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4. SUPREME-HN: a retrospective biomarker study assessing the prognostic value of PD-L1 expression in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

Author

Pai, Sara I, Cohen, Ezra EW, Lin, Derrick, Fountzilas, George, Kim, Edward S, Mehlhorn, Holger, Baste, Neus, Clayburgh, Daniel, Lipworth, Loren, Resteghini, Carlo, Shara, Nawar, Fujii, Takashi, Zhang, Jun, Stokes, Michael, Wang, Huifen, Twumasi-Ankrah, Philip, Wildsmith, Sophie, Khaliq, Asud, Melillo, Giovanni, and Shire, Norah

Subjects
Biomarker, Head and neck squamous cell carcinoma, Immuno-oncology, PD-L1, Prognosis, Programmed cell death ligand-1, Medical and Health Sciences, Immunology
Abstract

BACKGROUND:Programmed cell death ligand-1 (PD-L1) expression on tumor cells (TCs) is associated with improved survival in patients with head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy, although its role as a prognostic factor is controversial. This study investigates whether tumoral expression of PD-L1 is a prognostic marker in patients with recurrent and/or metastatic (R/M) HNSCC treated with standard chemotherapy. METHODS:This retrospective, multicenter, noninterventional study assessed PD-L1 expression on archival R/M HNSCC tissue samples using the VENTANA PD-L1 (SP263) Assay. PD-L1 high was defined as PD-L1 staining of ≥ 25% TC, with exploratory scoring at TC ≥ 10% and TC ≥ 50%. The primary objective of this study was to estimate the prognostic value of PD-L1 status in terms of overall survival (OS) in patients with R/M HNSCC. RESULTS:412 patients (median age, 62.0 years; 79.9% male; 88.2% Caucasian) were included from 19 sites in seven countries. 132 patients (32.0%) had TC ≥ 25% PD-L1 expression; 199 patients (48.3%) and 85 patients (20.6%) had TC ≥ 10% and ≥ 50%, respectively. OS did not differ significantly across PD-L1 expression (at TC ≥ 25% cutoff median OS: 8.2 months vs TC

Published
2019

5. A common deletion at BAK1 reduces enhancer activity and confers risk of intracranial germ cell tumors

Author

Sonehara, Kyuto, Kimura, Yui, Nakano, Yoshiko, Ozawa, Tatsuya, Takahashi, Meiko, Suzuki, Ken, Fujii, Takashi, Matsushita, Yuko, Tomiyama, Arata, Kishikawa, Toshihiro, Yamamoto, Kenichi, Naito, Tatsuhiko, Suzuki, Tomonari, Yamaguchi, Shigeru, Miwa, Tomoru, Sasaki, Hikaru, Kitagawa, Masashi, Ohe, Naoyuki, Fukai, Junya, Ogiwara, Hideki, Kawamura, Atsufumi, Miyawaki, Satoru, Matsuda, Fumihiko, Kiyokawa, Nobutaka, Ichimura, Koichi, Nishikawa, Ryo, Okada, Yukinori, and Terashima, Keita

Published
2022
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9. Validation and comparison of prognostic scoring systems in patients with head and neck squamous cell carcinoma treated with nivolumab

Author

Takenaka, Yukinori, primary, Takemoto, Norihiko, additional, Otsuka, Tomoyuki, additional, Nishio, Minako, additional, Tanida, Masashi, additional, Fujii, Takashi, additional, Hayashi, Kazuki, additional, Suzuki, Motoyuki, additional, Mori, Masashi, additional, Yamamoto, Yoshifumi, additional, Uno, Atsuhiko, additional, and Inohara, Hidenori, additional

Published
2024
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12. KLC1-ROS1 Fusion Exerts Oncogenic Properties of Glioma Cells via Specific Activation of JAK-STAT Pathway

