Research activity information

• Efficacy of Methionine Restriction and the PARP-inhibitor Olaparib and Their Combination on BRCA1 Mutant and Wild-type Triple-negative Breast Cancer Cell Lines.

  Mayuko Miki, Sachiko Inubushi, Qinghong Han, Shotaro Inoue, Tomonari Kunihisa, Hirokazu Tanino, Robert M Hoffman

  BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is a recalcitrant disease. The present study examined the efficacy of methionine restriction and the poly ADP-ribose polymerase (PARP)-inhibitor olaparib on BRCA1/2 wild-type and BRCA1 mutated TNBC cell lines. MATERIALS AND METHODS: The human BRCA1/2 wild-type cell line MDA-MB-231, and BRCA1-mutant cell lines MDA-MB-436 and HCC1937 were used to examine sensitivity to recombinant methioninase (rMETase) or a methionine-free medium or to olaparib or the combination of a methionine-free medium and olaparib. Cell viability was examined using the WST-8 reagent as well as by direct cell counting after Hoechst 33342 staining. RESULTS: MDA-MB-231 was sensitive to a methionine-free medium and rMETase and resistant to olaparib. The combination of olaparib and a methionine-free medium was not synergistic on MDA-MB-231 cells. MDA-MB-436 cells were not sensitive to a methionine-free medium but were sensitive to olaparib and rMETase. The combination of olaparib and a methionine medium was not synergistic in MDA-MB-436 cells. HCC1937 cells were sensitive to a methionine-free medium, partially sensitive to rMETase, partially resistant to olaparib, and sensitive to the combination of a methionine-free medium and olaparib. All three cell lines were sensitive to rMETase, with MDA-MB-436 being the most sensitive. CONCLUSION: Methionine restriction and olaparib showed synergistic efficacy on the BRCA1-mutant TNBC cell line HCC1937. The BRCA1-mutant cell line MDA-MB-436 was most sensitive to rMETase. The BRCA1/2 wild-type TNBC cell line MDA-MB-231 was sensitive to a methionine-free medium but resistant to olaparib. Therefore, methionine restriction has clinical potential for BRCA1/2 wild-type and BRCA1-mutant olaparib-resistant and -sensitive TNBC.

  Corresponding, Apr. 2025, Anticancer research, 45(4) (4), 1367 - 1372, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• MiR-575 in Exosomes of Vaginal Discharge Is Downregulated in Ovarian Cancer Patients.

  Maho Azumi, Sachiko Inubushi, Yoko Yano, Kenta Obata, Keitaro Yamanaka, Yoshito Terai

  BACKGROUND/AIM: Ovarian cancer is asymptomatic in its early stages, and often diagnosed at advanced stages, leading to a high recurrence rate. In recent years, exosomes have been shown to be useful for early-detection, prognosis prediction, and treatment of cancer. Although many studies of cancer-related exosomes using other bodily fluids have been reported, there are few studies examining vaginal discharge, but none related to ovarian cancer. In this study, we investigated a method for early-detection of ovarian cancer using vaginal discharge, which are physically close to the fallopian tubes, where ovarian cancer originates, and can be easily collected from outside the body. MATERIALS AND METHODS: Vaginal discharge was collected from 30 patients with ovarian cancer and 29 patients with benign gynecological diseases, and exosomal miRNAs were extracted. Samples from each group were submitted to miRNA microarray in order to examine miRNAs with significant differences in expression levels. We further narrowed down the list to four miRNAs based on literature and microarray data and examined the expression levels of miRNAs in the malignant and benign groups by RT-qPCR. RESULTS: MiR-575 expression was significantly decreased in the malignant group compared to the benign group (p=0.00861). qPCR results were analyzed for several patient characteristics and no significant differences were found. CONCLUSION: This is the first study to investigate exosomal miRNAs in vaginal discharge of ovarian cancer. Exosomal miR-575 in vaginal discharge may be used as a biomarker for ovarian cancer.

  2025, Cancer genomics & proteomics, 22(3) (3), 382 - 396, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Serum Exosomes Expressing CD9, CD63 and HER2 From Breast-Cancer Patients Decreased After Surgery of the Primary Tumor: A Potential Biomarker of Tumor Burden.

  Sachiko Inubushi, Tomonari Kunihisa, Marina Kuniyasu, Shotaro Inoue, Mayuko Yamamoto, Yuji Yamashita, Mayuko Miki, Sachiko Mizumoto, Motoi Baba, Robert M Hoffman, Hirokazu Tanino

  BACKGROUND/AIM: Exosomes are extracellular vesicles produced by both normal and cancer cells. Previous research has demonstrated that circulating exosomes derived from cancer cells may create a niche for future metastasis, distant from the primary tumor. In the present report, circulating exosomes were captured and quantified based on exosome-surface proteins in pre- and post-operative serum of breast cancer patients, focusing on the exosome markers CD9 and CD63, as well as HER2, a therapeutic target for breast cancer. MATERIALS AND METHODS: Eight breast cancer patients were recruited, and their pre- and post-operative serum samples were analyzed for CD63 and CD9; or CD9 and human epidermal growth factor receptor-2 (HER2), double-positive exosomes. An ExoCounter with antibody-conjugated beads was used to capture serum-derived exosomes. Sera from patients with tumors larger than 10 mm were used for analysis. The resected breast cancer was also histopathologically analyzed for the presence of HER2. RESULTS: CD63 and CD9 double-positive serum exosomes and CD9 and HER2 double-positive serum exosomes decreased after surgery in breast-cancer patients whose tumors expressed HER2, as determined by histopathological analysis. CONCLUSION: Serum exosomes expressing CD9, CD63 and HER2 are candidate biomarkers of tumor burden in HER2-positive breast-cancer patients.

  2024, Cancer genomics & proteomics, 21(6) (6), 580 - 584, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Induction of the DNA-Repair Gene POLQ only in BRCA1-mutant Breast-Cancer Cells by Methionine Restriction.

  Tomonari Kunihisa, Sachiko Inubushi, Hirokazu Tanino, Robert M Hoffman

  BACKGROUND/AIM: BRCA1/2 mutations in breast cancer cells impair homologous recombination and promote alternative end joining (Alt-EJ) for DNA-damage repair. DNA polymerase theta, encoded by POLQ, plays a crucial role in Alt-EJ, making it a potential therapeutic target, particularly in BRCA1/2-mutant cancers. Methionine restriction is a promising approach to target cancer cells due to their addiction to this amino acid. The present study investigated the expression of POLQ in BRCA1/2 wild-type and BRCA1-mutant breast cancer cells under methionine restriction. MATERIALS AND METHODS: POLQ mRNA expression was measured using qRT-PCR in BRCA1/2 wild-type (MDA-MB-231) and BRCA1- mutant (HCC1937 and MDA-MB-436) breast-cancer cells under normal, or serum-restricted, or serum- and methionine-restricted conditions. RESULTS: Compared to BRCA1/2 wild-type cells, BRCA1-mutant cells displayed significantly higher basal POLQ expression in normal medium. Methionine restriction further increased POLQ expression in the BRCA1-mutant cells but decreased it in the BRCA1/2 wild-type cells. CONCLUSION: The present findings suggest that methionine restriction showed differential effects on POLQ expression, potentially impacting Alt-EJ activity, in BRCA1/2 wild-type and BRCA1-mutant breast-cancer cells. Further investigation is needed to explore the potential of combining methionine restriction with DNA-repair inhibitors, such as PARP inhibitors, to overcome drug resistance in BRCA1/2 mutant cancers.

  2024, Cancer genomics & proteomics, 21(4) (4), 399 - 404, English, International magazine

  [Refereed]

  Scientific journal


• Target-Oriented Classification of Triple-negative Breast Cancer.

  Sachiko Mizumoto, Sachiko Inubushi, Mayuko Miki, Haruna Nakamura, Motoi Baba, Yuji Yamashita, Mayuko Yamamoto, Shotaro Inoue, Hirokazu Tanino, Tomonari Kunihisa

  BACKGROUND/AIM: Breast cancer that is estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor-2 (HER2)-negative is termed triple-negative breast cancer (TNBC). Cytotoxic chemotherapy remains the first choice of treatment against TNBC due to lack of specific therapeutic targets. TNBC is not classified based on therapeutic targets, but recently, the development of targeted therapies - including immune checkpoint inhibitors and poly (adenosine diphosphate-ribose) polymerase inhibitors - has gained attention. This study aimed to examine a novel target-oriented TNBC classification to further facilitate targeted therapy by classifying TNBC based on the breast cancer 1 (BRCA1)-like as well as the protein expression of HER2, programmed death ligand 1 (PD-L1), androgen receptor (AR), cytokeratin 5/6, and epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: We enrolled 17 patients with primary TNBC who did not receive preoperative chemotherapy and underwent surgery at the Kobe University Hospital, Japan, between January 1, 2018, and July 31, 2019. Immunohistochemical staining was performed on tumor specimens, while a BRCAness test was performed using multiplex ligation-dependent probe amplification (MLPA) analysis. A BRCAness score 0.5 or higher was considered BRCA1-like. RESULTS: Tumors were classified as HER2-low (immunohistochemistry score 1+ or 2+ and FISH negative), PD-L1 positive, AR positive, or BRCA1-like. HER2-low, PD-L1 positive, AR positive, and BRCA1-like were detected in 11 (64.7%), 4 (23.5%), 6 (35.3%), and 6 (35.3%) samples. The tumor of only one patient could not be classified into any of these categories. CONCLUSION: Almost all TNBC cases can be classified according to treatable targets.

