| 1. |
Tomoyasu Yoshihiro, Hiroshi Ariyama, Kyoko Yamaguchi, Takashi Imajima, Satoru Yamaga, Kenji Tsuchihashi, Taichi Isobe, Hitoshi Kusaba, Koichi Akashi, Eishi Baba, Inhibition of insulin-like growth factor-1 receptor enhances eribulin-induced DNA damage in colorectal cancer., Cancer science, 10.1111/cas.15558, 113, 12, 4207-4218, 2022.09, Microtubule targeting agents (MTAs) such as taxanes are broadly used for the treatment of patients with cancer. Although MTAs are not effective for treatment of colorectal cancer (CRC), preclinical studies suggest that a subset of patients with CRC, especially those with cancers harboring the BRAF mutation, could benefit from such agents. However, two MTAs, eribulin (Eri) and vinorelbine, have shown limited clinical efficacy. Here, we report that insulin-like growth factor 1 receptor (IGF-1R) signaling is involved in Eri resistance. Using CRC cell lines, we showed that Eri induces activation and subsequent translocation of IGF-1R to the nucleus. When the activation and/or nuclear translocation of IGF-1R was inhibited, Eri induced DNA damage and enhanced G2 /M arrest. In a xenograft model using the Eri-resistant SW480 cell line, the combination of Eri and the IGF-1R inhibitor linsitinib suppressed tumor growth more efficiently than either single agent. Thus, our results indicated that combination dosing with Eri and an IGF-1R inhibitor could overcome Eri resistance and offer a therapeutic opportunity in CRC.. |
| 2. |
Koki Uehara, Kenro Tanoue, Kyoko Yamaguchi, Hirofumi Ohmura, Mamoru Ito, Yuzo Matsushita, Kenji Tsuchihashi, Shingo Tamura, Hozumi Shimokawa, Taichi Isobe, Yoshihiro Shibata, Hiroshi Ariyama, Risa Tanaka, Hitoshi Kusaba, Hidetaka Yamamoto, Yoshinao Oda, Koichi Akashi, Eishi Baba, Preferential B cell differentiation by combined immune checkpoint blockade for renal cell carcinoma is associated with clinical response and autoimmune reactions., Cancer immunology, immunotherapy : CII, 10.1007/s00262-023-03505-4, 2023.08, Combined immune checkpoint blockade (ICB) is effective therapy for renal cell carcinoma (RCC). However, the dynamic changes in circulating B cells induced by combined ICB have not been clarified. The present study prospectively examined 22 patients scheduled to receive ICB for unresectable or metastatic RCC between March 2018 and August 2021. Eleven patients received combined therapy with anti-PD-1 (nivolumab) and anti-CTLA-4 (ipilimumab), and the other 11 patients received nivolumab monotherapy. Comprehensive phenotypes of circulating immune cells obtained prior to and after ICB therapy were analyzed by flow cytometry. Although the proportion of naïve B cells among total B cells was significantly decreased, that of switched memory B cells was significantly increased after combined therapy. In responders, the proportion of B cells among peripheral blood mononuclear cells was significantly higher prior to ICB therapy, and the proportion of switched memory B cells among total B cells tended to increase after ICB therapy. Of note, the proportion of plasmablasts among total B cells was significantly increased after ICB therapy in patients who developed severe immune-related adverse events (irAEs), and the proportion of B cells among peripheral blood decreased significantly. Furthermore, in four of five patients who developed immune-related hypophysitis following combined therapy, anti-pituitary antibody was detected in the serum. These results suggested that immune-related hypophysitis was closely related to the increase in circulating plasmablasts. Collectively, this study suggests that combined ICB promotes the differentiation of B cell populations, which is associated with efficient tumor suppression and development of irAEs.. |
| 3. |
Mamoru Ito, Michitaka Nakano, Hiroshi Ariyama, Kyoko Yamaguchi, Risa Tanaka, Yuichiro Semba, Takeshi Sugio, Kohta Miyawaki, Yoshikane Kikushige, Shinichi Mizuno, Taichi Isobe, Kenro Tanoue, Ryosuke Taguchi, Shohei Ueno, Takahito Kawano, Masaharu Murata, Eishi Baba, Koichi Akashi, Macrophages are primed to transdifferentiate into fibroblasts in malignant ascites and pleural effusions, Cancer Letters, 532, 215597, 2022.02. |
| 4. |
Kenji Tsuchihashi, Kyoko Yamaguchi, Ryosuke Taguchi, Kenichi Kohashi, Kayo Ijichi, Yuta Okumura, Michitaka Nakano, Akari Ohno, Tomonobu Hioki, Hozumi Shimokawa, Hiroshi Ariyama, Hitoshi Kusaba, Yoshinao Oda, Koichi Akashi, Eishi Baba, Spontaneous Regression of Metachronous Intra-Abdominal Desmoid Tumor in a Patient with Familial Adenomatous Polyposis, Case Reports in Oncology, 15, 71-77, 2022.02. |
| 5. |
Kyoko Yamaguchi, Kenji Tsuchihashi, Kunihiro Tsuji, Yosuke Kito, Kenro Tanoue, Hirofumi Ohmura, Mamoru Ito, Taichi Isobe, Hiroshi Ariyama, Hitoshi Kusaba, Koichi Akashi, Eishi Baba, Prominent PD-L1-positive M2 macrophage infiltration in gastric cancer with hyper-progression after anti-PD-1 therapy: A case report, Medicine（Baltimore）, 10.1097/MD.0000000000025773., 100, 19, e25773, 2021.05. |