Author

Fujii, Takashi, primary, Nakano, Yoshiko, additional, Hagita, Daichi, additional, Onishi, Nobuyuki, additional, Endo, Arumu, additional, Nakagawa, Masaya, additional, Yoshiura, Toru, additional, Otsuka, Yohei, additional, Takeuchi, Satoru, additional, Suzuki, Mario, additional, Shimizu, Yuzaburo, additional, Toyooka, Terushige, additional, Matsushita, Yuko, additional, Hibiya, Yuko, additional, Tomura, Satoshi, additional, Kondo, Akihide, additional, Wada, Kojiro, additional, Ichimura, Koichi, additional, and Tomiyama, Arata, additional

Published
2023
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14. COVID-19 severity is associated with the risk of gastrointestinal bleeding

Author

Hibiya, Shuji, primary, Fujii, Takashi, additional, Fujii, Toshimitsu, additional, Suzuki, Shinji, additional, Kondo, Mayumi, additional, Ooka, Shinya, additional, Furumoto, Yohei, additional, Azuma, Seishin, additional, Tanaka, Kei, additional, Kurata, Hitoshi, additional, Tanaka, Shohei, additional, Kurosaki, Masayuki, additional, Nagayama, Kazuyoshi, additional, Kusano, Fumihiko, additional, Iizuka, Yasuhiro, additional, Kawamura, Takahiro, additional, Ikemiyagi, Hidekazu, additional, Sakita, Shinya, additional, Yauchi, Tsunehito, additional, Watanabe, Hideki, additional, Kawamoto, Ami, additional, Matsuyama, Yusuke, additional, Ohtsuka, Kazuo, additional, and Okamoto, Ryuichi, additional

Published
2023
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19. Current and future perspective of IVUS tissue characterization of atherosclerotic plaque

Author

Hiro, Takafumi, Fujii, Takashi, Tobis, Jonathan M, and Matsuzaki, Masunori

Abstract

血管内エコー法(IVUS)では,以前より病理学的分類としての線維性hard plaqueと脂肪性soft plaqueに対応させるかのように,プラークのエコー輝度に応じて高輝度のものをhard plaque,低輝度度のものをs o f t p l a q u e とする分類が用いられる.しかし,著者らの検討によれば,プラークの線維領域および脂肪領域が,それぞれ必ず高輝度,低輝度に描出されるわけではなく,かなりの割合で逆に描出されうることが判明した。また,IVUSの機種によって画像が有意に違うことや,プラークの物理的硬度と比較しても低輝度ほど"soft"であるわけではないこともわかった.この限界を克服するため,これまでにRF信号を直接スペクトル解析する方法などが注目されているが,著者らはFractal解析やプラークのエコー輝度が超音波入射角度に依存性であることを利用して,組織性状を推定する方法を提唱してきた.その中で画像のFractal次元が線維領域で有意に低いことや,エコー輝度の超音波入射角度依存性がfibrous capに特に強く認められることが判明した.これらの画像処理法は,今後プラークの不安定性の定量評価に応用できる可能性を示唆していると考えられた.その他,三次元や長軸再構築像などを含めてIVUS技術は年々革新しており,動脈硬化プラークの組織性状診断の分野におけるIVUSの新たなる未来が期待される.

Published
1999

21. Impact of age at diagnosis of head and neck cancer on incidence of metachronous cancer

Author

Iwatsubo, Taro, Ishihara, Ryu, Morishima, Toshitaka, Maekawa, Akira, Nakagawa, Kentaro, Arao, Masamichi, Ohmori, Masayasu, Iwagami, Hiroyoshi, Matsuno, Kenshi, Inoue, Shuntaro, Nakahira, Hiroko, Matsuura, Noriko, Shichijo, Satoki, Kanesaka, Takashi, Yamamoto, Sachiko, Takeuchi, Yoji, Higashino, Koji, Uedo, Noriya, Miyashiro, Isao, Higuchi, Kazuhide, and Fujii, Takashi

Published
2019
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24. Woven Endo Bridge shape modification contributes to decrease in adequate occlusion rate after Woven Endo Bridge implantation for wide-neck bifurcation intracranial aneurysms.

