (HFL-I) cells were cultured in media containing no MRJPs (A), MRJPs at 0.1 mg/ml (B), 0.2 mg/ml (C), or 0.3 mg/ml (D), or bovine serum albumin (BSA) at 0.2 mg/ml (E). The mean population doubling levels of cells in media B, C, D, and E were increased by 12.4%, 31.2%, 24.0%, and 10.4%, respectively, compared with that in medium A. The cells in medium C also exhibited the highest relative proliferation activity, the lowest senescence, and the longest telomeres. Moreover, MRJPs up-regulated the expression of superoxide dismutase-1 (SOD1) and down-regulated the expression of mammalian target of rapamycin (MTOR), catenin beta like-1 (CTNNB1), and tumor protein p53 (TP53). Raman spectra analysis showed that there were two unique bands related to DNA synthesis materials, amide carbonyl group vibrations and aromatic hydrogens. These results suggest that MRJPs possess anti-senescence activity for the HFL-I cell line, and provide new knowledge illustrating the molecular mechanism of MRJPs as anti-senescence factors.
Animals ; Bees ; Cattle ; Cell Line ; Cell Proliferation ; Cellular Senescence/drug effects* ; Culture Media ; Dose-Response Relationship, Drug ; Fatty Acids/chemistry* ; Fibroblasts/drug effects* ; Humans ; Insect Proteins/chemistry* ; Lung/drug effects* ; Serum Albumin/metabolism* ; Spectrum Analysis, Raman ; Superoxide Dismutase-1/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; beta Catenin/metabolism*

OBJECTIVEThe aim of this study was to investigate the prognostic value of combined expression of Aurora A, Ki-67, p53 and p21 WAF1 in patients after curative resection of non-small cell lung cancer (NSCLC).

METHODSExpressions of Aurora A, Ki-67, p53 and p21 WAF1 in 58 tumor samples from resected primary NSCLCs were detected by immunohistochemistry. The correlation of proteins, survival and clinicopathological characteristics was analyzed.

RESULTSThe positive rates of Aurora A, Ki-67, p53 and p21 WAF1 expression were 89.7% (52/58), 53.4% (31/58), 46.6% (27/58) and 34.5% (20/58), respectively. Aurora A expression was positively correlated with nodal metastasis (69.2% vs. 37.8%, P = 0.045). The univariable analysis showed that the overall survival (OS) was 75.0%in patients with low Aurora A expression and 46.0% in patients with high Aurora A expression (P = 0.039). The 3-year survival rate was 40.0% in patients with positive expression of Aurora A and p53, 65.0% in the patients with positive expression of Aurora A or p53, and 82.1% in the patients with negative expression of Aurora A and p53 (P = 0.039). The Cox regression model showed that combined expression of Aurora and p53 is an independent factor affecting the prognosis of NSCLC patients (P = 0.015).

CONCLUSIONSOur findings suggest that the positive expression of Aurora A, Ki-67 and p53 proteins is an unfavorable factor affecting the prognosis for NSCLC patients, and the overexpression of Aurora A is an independent unfavorable factor association with shorter OS in NSCLC patients. Detection of positive Aurora A and p53 expression may be a useful predictive prognostic indicator for NSCLC patients.

Aurora Kinase A ; metabolism ; Carcinoma, Non-Small-Cell Lung ; metabolism ; mortality ; surgery ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Lung Neoplasms ; metabolism ; mortality ; surgery ; Prognosis ; Survival Analysis ; Survival Rate ; Tumor Suppressor Protein p53 ; metabolism

PURPOSE: The expression of p53 in patients with rectal cancer who underwent preoperative chemoradiationand and its potential prognostic significance were evaluated. MATERIALS AND METHODS: p53 expression was examined using immunohistochemistry in pathologic specimens from 210 rectal cancer patients with preoperative chemoradiotherapy and radical surgery. All patients were classified into two groups according to the p53 expression: low p53 (<50% nuclear staining) and high p53 (> or =50%) groups. RESULTS: p53 expression was significantly associated with tumor location from the anal verge (p=0.036). In univariate analysis, p53 expression was not associated with disease-free survival (p=0.118) or local recurrence-free survival (p=0.089). Multivariate analysis showed that tumor distance from the anal verge (p=0.006), ypN category (p=0.011), and perineural invasion (p=0.048) were independent predictors of disease-free survival; tumor distance from the anal verge was the only independent predictor of local recurrence-free survival. When the p53 groups were subdivided according to ypTNM category, disease-free survival differed significantly in patients with ypN+ disease (p=0.027) only. CONCLUSION: Expression of p53 in pathologic specimens as measured by immunohistochemical methods may have a significant prognostic impact on survival in patients with ypN+ rectal cancer with preoperative chemoradiotherapy. However, it was not an independent predictor of recurrence or survival.
Adult ; Aged ; *Chemoradiotherapy ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local/pathology ; Neoplasm Staging ; *Preoperative Care ; Prognosis ; Rectal Neoplasms/diagnosis/*metabolism/surgery/*therapy ; Tumor Suppressor Protein p53/analysis/immunology/*metabolism

OBJECTIVETo study the effect of hyperoxia exposure on the expression of p53 and proliferating cell nuclear antigen (PCNA) in fetal rat lung fibroblasts (LFs).

METHODSPrimary rat embryonic LFs were cultured in vitro. LFs grew to subconfluence and then were randomly divided into air and hyperoxia exposure (95% O₂, 5% CO₂) groups. After LFs were cultured for 12 and 24 hours, the proliferation was analyzed by MTT. p53 mRNA level was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). p53 and PCNA protein levels were determined by Western blot.

