- Acute Myeloid Leukemia Research
- CAR-T cell therapy research
- Lung Cancer Treatments and Mutations
- Glioma Diagnosis and Treatment
- RNA modifications and cancer
- Lymphoma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- PARP inhibition in cancer therapy
- Immune Cell Function and Interaction
- Cancer-related Molecular Pathways
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Peptidase Inhibition and Analysis
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Brain Metastases and Treatment
- Cancer Genomics and Diagnostics
- Cytokine Signaling Pathways and Interactions
- Hematological disorders and diagnostics
- Radiomics and Machine Learning in Medical Imaging
- Multiple Myeloma Research and Treatments
- Integrated Circuits and Semiconductor Failure Analysis
- Medicinal Plant Pharmacodynamics Research
- Cancer, Stress, Anesthesia, and Immune Response
- Single-cell and spatial transcriptomics
Moffitt Cancer Center
2017-2025
Weatherford College
2021
Flint Institute Of Arts
2021
Changzhou No.2 People's Hospital
2008-2020
Nanjing Medical University
2008-2020
Mayo Clinic
2010-2015
The University of Texas MD Anderson Cancer Center
2015
University of Kansas
2013
Second Affiliated Hospital of Nanjing Medical University
2011-2012
WinnMed
2010
Constitutive activation of signal transducer and activator transcription 3 (STAT3) signaling is frequently detected in cancer, promoting its emergence as a promising target for cancer treatment. Inhibiting constitutive STAT3 represents potential therapeutic approach. We used structure-based design to develop nonpeptide, cell-permeable, small molecule, termed LLL12, which targets STAT3. LLL12 was found inhibit phosphorylation (tyrosine 705) induce apoptosis indicated by the increases cleaved...
Abstract Purpose: The therapeutic benefit of temozolomide in glioblastoma multiforme (GBM) is limited by resistance. goal this study was to elucidate mechanisms resistance GBM. Experimental Design: We developed an vivo GBM model and used paired parental temozolomide-resistant tumors define the underlying development influence histone deacetylation (HDAC) inhibition. Results: Analysis resistant lines showed upregulation O6-methylguanine-DNA methyltransferase (MGMT) expression 3 5 xenografts....
Abstract Understanding the intrinsic mediators that render CD8 + T cells dysfunctional in tumor microenvironment is a requirement to develop more effective cancer immunotherapies. Here, we report C/EBP homologous protein (Chop), downstream sensor of severe endoplasmic reticulum (ER) stress, major negative regulator effector function tumor-reactive cells. Chop expression increased tumor-infiltrating cells, which correlates with poor clinical outcome ovarian patients. Deletion improves...
Sensitizing effects of poly-ADP-ribose polymerase inhibitors have been studied in several preclinical models, but a clear understanding predictive biomarkers is lacking. In this study, vivo efficacy veliparib combined with temozolomide (TMZ) was evaluated large panel glioblastoma multiforme (GBM) patient-derived xenografts (PDX) and potential were analyzed. The TMZ alone vs TMZ/veliparib compared 28 GBM PDX lines grown as orthotopic (8–10 mice per group); all tests statistical significance...
How genomic and transcriptomic alterations affect the functional proteome in lung cancer is not fully understood. Here, we integrate DNA copy number, somatic mutations, RNA-sequencing, expression proteomics a cohort of 108 squamous cell (SCC) patients. We identify three proteomic subtypes, two which (Inflamed, Redox) comprise 87% tumors. The Inflamed subtype enriched with neutrophils, B-cells, monocytes expresses more PD-1. Redox tumours are for oxidation-reduction glutathione pathways...
Myelodysplastic syndromes (MDS) are characterized by dysplastic and ineffective hematopoiesis that can result from aberrant expansion activation of myeloid-derived suppressor cells (MDSCs) within the bone marrow (BM) niche. MDSCs produce S100A9, which mediates premature death hematopoietic stem progenitor (HSPCs). The PD-1/PD-L1 immune checkpoint impairs responses inducing T-cell exhaustion apoptosis, but its role in MDS is uncharacterized. Here we report an increased expression PD-1 on...
Background Accumulation of regulatory T cells (Treg) has been described to often correlate with poor prognosis in many solid tumors. How Treg presence impinges on limited functionality and clonal composition tumor-associated CD8 +T important implications for their therapeutic targeting the tumor microenvironment. In present study, we investigated how accumulation Tregs contributes cell dysfunction constriction tumor-infiltrating cells. Methods Resected melanoma lung adenocarcinoma tissues...
Detection of disseminated cancer cells (DCC) in the bone marrow (BM) patients with breast is a critical predictor late recurrence and distant metastasis. Conventional therapies often fail to completely eradicate DCCs patients. In this study, we demonstrate that intratumoral priming antitumor CD4+ T-helper 1 (Th1) was able eliminate DCC burden organs prevent overt metastasis, independent CD8+ T cells. Intratumoral tumor antigen-specific Th1 enhanced their migration BM metastatic site...
Constitutive activation of signal transducer and activator transcription 3 (Stat3) signaling pathway plays an important role in several human cancers. Activation Stat3 is dependent on the phosphorylation at tyrosine residue 705 by upstream kinases subsequent nuclear translocation after dimerization. It remains unclear whether oncogenic involved oncogenesis bladder cancer.We found that elevated 19 100 (19%) cancer tissues as well cell lines, WH, UMUC-3 253J. To explore associated with growth...
