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 To explore the role of Nogo-A receptor antagonist NEP1-40 in regulating regeneration of neural cells and related Wnt signaling pathway in neonatal rats with hypoxic ischemic encephalopathy (HIBD).Methods A total of 40 HIBD rats were divided into HIBD group and HIBD + NEP1-40 group,20 rats in each group.PCR Test,Western Blot Analysis,IHC test for cell proliferation and 8-isoprostane detection were used to evaluate regulation of NgR transcription factors in Wnt signaling pathway and proliferation of neural cells.Results The expressions of c-Jun and cMyc,at the protein level,were up-regulated after treatment with Nogo-A receptor antagonist NEP1-40 for 7 days,and the same change was observed at gene expression and Ki-67.There was no significant change of 8-isoprostane.Conclusion The c-Jun and c-Myc are the main transcription factors in Wnt signaling pathway by inhibition of NgR,and meanwhile the proliferation of nerve cells in subventricular zone increase.

Objective To explore the role of Nogo-A receptor antagonist NEP1-40 in regulating regeneration of neural cells and related Wnt signaling pathway in neonatal rats with hypoxic ischemic encephalopathy (HIBD).Methods A total of 40 HIBD rats were divided into HIBD group and HIBD + NEP1-40 group,20 rats in each group.PCR Test,Western Blot Analysis,IHC test for cell proliferation and 8-isoprostane detection were used to evaluate regulation of NgR transcription factors in Wnt signaling pathway and proliferation of neural cells.Results The expressions of c-Jun and cMyc,at the protein level,were up-regulated after treatment with Nogo-A receptor antagonist NEP1-40 for 7 days,and the same change was observed at gene expression and Ki-67.There was no significant change of 8-isoprostane.Conclusion The c-Jun and c-Myc are the main transcription factors in Wnt signaling pathway by inhibition of NgR,and meanwhile the proliferation of nerve cells in subventricular zone increase.

OBJECTIVE: To detect the expression of ERβ in laryngeal carcinoma and the its correlation with the expression of epithelial-mesenchymal transition(EMT) specific biomarkers. METHOD: Picture MT-Pv9000 was used to detect ERβ and EMT in 72 cases of human aqueous laryngeal carcinoma and 8 cases of adjacent non-neoplastic laryngeal mucosa by immunohistochemistry. RESULT: The positive rates of ERβ in tumors and adjacent non-neoplastic laryngeal mucosa were 27.78% and 25.00%, respectively. The differences were not significant (P > 0.05). The abnormal expression rates of E-cadherin and β-catenin were 61.11% and 76.39% respectively. The expression of ERβ correlated negatively with the loss of E-cadherin, nuclear translocation of β-catenin and increased TNM stage. The differences were significant (P < 0.05). CONCLUSION The positive expressions of ERβ suggest a good prognosis in the differentiation, clinical stages and lymphatic metastasis of the laryngeal carcinoma. The underlying mechanism may be related with the abnormal expressions of E-cadherin and β-catenin.
Antigens, CD ; Biomarkers, Tumor ; metabolism ; Cadherins ; metabolism ; Epithelial-Mesenchymal Transition ; Estrogen Receptor beta ; metabolism ; Humans ; Immunohistochemistry ; Laryngeal Neoplasms ; metabolism ; Lymphatic Metastasis ; beta Catenin ; metabolism

Objective To investigate the expressions of AKT and ERK1/2 proteins in hypopharyngeal squamous cell carcinoma and normal hypopharyngeal mucosa. Methods The expressions of AKT and ERK1/2 proteins were exam-ined by immunohistochemical S-P technique in 60 patients with hypopharyngeal squamous cell carcinoma and 15 cases of normal hypopharyngeal mucosa . The relationship between expressions of AKT and ERK1/2 proteins and clinical pathologi-cal feathers was analyzed. Results The positive rates of the expressions of AKT and ERK1/2 were 78.3% (47/60) and 66.7%(40/60) in 60 cases of hypopharyngeal squamous cell carcinoma, which were significantly higher than those in 15 cas-es of normal hypopharyngeal mucosa [13.3%(2/15) and 6.7%(1/15), P<0.05]. The lower the degree of differentiation, the later the clinical stage, the higher the positive expression rates of AKT and ERK1/2. There were significantly higher expres-sions of AKT and ERK1/2 in patients with lymph node metastasis than those of patients without lymph node metastasis (P<0.05 or P<0.01). There was a positive correlation between expression levels of AKT and ERK1/2 (rs=0.400,P<0.05). Con-clusion There were higher expression levels of AKT and ERK1/2 in hypopharyngeal squamous cell carcinoma. The activa-tion of AKT and ERK1/2 proteins promotes hypopharyngeal occurrence, development and metastasis.

