88 results on '"Mitsuru Miyachi"'
Search Results
2. Reduced B7-H3 expression by PAX3-FOXO1 knockdown inhibits cellular motility and promotes myogenic differentiation in alveolar rhabdomyosarcoma
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Takuyo Kanayama, Mitsuru Miyachi, Yohei Sugimoto, Shigeki Yagyu, Ken Kikuchi, Kunihiko Tsuchiya, Tomoko Iehara, and Hajime Hosoi
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Medicine ,Science - Abstract
Abstract B7-H3 (also known as CD276) is associated with aggressive characteristics in various cancers. Meanwhile, in alveolar rhabdomyosarcoma (ARMS), PAX3-FOXO1 fusion protein is associated with increased aggressiveness and poor prognosis. In the present study, we explored the relationship between PAX3-FOXO1 and B7-H3 and the biological roles of B7-H3 in ARMS. Quantitative real time PCR and flow cytometry revealed that PAX3-FOXO1 knockdown downregulated B7-H3 expression in all the selected cell lines (Rh-30, Rh-41, and Rh-28), suggesting that PAX3-FOXO1 positively regulates B7-H3 expression. Gene expression analysis revealed that various genes and pathways involved in chemotaxis, INF-γ production, and myogenic differentiation were commonly affected by the knockdown of PAX3-FOXO1 and B7-H3. Wound healing and transwell migration assays revealed that both PAX3-FOXO1 and B7-H3 were associated with cell migration. Furthermore, knockdown of PAX3-FOXO1 or B7-H3 induced myogenin expression in all cell lines, although myosin heavy chain induction varied depending on the cellular context. Our results indicate that PAX3-FOXO1 regulates B7-H3 expression and that PAX3-FOXO1 and B7-H3 are commonly associated with multiple pathways related to an aggressive phenotype in ARMS, such as cell migration and myogenic differentiation block.
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- 2021
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3. Oncogenic role of HMGA2 in fusion-negative rhabdomyosarcoma cells
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Kazutaka Ouchi, Mitsuru Miyachi, Shigeki Yagyu, Ken Kikuchi, Yasumichi Kuwahara, Kunihiko Tsuchiya, Tomoko Iehara, and Hajime Hosoi
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HMGA2 ,Fusion-negative rhabdomyosarcoma ,Netropsin ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Background Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. There are two subtypes, fusion gene-positive RMS (FP-RMS) and fusion gene-negative RMS (FN-RMS), depending on the presence of a fusion gene, either PAX3-FOXO1 or PAX7-FOXO1. These fusion genes are thought to be oncogenic drivers of FP-RMS. By contrast, the underlying mechanism of FN-RMS has not been thoroughly investigated. It has recently been shown that HMGA2 is specifically positive in pathological tissue from FN-RMS, but the role of HMGA2 in FN-RMS remains to be clarified. Methods In this study, we used FN-RMS cell lines to investigate the function of HMGA2. Gene expression, cell growth, cell cycle, myogenic differentiation, tumor formation in vivo, and cell viability under drug treatment were assessed. Results We found that HMGA2 was highly expressed in FN-RMS cells compared with FP-RMS cells and that knockdown of HMGA2 in FN-RMS cells inhibited cell growth and induced G1 phase accumulation in the cell cycle and myogenic differentiation. Additionally, we showed using both gain-of-function and loss-of-function assays that HMGA2 was required for tumor formation in vivo. Consistent with these findings, the HMGA2 inhibitor netropsin inhibited the cell growth of FN-RMS. Conclusions Our results suggest that HMGA2 has important role in the oncogenicity of FP-RMS and may be a potential therapeutic target in patients with FN-RMS.
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- 2020
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4. The possible effects of the Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 on the practice of fertility preservation in female cancer patients in Japan
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Chisato Kunitomi, Miyuki Harada, Yuko Sanada, Akari Kusamoto, Yasushi Takai, Tatsuro Furui, Yuko Kitagawa, Mitsutoshi Yamada, Chie Watanabe, Koichiro Tsugawa, Hiroyuki Nishiyama, Hajime Hosoi, Mitsuru Miyachi, Kazuhiko Sugiyama, Yoshinobu Maeda, Akira Kawai, Toshio Hamatani, Keishi Fujio, Nao Suzuki, and Yutaka Osuga
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assisted reproductive technology ,breast cancer ,childhood, adolescent, and young adult (CAYA) ,fertility preservation ,oncofertility ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 ,Reproduction ,QH471-489 - Abstract
Abstract Purpose In 2017, the first guidelines for fertility preservation in cancer patients were published in Japan. However, the impact of the guidelines remains unknown. Therefore, the authors conducted a nationwide survey on cryopreservation procedures in the period from shortly before to after publication of the guidelines (2016–2019) and compared the results with our previous survey (2011–2015). The authors also surveyed reproductive specialists’ awareness of the guidelines and implementation problems. Methods The authors sent a questionnaire to 618 assisted reproductive technology facilities certified by the Japanese Society of Obstetrics and Gynecology. Results The authors received responses from 395 institutions (63.8%). Among them, 144 institutions conducted cryopreservation for cancer patients (vs. 126 in 2011–2015) and performed 2537 embryo or oocyte and 178 ovarian tissue cryopreservation procedures (vs. 1085 and 122, respectively). Compared with the previous period, indications were more varied and protocols for controlled ovarian stimulation were more standardized. Reproductive specialists’ interest in oncofertility was high, but many reported three main difficulties: selecting a treatment method, storing samples in the long term, and securing the necessary human resources. Conclusions The practice of fertility preservation in cancer patients in Japan has been considerably affected by the first Japanese guidelines.
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- 2022
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5. Detection of circulating fungal DNA by polymerase chain reaction in a fatal case of Cunninghamella bertholletiae infection
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Rika Hiramoto, Mitsuru Miyachi, Yoshihiro Nitta, Hideki Yoshida, Yasumichi Kuwahara, Kunihiko Tsuchiya, Tomoko Iehara, Kyoko Yarita, Katsuhiko Kamei, and Hajime Hosoi
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Cunninghamella bertholletiae ,Mucormycosis ,Zygomycosis ,Circulating DNA ,Internal transcribed spacer region ,Infectious and parasitic diseases ,RC109-216 - Abstract
Introduction: Cunninghamella bertholletiae although rarely causing mucormycosis, is responsible for the highest mortality among mucormycetes. The diagnosis of mucormycosis is challenged by the absence of specific biomarkers. Herein, we report a fatal case of C. bertholletiae infection and detection of its DNA in the serum by polymerase chain reaction (PCR). Presentation of case: A 23-year-old male with refractory osteosarcoma was admitted with multiple lung metastases. He was on oral voriconazole prophylaxis after pulmonary aspergillosis. He suffered from fever during temporary neutropenia following chemotherapy and showed several neurological and respiratory symptoms. Despite liposomal-amphotericin B administration, the symptoms rapidly progressed, and he died five days after the onset of neurological symptoms.We retrospectively evaluated the filamentous fungus isolated after his death from gastric juices. Based on the sequence of the internal transcribed spacer (ITS) region we identified the fungal isolate as C. bertholletiae. A 146-bp portion of the D1/D2 region was quantified by quantitative-PCR using DNA extracted from the serum. C. bertholletiae DNA load in the serum was 18.0 copies/μL on the day of onset of neurological symptoms, with the highest (101.0 copies/μL) on the day of his death. Discussion: Detection of circulating DNA of mucormycetes in the blood would greatly enhance the diagnosis of mucormycosis. Rapid diagnosis might alleviate mortality due to mucormycosis. Conclusion: The present case-report suggests that the quantification of C. bertholletiae DNA in the serum could be useful for the diagnosis and evaluation of mucormycosis pathogenesis in patients.
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- 2020
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6. Cytomegalovirus-associated biliary atresia
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Kazuki Kodo, Kenichi Sakamoto, Tomohiko Imai, Takeshi Ota, Mitsuru Miyachi, Jun Mori, Tomohiro Chiyonobu, Tetsuya Imura, and Hajime Hosoi
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Pediatrics ,RJ1-570 ,Surgery ,RD1-811 - Abstract
The pathogenesis of biliary atresia (BA) is propounded to be an immunological process, but the detailed mechanisms remain unclear. In recent studies with abnormal immunological findings, T cells have drawn attention in the mechanism of BA pathogenesis. Furthermore, cytomegalovirus (CMV) infection in BA patients resulted in elevated levels of helper T cells (Th1 and Th17) and reduction of regulatory T cells. Thus, CMV infection is considered as a cause of BA.We present the case of a 3-month-old boy who presented with intracerebral hemorrhage and finally died of liver failure. BA was diagnosed on autopsy and serum CMV-IgM was positive, but CMV antigen in the liver tissue was negative.Because CMV-associated BA has poor prognosis, compared with BA not associated with CMV, accurate classification of the type of BA is essential. Keywords: Biliary atresia, Cytomegalovirus, Cytomegalovirus-associated biliary atresia
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- 2018
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7. Synchronous bilateral lung adenocarcinomas associated with vulvar rhabdomyosarcoma in a 15-year-old girl
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Tatsuo Furuya, Hiroaki Tsunezuka, Satoru Okada, Daishiro Kato, Junichi Shimada, Mitsuru Miyachi, Tomoko Iehara, Hajime Hosoi, and Masayoshi Inoue
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Pediatrics ,RJ1-570 ,Surgery ,RD1-811 - Abstract
Pediatric malignancies are thought to be risk factors of second malignant neoplasms. However, lung cancer associated with rhabdomyosarcoma is extremely rare. When multiple pulmonary lesions are observed in cancer patients, resection is necessary to distinguish them from metastatic lesions. We report an extremely rare case of synchronous bilateral multiple lung cancers showing ground glass nodules (GGNs) associated with rhabdomyosarcoma in a 15-year-old girl with vulvar rhabdomyosarcoma. When we identify GGNs in adolescents with a history of rhabdomyosarcoma, we should consider lung cancer as a differential diagnosis in addition to pulmonary metastasis usually showing solid nodule. In the present case with tiny lesions, surgical resection using lipiodol-marking helped to ensure both an early diagnosis and curative treatment. Keywords: Synchronous bilateral multiple lung cancers, Adolescent, Rhabdomyosarcoma
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- 2018
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8. Successful treatment of a hepatic-hemangioendothelioma infant presenting with hypothyroidism and tetralogy of Fallot
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Akari Takai, Tomoko Iehara, Mitsuru Miyachi, Yoshiki Okumura, Tatsuji Hasegawa, Sachiko Tokuda, Kazuyuki Ikeda, Masaaki Yamagishi, Tatsuro Tajiri, and Hajime Hosoi
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Pediatrics ,RJ1-570 - Published
- 2018
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9. Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors
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Yoichi Naito, Saori Mishima, Kiwamu Akagi, Naomi Hayashi, Akira Hirasawa, Tomoro Hishiki, Ataru Igarashi, Masafumi Ikeda, Shigenori Kadowaki, Hiroaki Kajiyama, Motohiro Kato, Hirotsugu Kenmotsu, Yasuhiro Kodera, Keigo Komine, Takafumi Koyama, Osamu Maeda, Mitsuru Miyachi, Hiroshi Nishihara, Hiroyuki Nishiyama, Shouichi Ohga, Wataru Okamoto, Eiji Oki, Shigeru Ono, Masashi Sanada, Ikuo Sekine, Tadao Takano, Kayoko Tao, Keita Terashima, Katsuya Tsuchihara, Yasushi Yatabe, Takayuki Yoshino, and Eishi Baba
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Oncology ,Surgery ,Hematology ,General Medicine - Abstract
Background Clinical trials have reported the efficacy of tropomyosin receptor kinase (TRK) inhibitors against neurotrophic receptor tyrosine kinase (NTRK) fusion gene-positive advanced solid tumors. The accumulated evidence of tumor-agnostic agent has made since TRK inhibitors were approved and used in clinical practice. Therefore, we have revised the ‘Japan Society of Clinical Oncology (JSCO)/Japanese Society of Medical Oncology (JSMO)-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese Society of Pediatric Hematology/Oncology (JSPHO)’. Methods Clinical questions regarding medical care were formulated for patients with NTRK fusion-positive advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by JSCO, JSMO, and JSPHO voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO, and the public comments among all societies' members was done. Results The current guideline describes 3 clinical questions and 14 recommendations for whom, when, and how NTRK fusion should be tested, and what is recommended for patients with NTRK fusion-positive advanced solid tumors. Conclusion The committee proposed 14 recommendations for performing NTRK testing properly to select patients who are likely to benefit from TRK inhibitors.
