Basic research of cancer therapy by improving anticancer drug sensitivity through tumor vascular remodeling

• Project/Area Number: 17K08602
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Osaka City University
• Principal Investigator: Tomita Shuhei 大阪市立大学, 大学院医学研究科, 教授 (00263898)
• Co-Investigator(Kenkyū-buntansha): 松永 慎司 大阪市立大学, 大学院医学研究科, 講師 (30704910)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 低酸素 / がん微小環境 / 腫瘍血管 / 腫瘍免疫 / PHD阻害剤 / HIF / PHD阻害薬 / 自然免疫 / 癌微小環境 / 癌治療

Outline of Final Research Achievements

The tumor microenvironment (TME) polarizes tumor-infiltrating macrophages toward tumor support. Macrophage-abundant tumors are highly malignant and are the cause of poor prognosis and therapeutic resistance. In this study, we show that the prolyl hydroxylase (PHD) inhibitor FG-4592 (FG) inhibits tumor growth of macrophage-abundant tumors and prolongs mouse survival. FG not only normalizes tumor vessels and improves tumor oxygenation but also directly affects macrophages and activates phagocytosis through the PHD-hypoxia-inducible factor (HIF) axis. Remarkably, FG can promote phagocytic ability of the Ly6Clo subset of tumor-infiltrating macrophages, leading to tumor growth inhibition. Moreover, Ly6Cneg macrophages contributed to blood vessel normalization. Using a malignant tumor mouse model, we characterized macrophage function and subsets. Altogether, our findings suggest that the PHD inhibitor can promote the anti-tumor potential of macrophages to improve cancer therapy.

Academic Significance and Societal Importance of the Research Achievements

研究の成果は、がん微小環境が造り出す腫瘍血管と正常血管の違いを明確化することにより組織再構築の分子基盤の解明に繋がると考えられる。また、PHD-HIFを基軸としたシグナルを介して形質変換した腫瘍内マクロファージがもたらす抗腫瘍効果についても同様に詳細な分子機序を明らかにする契機となる。これら研究遂行は、現在の腫瘍免疫療法では難治性を示すがんに対して、自然免疫の活性化過程を標的とした新しい腫瘍免疫療法を創出する可能性を有しており、新規創薬研究分野にも繋がることが期待される。

Research Products

• [Int'l Joint Research] National Instututes of Health(米国)
• [Journal Article] Prolyl-hydroxylase inhibitors reconstitute tumor blood vessels in mice (2020)
  • Author(s): Nishide Shunji、Uchida Junji、Matsunaga Shinji、Tokudome Kentaro、Yamaguchi Takehiro、Kabei Kazuya、Moriya Taiki、Miura Katsuyuki、Nakatani Tatsuya、Tomita Shuhei
  • Journal Title: Journal of Pharmacological Sciences Volume: 143 Issue: 2 Pages: 122-126
  • DOI: 10.1016/j.jphs.2020.02.010
  • Peer Reviewed / Open Access
• [Journal Article] Yohimbine ameliorates lipopolysaccharide-induced acute kidney injury in rats (2020)
  • Author(s): Shimokawa Takaomi、Yoneda Kozo、Yamagata Masayo、Hayashi Kohei、Tomita Shuhei
  • Journal Title: European Journal of Pharmacology Volume: 871 Pages: 172917-172917
  • DOI: 10.1016/j.ejphar.2020.172917
  • Peer Reviewed
• [Journal Article] The effect of PHD inhibitor on tumor microenvironment and tumor immune response (2020)
  • Author(s): Matsunaga S, Tomita S.
  • Journal Title: Folia Pharmacologica Japonica Volume: 155 Issue: 1 Pages: 35-39
  • DOI: 10.1254/fpj.19119
  • NAID: 130007778893
  • ISSN: 0015-5691, 1347-8397
• [Journal Article] Effects of orally active hypoxia inducible factor alpha prolyl hydroxylase inhibitor, FG4592 on renal fibrogenic potential in mouse unilateral ureteral obstruction model (2020)
  • Author(s): Kabei Kazuya、Tateishi Yu、Shiota Masayuki、Osada-Oka Mayuko、Nishide Shunji、Uchida Junji、Nakatani Tatsuya、Matsunaga Shinji、Yamaguchi Takehiro、Tomita Shuhei、Miura Katsuyuki
  • Journal Title: Journal of Pharmacological Sciences Volume: 142 Issue: 3 Pages: 93-100
  • DOI: 10.1016/j.jphs.2019.12.002
  • Peer Reviewed / Open Access
• [Journal Article] Soluble urokinase-type plasminogen activator receptor represents exercise tolerance and predicts adverse cardiac events in patients with heart failure. (2020)
  • Author(s): Ishikawa H, Izumiya Y, Shibata A, Ichikawa Y, Yamaguchi T, Yamaguchi Y, Kitada R, Iwata S, Ehara S, Tomita S, Hanatani A, Yoshiyama M.
