Papers - MORITAKE Hiroshi
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Potential of boron neutron capture therapy (BNCT) for malignant peripheral nerve sheath tumors (MPNST). Reviewed
Fujimoto T, Andoh T, Sudo T, Fujita I, Fukase N, Takeuchi T, Sonobe H, Inoue M, Hirose T, Sakuma T,?Moritake H, Sugimoto T, Kawamoto T, Fukumori Y, Yamamoto S, Atagi S, Sakurai Y, Kurosaka M, Ono K, Ichikawa H, Suzuki M.
Appl Radiat Isot 2015.12
Language：English Publishing type：Research paper (scientific journal)
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Long-Term Morbidity and Mortality in Children with Chronic Graft-versus-Host Disease Classified by National Institutes of Health Consensus Criteria after Allogeneic Hematopoietic Stem Cell Transplantation. Reviewed
Inagaki J,?Moritake H, Nishikawa T, Hyakuna N, Okada M, Suenobu S, Nagai K, Honda Y, Shimomura M, Fukano R, Noguchi M, Kurauchi K, Tanioka S, Okamura J.
Biol Blood Marrow Transplant 2015.11
Language：English Publishing type：Research paper (scientific journal)
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Outcome of adolescent patients with acute myeloid leukemia treated with pediatric protocols Reviewed
Tomizawa D., Watanabe T., Hanada R., Horibe K., Horikoshi Y., Iwamoto S., Kinoshita A., Moritake H., Nakayama H., Shimada A., Taga T., Takahashi H., Tawa A., Terui K., Hori H., Kawano Y., Kikuta A., Manabe A., Adachi S.
International Journal of Hematology 102 ( 3 ) 318 - 326 2015.9
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
© 2015, The Japanese Society of Hematology. As past studies of adolescent and young adults (AYA) with acute myeloid leukemia (AML) reported conflicting results, we conducted a retrospective analysis using data from three Japanese pediatric AML studies. Among the 782 patients with de novo AML, 44 were classified as AYA (age ≥15 years at diagnosis), 164 as infants (0–1 year), 413 as younger children (2–11 years), and 161 as older children (12–14 years). While the 5-year event-free survival rate of AYA was not different among the groups, the five-year survival rate (54.7 %) was significantly lower than that of the other three groups (P = 0.019): 68.7 % for infants, 73.2 % for younger children, and 75.5 % for older children. No difference in the 5-year cumulative incidence of relapse was observed, but treatment-related death (TRD) of AYA was significantly higher (29.4 %) than that in infants (14.8 %), younger children (10.2 %), and older children (13.8 %). Multivariate analysis showed age ≥15 years old at diagnosis was associated with both poor survival rate and high TRD. Adolescents with AML had inferior survival due to a higher incidence of TRD, especially after failure of initial frontline treatment.
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Moritake H., Obara M., Sameshima N., Asada Y., Komatsu H., Hyakuna N., Sugita K., Ishida Y., Kato M., Tanizawa A., Deguchi T., Imamura T., Kitanaka A., Shimoda K., Kamimura S., Nunoi H.
International Journal of Hematology 102 ( 3 ) 349 - 356 2015.9
Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
© 2015, The Japanese Society of Hematology. Bone marrow necrosis (BMN) is a rare phenomenon in children with malignancies, occurring most commonly in patients with acute lymphoblastic leukemia (ALL). The pathophysiology of this phenomenon has not been identified. We analyzed seven BMN cases with ALL in order to elucidate the underlying mechanism. Serum high-mobility group box 1 (HMGB1), cytochrome C, cytokines, and chemokines were measured, and real-time quantitative reverse transcription-polymerase chain reaction (RQ-RT-PCR) and immunochemistry of death-related molecules were analyzed using bone marrow samples. The serum levels of 17 of 27 cytokines and chemokines were found to be significantly elevated in patients with BMN in comparison to those in healthy volunteers; however, IFN-γ and IL-10 were not elevated. The cytokine pattern was different to that reported in hemophagocytic lymphohistiocytosis. The HMGB1 and cytochrome C levels in patients with BMN were not elevated. RQ-RT-PCR revealed significant overexpression of Fas-ligand, perforin, and granzyme B in the bone marrow of patients with ALL complicated with BMN compared with that in healthy volunteers and in patients with ALL without BMN. On immunohistochemistry, we identified leukemic cell-eliciting Fas-ligand and macrophage-eliciting TNF-α. Thus, no close relationship with massive necrosis or the intrinsic pathway of apoptosis was identified in the occurrence of BMN. These results suggest that the massive cell death phenomenon called BMN is partially induced by the extrinsic pathway of apoptosis.