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- 2023
10. Investigation of Fertility Preservation Education Videos for Pediatric Patients Based on International and Historical Survey
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Yuriko Iwahata, Seido Takae, Hideyuki Iwahata, Kimikazu Matsumoto, Masahiro Hirayama, Junko Takita, Atsushi Manabe, Yuko Cho, Tomoaki Ikeda, Tadashi Maezawa, Mitsuru Miyachi, Dai Keino, Tomoe Koizumi, Tetsuya Mori, Naoki Shimizu, Teresa K. Woodruff, and Nao Suzuki
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Oncology ,Pediatrics, Perinatology and Child Health - Published
- 2023
11. Japanese Orthopaedic Association (JOA) clinical practice guidelines on the management of soft tissue tumors 2020 - Secondary publication
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Akira Kawai, Nobuhito Araki, Keisuke Ae, Toru Akiyama, Toshifumi Ozaki, Hirotaka Kawano, Toshiyuki Kunisada, Minako Sumi, Shunji Takahashi, Kazuhiro Tanaka, Satoshi Tsukushi, Norifumi Naka, Yoshihiro Nishida, Mitsuru Miyachi, Norio Yamamoto, Akihiko Yoshida, Tsukasa Yonemoto, Masahiro Yoshida, and Shintaro Iwata
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Orthopedics ,Japan ,Humans ,Soft Tissue Neoplasms ,Orthopedics and Sports Medicine ,Surgery ,Prognosis ,Algorithms - Abstract
These clinical practice guidelines are intended to provide recommendations based on the best evidence obtained to date on key issues in clinical practice to improve the prognosis, diagnostic and therapeutic processes for patients with soft tissue tumors.The Guidelines Development Committee and Systematic Review Committee were composed of a multidisciplinary team of specialists who play an important role in soft tissue tumor care. Clinical questions (CQs) were determined by choosing key decision-making points based on Algorithms for the diagnosis and treatment of soft tissue tumors. The guidelines were developed according to the "Medical Information Network Distribution Service (Minds) Handbook for Clinical Practice Guideline Development 2014" and "Minds Manual for Clinical Practice Guideline Development 2017." Recommendation strength was rated on two levels and the strength of evidence was rated on four levels. The recommendations were decided based on agreement by 70% or more voters.Twenty-two CQs were chosen by the Guidelines Development Committee. The Systematic Review Committee reviewed the evidence concerning each CQ, a clinical value judgment was added by experts, and the text of each recommendation was determined.We established 22 CQs and recommendations for key decision-making points in the diagnosis and treatment of soft tissue tumors according to the Minds Clinical Practice Guideline development methods. We hope that these guidelines will assist the decision-making of all medical staff engaged in the treatment and diagnosis of soft tissue tumors, and eventually lead to improved soft tissue tumor care in the country.
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- 2022
12. Supplementary Figure 1. from The Novel Histone Deacetylase Inhibitor, OBP-801, Induces Apoptosis in Rhabdoid Tumors by Releasing the Silencing of NOXA
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Hajime Hosoi, Toshiyuki Sakai, Yasumichi Kuwahara, Kunihiko Tsuchiya, Ken Kikuchi, Shigeki Yagyu, Mitsuru Miyachi, Hideki Yoshida, Kazutaka Ouchi, Chihiro Tomoyasu, Daisuke Kaneda, Tomoko Iehara, Yoshiki Katsumi, and Yohei Sugimoto
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Supplementary Figure 1.
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- 2023
13. Data from The Novel Histone Deacetylase Inhibitor, OBP-801, Induces Apoptosis in Rhabdoid Tumors by Releasing the Silencing of NOXA
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Hajime Hosoi, Toshiyuki Sakai, Yasumichi Kuwahara, Kunihiko Tsuchiya, Ken Kikuchi, Shigeki Yagyu, Mitsuru Miyachi, Hideki Yoshida, Kazutaka Ouchi, Chihiro Tomoyasu, Daisuke Kaneda, Tomoko Iehara, Yoshiki Katsumi, and Yohei Sugimoto
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Rhabdoid tumor is an aggressive, early childhood tumor. Biallelic inactivation of the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1)/integrase interactor 1 (INI1) gene is the only common genetic feature in rhabdoid tumors. Loss of SMARCB1 function results in downregulation of several tumor suppressor genes including p16, p21, and NOXA. The novel histone deacetylase inhibitor, OBP-801, induces p21 and has shown efficacy against various cancers. In our study, OBP-801 strongly inhibited the cell growth of all rhabdoid tumor cell lines in WST-8 assay. However, Western blotting and cell-cycle analysis revealed that OBP-801 did not activate the P21-RB pathway in some cell lines. p21 knockout indicated that p21 did not dominate the OBP-801 antitumor effect in rhabdoid tumor cell lines. We discovered that OBP-801 induced NOXA expression and caspase-dependent apoptosis in rhabdoid tumor cell lines independent of TP53. Chromatin immunoprecipitation assay showed that OBP-801 acetylated histone proteins and recruited RNA polymerase II to the transcription start site (TSS) of the NOXA promotor. Moreover, OBP-801 recruited BRG1 and BAF155, which are members of the SWI/SNF complex, to the TSS of the NOXA promotor. These results suggest that OBP-801 epigenetically releases the silencing of NOXA and induces apoptosis in rhabdoid tumors. OBP-801 strongly inhibited tumor growth in human rhabdoid tumor xenograft mouse models in vivo. Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and cleaved caspase-3 were stained in tumors treated with OBP-801. In conclusion, OBP-801 induces apoptosis in rhabdoid tumor cells by epigenetically releasing the silencing of NOXA, which is a key mediator of rhabdoid tumor apoptosis. The epigenetic approach for NOXA silencing with OBP-801 is promising for rhabdoid tumor treatment.
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- 2023
14. Supplementary Figure 3. from The Novel Histone Deacetylase Inhibitor, OBP-801, Induces Apoptosis in Rhabdoid Tumors by Releasing the Silencing of NOXA
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Hajime Hosoi, Toshiyuki Sakai, Yasumichi Kuwahara, Kunihiko Tsuchiya, Ken Kikuchi, Shigeki Yagyu, Mitsuru Miyachi, Hideki Yoshida, Kazutaka Ouchi, Chihiro Tomoyasu, Daisuke Kaneda, Tomoko Iehara, Yoshiki Katsumi, and Yohei Sugimoto
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Supplementary Figure 3.
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- 2023
15. Supplementary table from The Novel Histone Deacetylase Inhibitor, OBP-801, Induces Apoptosis in Rhabdoid Tumors by Releasing the Silencing of NOXA
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Hajime Hosoi, Toshiyuki Sakai, Yasumichi Kuwahara, Kunihiko Tsuchiya, Ken Kikuchi, Shigeki Yagyu, Mitsuru Miyachi, Hideki Yoshida, Kazutaka Ouchi, Chihiro Tomoyasu, Daisuke Kaneda, Tomoko Iehara, Yoshiki Katsumi, and Yohei Sugimoto
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Supplementary table
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- 2023
16. Supplementary Figure 2. from The Novel Histone Deacetylase Inhibitor, OBP-801, Induces Apoptosis in Rhabdoid Tumors by Releasing the Silencing of NOXA
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Hajime Hosoi, Toshiyuki Sakai, Yasumichi Kuwahara, Kunihiko Tsuchiya, Ken Kikuchi, Shigeki Yagyu, Mitsuru Miyachi, Hideki Yoshida, Kazutaka Ouchi, Chihiro Tomoyasu, Daisuke Kaneda, Tomoko Iehara, Yoshiki Katsumi, and Yohei Sugimoto
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Supplementary Figure 2.
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- 2023
17. Supplementary Data from Restoration of p53 Pathway by Nutlin-3 Induces Cell Cycle Arrest and Apoptosis in Human Rhabdomyosarcoma Cells
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Hajime Hosoi, Tomoko Iehara, Kunihiko Tsuchiya, Ken Kikuchi, Satoko Tsubai-Shimizu, Yoshiki Katsumi, Shigeki Yagyu, Naoki Kakazu, and Mitsuru Miyachi
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Supplementary Data from Restoration of p53 Pathway by Nutlin-3 Induces Cell Cycle Arrest and Apoptosis in Human Rhabdomyosarcoma Cells
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- 2023
18. Data from Restoration of p53 Pathway by Nutlin-3 Induces Cell Cycle Arrest and Apoptosis in Human Rhabdomyosarcoma Cells
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Hajime Hosoi, Tomoko Iehara, Kunihiko Tsuchiya, Ken Kikuchi, Satoko Tsubai-Shimizu, Yoshiki Katsumi, Shigeki Yagyu, Naoki Kakazu, and Mitsuru Miyachi
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Purpose: Seventy to eighty percent of rhabdomyosarcoma (RMS) tumors retain wild-type p53. The tumor suppressor p53 plays a central role in inducing cell cycle arrest or apoptosis in response to various stresses. p53 protein levels are regulated by MDM2 through ubiquitin-dependent degradation. In this study, we evaluated whether nutlin-3, a recently developed small-molecule antagonist of MDM2, has an effect on p53-dependent cell cycle arrest and apoptosis in cultured human RMS cell lines.Experimental Design: Five RMS cell lines with different p53 statuses and MDM2 expression levels were treated with nutlin-3. Gene expression patterns, cell viability, cell cycle, and apoptosis after nutlin-3 treatment, and antitumor activity of combination treatment with vincristine or actinomycin D were assessed.Results: Significant p53 activation was observed in wild-type p53 cell lines after nutlin-3 treatment. p53 activation led to cell cycle arrest in parallel with increased p21 expression. Furthermore, these cell lines underwent p53-dependent apoptosis, concomitant with elevation of proapoptotic genes and activation of caspase-3. The effect of nutlin-3 was almost the same in terms of half maximal inhibitory concentration and apoptosis whether or not MDM2 was overexpressed. Nutlin-3 did not induce either cell cycle arrest or apoptosis in p53 mutant cell lines. A combination of vincristine or actinomycin D with nutlin-3 enhanced the antitumor activity in RMS cell lines with wild-type p53.Conclusions: Nutlin-3 effectively restored p53 function in both normal MDM2 expression and MDM2 overexpression RMS cell lines with wild-type p53. p53 restoration therapy is a potential therapeutic strategy for refractory RMS with wild-type p53.
