A5055007805- Prostate Cancer Treatment and Research
- Ubiquitin and proteasome pathways
- Immune Cell Function and Interaction
- Estrogen and related hormone effects
- Hormonal and reproductive studies
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Oral microbiology and periodontitis research
- Urinary Bladder and Prostate Research
- Salivary Gland Disorders and Functions
- Immune Response and Inflammation
- Cancer, Lipids, and Metabolism
- CAR-T cell therapy research
- Gut microbiota and health
- Epigenetics and DNA Methylation
- NF-κB Signaling Pathways
- Cancer, Hypoxia, and Metabolism
- interferon and immune responses
- Adenosine and Purinergic Signaling
- Immune cells in cancer
- Cancer-related Molecular Pathways
- Sexual function and dysfunction studies
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
Showa University
2019-2025
Kyushu University
2009-2020
Tokyo Medical and Dental University
2017-2019
University of Occupational and Environmental Health Japan
2016
Jikei University School of Medicine
2016
University Health Network
2012-2015
Ontario Institute for Cancer Research
2013-2015
University of Toronto
2014
Ministry of Defense
2009
Isocitrate dehydrogenase-1 ( IDH1 ) R132 mutations occur in glioma, but their physiological significance is unknown. Here we describe the generation and characterization of brain-specific Idh1 R132H conditional knock-in (KI) mice. mutation results hemorrhage perinatal lethality. Surprisingly, intracellular reactive oxygen species (ROS) are attenuated Idh1-KI brain cells despite an apparent increase NADP + /NADPH ratio. also show high levels D-2-hydroxyglutarate (D2HG) that associated with...
Abstract We previously reported that resident γδ T cells in the peritoneal cavity rapidly produced IL-17 response to Escherichia coli infection mobilize neutrophils. found this study IL-17-producing did not produce IFN-γ or IL-4, similar Th17 cells. specifically express CD25 but CD122, whereas CD122+ IFN-γ. were decreased still present IL-2- CD25-deficient mice, suggesting a role of IL-2 for their maintenance. IFN-γ-producing selectively IL-15-deficient mice. Surprisingly, already detected...
Tumorigenesis results from dysregulation of oncogenes and tumor suppressors that influence cellular proliferation, differentiation, apoptosis, and/or senescence. Many gene products involved in these processes are substrates the E3 ubiquitin ligase Mule/Huwe1/Arf-BP1 (Mule), but whether Mule acts as an oncogene or suppressor vivo remains controversial. We generated K14Cre;Mule flox/flox(y) (Mule kKO) mice subjected them to DMBA/PMA-induced skin carcinogenesis, which depends on oncogenic Ras...
Isocitrate dehydrogenase-1 (Idh1) is an important metabolic enzyme that produces NADPH by converting isocitrate to α-ketoglutarate. Idh1 known reduce reactive oxygen species (ROS) induced in cells treatment with lipopolysaccharide (LPS) vitro. Here, we used Idh1-deficient knockout (Idh1 KO) mice investigate the role of antioxidant defense vivo. KO showed heightened susceptibility death LPS and exhibited increased serum levels inflammatory cytokines such as tumor necrosis factor-α...
Background:Although androgen deprivation therapy for advanced prostate cancer initially exerts excellent anticancer effects, most treated with eventually recurs as castration-resistant (CRPC). Although aberrant kinase activation has been proposed a mechanism of castration resistance, comprehensive profiles in CRPC remain unknown. Therefore, we aimed to elucidate the kinome well role key molecules.
Abstract Tyrosine kinase 2 (Tyk2), a member of the JAK family, is involved in IL-12- and IL-23-mediated signaling. In present study, we examined roles Tyk2 development myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) by using knockout (KO) mice. vitro differentiation Th1 but not Th17 cells was severely impaired KO CD4 T cells, although did respond to IL-23. mice showed complete resistance against EAE with no infiltration spinal cord....
Immunotherapy plays a significant role in the management of renal cell carcinoma (RCC) patients with metastatic disease because RCC is highly resistant to both chemotherapy and radiation therapy. Many reports illustrate various approaches treatment RCC, such as cytokine-, antigen- or dendritic cell- (DC-) based immunotherapy, safety effectiveness immunotherapy have been highlighted by multiple clinical trials. Although antitumor immune responses clinically outcomes achieved these trials,...
Although invasive and metastatic progression via the epithelial-mesenchymal transition (EMT) acquisition of resistance to castration are both critical steps in prostate cancer, molecular mechanism this interaction remains unclear. In study, we aimed elucidate signaling between EMT, apply information development a novel therapeutic concept using transforming growth factor-β (TGF-β) inhibitor SB525334 combined with androgen-deprivation therapy against cancer an vivo model. This study revealed...
