A5076693894- Sarcoma Diagnosis and Treatment
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- CAR-T cell therapy research
- Effects of Radiation Exposure
- Glioma Diagnosis and Treatment
- Virus-based gene therapy research
- Cancer Cells and Metastasis
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Chromosomal and Genetic Variations
- Ubiquitin and proteasome pathways
- Cancer-related molecular mechanisms research
- Plant tissue culture and regeneration
- Protein Degradation and Inhibitors
- Circular RNAs in diseases
- Radiation Therapy and Dosimetry
- Immunotherapy and Immune Responses
- RNA Research and Splicing
- Natural product bioactivities and synthesis
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- MicroRNA in disease regulation
Duke Medical Center
2015-2025
Duke University
2014-2024
Nanjing University of Chinese Medicine
2021-2024
Duke University Hospital
2023
Jiangsu Provincial Academy of Traditional Chinese Medicine
2021-2022
Radiation Oncology Associates
2015-2022
Sun Yat-sen University
2022
Guangzhou University of Chinese Medicine
2021
Oil Crops Research Institute
2006-2020
Chinese Academy of Agricultural Sciences
2006-2020
Nearly two-thirds of cancer patients are treated with radiation therapy (RT), often the intent to achieve complete and permanent tumor regression (local control). RT is primary treatment modality used local control for many malignancies, including locally advanced cervical cancer, head neck lung cancer. The addition concurrent platinum-based radiosensitizing chemotherapy improves patient survival. Enhanced outcomes chemoradiotherapy may result from increased direct killing cells effects on...
Metastasis causes most cancer deaths, but is incompletely understood. MicroRNAs can regulate metastasis, it not known whether a single miRNA metastasis in primary models vivo. We compared the expression of miRNAs metastatic and nonmetastatic mouse sarcomas found that microRNA-182 (miR-182) was markedly overexpressed some tumors metastasized to lungs. By utilizing genetically engineered mice with either deletion or overexpression miR-182 sarcomas, we discovered substantially decreased, while...
Abstract Immunotherapy fails to cure most cancer patients. Preclinical studies indicate that radiotherapy synergizes with immunotherapy, promoting radiation-induced antitumor immunity. Most preclinical immunotherapy utilize transplant tumor models, which overestimate patient responses. Here, we show sarcomas are cured by PD-1 blockade and radiotherapy, but identical treatment in autochthonous sarcomas, demonstrate immunoediting, decreased neoantigen expression, tumor-specific immune...
Combination of chemotherapy and immune checkpoint inhibitor therapy has greatly improved the anticancer effect on multiple malignancies. However, efficiency triple-negative breast cancer (TNBC) is limited, since most patients bear "cold" tumors with low tumor immunogenicity. Doxorubicin (DOX), one effective agents, can induce immunogenic cell death (ICD) thus initiating response.In this study, to maximize ICD induced by DOX, chitosan cell-penetrating peptide (R6F3)-modified nanoparticles...
Abstract Ionizing radiation induces cell death in the gastrointestinal (GI) epithelium by activating p53. However, p53 also prevents animal lethality caused radiation-induced acute GI syndrome. Through single-cell RNA-sequencing of irradiated mouse small intestine, we find that target genes are specifically enriched regenerating epithelial cells undergo fetal-like reversion, including revival stem (revSCs) promote survival after severe damage tract. Accordingly, mice with deleted epithelium,...
Genetically engineered mouse models that employ site-specific recombinase technology are important tools for cancer research but can be costly and time-consuming. The CRISPR-Cas9 system has been adapted to generate autochthonous tumours in mice, how these compare generated by conventional remains fully explored. Here we use multiple subtypes of primary sarcomas efficiently wild type genetically mice. These data demonstrate used soft tissue Primary with Cre had similar histology, growth...
Cancer development is influenced by hereditary mutations, somatic mutations due to random errors in DNA replication, or external factors. It remains unclear how distinct cell-intrinsic and -extrinsic factors affect oncogenesis within the same tissue type. We investigated murine soft-tissue sarcomas generated oncogenic alterations (KrasG12D activation p53 deletion), carcinogens (3-methylcholanthrene [MCA] ionizing radiation), both a potentially novel model (MCA plus deletion). Whole-exome...
Abstract Genotoxic cancer therapies, such as chemoradiation, cause haematological toxicity primarily by activating the tumour suppressor p53. While inhibiting p53-mediated cell death during therapy ameliorates haematologic toxicity, whether it also impacts carcinogenesis remains unclear. Here we utilize a mouse model of inducible p53 short hairpin RNA (shRNA) to show that temporarily blocking total-body irradiation (TBI) not only acute but improves long-term survival preventing lymphoma...
ATRX is one of the most frequently altered genes in solid tumors, and mutation especially frequent soft tissue sarcomas. However, role tumor development response to cancer therapies remains poorly understood. Here, we developed a primary mouse model sarcoma showed that Atrx-deleted tumors were more sensitive radiation therapy oncolytic herpesvirus. In absence Atrx, irradiated sarcomas had increased persistent DNA damage, telomere dysfunction, mitotic catastrophe. Our work also Atrx deletion...