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- 2023
19. Supplementary Figure S1 from Circulating Methylated-DCR2 Gene in Serum as an Indicator of Prognosis and Therapeutic Efficacy in Patients with MYCN Nonamplified Neuroblastoma
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Hajime Hosoi, Tadashi Sawada, Tohru Sugimoto, Akiko Misawa-Furihata, Toshihiko Imamura, Kunihiko Tsuchiya, Shinichi Tamura, Ken Kikuchi, Satoko Tsubai-Shimizu, Yoshiki Katsumi, Mitsuru Miyachi, Tomoko Iehara, Takahiro Gotoh, and Shigeki Yagyu
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Supplementary figure S1 (Online Only) Real-time PCR amplification plot and dissociation curve of DCR2 methylation analysis. A, DCR2 methylation analysis in KP-N-RTBM1 cell line DNA.
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- 2023
20. Supplementary Table 1 from Circulating Methylated-DCR2 Gene in Serum as an Indicator of Prognosis and Therapeutic Efficacy in Patients with MYCN Nonamplified Neuroblastoma
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Hajime Hosoi, Tadashi Sawada, Tohru Sugimoto, Akiko Misawa-Furihata, Toshihiko Imamura, Kunihiko Tsuchiya, Shinichi Tamura, Ken Kikuchi, Satoko Tsubai-Shimizu, Yoshiki Katsumi, Mitsuru Miyachi, Tomoko Iehara, Takahiro Gotoh, and Shigeki Yagyu
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Supplementary table 1 (Online Only) Primer sets used for DCR2 methylation analysis.
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- 2023
21. Data from Circulating Methylated-DCR2 Gene in Serum as an Indicator of Prognosis and Therapeutic Efficacy in Patients with MYCN Nonamplified Neuroblastoma
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Hajime Hosoi, Tadashi Sawada, Tohru Sugimoto, Akiko Misawa-Furihata, Toshihiko Imamura, Kunihiko Tsuchiya, Shinichi Tamura, Ken Kikuchi, Satoko Tsubai-Shimizu, Yoshiki Katsumi, Mitsuru Miyachi, Tomoko Iehara, Takahiro Gotoh, and Shigeki Yagyu
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Background:MYCN amplification (MNA) in neuroblastoma is a strong indicator of poor prognosis. However, some MYCN nonamplified (non-MNA) cases show poor outcomes, and examining the status of the gene requires an operation, which may have surgical complications. Therefore, a new marker is needed to identify cases of non-MNA neuroblastomas with poor prognoses using less risky procedures. Aberrant hypermethylation of the DCR2 promoter has recently been associated with rapidly progressing neuroblastoma. We aimed to develop a noninvasive DCR2 methylation assay for patients with neuroblastoma using serum DNA, which predominantly originates from tumor-released DNA.Methods: Using DNA-based real-time PCR, we simultaneously quantified a methylated-DCR2 specific sequence (M) and a reference sequence (R) located in the promoter region in serum DNA, and evaluated DCR2 methylation status as M/R ratios in 86 patients with neuroblastoma.Results: Serum DCR2 M/R ratios were strongly correlated with those in the tumor (r = 0.67; P = 0.002). DCR2 methylation was associated with stage both in the whole neuroblastoma group and in the non-MNA group (P < 0.001), and DCR2-methylated patients showed significantly poorer 5-year event-free survival in the whole neuroblastoma group (43% versus 84%; P < 0.001), especially in the non-MNA group (12% versus 96%;P < 0.001). Among five DCR2-methylated patients whose clinical courses were followed, serum M/R ratios were close to 0 in the patients in remission, whereas the ratios increased in patients who relapsed.Conclusions: Detection of methylated-DCR2 in serum DNA has promise as a noninvasive assay for predicting prognosis and therapeutic efficacy in neuroblastoma, especially in non-MNA cases. Furthermore, it might be a sensitive marker of tumor recurrence in DCR2-methylated cases.
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- 2023
22. In ovo chorioallantoic membrane assay as a xenograft model for pediatric rhabdomyosarcoma
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Chika Shoji, Ken Kikuchi, Hideki Yoshida, Mitsuru Miyachi, Shigeki Yagyu, Kunihiko Tsuchiya, Takaaki Nakaya, Hajime Hosoi, and Tomoko Iehara
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Cancer Research ,Oncology ,General Medicine - Published
- 2023
23. Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 for fertility preservation in childhood, adolescent, and young adult cancer patients: part 2
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Akiko Tozawa, Fuminori Kimura, Yasushi Takai, Takeshi Nakajima, Kimio Ushijima, Hiroaki Kobayashi, Toyomi Satoh, Miyuki Harada, Kohei Sugimoto, Shigehira Saji, Chikako Shimizu, Kyoko Akiyama, Hiroko Bando, Akira Kuwahara, Tatsuro Furui, Hiroshi Okada, Koji Kawai, Nobuo Shinohara, Koichi Nagao, Michio Kitajima, Souichi Suenobu, Toshinori Soejima, Mitsuru Miyachi, Yoko Miyoshi, Akihiro Yoneda, Akihito Horie, Yasushi Ishida, Noriko Usui, Yoshinobu Kanda, Nobuharu Fujii, Makoto Endo, Robert Nakayama, Manabu Hoshi, Tsukasa Yonemoto, Chikako Kiyotani, Natsuko Okita, Eishi Baba, Manabu Muto, Iwaho Kikuchi, Ken-ichirou Morishige, Koichiro Tsugawa, Hiroyuki Nishiyama, Hajime Hosoi, Mitsune Tanimoto, Akira Kawai, Kazuhiko Sugiyama, Narikazu Boku, Masato Yonemura, Naoko Hayashi, Daisuke Aoki, Nao Suzuki, and Yutaka Osuga
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Oncologists ,Young Adult ,Adolescent ,Japan ,Oncology ,Neoplasms ,Fertility Preservation ,Humans ,Surgery ,Hematology ,General Medicine ,Child ,Medical Oncology - Abstract
The Japan Society of Clinical Oncology (JSCO) published the “JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients” in 2017. This was the first guideline in cancer reproductive medicine in Japan. In the field of cancer reproductive medicine, close cooperation between an oncologist and a physician for reproductive medicine is important from before treatment initiation until long after treatment. The guideline takes into consideration disease specificity and provides opinions from the perspective of oncologists and specialists in reproductive medicine that are in line with the current state of the Japanese medical system. It is intended to serve as a reference for medical staff in both fields regarding the availability of fertility preservation therapy before the start of cancer treatment. Appropriate use of this guideline makes it easier to determine whether fertility preservation therapy is feasible and, ultimately, to improve survivorship in childhood, adolescent, and young adult cancer patients. In this article (Part 2), we describe details by organ/system and also for pediatric cancer.
- Published
- 2022
24. Reduced B7-H3 expression by PAX3-FOXO1 knockdown inhibits cellular motility and promotes myogenic differentiation in alveolar rhabdomyosarcoma
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Hajime Hosoi, Mitsuru Miyachi, Takuyo Kanayama, Kunihiko Tsuchiya, Yohei Sugimoto, Shigeki Yagyu, Ken Kikuchi, and Tomoko Iehara
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endocrine system ,B7 Antigens ,Science ,Blotting, Western ,Down-Regulation ,Biology ,Muscle Development ,Real-Time Polymerase Chain Reaction ,Flow cytometry ,Cell Movement ,Cell Line, Tumor ,Gene expression ,Myosin ,medicine ,Humans ,PAX3 Transcription Factor ,Rhabdomyosarcoma, Alveolar ,Myogenin ,Gene knockdown ,Multidisciplinary ,medicine.diagnostic_test ,Forkhead Box Protein O1 ,Cell Differentiation ,Cell migration ,Flow Cytometry ,medicine.disease ,musculoskeletal system ,Cell biology ,Cell culture ,Gene Knockdown Techniques ,embryonic structures ,Alveolar rhabdomyosarcoma ,Medicine ,Transcriptome ,hormones, hormone substitutes, and hormone antagonists - Abstract
B7-H3 (also known as CD276) is associated with aggressive characteristics in various cancers. Meanwhile, in alveolar rhabdomyosarcoma (ARMS), PAX3-FOXO1 fusion protein is associated with increased aggressiveness and poor prognosis. In the present study, we explored the relationship between PAX3-FOXO1 and B7-H3 and the biological roles of B7-H3 in ARMS. Quantitative real time PCR and flow cytometry revealed that PAX3-FOXO1 knockdown downregulated B7-H3 expression in all the selected cell lines (Rh-30, Rh-41, and Rh-28), suggesting that PAX3-FOXO1 positively regulates B7-H3 expression. Gene expression analysis revealed that various genes and pathways involved in chemotaxis, INF-γ production, and myogenic differentiation were commonly affected by the knockdown of PAX3-FOXO1 and B7-H3. Wound healing and transwell migration assays revealed that both PAX3-FOXO1 and B7-H3 were associated with cell migration. Furthermore, knockdown of PAX3-FOXO1 or B7-H3 induced myogenin expression in all cell lines, although myosin heavy chain induction varied depending on the cellular context. Our results indicate that PAX3-FOXO1 regulates B7-H3 expression and that PAX3-FOXO1 and B7-H3 are commonly associated with multiple pathways related to an aggressive phenotype in ARMS, such as cell migration and myogenic differentiation block.
