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Published Papers 【 display / non-display 】

• Trypanosoma cruzi assembles host cytoplasmic processing bodies to evade the innate immune response

  Eri Seto, Shinichiro Kina, Reika Kawabata-Iwakawa, Makiko Suzuki, Yoko Onizuka, Junko Nakajima-Shimada

  Biochim Biophys Acta Gen Subj   1868 ( 11 )   2024.11 [ Peer Review Accepted ]

  Type of publication: Research paper (other science council materials etc.)

• Higher overall survival rates of oral squamous cell carcinoma treated with metronomic neoadjuvant chemotherapy

  Shinichiro Kina, Sho Miyamoto, Reika Kawabata-Iwakawa, Mika Kina-Tanada, Masaru Ogawa, Satoshi Yokoo

  American Journal of Cancer Research ( e-Century Publishing Corporation )  14 ( 3 ) 1033 - 1051   2024 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• Exploring olfactory receptor family 7 subfamily C member 1 as a novel oral cancer stem cell target for immunotherapy

  Miyamoto, S; Hirohashi, Y; Morita, R; Miyazaki, A; Ogi, K; Kanaseki, T; Ide, K; Shirakawa, J; Tsukahara, T; Murai, A; Sasaya, T; Koike, K; Kina, S; Kawano, T; Goto, T; Ntege, EH; Shimizu, Y; Torigoe, T

  CANCER SCIENCE ( Cancer Science )  114 ( 9 ) 3496 - 3508   2023.09 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  The mortality rate of oral cancer has not improved over the past three decades despite remarkable advances in cancer therapies. Oral cancers contain a subpopulation of cancer stem cells (CSCs) that share characteristics associated with normal stem cells, including self-renewal and multi-differentiation potential. CSCs are tumorigenic, play a critical role in cancer infiltration, recurrence, and distant metastasis, and significantly contribute to drug resistance to current therapeutic strategies, including immunotherapy. Cytotoxic CD8+ T lymphocytes (CTLs) are key immune cells that effectively recognize peptide antigens presented by the major histocompatibility complex class I molecules. Increasing evidence suggests that cancer antigen-specific targeting by CTLs effectively regulates CSCs that drive cancer progression. In this study, we utilized data from public domains and performed various bioassays on human oral squamous cell carcinoma clinical samples and cell lines, including HSC-2 and HSC-3, to investigate the potential role of olfactory receptor family 7 subfamily C member 1 (OR7C1), a seven transmembrane G-protein-coupled olfactory receptor that is also expressed in nonolfactory tissues and was previously reported as a novel marker and target of colon cancer initiating cell-targeted immunotherapy, in CSC-targeted treatment against oral cancer. We found that the OR7C1 gene was expressed only in oral CSCs, and that CTLs reacted with human leukocyte antigen-A24-restricted OR7C1 oral CSC-specific peptides. Taken together, our findings suggest that OR7C1 represents a novel target for potent CSC-targeted immunotherapy in oral cancer.

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• EphA4 signaling is involved in the phenotype of well-differentiated oral squamous cell arcinoma with decreased tumor immunity