Author

Fujii, Takashi, Teranishi, Kohsuke, Kitamura, Takayuki, Mitome-Mishima, Yumiko, Kondo, Akihide, and Oishi, Hidenori

Abstract

Purpose: Recently, a novel device, the Woven Endo Bridge (WEB), was developed for wide-neck bifurcation intracranial aneurysms (WNBAs). The aim of this study is to investigate factors that contribute to adequate occlusion (AO) after the operation using detailed radiological images. Methods: The subjects were 29 patients with 29 aneurysms who received WEB implantation for WNBAs between December 2020 and April 2022. We assessed the contributing factors to AO by retrospectively comparing the AO group and non-AO group. Results: The mean age was 64.6 ± 13.1 years, and 18 were female (62.1%). The mean aneurysm dome width, aneurysm height, and aneurysm neck diameter were 4.8 ± 0.6 mm, 5.1 ± 0.6 mm, and 3.7 ± 0.6 mm, respectively. After about 6 months, 22 of 29 patients (75.9%) had AO. Complications were observed in 2 patients (6.9%), renal artery injury in one, and minor cerebral infarction in another, but the modified Rankin scale scores of both patients remained unchanged. Multivariate analysis extracted only WEB shape modification (WSM) as a contributing factor to AO (odds ratio: 0.912, p = 0.0287). Conclusion: WEB implantation for WNBAs was a treatment modality with acceptable efficacy and safety. WSM was the only significant factor contributing to non-AO after the treatment. We should clarify the mechanisms or causes of WSM to achieve AO after WEB implantation in future. [ABSTRACT FROM AUTHOR]

Published
2024
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25. KLC1-ROS1 Fusion Exerts Oncogenic Properties of Glioma Cells via Specific Activation of JAK-STAT Pathway.

Author

Fujii, Takashi, Nakano, Yoshiko, Hagita, Daichi, Onishi, Nobuyuki, Endo, Arumu, Nakagawa, Masaya, Yoshiura, Toru, Otsuka, Yohei, Takeuchi, Satoru, Suzuki, Mario, Shimizu, Yuzaburo, Toyooka, Terushige, Matsushita, Yuko, Hibiya, Yuko, Tomura, Satoshi, Kondo, Akihide, Wada, Kojiro, Ichimura, Koichi, and Tomiyama, Arata

Subjects
*THERAPEUTIC use of antineoplastic agents, *STAT proteins, *IN vitro studies, *KINESIN, *GENETIC mutation, *ONCOGENES, *CANCER invasiveness, *GLIOMAS, *MOLECULAR pathology, *JANUS kinases, *CELLULAR signal transduction, *IMMUNOBLOTTING, *COMPARATIVE studies, *PROTEIN-tyrosine kinase inhibitors, *PROTEIN-tyrosine kinases, *RESEARCH funding, *CELL proliferation, *TEMOZOLOMIDE, *CELL lines, *DRUG resistance in cancer cells, *CHILDREN
Abstract

Simple Summary: By examining the detailed molecular oncogenic mechanisms of KLC1-ROS1 fusion, the function of a novel RTK fusion was investigated to discover novel therapeutic targets for glioma. When wild-type ROS1 and KLC1-ROS1 fusions were expressed in human glioma cell lines, immunoblotting revealed that KLC1-ROS1 fusion specifically activated the JAK2–STAT3 axis compared with wild-type ROS1. Immunoprecipitation revealed a more efficient association of KLC1-ROS1 fusion with JAK2 compared with wild-type ROS1. A mutagenesis study of KLC1-ROS1 fusion demonstrated the essential roles of both the KLC1 and ROS1 domains in the serum factor-independent constitutive activation of the fusion. In addition, KLC1-ROS1 fusion induced the upregulation of cell proliferation and invasion compared to wild-type ROS1 in a JAK-STAT-dependent manner under serum deprivation. Overall, our results suggested that molecules other than RTKs may serve as novel therapeutic targets for gliomas with RTK fusions. Here, we investigated the detailed molecular oncogenic mechanisms of a novel receptor tyrosine kinase (RTK) fusion, KLC1-ROS1, with an adapter molecule, KLC1, and an RTK, ROS1, discovered in pediatric glioma, and we explored a novel therapeutic target for glioma that possesses oncogenic RTK fusion. When wild-type ROS1 and KLC1-ROS1 fusions were stably expressed in the human glioma cell lines A172 and U343MG, immunoblotting revealed that KLC1-ROS1 fusion specifically activated the JAK2-STAT3 pathway, a major RTK downstream signaling pathway, when compared with wild-type ROS1. Immunoprecipitation of the fractionated cell lysates revealed a more abundant association of the KLC1-ROS1 fusion with JAK2 than that observed for wild-type ROS1 in the cytosolic fraction. A mutagenesis study of the KLC1-ROS1 fusion protein demonstrated the fundamental roles of both the KLC1 and ROS1 domains in the constitutive activation of KLC1-ROS1 fusion. Additionally, in vitro assays demonstrated that KLC1-ROS1 fusion upregulated cell proliferation, invasion, and chemoresistance when compared to wild-type ROS1. Combination treatment with the chemotherapeutic agent temozolomide and an inhibitor of ROS1, JAK2, or a downstream target of STAT3, demonstrated antitumor effects against KLC1-ROS1 fusion-expressing glioma cells. Our results demonstrate that KLC1-ROS1 fusion exerts oncogenic activity through serum-independent constitutive activation, resulting in specific activation of the JAK-STAT pathway. Our data suggested that molecules other than RTKs may serve as novel therapeutic targets for RTK fusion in gliomas. [ABSTRACT FROM AUTHOR]