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- 2021
25. Correction to: Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 for fertility preservation in childhood, adolescent, and young adult cancer patients: part 2
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Akiko Tozawa, Fuminori Kimura, Yasushi Takai, Takeshi Nakajima, Kimio Ushijima, Hiroaki Kobayashi, Toyomi Satoh, Miyuki Harada, Kohei Sugimoto, Shigehira Saji, Chikako Shimizu, Kyoko Akiyama, Hiroko Bando, Akira Kuwahara, Tatsuro Furui, Hiroshi Okada, Koji Kawai, Nobuo Shinohara, Koichi Nagao, Michio Kitajima, Souichi Suenobu, Toshinori Soejima, Mitsuru Miyachi, Yoko Miyoshi, Akihiro Yoneda, Akihito Horie, Yasushi Ishida, Noriko Usui, Yoshinobu Kanda, Nobuharu Fujii, Makoto Endo, Robert Nakayama, Manabu Hoshi, Tsukasa Yonemoto, Chikako Kiyotani, Natsuko Okita, Eishi Baba, Manabu Muto, Iwaho Kikuchi, Ken-ichirou Morishige, Koichiro Tsugawa, Hiroyuki Nishiyama, Hajime Hosoi, Mitsune Tanimoto, Akira Kawai, Kazuhiko Sugiyama, Narikazu Boku, Masato Yonemura, Naoko Hayashi, Daisuke Aoki, Nao Suzuki, and Yutaka Osuga
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Oncology ,Surgery ,Hematology ,General Medicine - Published
- 2022
26. Identification of RCC1-LCK as a novel fusion gene in pediatric erythroid sarcoma
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Satoru Oya, Shinya Osone, Masanori Yoshida, Sota Nishimoto, Yoshihiro Taura, Hideki Yoshida, Mitsuru Miyachi, Tohru Inaba, Eiichi Konishi, Motohiro Kato, Toshihiko Imamura, and Tomoko Iehara
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Male ,Infant ,Nuclear Proteins ,hemic and immune systems ,Cell Cycle Proteins ,Sarcoma ,Hematology ,Leukemia, Myeloid, Acute ,Oncology ,Lymphocyte Specific Protein Tyrosine Kinase p56(lck) ,hemic and lymphatic diseases ,Pediatrics, Perinatology and Child Health ,Guanine Nucleotide Exchange Factors ,Humans ,Sarcoma, Myeloid - Abstract
Erythroid sarcoma is very rare form of pure erythroid leukemia with undetermined biological features. Here, we present an infant with a multifocal erythroid sarcoma, diagnosed because the tumor cells were positive for glycophorin A. After acute myeloid leukemia-oriented chemotherapy and surgical resection followed by cord blood transplantation, he has successfully maintained complete remission without any late effects. Total transcriptome analysis of the tumor identified a novel fusion gene, RCC1-LCK, and high LCK expression levels, suggesting that LCK overexpression was involved in leukemogenesis in this case.
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- 2022
27. Is perioperative chemotherapy recommended in childhood and adolescent patients with synovial sarcoma? A systematic review
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Akira Kawai, Yuya Saito, Kunihiko Tsuchiya, Tomoki Nakamura, Mitsuru Miyachi, Shintaro Iwata, and Akihiro Sudo
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Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,MEDLINE ,Soft Tissue Neoplasms ,Sarcoma, Synovial ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Child ,Prospective cohort study ,Retrospective Studies ,Chemotherapy ,business.industry ,Soft tissue sarcoma ,Soft tissue ,Sarcoma ,Retrospective cohort study ,General Medicine ,medicine.disease ,Chemotherapy regimen ,Synovial sarcoma ,Surgery ,030104 developmental biology ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Female ,business - Abstract
Objective Synovial sarcoma is the most common soft tissue sarcomas among childhood and adolescents, accounting for 8–10% of all soft tissue sarcoma. Synovial sarcoma is considered a relatively chemosensitive tumor compared with other soft tissue sarcomas. However, the role of perioperative chemotherapy in synovial sarcoma remains controversial. The purpose of this systematic review is to evaluate the role of perioperative chemotherapy in childhood and adolescent patients with synovial sarcoma. Methods We evaluated studies published between 1 January 1990 and 31 December 2017. The following databases were searched: MEDLINE, Cochrane database (via PubMed) and Ichushi (in Japanese). Results The search yielded 216 articles in English and Japanese. After the initial screening, based on the title and abstract, 160 articles were excluded. As a second screening, we then assessed the full text of the remaining 56 articles for eligibility. Finally, 10 articles were included in the systematic review. Surgical resection with R0 margin alone was recommended because of the excellent results of two prospective studies. Meta-analysis was performed using data from two retrospective studies of 261 patients. Perioperative chemotherapy did not have a significant effect on survival and event-free survival. Conclusions We weakly do not recommend perioperative chemotherapy in patients with non-metastatic synovial sarcoma ≤ 5 cm when R0 resection is acquired. There was no consensus concerning the role of perioperative chemotherapy in patients with synovial sarcoma > 5 cm or those with ≤5 cm who undergo R1 or R2 resection.
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- 2021
28. Novel Two MRT Cell Lines Established from Multiple Sites of a Synchronous MRT Patient
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Michael C. Frühwald, Satoaki Nakamura, Tsukasa Okuda, Kazutaka Ouchi, Tatsushi Yoshida, Pascal Johann, Hajime Hosoi, Shigehisa Fumino, Tomoko Iehara, Yasumichi Kuwahara, Eiichi Konishi, Kunihiko Tsuchiya, Tatsuro Tajiri, Hiroyasu Sasajima, Yoshiki Katsumi, Eisuke Ichise, and Mitsuru Miyachi
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Cancer Research ,Carcinogenesis ,Biology ,medicine.disease_cause ,Germline ,Neoplasms, Multiple Primary ,Exon ,Germline mutation ,Cell Line, Tumor ,medicine ,Cluster Analysis ,Humans ,Neoplasm ,SMARCB1 ,Rhabdoid Tumor ,Cell Proliferation ,Mutation ,Base Sequence ,Infant ,SMARCB1 Protein ,General Medicine ,DNA Methylation ,medicine.disease ,Xenograft Model Antitumor Assays ,Gene Expression Regulation, Neoplastic ,Oncology ,Cell culture ,Molecular mechanism ,Cancer research ,Female - Abstract
Background/aim Malignant rhabdoid tumor (MRT) is a rare, aggressive neoplasm found in young children, caused by inactivation of a single gene, SNF5 (INI1, SMARCB1). MRT cases with multifocal tumors at diagnosis are categorized as synchronous MRT, often with a germline mutation of SNF5. The aim of this study was to establish new models useful in clarifying the biological basis of synchronous MRT. Materials and methods We established two novel MRT cell lines, designated as KP-MRT-KS and KP-MRT-KSa, derived from different lesions and at a different time from a synchronous multifocal 7-month-old female MRT patient. Results Both cells showed typical morphology of MRT, with a compound genomic mutation in exons 2 and 5 of the SNF5 gene. The exon 2 mutation was found in the germline. Conclusion These cell lines could serve as powerful tools for unveiling the molecular mechanism of refractory synchronous MRT.
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- 2020
29. Oncogenic role of HMGA2 in fusion-negative rhabdomyosarcoma cells
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Tomoko Iehara, Hajime Hosoi, Yasumichi Kuwahara, Mitsuru Miyachi, Kazutaka Ouchi, Ken Kikuchi, Kunihiko Tsuchiya, and Shigeki Yagyu
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musculoskeletal diseases ,Cancer Research ,HMGA2 ,genetic structures ,lcsh:RC254-282 ,Fusion gene ,03 medical and health sciences ,Fusion-Negative Rhabdomyosarcoma ,0302 clinical medicine ,Genetics ,medicine ,Viability assay ,lcsh:QH573-671 ,Rhabdomyosarcoma ,Fusion-negative rhabdomyosarcoma ,030304 developmental biology ,0303 health sciences ,Gene knockdown ,Chemistry ,Cell growth ,lcsh:Cytology ,Netropsin ,Cell cycle ,medicine.disease ,musculoskeletal system ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,eye diseases ,Oncology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Primary Research ,human activities - Abstract
Background Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. There are two subtypes, fusion gene-positive RMS (FP-RMS) and fusion gene-negative RMS (FN-RMS), depending on the presence of a fusion gene, either PAX3-FOXO1 or PAX7-FOXO1. These fusion genes are thought to be oncogenic drivers of FP-RMS. By contrast, the underlying mechanism of FN-RMS has not been thoroughly investigated. It has recently been shown that HMGA2 is specifically positive in pathological tissue from FN-RMS, but the role of HMGA2 in FN-RMS remains to be clarified. Methods In this study, we used FN-RMS cell lines to investigate the function of HMGA2. Gene expression, cell growth, cell cycle, myogenic differentiation, tumor formation in vivo, and cell viability under drug treatment were assessed. Results We found that HMGA2 was highly expressed in FN-RMS cells compared with FP-RMS cells and that knockdown of HMGA2 in FN-RMS cells inhibited cell growth and induced G1 phase accumulation in the cell cycle and myogenic differentiation. Additionally, we showed using both gain-of-function and loss-of-function assays that HMGA2 was required for tumor formation in vivo. Consistent with these findings, the HMGA2 inhibitor netropsin inhibited the cell growth of FN-RMS. Conclusions Our results suggest that HMGA2 has important role in the oncogenicity of FP-RMS and may be a potential therapeutic target in patients with FN-RMS.
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- 2020
30. Japan society of clinical oncology/Japanese society of medical oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese society of pediatric hematology/oncology
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Shunsuke Kato, Yasuhiro Kodera, Yoichi Naito, Osamu Maeda, Shigeru Ono, Kiwamu Akagi, Keita Terashima, Fumio Nagashima, Katsuya Tsuchihara, Saori Mishima, Masafumi Ikeda, Wataru Okamoto, Yutaka Hatanaka, Hiroaki Kajiyama, Hajime Hosoi, Akira Hirasawa, Hiroyki Nishiyama, Yasushi Yatabe, Susumu Okano, Mitsuru Miyachi, Tadao Takano, Takayuki Yoshino, Hiroya Taniguchi, Hiroshi Nishihara, Ataru Igarashi, and Eiso Hiyama
- Subjects
0301 basic medicine ,Oncology ,Adult ,medicine.medical_specialty ,Pediatric Hematology/Oncology ,Antineoplastic Agents ,Medical Oncology ,Receptor tyrosine kinase ,Tropomyosin receptor kinase (TRK) inhibitor ,03 medical and health sciences ,Special Article ,0302 clinical medicine ,Japan ,Surgical oncology ,Internal medicine ,Neoplasms ,medicine ,Humans ,Receptor, trkA ,Child ,Protein Kinase Inhibitors ,Tumor-agnostic treatment ,Societies, Medical ,Advanced solid tumor ,Clinical Oncology ,Related factors ,Clinical practice guideline ,biology ,Kinase ,business.industry ,Neurotrophic receptor tyrosine kinase (NTRK) fusion ,Receptor Protein-Tyrosine Kinases ,General Medicine ,Guideline ,Hematology ,030104 developmental biology ,Systematic review ,030220 oncology & carcinogenesis ,biology.protein ,Surgery ,Gene Fusion ,business - Abstract
Background The development of novel antitumor agents and accompanying biomarkers has improved survival across several tumor types. Previously, we published provisional clinical opinion for the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair tumors. Recently, efficacy of tropomyosin receptor kinase inhibitors against neurotrophic receptor tyrosine kinase (NTRK) fusion gene-positive advanced solid tumors have been established as the second tumor-agnostic treatment, making it necessary to develop the guideline prioritized for these patients. Methods Clinical questions regarding medical care were formulated for patients with NTRK-positive advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by Japan Society of Clinical Oncology (JSCO) and Japanese Society of Medical Oncology (JSMO) voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and Japanese Society of Pediatric Hematology/Oncology, and the public comments among all Societies’ members was done. Results The current guideline describes 3 clinical questions and 15 recommendations for whom, when, and how NTRK fusion should be tested, and what is recommended for patients with NTRK fusion-positive advanced solid tumors. Conclusion In the NTRK guideline, the committee proposed 15 recommendations for performing NTRK testing properly to select patients who are likely to benefit from tropomyosin receptor kinase inhibitors.