  Corresponding, Nov. 2023, Anticancer research, 43(11) (11), 5067 - 5072, English, International magazine

  [Refereed]

  Scientific journal


• Protein corona formation on epigallocatechin gallate-Au nanoparticles suppressed tumor accumulation

  Chihiro Wakayama, Sachiko Inubushi, Tomonari Kunihisa, Sachiko Mizumoto, Motoi Baba, Hirokazu Tanino, Ik Sung Cho, Tooru Ooya

  Apr. 2023, JCIS Open, 9

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Methionine Restriction Increases Exosome Production and Secretion in Breast Cancer Cells.

  Sachiko Inubushi, Tomonari Kunihisa, Sachiko Mizumoto, Shotaro Inoue, Mayuko Miki, Atsushi Suetsugu, Hirokazu Tanino, Robert M Hoffman

  BACKGROUND/AIM: Methionine addiction is the elevated requirement for exogenous methionine for growth and survival of cancer cells, termed the Hoffman effect. Methionine-addicted cancer cells synthesize normal or excess amounts of methionine but still need an external source of methionine. Methionine restriction (MR) by either a methionine-free medium or in vivo by a low-methionine diet or by methioninase, selectively arrests cancer cells in the late S/G2 cell cycle phase, but not normal cells. The present study focuses on the comparison of production and secretion of exosomes by cancer cells under MR and normal conditions. MATERIALS AND METHODS: MDA-MB-231 cells (triple-negative breast cancer), containing exosomes labeled with CD63-GFP (CD63-GFP exosomes), were visualized by fluorescence microscopy. MDA-MB-231 cells expressing exosome-specific CD63-GFP were cultured in methionine-containing (MET+) or in methionine-free (MET-) DMEM conditions. Exosomes were isolated from conditioned medium of cultured MDA-MD-231 cells by ultracentrifugation and characterized by nanoparticle tracking analysis (NTA) and Western blotting. RESULTS: When MDA-MB-231-CD63-GFP cells were cultured under MR conditions, they arrested their growth and CD63-GFP-expressing exosomes were strongly increased in the cells. MR resulted in approximately a 2-fold increase in exosome production and secretion per cell, even though cell growth was arrested. Methionine restriction thus resulted in elevated exosome production and secretion per surviving cell. CONCLUSION: Exosome production and secretion in the cancer cells increased under MR, suggesting a relation between MR and exosome production and secretion.

  2023, Cancer genomics & proteomics, 20(5) (5), 412 - 416, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Reversion of methionine addiction of osteosarcoma cells to methionine independence results in loss of malignancy, modulation of the epithelial-mesenchymal phenotype and alteration of histone-H3 lysine-methylation

  Yusuke Aoki, Qinghong Han, Yasunori Tome, Jun Yamamoto, Yutaro Kubota, Noriyuki Masaki, Koya Obara, Kazuyuki Hamada, Justin D. Wang, Sachiko Inubushi, Michael Bouvet, Steven G. Clarke, Kotaro Nishida, Robert M. Hoffman

  Methionine addiction, a fundamental and general hallmark of cancer, known as the Hoffman Effect, is due to altered use of methionine for increased and aberrant transmethylation reactions. However, the linkage of methionine addiction and malignancy of cancer cells is incompletely understood. An isogenic pair of methionine-addicted parental osteosarcoma cells and their rare methionine-independent revertant cells enabled us to compare them for malignancy, their epithelial-mesenchymal phenotype, and pattern of histone-H3 lysine-methylation. Methionine-independent revertant 143B osteosarcoma cells (143B-R) were selected from methionine-addicted parental cells (143B-P) by their chronic growth in low-methionine culture medium for 4 passages, which was depleted of methionine by recombinant methioninase (rMETase). Cell-migration capacity was compared with a wound-healing assay and invasion capability was compared with a transwell assay in 143B-P and 143B-R cells in vitro. Tumor growth and metastatic potential were compared after orthotopic cell-injection into the tibia bone of nude mice in vivo. Epithelial-mesenchymal phenotypic expression and the status of H3 lysine-methylation were determined with western immunoblotting. 143B-P cells had an IC₅₀ of 0.20 U/ml and 143B-R cells had an IC₅₀ of 0.68 U/ml for treatment with rMETase, demonstrating that 143B-R cells had regained the ability to grow in low methionine conditions. 143B-R cells had reduced cell migration and invasion capability in vitro, formed much smaller tumors than 143B-P cells and lost metastatic potential in vivo, indicating loss of malignancy in 143B-R cells. 143B-R cells showed gain of the epithelial marker, ZO-1 and loss of mesenchymal markers, vimentin, Snail, and Slug and, an increase of histone H3K9me3 and H3K27me3 methylation and a decrease of H3K4me3, H3K36me3, and H3K79me3 methylation, along with their loss of malignancy. These results suggest that shifting the balance in histone methylases might be a way to decrease the malignant potential of cells. The present results demonstrate the rationale to target methionine addiction for improved sarcoma therapy.

  Frontiers Media SA, Nov. 2022, Frontiers in Oncology, 12, 1009548 - 1009548, English, International magazine

  [Refereed]

  Scientific journal


• Linkage of methionine addiction, histone lysine hypermethylation, and malignancy.

  Jun Yamamoto, Sachiko Inubushi, Qinghong Han, Yoshihiko Tashiro, Norihiko Sugisawa, Kazuyuki Hamada, Yusuke Aoki, Kentaro Miyake, Ryusei Matsuyama, Michael Bouvet, Steven G Clarke, Itaru Endo, Robert M Hoffman

  Methionine addiction, found in all types of cancer investigated, is because of the overuse of methionine by cancer cells for excess transmethylation reactions. In the present study, we compared the histone H3 lysine-methylation status and degree of malignancy between methionine-addicted cancer cells and their isogenic methionine-independent revertants, selected by their growth in low concentration of methionine. The methionine-independent revertans can grow on low levels of methionine or independently of exogenous methionine using methionine precursors, as do normal cells. In the methionine-independent revertants, the excess levels of trimethylated histone H3 lysine marks found in the methionine-addicted parental cancer cells were reduced or lost, and their tumorigenicity and experimental metastatic potential in nude mice were also highly reduced. Methionine addiction of cancer is linked with malignancy and hypermethylation of histone H3 lysines. The results of the present study thus provide a unique framework to further understand a fundamental basis of malignancy.

  Apr. 2022, iScience, 25(4) (4), 104162 - 104162, English, International magazine

  [Refereed]

  Scientific journal


• A Rare Case of Bilateral Pectoralis Major Muscle Defect and Abnormal Muscle

  Mayuko Yamamoto, Tomonari Kunihisa, Motoi Baba, Sachiko Mizumoto, Yuji Yamashita, Mayuko Miki, Sachiko Inubushi, Aoi Okamoto, Ryuhei Fujimoto, Hirokazu Tanino

  S. Karger {AG}, Mar. 2022, Case Reports in Oncology, 351 - 355

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Extent and Instability of Trimethylation of Histone H3 Lysine Increases With Degree of Malignancy and Methionine Addiction

  Jun Yamamoto, Yusuke Aoki, Sachiko Inubushi, Qinghong Han, Kazuyuki Hamada, Yoshihiko Tashiro, Kentaro Miyake, Ryusei Matsuyama, Michael Bouvet, Steven G. Clarke, Itaru Endo, Robert M. Hoffman

  Jan. 2022, CANCER GENOMICS & PROTEOMICS, 19(1) (1), 12 - 18, English

  [Refereed]

  Scientific journal


• Size Dependency of Selective Cellular Uptake of Epigallocatechin Gallate-modified Gold Nanoparticles for Effective Radiosensitization

  Ning Gan, Chihiro Wakayama, Sachiko Inubushi, Tomonari Kunihisa, Sachiko Mizumoto, Motoi Baba, Hirokazu Tanino, Tooru Ooya

  Dec. 2021, ACS APPLIED BIO MATERIALS, 5(1) (1), 355 - 365, English, International magazine

  [Refereed]

  Scientific journal


• Over-methylation of Histone H3 Lysines Is a Common Molecular Change Among the Three Major Types of Soft-tissue Sarcoma in Patient-derived Xenograft (PDX) Mouse Models

  YUSUKE AOKI, JUN YAMAMOTO, YASUNORI TOME, KAZUYUKI HAMADA, NORIYUKI MASAKI, SACHIKO INUBUSHI, YOSHIHIKO TASHIRO, MICHAEL BOUVET, ITARU ENDO, KOTARO NISHIDA, ROBERT M. HOFFMAN

  Dec. 2021, Cancer Genomics - Proteomics, 18(6) (6), 715 - 721, English

  [Refereed]

  Scientific journal


• Exosome-mediated radiosensitizing effect on neighboring cancer cells via increase in intracellular levels of reactive oxygen species

  Ai Nakaoka, Makiko Nakahana, Sachiko Inubushi, Hiroaki Akasaka, Mohammed Salah, Yoshiko Fujita, Hikaru Kubota, Mennaallah Hassan, Ryo Nishikawa, Naritoshi Mukumoto, Takeaki Ishihara, Daisuke Miyawaki, Takashi Sasayama, Ryohei Sasaki

