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Molecular and Cellular Physiology(Biology)

Jingushi KentaroSpecially Appointed Assosiate Professor / Lecturer

Using clinical specimens provided by the joint research facility, we are conducting (1) biomarker search and drug discovery research targeting extracellular vesicles released from cancer tissue, (2) analysis of bacterial flora information present in blood extracellular vesicles.

Research theme

Development of drug discovery and diagnostic agents targeting extracellular vesicles released directly from cancer tissue

Since cancer cell-released extracellular vesicles (EVs) harbors cancer cell-specific RNAs and proteins, it has been focused as a target for cancer biomarker and therapeutic target. However, in cancer patients, circulating EVs are mixed with large amount of whole organ-derived EV, which makes it hard to identify small population of cancer-specific EVs. Moreover, cancer cell line EVs, which has been secreted in the situation far from complexed tumor microenvironment does not mimic the circulating cancer cell EVs. Therefore, we have developed a novel EVs isolation method which enables EVs isolation directly from clinically resected tumor tissue (bona-fide cancer EV). Based on this unique technology, we are researching with the aim of developing novel drug discovery and diagnostic agents targeting cancer EVs.

Analysis of bacterial flora information present in blood extracellular vesicles

Recently, the existence of bacterial information (16S rRNA gene) in blood has been reported, but its mode of existence and pathological significance are unknown. We have discovered that bacterial information is contained in human blood EVs, and have succeeded in analyzing total bacterial information derived from the whole body including the intestinal flora. Furthermore, it has been clarified that bacterial information in the blood of cancer patients is useful for predicting the effects of drugs such as immune checkpoint inhibitors and predicting the prognosis of patients. Currently, we are proceeding with the analysis of blood bacterial information for various cancer types.

Representative achievements

Naito T, Jingushi K, Ueda K, Tsujikawa K, Azurocidin is loaded into small extracellular vesicles via its N-linked glycosylation and promotes intravasation of renal cell carcinoma cells. FEBS Letters, 2021,19,2522-2532.

Matsushita M, Hayashi T, Kayama H, Motooka D, Hase H, Jingushi K, Yamamichi G, Yumiba S, Tomiyama E, Koh Y, Hayashi Y, Nakano K, Wang C, Ishizuya Y, Kato T, Hatano K, Kawashima A, Ujike T, Uemura M, Imamura R, Pena MD, Gordetsky JB, Netto GJ, Tsujikawa K, Nakamura S, Takeda K, Nonomura N, Gut microbiota-derived short-chain fatty acids promote prostate cancer growth via IGF-1 signaling. Cancer Research, 2021,15,4014-4026.

Jingushi K, Aoki M, Ueda K, Kogaki T, Tanimoto M, Monoe Y, Ando M, Matsumoto T, Minami K, Ueda Y, Kitae K, Hase H, Nagata T, Takeda A, Yamamoto M, Kawahara K, Tabata K, Furukawa T, Sato M, Tsujikawa K, ALKBH4 promotes tumourigenesis with a poor prognosis in non-small-cell lung cancer. Scientific Reports, 2021,1,8677.

Tomiyama E, Matsuzaki K, Fujita K, Shiromizu T, Narumi R, Jingushi K, Koh Y, Matsushita M, Nakano K, Hayashi Y, Wang C, Ishizuya Y, Kato T, Hatano K, Kawashima A, Ujike T, Uemura M, Takao T, Adachi J, Tomonaga T, Nonomura N, Proteomic analysis of urinary and tissue-exudative extracellular vesicles to discover novel bladder cancer biomarkers. Cancer Science, 2021,5,2033- 2045.

Hirono T, Jingushi K, Nagata T, Sato M, Minami K, Aoki M, Takeda A, Umehara T, Egawa H, Nakatsuji Y, Kitae K, Ueda Y, Hase H, Yamamoto M, Shinsato Y, Kawahara K, Furukawa T, Tsujikawa K, MicroRNA-130b functions as an oncomiRNA in non-small cell lung cancer by targeting tissue inhibitor of metalloproteinase-2. Scientific Reports, 2019,1,6956.

Kawashima A, Kanazawa T, Jingushi K, Kato T, Ujike T, Nagahara A, Fujita K, Morimoto- Okazawa A, Iwahori K, Uemura M, Imamura R, Wada H, Nonomura N, Phenotypic analysis of tissue infiltrating lymphocytes in tumour microenvironment of bladder cancer and upper urinary tract carcinoma. Clinical Genitourinary Cancer, 2018,18,30245-30243.

Jingushi K, Uemura M, Nakano K, Hayashi Y, Wang C, Ishizuya Y, Yamamoto Y, Hayashi T, Kinouchi T, Matsuzaki K, Kato T, Kawashima A, Ujike T, Nagahara A, Fujita K, Ueda K, Tsujikawa K, Nonomura N, Leukocyte‐associated immunoglobulin‐like receptor 1 promotes tumorigenesis in RCC. Oncology Reports, 2019,2,1293-1303.

Hayashi T, Fujita K, Nojima S, Hayashi Y, Nakano K, Ishizuya Y, Wang C, Yamamoto Y, Kinouchi T, Matsuzaki K, Jingushi K, Kato T, Kawashima A, Nagahara A, Ujike T, Uemura M, Rodriguez Pena MDC, Gordetsky JB, Morii E, Tsujikawa K, Netto GJ, Nonomura N, High-fat diet-induced inflammation accelerates prostate cancer growth via IL6 signaling. Clinical Cancer Research, 2018,17,4309-4318.

Matsuzaki K, Fujita K, Hayashi Y, Matsushita M, Nojima S, Jingushi K, Kato T, Kawashima A, Ujike T, Nagahara A, Uemura M, Imamura R, Yamaguchi S, Fushimi H, Miyamoto H, Morii E, Nonomura N, STAT3 expression is a prognostic marker in upper urinary tract urothelial carcinoma. PLoS One, 2018,8,e0201256.

Jingushi K, Uemura M, Ohnishi N, Nakata W, Fujita K, Naito T, Fujii R, Saichi N, Nonomura N, Tsujikawa K, Ueda K, Extracellular vesicles isolated from human renal cell carcinoma tissues disrupt vascular endothelial cell morphology via azurocidin. International Journal of Cancer, 2018,3,607-617.