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- 2020
31. The histone deacetylase inhibitor OBP‐801 has in vitro / in vivo anti‐neuroblastoma activity
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Daisuke Kaneda, Tomoko Iehara, Ken Kikuchi, Yohei Sugimoto, Norio Nakagawa, Shigeki Yagyu, Mitsuru Miyachi, Eiichi Konishi, Toshiyuki Sakai, and Hajime Hosoi
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Histone Deacetylase Inhibitors ,Mice ,N-Myc Proto-Oncogene Protein ,Neuroblastoma ,Cell Line, Tumor ,Pediatrics, Perinatology and Child Health ,Animals ,Humans ,Peptides, Cyclic ,Cell Proliferation - Abstract
Patients with high-risk neuroblastoma have a poor prognosis; new therapeutic agents are therefore required. We investigated the antitumor effects of OBP-801, a novel histone deacetylase inhibitor, its underlying mechanism, and its potential as a therapeutic agent for patients with neuroblastoma.The study included five human neuroblastoma cell lines: IMR32, GOTO, KP-N-RTBM, SK-N-AS, and SH-SY5Y. We investigated cell proliferation, cell cycle status, protein expression patterns, and apoptosis in neuroblastoma cells after OBP-801 treatment in vitro. Cell survival rate and cell cycle were analyzed using the WST-8 assay and flow cytometry, respectively. Apoptosis was detected using annexin V staining, and the expression of apoptosis-related proteins was investigated by western blotting. The antitumor activity of OBP-801 was examined in an in vivo xenograft mouse model.Dose-effect curve analysis showed that the mean half-maximal inhibitory concentration value was 5.5 ± 5.9 nM for the MYCN-amplified cell lines (IMR32, GOTO, and KP-N-RTBM) and 3.1 ± 0.7 nM for the MYCN-nonamplified cell lines (SK-N-AS and SH-SY5Y). OBP-801 inhibited cell proliferation and growth in all the cell lines. It induced G2/M phase arrest through the p21 (CDKN1A) pathway, increasing histone H3 levels and, subsequently, apoptosis in human neuroblastoma cells. OBP-801 suppressed the growth of neuroblastoma cells in the mouse xenograft model.Overall, OBP-801 induces M-phase arrest and apoptosis in neuroblastoma cells via mitotic catastrophe. Our results indicate that OBP-801 is a promising therapeutic agent with fewer adverse effects for patients with neuroblastoma.
- Published
- 2022
32. The possible effects of the Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 on the practice of fertility preservation in female cancer patients in Japan
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Chisato Kunitomi, Miyuki Harada, Yuko Sanada, Akari Kusamoto, Yasushi Takai, Tatsuro Furui, Yuko Kitagawa, Mitsutoshi Yamada, Chie Watanabe, Koichiro Tsugawa, Hiroyuki Nishiyama, Hajime Hosoi, Mitsuru Miyachi, Kazuhiko Sugiyama, Yoshinobu Maeda, Akira Kawai, Toshio Hamatani, Keishi Fujio, Nao Suzuki, and Yutaka Osuga
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Reproductive Medicine ,Cell Biology - Abstract
In 2017, the first guidelines for fertility preservation in cancer patients were published in Japan. However, the impact of the guidelines remains unknown. Therefore, the authors conducted a nationwide survey on cryopreservation procedures in the period from shortly before to after publication of the guidelines (2016-2019) and compared the results with our previous survey (2011-2015). The authors also surveyed reproductive specialists' awareness of the guidelines and implementation problems.The authors sent a questionnaire to 618 assisted reproductive technology facilities certified by the Japanese Society of Obstetrics and Gynecology.The authors received responses from 395 institutions (63.8%). Among them, 144 institutions conducted cryopreservation for cancer patients (vs. 126 in 2011-2015) and performed 2537 embryo or oocyte and 178 ovarian tissue cryopreservation procedures (vs. 1085 and 122, respectively). Compared with the previous period, indications were more varied and protocols for controlled ovarian stimulation were more standardized. Reproductive specialists' interest in oncofertility was high, but many reported three main difficulties: selecting a treatment method, storing samples in the long term, and securing the necessary human resources.The practice of fertility preservation in cancer patients in Japan has been considerably affected by the first Japanese guidelines.
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- 2021
33. Indications for fertility preservation not included in the 2017 Japan Society of Clinical Oncology Guideline for Fertility Preservation in Pediatric, Adolescent, and Young Adult Patients treated with gonadal toxicity, including benign diseases
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Ken-ichirou Morishige, Masanori Ono, Nao Suzuki, Chikako Shimizu, Akira Kawai, Kazuhiko Sugiyama, Nobuharu Fujii, Yasushi Takai, Hiroyuki Nishiyama, Yumi Tsuchida, Yutaka Osuga, Kimikazu Matsumoto, Yoshinobu Kanda, Robert Nakayama, Mitsuru Miyachi, Tatsuro Furui, Narikazu Boku, Miyuki Harada, Atsuko Murashima, and Keishi Fujio
- Subjects
medicine.medical_specialty ,Adolescent ,media_common.quotation_subject ,Fertility ,Medical Oncology ,Young Adult ,Japan ,Surgical oncology ,Neoplasms ,medicine ,Humans ,Fertility preservation ,Young adult ,Child ,media_common ,Oncofertility ,business.industry ,Fertility Preservation ,Hematology ,General Medicine ,Guideline ,Gonadal toxicity ,Oncology ,Family medicine ,Surgery ,business ,Welfare - Abstract
In recent years, local governments in Japan have established a public financial support system for fertility preservation in pediatric, adolescent, and young adult cancer patients. Fertility preservation has become popular for patients with cancers included in the gonadal toxicity risk classification of the 2017 edition of the Guideline for Fertility Preservation in Children, Adolescents and Young Adult Cancer Patients from the Japan Society of Clinical Oncology. However, patients with cancer and non-cancer diseases that are not included in the Guideline’s gonadal toxicity risk classification also often receive treatment that may affect fertility, but they are often denied the opportunity of fertility preservation because no public financial support is available for diseases not listed in the Guideline. The national research project proposes including these diseases in the indications and treatment for fertility preservation. Therefore, we cooperated with the Japan Society for Fertility Preservation and the Ministry of Health, Labour and Welfare research group to solicit opinions from experts in each therapeutic area and reviewed the literature and overseas guidelines. This paper summarizes the findings of the project. We believe that it will be an important source of information for clinicians treating patients who need fertility preservation but note that the appropriateness of fertility preservation for the disorders listed in this report needs to be continuously reviewed as medical care advances.
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- 2021
34. Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 for fertility preservation in childhood, adolescent, and young adult cancer patients: part 1
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Miyuki Harada, Fuminori Kimura, Yasushi Takai, Takeshi Nakajima, Kimio Ushijima, Hiroaki Kobayashi, Toyomi Satoh, Akiko Tozawa, Kohei Sugimoto, Shigehira Saji, Chikako Shimizu, Kyoko Akiyama, Hiroko Bando, Akira Kuwahara, Tatsuro Furui, Hiroshi Okada, Koji Kawai, Nobuo Shinohara, Koichi Nagao, Michio Kitajima, Souichi Suenobu, Toshinori Soejima, Mitsuru Miyachi, Yoko Miyoshi, Akihiro Yoneda, Akihito Horie, Yasushi Ishida, Noriko Usui, Yoshinobu Kanda, Nobuharu Fujii, Makoto Endo, Robert Nakayama, Manabu Hoshi, Tsukasa Yonemoto, Chikako Kiyotani, Natsuko Okita, Eishi Baba, Manabu Muto, Iwaho Kikuchi, Ken-ichirou Morishige, Koichiro Tsugawa, Hiroyuki Nishiyama, Hajime Hosoi, Mitsune Tanimoto, Akira Kawai, Kazuhiko Sugiyama, Narikazu Boku, Masato Yonemura, Naoko Hayashi, Daisuke Aoki, Yutaka Osuga, and Nao Suzuki
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Oncologists ,Adolescent ,Fertility Preservation ,Hematology ,General Medicine ,Medical Oncology ,Young Adult ,Oncology ,Japan ,Neoplasms ,Humans ,Surgery ,Female ,Child - Abstract
In 2017, the Japan Society of Clinical Oncology (JSCO) published the JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients. These were the first Japanese guidelines to address issues of oncofertility. In this field of medicine, sustained close cooperation between oncologists and reproductive specialists is essential from the diagnosis of cancer until many years after completion of cancer treatment. These JSCO guidelines were intended to guide multidisciplinary medical staff in considering the availability of fertility preservation options and to help them decide whether to provide fertility preservation to childhood, adolescent, and young adult cancer patients before treatment starts, with the ultimate goal of improving patient survivorship. The guidelines are presented as Parts 1 and 2. This article (Part 1) summarizes the goals of the guidelines and the methods used to develop them and provides an overview of fertility preservation across all oncology areas. It includes general remarks on the basic concepts surrounding fertility preservation and explanations of the impacts of cancer treatment on gonadal function by sex and treatment modality and of the options for protecting/preserving gonadal function and makes recommendations based on 4 clinical questions. Part 2 of these guidelines provides specific recommendations on fertility preservation in 8 types of cancer (gynecologic, breast, urologic, pediatric, hematologic, bone and soft tissue, brain, and digestive).
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- 2021
35. Identifying Issues in Fertility Preservation for Childhood and Adolescent Patients with Cancer at Pediatric Oncology Hospitals in Japan
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Keishiro Amano, Kimikazu Matsumoto, Chikako Kiyotani, Seido Takae, Nao Suzuki, Akihito Horie, Hiroyuki Okimura, Tadashi Maezawa, Dai Keino, Maki Goto, Tomoaki Ikeda, Hiroki Takeuchi, Mitsuru Miyachi, Haruhiko Sago, Masahiro Hirayama, and Junko Takita
- Subjects
Response rate (survey) ,medicine.medical_specialty ,Adolescent ,business.industry ,Attendance ,Cancer ,Questionnaire ,Fertility Preservation ,medicine.disease ,Hospitals, Pediatric ,Medical Oncology ,Pediatric cancer ,Oncology ,Japan ,Family medicine ,Neoplasms ,Pediatrics, Perinatology and Child Health ,Medicine ,Humans ,Fertility preservation ,Young adult ,business ,Child ,Oncofertility - Abstract
Purpose: We conducted a questionnaire survey in 15 pediatric oncology hospitals in Japan to better understand the current status of fertility preservation in childhood and adolescents. Methods: The survey period was from September 2020 to December 2020. We mailed questionnaires to 64 departments involved in pediatric cancer treatments at the 15 hospitals. The primary outcomes were the timing of providing explanations on fertility preservation, presence of health care provider while providing explanations, cooperation between medical staff, and cooperation between hospitals. Results: The response rate was 100% (64/64). Regarding the time at which this information was provided, 79.6% of patients (43/54) received it before cancer treatment; 5.6% (3/54), after remission; and 14.8% (8/54), both time points. Nurses were mostly in attendance (70%) when oncologists provided information to patients. Nine (60%) hospitals did not have a reproductive department. Among these, 28.6% of the respondents referred patients to a reproductive facility that performed fertility preservation. Providing information about fertility preservation was challenging owing to the shortage of specific explanatory materials (35.1%) and the lack of cooperation between pediatric oncologists and reproductive endocrinologists (24.6%). Conclusion: Based on this survey, educational activities regarding fertility preservation centered on pediatric oncologists and nurses are needed. Furthermore, a system for providing explanatory materials for fertility preservation and encouraging cooperation at the physician and hospital levels is also needed (IRB No. H2020-111).