  Apr. 2021, ONCOLOGY REPORTS, 45(4) (4), 1 - 1, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Reversion from Methionine Addiction to Methionine Independence Results in Loss of Tumorigenic Potential of Highly-malignant Lung-cancer Cells

  Jun Yamamoto, Yusuke Aoki, Qinghong Han, Norihiko Sugisawa, Yu Sun, Kazuyuki Hamada, Hiroto Nishino, Sachiko Inubushi, Kentaro Miyake, Ryusei Matsuyama, Michael Bouvet, Itaru Endo, Robert M. Hoffman

  Feb. 2021, ANTICANCER RESEARCH, 41(2) (2), 641 - 643, English, International magazine

  [Refereed]

  Scientific journal


• Triple-Methyl Blockade With Recombinant Methioninase, Cycloleucine, and Azacitidine Arrests a Pancreatic Cancer Patient-Derived Orthotopic Xenograft Model

  Norihiko Sugisawa, Jun Yamamoto, Qinghong Han, Yuying Tan, Yoshihiko Tashiro, Hiroto Nishino, Sachiko Inubushi, Kazuyuki Hamada, Kei Kawaguchi, Michiaki Unno, Michael Bouvet, Robert M. Hoffman

  Jan. 2021, PANCREAS, 50(1) (1), 93 - 98, English, International magazine

  [Refereed]

  Scientific journal


• A Universal Gelfoam 3-D Histoculture Method to Establish Patient-derived Cancer Cells (3D-PDCC) Without Fibroblasts from Patient-derived Xenografts

  Jun Yamamoto, Norihiko Sugisawa, Kazuyuki Hamada, Hiroto Nishino, Kentaro Miyake, Ryusei Matsuyama, Sachiko Inubushi, Hirokazu Tanino, Michael Bouvet, Itaru Endo, Robert M. Hoffman

  Dec. 2020, ANTICANCER RESEARCH, 40(12) (12), 6765 - 6768, English, International magazine

  [Refereed]

  Scientific journal


• Histone methylation status of H3K4me3 and H3K9me3 under methionine restriction is unstable in methionine-addicted cancer cells, but stable in normal cells

  Jun Yamamoto, Qinghong Han, Sachiko Inubushi, Norihiko Sugisawa, Kazuyuki Hamada, Hiroto Nishino, Kentaro Miyake, Takafumi Kumamoto, Ryusei Matsuyama, Michael Bouvet, Itaru Endo, Robert M. Hoffman

  Dec. 2020, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 533(4) (4), 1034 - 1038, English, International magazine

  [Refereed]

  Scientific journal


• Co-implantation of Tumor and Extensive Surrounding Tissue Improved the Establishment Rate of Surgical Specimens of Human-Patient Cancer in Nude Mice: Toward the Goal of Universal Individualized Cancer Therapy

  Takuya Murata, Chihiro Hozumi, Yukihiko Hiroshima, Koichiro Shimoya, Atsushi Hongo, Sachiko Inubushi, Hirokazu Tanino, Robert M. Hoffman

  Nov. 2020, IN VIVO, 34(6) (6), 3241 - 3245, English

  [Refereed]

  Scientific journal


• Sutureless Surgical Orthotopic Implantation Technique of Primary and Metastatic Cancer in the Liver of Mouse Models

  Hiroto Nishino, Hannah M. Hollandsworth, Norihiko Sugisawa, Jun Yamamoto, Yoshihiko Tashiro, Sachiko Inubushi, Kazuyuki Hamada, Y. U. Sun, Hyein Lim, Siamak Amirfakhri, Filemoni Filemoni, Robert M. Hoffman, Michael Bouvet

  Nov. 2020, IN VIVO, 34(6) (6), 3153 - 3157, English

  [Refereed]

  Scientific journal


• A Non-invasive Imageable GFP-expressing Mouse Model of Orthotopic Human Bladder Cancer

  Y. U. Sun, Hiroto Nishino, Ming Zhao, Kentaro Miyake, Norihiko Sugisawa, Jun Yamamoto, Yoshihiko Tashiro, Sachiko Inubushi, Kazuyuki Hamada, Guangwei Zhu, Hyein Lim, Robert M. Hoffman

  Nov. 2020, IN VIVO, 34(6) (6), 3225 - 3231, English

  [Refereed]

  Scientific journal


• Oral recombinant methioninase increases TRAIL receptor-2 expression to regress pancreatic cancer in combination with agonist tigatuzumab in an orthotopic mouse model

  Jun Yamamoto, Kentaro Miyake, Qinghong Han, Yuying Tan, Sachiko Inubushi, Norihiko Sugisawa, Takashi Higuchi, Yoshihiko Tashiro, Hiroto Nishino, Yuki Homma, Ryusei Matsuyama, Sant P. Chawla, Michael Bouvet, Shree Ram Singh, Itaru Endo, Robert M. Hoffman

  Nov. 2020, CANCER LETTERS, 492, 174 - 184, English, International magazine

  [Refereed]

  Scientific journal


• Ischemia reperfusion-induced metastasis is resistant to PPAR gamma agonist pioglitazone in a murine model of colon cancer

  Yoshihiko Tashiro, Hiroto Nishino, Takashi Higuchi, Norihiko Sugisawa, Yasunari Fukuda, Jun Yamamoto, Sachiko Inubushi, Takeshi Aoki, Masahiko Murakami, Shree Ram Singh, Michael Bouvet, Robert M. Hoffman

  Oct. 2020, SCIENTIFIC REPORTS, 10(1) (1), 18565 - 18565, English, International magazine

  [Refereed]

  Scientific journal


• Novel artifact-robust and highly visible zinc solid fiducial marker for kilovoltage x-ray image-guided radiation therapy

  Tianyuan Wang, Sachiko Inubushi, Naoko Ikeo, Toshiji Mukai, Keisuke Okumura, Hiroaki Akasaka, Ryuichi Yada, Kenji Yoshida, Daisuke Miyawaki, Takeaki Ishihara, Ai Nakaoka, Ryohei Sasaki

  Oct. 2020, MEDICAL PHYSICS, 47(10) (10), 4703 - 4710, English, International magazine

  [Refereed]

  Scientific journal


• Oncogenic miRNAs Identified in Tear Exosomes From Metastatic Breast Cancer Patients (vol 40, pg 3091, 2020)

  Sachiko Inubushi, Hiroki Kawaguchi, Sachiko Mizumoto, Tomonari Kunihisa, Motoi Baba, Yukiya Kitayama, Toshifumi Takeuchi, Robert M. Hoffman, Hirokazu Tanino, Ryohei Sasaki

  Aug. 2020, ANTICANCER RESEARCH, 40(8) (8), 4805 - 4805, English


• Investigation of the potential of using TiO(2)nanoparticles as a contrast agent in computed tomography and magnetic resonance imaging

  Hiroaki Akasaka, Naritoshi Mukumoto, Masao Nakayama, Tianyuan Wang, Ryuichi Yada, Yasuyuki Shimizu, Sachiko Inubushi, Katsusuke Kyotani, Keisuke Okumura, Masanori Miyamoto, Ai Nakaoka, Kenta Morita, Yuya Nishimura, Chiaki Ogino, Ryohei Sasaki

  Aug. 2020, APPLIED NANOSCIENCE, 10(8) (8), 3143 - 3148, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Oncogenic miRNAs Identified in Tear Exosomes From Metastatic Breast Cancer Patients.

  Sachiko Inubushi, Hiroki Kawaguchi, Sachiko Mizumoto, Tomonari Kunihisa, Motoi Baba, Yukiya Kitayama, Toshifumi Takeuchi, Robert M Hoffman, Hirokazu Tanino, Ryohei Sasaki

  BACKGROUND/AIM: Exosomes are produced by normal and cancer cells. Exosomes are found in the serum of cancer patients and have been used for diagnosis and prognosis. Recently tears from non-cancer patients have been found to contain exosomes. In the present report we describe tears from advanced breast-cancer patients. MATERIALS AND METHODS: We found oncogenic miRNAs in the exosomes isolated from tear fluids obtained from five patients with metastatic breast cancer and compared them with tear exosomes form eight healthy volunteers. RESULTS: Tear exosomes had a significantly higher quantity of exosome markers than serum exosomes (CD9, CD63). Tear exosomes were subjected to quantitative reverse-transcription polymerase reaction (qRT-PCR), and western blot analysis to elucidate the status of miRNAs, previously reported in serum from patients with metastatic breast cancer. qRT-PCR and western-blot analysis revealed that breast-cancer-specific miR-21 and miR-200c were highly expressed in tear exosomes from metastatic breast cancer patients in contrast to tear exosomes from healthy volunteers. CONCLUSION: Tear exosomes can be a potential source of diagnostic and prognostic biomarkers for metastatic breast cancer, and possibly other cancers or diseases.

