OTUD4: A Potential Prognosis Biomarker for Multiple Human Cancers.

Background: Deubiquitinase OTU domain containing 4 (OTUD4) is initially identified as a K48-specific deubiquitinase and plays an important role in DNA damage repair signaling transduction. However, the expression level, prognostic role, biological function and mechanism of OTUD4 in multiple human cancers are unclear.

Methods: GEPIA online (http://gepia.

Knockdown of XB130 restrains cancer stem cell-like phenotype through inhibition of Wnt/β-Catenin signaling in breast cancer.

The cancer stem cells (CSCs) is a subset of cancer cells that possess stem cell properties, which plays a crucial role in the occurrence, metastasis, and recurrence of the tumor. XB130 is a novel adapter protein potentially serves as a functional factor in CSCs. To determine the role of CSCs in breast cancer, we focused on the study of XB130.

Downregulation of MMSET impairs breast cancer proliferation and metastasis through inhibiting Wnt/β-catenin signaling.

Background: Recently, the biggest challenge in the treatment of breast cancer is the metastasis of breast cancer cells. Multiple myeloma SET protein (MMSET), a histone lysine methyltransferase, overexpressed in various human cancers, was reported to be associated with carcinogenesis of human cancers.

Methods: Expression of MMSET in breast cancer cell lines and tissues was quantified by real-time PCR and Western blotting.

CHP2 Promotes Cell Proliferation in Breast Cancer via Suppression of FOXO3a.

Calcineurin B homologous protein isoform 2 (CHP2), an essential cofactor for Na/H exchanger isoform 1 (NHE1), is identified to be expressed in various malignant cell lines. However, the clinical significance and biological role of CHP2 in breast cancer remain to be established. Here, CHP2 was markedly overexpressed in breast cancer cells and clinical tumor specimens.

TRIP6 promotes cell proliferation in hepatocellular carcinoma via suppression of FOXO3a.

Thyroid hormone receptor-interacting protein 6 (TRIP6), a member of LIM family, acts as an adaptor protein and is overexpressed in several tumor types. However, the clinical significance and biological role of TRIP6 in HCC remains unknown. In our study, we found that TRIP6 was markedly overexpressed in HCC cells and clinical specimens compared with normal hepatocytes and adjacent non-tumor tissues.

Human Adenovirus Serotype 3 Vector Packaged by a Rare Serotype 14 Hexon.

Recombinant adenovirus serotype 3 (rAd3), which infects cells through the receptor desmoglein 2 (DSG2), has been investigated as a vector for gene therapy or vaccination. However, pre-existing anti-vector immunity may limit the practical application of rAd3. In this study, we investigated the seroprevalence and neutralizing antibody (NAb) titers to Ad3 and alternate serotypes in normal healthy adults in southern China.

Prevalence of neutralizing antibodies to common respiratory viruses in intravenous immunoglobulin and in healthy donors in southern China.

Background: Acute respiratory infections (ARIs) are a leading cause of death among children under the age of 5. However, there are no effective drugs for most of these severe viral infections. Passive immunotherapy with convalescent plasma or hyperimmune intravenous immunoglobulin (H-IVIG) is a potential therapeutic option for serious viral infections.

Mapping the epitope of neutralizing monoclonal antibodies against human adenovirus type 3.

Human adenovirus type 3 (HAdV-3) has produced a global epidemic in recent years causing serious diseases such as pneumonia in both pediatric and adult patients. Development of an effective neutralizing monoclonal antibody (MAb) and identification of its neutralizing epitope is important for the control of HAdV-3 infection. In this study, three neutralizing MAbs were generated, of which MAb 3D7 had a high neutralization titer of 4096 (approximately 0.

Antigenic variability among two subtypes of human adenovirus serotype 7.

Human adenovirus type 7 (HAdV-7) is one of the major serotypes responsible for acute respiratory infection. It is important to investigate the antigenic variabilities of different HAdV-7 genomic subtypes for vaccine development. Phylogenetic analysis of global HAdV-7 strains and major antigen proteins showed that HAdV-7 could be classified into two subtypes.

Construction and characterization of a recombinant human adenovirus type 3 vector containing two foreign neutralizing epitopes in hexon.

