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7. Precision cancer genome testing needs proficiency testing involving all stakeholders

Author

Maekawa, Masato, Taniguchi, Terumi, Nishio, Kazuto, Sakai, Kazuko, Matsushita, Kazuyuki, Nakatani, Kaname, Ishige, Takayuki, Ikejiri, Makoto, Nishihara, Hiroshi, Sunami, Kuniko, Yatabe, Yasushi, Hatanaka, Kanako C., Hatanaka, Yutaka, Yamamoto, Yoshihiro, Fukuyama, Keita, Oda, Shinya, Saito, Kayoko, Yokomura, Mamoru, Kubo, Yuji, Sato, Hiroko, Tanaka, Yoshinori, Fuchioka, Misa, Yamasaki, Tadashi, Matsuda, Koichiro, Kurachi, Kiyotaka, Funai, Kazuhiro, Baba, Satoshi, and Iwaizumi, Moriya

Published
2022
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8. Dysfunctional Sars-CoV-2-M protein-specific cytotoxic T lymphocytes in patients recovering from severe COVID-19

Author

Ogura, Hideki, Gohda, Jin, Lu, Xiuyuan, Yamamoto, Mizuki, Takesue, Yoshio, Son, Aoi, Doi, Sadayuki, Matsushita, Kazuyuki, Isobe, Fumitaka, Fukuda, Yoshihiro, Huang, Tai-Ping, Ueno, Takamasa, Mambo, Naomi, Murakami, Hiromoto, Kawaguchi, Yasushi, Inoue, Jun-ichiro, Shirai, Kunihiro, Yamasaki, Sho, Hirata, Jun-Ichi, and Ishido, Satoshi

Published
2022
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9. Contributions of CSF interleukin-6 elevation to the pathogenesis of myelin oligodendrocyte glycoprotein antibody–associated disease.

Author

Uzawa, Akiyuki, Mori, Masahiro, Masuda, Hiroki, Muto, Mayumi, Ohtani, Ryohei, Aoyama, Shinji, Matsushita, Kazuyuki, and Kuwabara, Satoshi

Subjects
MYELIN oligodendrocyte glycoprotein, CENTRAL nervous system diseases, CEREBROSPINAL fluid, NEUROLOGICAL disorders, CENTRAL nervous system, NEUROMYELITIS optica
Abstract

Background: Myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) is a rare neuroinflammatory disorder characterized by acute episodes of central nervous system (CNS) demyelination. Previous studies have reported elevated interleukin (IL)-6 in cerebrospinal fluid (CSF) of MOGAD patients. Objective: We examined if CSF IL-6 level increase is associated with clinical parameters in MOGAD. Methods: IL-6 levels were measured using 44 CSF samples during the acute phase and 6 samples during recovery from 34 MOGAD patients, as well as 65 CSF samples from 45 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4Ab + NMOSD), 107 samples from 76 multiple sclerosis patients, and 45 samples from neurodegenerative disease patients. Associations between IL-6 levels and clinical parameters in MOGAD were also evaluated. Results: CSF IL-6 levels were significantly comparably elevated during acute-phase in MOGAD and AQP4Ab + NMOSD, but declined following the acute phase. Among MOGAD patients, CSF IL-6 level was significantly correlated with CSF cell count, greater in patients with brain lesions than spinal cord lesions, and higher in CSF than serum, suggesting that excessive IL-6 is produced predominantly in CNS. Neurological recovery was tended to be poorer in MOGAD patients with higher CSF IL-6 level. Conclusion: CSF IL-6 may play important roles in the pathogenesis of MOGAD, especially in CNS inflammation. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Monoamine oxidase B rs1799836 G allele polymorphism is a risk factor for early development of levodopa-induced dyskinesia in Parkinson's disease

