- Angiogenesis and VEGF in Cancer
- Protease and Inhibitor Mechanisms
- Immune cells in cancer
- Endometrial and Cervical Cancer Treatments
- Cytokine Signaling Pathways and Interactions
- Circular RNAs in diseases
- Cell Adhesion Molecules Research
- Extracellular vesicles in disease
- Cancer Treatment and Pharmacology
- MicroRNA in disease regulation
- Ovarian cancer diagnosis and treatment
- Colorectal Cancer Treatments and Studies
- Cancer Mechanisms and Therapy
- Animal Genetics and Reproduction
- Cancer Cells and Metastasis
- Galectins and Cancer Biology
- Uterine Myomas and Treatments
- Chemokine receptors and signaling
- Cancer Genomics and Diagnostics
- Reproductive System and Pregnancy
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Sarcoma Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Molecular Biology Techniques and Applications
Osaka University
2016-2025
Osaka University Hospital
2018-2022
Soka University
2012-2018
Tokyo Women's Medical University
2018
University of Toronto
2007-2014
Sunnybrook Health Science Centre
2009-2014
Sunnybrook Research Institute
2014
University Health Network
2014
Health Sciences Centre
2009-2010
GlaxoSmithKline (Canada)
2010
Epithelial ovarian cancer (EOC) cells metastasize within the peritoneal cavity and directly encounter human mesothelial (HPMC) as initial step of metastasis. The contact between single layer involves direct communications that modulate progression but mechanisms are unclear. One candidate mediating cell-cell is exosomes, 30-100 nm membrane vesicles endocytic origin, through transfer proteins, mRNAs, or microRNAs. Therefore, goal was to mechanistically characterize how EOC-derived exosomes...
Abstract Granulocyte-colony stimulating factor (G-CSF) producing malignant tumor has been reported to occur in various organs and associated with poor clinical outcome. The aim of this study is investigate the significance G-CSF expression chemosensitivity uterine cervical cancer. data recurrent or advanced cancer patients who were treated platinum-based chemotherapy analyzed. Clinical samples, cell lines a mouse model employed examine mechanisms responsible for development chemoresistance...
microRNAs (miRNAs) stably exist in circulating blood and are encapsulated extracellular vesicles such as exosomes. The aims of this study were to identify which exosomal miRNAs highly produced from epithelial ovarian cancer (EOC) cells, analyze whether serum miRNA can be used discriminate patients with EOC healthy volunteers, investigate the functional role progression.Exosomes collected culture media serous cell lines, namely TYK-nu HeyA8 cells. An microarray revealed that several including...
Significance The poor prognosis of epithelial ovarian cancer (EOC) has not improved for several decades because drug resistance to current anticancer drugs. Furthermore, few molecularly targeted agents are effective EOC, likely EOC high tumor heterogeneity. Discovering new targets and mechanisms involved in the progression is therefore sorely needed. Our multiple CRISPR RNAi-based vivo loss-of-function screens have identified candidate targets, including druggable oncogene KPNB1, whose...
Abstract Ovarian cancer is largely diagnosed at advanced stages upon detection of multiple peritoneal dissemination, resulting in poor outcomes. CD47 overexpressed tumors, facilitates tumor immune evasion, and located on exosomes. We aimed to investigate the role exosomal ovarian progression. Prognostic significance expression was examined using a public database including 1,435 patients validated with 26 our institution. associated progression-free survival inversely correlated macrophage...
Abstract Low-dose metronomic chemotherapy has shown promising activity in many preclinical and some phase II clinical studies involving various tumor types. To evaluate further the potential therapeutic impact of for ovarian cancer, we developed a model advanced human cancer tested low-dose regimens alone or concurrent combination with an antiangiogenic drug, pazopanib. Clones SKOV-3 carcinoma cell line expressing secretable β-subunit choriogonadotropic (β-hCG) protein firefly luciferase...
microRNAs (miRNAs) stably exist in circulating blood encapsulated extracellular vesicles such as exosomes; therefore, serum miRNAs have the potential to serve novel cancer biomarkers. New diagnostic markers detect high grade serous ovarian (HGSOC) are urgently needed. The aim of this study was identify specific HGSOC and analyze whether miRNA can discriminate patients from healthy controls or with malignancies other histological types.Exosomes cell lines were collected exosomal extracted....
