口腔生化学 / Biochemistry

がん細胞は、好気的条件下でもATP産生の最終産物として乳酸に代謝される解糖系に依存している。そのため、がん組織の細胞外pHは酸性に傾いていることが多い。このような特徴は、ワールブルグ効果(好気的解糖)として広く認識されている。私たちは、ワールブルグ効果によって作られる酸性の細胞外微小環境が細胞に与える影響に着目しています。酸性細胞外微小環境は、様々な因子:例えば、マトリックスメタロプロテアーゼ(MMP9、MMP13)、N-カドヘリン、ビメンチンなどの発現を通じて、がん細胞の浸潤・転移を促進することを見出しています。こちらもご覧ください。

Cancer cells depend on the glycolytic system metabolizing to lactate as the final product for ATP production even under aerobic conditions. Therefore, the extracellular pH of cancer tissue is often acidic. These characteristics are widely recognized as the Warburg effect (aerobic glycolysis). We are focusing the effects of the acidic extracellular microenvironment created by the Warburg effect on cells. We have found that the acidic extracellular microenvironment promotes cancer cell invasion and metastasis through the expression of various factors: e.g., matrix metalloproteinases (MMP9 and MMP13), N-cadherin, vimentin, etc.

 

パブリックデータベース(CV in public databases)

職歴(Employment):

ORCID ID、Researchmap、

業績(References)・被引用件数(Number of citations):

PubMed、 ResearchGate、Google Scholar Profile

助成金(Grants): 

　Grants-in-Aid for Scientific Research(KAKEN)

雑誌編集活動(Editorial board activities):

• Cancer Cell International (Editor-in-Chief, Recipient of Springer Nature Editorial Leadership Awards 2022, 23 August 2022)
• Mediators of Inflammation (Associate Editor)
• Oncology Letters (Editorial Board)
• Cell Biology International (Advisory Panel)