  Lead, Jun. 2020, Anticancer research, 40(6) (6), 3091 - 3096, English, International magazine

  [Refereed]

  Scientific journal


• Oral Recombinant Methioninase Prevents Nonalcoholic Fatty Liver Disease in Mice on a High Fat Diet

  Yoshihiko Tashiro, Qinghong Han, Yuying Tan, Norihiko Sugisawa, Jun Yamamoto, Hiroto Nishino, Sachiko Inubushi, Yu Sun, Hyein Lim, Takeshi Aoki, Masahiko Murakami, Yoshihisa Takahashi, Michael Bouvet, Robert M. Hoffman

  May 2020, IN VIVO, 34(3) (3), 979 - 984, English

  [Refereed]

  Scientific journal


• Oral Recombinant Methioninase Inhibits Diabetes Onset in Mice on a High-fat Diet

  Yoshihiko Tashiro, Qinghong Han, Yuying Tan, Norihiko Sugisawa, Jun Yamamoto, Hiroto Nishino, Sachiko Inubushi, Yu Sun, Guangwei Zhu, Hyein Lim, Takeshi Aoki, Masahiko Murakami, Michael Bouvet, Robert M. Hoffman

  May 2020, IN VIVO, 34(3) (3), 973 - 978, English

  [Refereed]

  Scientific journal


• Eribulin Regresses a Cisplatinum-resistant Rare-type Triple-negative Matrix-producing Breast Carcinoma Patient-derived Orthotopic Xenograft Mouse Model

  Jun Yamamoto, Takuya Murata, Norihiko Sugisawa, Takashi Higuchi, Yoshihiko Tashiro, Hiroto Nishino, Sachiko Inubushi, Yu Sun, Hyein Lim, Kentaro Miyake, Koichiro Shimoya, Tsunehisa Nomura, Junichi Kurebayashi, Hirokazu Tanino, Chihiro Hozumi, Michael Bouvet, Shree Ram Singh, Itaru Endo, Robert M. Hoffman

  May 2020, ANTICANCER RESEARCH, 40(5) (5), 2475 - 2479, English, International magazine

  [Refereed]

  Scientific journal


• A Single Low Dose of Eribulin Regressed a Highly Aggressive Triple-negative Breast Cancer in a Patient-derived Orthotopic Xenograft Model.

  Hye In Lim, Jun Yamamoto, Sachiko Inubushi, Hiroto Nishino, Yoshihiko Tashiro, Norihiko Sugisawa, Quinhong Han, Y U Sun, Hee Jun Choi, Seok Jin Nam, Moon Bo Kim, Ji Sun Lee, Chihiro Hozumi, Michael Bouvet, Shree Ram Singh, Robert M Hoffman

  May 2020, Anticancer research, 40(5) (5), 2481 - 2485, English, International magazine

  [Refereed]

  Scientific journal


• A Triple-negative Matrix-producing Breast Carcinoma Patient-derived Orthotopic Xenograft (PDOX) Mouse Model Is Sensitive to Bevacizumab and Vinorelbine, Regressed by Eribulin and Resistant to Olaparib

  Jun Yamamoto, Takuya Murata, Yoshihiko Tashiro, Takashi Higuchi, Norihiko Sugisawa, Hiroto Nishino, Sachiko Inubushi, Yu Sun, Hyein Lim, Kentaro Miyake, Atsushi Hongo, Tsunehisa Nomura, Wataru Saitoh, Takuya Moriya, Hirokazu Tanino, Chihiro Hozumi, Michael Bouvet, Shree Ram Singh, Itaru Endo, Robert M. Hoffman

  May 2020, ANTICANCER RESEARCH, 40(5) (5), 2509 - 2514, English, International magazine

  [Refereed]

  Scientific journal


• Antibody-Conjugated Signaling Nanocavities Fabricated by Dynamic Molding for Detecting Cancers Using Small Extracellular Vesicle Markers from Tears

  Toshifumi Takeuchi, Kisho Mori, Hirobumi Sunayama, Eri Takano, Yukiya Kitayama, Taku Shimizu, Yuzuki Hirose, Sachiko Inubushi, Ryohei Sasaki, Hirokazu Tanino

  Apr. 2020, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 142(14) (14), 6617 - 6624, English, International magazine

  [Refereed]

  Scientific journal


• Oral Recombinant Methioninase Prevents Obesity in Mice on a High-fat Diet

  Yoshihiko Tashiro, Qinghong Han, Yuying Tan, Norihiko Sugisawa, Jun Yamamoto, Hiroto Nishino, Sachiko Inubushi, Takashi Higuchi, Takeshi Aoki, Masahiko Murakami, Robert M. Hoffman

  Mar. 2020, IN VIVO, 34(2) (2), 489 - 494, English

  [Refereed]

  Scientific journal


• 放射線治療 QOLを考慮した局所治療 小児がんに対する吸収性スペーサー留置を併用した粒子線治療

  佐々木 良平, 出水 祐介, 岩田 宏満, 亀井 美智, 文野 誠久, 赤坂 浩亮, 王 天縁, 妹尾 悟史, 犬伏 祥子, 宮脇 大輔, 吉田 賢史, 小松 昇平, 福本 巧

  (一社)日本小児血液・がん学会, Sep. 2019, 日本小児血液・がん学会雑誌, 56(2) (2), 148 - 152, Japanese

  [Refereed]


• Amelioration of Radiation Enteropathy by Dietary Supplementation With Reduced Coenzyme Q10

  Yasuyuki Shimizu, Naritoshi Mukumoto, Nelly Idrus, Hiroaki Akasaka, Sachiko Inubushi, Kenji Yoshida, Daisuke Miyawaki, Takeaki Ishihara, Yoshiaki Okamoto, Takahiro Yasuda, Makiko Nakahana, Ryohei Sasaki

  Apr. 2019, ADVANCES IN RADIATION ONCOLOGY, 4(2) (2), 237 - 245, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Innentitelbild: A Pretreatment‐Free, Polymer‐Based Platform Prepared by Molecular Imprinting and Post‐Imprinting Modifications for Sensing Intact Exosomes (Angew. Chem. 6/2019)

  Kisho Mori, Mitsuhiro Hirase, Takahiro Morishige, Eri Takano, Hirobumi Sunayama, Yukiya Kitayama, Sachiko Inubushi, Ryohei Sasaki, Masakazu Yashiro, Toshifumi Takeuchi

  Wiley, Feb. 2019, Angewandte Chemie, 131(6) (6), 1536 - 1536

  Scientific journal


• Inside Cover: A Pretreatment‐Free, Polymer‐Based Platform Prepared by Molecular Imprinting and Post‐Imprinting Modifications for Sensing Intact Exosomes (Angew. Chem. Int. Ed. 6/2019)

  Kisho Mori, Mitsuhiro Hirase, Takahiro Morishige, Eri Takano, Hirobumi Sunayama, Yukiya Kitayama, Sachiko Inubushi, Ryohei Sasaki, Masakazu Yashiro, Toshifumi Takeuchi

  Wiley, Feb. 2019, Angewandte Chemie International Edition, 58(6) (6), 1522 - 1522

  Scientific journal


• A Pretreatment-Free, Polymer-Based Platform Prepared by Molecular Imprinting and Post-Imprinting Modifications for Sensing Intact Exosomes

  Kisho Mori, Mitsuhiro Hirase, Takahiro Morishige, Eri Takano, Hirobumi Sunayama, Yukiya Kitayama, Sachiko Inubushi, Ryohei Sasaki, Masakazu Yashiro, Toshifumi Takeuchi

  Feb. 2019, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 58(6) (6), 1612 - 1615, English, International magazine

  [Refereed]

  Scientific journal


• Evaluation of a Small Animal Irradiation System for Animal Experiments Using EBT3 Model GAFCHROMIC™ Film.

  Yasuyuki Shimizu, Hiroaki Akasaka, Daisuke Miyawaki, Naritoshi Mukumoto, Masao Nakayama, Tianyuan Wang, Saki Osuga, Sachiko Inubushi, Ryuichi Yada, Yasuo Ejima, Kenji Yoshida, Takeaki Ishihara, Ryohei Sasaki

  Jan. 2018, The Kobe journal of medical sciences, 63(3) (3), E84-E91 - E91, English, Domestic magazine

  [Refereed]

  Scientific journal


• MGDG extracted from spinach enhances the cytotoxicity of radiation in pancreatic cancer cells.

  Hiroaki Akasaka, Yoshiyuki Mizushina, Kenji Yoshida, Yasuo Ejima, Naritoshi Mukumoto, Tianyuan Wang, Sachiko Inubushi, Masao Nakayama, Yuki Wakahara, Ryohei Sasaki

  Nov. 2016, Radiation oncology (London, England), 11(1) (1), 153 - 153, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Biological and Biochemical Characterization of Mice Expressing Prion Protein Devoid of the Octapeptide Repeat Region after Infection with Prions

  Yoshitaka Yamaguchi, Hironori Miyata, Keiji Uchiyama, Akira Ootsuyama, Sachiko Inubushi, Tsuyoshi Mori, Naomi Muramatsu, Shigeru Katamine, Suehiro Sakaguchi

  Aug. 2012, PLOS ONE, 7(8) (8), e43540, English, International magazine

  [Refereed]

  Scientific journal


• Identification of Annexin A1 as a Novel Substrate for HAP-Mediated Ubiquitylation

  Tetsu Shimoji, Kyoko Murakami, Yuichi Sugiyama, Mami Matsuda, Sachiko Inubushi, Junichi Nasu, Masayuki Shirakura, Tetsuro Suzuki, Takaji Wakita, Tatsuya Kishino, Hak Hotta, Tatsuo Miyamura, Ikuo Shoji

  Apr. 2009, JOURNAL OF CELLULAR BIOCHEMISTRY, 106(6) (6), 1123 - 1135, English, International magazine

  [Refereed]

  Scientific journal


• Hepatitis C virus NS5A protein interacts with and negatively regulates the non-receptor protein tyrosine kinase Syk

  Sachiko Inubushi, Motoko Nagano-Fujii, Kikurni Kitayama, Motofumi Tanaka, Chunying An, Hiroshi Yokozaki, Hirohei Yamamura, Hideko Nuriya, Michinori Kohara, Kiyonao Sada, Hak Hotta

  Lead, May 2008, JOURNAL OF GENERAL VIROLOGY, 89(Pt 5) (Pt 5), 1231 - 1242, English, International magazine

  [Refereed]

  Scientific journal


• Structural gene and strain specificity of a novel cysteine protease produced by Staphylococcus aureus isolated from a diseased chicken.