Author

Kakinuma, Shoko, Beppu, Minako, Sawai, Setsu, Nakayama, Akitoshi, Hirano, Shigeki, Yamanaka, Yoshitaka, Yamamoto, Tatsuya, Masafumi, Chigusa, Aisihaer, Xiamuxiya, Aersilan, Alimasi, Gao, Yue, Sato, Kenichi, Sakae, Itoga, Ishige, Takayuki, Nishimura, Motoi, Matsushita, Kazuyuki, Satoh, Mamoru, Nomura, Fumio, Kuwabara, Satoshi, and Tanaka, Tomoaki

Published
2020
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15. Genetic profiles of Barrett’s esophagus and esophageal adenocarcinoma in Japanese patients

Author

Tokunaga, Mamoru, Okimoto, Kenichiro, Akizue, Naoki, Ishikawa, Kentaro, Hirotsu, Yosuke, Amemiya, Kenji, Ota, Masayuki, Matsusaka, Keisuke, Nishimura, Motoi, Matsushita, Kazuyuki, Ishikawa, Tsubasa, Nagashima, Ariki, Shiratori, Wataru, Kaneko, Tatsuya, Oura, Hirotaka, Kanayama, Kengo, Ohta, Yuki, Taida, Takashi, Saito, Keiko, Matsumura, Tomoaki, Chiba, Tetsuhiro, Mochizuki, Hitoshi, Arai, Makoto, Kato, Jun, Ikeda, Jun-ichiro, Omata, Masao, and Kato, Naoya

Published
2021
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16. Serum anti-DIDO1, anti-CPSF2, and anti-FOXJ2 antibodies as predictive risk markers for acute ischemic stroke

Author

Hiwasa, Takaki, Wang, Hao, Goto, Ken-ichiro, Mine, Seiichiro, Machida, Toshio, Kobayashi, Eiichi, Yoshida, Yoichi, Adachi, Akihiko, Matsutani, Tomoo, Sata, Mizuki, Yamagishi, Kazumasa, Iso, Hiroyasu, Sawada, Norie, Tsugane, Shoichiro, Kunimatsu, Mitoshi, Kamitsukasa, Ikuo, Mori, Masahiro, Sugimoto, Kazuo, Uzawa, Akiyuki, Muto, Mayumi, Kuwabara, Satoshi, Kobayashi, Yoshio, Ohno, Mikiko, Nishi, Eiichiro, Hattori, Akiko, Yamamoto, Masashi, Maezawa, Yoshiro, Kobayashi, Kazuki, Ishibashi, Ryoichi, Takemoto, Minoru, Yokote, Koutaro, Takizawa, Hirotaka, Kishimoto, Takashi, Matsushita, Kazuyuki, Kobayashi, Sohei, Nomura, Fumio, Arasawa, Takahiro, Kagaya, Akiko, Maruyama, Tetsuro, Matsubara, Hisahiro, Tomiita, Minako, Hamanaka, Shinsaku, Imai, Yushi, Nakagawa, Tomoo, Kato, Naoya, Terada, Jiro, Matsumura, Takuma, Katsumata, Yusuke, Naito, Akira, Tanabe, Nobuhiro, Sakao, Seiichiro, Tatsumi, Koichiro, Ito, Masaaki, Shiratori, Fumiaki, Sumazaki, Makoto, Yajima, Satoshi, Shimada, Hideaki, Shirouzu, Mikako, Yokoyama, Shigeyuki, Kudo, Takashi, Doi, Hirofumi, Iwase, Katsuro, Ashino, Hiromi, Li, Shu-Yang, Kubota, Masaaki, Tomiyoshi, Go, Shinmen, Natsuko, Nakamura, Rika, Kuroda, Hideyuki, and Iwadate, Yasuo

Published
2021
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17. Serum anti-AP3D1 antibodies are risk factors for acute ischemic stroke related with atherosclerosis

