A5057394028- Prostate Cancer Treatment and Research
- Chemokine receptors and signaling
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Estrogen and related hormone effects
- Cancer, Stress, Anesthesia, and Immune Response
- Immune Cell Function and Interaction
- Nuclear Receptors and Signaling
- Cancer, Lipids, and Metabolism
- Prostate Cancer Diagnosis and Treatment
- RNA modifications and cancer
- NF-κB Signaling Pathways
- Cytokine Signaling Pathways and Interactions
- Urinary Bladder and Prostate Research
- interferon and immune responses
- Immune Response and Inflammation
- Hormonal and reproductive studies
- Retinoids in leukemia and cellular processes
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- PI3K/AKT/mTOR signaling in cancer
- T-cell and B-cell Immunology
- Inflammatory mediators and NSAID effects
- Peptidase Inhibition and Analysis
- Antioxidant Activity and Oxidative Stress
National Health Research Institutes
2014-2024
Institute of Immunology
2014
University of Rochester Medical Center
1999-2013
China Medical University
2013
China Medical University Hospital
2013
University of Toronto
2005-2011
Ontario Institute for Cancer Research
2007-2011
University Health Network
2005-2011
University of Rochester
2002-2007
Breast Cancer Research Foundation
2005
Cutaneous wounds heal more slowly in elderly males than females, suggesting a role for sex hormones the healing process. Indeed, androgen/androgen receptor (AR) signaling has been shown to inhibit cutaneous wound healing. AR is expressed several cell types skin, including keratinocytes, dermal fibroblasts, and infiltrating macrophages, but exact of androgen/AR these different remains unclear. To address this question, we generated studied cell-specific knockout (ARKO) mice. General...
Abstract Infiltrating macrophages are a key component of inflammation during tumorigenesis, but the direct evidence such linkage remains unclear. We report here that persistent coculturing immortalized prostate epithelial cells with macrophages, without adding any carcinogens, induces tumorigenesis and induction involves alteration signaling macrophage androgen receptor (AR)-inflammatory chemokine CCL4–STAT3 activation as well epithelial-to-mesenchymal transition downregulation p53/PTEN...
Previous studies have found that tumor-associated macrophages (TAMs) promote cancer progression. We previously reported TAMs prostate metastasis via activation of the CCL2-CCR2 axis. The CCR4 (receptor CCL17 and CCL22) expression level in breast was to be associated with lung metastasis. aim this study elucidate role CCR2 were expressed human cell lines tissues. In vitro co-culture cells resulted increased CCL2 levels cells. addition induced CCL22 production migration invasion enhanced...
Upon binding to androgen, the androgen receptor (AR) can translocate into nucleus and bind response element(s) modulate its target genes. Here we have shown that MG132, a 26 S proteasome inhibitor, suppressed AR transactivation in an androgen-dependent manner prostate cancer LNCaP PC-3 cells. In contrast, MG132 showed no suppressive effect on glucocorticoid transactivation. Additionally, transfection of PSMA7, subunit, enhanced dose-dependent manner. The suppression by may then result...
Tumor necrosis factor receptor 1-associated death domain protein (TRADD) is the core adaptor recruited to TNF 1 (TNFR1) upon TNFα stimulation. In cells from TRADD-deficient mice, TNFα-mediated apoptosis and TNFα-stimulated NF-κB, JNK, ERK activation are defective. TRADD also important for germinal center formation, DR3-mediated costimulation of T cells, inflammatory responses in vivo . deficiency does not enhance IFNγ-induced signaling. Importantly, has a novel role TLR3 TLR4 participates...
Smad proteins have been demonstrated to be key components in the transforming growth factor β signaling cascade. Here we demonstrate that Smad4, together with Smad3, can interact androgen receptor (AR) DNA-binding and ligand-binding domains, which may result modulation of 5α-dihydrotestosterone-induced AR transactivation. Interestingly, prostate PC3 LNCaP cells, addition Smad3 enhance transactivation, co-transfection Smad4 then repress transactivation various response element-promoter...
Abstract Early studies suggested macrophages might play roles in inflammation-associated benign prostatic hyperplasia (BPH) development, yet the underlying mechanisms remain unclear. Here we first showed that CD68+ were identified both epithelium and stromal area of human BPH tissues. We then established an vitro co-culture model with prostate epithelial macrophage cell lines to study potential impacts infiltrating development found co-culturing cells promoted migration macrophages. In a...
Understanding the mechanism of chemoresistance and disease progression in patients with prostate cancer is important for developing novel treatment strategies. In particular, resistance to cabazitaxel a major challenge docetaxel‐resistant castration‐resistant (CRPC) because often administered as last resort. However, by which develops still unclear. C‐C motif chemokine ligands (CCL) were shown contribute castration cells via an autocrine mechanism. Therefore, we focused on CCL key factors...
