A5036771873- Cancer-related gene regulation
- Bone Metabolism and Diseases
- RNA Research and Splicing
- Bone health and treatments
- Cancer-related molecular mechanisms research
- Synthesis and Catalytic Reactions
- RNA modifications and cancer
- Immune cells in cancer
- Bone health and osteoporosis research
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Ferroptosis and cancer prognosis
- Monoclonal and Polyclonal Antibodies Research
- Anesthesia and Neurotoxicity Research
- Circular RNAs in diseases
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Renin-Angiotensin System Studies
- Ion channel regulation and function
- Hormonal Regulation and Hypertension
- Immune Cell Function and Interaction
- Neuroscience and Neuropharmacology Research
- Pancreatitis Pathology and Treatment
- Pain Mechanisms and Treatments
- RNA Interference and Gene Delivery
Amgen (United States)
2010-2025
Guangzhou Medical University
2025
Central South University
2011-2024
Second Xiangya Hospital of Central South University
2018-2024
John Hunter Hospital
2017-2024
Fudan University
2020-2022
Guangxi Medical University
2021-2022
Huashan Hospital
2020-2022
Massachusetts General Hospital
2022
Harvard University
2022
Abstract RANKL is a TNF family member that mediates osteoclast formation, activation, and survival by activating RANK. The proresorptive effects of are prevented binding to its soluble inhibitor osteoprotegerin (OPG). Recombinant human OPG-Fc recognizes from multiple species reduced bone resorption increased volume, density, strength in number rodent models disease. clinical development was discontinued favor denosumab, fully monoclonal antibody specifically inhibits primate RANKL. Direct...
Abstract Therapeutic enhancement of fracture healing would help to prevent the occurrence orthopedic complications such as nonunion and revision surgery. Sclerostin is a negative regulator bone formation, treatment with sclerostin monoclonal antibody (Scl-Ab) results in increased formation mass animal models. Our objective was investigate effects systemic administration Scl-Ab two models healing. In both closed femoral model rats fibular osteotomy cynomolgus monkeys, significantly strength...
Abstract Inhibition of the Wnt antagonist sclerostin increases bone mass in patients with osteoporosis and preclinical animal models. Here we show increased levels Dickkopf-1 (DKK-1) animals treated antibody, suggesting a negative feedback mechanism that limits Wnt-driven formation. To test our hypothesis co-inhibition both factors further mass, engineer first-in-class bispecific antibody single residue pair mutations Fab region to promote efficient stable cognate light–heavy chain pairing....
Therapeutic approaches are needed to promote T cell-mediated destruction of poorly immunogenic, "cold" tumors typically associated with minimal response immune checkpoint blockade (ICB) therapy. Bispecific cell engager (BiTE) molecules induce redirected lysis cancer cells by polyclonal and have demonstrated promising clinical activity against solid in some patients. However, little is understood about the key factors that govern responses these therapies. Using an immunocompetent mouse model...
Diffuse intrinsic pontine glioma (DIPG) is a rare and fatal pediatric brain tumor. Mutation of p53-induced protein phosphatase 1 (PPM1D) in DIPG cells promotes tumor cell proliferation, inhibition PPM1D expression with mutation effectively reduces the proliferation activity cells. Panobinostat kills cells, but its systemic toxicity low blood-brain barrier (BBB) permeability limits application. In this paper, nano drug delivery system based on functionalized macrophage exosomes panobinostat...
One of the most robust synthetic lethal interactions observed in multiple functional genomic screens has been dependency on PRMT5 cancer cells with MTAP deletion. We report discovery clinical stage MTA-cooperative inhibitor AMG 193, which preferentially binds presence MTA and potent biochemical cellular activity MTAP-deleted across lineages. In vitro, inhibition induces DNA damage, cell cycle arrest, aberrant alternative mRNA splicing cells. human line patient-derived xenograft models, 193...