  • Journal Title: Heart Vessels. Volume: 35 Issue: 5 Pages: 681-688
  • DOI: 10.1007/s00380-019-01538-3
  • NAID: 120006936889
  • Peer Reviewed / Open Access
• [Journal Article] The effects of eribulin on breast cancer microenvironment identified using eribulin-resistant breast cancer cell lines. (2020)
  • Author(s): Goto W, Kashiwagi S, Asano Y, Takada K, Takahashi K, Fujita H, Takashima T, Shibutani M, Amano R, Tomita S, Hirakawa K, Ohira M.
  • Journal Title: Anticancer Research Volume: 39 Issue: 8 Pages: 4031-4041
  • DOI: 10.21873/anticanres.13559
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Controlling the Phenotype of Tumor-Infiltrating Macrophages via the PHD-HIF Axis Inhibits Tumor Growth in a Mouse Model (2019)
  • Author(s): Nishide Shunji、Matsunaga Shinji、Shiota Masayuki、Yamaguchi Takehiro、Kitajima Shojiro、Maekawa Yoichi、Takeda Norihiko、Tomura Michio、Uchida Junji、Miura Katsuyuki、Nakatani Tatsuya、Tomita Shuhei
  • Journal Title: iScience Volume: 21 Pages: 205-205
  • DOI: 10.1016/j.isci.2019.10.031
  • Peer Reviewed / Open Access
• [Journal Article] Clinical verification of dynamic monitoring of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in primary endocrine therapy for advanced breast cancer (2019)
  • Author(s): Takada K, Kashiwagi S, Asano Y, Goto W, Takahashi K, Shibutani M, Amano R, Takashima T, Tomita S, Hirakawa K, Ohira M.
  • Journal Title: Anticancer Res Volume: 39 Issue: 10 Pages: 55815588-55815588
  • DOI: 10.21873/anticanres.13752
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Improving the safety of high-concentration potassium chloride injection. (2019)
  • Author(s): Nakatani K, Nakagami-Yamaguchi E, Shinoda Y, Tomita S, Nakatani T.
  • Journal Title: BMJ Open Qual. Volume: 8 Issue: 2 Pages: e000666-e000666
  • DOI: 10.1136/bmjoq-2019-000666
  • Peer Reviewed
• [Journal Article] Verification of the effects of calcium channel blockers on the immune microenvironment of breast cancer. (2019)
  • Author(s): Takada K, Kashiwagi S, Asano Y, Goto W, Takahashi K, Fujita H, Takashima T, Tomita S, Hirakawa K, Ohira M.
  • Journal Title: BMC Cancer Volume: 19 Issue: 1 Pages: 615-615
  • DOI: 10.1186/s12885-019-5828-5
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic value of quality of life in endocrine therapy for elderly patients with breast cancer: a retrospective study (2019)
  • Author(s): Takada K, Kashiwagi S, Asano Y, Goto W, Takahashi K, Shibutani M, Amano R, Takashima T, Tomita S, Hirakawa K, Ohira M
  • Journal Title: Anticancer Res Volume: 39 Issue: 6 Pages: 29412950-29412950
  • DOI: 10.21873/anticanres.13424
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical outcomes of recombinant human-soluble thrombomodulin treatment for disseminated intravascular coagulation in solid Tumors. (2019)
  • Author(s): Kashiwagi S, Asano Y, Takahashi K, Shibutani M, Amano R, Tomita S, Hirakawa K, Ohira M.