The "antigen capsid-incorporation" strategy has been developed for adenovirus-based vaccines in the context of several diseases. Exogenous antigenic peptides incorporated into the adenovirus capsid structure can induce a robust and boosted antigen-specific immune response. Recently, we sought to generate a multivalent adenovirus type 3 (Ad3) vaccine vector by incorporating multiple epitopes into the major adenovirus capsid protein, hexon.

Protection against enterovirus 71 with neutralizing epitope incorporation within adenovirus type 3 hexon.

Enterovirus 71 (EV71) is responsible for hand, foot and mouth disease with high mortality among children. Various neutralizing B cell epitopes of EV71 have been identified as potential vaccine candidates. Capsid-incorporation of antigens into adenovirus (Ad) has been developed for a novel vaccine approach.

Pyridine-derived γ-secretase modulators.

SAR of a novel series of pyridine-derived γ-secretase modulators is described. Compound 5 was found to be a potent modulator in vitro, which on further profiling, was found to decrease Aβ42 and Aβ40, and maintain (or increase) the levels of total Aβ. Furthermore, representative compounds 1 and 5 demonstrated in vivo efficacy to lower Aβ42 in the brain without altering Notch processing in the peripheral.

Construction and characterization of human adenovirus serotype 3 packaged by serotype 7 hexon.

Human adenovirus serotype 3 (Ad3) and serotype 7 (Ad7) are important pathogens causing respiratory tract diseases such as acute respiratory disease in pediatric and adult patients, but the immunodominant targets of Ad3- and Ad7-specific neutralizing antibodies (NAbs) remain unclear. A chimeric Ad vector, Ad3/H7, was constructed by replacing the Ad3 hexon gene (H3) with the hexon gene (H7) of Ad7. The chimeric viruses were successfully rescued in HEp-2 cells, and the Ad7 hexon was able to encapsidate the Ad3 genome, and functioned as efficiently as the Ad3 hexon.

Complete genome analysis of a novel E3-partial-deleted human adenovirus type 7 strain isolated in Southern China.

Human adenovirus (HAdV) is a causative agent of acute respiratory disease, which is prevalent throughout the world. Recently there are some reports which found that the HAdV-3 and HAdV-5 genomes were very stable across 50 years of time and space. But more and more recombinant genomes have been identified in emergent HAdV pathogens and it is a pathway for the molecular evolution of types.

Tricyclic compounds containing nonenolizable cyano enones. A novel class of highly potent anti-inflammatory and cytoprotective agents.

Forty-four novel tricycles containing nonenolizable cyano enones (TCEs) were designed and synthesized on the basis of a semisynthetic pentacyclic triterpenoid, bardoxolone methyl, which is currently being developed in phase II clinical trials for the treatment of severe chronic kidney disease in diabetic patients. Most of the TCEs having two different kinds of nonenolizable cyano enones in rings A and C are highly potent suppressors of induction of inducible nitric oxide synthase stimulated with interferon-γ and are highly potent inducers of the cytoprotective enzymes heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Among these compounds, (±)-(4bS,8aR,10aS)-10a-ethynyl-4b,8,8-trimethyl-3,7-dioxo-3,4b,7,8,8a,9,10,10a-octahydrophenanthrene-2,6-dicarbonitrile ((±)-31) is the most potent in these bioassays in our pool of drug candidates including semisynthetic triterpenoids and synthetic tricycles.

Construction and characterization of a replication-competent human adenovirus type 3-based vector as a live-vaccine candidate and a viral delivery vector.

In southern China, as well as in neighboring Asian regions, human adenovirus type 3 (HAdV-3) outbreaks have become very prevalent in recent years. To address this problem regionally and globally, a recombinant virus has been constructed, containing a full-length infectious genomic clone of HAdV-3, to act as a vaccine. This was constructed by using a bacterial homologous recombination mechanism and was based on the cloning, manipulation and maintenance of the full-length adenovirus genome as a stable plasmid in E.

[Epidemiological study of human type 5 adenovirus in Guangzhou using chemiluminescence for neutralizing antibody assay].

Objective: To establish a high-throughput chemiluminescence assay of serotype 5 specific neutralizing antibody and understand the epidemiology of this antibody in the healthy adults and children in Guangzhou.