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Psychosocial difficulties in adolescent and young adult survivors of childhood cancer Reviewed
Takei Y., Ogata A., Ozawa M., Moritake H., Hirai K., Manabe A., Suzuki S.
Pediatrics International 57 ( 2 ) 239 - 246 2015.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Pediatrics International
© 2014 Japan Pediatric Society. Background With a large number of children surviving cancer worldwide, numerous investigations have assessed psychological and social adjustment among childhood cancer survivors. According to these studies, it is unclear whether childhood cancer survivors successfully adjust to daily life after being discharged from hospital, especially for adolescent and young adult survivors who have unique needs and concerns. The primary aim of this study was to identify the factors underlying psychosocial difficulties faced by adolescent and young adult survivors in their day-to-day lives after being discharged from hospital. Methods Semi-structured interviews were conducted. Twenty-five childhood cancer survivors were recruited from two regional cancer institutions in Japan. Content analysis was applied to the responses. Results Nineteen attributes were extracted and classified into four categories as follows: physical difficulties, interpersonal difficulties, behavioral difficulties, and uncertainty about the future. The attributes indicated by > 50% of the participants were "I am worried about not feeling well," "I have difficulty continuing treatment in daily life," "I have difficulty moving my body," "I have to be absent from school or work because of illness," and "I am left behind academically." Conclusions This study identified important factors of psychosocial day-to-day difficulties. Clinically, these results suggest that it is important to watch for these signs and to provide early support to survivors so that their daily life and development are not hindered by the treatment and its side-effects, and to offer long-term support focusing on individual patient characteristics such as sex, age, and cancer history.
DOI： 10.1111/ped.12495
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Proposed strategy for the use of high-dose chemotherapy with stem cell rescue and intrathecal topotecan without whole-brain irradiation for infantile classic medulloblastoma. Reviewed
Yamada A., Moritake H., Kamimura S., Yamashita S., Takeshima H., Nunoi H
Pediatr Blood & Cancer 2014.12
Language：English Publishing type：Research paper (scientific journal)
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プロプラノロールが著効した耳下腺部乳児血管腫の２例 Reviewed
下之段秀美、原田雅子、木下真理子、澤 大介、児嶋ひとみ、上村幸代、盛武 浩、松田圭三、布井博幸
宮崎県医師会雑誌 38 ( 2 ) 110 - 114 2014.9
Language：Japanese Publishing type：Case report
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Sakaguchi H., Nishio N., Hama A., Kawashima N., Wang X., Narita A., Doisaki S., Xu Y., Muramatsu H., Yoshida N., Takahashi Y., Kudo K., Moritake H., Nakamura K., Kobayashi R., Ito E., Yabe H., Ohga S., Ohara A., Kojima S.
