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所属 |
医学部 医学科 発達泌尿生殖医学講座小児科学分野 |
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職名 |
特別准教授 |
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外部リンク |
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Nagasawa S., Yamada A., Kinoshita M., Kamimura S., Moritake H.
Pediatrics international : official journal of the Japan Pediatric Society 64 ( 1 ) e14970 2022年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Pediatrics international : official journal of the Japan Pediatric Society
DOI： 10.1111/ped.14970
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Kinoshita M., Yamada A., Saito Y., Kamimura S., Moritake H.
Pediatrics international : official journal of the Japan Pediatric Society 64 ( 1 ) e14975 2022年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Pediatrics international : official journal of the Japan Pediatric Society
DOI： 10.1111/ped.14975
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Yoshikawa N., Yamada A., Yokota T., Yamada Y., Kinoshita M., Moritake H., Ikeda R.
Cancers 13 ( 18 ) 2021年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cancers
Intrathecal administration of anticancer drugs is an effective dosage strategy, but the elimination of intraventricular drugs is not uniform in all patients. For safety, a system to evaluate local pharmacokinetics in the ventricles after administration is desired. In this study, we developed a simple and reproducible method to measure topotecan concentration in the cerebrospinal fluid (CSF) and confirmed its clinical applicability. High-performance liquid chromatography (HPLC) analysis was performed using a C18 column to measure the total topotecan concentration in the CSF. Clinical CSF samples were obtained from a 1-year old child with poor CSF absorption and stagnation. The patient received topotecan via an intraventricular subcutaneous reservoir. The HPLC method complied with the validation criteria. The lower limit of quantitation of this method was 0.04 µM. Using the developed method, we could determine the difference in topotecan CSF concentrations at 24 and 48 h after administration. The patient’s topotecan elimination rate was extremely low, and signs of adverse effects were observed at high CSF concentration of topotecan. The developed method could detect the delay in topotecan elimination after intrathecal injection. The findings of this study are valuable for the development of personalized treatments for the intrathecal administration of anticancer drugs.
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Yamada A., Kinoshita M., Kamimura S., Nakame K., Moritake H.
Journal of Pediatric Hematology/Oncology 44 ( 2 ) E589 - E592 2021年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Pediatric Hematology/Oncology
Neuroblastoma with bone metastasis is well known to have an extremely poor prognosis. We experienced the case of a patient with adrenal ganglioneuroblastoma (GNB) with metastases of subcutaneous nodules, a lymph node, and multiple bones. A pathologic examination of tumors from different sites revealed both GNB and ganglioneuroma. A genetic comparison between these tumors identified the same molecular signatures, suggesting the possibility of spontaneous differentiation in the remaining GNB. The patient has been healthy without aggressive chemotherapy, and the patient's pathologic urinary catecholamines normalized. Even if unusual, we have to recognize probable spontaneous differentiation from neuroblastoma to GNB and then to ganglioneuroma, even in sites of bone metastasis.
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Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia
Saito Y., Kinoshita M., Yamada A., Kawano S., Liu H.S., Kamimura S., Nakagawa M., Nagasawa S., Taguchi T., Yamada S., Moritake H.
Cancer Science 112 ( 12 ) 4944 - 4956 2021年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cancer Science
Diverse metabolic changes are induced by various driver oncogenes during the onset and progression of leukemia. By upregulating glycolysis, cancer cells acquire a proliferative advantage over normal hematopoietic cells; in addition, these changes in energy metabolism contribute to anticancer drug resistance. Because leukemia cells proliferate by consuming glucose as an energy source, an alternative nutrient source is essential when glucose levels in bone marrow are insufficient. We profiled sugar metabolism in leukemia cells and found that mannose is an energy source for glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway. Leukemia cells express high levels of phosphomannose isomerase (PMI), which mobilizes mannose to glycolysis; consequently, even mannose in the blood can be used as an energy source for glycolysis. Conversely, suppression of PMI expression or a mannose load exceeding the processing capacity of PMI inhibited transcription of genes related to mitochondrial metabolism and the TCA cycle, therefore suppressing the growth of leukemia cells. High PMI expression was also a poor prognostic factor for acute myeloid leukemia. Our findings reveal a new mechanism for glucose starvation resistance in leukemia. Furthermore, the combination of PMI suppression and mannose loading has potential as a novel treatment for driver oncogene-independent leukemia.
DOI： 10.1111/cas.15138
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Prevention of cisplatin-induced hearing-loss by sodium thiosulfate in medulloblastoma
Harao T., Yamada A., Kinoshita M., Kamimura S., Moritake H.
Pediatrics International 62 ( 10 ) 1204 - 1206 2020年10月
記述言語：日本語 掲載種別：速報，短報，研究ノート等（学術雑誌） 出版者・発行元：Pediatrics International
DOI： 10.1111/ped.14271