OBJECTIVE: to explore the relationship between the maxillary sinus volume and the amount of alveolar bone, and the effect of molar loss upon the maxillary sinus was further analyzed,by measuring adult maxillary sinus volume, sinus ridge distance, and calculating the gasification coefficient of maxillary sinus. METHOD: One hundred and ninety cases (361 maxillary sinus) with CT examinations were collected, they were divided into group A and group B, 121 cases (242 maxillary sinus) of normal subjects served as group A, 42 cases (65 maxillary sinus) with molar part off were B group, in which 31 maxillary sinus with a molar loss were group B1,22 maxillary sinus with two molar loss were B2 group,12 maxillary sinus with three molar loss (one molar remains) were B3 group, 27 cases (54 maxillary sinus) with upper teeth off were C group. Bymeasureing the maxillary sinus volume, sinus ridge distance and the size of the maxillary sinus, calculating the gasification coefficient, we analyzed the relationship between maxillary volume and sinus ridge distance, and comparatively analyzed the differences among the three groups in the size, gasification coefficient, volume of maxillary sinus and sinus ridge distance. RESULT: In the normal group,the volume of maxillary sinus and sinus ridge distance had a correlation coefficient of -0. 63,(P< 0.05); Sinus ridge distance in group A was larger than the other two groups (P<0.05), and larger in B group than in C group (P<0. 05), anteroposterior maxillary sinus diameter and reft-right diameter in C group was greater than in A group and B group(P<0.05), group C gasification coeffiecent was less than A group and B group (P<0. 05). CONCLUSION The volume of maxillary sinus is negatively correlated with the amont of alveolar bone; Upper teeth's shedding promotes maxillary sinus deformation; Maxiuary sinus volume has a tendency to decrease.
Adult ; Humans ; Maxilla ; Maxillary Sinus ; anatomy & histology ; diagnostic imaging ; Molar ; Radiography ; Tooth Loss

10.3969/j.issn.1007-3969.2013.05.002

OBJECTIVE: Evaluating the function of the internal jugular vein after selective neck dissection on patients affected by squamous cell carcinoma of the head and neck by color Doppler ultrasonography. METHOD: Forty patients (76 internal jugular veins) who had undergone bilateral selective neck dissection(36 patients) or unilateral selective neck dissection (4 patients) were collected and divided into 2 groups depending on operation area. Group A consisted of 39 internal jugular veins (IJVs) which dissected level II, III and group B included 37 IJVs which disseted level II - IVor II - V spring the IJV. All patients underwent Doppler ultrasonography before and after selective neck dissection at the 1st and 3rd postoperative months. The following measurements were assessed in each test: presence of thrombosis, expiratory jugular flow, expiratory caliber, area both during expiratory and Valsalva maneuver, expiratory flow speed, Valsalva flow speed. All data were statistically analyzed in two groups by comparisons of preoperative conditions and postoperative conditions. RESULT: (1) None of the 76 internal jugular veins showed thrombosis before or after selective neck dissection. (2) Patency rate at the 1st and 3rd postoperative months were respectively 85.5% and 96.1%. Patency rate of the internal jugular vein in two groups showed no significant changes at the 1st and 3rd postoperative months (P > 0.05). (3) In group A, Valsalva flow speed showed no significant changes at the 1st postoperative months (P > 0.05), compared with preoperative; The remainings showed significant difference. Expiratory calibe, area during Valsalva maneuve, expiratory flow speed and Valsalva flow speed had significant difference at the 3rd postoperative months (P < 0.05), compared with preoperative. In group B, Valsalva flow speed showed no significant changes at the 1st postoperative months (P > 0.05), compared with preoperative; The remainings showed significant difference. Expiratory jugular flow had no significant difference at the 3rd postoperative months (P > 0.05), compared with preoperative; The remainings showed significant difference. All parameters at the 3rd postoperative months had significant difference compared with 1st postoperative months between these two groups, excepting expiratory flow speed. (4) Differences of the operation area had no significant impact on indications of the internal jugular vein (P > 0.05). CONCLUSION (1) None of the internal jugular veins showed thrombosis after selective neck dissection. The results indicate that thrombosis of the internal jugular veins can be avoided though careful operation, proper operative skill, appropriate management postoperation. (2) Although most of the parameters changed at early stage after selective neck dissection, many of them improved at the 3rd postoperative months, and expiratory jugular flow recovered to the normal range. The results indicate that the internal jugular veins can basically maintain its normal function at long time postoperation.
Carcinoma, Squamous Cell ; surgery ; Head and Neck Neoplasms ; surgery ; Humans ; Jugular Veins ; diagnostic imaging ; physiology ; Neck Dissection ; adverse effects ; Postoperative Period ; Regional Blood Flow ; physiology ; Ultrasonography, Doppler ; Vascular Patency ; Venous Thrombosis ; prevention & control