業績(References): 2010-Present

(1) Peer-reviewed/invited papers

1. Kobayashi-Sakamoto M, Maeda T, Yusa J, Shimada T, Tani H, Kato Y, Hirose K. Bovine lactoferrin suppresses the cathepsin-dependent pathway of SARS-CoV-2 entry in vitro. Int Dairy J 148, 105805, January 2024. doi: 10.1016/j.idairyj.2023.105805 [Publisher site]
2. Kanamori K, Ozawa S, Iwabuchi H, Ikoma T, Suzuki K, Tanaka K, Yoshimura Sawai N, Abe T, Kato Y, Hata RI, Kobayashi M. GPRC5B (G protein-coupled receptor class C group 5 member B) suppresses glucose starvation-induced apoptosis in head-and-neck squamous cell carcinoma. Biomed Res 44(1):1-7, 2023. doi: 10.2220/biomedres.44.1 [Pub-Med]
3. Hatori T, Maeda T, Suzuki A, Takahashi K, Kato Y. SPARC is a decoy counterpart for c‑Fos and is associated with osteoblastic differentiation of bone marrow stromal cells by inhibiting adipogenesis. Mol Med Rep 27(2): 50, 2023. doi: 10.3892/mmr.2023.12937 [Pub-Med]
4. Takahashi K, Yamazaki K, Yamazaki M, Kato Y, Baba Y. Personalized medicine based on the pathogenesis and risk assessment of endodontic–periodontal lesions. J Pers Med 12(10): 1688. doi: 10.3390/jpm12101688 [Pub-Med]
5. Baba Y, Kato Y, Takahashi K. Acute bacterial epiglottitis and COVID-induced angioedema of the larynx are possible differential diagnoses. Intern Med. Online ahead of print. doi: 10.2169/internalmedicine.0809-22 [Pub-Med]
6. Furuya G, Katoh H, Atsumi S, Hashimoto I, Komura D, Hatanaka R, Senga S, Hayashi S, Akita S, Matsumura H, Miura A, Mita H, Nakakido M, Nagatoishi S, Sugiyama A, Suzuki R, Konishi H, Yamamoto A, Abe H, Hiraoka N, Aoki K, Kato Y, Seto Y, Yoshimura C, Miyadera K, Tsumoto K, Ushiku T, Ishikawa S. Nucleic Acid-triggered Tumoral Immunity Propagates pH-selective Therapeutic Antibodies through Tumor-driven Epitope Spreading. Cancer Sci, 2022 Sep 22. doi: 10.1111/cas.15596. Online ahead of print [Pub-Med]
7. Baba Y, Kato Y, Takahashi K. Proposal for a paradigm shift in personalized medicine for patients with a maxillary edentulous jaw by ENT specialist and dentist cooperation. J Pers Med 12(8): 1289. doi: 10.3390/jpm12081289 [Pub-Med]
8. Kobayashi-Sakamoto M, Maeda T, Kimura M, Yusa J, Ito H, Tani H, Kato Y, Hirose K. Bovine lactoferrin increases the poly(I:C)-induced antiviral response in vivo. Biochem Cell Biol 100(4): 338-348. doi: 10.1139/bcb-2021-0342 [Pub-Med]
9. Baba Y, Takada S, Kato Y. In reference to risk perception of septic shock with multiple organ failure due to acute exacerbation of an infectious dental disease. Ther Clin Risk Manag 17: 1163-1164, 2021. doi: 10.2147/TCRM.S342486 [Pub-Med]
10. Funakawa T, Kawanabe H Usami A, Takahashi K, Kato Y, Baba Y. The importance of early detection for postoperative maxillary cyst before dental implantation: A case report. Int J Surg Case Rep 86: 106370, 2021. doi: 10.1016/j.ijscr.2021.106370 [Pub-Med]
11. Baba Y, Kato Y. Letter to the Editor: In reference to COVID-19 and the otolaryngologist: preliminary evidence-based review. Laryngoscope 131: E1460, 2021. doi: 10.1002/lary.29412 [Pub-Med]
12. Baba Y, Takada S, Segawa H, Kato Y. Different management between emergent infectious diseases and emergent non-infectious diseases during COVID-19 pandemic in a head and neck unit. Braz J Infect Dis S1413-8670(20), 30106–301069, 2020. doi: 10.1016/j.bjid.2020.07.007 [Pub-Med]
13. Kojima T, Maeda T, Suzuki A, Yamamori T, Kato Y. Intracellular zinc-dependent TAS2R8 gene expression through CTCF activation. Biomed Res (Tokyo) 41 (5), 217–225, 2020. doi: 10.2220/biomedres.41.217 [Pub-Med]
14. Suzuki-Yamazaki M, Takahashi K, Takada S, Kato Y, Baba Y. A successful treatment regimen for the prevention of sinusitis after maxillary sinus floor elevation surgery in a high-risk case. Case Rep Otolaryngol 2020, 6869805, 2020. doi: 10.1155/2020/6869805 [Pub-Med]
15. Kobayashi-Sakamoto M, Maeda T, Yusa J, Kato Y, Kiyoura Y. RANK-RANKL signaling upregulates Il-10 mRNA expression in mucosal Candida infection in vivo. Microb Pathog 149, 104285, 2020. doi: 10.1016/j.micpath.2020.104285 [Pub-Med]
