A5033630409- Immune Cell Function and Interaction
- HIV Research and Treatment
- TGF-β signaling in diseases
- Monoclonal and Polyclonal Antibodies Research
- Bone Metabolism and Diseases
- Cancer Immunotherapy and Biomarkers
- Growth Hormone and Insulin-like Growth Factors
- HIV/AIDS drug development and treatment
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Hepatitis B Virus Studies
- Cytokine Signaling Pathways and Interactions
- Metabolism, Diabetes, and Cancer
- Hepatitis C virus research
- Bone health and treatments
- CAR-T cell therapy research
- Immune cells in cancer
- Chemical Synthesis and Analysis
- Bacteriophages and microbial interactions
- Cancer, Hypoxia, and Metabolism
- NF-κB Signaling Pathways
- Estrogen and related hormone effects
- Protein Kinase Regulation and GTPase Signaling
- Prostate Cancer Treatment and Research
- Pancreatic and Hepatic Oncology Research
Second Hospital of Shandong University
2022-2025
Pfizer (United States)
2017-2024
Jiangnan University
2022
Erasmus MC
2019
National Institute for Public Health and the Environment
2019
La Roche College
2006-2016
Roche (China)
2015
Roche (Switzerland)
2006-2015
Roche (United States)
2007-2013
Singapore Institute for Clinical Sciences
2012
In addition to being an important receptor in leukocyte activation and mobilization, CCR5 is the essential coreceptor for human immunodeficiency virus (HIV). A large number of small-molecule antagonists have been reported that show potent activities blocking chemokine function HIV entry. To facilitate design development next generation antagonists, docking models major classes were created by using site-directed mutagenesis homology modeling. Five clinical candidates: maraviroc, vicriviroc,...
Immune checkpoint inhibitors (ICI) targeting PD1, PDL1, or CTLA4 are associated with immune-related adverse events (irAE) in multiple organ systems including myocarditis. The pathogenesis and early diagnostic markers for ICI-induced myocarditis poorly understood, there is currently a lack of laboratory animal model to enhance our understanding. We aimed develop such using cynomolgus monkeys.Chinese-origin monkeys were dosed intravenously vehicle nivolumab 20 mg/kg plus ipilimumab 15 once...
Glucocorticoid in excess suppresses bone formation vivo and disrupts matrix protein synthesis by osteoblasts vitro. In contrast, transforming growth factor β (TGF-β) potently enhances apposition. The rat TGF-β type I receptor gene promoter contains cis-acting elements for transcription CBFa1, which increases parallel with osteoblast differentiation. Here we present molecular data linking these events. We show that previously unexplained effects of glucocorticoid on loss may be mediated part...
Abstract The use of cytokines for immunotherapy shows clinical efficacy but is frequently accompanied by severe adverse events caused excessive and systemic immune activation. Here, we set out to address these challenges engineering a fusion protein single, potency-reduced, IL15 mutein PD1-specific antibody (anti-PD1-IL15m). This immunocytokine was designed deliver PD1-mediated, avidity-driven IL2/15 receptor stimulation PD1+ tumor-infiltrating lymphocytes (TIL) while minimally affecting...
Abstract Background Neoadjuvant chemotherapy (NAC) has become a standard treatment strategy for breast cancer (BC). However, owing to the high heterogeneity of these tumors, it is unclear which patient population most likely benefit from NAC. Multi-omics offer an improved approach uncovering genomic and transcriptomic changes before after NAC in BC identifying molecular features associated with sensitivity. Methods We performed whole-exome RNA sequencing on 233 samples (including matched...
In this study, we describe novel tetravalent, bispecific antibody derivatives that bind two different epitopes on the HIV coreceptor CCR5. The basic protein formats applied were derived from Morrison-type antibodies: whole IgGs to which connected single-chain antibodies (scFvs) via (Gly4Ser)n sequences at either C or N terminus of light chain heavy chain. By design optimization, including disulfide stabilization scFvs introduction 30-amino-acid linkers, stable molecules could be obtained in...
Cancer cells harness immune checkpoints such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO1) to evade control. Checkpoint inhibitors have demonstrated durable anti-tumor efficacy in human preclinical models. Liver toxicity is one of the common immune-related adverse events associated with checkpoint (CPIs) its frequency severity often increase significantly during CPI combination therapies. We aim develop a mouse...
Purpose To analysis the correlation between EGFR mutations and clinicopathological features in lung adenocarcinomas. Methods 139 adenocarcinoma cases from Second Hospital of Shandong University were conducted molecular detection mutations. Multiple characteristics collected analyzed to identify relationship with The amplification refractory mutation system (ARMS) was performed detect Results During cases, 96 had associated smoking history (P=0.0311), tumor size (P=0.0247), subtype...
Organization of the transforming growth factor-beta (TGF-beta) type I receptor (TRI) promoter predicts constitutive transcription, although its activity increases with differentiation status in cultured osteoblasts. Several sequences rat TRI comprise cis-acting elements for CBFa (AML/PEBP2alpha) transcription factors. By gel mobility shift and immunological analyses, a principal osteoblast-derived nuclear factor that binds to these sites is CBFa1 (AML-3/PEBP2alphaA). Rat levels parallel...
Enzalutamide and apalutamide are two androgen receptor inhibitors approved for the treatment of castration-resistant prostate cancer (CRPC) nonmetastatic (nmCRPC), respectively. Apalutamide is associated with an increased incidence skin rash above placebo groups in SPARTAN trial nmCRPC TITAN metastatic castration-sensitive patients. On contrary, rate across all clinical trials (including PROSPER [nmCRPC]) enzalutamide similar to placebo. We hypothesized that apalutamide-associated patients...