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- 2021
36. [Promotion of Equal Access to Medical Services for Children, Adolescent and Young Adult(CAYA)Cancer Patients with Reproductive Problems-A Nationwide Expansion of the Regional Oncofertility Network in Japan]
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Motoki, Takenaka, Tatsuro, Furui, Seido, Takae, Yodo, Sugishita, Tai, Kawahara, Kosuke, Shigematsu, Fuminori, Kimura, Akihito, Horie, Tetsuaki, Hara, Masashi, Kato, Hiroyuki, Nishiyama, Tatsuya, Suzuki, Mitsuru, Miyachi, Kenji, Kanenishi, Komei, Kubo, Satoru, Nakayama, Hiroaki, Kajiyama, Yasushi, Takai, and Nao, Suzuki
- Subjects
Oncologists ,Young Adult ,Fertility ,Adolescent ,Japan ,Neoplasms ,Fertility Preservation ,Humans ,Child - Abstract
Fertility preservation is important for Children, Adolescent and Young Adult(CAYA)cancer patients. Although a regional oncofertility network was established in Japan in 2012, regional inequality persists. This study was aimed at expanding the oncofertility network throughout Japan.Oncologists, reproductive medicine specialists, and administrative officials from 24 regions, currently without a regional oncofertility network, conferred to discuss problems and strategies for network expansion.Regional oncofertility networks had already been established in 4 of 24 regions. Consultation and support and a collaboration system between facilities and individual doctors were found in 13 and 14 regions, respectively. Regarding which organization should lead the network operation, the regions(number)chose the prefecture (10), prefectural cancer centers(10), and OB/GYN department of hospitals specializing in cancer treatment(9). Obstacles to establishing a regional oncofertility network were the lack of manpower(21), budget(19), know-how(16), and specialists( 12).CAYA cancer patients need equal access to oncofertility networks, and a public support system is essential for preserving the fertility of cancer patients. We should organize a oncofertility network in association with prefectural administration. Medical staff training and supply of materials using the Oncofertility Consortium Japan system are required to promote the oncofertility network throughout Japan.
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- 2020
37. Proton beam therapy for children and adolescents and young adults (AYAs): JASTRO and JSPHO Guidelines
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Etsuyo Ogo, Hajime Hosoi, Toshinori Soejima, Tomohei Nakao, Atsufumi Kawamura, Norihiro Aibe, Ako Hosono, Ryoko Suzuki, Hidekazu Masaki, Hideyuki Sakurai, Keisuke Ae, Mitsuru Miyachi, Akira Matsumura, Takashi Fukushima, Miwako Nozaki, Takashi Saito, Hiromitsu Iwata, Hiroshi Fuji, Yoshiyuki Kosaka, Takashi Yamamoto, Hideyuki Harada, Minako Sumi, Masashi Mizumoto, Yuji Ishida, Takayuki Hashimoto, Takayuki Matsuo, Tetsuo Akimoto, Mitsuru Takahashi, Hiroko Fukushima, Naoyuki Shigematsu, Akinori Takada, Atsushi Motegi, Keita Terashima, Yusuke Demizu, Junjiro Oshima, and K. Moriwaki
- Subjects
0301 basic medicine ,Adult ,Pediatrics ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Dose distribution ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Neoplasms ,Radiation oncology ,Proton Therapy ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Young adult ,Adverse effect ,Child ,Societies, Medical ,business.industry ,Cancer ,General Medicine ,Guideline ,medicine.disease ,humanities ,Radiation therapy ,030104 developmental biology ,Oncology ,Reduced fertility ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,business - Abstract
Children and adolescents and young adults (AYAs) with cancer are often treated with a multidisciplinary approach. This includes use of radiotherapy, which is important for local control, but may also cause adverse events in the long term, including second cancer. The risks for limited growth and development, endocrine dysfunction, reduced fertility and second cancer in children and AYAs are reduced by proton beam therapy (PBT), which has a dose distribution that decreases irradiation of normal organs while still targeting the tumor. To define the outcomes and characteristics of PBT in cancer treatment in pediatric and AYA patients, this document was developed by the Japanese Society for Radiation Oncology (JASTRO) and the Japanese Society of Pediatric Hematology/Oncology (JSPHO).
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- 2020
38. [Development of Novel Therapeutic Strategies for Childhood Cancer in Japan]
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Mitsuru, Miyachi and Hajime, Hosoi
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Adolescent ,Japan ,Neoplasms ,Humans ,Child ,Prognosis - Abstract
Development of standard and new treatment in childhood cancer, like adult cancer, has been driven by the results of clinical trials. In Japan, the Japan Children's Cancer Group(JCCG)was formed in 2014, and is currently conducting clinical trials based on a common platform. Development of standard treatment for childhood cancer is divided into intensification of treatment to improve prognosis in patients with poor prognosis, and development of treatment to reduce acute toxicity and long-term complications in patients with favorable prognosis while maintaining survival. Despite the difficulty in conducting clinical trials with sufficient power in childhood cancer, especially in Japan, international collaboration have enabled international randomized controlled trials. In childhood cancer with a small number of cases, the number of international clinical trials is expected to increase in the future, and the results of confirmatory studies are expected to be found more quickly. When developing treatments for cancer types that widely arise from childhood to adulthood, it is necessary for multidisciplinary medical professionals who treat adults and children to participate from the stage of the development of a clinical trial. We believe that this will make it possible to conduct trials to create high-quality evidence for a wide range of age groups. Developing new treatments for childhood cancer is often done in investigator-initiated clinical trials, but requires the understanding of the regulatory authorities, Clinical Research Organization(CRO), and research funders involved in the trial. In addition, childhood cancer researchers need to work with patient groups to appeal to relevant stakeholders so that new treatments for childhood cancer can be developed through industry-initiated trials rather than investigator-initiated trials.
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- 2020
39. Detection of circulating fungal DNA by polymerase chain reaction in a fatal case of Cunninghamella bertholletiae infection
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Yoshihiro Nitta, Kunihiko Tsuchiya, Tomoko Iehara, Hideki Yoshida, Katsuhiko Kamei, Yasumichi Kuwahara, Kyoko Yarita, Rika Hiramoto, Mitsuru Miyachi, and Hajime Hosoi
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0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,030106 microbiology ,Cunninghamella bertholletiae ,Infectious and parasitic diseases ,RC109-216 ,Neutropenia ,Gastroenterology ,Article ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Zygomycosis ,law ,Internal medicine ,medicine ,Mucormycosis ,Circulating DNA ,030212 general & internal medicine ,Polymerase chain reaction ,Voriconazole ,Chemotherapy ,Lung ,biology ,business.industry ,biology.organism_classification ,medicine.disease ,Infectious Diseases ,medicine.anatomical_structure ,Internal transcribed spacer region ,business ,medicine.drug - Abstract
Introduction Cunninghamella bertholletiae although rarely causing mucormycosis, is responsible for the highest mortality among mucormycetes. The diagnosis of mucormycosis is challenged by the absence of specific biomarkers. Herein, we report a fatal case of C. bertholletiae infection and detection of its DNA in the serum by polymerase chain reaction (PCR). Presentation of case A 23-year-old male with refractory osteosarcoma was admitted with multiple lung metastases. He was on oral voriconazole prophylaxis after pulmonary aspergillosis. He suffered from fever during temporary neutropenia following chemotherapy and showed several neurological and respiratory symptoms. Despite liposomal-amphotericin B administration, the symptoms rapidly progressed, and he died five days after the onset of neurological symptoms. We retrospectively evaluated the filamentous fungus isolated after his death from gastric juices. Based on the sequence of the internal transcribed spacer (ITS) region we identified the fungal isolate as C. bertholletiae. A 146-bp portion of the D1/D2 region was quantified by quantitative-PCR using DNA extracted from the serum. C. bertholletiae DNA load in the serum was 18.0 copies/μL on the day of onset of neurological symptoms, with the highest (101.0 copies/μL) on the day of his death. Discussion Detection of circulating DNA of mucormycetes in the blood would greatly enhance the diagnosis of mucormycosis. Rapid diagnosis might alleviate mortality due to mucormycosis. Conclusion The present case-report suggests that the quantification of C. bertholletiae DNA in the serum could be useful for the diagnosis and evaluation of mucormycosis pathogenesis in patients.
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- 2020
40. The Novel Histone Deacetylase Inhibitor, OBP-801, Induces Apoptosis in Rhabdoid Tumors by Releasing the Silencing of
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Kunihiko Tsuchiya, Hajime Hosoi, Tomoko Iehara, Chihiro Tomoyasu, Ken Kikuchi, Hideki Yoshida, Yohei Sugimoto, Yasumichi Kuwahara, Kazutaka Ouchi, Daisuke Kaneda, Yoshiki Katsumi, Shigeki Yagyu, Toshiyuki Sakai, and Mitsuru Miyachi
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0301 basic medicine ,Cancer Research ,medicine.drug_class ,Mice, Nude ,Apoptosis ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,Gene silencing ,Animals ,Humans ,Epigenetics ,SMARCB1 ,Rhabdoid Tumor ,Cell growth ,Chemistry ,Histone deacetylase inhibitor ,Chromatin ,Histone Deacetylase Inhibitors ,030104 developmental biology ,Oncology ,Proto-Oncogene Proteins c-bcl-2 ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Chromatin immunoprecipitation - Abstract
Rhabdoid tumor is an aggressive, early childhood tumor. Biallelic inactivation of the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1)/integrase interactor 1 (INI1) gene is the only common genetic feature in rhabdoid tumors. Loss of SMARCB1 function results in downregulation of several tumor suppressor genes including p16, p21, and NOXA. The novel histone deacetylase inhibitor, OBP-801, induces p21 and has shown efficacy against various cancers. In our study, OBP-801 strongly inhibited the cell growth of all rhabdoid tumor cell lines in WST-8 assay. However, Western blotting and cell-cycle analysis revealed that OBP-801 did not activate the P21-RB pathway in some cell lines. p21 knockout indicated that p21 did not dominate the OBP-801 antitumor effect in rhabdoid tumor cell lines. We discovered that OBP-801 induced NOXA expression and caspase-dependent apoptosis in rhabdoid tumor cell lines independent of TP53. Chromatin immunoprecipitation assay showed that OBP-801 acetylated histone proteins and recruited RNA polymerase II to the transcription start site (TSS) of the NOXA promotor. Moreover, OBP-801 recruited BRG1 and BAF155, which are members of the SWI/SNF complex, to the TSS of the NOXA promotor. These results suggest that OBP-801 epigenetically releases the silencing of NOXA and induces apoptosis in rhabdoid tumors. OBP-801 strongly inhibited tumor growth in human rhabdoid tumor xenograft mouse models in vivo. Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and cleaved caspase-3 were stained in tumors treated with OBP-801. In conclusion, OBP-801 induces apoptosis in rhabdoid tumor cells by epigenetically releasing the silencing of NOXA, which is a key mediator of rhabdoid tumor apoptosis. The epigenetic approach for NOXA silencing with OBP-801 is promising for rhabdoid tumor treatment.
