A5036764473- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- Nanoplatforms for cancer theranostics
- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- Cancer Research and Treatments
- Prostate Cancer Treatment and Research
- Metabolism, Diabetes, and Cancer
- Gut microbiota and health
- Phagocytosis and Immune Regulation
- Pancreatic function and diabetes
- Ubiquitin and proteasome pathways
- Estrogen and related hormone effects
- Liver physiology and pathology
- Vitamin D Research Studies
- Cancer Immunotherapy and Biomarkers
- Tryptophan and brain disorders
- Cancer, Lipids, and Metabolism
- Acute Myeloid Leukemia Research
- Histone Deacetylase Inhibitors Research
- Cancer, Stress, Anesthesia, and Immune Response
- Natural Compounds in Disease Treatment
- Cancer Cells and Metastasis
- Herpesvirus Infections and Treatments
- Metal-Catalyzed Oxygenation Mechanisms
University of Miami
2020-2025
Washington State University
2016-2018
Athira Pharma (United States)
2016
Abstract In pancreatic cancer, the robust fibroinflammatory stroma contributes to immune suppression and renders tumors hypoxic, altering intratumoral metabolic pathways leading poor survival. One enzyme activated during hypoxia is lactate dehydrogenase A (LDHA). As a result of its promiscuous activity under hypoxia, LDHA produces L-2 hydroxyglutarate (L-2HG), an epigenetic modifier, that regulates tumor transcriptome. However, role L-2HG in remodeling microenvironment not known. Here we...
Obesity causes chronic inflammation and changes in gut microbiome. However, how this contributes to poor survival therapy resistance patients with pancreatic cancer remain undetermined. Our current study shows that high fat diet-fed obese tumor bearing mice do not respond standard of care gemcitabine paclitaxel when compared corresponding control mice. C57BL6 were put on diet for 1 month following tumors implanted both groups. Microbiome lean (control) (high fed) was analyzed. Fecal matter...
<div>Abstract<p>Castration-resistant prostate cancer (CRPC) is incurable and fatal, making the second leading cancer-related cause of death for American men. CRPC results from therapeutic resistance to standard-of-care androgen deprivation (AD) treatments, through incompletely understood molecular mechanisms, lacks durable options. In this study, we identified enhanced soluble guanylyl cyclase (sGC) signaling as a mechanism that restrains initiation growth. Patients with...
<p>figures, legends and references associated with Supplementary figures</p>
The efficacy of strategies targeting oncogenic RAS, prevalent in lung adenocarcinoma (LUAD), is limited by rapid adaptive resistance mechanisms. These include loss RAS addiction and hyperactivation downstream signaling pathways, such as PI3K/AKT. We previously reported that RAS-driven LUAD cells possess an enhanced reliance on MTH1, the mammalian 8-oxodGTPase, to prevent genomic incorporation oxidized nucleotides, MTH1 depletion compromises tumorigenesis signaling. Here, we show elevated...
Allogeneic hematopoietic stem cell transplantation (aHSCT) can cure patients with otherwise fatal leukemias and lymphomas. However, the benefits of aHSCT are limited by graft-versus-host disease (GVHD). Minnelide, a water-soluble analog triptolide, has demonstrated potent antiinflammatory antitumor activity in several preclinical models proven both safe efficacious clinical trials for advanced gastrointestinal malignancies. Here, we tested effectiveness Minnelide preventing acute GVHD as...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive KRAS-driven cancer that remains one of the most lethal all human malignancies. Oncogenic KRAS relies on elevated reactive oxygen species (ROS) to support pro-tumorigenic signaling. However, these ROS levels can also evoke tumor suppressive oxidative stress; thus cancers must evolve protective redox adaptations mitigate ROS-induced anti-tumor consequences. Here we report a unique adaptation centered maintenance nucleotide pool...
Castration-resistant prostate cancer (CRPC) is incurable and fatal, making the second-leading cancer-related cause of death for American men. CRPC results from therapeutic resistance to standard-of-care androgen deprivation (AD) treatments, through incompletely understood molecular mechanisms, lacks durable options. Here, we identified enhanced soluble guanylyl cyclase (sGC) signaling as a mechanism that restrains initiation growth. Patients with aggressive, fatal exhibited significantly...