RESULTSAfter 12 and 24 hours of culture the growth inhibition rate of LFs was 8% and 23% respectively in the hyperoxia exposure group. p53 mRNA and protein levels increased significantly (P<0.01) in the hyperoxia exposure group after 12 and 24 hours of culture compared with the air exposure group. Hyperoxia exposure decreased PCNA expression after 24 hours of culture (P<0.01).

CONCLUSIONSHyperoxia exposure increases p53 level and decreases PCNA expression, resulting in inhibitions of LFs proliferation and DNA repair.

Animals ; Cell Proliferation ; Female ; Fibroblasts ; metabolism ; Hyperoxia ; metabolism ; pathology ; Lung ; cytology ; metabolism ; Proliferating Cell Nuclear Antigen ; analysis ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Tumor Suppressor Protein p53 ; analysis ; genetics

In recent years, large numbers of non-coding RNAs (ncRNAs) have been identified in C. elegans but their functions are still not well studied. In C. elegans, CEP-1 is the sole homolog of the p53 family of genes. In order to obtain transcription profiles of ncRNAs regulated by CEP-1 under normal and UV stressed conditions, we applied the 'not-so-random' hexamers priming strategy to RNA sequencing in C. elegans, This NSR-seq strategy efficiently depleted rRNA transcripts from the samples and showed high technical replicability. We identified more than 1,000 ncRNAs whose apparent expression was repressed by CEP-1, while around 200 were activated. Around 40% of the CEP-1 activated ncRNAs promoters contain a putative CEP-1-binding site. CEP-1 regulated ncRNAs were frequently clustered and concentrated on the X chromosome. These results indicate that numerous ncRNAs are involved in CEP-1 transcriptional network and that these are especially enriched on the X chromosome in C. elegans.
Animals ; Binding Sites ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins ; genetics ; metabolism ; High-Throughput Nucleotide Sequencing ; Promoter Regions, Genetic ; RNA, Untranslated ; metabolism ; Sequence Analysis, RNA ; Transcriptome ; radiation effects ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Ultraviolet Rays ; X Chromosome

OBJECTIVETo investigate the predictive value of seven gastric cancer-associated factors on neoadjuvant chemotherapy in patients with advanced gastric cancer.

METHODSExpressions of C-met, EGFR, HER2, Ki-67, MMP7, P53 and TOPOII were detected by immunohistochemistry in gastric cancer tissues of 53 cases before and after mFOLFOX7 neoadjuvant chemotherapy. Chemotherapy efficacy was evaluated according to RECIST 1.1 standard combined with histopathology, and the relationship between various genes and chemotherapy efficacy was analyzed by univariate and logistic multivariate regression analyses.

RESULTSThe clinical response rate was 52.8% (28/53) in neoadjuvant chemotherapy, including complete response in none, partial response in 28 cases (52.8%), stable disease in 24 cases (45.3%) and progressive disease in 1 case (1.9%). The expressions of all the genes were not significantly different before and after neoadjuvant chemotherapy (P>0.05). Neoadjuvant chemotherapy efficacy was 83.3% (10/12) in the patients of HER2 positive expression and 43.9% (18/41) in the patients of HER2 negative expression. The former was significant higher than the latter (P=0.016). Response rate of patients with P53 positive expression was 35.7% (10/28), significantly lower than 72.0% (18/25) of those with P53 negative expression (P=0.008). Six patients with both HER2 positive expression and P53 negative expression showed better efficacy. The expressions of C-met, EGFR, Ki-67, MMP7 and TOPOII were not associated with response to neoadjuvant chemotherapy (P>0.05). HER2 and P53 were independent influencing factors of neoadjuvant chemotherapy (P<0.05).

CONCLUSIONExpressions of HER2 and P53 have great value in the prediction of mFOLFOX7 neoadjuvant chemotherapy efficacy, suggesting that as independent factors, HER2 and P53 may be used to predict the efficacy before chemotherapy.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Chemotherapy, Adjuvant ; Female ; Fluorouracil ; therapeutic use ; Humans ; Leucovorin ; therapeutic use ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Organoplatinum Compounds ; therapeutic use ; Receptor, ErbB-2 ; metabolism ; Stomach Neoplasms ; drug therapy ; metabolism ; Treatment Outcome ; Tumor Suppressor Protein p53 ; metabolism

Biomarkers, Tumor ; genetics ; metabolism ; Carcinoma, Transitional Cell ; genetics ; metabolism ; pathology ; Cyclin-Dependent Kinase Inhibitor p27 ; metabolism ; Humans ; Ki-67 Antigen ; metabolism ; Microsatellite Repeats ; Mutation ; Neoplasm Grading ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; Pathology, Molecular ; Receptor, Fibroblast Growth Factor, Type 3 ; genetics ; metabolism ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Urinary Bladder Neoplasms ; genetics ; metabolism ; pathology

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Basigin ; analysis ; Biomarkers, Tumor ; analysis ; genetics ; Carcinoma, Transitional Cell ; drug therapy ; genetics ; metabolism ; Gene Expression Profiling ; Humans ; In Situ Hybridization, Fluorescence ; Inhibitor of Apoptosis Proteins ; analysis ; Mutation ; Neoplasm Recurrence, Local ; metabolism ; Nuclear Proteins ; analysis ; Receptor, Fibroblast Growth Factor, Type 3 ; analysis ; genetics ; Tumor Suppressor Protein p53 ; analysis ; genetics ; Urinary Bladder Neoplasms ; drug therapy ; genetics ; metabolism