PARP inhibition can enhance the efficacy of temozolomide and prolong survival in orthotopic glioblastoma (GBM) xenografts. The aim this study was to evaluate combination inhibitor rucaparib with correlate pharmacokinetic pharmacodynamic studies patient-derived GBM xenograft models. highly effective vitro short-term explant cultures derived from GBM12, and, similarly, (dosed for 5 days every 28 3 cycles) significantly prolonged time tumor regrowth by 40% heterotopic In contrast, addition had...
Abstract Background Stat3 has been classified as a proto-oncogene and constitutive signaling appears to be involved in oncogenesis of human cancers. However, whether plays role the survival growth osteosarcomas, rhabdomyosarcomas, soft-tissue sarcomas is still unclear. Methods To examine activated rhabdomyosarcomas other we analyzed sarcoma tissue microarray slides cell lines using immunohistochemistry Western blot analysis, respectively, with phospho-specific antibody. pathway important for...
Abstract Background Colorectal carcinoma is one of the major causes morbidity and mortality in Western World. Novel therapeutic approaches are needed for colorectal carcinoma. Curcumin, active component yellow pigment turmeric, has been reported to have several anti-cancer activities including anti-proliferation, anti-invasion, anti-angiogenesis. Clinical trials suggested that curcumin may serve as a potential preventive or agent cancer. Methods We compared inhibitory effects novel...
Abstract MYC oncoproteins regulate transcription of genes directing cell proliferation, metabolism, and tumorigenesis. A variety alterations drive expression in acute myeloid leukemia (AML), enforced hematopoietic progenitors is sufficient to induce AML. Here we report that AML progenitor growth survival rely on MYC-directed suppression Transcription Factor EB (TFEB), a master regulator the autophagy–lysosome pathway. Notably, although originally identified as an oncogene, TFEB functions...
Abstract Florida ranks second in cancer burden the United States. The CAncer RESearch (FL CARES) Network (https://floridacancernetwork.org/) is a statewide collaboration dedicated to advancing research and improving patient outcomes through education, collaborative initiatives, focus on reducing health disparities by leveraging advanced computational approaches. Funded State of Bankhead-Coley Cancer Research Program, FL CARES comprises six organizations, including Florida's three...
Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive malignancy. Though molecular underpinnings this cancer have been largely unexplored, recurrent chromosomal breakpoints affecting noncoding region on chr19q13, which includes chromosome 19 microRNA cluster (C19MC), reported in several cases. We performed comprehensive profiling samples from 14 patients diagnosed with UESL. Congruent prior reports, we identified structural variants chr19q13 10 13 evaluable tumors....
Abstract The Signal Transducer and Activator of Transcription (STAT) proteins comprise a family latent transcription factors with diverse functions. STAT3 has well established roles in cell proliferation, growth survival, its persistent activation been detected high frequency many human cancers. As constitutive appears to be vital for the continued survival these cancerous cells, it emerged as an attractive target chemotherapeutics. We examined whether inhibitory activities bioactive...
Temozolomide (TMZ) is important chemotherapy for glioblastoma multiforme (GBM), but the optimal dosing schedule unclear. The efficacies of different clinically relevant regimens were compared in a panel 7 primary GBM xenografts an intracranial therapy evaluation model. Protracted TMZ (TMZ daily M–F, 3 wk every 4) provided superior survival to placebo-treated group 1 4 O6-DNA methylguanine-methyltransferase (MGMT) promoter hypermethylated lines (GBM12) and none MGMT unmethylated lines, while...
While HDAC inhibitors have shown promise in hematologic cancers, their efficacy remains limited solid cancers. In the present study, we evaluated immunomodulatory properties of HDAC6 inhibitor, Citarinostat (ACY241) on lung tumor immune compartment and its therapeutic potential combination with Oxaliplatin. As a single agent, ACY241 treatment promoted increased infiltration, activation, proliferation, effector function T cells tumors adenocarcinoma-bearing mice. Furthermore, tumor-associated...
Evidence from human and animal studies suggests that chronic behavioral stress resulting activation of the sympathetic nervous system may influence initiation progression tumors. However, underlying mechanisms for these observations are poorly understood. The purpose this study is to explore effects adrenergic signaling on cell line models derived normal cells presumed originate epithelial ovarian cancers. Here we explored stress-related hormone, norepinephrine, transcriptional program...
Abstract DNA methylation signatures in tumors could serve as reliable biomarkers that are accessible archival tissues for tracking the epigenetic dynamics shaped by both cancer cells and tumor microenvironment. However, given ultrahigh dimensionality noncollapsible nature of data, it remains challenging to screen all CpG sites identify most promising marker panels. In this article, we introduce concept tumor-based expression quantitative trait (eQTM) prioritization systematic mining...
Gamma-delta T cells (γδ cells) play a crucial role in both innate and adaptive immunity within tumors, yet their presence prognostic value cancer remain underexplored. This study presents large-scale analysis of γδ cell receptor TCR) reads from 11,000 tumor samples spanning 33 types, utilizing the TRUST4 algorithm. Our findings reveal extensive diversity TCR clonality gene expression, underscoring potential as biomarkers various cancers. We further demonstrate utility gamma (TRG) delta (TRD)...