Objective To investigate the hospitalized patients incidence of nutritional risk and nutritional support in six departments (general surgery, thoracic surgery, gastroenterology, neurology, urology and respirology) in a middle hospital and in the medical/surgical departments in a small hospital, so provide reference for rational nutritional support for patients. Method Nutritional Risk Screening 2002 was used to assess the existence of nutritional risk and the necessity of nutritional support. Results The overall prevalence of the nutrition risk was 25% in the six departments in the middle hospital; more specifically, the prevalence of nutrition risk arranged from 18% to 31% in these six departments: 31% in the department of respiratory medicine, 29% in the department of neurology, 27% in the department of urology, 23% in the department of thoracicsurgery, 22% in the department of gastroenterology, and 18% in the department of general surgery. For those at nutritional risk, the nutritional support rate was 24%. For non-risky patients, 9% received nutritional support. The overall prevalence of nutrition risk was 18% in the small hospital; more specifically, the prevalence of nutrition risk was 29% in the department of internal medicine and 7% in the department of surgery. For those at nutritional risk, the nutritional support rate was 24%.For non-risky patients, the nutritional support rate was 4%. Conclusions Certain nutritional risk and malnutrition exist in inpatients in the middle and small hospitals in Shijiazhuang. The applications of parenteral and enteral nutritions still have some problems. It is of particular importance to further promote the application of evidence-based parenteral/enteral nutrition guidelines in middle and small hospitals to standardize the application of nutritional support.

Objective To construct a recombinant adenoviral vector carrying and co-expressing human inhibitor of growth 4(ING4) and human interleukin-24(IL-24) mediated by poly( A)-Promoter[Ad-ING4-poly(A)-Promoter-IL-24, referred to as Ad-ING4-IL-24] and explore its effect on the growth of HepG-2 human hepatocellular carcinoma cellsin vitro. Methods The poly(A)-Promoter(hEFl-elF4g) (Sal Ⅰ and Not Ⅰ ), ING4 ( Bgl Ⅱ and Sal Ⅰ ), and IL-24 ( Xho Ⅰ and Xba Ⅰ ) fragments were amplified by PCRusing pORF-mbcl-2α, pcDNA3.0-IL-24, and pcDNA3.0-ING4 plasmids as templates and subcloned into pAdTrack-CMV transfer vector to form pAdTrack-CMV-ING4-poly (A)-Promoter-lL-24, respectively. The pAdTrack-CMV-ING4-poly (A)-Promoter-IL-24 transfer vector linearized with Pme Ⅰ digestion and pAdEasy-1 backbone vector was further cotransformed into the bacteria BJ5183 competent cells for homologous recombination. The resultant pAdEasy-l-pAdTrack-CMV-ING4-poly ( A )-Promoter-IL-24 homologous recombinant plasmids were linearized with Pac Ⅰ digestion and transfected into the human embryonic kidney 293 (QBI-293A) cells by liposome, leading to formation of the recombinant adenoviruses Ad-ING4-IL-24co-expressing ING4 and IL-24. The Ad-ING4-IL-24 were amplified in QBI-293A cells and its titer was up to 3.5 × 109 PFU/ml. Adenovirus-mediated ING4 and IL-24 genes expression in HepG-2 cells was examined by RT-PCR and Western blot. The growth-suppressing and apoptosis-inducingg effect of Ad-ING4-IL-24 coexpressing ING4 and IL-24 on HepG-2 human hepatocellular carcinoma cells was assessed by MTT assay and FCM, respectively. Results DNA sequencing showed that the ING4, poly (A)-Promoter, and IL-24 fragments subcloned into pAdTrack-CMV plasmids were completely identical to those reported in GenBank.ING4 and IL-24 gene mediated by adenovirus could both successfully express in HepG-2 cells. Adenovirusmediated ING4 and IL-24 co-expression significantly suppressed HepG-2 hepatocellular carcinoma cell growth and induced cell apoptosis, and the effect of Ad-ING4-IL-24 group was more significant than AdING4 and Ad-IL-24 group. Conclusion The adenoviral vector co-expressing ING4 and IL-24 mediated by poly(A)-Promoter(Ad-ING4-IL-24) was successfully constructed. Ad-ING4-IL-24 had marked anti-tumor effect in suppressing HepG-2 human hepatocellular carcinoma cell growth and inducing cell apoptosis in vitro. Compared with Ad-ING4 and Ad- IL-24, Ad-ING4-IL-24 enhanced anti-tumor effect.