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- 2020
41. Cytomegalovirus-associated biliary atresia
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Takeshi Ota, Jun Mori, Tetsuya Imura, Kenichi Sakamoto, Tomohiko Imai, Mitsuru Miyachi, Tomohiro Chiyonobu, Kazuki Kodo, and Hajime Hosoi
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Intracerebral hemorrhage ,Poor prognosis ,business.industry ,lcsh:RJ1-570 ,lcsh:Surgery ,Congenital cytomegalovirus infection ,virus diseases ,lcsh:Pediatrics ,Autopsy ,lcsh:RD1-811 ,medicine.disease ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Biliary atresia ,030220 oncology & carcinogenesis ,Liver tissue ,Pediatrics, Perinatology and Child Health ,Immunology ,medicine ,030211 gastroenterology & hepatology ,Surgery ,business - Abstract
The pathogenesis of biliary atresia (BA) is propounded to be an immunological process, but the detailed mechanisms remain unclear. In recent studies with abnormal immunological findings, T cells have drawn attention in the mechanism of BA pathogenesis. Furthermore, cytomegalovirus (CMV) infection in BA patients resulted in elevated levels of helper T cells (Th1 and Th17) and reduction of regulatory T cells. Thus, CMV infection is considered as a cause of BA.We present the case of a 3-month-old boy who presented with intracerebral hemorrhage and finally died of liver failure. BA was diagnosed on autopsy and serum CMV-IgM was positive, but CMV antigen in the liver tissue was negative.Because CMV-associated BA has poor prognosis, compared with BA not associated with CMV, accurate classification of the type of BA is essential. Keywords: Biliary atresia, Cytomegalovirus, Cytomegalovirus-associated biliary atresia
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- 2018
42. Cancer-Specific Energy Metabolism in Rhabdomyosarcoma Cells Is Regulated by MicroRNA
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Yukihiro Akao, Maki Ohishi, Kohei Taniguchi, Ken Kikuchi, Yuki Kuranaga, Hajime Hosoi, Mitsuru Miyachi, Nobuhiko Sugito, Tomoyoshi Soga, and Yuko Ito
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Male ,musculoskeletal diseases ,0301 basic medicine ,Adolescent ,Oncogene Proteins, Fusion ,genetic structures ,Mice, Nude ,Biology ,Biochemistry ,Heterogeneous-Nuclear Ribonucleoproteins ,Mice ,Young Adult ,03 medical and health sciences ,Downregulation and upregulation ,Cell Line, Tumor ,Drug Discovery ,microRNA ,Genetics ,medicine ,Animals ,Humans ,Paired Box Transcription Factors ,Gene silencing ,Rhabdomyosarcoma, Embryonal ,Child ,Rhabdomyosarcoma ,Molecular Biology ,Rhabdomyosarcoma, Alveolar ,Mice, Inbred BALB C ,Cell Death ,Infant ,PTBP1 ,musculoskeletal system ,medicine.disease ,Xenograft Model Antitumor Assays ,Warburg effect ,MicroRNAs ,030104 developmental biology ,Cell culture ,Child, Preschool ,Cancer research ,Molecular Medicine ,Female ,Ectopic expression ,Energy Metabolism ,Polypyrimidine Tract-Binding Protein - Abstract
Rhabdomyosarcoma (RMS) is a soft tissue sarcoma and is most frequently found in children. In RMS, there are two major subtypes, that is, embryonal RMS and alveolar RMS (ARMS). ARMS has exclusively the worse prognosis and is caused by formation of the chimeric PAX3-FOXO1 gene. Regarding cancer, the Warburg effect is known as a feature of cancer-specific metabolism. Polypyrimidine tract-binding protein 1 (PTBP1), a splicer of pyruvate kinase muscle (PKM) mRNA, is a positive regulator of cancer-specific energy metabolism. We investigated the expression and effects of muscle-specific miR-1 and miR-133b on RMS cells (RD, KYM-1, Rh30, and Rh41) from the view of energy metabolism and regulation of the chimeric gene. As a result, downregulated miR-1 and miR-133b/upregulated PTBP1 were found in RMS cell lines as well as in RMS clinical cases. Ectopic expression of either miR in both types of RMS cells induced autophagic cell death through silencing of PTBP1. Interestingly, we validated that miR-133b also knock downed PAX3-FOXO1. Moreover, we found that PAX3-FOXO1 positively regulated the PKM2-dominant expression through enhanced expression of PTBP1. These findings suggest that the miR-1 and miR-133b/PTBP1 axis and miR-133b/PAX3-FOXO1/PTBP1 axis contributed to the maintenance of cancer-specific energy metabolism.
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- 2017
43. DIPG-04. THERAPEUTIC STRATEGY FOR DIFFUSE MIDLINE GLIOMAS. A SINGLE CENTER EXPERIENCE
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Toshiki Nagai, Daisuke Umebayashi, Hajime Hosoi, Tomoko Iehara, Seisuke Tanigawa, Shigeki Yagyu, Tamaki Morisako, Kazunori Tatsuzawa, Hayato Takeuchi, Yoshinobu Takahashi, Mitsuru Miyachi, Takumi Yamanaka, and Naoya Hashimoto
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Cancer Research ,medicine.medical_specialty ,business.industry ,Diffuse Midline Glioma/DIPG ,Single Center ,medicine.disease ,Surgical specimen ,Cervical spine ,Oncology ,Glioma ,medicine ,AcademicSubjects/MED00300 ,AcademicSubjects/MED00310 ,Neurology (clinical) ,Radiology ,Spinal Neoplasms ,business ,Therapeutic strategy - Abstract
INTRODUCTION Diffuse midline gliomas have unfavorable prognoses due to the difficulty of surgery and chemo-radiation resistances. The purpose of this study is to overview our surgical experiences and prognoses of this challenging neoplasm. MATERIALS AND METHODS Five patients of diffuse midline gliomas who were treated between 2016 and 2019 were enrolled. Tumor locations, surgical procedures, molecular diagnoses, and prognoses were retrospectively reviewed. RESULTS There were 3 male and 2 female patients, and the median age was 15 years ranged from 7 to 21 years. Tumors were located at the basal ganglia in 1 patient, thalamus in 1, brain stem in 2, and cervical spine in 1. Mutations of H3 K27M genes were detected in 4 surgically treated patients, except for 1 patient, who were radiologically diagnosed as diffuse intrinsic pontine glioma (DIPG). Focal irradiation of ranged 35 to 54Gy were administered in all cases along with temozolomide in 2 cases and bevacizumab in 2 cases. The median survival time was 13 months ranged from 4 to 18 months. DISCUSSION Supratentorial tumors were maximumly resected, whereas just biopsies were performed in cases of exophytic brain stem and spinal tumors. Diagnosis of DIPG was made without using surgical specimens. Therapeutic strategies should be discussed with a concern to the patients’ qualities of life for this tumor entity with dismal prognosis.
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- 2020
44. Sorafenib Therapy for Pediatric Acute Myeloid Leukemia with FMS-like Tyrosine Kinase 3-internal Tandem Duplication Mutations: 2 Case Reports
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Shinichi Tamura, Mitsuru Miyachi, Akari Takai, Sachiko Kawashima-Goto, Takuya Nakatani, Shinya Osone, Hajime Hosoi, Toshihiko Imamura, Takuyo Kanayama, Atsuya Sugimoto, Hiroyuki Ishida, and Yusuke Tsuma
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Male ,Niacinamide ,Sorafenib ,Oncology ,medicine.medical_specialty ,Myeloid ,medicine.medical_treatment ,Pharmacology ,Drug Administration Schedule ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,hemic and lymphatic diseases ,Internal medicine ,Humans ,Medicine ,Child ,neoplasms ,Salvage Therapy ,Chemotherapy ,business.industry ,Phenylurea Compounds ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,medicine.disease ,female genital diseases and pregnancy complications ,digestive system diseases ,Transplantation ,Leukemia, Myeloid, Acute ,Leukemia ,Treatment Outcome ,surgical procedures, operative ,medicine.anatomical_structure ,fms-Like Tyrosine Kinase 3 ,Tandem Repeat Sequences ,Child, Preschool ,030220 oncology & carcinogenesis ,Mutation ,Pediatrics, Perinatology and Child Health ,Fms-Like Tyrosine Kinase 3 ,Female ,business ,030215 immunology ,medicine.drug - Abstract
Sorafenib is a promising agent for treating pediatric refractory acute myeloid leukemia (AML) exhibiting FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD); however, its optimal use needs to be established. We report 2 cases of refractory pediatric FLT3-ITD-positive AML treated with sorafenib. Case 1 underwent stem cell transplantation (SCT) without entering remission, despite the use of chemotherapy. This patient relapsed despite receiving post-SCT sorafenib. Chemotherapy combined with sorafenib successfully achieved complete remission in case 2. This patient received post-SCT sorafenib and remains in complete remission. The combination of pre-SCT and post-SCT sorafenib may thus be effective for pediatric refractory FLT3-ITD-positive AML.