  • Journal Title: Anticancer research Volume: 39 Issue: 5 Pages: 2259-2264
  • DOI: 10.21873/anticanres.13342
  • Peer Reviewed / Open Access
• [Journal Article] A dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, attenuates cardiac dysfunction after myocardial infarction independently of DPP-4 (2019)
  • Author(s): Yamaguchi Takehiro、Watanabe Ayano、Tanaka Masako、Shiota Masayuki、Osada-Oka Mayuko、Sano Soichi、Yoshiyama Minoru、Miura Katsuyuki、Kitajima Shojiro、Matsunaga Shinji、Tomita Shuhei、Iwao Hiroshi、Izumi Yasukatsu
  • Journal Title: Journal of Pharmacological Sciences Volume: 139 Issue: 2 Pages: 112-119
  • DOI: 10.1016/j.jphs.2018.12.004
  • Peer Reviewed / Open Access
• [Journal Article] Clinical verification of the relationship between smoking and the immune microenvironment of breast cancer (2019)
  • Author(s): Takada Koji、Kashiwagi Shinichiro、Asano Yuka、Goto Wataru、Takahashi Katsuyuki、Fujita Hisakazu、Takashima Tsutomu、Tomita Shuhei、Hirakawa Kosei、Ohira Masaichi
  • Journal Title: Journal of Translational Medicine Volume: 17 Issue: 1 Pages: 13-13
  • DOI: 10.1186/s12967-019-1773-y
  • Peer Reviewed / Open Access
• [Journal Article] Possibility of avoiding axillary lymph node dissection by immune microenvironment monitoring in preoperative chemotherapy for breast cancer (2018)
  • Author(s): Takada Koji、Kashiwagi Shinichiro、Goto Wataru、Asano Yuka、Takahashi Katsuyuki、Fujita Hisakazu、Takashima Tsutomu、Tomita Shuhei、Hirakawa Kosei、Ohira Masaichi
  • Journal Title: Journal of Translational Medicine Volume: 16 Issue: 1 Pages: 318-318
  • DOI: 10.1186/s12967-018-1692-3
  • Peer Reviewed / Open Access
• [Journal Article] Predictive value of lymphocyte-to-monocyte ratio in the preoperative setting for progression of patients with breast cancer (2018)
  • Author(s): Goto Wataru、Kashiwagi Shinichiro、Asano Yuka、Takada Koji、Takahashi Katsuyuki、Hatano Takaharu、Takashima Tsutomu、Tomita Shuhei、Motomura Hisashi、Hirakawa Kosei、Ohira Masaichi
  • Journal Title: BMC Cancer Volume: 18 Issue: 1 Pages: 1137-1137
  • DOI: 10.1186/s12885-018-5051-9
  • Peer Reviewed / Open Access
• [Journal Article] Significance of intrinsic breast cancer subtypes on the long-term prognosis after neoadjuvant chemotherapy (2018)
  • Author(s): Goto Wataru、Kashiwagi Shinichiro、Takada Koji、Asano Yuka、Takahashi Katsuyuki、Fujita Hisakazu、Takashima Tsutomu、Tomita Shuhei、Hirakawa Kosei、Ohira Masaichi
  • Journal Title: Journal of Translational Medicine Volume: 16 Issue: 1 Pages: 307-307
  • DOI: 10.1186/s12967-018-1679-0
  • Peer Reviewed / Open Access
• [Journal Article] Predictive value of improvement in the immune tumour microenvironment in patients with breast cancer treated with neoadjuvant chemotherapy (2018)
  • Author(s): Goto Wataru、Kashiwagi Shinichiro、Asano Yuka、Takada Koji、Takahashi Katsuyuki、Hatano Takaharu、Takashima Tsutomu、Tomita Shuhei、Motomura Hisashi、Ohsawa Masahiko、Hirakawa Kosei、Ohira Masaichi
  • Journal Title: ESMO Open Volume: 3 Issue: 6 Pages: e000305-e000305
  • DOI: 10.1136/esmoopen-2017-000305
  • Peer Reviewed / Open Access
• [Journal Article] Significance of re-biopsy for recurrent breast cancer in the immune tumour microenvironment (2018)