Abstract Oncogenic RAS signaling is mediated by reactive oxygen species (ROS) signaling. However, oncogenic ROS also evoke tumor suppressive damage, necessitating adaptive redox protective mechanisms. We previously reported that MTH1, the main mammalian 8-oxodGTPase, comprises one such critical adaptation. High MTH1 expression significantly correlates with poor disease-free survival in several KRAS-driven tumors. have shown RAS-driven xenograft cancer models for maintenance of ROS-driven and...
Pancreatic cancer is among the leading causes of death in USA, with limited effective treatment options. A major contributor toward formation and persistence pancreatic dysregulation hepatocyte growth factor (HGF)/Met (HGF receptor) macrophage-stimulating protein (MSP)/Ron (MSP systems. These systems normally mediate a variety cellular behaviors including proliferation, survival, migration, but are often overactivated contribute progression. Previous studies have shown that HGF must dimerize...
Abstract Castration-resistant prostate cancer (CRPC) is fatal and therapeutically under-served. We describe a novel CRPC-restraining role for the vasodilatory soluble guanylyl cyclase (sGC) pathway. discovered that sGC subunits are dysregulated during CRPC progression its catalytic product, cyclic GMP (cGMP), lowered in patients. Abrogating heterodimer formation castration-sensitive (CSPC) cells inhibited androgen deprivation (AD)-induced senescence, promoted castration-resistant tumor...
Pancreatic cancer is a leading cause of deaths in the USA and characterized by an exceptionally poor long-term survival rate compared with other major cancers. The hepatocyte growth factor (HGF) macrophage stimulating protein (MSP) systems are frequently over-activated pancreatic significantly contribute to progression, metastasis, chemotherapeutic resistance. Small molecules homologous ‘hinge’ region HGF, which participates its dimerization activation, had been developed shown bind HGF high...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive KRAS-driven cancer that remains one of the most lethal all human malignancies. Oncogenic KRAS relies on elevated reactive oxygen species (ROS) to support pro-tumorigenic signaling. However, these ROS levels can also evoke tumor suppressive oxidative stress; thus cancers must evolve protective redox adaptations mitigate ROS-induced anti-tumor consequences. Here we report a unique adaptation centered maintenance nucleotide pool...
377 Background: Metformin impacts immune response in several ways. It protects CD8 TILs from apoptotic death, downregulates CD39 and CD73, reduces MDSC activity suppresses the transcription of PD1 thus enhancing CD8+ T cell antitumor (Ma et al, 2000, Nature). There is limited data on immunologic impact metformin treatment hormone sensitive prostate cancer. Methods: We conducted an open label, randomized, phase II trial bicalutamide with or without patients high risk, biochemically recurrent...
<div>Abstract<p>In pancreatic cancer, the robust fibroinflammatory stroma contributes to immune suppression and renders tumors hypoxic, altering intratumoral metabolic pathways leading poor survival. One enzyme activated during hypoxia is lactate dehydrogenase A (LDHA). As a result of its promiscuous activity under hypoxia, LDHA produces L-2 hydroxyglutarate (L-2HG), an epigenetic modifier, that regulates tumor transcriptome. However, role L-2HG in remodeling microenvironment not...
<p>RNA seq data file after treatment of S2VP10 cells with L-2HG</p>
<p>RNA seq data file after treatment of MIA-PACA2 cells with L-2HG</p>
<p>Supplementary Figures and methods</p>
<div>Abstract<p>In pancreatic cancer, the robust fibroinflammatory stroma contributes to immune suppression and renders tumors hypoxic, altering intratumoral metabolic pathways leading poor survival. One enzyme activated during hypoxia is lactate dehydrogenase A (LDHA). As a result of its promiscuous activity under hypoxia, LDHA produces L-2 hydroxyglutarate (L-2HG), an epigenetic modifier, that regulates tumor transcriptome. However, role L-2HG in remodeling microenvironment not...
<p>RNA seq data file after treatment of MIA-PACA2 cells with L-2HG</p>
<p>Supplementary Figures and methods</p>
<p>RNA seq data file after treatment of S2VP10 cells with L-2HG</p>