A5100346580- Cancer Immunotherapy and Biomarkers
- Chronic Lymphocytic Leukemia Research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Lymphoma Diagnosis and Treatment
- Immune cells in cancer
- PI3K/AKT/mTOR signaling in cancer
- CAR-T cell therapy research
- Cancer-related Molecular Pathways
- Melanoma and MAPK Pathways
- Monoclonal and Polyclonal Antibodies Research
- PARP inhibition in cancer therapy
- Cell death mechanisms and regulation
- Cancer Cells and Metastasis
- Cancer Mechanisms and Therapy
- RNA Interference and Gene Delivery
- DNA Repair Mechanisms
- Glioma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Computational Drug Discovery Methods
- Synthesis and biological activity
- Copper-based nanomaterials and applications
- Plant Micronutrient Interactions and Effects
- Polyamine Metabolism and Applications
- Multiple Sclerosis Research Studies
BeiGene (China)
2015-2024
South China University of Technology
2024
Nanjing University of Chinese Medicine
2024
University of Amsterdam
2024
Amsterdam University Medical Centers
2024
Renji Hospital
2024
Shanghai Jiao Tong University
2024
Nanjing Drum Tower Hospital
2024
Tianjin Medical University General Hospital
2023
First Hospital of China Medical University
2023
Aberrant activation of Bruton's tyrosine kinase (BTK) plays an important role in pathogenesis B-cell lymphomas, suggesting that inhibition BTK is useful the treatment hematological malignancies. The discovery a more selective on-target covalent inhibitor high value. Herein, we disclose and preclinical characterization potent, selective, irreversible as our clinical candidate by using vitro potency, selectivity, pharmacokinetics (PK), vivo pharmacodynamic for prioritizing compounds. Compound...
Abstract Purpose: Glioblastoma is the most aggressive primary brain tumor in adults with a median survival of 15–20 months. Numerous approaches and novel therapeutics for treating glioblastoma have been investigated setting phase III clinical trials, including recent analysis immune checkpoint inhibitor, nivolumab (anti-PD-1), which failed to improve recurrent patient survival. However, rather than abandoning inhibitor treatment glioblastoma, has shown promise other types cancer, ongoing...
Abstract Venetoclax, the first-generation inhibitor of apoptosis regulator B-cell lymphoma 2 (BCL2), disrupts interaction between BCL2 and proapoptotic proteins, promoting in malignant cells. Venetoclax is mainstay therapy for relapsed chronic lymphocytic leukemia under investigation multiple clinical trials treatment various cancers. Although venetoclax can result high rates durable remission, relapse has been widely observed, indicating emergence drug resistance. The G101V mutation...
Pamiparib, an investigational Poly (ADP-ribose) polymerase (PARP) inhibitor in clinical development, demonstrates excellent selectivity for both PARP1 and PARP2, superb anti-proliferation activities tumor cell lines with BRCA1/2 mutations or HR pathway deficiency (HRD). Pamiparib has good bioavailability is 16-fold more potent than olaparib efficacy study using BRCA1 mutated MDA-MB-436 breast cancer xenograft model. also shows strong anti-tumor synergy temozolomide (TMZ), a DNA alkylating...
Poly (ADP-ribose) polymerase (PARP) plays a significant role in DNA repair responses; therefore, this enzyme is targeted by PARP inhibitors cancer therapy. Here we have developed number of fused tetra- or pentacyclic dihydrodiazepinoindolone derivatives with excellent enzymatic and cellular PARylation inhibition activities. These efforts led to the identification pamiparib (BGB-290, 139), which displays PARP-1 PARP-2 IC50 1.3 0.9 nM, respectively. In assay, compound inhibits activity = 0.2...
Programmed cell death protein 1 (PD-1), an immune checkpoint receptor expressed by activated T, B, and NK cells, is a well-known target for cancer immunotherapy. Tislelizumab (BGB-A317) anti-PD-1 antibody that has recently been approved treatment of Hodgkin's lymphoma urothelial carcinoma. Here, we show tislelizumab displayed remarkable antitumor efficacy in B16F10/GM-CSF mouse model. Structural biology Surface plasmon resonance (SPR) analyses revealed unique epitopes tislelizumab,...
Pancreatic cancer (PC) is a serious disease with high mortality. The tumor microenvironment plays key role in the occurrence and development of PC. purpose this study to analyze trends by year, country, institution, journal, reference keyword publications on PC predict future research hotspots.The Web Science Core Collection was used search for publications. We analyzed contributions various countries/regions, institutes, authors identified hotspots promising using CiteSpace VOSviewer...
Abstract Novel strategies to facilitate tumor‐specific drug delivery and restore immune attacks remain challenging in overcoming the current limitations of chemoimmunotherapy. An antitumor chemoimmunotherapy system comprising bioorthogonal reaction‐ready group tetrazine (TZ) modified with an anti‐PD‐L1 antibody (αPD‐L1 TZ ) TZ‐activatable prodrug vinyl ether‐doxorubicin (DOX‐VE) for self‐reinforced anti‐tumor is proposed. The αPD‐L1 effectively disrupts PD‐L1/PD‐1 interaction activates DOX...