  Shotaro Takeuchi, Kazue Matsunaga, Sachiko Inubushi, Hiroki Higuchi, Keisuke Imaizumi, Toshio Kaidoh

  Oct. 2002, Veterinary microbiology, 89(2-3) (2-3), 201 - 10, English, International magazine

  [Refereed]

  Scientific journal


• Genetic and enzymatic analyses of metalloprotease (aureolysin) from Staphylococcus aureus isolated from domestic animals.

  Shotaro Takeuchi, Minoru Saito, Keisuke Imaizumi, Toshio Kaidoh, Hiroki Higuchi, Sachiko Inubushi

  Jan. 2002, Veterinary microbiology, 84(1-2) (1-2), 135 - 42, English, International magazine

  [Refereed]

  Scientific journal

• マイクロ波散乱場断層イメージング技術による乳房画像診断

  稲垣明里, 稲垣明里, 平井綾華, 谷野裕一, 谷野裕一, 平尾益美, 福田千紘, 田根香織, 橋本一樹, 佐久間淑子, 廣利浩一, 金昇晋, 高尾信太郎, 高尾信太郎, 松本元, 結縁幸子, 矢田善弘, 矢内勢司, 門澤秀一, 大久保ゆうこ, 大段仁奈, 御勢文子, 一ノ瀬庸, 田代敬, 山神和彦, 山神和彦, 渡邊奈津子, 小西豊, 鶴原知子, 山元奈穂, 山本直哉, 岡本交二, 岡本交二, 山本真由子, 大谷真紀子, 松尾容子, 橋本舞雪, 井上翔太朗, 馬場基, 水本紗千子, 三木万由子, 犬伏祥子, 國久智成, 國久智成, 八木潤子, 河野誠之, 美馬勇輝, 弓井孝佳, 中島義晴, 木村憲明, 木村憲明, 木村建次郎, 木村建次郎, 木村建次郎, 木村建次郎

  2023, 日本乳癌画像研究会プログラム・抄録集, 32nd (Web)


• Measurement of permittivity distribution in a healthy female breast by microwave mammography

  稲垣明里, 稲垣明里, 平井綾華, 木村建次郎, 木村建次郎, 木村建次郎, 木村建次郎, 高尾信太郎, 高尾信太郎, 佐久間淑子, 田根香織, 廣利浩一, 金昇晋, 結縁幸子, 松本元, 田代敬, 山神和彦, 山神和彦, 岡本交二, 岡本交二, 犬伏祥子, 國久智成, 國久智成, 谷野裕一, 谷野裕一, 弓井孝佳, 中島義晴, 木村憲明, 木村憲明

  2023, 応用物理学会春季学術講演会講演予稿集(CD-ROM), 70th


• 乳房脂肪組織の誘電分散とマイクロ波マンモグラフィへの影響

  稲垣明里, 稲垣明里, 平井綾華, 木村建次郎, 木村建次郎, 木村建次郎, 木村建次郎, 馬場基, 谷野裕一, 谷野裕一, 高尾信太郎, 高尾信太郎, 佐久間淑子, 田根香織, 廣利浩一, 金昇晋, 犬伏祥子, 國久智成, 國久智成, 岡本交二, 岡本交二, 結縁幸子, 松本元, 田代敬, 山神和彦, 山神和彦, 中島義晴, 弓井孝佳, 木村憲明, 木村憲明

  2023, 日本乳癌学会学術総会(CD-ROM), 31st


• コエンザイムQ10摂取マウスの放射線防護の可能性

  清水康之, 犬伏祥子, 平修, 佐々木良平

  2019, 質量分析総合討論会講演要旨集, 67th


• 小児がんに対する吸収性スペーサー留置を併用した粒子線治療

  佐々木良平, 出水祐介, 岩田宏満, 亀井美智, 文野誠久, 赤坂浩亮, 王天縁, 妹尾悟史, 犬伏祥子, 宮脇大輔, 吉田賢史, 小松昇平, 福本巧

  2019, 日本小児血液・がん学会雑誌(Web), 56(2) (2)


• インタクトエクソソームによる乳がん高速検知のための抗体融合分子インプリントセンシングチップ

  竹内俊文, 森貴翔, 清水拓, 広瀬柚月, 高野恵里, 砂山博文, 北山雄己哉, 犬伏祥子, 佐々木良平, 谷野裕一

  2019, 応用物理学会秋季学術講演会講演予稿集(CD-ROM), 80th


• 放射線治療:QOLを考慮した局所治療 小児がんに対する吸収性スペーサーの開発

  佐々木 良平, 岩田 宏満, 亀井 美智, 出水 祐介, 文野 誠久, 中尾 朋平, 淡河 恵津世, 王 天縁, 妹尾 悟史, 犬伏 祥子

  (一社)日本小児血液・がん学会, Oct. 2018, 日本小児血液・がん学会雑誌, 55(4) (4), 169 - 169, Japanese


• 過酸化チタンナノ粒子の併用による放射線増感治療法の開発

  西村 勇哉, 森田 健太, 荻野 千秋, 犬伏 祥子, 佐々木 良平, 近藤 昭彦

  日本DDS学会, May 2018, 日本DDS学会学術集会プログラム予稿集, 34回, 204 - 204, Japanese


• Development of bioabsorbable spacer for pediatric malignant tumors

  佐々木良平, 岩田宏満, 亀井美智, 出水祐介, 文野誠久, 中尾朋平, 中尾朋平, 淡河恵津世, 王天縁, 妹尾悟史, 犬伏祥子

  2018, 日本小児血液・がん学会雑誌(Web), 55(4) (4)


• 放射線照射時における子宮頸部腺がん細胞から分泌される細胞外小胞体の機能解析-子宮温存を目指した子宮頸部腺がんの放射線治療抵抗性の克服にむけて-

  犬伏祥子, 吉田賢史, 佐々木良平

  2018, 女性健康科学研究会誌, 7(1) (1)


• パラボリック・フライトを想定したマウスにおける過重力ストレスへの反応の解析

  TOMINAGA Daisuke, TOMINAGA Daisuke, INUBUSHI Sachiko, INUBUSHI Sachiko, HOMMA Atsuko, HOMMA Atsuko, OCHIAI Toshimasa, OCHIAI Toshimasa, OHIRA Yoshinobu, OHIRA Yoshinobu, YOSHIOKA Mitsuhiro, YOSHIOKA Mitsuhiro

  2013, 日本分子生物学会年会プログラム・要旨集(Web), 36th


• プリオン蛋白過剰発現誘導性細胞死の分子機構

  森 剛志, 村松 直美, 犬伏 祥子, 山口 仁孝, 矢野 雅司, 藤田 浩司, 坂口 末廣

  (公社)日本生化学会, Dec. 2010, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 83回・33回, 4P - 0648, Japanese


• プリオン蛋白の過剰発現は細胞死を誘導する

  森剛志, 村松直美, 犬伏祥子, 山口仁孝, 坂口末廣

  2010, 日本ウイルス学会学術集会プログラム・抄録集, 58th


• C型肝炎ウイルス感染によるインスリン抵抗性誘導の分子機序について

  井出良浩, 兼田崇作, 犬伏祥子, 足達哲也, LIN Deng, 勝二郁夫, 堀田博

  2009, 日本ウイルス学会学術集会プログラム・抄録集, 57th


• C型肝炎ウイルスコア蛋白質の安定性調節因子E6AP及びPA28γの相互作用解析

  山下亮輔, 福田浩一郎, 犬伏祥子, 村上恭子, 鈴木哲朗, 森石恆司, 松浦善治, DENG Lin, 井出良浩, 堀田博, 勝二郁夫

  2009, 日本分子生物学会年会講演要旨集, 32nd(Vol.1) (Vol.1)


• ペグインターフェロン/リバビリン併用療法におけるHCV CoreおよびNS5Aの多様性によるSVR予測因子とNon-SVR予測因子の検討

  エルシャーミ アーメド, 足達哲也, 犬伏祥子, 勝二郁夫, 堀田博

  2008, 日本ウイルス学会学術集会プログラム・抄録集, 56th


• 癌抑制タンパク質として知られる非受容体型チロシンキナーゼSykとC型肝炎ウイルスNS5Aとの相互作用

  堀田博, 犬伏祥子, 定清直, 長野基子

  (一社)日本肝臓学会, Apr. 2007, 肝臓, 48(Suppl.1) (Suppl.1), A67 - A67, Japanese


• Hepatitis C virus NS5A protein associates with and negatively regulates a non-receptor protein-tyrosine kinase Syk.

