A5057255416- Sphingolipid Metabolism and Signaling
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Immune cells in cancer
- Drug Transport and Resistance Mechanisms
- Cancer, Hypoxia, and Metabolism
- Breast Cancer Treatment Studies
- Cancer, Lipids, and Metabolism
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- MicroRNA in disease regulation
- Cancer-related Molecular Pathways
- Endoplasmic Reticulum Stress and Disease
- Epigenetics and DNA Methylation
- Advanced Breast Cancer Therapies
- Pancreatic and Hepatic Oncology Research
- Cancer Research and Treatments
- Colorectal Cancer Treatments and Studies
- BRCA gene mutations in cancer
- Erythrocyte Function and Pathophysiology
- Angiogenesis and VEGF in Cancer
- Fibroblast Growth Factor Research
Roswell Park Comprehensive Cancer Center
2016-2025
University at Buffalo, State University of New York
2016-2025
Yokohama City University
2013-2025
Jacobs (United States)
2019-2025
Niigata University
2014-2025
Fukushima Medical University
2018-2025
Tokyo Medical University
2014-2025
Yokohama City University Medical Center
2013-2025
Gifu University
2021-2024
Holy Cross Hospital
2023
Abstract Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid mediator that promotes breast cancer progression by diverse mechanisms remain somewhat unclear. Here we report pharmacologic evidence of critical role for sphingosine kinase 1 (SphK1) in producing S1P and mediating tumor-induced hemangiogenesis lymphangiogenesis murine model metastasis. levels increased both the tumor circulation. In agreement, serum were significantly elevated stage IIIA human patients, compared with...
Bile acids have been shown to be important regulatory molecules for cells in the liver and gastrointestinal tract. They can activate various cell signaling pathways including extracellular regulated kinase (ERK)1/2 protein B (AKT) as well G-protein-coupled receptor (GPCR) membrane-type bile acid (TGR5/M-BAR). Activation of ERK1/2 AKT by conjugated has reported sensitive pertussis toxin (PTX) dominant-negative Gα(i) primary rodent hepatocytes. However, GPCRs responsible activation these not...
Sphingosine 1-phosphate (S1P), a potent sphingolipid mediator produced by sphingosine kinase isoenzymes (SphK1 and SphK2), regulates diverse cellular processes important for breast cancer progression acting in an autocrine and/or paracrine manner. Here we show that SphK1, but not SphK2, increased S1P export from MCF-7 cells. Whereas both estradiol (E2) epidermal growth factor-activated SphK1 production of S1P, only E2 stimulated rapid release dihydro-S1P E2-induced required estrogen...
Bile duct obstruction is a potent stimulus for cholangiocyte proliferation, especially large cholangiocytes. Our previous studies reported that conjugated bile acids (CBAs) activate the protein kinase B (AKT) and extracellular signal-regulated 1 2 (ERK1/2) signaling pathways through sphingosine 1-phosphate receptor (S1PR) in hepatocytes cholangiocarcinoma cells. It also has been taurocholate (TCA) promotes proliferation protects cholangiocytes from ligation (BDL)-induced apoptosis. However,...
CD8 T cell is an essential component of tumor-infiltrating lymphocytes (TIL) and tumor immune microenvironment (TIME). Using the xCell score whole gene expression data, we estimated these cells in total 3837 breast cancer patients from TCGA, METABRIC various GEO cohorts. The correlated strongly with genes. was highest for triple-negative (TNBC), a high associated cytolytic activity better survival TNBC but not other subtypes. In TNBC, tumors had enriched interferon (IFN)-α IFN-γ response...
Although obesity with associated inflammation is now recognized as a risk factor for breast cancer and distant metastases, the functional basis these connections remain poorly understood. Here, we show that in patients animal models, sufficient cause increased expression of bioactive sphingolipid mediator sphingosine-1-phosphate (S1P), which mediates pathogenesis. A high-fat diet was to upregulate sphingosine kinase 1 (SphK1), enzyme produces S1P, along its receptor S1PR1 syngeneic...
Abstract Tumor associated macrophages (TAMs) play a critical role in biology of various cancers, including breast cancer. In the current study, we defined “M1” macrophage and “M1”/“M2” ratio by transcriptomic signatures using xCell. We investigated association between high level or tumor immune microenvironment analyzing transcriptome publicly available cohorts, TCGA METABRIC. found that tumors were not with prolonged survival compared low tumors, response to neoadjuvant chemotherapy....
Vascular endothelial growth factor-A (VEGFA) is a key inducer of angiogenesis, responsible for generating new blood vessels in the tumor microenvironment (TME) and facilitating metastasis. Notably, Avastin, which targets VEGFA, failed to demonstrate any significant benefit clinical trials breast cancer (BC). This study aimed investigate relevance VEGFA gene expression BC. A total 7,336 BC patients across eight independent cohorts: ISPY2 (GSE173839), Sweden Cancerome Analysis Network-Breast...
Mice generated by disrupting the clotting factor IX gene exhibit severe bleeding disorder and closely resemble phenotype seen in hemophilia B patients. Here we demonstrate that a single intraportal injection of recombinant adeno-associated virus (AAV) vector encoding canine cDNA under control liver-specific enhancer/promoter leads to long-term complete correction disorder. High level expression up 15-20 microgram/ml was detected plasma mice injected with 5.6 x 10(11) particles an AAV for >5...
Bile acids are important hormones during the feed/fast cycle, allowing liver to coordinately regulate nutrient metabolism. How they accomplish this has not been fully elucidated. Conjugated bile activate both ERK1/2 and AKT signaling pathways via sphingosine 1-phosphate receptor 2 (S1PR2) in rodent hepatocytes vivo. Here, we report that feeding mice a high-fat diet, infusion of taurocholate into chronic fistula rat, or overexpression gene encoding S1PR2 mouse significantly upregulated...
Sphingosine-1-phosphate (S1P), a ligand for 5 specific receptors, is potent lipid mediator that plays important roles in lymphocyte trafficking and immune responses. S1P produced inside cells therefore must be secreted to exert its effects through these receptors. Spinster 2 (Spns2) one of the cell surface transporters thought secrete S1P. We have shown Spns2 can export endogenous from also dihydro-S1P, which active at all Moreover, Spns2–/– mice decreased levels both phosphorylated...
The vast majority of breast cancer death is a result metastasis. Thus, accurate identification patients who are likely to have metastasis expected improve survival. G2M checkpoint plays critical role in cell cycle. We hypothesized that tumors with high activity pathway genes more aggressive and metastasize. To test this, we used the single-sample gene set variation analysis method calculate score for Hallmark using expression data total 4626 samples from 12 human cohorts. As expected,...