Oncogenic BRAF, which drives cell transformation and proliferation, has been detected in approximately 50% of human malignant melanomas 5% to 15% colorectal cancers. Despite the remarkable clinical activities achieved by vemurafenib dabrafenib treating BRAF(V600E) metastatic melanoma, their efficacy cancer is far less impressive. Prior studies suggested that feedback activation EGFR MAPK signaling upon BRAF inhibition might contribute relative unresponsiveness first-generation inhibitors....
Abstract Background The introduction of the anti-PD-1 antibody has greatly improved clinical outcomes patients with non-small cell lung cancer (NSCLC). In this study, we retrospectively analyzed efficacy PD-1 antibody-based therapy in locally advanced inoperable or metastatic NSCLC and reported an association between peripheral blood biomarkers response these patients. Methods This single-center study included medical record data treated as a first-line subsequent line treatment, either...
Abstract BTK, an essential component of the BCR pathway, has emerged as novel target in treatment B-cell malignancies. Although Ibrutinib, first-in-class irreversible inhibitor showed promising clinical activity, recent study revealed that ibrutinib could antagonize rituximab induced antigen-dependent cell-mediated cytotoxicity (ADCC) by inhibiting ITK kinase activity (Kohrt et. al., 2013), suggesting potential limitations its application. BGB-3111 is a novel, highly selective, second...
The mutation of K-RAS represents one the most frequent genetic alterations in cancer. Targeting downstream effectors RAS, including MEK and ERK, has limited clinical success cancer patients with mutations. reduced sensitivity K-RAS-mutated cells to certain inhibitors (MEKi) is associated feedback phosphorylation by C-RAF reactivation mitogen-activated protein kinase (MAPK) signaling. Here, we report that RAF dimer lifirafenib (BGB-283) compound C show a strong synergistic effect MEKi,...
Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease of the central nervous system that involves B-cell receptor signaling as well astrocyte–microglia interaction, which both contribute to evolution NMOSD lesions. Main body Through transcriptomic and flow cytometry analyses, we found Bruton’s tyrosine kinase (BTK), a crucial protein was upregulated in blood cerebrospinal fluid patients. Blockade BTK with zanubrutinib, highly specific...
Abstract Liver metastasis (LM) is an important factor leading to colorectal cancer (CRC) mortality. However, the effect of T‐cell exhaustion on LM in CRC unclear. Single‐cell sequencing data derived from Gene Expression Omnibus database. Data were normalized using Seurat package and subsequently clustered annotated into different cell clusters. The differentiation trajectories epithelial cells T characterized based pseudo‐time analysis. Single‐sample gene set enrichment analysis (ssGSEA) was...
Abstract The ability to evade apoptosis is a hallmark of cancer. B-cell lymphoma-2 (Bcl-2), an anti-apoptosis protein, overexpressed and leads oncogenesis or drug resistance in various tumor types, including lymphoma leukemia. Bcl-2 well-validated target for B cell malignancies as demonstrated by inhibitor venetoclax which was recently approved the treatment chronic lymphocytic leukemia (CLL) currently phase III clinical development other hematologic malignancies. With longer term treatment,...
Purpose/Aim of the study: Interleukin (IL)-35 is a newly identified IL-12 cytokine family member and reveals immunosuppressive activity to CD8+ T cells in inflammation, infectious diseases, cancers. However, little known regarding IL-35 function osteosarcoma. Thus, aim current study was investigate regulatory Materials methods: Thirty-five osteosarcoma patients 20 healthy individuals were enrolled. Serum CD4+CD25+CD127dim/- (Tregs) purified. concentration serum cultured supernatants measured...
Abstract Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor expressed by activated T, B, and NK cells, which interacts with its ligand PD-L1/L2 to inhibit T-cell proliferation effector functions such as tumor killing cytokine production. Two anti-PD-1 antibodies approved the FDA, pembrolizumab nivolumab, have shown efficacy in many cancer types, nevertheless there are some indications where limited observed. Tislelizumab (BGB-A317), investigational antibody, has...
Neovascular age related macular degeneration (nAMD) leads to severe vision loss worldwide and is characterized by the formation of choroidal neovascularization (CNV) fibrosis. In current study, we aimed investigate effect blockade for platelet derived growth factor receptor-β (PDGFR-β) on fibrosis in laser-induced CNV model mice. Firstly, presence PDGFR-β lesions were confirmed. Intravitreal injection neutralizing antibody significantly reduced size subretinal Additionally, hyperreflective...
The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas13d system was adapted as a powerful tool for targeting viral RNA sequences, making it promising approach antiviral strategies. Understanding the influence of template structure on Cas13d binding and cleavage efficiency is crucial optimizing its therapeutic potential. In this study, we investigated effect local secondary activity. To do so, varied stability hairpin containing severe acute respiratory syndrome...