  INUBUSHI Sachiko, NAGANO-FUJII Motoko, AN Chunying, KITAYAMA Kikumi, YOKOZAKI Hiroshi, YAMAMURA Hirohei, IKEDA Masanori, KATO Nobuyuki, SADA Kiyonao, HOTTA Hak

  2006, 生化学


• C型肝炎ウイルス感染が非受容体型チロシンキナーゼSykに及ぼす影響

  犬伏祥子, 長野基子, 北山喜久美, 定清直, 堀田博

  2006, 日本ウイルス学会学術集会プログラム・抄録集, 54th


• C型肝炎ウイルスNS5Aは非受容体型チロシンキナーゼSykに会合しそのキナーゼ活性を負に制御する

  長野基子, 犬伏祥子, 田中基文, 安春英, 野村亮太, 定清直, 堀田博

  2005, 日本ウイルス学会学術集会プログラム・抄録集, 53rd


• Arcanobacterium pyogenesが産生するpyolysinの機能ドメインの解析

  今泉 圭介, 齋藤 稔, 犬伏 祥子, 海藤 敏雄, 竹内 正太郎

  (公社)日本獣医学会, Sep. 2001, 日本獣医学会学術集会講演要旨集, 132回, 161 - 161, Japanese


• Arcanobacterium pyogenesが産生するpyolysinの機能ドメインの解析

  今泉 圭介, 斉藤 稔, 犬伏 祥子, 海藤 敏雄, 竹内 正太郎

  (公社)日本獣医学会, Mar. 2001, 日本獣医学会学術集会講演要旨集, 131回, 73 - 73, Japanese


• 鶏由来黄色ブドウ球菌のチオールプロテアーゼの株特異性と部分的な塩基配列

  竹内正太郎, 犬伏祥子, 松永和恵, 今泉圭介, 海藤敏雄

  2001, 日本獣医学会学術集会講演要旨集, 132nd

• The current status of space modulated radiotherapy

  Sasaki R, Wang TY, Akasaka H, Inubushi S, Yoshida K, Komatsu S, Demizu Y, Fukumoto T

  Joint work, Oct. 2016


• Medical Application of Nonwoven Fabrics - Intra-abdominal Spacers for Particle Therapy

  May 2016

• Exploration of Ligand Modified Gold Nanoparticles to Enhance Tumor Accumulation

  和田百世, 若山千紘, 犬伏洋子, 國久智成, 谷野裕一, 大谷亨, 大谷亨, 大谷亨

  日本バイオマテリアル学会大会予稿集(Web), 2023


• マイクロ波散乱場断層イメージング技術による乳房画像診断

  稲垣明里, 稲垣明里, 平井綾華, 谷野裕一, 谷野裕一, 平尾益美, 福田千紘, 田根香織, 橋本一樹, 佐久間淑子, 廣利浩一, 金昇晋, 高尾信太郎, 高尾信太郎, 松本元, 結縁幸子, 矢田善弘, 矢内勢司, 門澤秀一, 大久保ゆうこ, 大段仁奈, 御勢文子, 一ノ瀬庸, 田代敬, 山神和彦, 山神和彦, 渡邊奈津子, 小西豊, 鶴原知子, 山元奈穂, 山本直哉, 岡本交二, 岡本交二, 山本真由子, 大谷真紀子, 松尾容子, 橋本舞雪, 井上翔太朗, 馬場基, 水本紗千子, 三木万由子, 犬伏祥子, 國久智成, 國久智成, 八木潤子, 河野誠之, 美馬勇輝, 弓井孝佳, 中島義晴, 木村憲明, 木村憲明, 木村建次郎, 木村建次郎, 木村建次郎, 木村建次郎

  日本乳癌画像研究会プログラム・抄録集, 2023


• Measurement of permittivity distribution in a healthy female breast by microwave mammography

  稲垣明里, 稲垣明里, 平井綾華, 木村建次郎, 木村建次郎, 木村建次郎, 木村建次郎, 高尾信太郎, 高尾信太郎, 佐久間淑子, 田根香織, 廣利浩一, 金昇晋, 結縁幸子, 松本元, 田代敬, 山神和彦, 山神和彦, 岡本交二, 岡本交二, 犬伏祥子, 國久智成, 國久智成, 谷野裕一, 谷野裕一, 弓井孝佳, 中島義晴, 木村憲明, 木村憲明

  応用物理学会春季学術講演会講演予稿集(CD-ROM), 2023


• 乳房脂肪組織の誘電分散とマイクロ波マンモグラフィへの影響

  稲垣明里, 稲垣明里, 平井綾華, 木村建次郎, 木村建次郎, 木村建次郎, 木村建次郎, 馬場基, 谷野裕一, 谷野裕一, 高尾信太郎, 高尾信太郎, 佐久間淑子, 田根香織, 廣利浩一, 金昇晋, 犬伏祥子, 國久智成, 國久智成, 岡本交二, 岡本交二, 結縁幸子, 松本元, 田代敬, 山神和彦, 山神和彦, 中島義晴, 弓井孝佳, 木村憲明, 木村憲明

  日本乳癌学会学術総会(CD-ROM), 2023


• Optimization of Epigallocatechin Gallate-Modified Gold Nanoparticles for High Tumor Accumulation

  WAKAYAMA Chihiro, GAN Ning, INUBUSHI Sachiko, BABA Motoi, TANINO Hirokazu, OOYA Tooru

  日本バイオマテリアル学会大会予稿集(Web), 2021


• インタクトエクソソームによる乳がん高速検知のための抗体融合分子インプリントセンシングチップ

  竹内俊文, 森貴翔, 清水拓, 広瀬柚月, 高野恵里, 砂山博文, 北山雄己哉, 犬伏祥子, 佐々木良平, 谷野裕一

  応用物理学会秋季学術講演会講演予稿集(CD-ROM), Sep. 2019, Japanese


• 放射線治療 QOLを考慮した局所治療 小児がんに対する吸収性スペーサー留置を併用した粒子線治療

  佐々木 良平, 出水 祐介, 岩田 宏満, 亀井 美智, 文野 誠久, 赤坂 浩亮, 王 天縁, 妹尾 悟史, 犬伏 祥子, 宮脇 大輔, 吉田 賢史, 小松 昇平, 福本 巧

  日本小児血液・がん学会雑誌, Sep. 2019, Japanese, (一社)日本小児血液・がん学会


• コエンザイムQ10摂取マウスの放射線防護の可能性

  清水康之, 犬伏祥子, 平修, 佐々木良平

  質量分析総合討論会講演要旨集, 2019


• 小児がんに対する吸収性スペーサー留置を併用した粒子線治療

  佐々木良平, 出水祐介, 岩田宏満, 亀井美智, 文野誠久, 赤坂浩亮, 王天縁, 妹尾悟史, 犬伏祥子, 宮脇大輔, 吉田賢史, 小松昇平, 福本巧

  日本小児血液・がん学会雑誌(Web), 2019, Japanese


• 放射線治療:QOLを考慮した局所治療 小児がんに対する吸収性スペーサーの開発

  佐々木 良平, 岩田 宏満, 亀井 美智, 出水 祐介, 文野 誠久, 中尾 朋平, 淡河 恵津世, 王 天縁, 妹尾 悟史, 犬伏 祥子

  日本小児血液・がん学会雑誌, Oct. 2018, Japanese, (一社)日本小児血液・がん学会


• 放射線照射によって分泌された子宮頸部腺がん細胞由来エクソソームのBystander効果の検討

  犬伏 祥子, 佐々木良平

  日本細胞外小胞学会 2018, Aug. 2018, English, Domestic conference

  Poster presentation


• 過酸化チタンナノ粒子の併用による放射線増感治療法の開発

  西村勇哉, 森田健太, 荻野千秋, 犬伏祥子, 佐々木良平, 近藤昭彦

  日本DDS学会学術集会プログラム予稿集, May 2018, Japanese


• Bystander effect of exosomes derived from cervical adenocarcinoma cells in response to irradiation

  Inubushi Sachiko

  ISEV 2019, May 2018, English, International conference

  Poster presentation


• Development of bioabsorbable spacer for pediatric malignant tumors

  佐々木良平, 岩田宏満, 亀井美智, 出水祐介, 文野誠久, 中尾朋平, 中尾朋平, 淡河恵津世, 王天縁, 妹尾悟史, 犬伏祥子

  日本小児血液・がん学会雑誌(Web), 2018


• Effects of hypergravity on serotonin-related gene expression in the mouse brain

  M. Yoshioka, S. Inubushi, T. Ochiai, M. Miyamoto, Y. Ohira, H. Ohta

  Oct. 2013


• パラボリック・フライトを想定したマウスにおける過重力ストレスへの反応の解析

  TOMINAGA Daisuke, INUBUSHI Sachiko, HOMMA Atsuko, OCHIAI Toshimasa, OHIRA Yoshinobu, YOSHIOKA Mitsuhiro

