A5044217766- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Bladder and Urothelial Cancer Treatments
- Acute Ischemic Stroke Management
- Renin-Angiotensin System Studies
- DNA Repair Mechanisms
- Cancer, Hypoxia, and Metabolism
- Adrenal and Paraganglionic Tumors
- Cellular transport and secretion
- Immune cells in cancer
- Nitric Oxide and Endothelin Effects
- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Congenital heart defects research
- PI3K/AKT/mTOR signaling in cancer
- Genomics and Rare Diseases
- Receptor Mechanisms and Signaling
- Mitochondrial Function and Pathology
- Hormonal Regulation and Hypertension
- Moyamoya disease diagnosis and treatment
- Melanoma and MAPK Pathways
- Macrophage Migration Inhibitory Factor
- CNS Lymphoma Diagnosis and Treatment
Sichuan University
2010-2025
The University of Texas Health Science Center at San Antonio
2013-2024
The University of Texas at San Antonio
2021-2024
West China Hospital of Sichuan University
2010-2023
Chengdu Second People's Hospital
2023
The University of Texas Health Science Center at Houston
2019-2022
University of Tripoli Lebanon
2022
Mays Cancer Center at UT Health San Antonio
2021
Audie L. Murphy Memorial VA Hospital
2020
Novartis (Switzerland)
1992
Pheochromocytomas and paragangliomas are highly vascular tumors of the autonomic nervous system. Germline mutations, including those in hypoxia-related genes, occur one third cases, but somatic mutations infrequent these tumors. Using exome sequencing six paired constitutive tumor DNA from sporadic pheochromocytomas paragangliomas, we identified a mutation HIF2A ( EPAS1 ) gene. Screening an additional 239 pheochromocytomas/paragangliomas uncovered three other variants (4/167, 2.3%) not...
TMEM127 is an endosome-associated tumor suppressor gene in pheochromocytomas, neuroendocrine tumors that can co-occur with renal cell carcinomas (RCCs). loss leads to increased mTOR signaling. However, the spectrum of mutation and how interact tumorigenesis remains unknown. Here, we report germline mutations occur RCCs some mutant proteins, unlike wild-type (WT) TMEM127, fail cooperate activated early endosomal GTPase, Rab5, inhibit Tmem127-null mouse embryonic fibroblasts (MEFs) are...
Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate immunopathologic effects in breast, colon, and ovarian cancers melanomas, but bladder cancer (BC) are unreported. We show here that BC PD-L1 mouse MB49 human RT4, UM-UC3, UM-UC-14 cells regulate important pathologic pathways processes, including not reported other cancers. α-PD-L1 antibodies reduced cell proliferation vitro, demonstrating direct signaling effects. promoted mammalian target of rapamycin complex (mTORC1)...
To investigate the time-varying association between blood pressure (BP) and malignant brain edema (MBE) risk after large hemispheric infarction (LHI). We prospectively enrolled LHI patients (CT hypodensity > 1/3 middle cerebral artery territory within 6 h or 1/2 6-48 of onset) from registry cohort. BP was recorded hourly analyzed for 24 in two 12-hour epochs onset: 1-12 13-24 h. MBE defined as neurological deterioration symptoms with midline shift ≥ 5 mm. Generalized estimating equation...
Absolute hyperglycemia at admission has been shown to be associated with the development of cerebral edema (CED) after acute infarction. Stress is a more objective reflection hyperglycemic state than absolute hyperglycemia. However, studies on associations between stress and CED are limited. We aimed explore hyperglycemia, measured by ratio (SHR), poor functional outcome infarction.Patients middle artery infarction admitted Department Neurology, West China Hospital Sichuan University, within...
The IL2 receptor (IL2R) is an attractive cancer immunotherapy target that controls immunosuppressive T regulatory cells (Treg) and antitumor cells. Here we used IL2Rβ-selective IL2/anti-IL2 complexes (IL2c) to stimulate effector preferentially in the orthotopic mouse ID8agg ovarian model. Despite strong tumor rejection, IL2c unexpectedly lowered microenvironmental CD8+/Treg ratio. reduced Treg suppression induced a fragile phenotype, helping explain improved efficacy despite numerically...
Abstract Introduction Aging is the biggest cancer risk, and immune checkpoint (IC) inhibition (ICI) a revolutionary immunotherapy approach. Nonetheless, there are limited preclinical/clinical data regarding aging effects on ICI outcomes or age IC expression in different organs tumors. Methods Flow cytometry assessed non‐immune cells various young aged BL6 mice. Comparisons: versus naïve WT interferon‐γ KO mice challenged with B16F10 melanoma treated αPD‐1 αPD‐L1 ICI. We co‐cultured T myeloid...