  Kina, S; Kawabata-Iwakawa, R; Miyamoto, S; Kato, T; Kina-Tanada, M; Arasaki, A

  EUROPEAN JOURNAL OF PHARMACOLOGY ( European Journal of Pharmacology )  945   175611 - 175611   2023.04 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Metronomic chemotherapy is defined as a high-frequency low-dose schedule of chemotherapy drug administration. Although metronomic chemotherapy is widely used, the mechanisms underlying resistance to metronomic chemotherapy remain unclear. Therefore, we herein conducted a single institutional phase I/II trial to assess the efficacy and safety of metronomic chemotherapy with bleomycin plus S-1, an oral 5-FU prodrug, in the neoadjuvant setting for patients with oral squamous cell carcinoma (OSCC). The response rate of well-differentiated OSCC to metronomic chemotherapy was significantly lower. We investigated differences in molecular profiles between poorly or moderately differentiated head and neck squamous cell carcinoma (HNSCC) and well-differentiated HNSCC from patients with HNSCC TCGA data. EphA4 expression positively correlated with histological differentiation. An upstream regulator analysis correlated with EphA4 expression identified pathways associated with decreased mTORC1 signaling and T cell activation, including TCR, CD3, CD28, and CD40LG. An EphA4 blocking peptide (KYL) induced mTOR activation in well-differentiated OSCC cell lines. Plasmacytoid dendritic cell and CD8+ T cell numbers were higher in the microenvironment of poorly or moderately differentiated HNSCC than in that of well-differentiated HNSCC. Well-differentiated HNSCC had the characteristics of "cold tumors" (immune-excluded tumors). Moreover, KYL used with chemotherapeutic drugs synergistically increased cancer cell death. Well-differentiated OSCC is depleted of immune cells, which may be partly explained by the receptor tyrosine kinase EphA4.

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• Cytological characteristics of premalignant cervical epithelial lesions in postmenopausal women based on endocrine indices and parakeratosis

  Sugisawa, A; Toyoda, Z; Tanabe, Y; Uehara, K; Oshiro, A; Yamazato, R; Sakamoto, C; Yogi, S; Kurima, K; Kina, S; Sakiyama, M; Kinjo, T

  MENOPAUSE-THE JOURNAL OF THE MENOPAUSE SOCIETY ( Menopause )  30 ( 2 ) 193 - 200   2023.02 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Abstract Objective To identify useful cytological findings for detecting premalignant lesions in postmenopausal women, cervicovaginal smear samples were analyzed and compared between women with or without premalignant lesions based on endocrine indices and presence of parakeratosis (PK). Methods The cervicovaginal smear samples of postmenopausal women with premalignant lesions (n = 94) and those who were without (n = 344), who were diagnosed between 2012 and 2014 were retrieved and analyzed. Women cytologically diagnosed with malignancy or those with suspicion of malignancy were excluded from this study. Cytological endocrine indices, such as the maturation index (MI) and eosinophilic index (EI) and the prevalence of PK were compared between the groups and analyzed using the 2 × 2 χ² test. The association of endocrine indices combined with the presence of PK and histological findings was also evaluated. Results Postmenopausal women with premalignant lesions had higher endocrine indices (EI of ≥11%; 65% vs. 43%, P < 0.01, f = 0.18) and a higher prevalence of PK positivity (PK ≥ 1; 46% vs. 7%, P < 0.01, f = 0.44) than those without lesions. Further analysis indicated that the combination of high EI and the presence of PK in postmenopausal women with cytological premalignant cases was highly associated with histological squamous intraepithelial lesions (SIL) (86% in women with premalignant lesions vs. 53% in those without; P = 0.01, f = 0.34). Conclusion Our research demonstrated that high EI and PK positivity were correlated with SIL in postmenopausal women. These cytological findings could provide potential diagnostic clues for detecting dysplasia.

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Grant-in-Aid for Scientific Research 【 display / non-display 】

Grant-in-Aid for Scientific Research 【 display / non-display 】

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2024.04  -  2027.03 

  Direct: 3,600,000 (YEN)  Overheads: 4,680,000 (YEN)  Total: 1,080,000 (YEN)

• PARP activity in HPV-positive oropharyngeal carcinoma: the mechanism of favorable prognosis and development of effective therapy

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2024.04  -  2027.03 

  Direct: 3,500,000 (YEN)  Overheads: 4,550,000 (YEN)  Total: 1,050,000 (YEN)

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2021.04  -  2024.03 

  Direct: 3,200,000 (YEN)  Overheads: 4,160,000 (YEN)  Total: 960,000 (YEN)

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2020.04  -  2023.03 

  Direct: 3,400,000 (YEN)  Overheads: 4,420,000 (YEN)  Total: 1,020,000 (YEN)

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2017.04  -  2020.03 

  Direct: 3,700,000 (YEN)  Overheads: 1,110,000 (YEN)  Total: 4,810,000 (YEN)

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