16. Baba Y, Kato Y. Letter to the Editor (Confusion of epipen trainer with epipen caused by a pharmacist). J Paediatr Child Health 56(5), 826-827, 2020. doi: 10.1111/jpc.14884 [Pub-Med]
17. Sutoo S, Maeda T, Suzuki A, Kato Y. Adaptation to chronic acidic extracellular pH elicits a sustained increase in lung cancer cell invasion and metastasis. Clin Exp Metastasis 37(1), 133-144, 2020. doi: 10.1007/s10585-019-09990-1[Pub-Med]
18. Nagaoka M, Maeda T, Chatani M, Handa K, Yamakawa T, Kiyohara S, Negishi-Koga T, Kato Y, Takami M, Niida S, Lang SC, Kruger MC, Suzuki K. A Delphinidin-Enriched Maqui Berry Extract Improves Bone Metabolism and Protects against Bone Loss in Osteopenic Mouse Models. Antioxidants (Basel) 8(9), E386, 2019. doi: 10.3390/antiox8090386 [Pub-Med]
19. Nagaoka M, Maeda T, Moriwaki S, Nomura A, Kato Y, Niida S, Kruger MC, Suzuki K.. Petunidin, a B-ring 5'-O-methylated derivative of delphinidin, stimulates osteoblastogenesis and reduces sRANKL-induced bone loss. Int J Mol Sci 20(11), 2795, 2019. doi: 10.3390/ijms20112795 [Pub-Med]
20. 渡部敏恵,衛藤雅昭,小池勇一,佐藤 研,加藤靖正,馬場 優. 4種ウイルス感染症における抗体陽性率および感受性率の年次推移について-麻疹・風疹・ムンプス・水筒の血清抗体価解析-. Campus Health 56(2), 104-110, 2019. doi: 10.18632/oncotarget.20826 [Publisher site] (in Japanese)
21. Zijlstra A, Von Lersner A, Yu D, Borrello, B, Oudin M, Kang Y, Sahai E, Fingleton B, Stein U, Cox T, Price J, Kato Y, Welm A, Aguirre-Ghiso J. The importance of developing therapies targeting the biological spectrum of metastatic disease. Clin Exp Metastasis 36(4), 305–309, 2019. doi: 10.1007/s10585-019-09972-3 [Pub-Med]
22. Sumida R, Maeda T, Kawahara I, Yusa J, Kato Y. Platelet?rich fibrin increases the osteoprotegerin/receptor activator of nuclear factor?κB ligand ratio in osteoblasts. Exp Ther Med, 2019. doi: https://doi.org/10.3892/etm.2019.7560 [Publisher site]
23. Yang XY, Ozawa S, Kato Y, Maehata Y, Izukuri K, Ikoma T, Kanamori K, Akasaka T, Suzuki K, Iwabuchi H, Kurata SI, Katoh I, Sakurai T, Kiyono T, Hata RI. C-X-C Motif Chemokine Ligand 14 is a Unique Multifunctional Regulator of Tumor Progression. Int J Mol Sci 20(8), E1872, 2019. doi: 10.3390/ijms20081872 [Pub-Med]
24. Kato Y, Maeda T, Suzuki A, Baba Y. Cancer metabolism: New insights into classic characteristics. Jpn Dent Sci Rev 54(1), 8-21, 2018. doi: 10.1016/j.jdsr.2017.08.003 [Pub-Med]
25. Baba Y, Kato Y. Deguelin, a novel anti-tumorigenic agent in human esophageal squamous cell carcinoma. EBioMedicine 26(10), 10, 2017. doi: 10. doi: 10.1016/j.ebiom.2017.11.010 [Pub-Med]
26. Fingleton B, Lange K, Caldwell B, Bankaitis KV; Board of the Metastasis Research Society (Kang Y, Yu D, Aguirre-Ghiso J, Cox TR, Erler JT, Gelman IH, Hurst DR, Kato Y, Lynch CC, Price JT, Samant RS, Sleeman J, Stein U, Zijlstra A). Perspective on the interpretation of research and translation to clinical care with therapy-associated metastatic breast cancer progression as an example. Clin Exp Metastasis 34(8), 443-447, 2017. doi: 10.1007/s10585-017-9872-8 [Pub-Med]
27. Maeda T, Suzuki A, Koga K, Miyamoto C, Maehata Y, Ozawa S, Hata RI, Nagashima Y, Nabeshima K, Miyazaki K, Kato Y. TRPM5 mediates acidic extracellular pH signaling and TRPM5 inhibition reduces spontaneous metastasis in mouse B16-BL6 melanoma cells. Oncotarget 8(45), 78312-78326, 2017. doi: 10.18632/oncotarget.20826 [Pub-Med]
28. Baba Y, Kato Y. Promising biomarkers to predict the efficacy of inhibitors of the epidermal growth factor receptor tyrosine kinase in head and neck squamous cell carcinoma. Biomarkers J 3:6, 2017. doi: 10.21767/2472-1646.100028 [Publisher site]
29. Baba Y, Maeda T, Suzuki A, Takada S, Fujii M, Kato Y. Deguelin Potentiates Apoptotic activity of an EGFR tyrosine kinase inhibitor (AG1478) in PIK3CA-mutated head and neck squamous cell carcinoma. Int J Mol Sci 18(2), E262, 2017. doi: 10.3390/ijms18020262 [Pub-Med]