// Yasuto Kinose 1 , Kenjiro Sawada Koji Nakamura Ikuko Aska Toda Erika Nakatsuka Kae Hashimoto Seiji Mabuchi Kazuhiro Takahashi 2 Hirohisa Kurachi 3 Ernst Lengyel 4 and Tadashi Kimura Department of Obstetrics Gynecology, Osaka University Graduate School Medicine, Suita, Osaka, Japan Yamagata Faculty Yamagata, Medical Center Research Institute for Maternal Child Health, Izumi, Departments Gynecology/Section Gynecologic Oncology, Chicago, IL, USA Correspondence to: Sawada, email: Keywords :...
Ovarian cancer remains the most lethal gynecologic and new targeted molecular therapies against this miserable disease continue to be challenging. In study, we analyzed expressional patterns of Interleukin-6 (IL-6) its receptor (IL-6R) expression in ovarian tissues, evaluated impact these expressions on clinical outcomes patients, found that a high-level IL-6R but not IL-6 cells is an independent prognostic factor. vitro analyses using cell lines, while six (RMUG-S, RMG-1, OVISE, A2780,...
RNA interference is a powerful gene-silencing tool with potential clinical applications. However, its therapeutic use challenging because suitable carriers are unavailable. Exosomes stable small endogenous vesicles that can transport functional molecules to target cells, making them ideal interfering (siRNA) carriers. Herein, we elucidated the of patient-derived exosomes as an siRNA carrier for ovarian cancer (OC) treatment. The were extracted from culture medium primary fibroblasts...
Abstract Vascular endothelial growth factor (VEGF)–induced cell migration is an important component of tumor angiogenesis. Rho and Rho-associated kinase (ROCK) are key regulators focal adhesion, stress fiber formation, thus motility. Inhibitors this pathway have been shown to inhibit motility In study, we investigated the antiangiogenic effect fasudil, one ROCK inhibitors. Fasudil inhibited VEGF-induced migration, viability, tube formation in vitro human umbilical vein cells. was reduced by...
Acquired resistance to antiangiogenic drugs, such as sorafenib, is a major clinical problem. We studied development of sorafenib in new preclinical models human hepatocellular carcinoma (HCC) along with strategy delay resistance—combination metronomic chemotherapy. Three different xenograft were using Hep3B HCC cells, which are highly responsive namely, orthotopic and subcutaneous transplant severe combined immunodeficient mice, an nude mice. The complementary DNA for the β-subunit...
// Hiromasa Kuroda 1, * , Seiji Mabuchi Eriko Yokoi Naoko Komura 1 Katsumi Kozasa Yuri Matsumoto Mahiru Kawano Ryoko Takahashi Tomoyuki Sasano Kotaro Shimura Michiko Kodama Kae Hashimoto Kenjiro Sawada Eiichi Morii 2 and Tadashi Kimura Department of Obstetrics Gynecology, Osaka University Graduate School Medicine, Osaka, Japan Pathology, These authors contributed equally to this work Correspondence to: Mabuchi, email: smabuchi@gyne.med.osaka-u.ac.jp Keywords: MDSC; CSC; prostaglandin E2;...
Ovarian clear cell carcinoma (OCCC), particularly advanced or recurrent settings, is generally resistant to platinum-based chemotherapy, warranting novel therapeutic strategies. Mutations in the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway are frequently reported OCCC. Therefore, we hypothesized that PI3K/mTOR dual inhibitor, GSK458, and arsenic trioxide may exert synergistic anti-tumor effects on We investigated trioxide, combination...
<p>The effect on DNA damage activated by GSK458-As2O3 plus olaparib or carboplatin in OCCC cells.</p>
<p>Combination treatment with GSK458 and As2O3 shows anti-tumor effects in OCCC cells. Figure.</p>
<p>The effect on DNA damage activated by GSK458-As2O3 plus olaparib or carboplatin in OCCC cells.</p>
<p>Knockdown of PTEN partially inhibited autophagy flux induced by GSK458 and As2O3 combination.</p>
<p>Supplementary Materials and Methods</p>
<p>Effects of PTEN knockdown on the expression PI3K/AKT/mTOR pathway, cell proliferation treated with GSK458, As2O3, or combination. Figure.</p>
<p>Heatmap of angiogenesis-related genes and autophagy-related from RNA sequence after combinaton treatment with GSK458 As2O3.</p>