Insulin-like growth factor-I (IGF-I) is a key factor in bone remodeling. In osteoblasts, IGF-I synthesis enhanced by parathyroid hormone and prostaglandin E<sub>2</sub>(PGE<sub>2</sub>) through cAMP-activated protein kinase. rats, estrogen loss after ovariectomy leads to rise serum an increase remodeling, both of which are reversed treatment. To examine estrogen-dependent regulation expression at the molecular level, primary fetal rat osteoblasts were co-transfected with receptor (hER,...
Transcription factor CCAAT/enhancer-binding protein δ (C/EBPδ) is normally associated with acute-phase gene expression. However, it expressed constitutively in primary osteoblast cultures where increases insulin-like growth I synthesis a cAMP-dependent way. Here we show that the 3′ proximal region of C/EBPδ promoter contains binding sequence for Runt domain Runx2, which essential osteogenesis. This directed high reporter expression osteoblasts, and specifically bound Runx2 osteoblast-derived...
Insulin-like growth factor-I (IGF-I) plays a key role in skeletal by stimulating bone cell replication and differentiation. We previously showed that prostaglandin E2 (PGE2) other cAMP-activating agents enhanced IGF-I gene transcription cultured primary rat osteoblasts through promoter 1, the major promoter, identified short segment of termed HS3D, was essential for hormonal regulation expression. now demonstrate CCAAT/enhancer-binding protein (C/EBP) δ is component PGE2-stimulated...
Maximal gene expression driven by the promoter for transforming growth factor β type I receptor (TGF-βRI) occurs with a 1.0-kilobase pair fragment immediately upstream of exon 1. This region lacks typical TATA box but contains CCAAT boxes, multiple Sp1, and PEBP2/CBFα binding sites among other possiblecis-acting elements. Alterations within two sequences do not mitigate reporter basal promoter, no nuclear binds to oligonucleotides encompassing these sites. In contrast, deletions or...
During antiviral therapy, specific delivery of interferon-α (IFNα) to infected cells may increase its efficacy, trigger a localized immune reaction, and reduce the side effects caused by systemic administration. Two T-cell receptor-like antibodies (TCR-L) able selectively bind hepatitis B virus (HBV)-infected hepatocytes chronic patients recognize core (HBc18-27) surface (HBs183-91) HBV epitopes associated with different human leukocyte antigen (HLA)-A*02 alleles (A*02:01, A*02:02, A*02:07,...
A panel of four CCR5 monoclonal antibodies (mAbs) recognizing different epitopes on was examined in CCR5-mediated cell-cell fusion assay, alone or combination with a variety small molecule antagonists. Although no antagonism observed between any the inhibitors, surprisingly potent synergy mAbs and antagonists, synergistic activity confirmed other antiviral assays. Strong also inhibitors human immunodeficiency virus (HIV) inhibitor enfuvirtide. There inhibitors; however, parts CCR5. In all...
CD81 is a required receptor for hepatitis C virus (HCV) infection of human hepatocytes in vitro . We generated several high‐affinity anti‐human monoclonal antibodies (mAbs) that demonstrated potent, specific, and cross‐genotype inhibition HCV entry. One these mAbs, K04, was administered to liver chimeric mice before or after determine its ability prevent spread infection, respectively. All vehicle control established reaching steady‐state levels serum RNA by day 21. Pretreatment with K04...
Insulin-like growth factor-I (IGF-I) plays a major role in promoting skeletal by stimulating bone cell replication and differentiation. Prostaglandin E2 other agents that induce cAMP production enhance IGF-I gene transcription cultured rat osteoblasts through DNA element termed HS3D, located the proximal part of promoter. We previously determined CCAAT/enhancer-binding protein δ (C/EBPδ) is key cAMP-stimulated regulator these cells showed it transactivates promoter HS3D site. now have...
Abstract Glucocorticoid has complex effects on osteoblasts. Several of these changes appear to be related steroid concentration, duration exposure, or specific growth factor expression activity within bone. One important bone factor, insulin-like I (IGF-I), is induced in osteoblasts by hormones such as PGE2 that increase intracellular cAMP levels. In this way, activates transcription CCAAT/enhancer-binding protein-δ (C/EBPδ) and enhances its binding a control element found exon 1 the IGF-I...
The proportion of transforming growth factor-β (TGF-β) binding among conventional membrane receptors on bone cells can vary with hormone or factor treatment the state osteoblast-like activity and appears to determine nature its biological effects. Therefore, functional TGF-β receptor stability could be an important aspect regulation. Suppression protein synthesis reduced types I II t1/2 2 h betaglycan 6 h. In contrast, suppression mRNA transcription at least 3-fold more slowly each site....
PF-07209960 is a novel bispecific fusion protein composed of an anti-PD-1 antibody and engineered IL-15 cytokine mutein with reduced binding affinity to its receptors. The pharmacokinetics (PK), pharmacodynamics (PD), toxicity were evaluated following once every other week subcutaneous (SC) or intravenous (IV) administration cynomolgus monkeys in repeat-dose PKPD (0.01–0.3 mg/kg/dose) GLP study (0.1–3 mg/kg/dose). showed dose dependent terminal T1/2 8 13 hours IV at 0.03 0.1 mg/kg,...
<sec><b>Objective</b>Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2 (HER2)-positive (+) breast cancer patients and remains a clinical challenge. Pyrotinib is novel tyrosine kinase inhibitor that has shown efficacy the treatment of HER2+ cancer. However, pyrotinib with primary unknown. </sec><sec><b>Methods</b>HER2+ cells sensitive or primarily resistant were treated trastuzumab, pyrotinib, combination. Cell proliferation, migration, invasion,...