The tumor suppressor p53 (Trp53), also known as p53, is the most commonly mutated gene in cancer. Canonical DNA damage response pathways are well characterized and classically thought to underlie suppressive effect of p53. Challenging this dogma, mouse models have revealed that p53-driven apoptosis cell cycle arrest dispensable for suppression. Here, we investigated inverse context a mutation predicted drive expression canonical targets but detected human We established novel model with...
Abstract Undifferentiated pleomorphic sarcoma (UPS) is among the most common soft tissue sarcomas (STS) in adults. For decades, little therapeutic progress has been made for STSs, including UPSs. Targeted therapies tumors driven by specific genetic mutations have proven to be more effective than standard chemotherapies. However, molecular pathogenesis of UPSs remains unknown, hindering development targeted Approximately 65% harbor TP53 mutations, but somatic mutation Trp53 alone insufficient...
Hypoxia is a major cause of radiation resistance, which may predispose to local recurrence after therapy. While hypoxia increases tumor cell survival exposure because there less oxygen oxidize damaged DNA, it remains unclear whether signaling pathways triggered by contribute resistance. For example, intratumoral can increase inducible factor 1 alpha (HIF-1α), regulate that sensitization or To clarify the role HIF-1α in regulating response radiation, we generated novel genetically engineered...
Diffuse intrinsic pontine glioma (DIPG) kills more children than any other type of brain tumor. Despite clinical trials testing many chemotherapeutic agents, palliative radiotherapy remains the standard treatment. Here, we utilized Cre/loxP technology to show that deleting Ataxia telangiectasia mutated (Atm) in primary mouse models DIPG can enhance tumor radiosensitivity. Genetic deletion Atm improved survival mice with p53-deficient but not p53 wild-type gliomas after radiotherapy. Similar...
Stereotactic body radiotherapy is utilized to treat lung cancer. The mechanism of tumor response high-dose (HDRT) controversial, with competing hypotheses increased direct cell killing versus indirect effects on stroma including endothelial cells. Here we used dual recombinase technology in a primary murine cancer model test whether cells or are critical HDRT targets. Lenti-Cre deleted one two copies ataxia-telangiectasia mutated gene (
Carbon ion therapy (CIT) offers several potential advantages for treating cancers compared with X-ray and proton radiotherapy, including increased biological efficacy more conformal dosimetry. However, CIT potency has not been characterized in primary tumor animal models. Here, we calculate the relative effectiveness (RBE) of carbon ions X-rays an autochthonous mouse model soft tissue sarcoma. We used Cre/loxP technology to generate sarcomas
Haploinsufficiency in the tumor suppressor NF1 contributes to pathobiology of neurofibromatosis type 1, but a related role has not been established malignant peripheral nerve sheath tumors (MPNST) where mutations also occur. Patients with NF1-associated MPNST appear have worse outcomes than patients sporadic MPNST, mechanism underlying this correlation is understood. To define impact stromal genetics on biology malignancy, we developed unique mouse models that reflect patient-associated...
Abstract Diverse tumor metabolic phenotypes are influenced by the environment and genetic lesions. Whether these extend to rhabdomyosarcoma (RMS) how they might be leveraged design new therapeutic approaches remains an open question. Thus, we utilized a Pax7 Cre-ER-T2/+ ; Nras LSL-G12D/+ p53 fl/fl (P7NP) murine model of sarcoma with mutations that most frequently occur in human embryonal RMS. To study metabolism, infuse 13 C-labeled glucose or glutamine into mice sarcomas show consume more...
Lung cancer (LC) is the highest lethality in all tumors. Non-small cell lung (NSCLC) accounts for about 80% of LC. Acanthopanax senticosus polysaccharide (ASPS) extracted from root (AS). Herein, we examined effect and molecular mechanism ASPS on NSCLC. The proliferation, invasion migration NCI-H520 cells were detected by counting kit-8 (CCK-8), transwell assay wound healing assay, respectively. epithelial-mesenchymal transition (EMT) Wnt/β-catenin pathway-related factors evaluated using...
Soft-tissue sarcomas (STS) are rare malignancies showing lineage differentiation toward diverse mesenchymal tissues. Half of all high-grade STSs develop lung metastasis with a median survival 15 months. Here, we used genetically engineered mouse model that mimics undifferentiated pleomorphic sarcoma (UPS) to study the molecular mechanisms driving metastasis. High-grade were generated Cre recombinase technology using mice conditional mutations in
Maize is an important oil seed crop and a major food in different parts of the world. Since maize has relatively lower content as compared to other crops, efforts are continuing improve its percentage. In this study, we analyzed two contrasting genotypes with differential accumulation percentages. High oil-content (HOC) had 11% while low (LOC) significantly (5.4%). Transmission electron microscopy revealed higher bodies HOC embryo LOC maize. Comparative RNA-sequencing analysis at...
Abstract Mouse models of radiation-induced thymic lymphoma are widely used to study the development blood cancers and gain insights into biology human T-cell lymphoblastic leukemia/lymphoma. Here we aimed identify key oncogenic drivers for by performing whole-exome sequencing using tumors paired normal tissues from mice with without irradiation. Thymic lymphomas irradiated wild-type (WT), p53+/−, KrasLA1 were not observed harbor significantly higher numbers nonsynonymous somatic mutations...