  日本分子生物学会年会プログラム・要旨集(Web), 2013, English


• プリオン蛋白の過剰発現は細胞死を誘導する

  森剛志, 村松直美, 犬伏祥子, 山口仁孝, 坂口末廣

  日本ウイルス学会学術集会プログラム・抄録集, Oct. 2010, Japanese


• プリオン蛋白過剰発現誘導性細胞死の分子機構

  森剛志, 村松直美, 犬伏祥子, 山口仁孝, 矢野雅司, 藤田浩司, 坂口末廣

  生化学, 2010, Japanese


• C型肝炎ウイルス感染によるインスリン抵抗性誘導の分子機序について

  井出良浩, 兼田崇作, 犬伏祥子, 足達哲也, LIN Deng, 勝二郁夫, 堀田博

  日本ウイルス学会学術集会プログラム・抄録集, Oct. 2009, Japanese


• C型肝炎ウイルスコア蛋白質の安定性調節因子E6AP及びPA28γの相互作用解析

  山下亮輔, 福田浩一郎, 犬伏祥子, 村上恭子, 鈴木哲朗, 森石恆司, 松浦善治, DENG Lin, 井出良浩, 堀田博, 勝二郁夫

  日本分子生物学会年会講演要旨集, 2009, Japanese


• ペグインターフェロン/リバビリン併用療法におけるHCV CoreおよびNS5Aの多様性によるSVR予測因子とNon‐SVR予測因子の検討

  エルシャーミ アーメド, 足達哲也, 犬伏祥子, 勝二郁夫, 堀田博

  日本ウイルス学会学術集会プログラム・抄録集, Oct. 2008, Japanese


• ペグインターフェロン/リバビリン併用療法におけるHCV CoreおよびNS5Aの多様性によるSVR予測因子とNon-SVR予測因子の検討

  エルシャーミ アーメド, 足達哲也, 犬伏祥子, 勝二郁夫, 堀田博

  日本ウイルス学会学術集会プログラム・抄録集, 2008


• C型肝炎ウイルス感染が非受容体型チロシンキナーゼSykに及ぼす影響

  犬伏祥子, 長野基子, 北山喜久美, 定清直, 堀田博

  日本ウイルス学会学術集会プログラム・抄録集, Nov. 2006, Japanese


• Hepatitis C virus NS5A protein associates with and negatively regulates a non-receptor protein-tyrosine kinase Syk.

  INUBUSHI Sachiko, NAGANO‐FUJII Motoko, AN Chunying, KITAYAMA Kikumi, YOKOZAKI Hiroshi, YAMAMURA Hirohei, IKEDA Masanori, KATO Nobuyuki, SADA Kiyonao, HOTTA Hak

  生化学, 2006, English


• C型肝炎ウイルスNS5Aは非受容体型チロシンキナーゼSykに会合しそのキナーゼ活性を負に制御する

  長野基子, 犬伏祥子, 田中基文, 安春英, 野村亮太, 定清直, 堀田博

  日本ウイルス学会学術集会プログラム・抄録集, Nov. 2005, Japanese


• Arcanobacterium pyogenesが産生するpyolysinの機能ドメインの解析

  今泉圭介, 斎藤稔, 犬伏祥子, 海藤敏雄, 竹内正太郎

  日本獣医学会学術集会講演要旨集, Sep. 2001, Japanese

• 乳癌の早期診断のための涙液バイオマーカーの探索

  犬伏 祥子

  日本学術振興会, 科学研究費助成事業, 基盤研究(B), 神戸大学, 01 Apr. 2024 - 31 Mar. 2027


• Early diagnosis of ovarian cancer using vaginal secretion extracted miRNA and development of nucleic acid therapy using artificial exosomes

  寺井 義人, 高橋 良輔, 笹川 勇樹, 出口 雅士, 長又 哲史, 犬伏 祥子, 竹内 俊文, 南 康博, 谷村 憲司, 若橋 宣, 遠藤 光晴

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, Apr. 2024 - Mar. 2027


• 涙液を用いた新しい乳癌早期診断法の確立

  國久 智成, 谷野 裕一, 犬伏 祥子, 竹内 俊文

  日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 01 Apr. 2021 - 31 Mar. 2024

  乳癌は女性のがんの中では一番罹患者数が多く、また他のがんに比べて比較的若くに発症することなどの特徴を持つ疾患である。一方乳癌は検診などによる早期発見によって、早期治療介入につながり、予後が改善することがわかっている。一般的に乳癌の早期発見のために、マンモグラフィを用いた検診が行われている。研究者らはマンモグラフィよりも簡便、低侵襲、高感度な検査方法を模索するうちに、涙液中に乳癌由来のマイクロRNAが含まれていることを発見した。次に涙液中の乳癌由来物質の中で、より特異性の高い物質として細胞外小胞に着目するようになった。リキッドバイオプシーの手法としてエクソソームなどの細胞外小胞を超高感度に検出する方法として竹内らの開発したTearExo法を用いることとし、共同研究として乳癌患者の涙液を測定し、その結果を報告した。TearExo法は、細胞外小胞の表面に発現しているタンパク質に対する抗体と蛍光レポーター分子を導入したナノ空孔をもつセンサチップを用いて、細胞外小胞を超高感度に自動分析する方法である。新たな乳癌早期診断法として、細胞外小胞を腫瘍マーカーとした超高感度で選択性の高い乳癌のリキッドバイオプシーを確立することを本研究の目的としている。 今後TearExo法の臨床応用に向けて、より多くの検体を用いた精度の検証が必要であると考える。そのため目標症例数を100例とし、涙液のサンプリングと計測を予定している。今年度は研究計画書を作成し、神戸大学の倫理委員会の承認を得ることができた。これまではTearExo法の測定は少数の検体で行ってきたが、今後は安定した基板の大量生産が必要となったので、そのシステム構築を行っている。


• Development and application of an early detection method for postoperative recurrence of colorectal cancer using tears

  松田 武, 掛地 吉弘, 山下 公大, 竹内 俊文, 谷野 裕一, 犬伏 祥子, 向山 順子, 中野 秀雄, 藤田 貢

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2021 - 31 Mar. 2024

  本研究は、Liquid biopsy による原発性大腸癌術後再発の早期検出法の開発を目的とし、患者検体の採取および解析手段として涙液由来エクソソーム検出法 （TearExo 法) を用いる。これまでの成果と併せて述べると、本手法は①症例検体集積が簡便であり、迅速な前向き研究が実施可能、②エクソソームを確保するための抗体は変更可能で、病態・患者特異的に最適化したエクソソーム解析が可能、等の利点がある。転移臓器別抗体および患者個別抗体によるエクソソームを検出することで、個別検出を目指した次世代型精密医療の基盤構築を試みる。 まず、大腸癌細胞株を用いたエクソソーム検出と確認を行う。採取されたexosomeをmiRNA検出で確認する。大腸癌細胞株由来や大腸癌原発巣切除例組織培養液由来のエクソソームの単球系細胞への影響を検討する。この部分は超遠心とELISA 法で検証する。エクソソームと単球系細胞への影響を検討する。超遠心とELISA 法で検証し、RNAシーケンスを行う。さらに、大腸癌原発巣切除例のエクソソーム検出と定量を行うために、術前後でTearExo 法の検証を行う。さらに、同系が確立されれば、大腸癌同時性肝転移症例、同時性肺転移症例に対するエクソソーム検出とエクソソームの解析を行う。術前後でTearExo 法でのエクソソーム検証を行う。さらに、原発性大腸癌切除例に対するエクソソーム検出例の集積と観察研究を行い、大規模前向き臨床研究へと進めたい。 本研究の成果は、大腸癌の再発の早期検出のみならず、臓器指向性転移の検出方法が期待され、臓器別のフォローを重点的に行うことにより、早期発見と早期治療による治療性の向上を目指すものである。


• Subset cell analysis of gynecological cancer-associated fibroblast that induce lymph node metastasis.

  村田 卓也, 本郷 淳司, 下屋 浩一郎, 谷野 裕一, 犬伏 祥子

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kawasaki Medical School, 01 Apr. 2021 - 31 Mar. 2024

  2021年4月から婦人科がんの手術検体10例において線維芽細胞様の初代培養細胞のクローンの樹立を試み、12クローンの樹立に成功した。その内訳は、卵巣がん大網転移1症例の組織から4クローン、子宮体がん5症例から計8クローンであった。また、漿液性卵巣がん1症例について線維芽細胞様クローンの樹立が現在進行中である。樹立した子宮体がんの線維芽細胞様細胞の6クローンのうち5クローンについて、Cytokeratin陰性、Vimentin陽性Cytokeratin、Vimentin、Smooth Muscle Actin (SMA) 陽性を確認し、がん関連線維芽細胞 (以下、CAFと略す) であることを確認した。うち1クローンについては、サイトケラチンが陽性となり、細胞の属性について精査する予定である。また、1クローンについては、microRNAのExsome解析を行なった。 子宮体がんから樹立した子宮体がん細胞株HEC1B/GFPに対する共培養系を開発した。培養well内に挿入するチャンバーにコラーゲンゲル層を作製し、その表面上でがん細胞を培養することにより、HEC1B/GFPを良好な形態を維持した状態で培養が可能であることがわかった。well底でCAFを培養し、共培養を行って解析した結果、子宮体がんCAFの6株のいずれもが、がん細胞の増殖を促進した。 CAFの転移誘発能の阻害戦略から見出した低分子化合部に関して、転移阻害剤として特許出願を行なった。


• がん早期診断における涙液エクソソームの有用性の検討

  犬伏 祥子

  日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 01 Apr. 2021 - 31 Mar. 2024