Author

Li, Shu-Yang, Yoshida, Yoichi, Kobayashi, Eiichi, Kubota, Masaaki, Matsutani, Tomoo, Mine, Seiichiro, Machida, Toshio, Maezawa, Yoshiro, Takemoto, Minoru, Yokote, Koutaro, Kobayashi, Yoshio, Takizawa, Hirotaka, Sata, Mizuki, Yamagishi, Kazumasa, Iso, Hiroyasu, Sawada, Norie, Tsugane, Shoichiro, Kobayashi, Sohei, Matsushita, Kazuyuki, Nomura, Fumio, Matsubara, Hisahiro, Sumazaki, Makoto, Ito, Masaaki, Yajima, Satoshi, Shimada, Hideaki, Iwase, Katsuro, Ashino, Hiromi, Wang, Hao, Goto, Kenichiro, Tomiyoshi, Go, Shinmen, Natsuko, Nakamura, Rika, Kuroda, Hideyuki, Iwadate, Yasuo, and Hiwasa, Takaki

Published
2021
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26. The Link of mRNA and rRNA Transcription by PUF60/FIR through TFIIH/P62 as a Novel Therapeutic Target for Cancer.

Author

Kitamura, Kouichi, Hoshino, Tyuji, Okabe, Atsushi, Fukuyo, Masaki, Rahmutulla, Bahityar, Tanaka, Nobuko, Kobayashi, Sohei, Tanaka, Tomoaki, Shida, Takashi, Ueda, Mashiro, Minamoto, Toshinari, Matsubara, Hisahiro, Kaneda, Atsushi, Ishii, Hideshi, and Matsushita, Kazuyuki

Subjects
RIBOSOMAL RNA, ISOTHERMAL titration calorimetry, RNA polymerases, X-ray crystallography, PROTEIN-protein interactions
Abstract

The interaction between mRNA and ribosomal RNA (rRNA) transcription in cancer remains unclear. RNAP I and II possess a common N-terminal tail (NTT), RNA polymerase subunit RPB6, which interacts with P62 of transcription factor (TF) IIH, and is a common target for the link between mRNA and rRNA transcription. The mRNAs and rRNAs affected by FUBP1-interacting repressor (FIR) were assessed via RNA sequencing and qRT-PCR analysis. An FIR, a c-myc transcriptional repressor, and its splicing form FIRΔexon2 were examined to interact with P62. Protein interaction was investigated via isothermal titration calorimetry measurements. FIR was found to contain a highly conserved region homologous to RPB6 that interacts with P62. FIRΔexon2 competed with FIR for P62 binding and coactivated transcription of mRNAs and rRNAs. Low-molecular-weight chemical compounds that bind to FIR and FIRΔexon2 were screened for cancer treatment. A low-molecular-weight chemical, BK697, which interacts with FIRΔexon2, inhibited tumor cell growth with rRNA suppression. In this study, a novel coactivation pathway for cancer-related mRNA and rRNA transcription through TFIIH/P62 by FIRΔexon2 was proposed. Direct evidence in X-ray crystallography is required in further studies to show the conformational difference between FIR and FIRΔexon2 that affects the P62–RBP6 interaction. [ABSTRACT FROM AUTHOR]

Published
2023
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29. Carcinogenic potential in regenerated mucosa after endoscopic resection of esophageal squamous cell carcinoma.

Author

Akizue, Naoki, Okimoto, Kenichiro, Hirotsu, Yosuke, Amemiya, Kenji, Kaneko, Tatsuya, Ohta, Yuki, Taida, Takashi, Saito, Keiko, Matsumura, Tomoaki, Nishimura, Motoi, Matsushita, Kazuyuki, Mochizuki, Hitoshi, Chiba, Tetsuhiro, Arai, Makoto, Kato, Jun, Omata, Masao, and Kato, Naoya

Subjects
SQUAMOUS cell carcinoma, ENDOSCOPIC surgery, MUCOUS membranes, ESOPHAGEAL cancer, GENETIC variation, GENETIC mutation
Abstract