The androgen receptor (AR) binds to response elements and regulates target genes via a mechanism involving coregulators. Here we demonstrate that the AR can interact with testicular orphan receptor-4 (TR4) function as repressor down-regulate TR4 by preventing binding its DNA. Interestingly, heterodimerization of also allows repress gene expression. Simultaneous exposure both receptors therefore could result in bidirectional suppression their genes. Together, these data coupling two different...
Fas-associated death domain (FADD) and caspase-8 are key signal transducers for receptor–induced apoptosis, whereas cellular FLICE-inhibitory protein (cFLIP) antagonizes this process. Interestingly, FADD also play a role in T cell development receptor (TCR)–mediated proliferative responses. To investigate the underlying mechanism, we generated cFLIP-deficient cells by reconstituting Rag−/− blastocysts with embryonic stem cells. These Rag chimeric mutant mice (rcFLIP−/−) had severely reduced...
Regulation of phosphoenolpyruvate carboxykinase (PEPCK), the key gene in gluconeogenesis, is critical for glucose homeostasis response to quick nutritional depletion and/or hormonal alteration.Here, we identified testicular orphan nuclear receptor 4 (TR4) as a PEPCK regulator modulating via transcriptional mechanism. TR4 transactivates 490-bp promoter-containing luciferase reporter activity by direct binding responsive element (TR4RE) located at -451 -439 promoter region. Binding TR4RE was...
Endotoxicity originating from a dangerous debris (i.e., lipopolysaccharide, LPS) of Gram-negative bacteria is challenging clinical problem, but no drugs or therapeutic strategies that can successfully address this issue have been identified yet. In study, we report subnanometer gold cluster efficiently block endotoxin activity to protect against sepsis. The blocker consists nanocluster serves as flakelike substrate and coating short alkyl motifs act an adhesive dock with LPS by compacting...
Early reports showed that androgen receptor (AR) NH2- and COOH-terminal (N-C) interaction was important for full AR function. However, the influence of these interactions on in vivo effects remains unclear. Here we tested some AR-associated peptides coregulators to determine their influences N-C interaction, transactivation, coregulator The results coactivators such as ARA70N, gelsolin, ARA54, SRC-1 can enhance transactivation but differential interaction. In contrast, corepressors ARA67...
TNF receptor-associated factor 2 (TRAF2) is a key intracellular signaling mediator that acts downstream of not only TNFα but also various members the superfamily. Here, we report that, despite their lack signaling, TRAF2(-/-)TNFα(-/-) mice develop an inflammatory disorder characterized by autoantibody accumulation and organ infiltration T cells with phenotypes activated, effector, memory cells. RAG1(-/-) reconstituted bone marrow showed increased numbers hyperactive rapidly developed...
// Kouji Izumi 1 , Atsushi Mizokami Hsiu-Ping Lin 2 Hui-Min Ho Hiroaki Iwamoto Aerken Maolake Ariunbold Natsagdorj Yasuhide Kitagawa Yoshifumi Kadono Hiroshi Miyamoto 3 Chiung-Kuei Huang 4 Mikio Namiki and Wen-Jye Department of Integrative Cancer Therapy Urology, Kanazawa University Graduate School Medical Science, Kanazawa, Japan Immunology Research Center, National Health Institutes, Zhunan, Miaoli County, Taiwan Departments Pathology Johns Hopkins Medicine, Baltimore, MD, USA The Warren...
14-3-3σ regulates cytokinesis and cell cycle arrest induced by DNA damage but its role in the immune system is unknown. Using gene-targeted 14-3-3σ-deficient (i.e., KO) mice, we studied of B-cell functions. Total numbers B cells were reduced spontaneous apoptosis peripheral cells. Upon antigen receptor engagement vitro, KO did not proliferate properly or up-regulate CD86. In response to T cell-independent antigens, showed poor secretion antigen-specific IgM. This deficit led increased...
Early studies suggest that TR4 nuclear receptor is a key transcriptional factor regulating various biological activities, including reproduction, cerebella development, and metabolism. Here we report mice lacking ( −/− ) exhibited increasing genome instability defective oxidative stress defense, which are associated with premature aging phenotypes. At the cellular level, observed rapid growth arrest less resistance to DNA damage in mouse embryonic fibroblasts (MEFs) vitro. Restoring or...
Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity the prostate bone metastasis microenvironment. Growth migration of human cells were assayed cocultures with stromal cells. LNC aP significantly increased when co‐cultured isolated from metastases. Cytokine array analysis conditioned medium cell cultures identified CCL 5 as a concentration‐dependent promoter migration. was suppressed C‐C motif ligand ( 5) neutralizing...
In situ hybridization analysis demonstrated that abundant testicular orphan receptor (TR4) transcripts were detected in kidney, intestine, and bone, which are vitamin D3 target organs. Cell transfection studies also the expression of gene, 25-hydroxyvitamin 24-hydroxylase, can be repressed by TR4 through high affinity binding (Kd = 1.32 nM) to direct repeat 3 response element (DR3VDRE). This TR4-mediated repression DR3VDRE is contrast our earlier report could induce thyroid hormone genes...