  • Author(s): Takada Koji、Kashiwagi Shinichiro、Goto Wataru、Asano Yuka、Takahashi Katsuyuki、Hatano Takaharu、Takashima Tsutomu、Tomita Shuhei、Motomura Hisashi、Ohsawa Masahiko、Hirakawa Kosei、Ohira Masaichi
  • Journal Title: British Journal of Cancer Volume: 119 Issue: 5 Pages: 572-579
  • DOI: 10.1038/s41416-018-0197-4
  • Peer Reviewed / Open Access
• [Journal Article] Novel evaluation scale for QOL (QOL-ACD-BP) in preoperative chemotherapy for breast cancer (2018)
  • Author(s): Takada Koji、Kashiwagi Shinichiro、Goto Wataru、Asano Yuka、Takahashi Katsuyuki、Morisaki Tamami、Takashima Tsutomu、Tomita Shuhei、Hirakawa Kosei、Ohira Masaichi
  • Journal Title: Journal of Cancer Research and Clinical Oncology Volume: 144 Issue: 8 Pages: 1547-1559
  • DOI: 10.1007/s00432-018-2670-0
  • Peer Reviewed / Open Access
• [Journal Article] Hypoxia-inducible factor-2 alpha up-regulates CD70 under hypoxia and enhances anchorage-independent growth and aggressiveness in cancer cells (2018)
  • Author(s): Kitajima Shojiro、Lee Kian Leong、Fujioka Masaki、Sun Wendi、You Jia、Chia Grace Sushin、Wanibuchi Hideki、Tomita Shuhei、Araki Marito、Kato Hiroyuki、Poellinger Lorenz
  • Journal Title: Oncotarget Volume: 9 Issue: 27 Pages: 19123-19135
  • DOI: 10.18632/oncotarget.24919
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Significance of the Neutrophil?to?Lymphocyte Ratio in Endocrine Therapy for Stage IV Breast Cancer (2018)
  • Author(s): Iimori N, Kashiwagi S, Asano Y, Goto W, Takada K, Takahashi K, Hatano T, Takashima T, Tomita S, Motomura H, Hirakawa K, Ohira M.
  • Journal Title: In Vivo Volume: 32 Issue: 3
  • DOI: 10.21873/invivo.11292
  • Peer Reviewed
• [Journal Article] Use of the tumor-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to combination therapy with pertuzumab, trastuzumab, and docetaxel for advanced HER2-positive breast cancer (2018)
  • Author(s): Takada Koji、Kashiwagi Shinichiro、Goto Wataru、Asano Yuka、Takahashi Katsuyuki、Takashima Tsutomu、Tomita Shuhei、Ohsawa Masahiko、Hirakawa Kosei、Ohira Masaichi
  • Journal Title: Journal of Translational Medicine Volume: 16 Issue: 1 Pages: 86-86
  • DOI: 10.1186/s12967-018-1460-4
  • Peer Reviewed / Open Access
• [Journal Article] Prediction of the treatment response to pre-operative chemotherapy in breast cancer by the checkpoint protein expression (2018)
  • Author(s): Asano Y, Kashiwagi S, Goto W, Takada K, Takahashi K, Morisaki T, Fujita H, Takashima T, Tomita S, Ohsawa M, Hirakawa K, Ohira M.
  • Journal Title: Journal of translational Medicine Volume: 16 Issue: 1 Pages: 87-87
  • DOI: 10.1186/s12967-018-1458-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prediction of Treatment Response to Neoadjuvant Chemotherapy in Breast Cancer by Subtype Using Tumor-infiltrating Lymphocytes (2018)
  • Author(s): Asano Y, Kashiwagi S, Goto W, Takada K, Takahashi K, Hatano T, Takashima T, Tomita S, Motomura H, Ohsawa M, Hirakawa K, Ohira M.
  • Journal Title: Anticancer Research Volume: 38 Issue: 4 Pages: 2311-2321
  • DOI: 10.21873/anticanres.12476
  • Peer Reviewed / Open Access
• [Journal Article] Study on the progression types of cancer in patients with breast cancer undergoing eribulin chemotherapy and tumor microenvironment (2018)
  • Author(s): Kashiwagi S, Tsujio G, Asano Y, Goto W, Takada K, Takahashi K, Morisaki T, Fujita H, Takashima T, Tomita S, Ohsawa M, Hirakawa K, Ohira M.