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- 2017
45. The histone deacetylase inhibitor OBP-801 has in vitro/in vivo anti-neuroblastoma activity.
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Daisuke Kaneda, Tomoko Iehara, Ken Kikuchi, Yohei Sugimoto, Norio Nakagawa, Shigeki Yagyu, Mitsuru Miyachi, Eiichi Konishi, Toshiyuki Sakai, and Hajime Hosoi
- Abstract
Background: Patients with high-risk neuroblastoma have a poor prognosis; new therapeutic agents are therefore required. We investigated the antitumor effects of OBP-801, a novel histone deacetylase inhibitor, its underlying mechanism, and its potential as a therapeutic agent for patients with neuroblastoma. Methods: The study included five human neuroblastoma cell lines: IMR32, GOTO, KP-N-RTBM, SK-N-AS, and SH-SY5Y. We investigated cell proliferation, cell cycle status, protein expression patterns, and apoptosis in neuroblastoma cells after OBP-801 treatment in vitro. Cell survival rate and cell cycle were analyzed using the WST-8 assay and flow cytometry, respectively. Apoptosis was detected using annexin V staining, and the expression of apoptosis-related proteins was investigated by western blotting. The antitumor activity of OBP-801 was examined in an in vivo xenograft mouse model. Results: Dose–effect curve analysis showed that the mean half-maximal inhibitory concentration value was 5.5 ± 5.9 nM for the MYCN-amplified cell lines (IMR32, GOTO, and KP-N-RTBM) and 3.1 ± 0.7 nM for the MYCN-nonamplified cell lines (SK-N-AS and SH-SY5Y). OBP-801 inhibited cell proliferation and growth in all the cell lines. It induced G2/M phase arrest through the p21 (CDKN1A) pathway, increasing histone H3 levels and, subsequently, apoptosis in human neuroblastoma cells. OBP-801 suppressed the growth of neuroblastoma cells in the mouse xenograft model. Conclusions: Overall, OBP-801 induces M-phase arrest and apoptosis in neuroblastoma cells via mitotic catastrophe. Our results indicate that OBP-801 is a promising therapeutic agent with fewer adverse effects for patients with neuroblastoma. [ABSTRACT FROM AUTHOR]
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- 2022
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- View/download PDF
46. Synchronous bilateral lung adenocarcinomas associated with vulvar rhabdomyosarcoma in a 15-year-old girl
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Masayoshi Inoue, Satoru Okada, Junichi Shimada, Hiroaki Tsunezuka, Hajime Hosoi, Mitsuru Miyachi, Tatsuo Furuya, Tomoko Iehara, and Daishiro Kato
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medicine.medical_specialty ,Metastatic lesions ,media_common.quotation_subject ,lcsh:Surgery ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Girl ,Lung cancer ,Rhabdomyosarcoma ,neoplasms ,media_common ,Lung ,business.industry ,lcsh:RJ1-570 ,Cancer ,Nodule (medicine) ,lcsh:Pediatrics ,lcsh:RD1-811 ,medicine.disease ,female genital diseases and pregnancy complications ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Surgery ,Radiology ,Differential diagnosis ,medicine.symptom ,business - Abstract
Pediatric malignancies are thought to be risk factors of second malignant neoplasms. However, lung cancer associated with rhabdomyosarcoma is extremely rare. When multiple pulmonary lesions are observed in cancer patients, resection is necessary to distinguish them from metastatic lesions. We report an extremely rare case of synchronous bilateral multiple lung cancers showing ground glass nodules (GGNs) associated with rhabdomyosarcoma in a 15-year-old girl with vulvar rhabdomyosarcoma. When we identify GGNs in adolescents with a history of rhabdomyosarcoma, we should consider lung cancer as a differential diagnosis in addition to pulmonary metastasis usually showing solid nodule. In the present case with tiny lesions, surgical resection using lipiodol-marking helped to ensure both an early diagnosis and curative treatment. Keywords: Synchronous bilateral multiple lung cancers, Adolescent, Rhabdomyosarcoma
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- 2018
47. Mutations in the RAS pathway as potential precision medicine targets in treatment of rhabdomyosarcoma
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Hajime Hosoi, Toshiyuki Sakai, Mitsuru Miyachi, Ken Kikuchi, Shigeki Yagyu, Tatsuro Tajiri, Norio Nakagawa, and Tomoko Iehara
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0301 basic medicine ,Neuroblastoma RAS viral oncogene homolog ,genetic structures ,Biophysics ,Mice, Nude ,Gene mutation ,Biology ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Coumarins ,Cell Line, Tumor ,Rhabdomyosarcoma ,medicine ,Animals ,Humans ,HRAS ,Precision Medicine ,Child ,Molecular Biology ,Protein Kinase Inhibitors ,Mice, Inbred BALB C ,MEK inhibitor ,Cell Cycle ,Cell Biology ,Cell cycle ,medicine.disease ,030104 developmental biology ,Cell culture ,030220 oncology & carcinogenesis ,Mutation ,Cancer research ,ras Proteins ,Female ,G1 phase ,Signal Transduction - Abstract
Precision medicine strategies for treating rhabdomyosarcoma (RMS), a childhood malignancy, have not been developed. We examined the effect of CH5126766, a potent selective dual RAF/MEK inhibitor, on RMS cell lines. Among the eleven cell lines studied, one NRAS and two HRAS mutated cell lines were detected. CH5126766 inhibited the proliferation and growth in all of the RAS-mutated RMS cell lines, while it induced G1 cell cycle arrest in two of them. G1 cell cycle arrest was accompanied by p21 up-regulation and RB dephosphorylation. CH5126766 also suppressed the in vivo growth of RAS-mutated RMS tumor, and the mice showed improved survival. Thus, our results demonstrate that CH5126766 is an effective RAF/MEK inhibitor in RAS-mutated RMS. This study not only shows that in RMS, mutations in the RAS pathway can be a target for precision medicine, but also demonstrates that the evaluation of the gene mutation status is important in childhood malignancies.
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- 2019
48. Identification of a novel BOC-PLAG1 fusion gene in a case of lipoblastoma
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Hajime Hosoi, Hideki Yoshida, Akimasa Tomida, Mitsuru Miyachi, Takeshi Okamoto, Yohei Sugimoto, Katsutsugu Umeda, Eiichi Konishi, Kunihiko Tsuchiya, Kazutaka Ouchi, Norio Nakagawa, Tomoko Iehara, and Yoshihiro Nitta
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0301 basic medicine ,Sequence analysis ,Biophysics ,Gene Expression ,Chromosomal translocation ,Receptors, Cell Surface ,Biology ,Biochemistry ,Fusion gene ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Rapid amplification of cDNA ends ,medicine ,Adipocytes ,Humans ,Oncogene Fusion ,Child ,Molecular Biology ,Gene ,Back ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Cell Biology ,DNA, Neoplasm ,medicine.disease ,DNA-Binding Proteins ,030104 developmental biology ,Fusion transcript ,030220 oncology & carcinogenesis ,Immunoglobulin G ,Cancer research ,Lipoblastoma ,Female - Abstract
Lipoblastoma is a rare benign adipose tissue tumor that occurs mostly in infants and children. Histological diagnosis of lipoblastoma is sometimes difficult because it closely resembles other lipomatous tumors. The detection of PLAG1 gene rearrangement is useful for the diagnosis of lipoblastoma. Four PLAG1 fusion partner genes are known in lipoblastoma: HAS2 at 8q24.1, COL1A2 at 7q22, COL3A1 at 2q32, and RAB2A at 8q12. Herein, we describe a novel fusion gene in a case of lipoblastoma of left back origin. We identified a potential PLAG1 fusion partner using 5′ rapid amplification of cDNA ends, and sequence analysis revealed the novel fusion gene, BOC-PLAG1. The BOC-PLAG1 fusion transcript consists of the first exon of the BOC gene fused to exon 2 or exon 3 of the PLAG1 gene. PLAG1 expression was found to be 35.7 ± 2.1 times higher in the tumor specimen than in human adipocytes by qRT-PCR. As a result of the translocation, the constitutively active promoter of BOC leads to PLAG1 overexpression. The identification of the BOC-PLAG1 fusion gene will lead to more accurate diagnosis of lipoblastoma.
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- 2019
49. [Erratum] OBP‑801, a novel histone deacetylase inhibitor, induces M‑phase arrest and apoptosis in rhabdomyosarcoma cells
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Hajime Hosoi, Toshiyuki Sakai, Kunihiko Tsuchiya, Ken Kikuchi, Mitsuru Miyachi, Shigeki Yagyu, Chihiro Tomoyasu, Tomoko Iehara, and Daisuke Kaneda
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0301 basic medicine ,Cancer Research ,Cell cycle checkpoint ,Transcription, Genetic ,medicine.drug_class ,Mice, Nude ,Antineoplastic Agents ,Apoptosis ,Histone Deacetylases ,Inhibitor of Apoptosis Proteins ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Rhabdomyosarcoma ,Survivin ,medicine ,Animals ,Humans ,Cell Proliferation ,Mice, Inbred BALB C ,Chemistry ,Cell growth ,Cell Cycle ,Histone deacetylase inhibitor ,General Medicine ,Cell cycle ,medicine.disease ,Xenograft Model Antitumor Assays ,Pediatric cancer ,Histone Deacetylase Inhibitors ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,M Phase Cell Cycle Checkpoints ,Female ,Histone deacetylase ,Erratum - Abstract
Rhabdomyosarcoma (RMS) is an aggressive pediatric cancer of musculoskeletal origin. Despite multidisciplinary approaches, such as surgical resection, irradiation, and intensive chemotherapy, adopted for its treatment, the prognosis of patients with high‑risk RMS remains poor. Thus, molecularly targeted therapies are required to improve patient survival and minimize side effects. Histone deacetylases (HDACs) modify transcription by deacetylation of the lysine residues in chromatin histone tails and several non‑histone proteins. HDAC inhibitors, classes of compounds targeted to various HDAC proteins, are being studied for their roles in several types of cancers in a rigorous manner. This study aimed to investigate the potential of a novel HDAC inhibitor, OBP‑801, as a therapeutic agent for the treatment of RMS. We used 8 RMS cell lines in this study. Protein expression patterns, cell proliferation, cell cycle status, and apoptosis in RMS cells after OBP‑801 treatment in vitro were investigated. We also studied the antitumor activity of OBP‑801 in an in vivo xenograft mouse model. We observed cell cycle arrest at the M‑phase and apoptosis in all RMS cell lines after exposure to pharmacological levels of OBP‑801 for 24 h. Immunofluorescence staining revealed that OBP‑801 may induce mitotic catastrophe via chromosome misalignment and reduced survivin expression, ultimately leading to apoptosis. Our results demonstrated that the novel HDAC inhibitor OBP‑801 was an effective inhibitor of RMS cell line proliferation and may be a potent therapeutic option for RMS.
- Published
- 2019
50. A prospective evaluation of liquid biopsy for detecting MYCN amplification in neuroblastoma patients
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Hajime Hosoi, Kazutaka Ouchi, Shigeki Yagyu, Ken Kikuchi, Hideki Yoshida, Tohru Sugimoto, Takahiro Gotoh, Mitsuru Miyachi, and Tomoko Iehara
- Subjects
0301 basic medicine ,Male ,Cancer Research ,medicine.medical_specialty ,Gastroenterology ,Prospective evaluation ,Disease-Free Survival ,03 medical and health sciences ,Neuroblastoma ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,In patient ,Prospective Studies ,Liquid biopsy ,N-Myc Proto-Oncogene Protein ,business.industry ,Gene Amplification ,Liquid Biopsy ,Infant ,General Medicine ,medicine.disease ,Prognosis ,030104 developmental biology ,Oncology ,Cell-free fetal DNA ,MYCN Gene Amplification ,030220 oncology & carcinogenesis ,Child, Preschool ,Mycn amplification ,Risk stratification ,Female ,business - Abstract
Background Our previous study reported a method for determining MYCN gene amplification (MNA) status using cell-free DNA in serum. We prospectively analyzed the serum MNA status using sera obtained before the initial diagnosis from patients with neuroblastoma and evaluated the utility of this method. Methods Eighty patients were enrolled in the study. The serum MYCN/NAGK ratio was assessed for all cases. Results Fifteen cases showed serum MNA, while 65 did not. Of the 80 total patients, tumor samples for a genetic analysis were not obtained from 27 due to the patients’ condition or other reasons. For the 43 of 80 cases that had both serum and tumor samples analyzed, the serum-based MNA status matched to tumor-based MNA status (P < 0.001). The sensitivity and the specificity were 100%, respectively. Seven of 15 cases who diagnosed as MNA by serum-based MNA status were Conclusion The serum-based MNA status was useful for precisely predicting the MNA status in tumor and it has clinical benefits for predicting risk stratification in patients for whom obtaining tumor samples is difficult.
- Published
- 2019
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