Abstract Oncogenic Ras mutants, frequently detected in human cancers, are high-priority anticancer drug targets. However, direct inhibition of oncogenic mutants with small molecules has been extremely challenging. Here we report the development a IgG1 format antibody, RT11, which internalizes into cytosol living cells and selectively binds to activated GTP-bound form various block interactions effector proteins, thereby suppressing downstream signalling exerting anti-proliferative effects...

V-set and Ig domain-containing 4 (VSIG4, CRIg, or Z39Ig), a newly identified B7-related cosignaling molecule, is complement receptor coinhibitory ligand that negatively regulates T-cell immunity. Despite its exclusive expression on liver Kupffer cells (KCs) play key roles in tolerance, the physiological role of VSIG4 tolerance remains undefined. Mice lacking had poor survival rates severe pathology concanavalin A (ConA)-induced hepatitis (CIH) model, which could be prevented by adoptive...

The inhibitory effect of curcumin and its synergism with 5-fluorouracil (5-FU) on the growth AGS human gastric carcinoma cell line was examined. Cell cycle analysis used to elucidate mechanisms for inhibition by curcumin. Curcumin significantly inhibited cells in a dose- time-dependent manner (P < .05). caused 34% decrease proliferation at 5 μmol/L, 51% 10 92% 25 μmol/L after 4 days treatment. When (10 μmol/L) removed 24-hour exposure, pattern curcumin-treated similar that control cells,...

Abstract Regulatory T cells (Treg) are targeted for cancer immunotherapy because they suppress antitumor immunity. Although the importance of neuropilin-1 (NRP1) in stability and function intratumoral Tregs is well-documented, targeting NRP1+ anticancer has not been well explored. Here, we found that an NRP1 antagonist [Fc(AAG)-TPP11], generated by fusion NRP1-specific binding peptide TPP11 with C-terminus effector function–deficient immunoglobulin Fc(AAG) variant, inhibits Treg stability....

Redirecting pre-existing virus-specific cytotoxic CD8+ T lymphocytes (CTLs) to tumors by simulating a viral infection of the tumor cells has great potential for cancer immunotherapy. However, this strategy is limited lack amenable method antigen delivery into cytosol target tumors. Here, we addressed limit developing cell epitope-delivering antibody, termed TEDbody, which was engineered deliver MHC-I epitope peptide fusion with tumor-specific cytosol-penetrating antibody.To direct human...

ABSTRACT: Bacillus circulans, Brevibacillus brevis, B. licheniformis, coagulans, subtilis, and sterothermophillus were isolated identified from chungkukjangs (Korean traditional soybean paste fermented for a few day). Chungkukjang was prepared on laboratory scale with soybeans the strains. Characteristics of including slime material content, free amino acid sensory qualities, antimutagenicity determined. The content material, which is an important indicator quality chungkukjang, highest in...

The protein V-set and Ig domain-containing 4 (VSIG4), a novel B7 family-related macrophage with the capacity to inhibit T-cell activation, has potential role in cancer. Here we suggest its possibility as therapeutic target prognostic biomarker of ovarian cancer.Between January 2011 June 2015, tumor tissues peripheral blood samples were obtained during surgery from 10 patients benign tumors 22 cancers. Messenger RNA expression levels VSIG4 cancer examined by reverse transcription polymerase...

Development of antagonistic antibody (Ab) against interleukin-4 receptor alpha (IL-4Rα) subunit IL-4/IL-13 receptors is a promising therapeutic strategy for T helper 2 (TH2)-mediated allergic diseases such as asthma and atopic dermatitis. Here we isolated anti-human IL-4Rα Abs from large yeast surface-displayed human Ab library further engineered their complementarity-determining regions to improve the affinity using display technology, finally generating candidate Ab, 4R34.1.19. When...