  • Journal Title: Journal of translational Medicine Volume: 16 Issue: 1 Pages: 54-54
  • DOI: 10.1186/s12967-018-1443-5
  • Peer Reviewed / Open Access
• [Journal Article] Role of hypoxia-inducible factor-1 in the development of renal fibrosis in mouse obstructed kidney: Special references to HIF-1 dependent gene expression of profibrogenic molecules (2018)
  • Author(s): Kabei Kazuya、Tateishi Yu、Nozaki Masakazu、Tanaka Masako、Shiota Masayuki、Osada-Oka Mayuko、Nishide Shunji、Uchida Junji、Nakatani Tatsuya、Tomita Shuhei、Miura Katsuyuki
  • Journal Title: Journal of Pharmacological Sciences Volume: 136 Issue: 1 Pages: 31-38
  • DOI: 10.1016/j.jphs.2017.12.004
  • Peer Reviewed / Open Access
• [Journal Article] Mesenchymal?epithelial Transition and Tumor Vascular Remodeling in Eribulin Chemotherapy for Breast Cancer (2018)
  • Author(s): Kashiwagi S, Asano Y, Goto W, Takada K, Takahashi K, Hatano T, Tanaka S, Takashima T, Tomita S, Motomura H, Ohsawa M, Hirakawa K, Ohira M.
  • Journal Title: Anticancer Research Volume: 38 Issue: 1 Pages: 401-410
  • DOI: 10.21873/anticanres.12236
  • Peer Reviewed / Open Access
• [Journal Article] Red ginseng extracts attenuate skin inflammation in atopic dermatitis through p70 ribosomal protein S6 kinase activation (2018)
  • Author(s): Osada-Oka Mayuko、Hirai Sayaka、Izumi Yasukatsu、Misumi Kazuhiro、Samukawa Keiichi、Tomita Shuhei、Miura Katsuyuki、Minamiyama Yukiko、Iwao Hiroshi
  • Journal Title: Journal of Pharmacological Sciences Volume: 136 Issue: 1 Pages: 9-15
  • DOI: 10.1016/j.jphs.2017.11.002
  • Peer Reviewed
• [Journal Article] Mesenchymal-epithelial Transition and Tumor Vascular Remodeling in Eribulin Chemotherapy for Breast Cancer. (2018)
  • Author(s): Kashiwagi S, Asano Y, Goto W, Takada K, Takahashi K, Hatano T, Tanaka S, Takashima T, Tomita S, Motomura H, Ohsawa M, Hirakawa K, Ohira M
  • Journal Title: Anticancer Res Volume: 38 Pages: 401-410
  • Peer Reviewed
• [Journal Article] Roles of hypoxia inducible factor-1α in the temporomandibular joint (2017)
  • Author(s): Mino-Oka A, Izawa T, Shinohara T, Mori H, Yasue A, Tomita S, Tanaka E
  • Journal Title: Archives of Oral Biology Volume: 73(1) Pages: 274-281
  • DOI: 10.1016/j.archoralbio.2016.10.028
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dietary tryptophan alleviates dextran sodium sulfate-induced colitis through aryl hydrocarbon receptor in mice. (2017)
  • Author(s): Islam J, Sato S, Watanabe K, Watanabe T, Ardiansyah, Hirahara K, Aoyama Y, Tomita S, Aso H, Komai M, Shirakawa H
  • Journal Title: J Nutr Biochem Volume: 42 Pages: 43-50
  • DOI: 10.1016/j.jnutbio.2016.12.019
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Use of tumor-infiltrating lymphocytes (TILs) to predict the treatment response to eribulin chemotherapy in breast cancer. (2017)
  • Author(s): Kashiwagi S, Asano Y, Goto W, Takada K, Takahashi K, Noda S, Takashima T, Onoda N, Tomita S, Ohsawa M, Hirakawa K, Ohira M.
  • Journal Title: PLoS ONE Volume: 12 Issue: 2 Pages: e0170634-e0170634
  • DOI: 10.1371/journal.pone.0170634
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tumour blood vessel normalisation by prolyl hydroxylase inhibitor repaired sensitivity to chemotherapy in a tumour mouse model. (2017)
  • Author(s): Koyama S, Matsunaga S, Imanishi M, Maekawa Y, Kitano H, Takeuchi H, Tomita S
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 45621-45621
  • DOI: 10.1038/srep45621
  • NAID: 120006535012
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Reoxygenation with 100% Oxygen Following Hypoxia in Mice Causes Apoptosis. (2017)
  • Author(s): Nishimura Y, Ueki M, Imanishi M, Tomita S, Ueno M, Morishita J, Nishiyama T.