30. Maeda T, Yuzawa S, Suzuki A, Baba Y, Nishimura Y, Kato Y. RhoA mediates the expression of acidic extracellular pH-induced matrix metalloproteinase-9 mRNA through phospholipase D1 in mouse metastatic B16-BL6 melanoma cells. Int J Oncol 48(3), 1251-1257, 2016. doi: 10.3892/ijo.2016.3322 [Pub-Med]
31. Baba Y, Kato Y. The role of bevacizumab in the management of head and neck squamous cell carcinoma patients. Chemotherapy 4(3); 1000163, 2015. doi: 10.4172/2167-7700.1000163 [Publisher site]
32. Maeda T, Suzuki A, Yuzawa S, Baba Y, Kimura Y, Kato Y. Mineral trioxide aggregate induces osteoblastogenesis via Atf6. Bone Rep 2, 36-43, 2015. doi:10.1016/j.bonr.2015.03.003 [Pub-Med]
33. Nishiyama T, Kato Y, Baba Y. Nasopharyngeal leiomyomatous hamartoma: case report. BMC Ear Nose Throat Disord 14: 5, 2014. doi: 10.1186/1472-6815-14-5 [Pub-Med]
34. Kobayashi R, Terakawa J, Kato Y, Azimi S, Inoue N, Ohmori Y, Hondo E. The contribution of leukemia inhibitory factor (LIF) for embryo implantation differs among strains of mice. Immunobiology 219(7): 512-21, 2014. doi: 10.1016/j.imbio.2014.03.011 [Pub-Med]
35. Hata R, Izukuri K, Kato Y, Sasaki S, Mukaida N, Maehata Y, Miyamoto C, Akasaka T, Yang X, Nagashima Y, Takeda K, Kiyono T, Taniguchi M. Suppressed rate of carcinogenesis and decreases in tumour volume and lung metastasis in CXCL14/BRAK transgenic mice. Sci Rep 5, 9083, 2015. doi:10.1038/srep09083 [Pub-Med]
36. Suzuki A, Maeda T, Baba Y, Shimamura K, Kato Y. Acidic extracellular pH promotes epithelial mesenchymal transition in Lewis lung carcinoma model. Cancer Cell Int, 2014, 14: 129. doi:10.1186/s12935-014-0129-1 [Pub-Med]
37. Baba Y, Fujii M, Maeda T, Suzuki A, Yuzawa S, Kato Y. Deguelin induced apoptosis by targeting both EGFR-Akt and IGF1R-Akt pathways in head and neck squamous cell cancer cell lines. BioMed Res Int 657179, 2014. doi: 10.1155/2015/657179 [Pub-Med]
38. Baba Y, Kato Y. Hemangioma with phleboliths in the floor of the mouth presenting as a submental swelling: a case report. J Med Cases 2(1): 28-30, 2011. [Publisher site]
39. Baba Y, Kato Y, Ogawa K. Unusual computed tomography findings of radionecrosis after chemoradiation of stage IV hypopharyngeal cancer: a case report. J Med Case Rep 5(1): 25, 2011. [Pub-Med]
40. Baba Y, Kato Y, Ogawa K. Hyperplasia of lymphoid structures in the hypopharynx: a case report. J Med Case Rep 4: 388, 2010. [Pub-Med]
41. Nakazaki K, Kato Y, Taguchi T, Inayama Y, Ishiguro Y, Tsukuda M. Heterozygous mutation (G/G→G/A) at nt 2607 of the EGFR gene is closely associated with increases in EGFR copy number and mRNA half life, but impaired EGFR protein synthesis in squamous cell carcinomas of the head and neck - implication for gefitinib efficacy. Oncol Lett 1: 1017-1020, 2010. [Pub-Med]
42. Maehata Y, Ozawa S, Kobayashi K, Kato Y, Yoshino F, Miyamoto C, Izukuri K, Kubota E, Hata RI, Lee MC. Reactive oxygen species (ROS) reduce the expression of BRAK/CXCL14 in human head and neck squamous cell carcinoma cells. Free Radical Res 44(8): 913-924, 2010. [Pub-Med]
43. Ozawa S, Ito S, Kato Y, Kubota E, Hata RI. Human p38delta MAP kinase mediates UV irradiation induced up-regulation of the gene expression of chemokine BRAK/CXCL14. Biochem Biophys Res Commun 396(4) 1060-1064, 2010. [Pub-Med]
44. Komori R, Ozawa S, Kato Y, Shinji H, Kimoto S, Hata RI. Functional characterization of proximal promoter of gene for human chemokine BRAK/CXCL14. Biomed Res 31(2): 123-131, 2010. [Pub-Med]
45. Sato K, Ozawa S, Izukuri K, Kato Y, Hata RI. Expression of tumor-suppressing chemokine BRAK/ CXCL14 reduces cell migration rate of HSC-3 tongue carcinoma cells and stimulates attachment to collagen and formation of elongated focal adhesions in vitro. Cell Biol Int 34: 513-522, 2010. [Pub-Med]
46. Baba Y, Kato Y, Ogawa K. Inostamycin prevents malignant phenotype of cancer: inhibition of phosphatidylinositol synthesis provides a therapeutic advantage for head and neck squamous cell carcinoma. Cell Biol Int 34(2):171-175, 2010. [Pub-Med]