Interleukin-12 (IL12) (p35/p40 complex) is a heterodimeric cytokine with potent anti-tumor activity. However, its short serum half-life and high dose-related toxicities limit clinical efficacy. Here, we constructed immunoglobulin Fc-fused mouse IL12 (mIL12) in monovalent binding format (mono-mIL12-Fc) to generate long-acting mIL12 the naturally occurring form. Mono-mIL12-Fc exhibited much longer plasma than recombinant mIL12, enabling twice-weekly systemic injections remove established...

The kind of salt used in doenjang preparation is one the most important factors that affect chemopreventive activities doenjang. Bamboo (BS) known to exert various therapeutic effects on several diseases. In this study, antimutagenic and anticlastogenic methanol extracts made with either one-time heat-treated BS (BS1-D), nine-times (BS9-D), sun-dried (SDS-D), or purified (PS-D) using Ames test micronucleus test. BS1-D BS9-D showed higher inhibitory than PS-D SDS-D mutagenicity induced by...

West Nile virus (WNV) has emerged globally as an increasingly important pathogen for humans and domestic animals. Studies of the evolutionary diversity over its known history will help to elucidate conserved sites, characterize their correspondence other pathogens relevance immune system. We describe a large-scale analysis entire WNV proteome, aimed at identifying characterizing evolutionarily amino acid sequences. This study, which used 2,746 protein sequences collected from NCBI GenPept...

Patients with severe eosinophilic asthma (SEA; characterized by persistent eosinophilia in blood and airway tissues) experience frequent exacerbations poor clinical outcomes. Interleukin 5 (IL-5) IL-5 receptor alpha subunit (IL-5α) play key roles maintenance, relevant therapeutic strategies include the development of antibodies (Abs) against or IL-5α to control eosinophilia. Benralizumab, an anti–IL-5α Ab that depletes eosinophils mainly via Ab-dependent cell-mediated cytotoxicity through...

Tumor-targeting antibody (Ab)-fused cytokines, referred to as immunocytokines, are designed increase antitumor efficacy and reduce toxicity through the tumor-directed delivery of cytokines. However, poor localization intratumoral penetration especially in solid tumors, pose a challenge effectively stimulate immune cells kill tumor within microenvironment. Here, we investigated influence antigen-binding kinetics murine interleukin 12 (mIL12)-based immunocytokine on diffusive penetration,...

This report describes the identification and bioinformatics analysis of HLA-DR4-restricted HIV-1 Gag epitope peptides, application dendritic cell mediated immunization DNA plasmid constructs. BALB/c (H-2d) HLA-DR4 (DRA1*0101, DRB1*0401) transgenic mice were immunized with immature cells transfected by a recombinant encoding lysosome-associated membrane protein-1/HIV-1 (pLAMP/gag) chimera antigen. Three protocols compared: 1) primary subcutaneous 1×105 electroporation pLAMP/gag plasmid,...

Phylogenetic relatedness and cocirculation of several major human pathogen flaviviruses are recognized as a possible cause deleterious immune responses to mixed infection or immunization call for greater understanding the inter-Flavivirus protein homologies. This study focused on identification leukocyte antigen (HLA)-restricted West Nile virus (WNV) T-cell ligands characterization their distribution in reported sequence data WNV other flaviviruses. H-2-deficient mice transgenic either A2,...

The Korean fermented vegetable food, kimchi, has been demonstrated to have anticancer functional properties. This study examined the effect of kimchi samples, methanol extracts commercially grown baechu cabbage (CK) and organically (OK), as well dichloromethane fraction (DCM fr.) from CK, active compound (AC), which identified largely β-sitosterol, DCM fr., on Ras-dependent signaling pathway. OK, fr. exhibited a greater inhibition against proliferation Rat2 fibroblasts transformed with...

The effects of kimchis intake on Helicobacter pylori infection in the stomach, counts lactic acid bacteria large intestine, and bacterial enzymes (β-glucosidase, β-glucuronidase) pH feces were examined. A total 20 participants (age range 34~57) assessed for H. status by ¹³C urea breath test. Fourteen eliminated because they pylori-negative. This study consisted 4 consecutive phase, each which lasted weeks. Three hundred grams kimchi administered to pylori-infected subjects during followed...