  • Journal Title: Shock Volume: 48 Issue: 5 Pages: 590-594
  • DOI: 10.1097/shk.0000000000000891
  • Peer Reviewed
• [Journal Article] Circulating tumor cell clusters-associated gene plakoglobin is a significant prognostic predictor in patients with breast cancer (2017)
  • Author(s): Goto Wataru、Kashiwagi Shinichiro、Asano Yuka、Takada Koji、Takahashi Katsuyuki、Hatano Takaharu、Takashima Tsutomu、Tomita Shuhei、Motomura Hisashi、Ohsawa Masahiko、Hirakawa Kosei、Ohira Masaichi
  • Journal Title: Biomark Res Volume: 5 Issue: 1 Pages: 19-19
  • DOI: 10.1186/s40364-017-0099-2
  • Peer Reviewed / Open Access
• [Journal Article] Heat shock protein 70 inhibitors suppress androgen receptor expression in LNCaP95 prostate cancer cells (2017)
  • Author(s): Kita Kazuaki、Shiota Masayuki、Tanaka Masako、Otsuka Asuka、Matsumoto Masaki、Kato Minoru、Tamada Satoshi、Iwao Hiroshi、Miura Katsuyuki、Nakatani Tatsuya、Tomita Shuhei
  • Journal Title: Cancer Sci Volume: 108 Issue: 9 Pages: 1820-1827
  • DOI: 10.1111/cas.13318
  • Peer Reviewed / Open Access
• [Journal Article] Using TILs to Predict Therapeutic Effect of Chemotherapy (Pertuzumab, Trastuzumab, Docetaxel) on HER2-positive Breast Cancer. (2017)
  • Author(s): Kashiwagi S, Asano Y, Goto W, Takada K, Takahashi K, Hatano T, Takashima T, Tomita S, Motomura H, Ohsawa M, Hirakawa K, Ohira M
  • Journal Title: Anticancer Res Volume: 37 Pages: 5623-5630
  • Peer Reviewed
• [Journal Article] Prediction of survival after neoadjuvant chemotherapy for breast cancer by evaluation of tumor-infiltrating lymphocytes and residual cancer burden (2017)
  • Author(s): Asano Yuka、Kashiwagi Shinichiro、Goto Wataru、Takada Koji、Takahashi Katsuyuki、Hatano Takaharu、Noda Satoru、Takashima Tsutomu、Onoda Naoyoshi、Tomita Shuhei、Motomura Hisashi、Ohsawa Masahiko、Hirakawa Kosei、Ohira Masaichi
  • Journal Title: BMC Cancer Volume: 17 Issue: 1 Pages: 888-888
  • DOI: 10.1186/s12885-017-3927-8
  • Peer Reviewed / Open Access
• [Presentation] Alteration the phenotype of tumor-infiltrating macrophages via the PHD-HIF axis inhibits tumor growth in mice. (2020)
  • Author(s): Shunji Nishide, Shinji Matsunaga, Takehiro Yamaguchi, Norihiko Takeda, Junji Uchida, Katsuyuki Miura, Tatsuya Nakatani and Shuhei Tomita
  • Organizer: Keystone Symposia -Hypoxia: Molecules, Mechanisms and Disease-
  • Int'l Joint Research
• [Presentation] PHD阻害剤による腫瘍浸潤マクロファージの表現型変化は腫瘍環境改善を誘導する (2020)
  • Author(s): 松永 慎司、西出 峻治、徳留 健太郎、山口 雄大、冨田 修平
  • Organizer: 第93回日本薬理学会
• [Presentation] 胎児期低酸素ストレス負荷による自閉症様症状の発現には抑制性シナプス関連遺伝子の発現低下が関与する (2020)
  • Author(s): 徳留 健太郎、松永 慎司、山口 雄大、冨田 修平
  • Organizer: 第93回日本薬理学会
• [Presentation] リナグリプチンは心筋梗塞後のDPP-4非依存的に左室リモデリングを抑制する (2020)
  • Author(s): 山口 雄大、泉 康雄、塩田 正之、松永 慎司、德留 健太郎、三浦 克之、岩尾 洋、冨田 修平
  • Organizer: 第93回日本薬理学会
• [Presentation] リポポリサッカライド誘発性腎障害に対するヨヒンビンの効果 (2020)
  • Author(s): 下川 隆臣、山形 雅代、林 耕平、冨田 修平、米田 耕造
  • Organizer: 第93回日本薬理学会
• [Presentation] 肺血管内皮細胞由来低酸素応答因子 HIF が肺高血圧症の 病態形成に果たす役割 (2018)
  • Author(s): 冨田修平，山口雄大，松永慎司
  • Organizer: 第47回日本心脈管作動物質学会年会
• [Presentation] The role of HIF-1 in the development of renal fibrosis with special reference to HIF-1 dependent gene expression. (2018)
  • Author(s): Kabei K., Nozaki M., Uchida J., Nakatani T., Tomita S. and Miura K
  • Organizer: ISN Frontiers 2018, Feb.22-25, Tokyo
  • Int'l Joint Research
• [Presentation] Prolyl Hydroxylase inhibitor repaired chemo-sensitivity through tumor blood vessel normalization in tumor mouse model. (2018)
  • Author(s): Shinji Matsunaga, Shunji Nishide, Masayuki Shiota, Takehiro Yamaghchi, Shojiro Kitajima, Katsuyuki Miura and Shuhei Tomita.