Published
2024
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30. Post-operative progress of arm abduction function and rate of lymph node metastasis around the region of the accessory nerve: a multicentre prospective observational study

Author

Tomioka, Toshifumi, primary, Beppu, Takeshi, additional, Onitsuka, Tetsuro, additional, Fujimoto, Yasushi, additional, Kawabata, Kazuyoshi, additional, Matsuura, Kazuto, additional, Fujii, Takashi, additional, Hayashi, Ryuichi, additional, and Asakage, Takahiro, additional

Published
2023
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31. Feasibility of Simple Evaluation of Coronary Artery Calcium Using a Number of Chest Computed Tomography Slices: A Multicenter Study

Author

Yamamoto, Hideya, primary, Fujimoto, Shinichiro, additional, Aoshima, Chihiro, additional, Minamino, Tohru, additional, Fujii, Takashi, additional, Wakabayashi, Shinichi, additional, Urabe, Yoji, additional, Ueda, Hironori, additional, Kunita, Eiji, additional, Abe, Mitsunori, additional, and Higashino, Hiroshi, additional

Published
2023
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32. BOT-3 GENOME-WIDE ASSOCIATION STUDY OF INTRACRANIAL GERM CELL TUMORS: A COMMON DELETION ATBAK1 ATTENUATES THE ENHANCER ACTIVITY AND CONFERS RISK FOR THE BRAIN TUMORS IN CHILDREN ADOLESCENTS AND YOUNG ADULTS

Author

Terashima, Keita, primary, Sonehara, Kyuto, additional, Kimura, Yui, additional, Nakano, Yoshiko, additional, Ozawa, Tatsuya, additional, Takahashi, Meiko, additional, Suzuki, Ken, additional, Fujii, Takashi, additional, Matsushita, Yuko, additional, Tomiyama, Arata, additional, Suzuki, Tomonari, additional, Yamaguchi, Shigeru, additional, Miwa, Tomoru, additional, Sasaki, Hikaru, additional, Kitagawa, Masashi, additional, Ohe, Naoyuki, additional, Fukai, Junya, additional, Ogiwara, Hideki, additional, Kawamura, Atsufumi, additional, Miyawaki, Satoru, additional, Matsuda, Fumihiko, additional, Kiyakawa, Nobutaka, additional, Ichimura, Koichi, additional, Nishikawa, Ryo, additional, and Okada, Yukinori, additional

Published
2022
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44. Potential of preimplantation genomic selection using the blastomere separation technique in bovine in vitro fertilized embryos