Methods: Using rAd5 carrying the reporter gene of secreted alkaline phosphatases (SEAP), serum samples from 116 healthy adults and 94 healthy children were examined with chemiluminescence assay to detect the presence of Ad5 neutralizing antibody. The reliability of this assay was tested against conventional cytopathic effect observation.

Promoter hypermethylation of multiple genes in gastric lymphoma.

Aberrant hypermethylation of CpG islands in the promoter region of tumor suppressor and other important genes in neoplastic cells of lymphoma has been demonstrated to be one of the mechanisms for epigenetic loss of gene function. In this study, we analyzed promoter hypermethylation of the following genes in 49 cases of primary gastric lymphoma (PGL): ATM, p16INK4a(CDKN2A), hMLH1, MGMT, DAPK, and CDH1(ECAD). The PGL cases studied included 26 (53%) cases of diffuse large B-cell lymphoma (DLBCL), 12 (25%) cases of extranodal marginal zone lymphoma (MZL), 7 (14%) cases of MZL with large cell transformation (MZL/DLBCL), 1 (2%) case of follicular lymphoma (FL), one (2%) case of Burkitt-like lymphoma (BL), one case (2%) of lymphoplasmacytic lymphoma (LPL) and one case (2%) of peripheral T-cell lymphoma.

Promoter hypermethylation for molecular nodal staging in non-small cell lung cancer.

Context: Even among cases of non-small cell lung cancer (NSCLC) in the most favorable stage (IA), the disease-specific mortality is 25% or greater. One plausible explanation implicates the simplistic standard pathologic procedures used to designate lymph node involvement. A more sensitive assessment of the nodal status may improve staging.

Novel tricyclic compounds having acetylene groups at C-8a and cyano enones in rings A and C: highly potent anti-inflammatory and cytoprotective agents.

Novel C-8a functionalized tricyclic compounds having cyano enones in rings A and C have been synthesized and biologically evaluated. Among them, compounds with acetylene groups at C-8a show extremely high potency in in vitro and in vivo bioassays for anti-inflammatory and cytoprotective activities. Both in vitro and in vivo potencies are markedly higher than those of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), which is being evaluated as an anticancer drug in phase I clinical trials.

Design, synthesis, and anti-inflammatory activity both in vitro and in vivo of new betulinic acid analogues having an enone functionality in ring A.

Fifteen new betulinic acid analogues were designed, synthesized, and tested for anti-inflammatory activity. Many of these analogues effectively suppress nitric oxide (NO) production in RAW cells stimulated with interferon-gamma. Analogue 10 is highly and orally active in vivo for induction of the anti-inflammatory and cytoprotective enzyme, heme oxygenase-1.

Comparative genomic analysis of two strains of human adenovirus type 3 isolated from children with acute respiratory infection in southern China.

Human adenovirus type 3 (HAdV-3) is a causative agent of acute respiratory disease, which is prevalent throughout the world, especially in Asia. Here, the complete genome sequences of two field strains of HAdV-3 (strains GZ1 and GZ2) isolated from children with acute respiratory infection in southern China are reported (GenBank accession nos DQ099432 and DQ105654, respectively). The genomes were 35,273 bp (GZ1) and 35,269 bp (GZ2) and both had a G+C content of 51 mol%.

Methylation profiling of archived non-small cell lung cancer: a promising prognostic system.

Purpose: Enhanced prognostication power is becoming more desirable in clinical oncology. In this study, we explored the prognostic potential of multigene hypermethylation profiling in non-small-cell lung cancer.

Experimental Design: We evaluated a panel of eight genes (p16, APC, ATM, hMLH1, MGMT, DAPK, ECAD, and RASSF1A) using methylation-specific PCR in 105 archived specimens of non-small-cell lung cancer representing all stages of the illness.

Involvement of p53 and p16 tumor suppressor genes in recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma.

Recessive dystrophic epidermolysis bullosa (RDEB) is an autosomal recessive disorder characterized by the loss of collagen type VII, an intrinsic component of the anchoring fibrils, which attach the epidermis to the dermis. Of the genetic blistering disorders, RDEB has the highest rate of morbidity and mortality, with morbidity arising from fusion of digits in a mitten-glove deformity and growth retardation associated with anemia. The leading cause of death in RDEB is cutaneous squamous cell carcinoma, which causes death through invasion and metastasis.