  乳がんの死亡率は上昇の一途をたどっており、現在では日本人女性の11人に1人が乳がんにかかるといわれ、早期発見により適切な治療が行われれば良好な経過が期待できるといわれているものの実に年間約13.000人の女性が乳がんでなくなっており、その対策は急務である。一方で乳癌の発症延齢は40歳代と 60歳代後半と2つのピークがあり、40代～50代女性のがん死亡原因の第1位である。そのため40歳から健診が勧められているが、乳がんの検診率は約40%と先進国の中で最も低い。仕事や育児、介護などに追われている40代～50代女性には検診に行くこと自体のハードルの高さが問題となっている。近年はさまざまな体液を用いたがんの早期診断研究がなされており、その社会実現性も高いと考えるが、血液はやはり侵襲性が高く、尿は女性にとって心理的侵襲性も少なくないといえる。特に乳がんや子宮頸癌などは20-30代女性で急増しており、20代からのがんの早期診断という点で、より気軽に採取が可能である体液サンプルを利用した早期診断方法が必要であると考え、涙に着目した。申請者らは乳がん転移患者から涙液由来エクソソームを採取し、oncogenic miRNAが高発現していることを明らかにした。しかし、この涙液由来エクソソーム内にがん細胞から放出されたエクソソームが含まれているのかなど涙液の有効性について疑念は拭えない状態であった。そのため、涙液にがん細胞由来エクソソームが含まれており、涙液エクソソームががんの早期診断に有用であることを明らかにする必要があると考え本研究の着手した。 21年度は倫理委員会からの承認を得て、前向きに35例の患者の涙サンプルの採取を実施し現在順次解析に取り組んでいる。


• Usefulness of exosome-derived PDL1 in radiation therapy

  HARADA AYA

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2019 - 31 Mar. 2022

  The purpose of this study is to evaluate usefulness of exosome-derived PDL1 as a biomarker in patients with unresectable non-small cell lung cancer treated wit curative chemoradiotherapy. We have obtained blood samples sequentially from patients with stage III non-small cell lung cancer. We have established quantitative methods to measure the exosome-derived PDL1, and have compared pre- and post-treatment blood samples with evaluating occurrence of tumor recurrence or tumor control.Then, we clarified possibilities whether the exosome-derived PDL1 could be an useful biomarker of effectiveness of curative chemoradiotherapy. Moreover, it seems another aspect and cutting edge view point to compare the exosome-derived PDL1 and soluble PDL1 in the serum.


• Development of Theranostic particle beam therapy using titanium peroxide nanoparticles

  Akasaka Hiroaki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2019 - 31 Mar. 2022

  We developed a novel titanium peroxide nanoparticles and reported that it generates a large amount of reactive oxygen species by X-ray irradiation and amplify the antitumor effect of radiation. Radiation causes cell death by generating reactive oxygen species (ROS) inside and outside the cell, but most radiation-resistant tumors overexpress antioxidants which have a ROS-scavenging effect. And, erasing ROS generated by radiation is one of the causes of intractability, and it is an issue for improving treatment results. A goal during this grant period was adding a drug delivery function to titanium peroxide nanoparticles to induce the target tumor with high efficiency and accuracy. Throughout the subsidy period, research on the addition of drug delivery capability to titanium peroxide nanoparticles has progressed significantly, and we have succeeded in developing a drug delivery system that efficiently transports titanium peroxide nanoparticles to cells expressing specific antibodies.


• Development of a new radiosensitizer utilizing the cell specificity of exosomes

  Inubushi Sachiko

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2018 - 31 Mar. 2021

  The precise mechanism of intercellular communication between cancer cells following radiation exposure is unclear. The present study aimed to identify novel roles of exosomes released from irradiated cells to neighboring cancer cells.Further analysis using miRNA mimics and reverse transcription-quantitative PCR identified miR-6823-5p as a potential candidate to inhibit SOD1, leading to increased intracellular ROS levels and DNA damage. The present study is the first to demonstrate that irradiated exosomes enhance the radiation effect via increasing intracellular ROS levels in cancer cells.


• Development of novel radiosensitizer by using mesenchymal cell-derived microRNA

  Matsuo Yoshiro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2017 - 31 Mar. 2020

  After establishing the culture methods of adipose-derived mesenchymal stem cell, Panc-1 cells were irradiated using particle beams. As particle beams, in addition to proton and carbon ion beams which currently used in clinical practice, we used also helium ion beams. In the colony formation assay, α value and β value were calculated based on the LQ model. The reproducibility was also examined and confirmed. Regarding the introduction of microRNA, several microRNAs were selected and examined. However, it was difficult to obtain good introduction and evaluate sensitizing effect. It was considered necessary to further study various conditions including the problem of transfection efficiency.


• Next-generation bioabsorbable spacer for miminum invasive radiotherapy

  SASAKI RYOHEI

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2016 - 31 Mar. 2019

  We have developed a novel bioabsorbable polyglycolic acid (PGA) spacer. This is a promising method designed to allow for increased tumor dose while limiting exposure to adjacent organs without remaining a foreign body after the treatment. In the preclinical animal study, biological safety was evaluated, resulting that no weight loss or appetite loss was observed. There were minimum adhesion, and a Seprafilm helped to decrease those adhesions. With long term observation in animals, the PGA spacer was slowly decreased in size and seemed to be useful and safe for clinical application Then, a first-in-human phase I clinical study using the PGA spacer aimed to evaluate the safety and efficacy of SMPT in patients with unresectable malignant tumor located adjacent to normal organs.

  Competitive research funding


• A novel strategy for radiosensitization using titanium peroxide nanoparticles

  SASAKI RYOHEI

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research, Grant-in-Aid for Challenging Exploratory Research, Kobe University, 01 Apr. 2016 - 31 Mar. 2019

  Polyacrylic acid (PAA)-modified titanium peroxide nanoparticles (PAA-TiOxNPs) are promising radiosensitizers. PAA-TiOxNPs were synthesized from commercial TiO2 nanoparticles that were modified with PAA and functionalized by H2O2treatment. To realize practical clinical uses for PAA-TiOxNPs, their tissue distribution and acute toxicity were evaluated using healthy mice and mice bearing tumors derived from xenografted Mhuman pancreatic cancer cells. Such high accumulation could be associated with enhanced permeability and retention effects of the tumor, as PAA-TiOxNPs are composed of inorganic particles and polymers, without tumor-targeting molecules.

  Competitive research funding


• Development of radioprotective agents for the intestine in radiotherapy

  EJIMA YASUO, SASAKI Ryohei, YOSHIDA Kenji, MIYAWAKI Daisuke, OSUGA Saki, INUBUSHI Sachiko, MUKUMOTO Naritoshi, AKASAKA Hiroaki, SHIMIZU Yasuyuki, UCHIDA Ray

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2013 - 31 Mar. 2016

  Protection of normal structure of the intestine is important under intense radiation therapy. We focused on the reduced form of Coenzyme Q10 (reduced-CoQ10), which is an antioxidant and naturally available in the human body, and examined its radioprotective effect on the small intestine of mice. Reduced-CoQ10, when administered orally, diminished the radiation-mediated damage of villi and apoptosis in intestinal crypt cells, and also reduced reactive oxygen species (ROS) production upon irradiation. In contrast to that in normal cells, reduced-CoQ10 did not diminish the cytotoxic effects of irradiation in tumor cells in vitro, but decreased their survival by increasing ROS production. Further, to clarify the metabolic changes induced by reduced-CoQ10 and irradiation, metabolomics analysis of mice serum and intestinal tissue samples was performed. Metabolomic profiling identified taurine as a potential biomarker for radiation-mediated damage of the intestine.


• 初代肝培養細胞を用いた、HCV感染時におけるアポトーシスの解析

  犬伏 祥子

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS Fellows, Grant-in-Aid for JSPS Fellows, Kobe University, 2008 - 2009

  昨年度、我々はヒト初代肝培養細胞(HuS-E/2 cell)におけるHCV複製効率は非常に低い事を明らかにした。本年度は、より複製効率をあげるため、より生体に近い感染実験系を構築し、HuS-E/2細胞を用いた3次元培養を試みた。 今回我々は、Thermoreversible gelation polymer gel(TGP gel)を用いHuS-E/2 cellを3次元培養下でpre-cultureした後、HCVを感染させ、細胞内HCV RNAについてreal-time PCR法で解析したところ、感染後HCV RNA量は経時的に減少した。しかし、数日後からHCV RNA量の増加が認められた。また、HCV RNA量においては2次元培養した時と比べ、有意に複製が増加している事が明らかとなった。次に、この感染効率の上昇は何に起因しているのかを明らかにする事を試みた。現在、HCVのentryに必要な分子は主として、tetraspanin CD81,scavenger receptor B-1(CE-B1)及びタイトジャンクション分子であるClaudin1およびoccludin等が報告されている。今回我々は、2次元培養時、および3次元培養時におけるCD81, Claudin1, Occludinの細胞内局在について検討したところ、HuS-E/2細胞の3次元培養時においてClaudinは細胞膜上に局在するのに対し、2次元培養時においては細胞質および核内に局在している事が明らかとなった。CD81およびOccludinにおいては2次元および3次元培養時共に細胞膜上に局在している事が明らかとなった。今後、3次元培養感染系を用いて、caspase-3等のアポトーシスマーカーについて解析し、HCV感染による細胞増殖抑制がアポトーシスによるものかを明らかにしようと考えている。

• 放射線治療用スペーサー

  佐々木 良平, 福本 巧, 犬伏 祥子, 小畑 勉, 田上 佳孝

  特願2016-181028, 15 Sep. 2016, 国立大学法人神戸大学, 金井重要工業株式会社, アルフレッサファーマ株式会社, 特開2018-042855, 22 Mar. 2018

  Patent right

  IRI