Author

FUJII, Takashi, NAITO, Akira, MORIYASU, Satoru, and KAGEYAMA, Soichi

Subjects
Cryopreservation, Blastomeres, Genotype, Bovine, Cell Separation, Fertilization in Vitro, Genomics, Blastomere separation, Embryo Transfer, Polymorphism, Single Nucleotide, Vitrification, Embryo Culture Techniques, Blastocyst, Embryo, Pregnancy, In vitro fertilization, Preimplantation genomic selection, embryonic structures, Animals, Pregnancy, Animal, Cattle, Female, Technology Report, Preimplantation Diagnosis
Abstract

Preimplantation genomic selection combined with an in vitro embryo production system is expected as a means of accelerating genetic improvement in cattle. While micromanipulation-based biopsy approaches are often used to collect embryonic cells for genetic testing, they require expensive equipment and sophisticated skills, hindering the adoption of this system. In the present study, to develop a simple method for preimplantation genomic selection using the blastomere separation (BS) technique in bovine in vitro fertilized embryos, we examined the accuracy of single nucleotide polymorphism (SNP) genotyping and optimal cryopreservation method in demi-blastocysts produced by the BS technique. We demonstrated reliable SNP genotyping using DNA derived from demi-blastocysts. We indicated a suitable equilibrium time in vitrification solution for demi-blastocysts and succeeded obtaining pregnancies by the transfer of vitrified demi-blastocysts. In conclusion, our findings suggest that the BS technique provides a simple method for preimplantation genomic selection in bovine in vitro fertilized embryos.

Published
2021

45. リンパ節のPET/CTによるSUVmaxに重み付け係数を乗じてCECTの最大短径を加えた新しいcombined indexによる舌癌の臨床的N0症例の潜在的リンパ節転移の評価

Author

Kanamura, Ryo, Suzuki, Motoyuki, Otozai, Shinji, Yoshii, Tadashi, Okamoto, Hidehiko, Kitamura, Yoshiaki, Abe, Koji, Fujii, Takashi, and Takeda, Noriaki

Subjects
Tongue cancer, lymph node metastasis, PET/CT, clinical N0 neck, occult nodal metastasis
Abstract

To predict occult nodal metastasis in clinical N0 patients with tongue cancer, we developed combined index (CI) : SUVmax of the largest lymph node in PET/CT by weighting coefficient plus its maximum minor axis (< 10 mm) in contrast-enhanced CT (CECT). In this retrospective study, 57 clinical N0 patients with tongue cancer, who underwent elective supraomohyoid neck dissection at cervical levels of I-III were enrolled. The cutoff value of SUVmax of 2.0 obtained using receiver operating characteristic (ROC) analysis predicted the postoperative positive cervical levels containing metastatic lymph nodes from clinical N0 cervical levels in tongue cancer patients with a sensitivity of 54.5% and a specificity of 78.2%. The cutoff value of CI with weighting coefficient of 1.5 obtained using ROC analysis was 9.8 at the maximum area under the curve of 0.750. The cutoff value of 9.8 predicted the postoperative positive cervical levels containing metastatic lymph nodes from clinical N0 cervical levels in tongue cancer patients with a sensitivity of 68.2% and a specificity of 81.5%. These findings suggest that CI of functional PET/CT and morphological CECT components might improve the diagnostic performance of occult nodal metastasis to select clinical N0 patients with tongue cancer preferable for elective neck dissection.

Published
2021

46. Abstract 5210: Tumor immune characterization identifies age-stratified biomarkers for nivolumab in patients with head and neck squamous cell carcinoma: A nationwide collaborative study in Japan