Background and Aim: Little is known about genetic mutations in the regenerated mucosa (RM) after endoscopic resection (ER) of esophageal carcinoma. Thus, this study investigates the status of genetic variation in RM after ER of esophageal squamous cell carcinoma (ESCC). Methods: The study cohort included 19 patients with ESCC. We used an esophageal carcinoma panel to identify target sequences for squamous cell carcinoma (SCC), background mucosa (BM), and RM after ER of ESCC. We used OncoKB to check whether each mutation was a putative driver. Results: We identified 77 mutations of 32 genes in SCC, 133 mutations of 34 genes in BM, and 100 mutations of 29 genes in RM. Putative driver mutations were identified in 20 mutations in 14 cases in SCC, 16 mutations in 10 cases in BM, and 7 mutations in 11 cases in RM. The rate of putative driver mutations to total mutations was significantly lower in RM (26% in SCC vs 12% in BM vs 7% in RM, P = 0.009). Additionally, the rate of cases with TP53 putative driver mutations was significantly lower in RM (63% in SCC vs 37% in BM vs 16% in RM, P = 0.011). The percentage of putative driver mutations and the percentage of cases with a putative driver of TP53 were significantly lower in RM. Conclusion: Esophageal RM after ER of ESCC could have a lower risk of carcinogenesis. [ABSTRACT FROM AUTHOR]

Published
2023
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33. Validity of pathological diagnosis for early colorectal cancer in genetic background.

Author

Okimoto, Kenichiro, Hirotsu, Yosuke, Arai, Makoto, Amemiya, Kenji, Akizue, Naoki, Ohta, Yuki, Taida, Takashi, Saito, Keiko, Ohyama, Hiroshi, Matsumura, Tomoaki, Nishimura, Motoi, Matsushita, Kazuyuki, Matsusaka, Keisuke, Oyama, Toshio, Mochizuki, Hitoshi, Chiba, Tetsuhiro, Kato, Jun, Ikeda, Jun‐ichiro, Yokosuka, Osamu, and Kato, Naoya

Subjects
COLORECTAL cancer, EARLY diagnosis, GENETIC profile, WNT genes, WNT signal transduction, DNA mismatch repair
Abstract

Background: This study aimed to investigate the validity of pathological diagnosis of early CRC (E‐CRC) from the genetic background by comparing data of E‐CRC to colorectal adenoma (CRA) and The Cancer Genome Atlas (TCGA) on advanced CRC (AD‐CRC). Methods: TCGA data on AD‐CRC were studied in silico, whereas by next‐generation sequencer, DNA target sequences were performed for endoscopically obtained CRA and E‐CRC samples. Immunohistochemical staining of mismatch repair genes and methylation of MLH1 was also performed. The presence of oncogenic mutation according to OncoKB for the genes of the Wnt, MAPK, and cell‐cycle–signaling pathways was compared among CRA, E‐CRC, and AD‐CRC. Results: The study included 22 CRA and 30 E‐CRC lesions from the Chiba University Hospital and 212 AD‐CRC lesions from TCGA data. Regarding the number of lesions with driver mutations in the Wnt and cell‐cycle–signaling pathways, E‐CRC was comparable to AD‐CRC, but was significantly greater than CRA. CRA had significantly more lesions with a driver mutation for the Wnt signaling pathway only, versus E‐CRC. Conclusions: In conclusion, the definition of E‐CRC according to the Japanese criteria had a different genetic profile from CRA and was more similar to AD‐CRC. Based on the main pathway, it seemed reasonable to classify E‐CRC as adenocarcinoma. The pathological diagnosis of E‐CRC according to Japanese definition seemed to be valid from a genetic point of view. [ABSTRACT FROM AUTHOR]

Published
2023
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36. NY-ESO-1 autoantibody as a tumor-specific biomarker for esophageal cancer: screening in 1969 patients with various cancers

Author

Oshima, Yoko, Shimada, Hideaki, Yajima, Satoshi, Nanami, Tatsuki, Matsushita, Kazuyuki, Nomura, Fumio, Kainuma, Osamu, Takiguchi, Nobuhiro, Soda, Hiroaki, Ueda, Takeshi, Iizasa, Toshihiko, Yamamoto, Naoto, Yamamoto, Hiroshi, Nagata, Matsuo, Yokoi, Sana, Tagawa, Masatoshi, Ohtsuka, Seiko, Kuwajima, Akiko, Murakami, Akihiro, and Kaneko, Hironori