Chemopreventive and potential therapeutic effects of soy isoflavones have been shown to be effective in numerous preclinical studies as well clinical prostate cancer. Although the inhibition androgen receptor signaling has supposed one mechanism underlying their effects, precise remains unclear. Thus, this study aimed clarify mechanism. Among isoflavones, equol suppressed prostate‐specific antigen expression most potently androgen‐dependent LNC aP cells. However, inhibitory effect on...
What’s known on the subject? and What does study add? So far, transcription factor Twist1 has been reported to regulate Y‐box binding protein‐1 (YB‐1) expression play important roles in tumour growth, invasion drug resistance. This revealed that bladder cancer cells, regulated YB‐1 both promote malignant potentials including anticancer‐drug Although relation between Twist1/YB‐1 signaling resistance have suggested, their remain unknown. functional importance cancer, indicating are promising...
Although numerous epidemiological studies show aspirin to reduce risk of prostate cancer, the mechanism this effect is unclear. Here, we first confirmed that downregulated androgen receptor (AR) and prostate-specific antigen in cancer cells. We also found upregulated prostaglandin subtype EP3 but not EP2 or EP4. The antagonist L798106 knockdown increased AR expression cell proliferation, whereas agonist sulprostone decreased them, indicating affects expression. Additionally, ( PTGER3 )...
Klebsiella spp., an opportunistic infectious organism, is commensal in the nasal and oral cavities of humans. Recently, it has been reported that spp. ectopically colonize intestinal tract induce accumulation Th1 cells. For bacteria to tract, they need compete for nutrients with indigenous bacteria. Therefore, we focused on mannose, a mucus-derived sugar, mannose phosphotransferase system (PTS) (ManXYZ), mechanism uptake, terms their effects colonization immune responses We generated...
BACKGROUND Taxanes are the only cytotoxic chemotherapeutic agents proved to prolong survival in patients with castration‐resistant prostate cancer. However, because of intrinsic and acquired resistances taxanes, their therapeutical efficiencies modest, bringing a few months benefit. Y‐box binding protein‐1 (YB‐1) promotes cancer cell resistance various anticancer treatments, including taxanes. Here, we aimed elucidate mechanism taxane by YB‐1 examined overcoming targeting signaling. METHODS...
Significance T-cell homeostasis is a tightly regulated process that ensures constant number of naïve T cells in the periphery an organism. Mechanisms promote survival and homeostatic proliferation peripheral are essential for maintaining this balance thus effective immunity against pathogens incipient tumors. We have identified UV radiation resistance-associated gene (UVRAG), autophagic tumor suppressor many cell lineages, as novel nonautophagic regulator homeostasis. Furthermore, our...
Abstract BACKGROUND Prostate cancer is the most commonly diagnosed non‐cutaneous in American men. Unfortunately, few successful therapies for castration‐resistant prostate (CRPC) exist. The protein kinase A (PKA) pathway a critical mediator of cellular proliferation and differentiation various normal cancerous cells. However, PKA activity mechanism regulation CRPC remain unclear. Then, this study, we intended to reveal CRPC. METHODS Western blotting, quantitative real‐time polymerase chain...
Bladder cancer patients who are refractory to chemotherapy have a poor prognosis. Furthermore, additional chemotherapies provide little benefit relapsed after an initial response. Recently, it was reported that several molecular pathways implicated in bladder carcinogenesis, including the epidermal growth factor receptor (EGFR) pathway, vascular endothelial (VEGF) pathway and Ras-MAPK pathway. We hypothesized sunitinib would be effective as is oral inhibitor of multiple tyrosine kinases,...
Previously, we have shown that Y-box binding protein-1 (YB-1) regulates androgen receptor (AR) expression and contributes to castration resistance. However, the mechanism of YB-1 activation remains unknown. In this study, aimed elucidate role in relation resistance as well enzalutamide resistance, with a view developing novel therapeutic concept for castration-resistant prostate cancer (CRPC) treatment.The phosphorylation levels ribosomal S6 kinase 1 (RSK1), AR were examined by quantitative...
Abstract IL‐15 is a pleiotropic cytokine involved in host defense as well autoimmunity. IL‐15‐deficient mice show decrease of memory phenotype (MP) CD8 + T cells, which develop naturally naïve and whose origin unclear. It has been shown that self‐specific cells developed male H‐Y antigen‐specific TCR transgenic share many similarities with occurring MP normal mice. In this study, we found but not female decreased when they were crossed mice, mainly due to impaired peripheral maintenance. The...