The TMEM127 tumor suppressor gene encodes a transmembrane protein of unknown function mutated in pheochromocytomas and, rarely, renal cancers. Tumors with inactivating mutations have increased mTORC1 signaling by undefined mechanisms. Here we report that interacts the lysosome-anchored complex comprised Rag GTPases, LAMTOR pentamer (or 'ragulator') and vATPase, which controls amino acid-mediated activation. We found under nutrient-rich conditions expression reduces recruitment to Rags. In...
Anti-programmed death-ligand 1 (αPD-L1) immunotherapy is approved to treat bladder cancer (BC) but effective in <30% of patients. Interleukin (IL)-2/αIL-2 complexes (IL-2c) that preferentially target IL-2 receptor β (CD122) augment CD8
Abstract Understanding the molecular components of insulin signaling is relevant to effectively manage resistance. We investigated phenotype TMEM127 tumor suppressor gene deficiency in vivo. Whole-body Tmem127 knockout mice have decreased adiposity and maintain sensitivity, low hepatic fat deposition peripheral glucose clearance after a high-fat diet. Liver-specific adipose-specific deletion partially overlap global loss: liver promotes gluconeogenesis inhibits uptake, while adipose...
Tumor intracellular programmed cell death ligand-1 (PDL1) mediates pathologic signals that regulate clinical treatment responses distinctly from surface-expressed PDL1 targeted by αPDL1 immune checkpoint blockade antibodies.
Abstract Context TMEM127 is a poorly known tumor suppressor gene associated with pheochromocytomas, paragangliomas, and renal carcinomas. Our incomplete understanding of function has limited our ability to predict variant pathogenicity. Purpose To better understand the transmembrane protein we undertook cellular molecular evaluation patient-derived germline variants. Design Subcellular localization steady-state levels tumor-associated, transiently expressed variants were compared wild-type...
The interaction between tumor surface-expressed PDL1 and immune cell PD1 for the evasion of antitumor immunity is well established targeted by FDA-approved anti-PDL1 anti-PD1 antibodies. Nonetheless, recent studies highlight immunopathogenicity tumor-intrinsic signals that can contribute to resistance small molecules, cytotoxic chemotherapy, αPD1 immunotherapy. As genetic depletion not currently clinically tractable, we screened drugs identify those significantly deplete PDL1. Among...
Purpose Plasma osmolality, a marker of dehydration, is associated with cardiovascular mortality. We aimed to investigate whether elevated plasma osmolality case fatality within 1 year after severe acute ischemic stroke. Materials and methods included stroke patients (defined as National Institutes Health Stroke Scale ≥15 score) 24 hours from symptom onset admitted the Department Neurology, West China Hospital between January 2017 June 2019. Admission was calculated using equation...
Endothelin-1 (ET-1) is a potent peptidic vasoconstrictor. This peptide has been shown to be cleared rapidly by the kidney. The purpose of present study was assess involvement renal proteolytic enzymes in clearance/degradation ET-1. Incubation ET-1 with cytosolic fraction rat kidney homogenate resulted decrease contractile activity on rabbit aortic rings when compared untreated chromatographed anion-exchange and concanavalin A columns. partially purified enzyme cleaved off C-terminal...
Endothelin is a potent peptide vasoconstrictor. The final step in the processing of endothelin has been postulated to be cleavage Trp21-Val22 bond proendothelin by putative endothelin-converting enzyme. A soluble extract primary porcine aortic endothelial cells was found contain an enzyme activity that converted proendothelin-1 (proET-1) endothelin-1 (ET-1)-like as determined rabbit ring contraction assay. This partially purified DE52 ion-exchange chromatography. Incubation proET-1 with...
<b><i>Background:</i></b> Limited data exist on the significance of acute cerebral microinfarcts (A-CMIs) in context ischemic stroke (AIS). We aimed to determine profile and prognostic A-CMIs magnetic resonance imaging (MRI) patients presenting with AIS. <b><i>Methods:</i></b> A prospective single-center series AIS who had 3T MRIs between March 2013 December 2019. The presence, number, location diffusion-weighted imaging, markers small vessel...
Abstract Background Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder unclear causes. Paraneoplastic etiology may be a cause. We report case of CLIPPERS parotid carcinoma. Case presentation A 54-year-old man history lymphoma was hospitalized pontocerebellar syndrome. Brain MRI revealed that the pons and cerebellum were “peppered” punctate curvilinear lesions supported diagnosis CLIPPERS. The relapse excluded...