Published
2016
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46. RG64--high count rate low noise multichannel ASIC with energy window selection and continuous readout mode

Author

Szczygiel, Robert, Grybos, Pawel, Maj, Piotr, Tsukiyama, Akira, Matsushita, Kazuyuki, and Taguchi, Takeyoshi

Subjects
Application-specific integrated circuits -- Design and construction, Custom integrated circuits -- Design and construction, Radiography -- Methods, Silicon diodes -- Usage, Application-specific integrated circuit, Custom IC, Business, Electronics, Electronics and electrical industries
Abstract

We report on the performance of a low noise and high count rate readout ASIC with binary architecture and energy window selection for X-ray imaging applications using semiconductor detectors. The ASIC called RG64 is designed in 0.35 [micro]m CMOS process and its total area is 3900 x 5000 [micro][m.sup.2]. The core of RG64 consists of 64 readout channels. Each channel is built of a charge sensitive amplifier with a second order shaper of peaking time 75 ns, two independent discriminators with an 8-bit offset correction circuit and two independent 20-bit counters with RAM memory buffers. The ENC of the circuit reaches the value of about 126 el. rms with 1 pF input load and 5 mW power consumption per single channel. The mean gain in the multichannel ASIC is about 50 [micro]V/el., with the dispersion from channel to channel of 0.9% (on one sigma level). The deviation of the effective threshold voltage spread for given energy can be reduced to less than 7 el. rms (calculated to the charge sensitive amplifier input). High count rate measurements have been performed up to 2 Mcps of average rate of input pulses, both for AC and DC coupled silicon strip detectors with X-ray photons of energy 8.04 keV. The RG64 can operate both in the continuous readout mode and in the readout mode separate from exposure. Index Terms--Low-noise electronics, mixed signal circuits.

Published
2009

47. Multiple cancer type classification by small RNA expression profiles with plasma samples from multiple facilities.

Author

Suzuki, Kuno, Igata, Hideyoshi, Abe, Motoki, Yamamoto, Yusuke, Iwanaga, Terunao, Kanzaki, Hiroaki, Kato, Naoya, Tanaka, Nobuko, Kawasaki, Kenji, Matsushita, Kazuyuki, Samashima, Ryu, Tsukino, Keiji, Yokomizo, Akira, Miyashita, Yosuke, Sumiyoshi, Issei, Takahashi, Kazuhisa, Serizawa, Nobuko, Tomishima, Ko, Nagahara, Akihito, and Ishizuka, Yumiko

Abstract

Liquid biopsy is expected to be a promising cancer screening method because of its low invasiveness and the possibility of detecting multiple types in a single test. In the last decade, many studies on cancer detection using small RNAs in blood have been reported. To put small RNA tests into practical use as a multiple cancer type screening test, it is necessary to develop a method that can be applied to multiple facilities. We collected samples of eight cancer types and healthy controls from 20 facilities to evaluate the performance of cancer type classification. A total of 2,475 cancer samples and 496 healthy control samples were collected using a standardized protocol. After obtaining a small RNA expression profile, we constructed a classification model and evaluated its performance. First, we investigated the classification performance using samples from five single facilities. Each model showed areas under the receiver curve (AUC) ranging from 0.67 to 0.89. Second, we performed principal component analysis (PCA) to examine the characteristics of the facilities. The degree of hemolysis and the data acquisition period affected the expression profiles. Finally, we constructed the classification model by reducing the influence of these factors, and its performance had an AUC of 0.76. The results reveal that small RNA can be used for the classification of cancer types in samples from a single facility. However, interfacility biases will affect the classification of samples from multiple facilities. These findings will provide important insights to improve the performance of multiple cancer type classifications using small RNA expression profiles acquired from multiple facilities. [ABSTRACT FROM AUTHOR]

Published
2022
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