  • Organizer: 18th World Congress of Basic and Clinical Pharmacology, July 1-6, Kyoto
  • Int'l Joint Research
• [Presentation] Dipeptidyl Peptidase-4 (DPP-4) inhibition Attenuates Cardiac Dysfunction after Myocardial Infarction Independently of DPP-4. (2018)
  • Author(s): Yamaguchi T, Izumi Y, Shiota M, Tanaka M, Osada-Oka M, Matsunaga S, Kitajima S, Miura K, Iwao H, Tomita S
  • Organizer: 18th World Congress of Basic and Clinical Pharmacology, July 1-6, Kyoto
  • Int'l Joint Research
• [Presentation] Hypoxia-inducible factor-1α regulates energy fuel metabolism and mediates metabolic plasticity during ammonia stress response in ovarian cancer stem-like cells. (2018)
  • Author(s): Shojiro Kitajima, Kian Leong Lee, Hiroki Hikasa, Shinji Matsunaga, Takehiro Yamaguchi, Shuhei Tomita, Marito Araki, Hiroyuki Kato and Lorenz Poellinger
  • Organizer: 18th World Congress of Basic and Clinical Pharmacology, July 1-6, Kyoto
  • Int'l Joint Research
• [Presentation] The role of HIF-1 in the development of renal fibrosis in mouse UUO model with special reference to HIF-1 dependent gene expression. (2018)
  • Author(s): Kabei K., Osada-Oka M.,Nozaki M., Shiota M., Tanaka M., Tomita S. and Miura K.
  • Organizer: 18th World Congress of Basic and Clinical Pharmacology, July 1-6, Kyoto
  • Int'l Joint Research
• [Presentation] The new role of HIF-1 in the development of renal fibrosis in mouse UUO model. (2018)
  • Author(s): Kabei K., Uchida J., Tateishi Y., Nishide S., Kosoku A., Iwai T., Kuwabara N., Nakatani T. and Miura K.
  • Organizer: 18th World Congress of Basic and Clinical Pharmacology, July 1-6, Kyoto
  • Int'l Joint Research
• [Presentation] 血管リモデリングにおける平滑筋由来HIF-1αの役割 (2017)
  • Author(s): 冨田修平
  • Organizer: 第46回日本心脈管作動物質学会
• [Presentation] Role of hypoxia inducible factor-1 in Vascular Remodeling (2017)
  • Author(s): Shuhei Tomita
  • Organizer: 第94回日本生理学会大会
• [Book] カラー 新しい薬理学 (2018)
  • Author(s): 石井邦明、西山 成
  • Total Pages: 588
  • Publisher: 西村書店
  • ISBN: 9784890134854
• [Remarks]
  • URL: http://www.med.osaka-cu.ac.jp/departments/bunshi-pharmacology.shtml
• [Patent(Industrial Property Rights)] 腫瘍関連マクロファージ賦活化剤 (2019)
  • Inventor(s): 冨田修平・松永慎司・西出峻治・内田潤次
  • Industrial Property Rights Holder: 冨田修平・松永慎司・西出峻治・内田潤次
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2019-143014
  • Filing Date: 2019