Increasing evidence suggests that microRNAs (miRNAs) play a critical role in tumorigenesis. Decreased expression of miR‑382 has been observed various types cancers. However, the biological function miRNA-382 ovarian cancer is still largely unknown. Here, we found was downregulated human tissues and cell lines. inhibited proliferation, migration, invasion epithelial-mesenchymal transition (EMT). Furthermore, identified receptor tyrosine kinase orphan 1 (ROR1) as target miR‑382, rescued...
Humoral hypercalcemia of malignancy (HHM) is mediated primarily by skeletal and renal responses to tumor-derived PTHrP. PTHrP mobilizes calcium from bone inducing the expression receptor activator for nuclear factor-kappaB ligand (RANKL), a protein that essential osteoclast formation, activation, survival. RANKL does not influence reabsorption, so inhibition rational approach selectively block, thereby reveal, relative contribution HHM. We used inhibitor osteoprotegerin (OPG) evaluate role...
Abstract Tumor-associated macrophages (TAMs) are abundant in solid tumors where they exhibit immunosuppressive and pro-tumorigenic functions. Inhibition of TAM proliferation survival through CSF1R blockade has been widely explored as a cancer immunotherapy. To further define mechanisms regulating CSF1R-targeted therapies, we systematically evaluated the effect anti-CSF1R treatment on tumor growth microenvironment (TME) inflammation across multiple murine models. Despite substantial...
Abstract MCL1 inhibitors are an emerging class of therapeutics targeting key protein-protein interactions between and BH3 domain containing pro-apoptotic BCL-2 family members. Several have entered clinical trials including AMG 176, currently in Phase I development for hematologic malignancies. However, all existing stage being administered intravenously. Here we describe the discovery preclinical evaluation 397, first orally inhibitor development. The pursuit bioavailable with acceptable...
Abstract Background Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are involved in the hypoxia-related cancer process and play pivotal roles enabling malignant cells to survive under hypoxic stress. However, molecular crosstalk between lncRNAs hypoxia signaling cascades non-small cell lung (NSCLC) remains largely elusive. Methods Firstly, we identified differentially expressed lncRNA susceptibility candidate 15 (CASC15) as associated with NSCLC based on...
To determine the association between olfactory function and cognition in patients rodents.Perioperative neurocognitive disorders include delayed recovery (dNCR). The contribution of to dNCR remains undetermined. It is unknown whether odor enrichment could mitigate dNCR.We performed a prospective observational cohort study potential impairment patients. We assessed effects anesthesia/surgery on cognitive mice using block test Barnes maze. measured interleukin-6 (IL-6), mature protein,...
MTAP deletion occurs in 10-15% of all human cancers due to its proximity the tumor suppressor gene CDKN2A. The loss leads accumulation methylthioadenosine (MTA), which shares structural similarity S-adenosyl methionine (SAM), methyl donor for cell-essential protein arginine methyltransferase 5 (PRMT5). By competing with SAM, MTA partially inhibits PRMT5, making MTAP-deleted tumors susceptible further PRMT5 inhibition. Herein, we report discovery MTA-cooperative inhibitor AMG 193, a molecule...
RANKL is an essential mediator of bone resorption, and its activity inhibited by osteoprotegerin (OPG). Transgenic (Tg) rats were engineered to continuously overexpress OPG study the effects continuous long-term inhibition on volume, density, strength. Lumbar vertebrae, femurs, blood obtained from 1-yr-old female OPG-Tg (n = 32) age-matched wildtype (WT) controls 23). had significantly greater serum (up 260-fold) lower TRACP5b osteocalcin compared with WT controls. Vertebral histomorphometry...
<p>Supplementary Methods: SDMA Imaging Assay, ELISA, Immunohistochemistry</p>
<p>Supplementary Figure S6. AM-9747 treatment results in increased DNA damage and cellular senescence BxPC-3 cells</p>
<p>Supplementary Figure S8. AMG 193 treatment in BxPC-3 tumors does not affect circulating blood cells</p>