(2) Books in Japanese

1. 加藤靖正.第1章 生化学に必要な化学の基礎,第15章 癌の生化学,In: スタンダード生化学・口腔生化学第4版(編集・執筆:荒川俊哉,池尾　隆,加藤靖正,古株彰一郎,近藤信夫,自見英治郎,鈴木直人,半田慶介,坂東健二郎,平塚浩一;執筆:川木晴美,高井理衣,髙田鮎子,髙山英次,田邉奈津子,津田啓方,堂前英資,藤田　厚,吉川美弘; ISBN: 978-4-7624-3633-8), 学研書院, 東京, p.2-11; 318-331, 2023. [Publisher site]
2. 馬場 優, 高田 訓, 加藤靖正.口腔癌におけるEGFR阻害剤の効果予測因子. BIO Clinica 34(9), 39-41, 2019. [Publisher site]
3. 加藤靖正,前田豊信,鈴木厚子.酸性細胞外pH:がん転移に関連する微小環境. 細胞 50(5), 32-36, 2018.[Publisher site]
4. 加藤靖正.第2章 がんはどうしてできるか,In: 口腔生化学第6版(監修:早川太郎、須田立雄、木崎治俊; ISBN: 978-4-263-456-45-3),医歯薬出版,東京,p. 301-338, 2018. [Publisher site]

(3) Books in English

1. Baba Y, Nishiyama T, Kato Y. Diagnosis and treatment of accessory parotid gland tumors, In: International manual of oncology practice (Eds: de Mello RA, Tavares A, Mountzios G; ISBN: 978-3-319-21682-9), Springer, Cham, Switzerland, p.123-140, 2012. doi: 10.1007/978-3-319-21683-6 [Publisher site]
2. Baba Y, Fujii M, Tokumaru Y, Kato Y. Overcoming resistance to EGFR inhibitor in head and neck cancer (Chapter 1), In: The research and biology of cancer II (Eds: Shoja MM, Agutter PS, Tubbs RS, Ghanei M, Ghabili K, Harris A, Loukas M; ISBN: 978-14775549-9-9), iConcept Press, Hong Kong, China, p.1-18, 2012.
3. Baba Y, Fujii M, Tokumaru Y, Kato Y. A proposal for a new strategy in head and neck cancer: combination therapy targeting the PI3kinase/Akt and EGFR signaling pathways (Chapter 12), In: Hypothesis in clinical medicine (Eds: Shoja MM, Agutter PS, Tubbs RS, Ghanei M, Ghabili K, Harris A, Loukas M; ISBN: 978-1-62257-285-4), Nova Science Publishers, New York, USA, p.181-198, 2012. [Publisher site]
4. Baba Y, Fujii M, Tokumaru Y, Kato Y. Cell Signalings and the Communications in Head and Neck Cancer, In: Head and Neck Cancer (Ed: Agulnik, M; ISBN: 978-953-51-0236-6), InTech, Rijeka, p.123-140, 2012. [Publisher site]

• 日本がん転移学会 (評議委員)
• 歯科基礎医学会 (理事)
• 日本生化学会(代議員)
• 日本結合組織学会 (評議委員)
• 日本歯科医学教育学会(平成29年～令和2年度代議員)
• 奥羽大学歯学会 (評議委員)
• Cancer Cell International (co-Editor-in-Chief, Sept 2020 - at present)
• The Metastasis Research Society (Board of Directors, 2016-2020 )
• American Society of Biochemistry and Molecular Biology (Regular member)
• International Society of Cancer Metabolism (Regular member)

【特許】

1. 発明の名称:骨形成促進剤及び骨形成促進装置
   発明者: 加藤靖正,前田豊信,鈴木厚子,藤山敬至,塩沢亜弥
   出願日: 平成27年10月28日
   出願番号: 特願2015-212328
   公開番号: 特開 2017-081856
   登録日: 2019年11月15日
   特許番号: 6614916


2. 発明の名称:頭頚部癌抑制剤および医薬組成物
   発明者:畑隆一郎,加藤靖正,小澤重幸,久保田英朗
   出願日:2005年9月20日
   出願番号:特願2005-271397
   登録日:2011年8月19日
   特許番号:4805641