Author

Tsujikawa, Takahiro, primary, Ohno, Kazuchika, additional, Saburi, Sumiyo, additional, Mitsuda, Junichi, additional, Yoshimura, Kanako, additional, Kimura, Alisa, additional, Morimoto, Hiroki, additional, Ohmura, Gaku, additional, Arai, Akihito, additional, Ogi, Hiroshi, additional, Shibata, Saya, additional, Ariizumi, Yosuke, additional, Tasaki, Akihisa, additional, Takahashi, Ryosuke, additional, Tateishi, Yumiko, additional, Kawabe, Hiroaki, additional, Ikeda, Sadakatsu, additional, Morita, Kei-ichi, additional, Tsunoda, Tatsuhiko, additional, Akashi, Takumi, additional, Kurata, Morito, additional, Imoto, Issei, additional, Shimizu, Yasushi, additional, Watanabe, Akihito, additional, Asada, Yukinori, additional, Hayashi, Ryuichi, additional, Saito, Yuki, additional, Ozawa, Hiroyuki, additional, Tsukahara, Kiyoaki, additional, Oridate, Nobuhiko, additional, Horii, Arata, additional, Maruo, Takashi, additional, Hanai, Nobuhiro, additional, Inohara, Hidenori, additional, Iwai, Hiroshi, additional, Fujii, Takashi, additional, Nibu, Ken-ichi, additional, Iwae, Shigemichi, additional, Ueda, Tsutomu, additional, Yasumatsu, Ryuji, additional, Umeno, Hirohito, additional, Masuda, Muneyuki, additional, Itoh, Kyoko, additional, Hirano, Shigeru, additional, and Asakage, Takahiro, additional

Published
2022
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49. Weekly Cisplatin Plus Radiation for Postoperative Head and Neck Cancer (JCOG1008): A Multicenter, Noninferiority, Phase II/III Randomized Controlled Trial

Author

Kiyota, Naomi, Tahara, Makoto, Mizusawa, Junki, Kodaira, Takeshi, Fujii, Hirofumi, Yamazaki, Tomoko, Mitani, Hiroki, Iwae, Shigemichi, Fujimoto, Yasushi, Onozawa, Yusuke, Hanai, Nobuhiro, Ogawa, Takenori, Hara, Hiroki, Monden, Nobuya, Shimura, Eiji, Minami, Shujiro, Fujii, Takashi, Tanaka, Kaoru, Homma, Akihiro, Yoshimoto, Seiichi, Oridate, Nobuhiko, Omori, Koichi, Ueda, Tsutomu, Okami, Kenji, Ota, Ichiro, Shiga, Kiyoto, Sugasawa, Masashi, Asakage, Takahiro, Saito, Yuki, Murono, Shigeyuki, Nishimura, Yasumasa, Nakamura, Kenichi, Hayashi, Ryuichi, and the Head and Neck Cancer Study Group of the Japan Clinical Oncology Group (JCOG-HNCSG)

Subjects
Cancer Research, Oncology, Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Squamous Cell, Humans, Chemoradiotherapy, Cisplatin
Abstract

PURPOSE The standard treatment for postoperative high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is chemoradiotherapy with 3-weekly cisplatin (100 mg/m2). However, whether chemoradiotherapy with weekly cisplatin (40 mg/m2) yields comparable efficacy with 3-weekly cisplatin in postoperative high-risk LA-SCCHN is unknown. PATIENTS AND METHODS In this multi-institutional open-label phase II/III trial, patients with postoperative high-risk LA-SCCHN were randomly assigned to receive either chemoradiotherapy with 3-weekly cisplatin (100 mg/m2) or with weekly cisplatin (40 mg/m2) to confirm the noninferiority of weekly cisplatin. The primary end point of phase II was the proportion of treatment completion, and that of phase III was overall survival. A noninferiority margin of hazard ratio was set at 1.32. RESULTS Between October 2012 and December 2018, a total of 261 patients were enrolled (3-weekly cisplatin, 132 patients; weekly cisplatin, 129 patients). At the planned third interim analysis in the phase III part, after a median follow-up of 2.2 (interquartile range 1.19-3.56) years, chemoradiotherapy with weekly cisplatin was noninferior to 3-weekly cisplatin in terms of overall survival, with a hazard ratio of 0.69 (99.1% CI, 0.374 to 1.273 [< 1.32], one-sided P for noninferiority = .0027 < .0043). Grade 3 or more neutropenia and infection were less frequent in the weekly arm (3-weekly v weekly, 49% v 35% and 12% v 7%, respectively), as were renal impairment and hearing impairment. No treatment-related death was reported in the 3-weekly arm, and two (1.6%) in the weekly arm. CONCLUSION Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN. These findings suggest that chemoradiotherapy with weekly cisplatin can be a possible treatment option for these patients.

Published
2022

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