Haematologica 99 ( 8 ) 1312 - 1316 2014.8
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Haematologica
Predicting the response to immunosuppressive therapy could provide useful information to help the clinician define treatment strategies for patients with aplastic anemia. In our current study, we evaluated the relationship between telomere length of lymphocytes at diagnosis and the response to immunosuppressive therapy in 64 children with aplastic anemia, using flow fluorescence in situ hybridization. Median age of patients was ten years (range 1.5-16.2 years). Severity of the disease was classified as very severe in 23, severe in 21, and moderate in 20 patients. All patients were enrolled in multicenter studies using antithymocyte globulin and cyclosporine. The response rate to immunosuppressive therapy at six months was 52% (33 of 64). The probability of 5-year failure-free survival and overall survival were 56% (95% confidence interval (CI): 41-69%) and 97% (95%CI: 87-99%), respectively. Median telomere length in responders was -0.4 standard deviation (SD) (-2.7 to +3.0 SD) and -1.5 SD (-4.0 to +1.6 (SD)) in non-responders (P < 0.001). Multivariate analysis showed that telomere length shorter than -1.0 SD (hazard ratio (HR): 22.0; 95%CI: 4.19-115; P < 0.001), platelet count at diagnosis less than 25×10 9 /L (HR: 13.9; 95%CI: 2.00-96.1; P=0.008), and interval from diagnosis to immunosuppressive therapy longer than 25 days (HR: 4.81; 95%CI: 1.15-20.1; P=0.031) were the significant variables for poor response to immunosuppressive therapy. Conversely to what has been found in adult patients, measurement of the telomere length of lymphocytes at diagnosis is a promising assay in predicting the response to immunosuppressive therapy in children with aplastic anemia. © 2014 Ferrata Storti Foundation.
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Nakayama H., Tabuchi K., Tawa A., Tsukimoto I., Tsuchida M., Morimoto A., Yabe H., Horibe K., Hanada R., Imaizumi M., Hayashi Y., Hamamoto K., Kobayashi R., Kudo K., Shimada A., Miyamura T., Moritake H., Tomizawa D., Taga T., Adachi S.
International Journal of Hematology 100 ( 2 ) 171 - 179 2014.8
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
The outcomes of children with relapsed acute myeloid leukemia (AML) are known to be poor, but remain obscure. We retrospectively analyzed 71 patients who had relapsed following first-line treatment under the AML99 protocol. We investigated the time and site of recurrence, response to re-induction therapy, and performance of hematopoietic stem cell transplantation (HSCT) in relapsed cases, and performed a multivariate analysis to identify prognostic factors. The 5-year overall-survival (OS) rate after relapse was 37 %. Of 71 patients, three died without any anti-leukemic therapy and two underwent allogeneic HSCT. The remaining 66 patients received re-induction chemotherapy, and 33 (50 %) achieved second CR (CR2). Twenty-two of 25 (88 %) late relapse patients and 11 of 41 (27 %) early relapse patients achieved CR2 (P < 0.001). Twenty-nine CR2 cases and 35 non-CR2 cases underwent allogeneic HSCT. The 5-year OS rate was significantly higher in patients who underwent HSCT in CR2 than those in non-CR2 (66 vs. 17 %, P < 0.000001). Multivariate analysis indicated that early relapse (P < 0.05) and the positivity of the FMS-like tyrosine kinase 3-internal tandem duplication (P < 0.05) were adverse prognostic factors for survival. In conclusion, the etiology of relapsed pediatric AML needs to be elucidated and effective chemotherapy should be administered to obtain CR2. © 2014 The Japanese Society of Hematology.
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Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: A Japanese retrospective study by the Kyushu-Yamaguchi Children’s Cancer Study Group. Reviewed
Moritake H, Kamimura S, Nunoi H, Nakayama H, Suminoe A, Inada H, Inagaki J, Yanai F, Okamoto Y, Shinkoda Y, Shimomura M, Itonaga N, Hotta N, Hidaka Y, Ohara O, Yanagimachi M, Nakajima N, Okamura J, Kawano Y
Int J Hematol 2014.7
Language：English Publishing type：Research paper (scientific journal)
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Andoh T., Fujimoto T., Sudo T., Suzuki M., Sakurai Y., Sakuma T., Moritake H., Sugimoto T., Takeuchi T., Sonobe H., Epstein A., Fukumori Y., Ono K., Ichikawa H.
Applied Radiation and Isotopes 88 59 - 63 2014.6
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Applied Radiation and Isotopes
Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In our previous study, the tumor disappeared under boron neutron capture therapy (BNCT) on subcutaneously-transplanted CCS-bearing animals. In the present study, the tumor disappeared under this therapy on model mice intramuscularly implanted with three different human CCS cells. BNCT led to the suppression of tumor-growth in each of the different model mice, suggesting its potentiality as an alternative to, or integrative option for, the treatment of CCS. © 2013 Elsevier Ltd.
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Kawano N., Tasaki A., Kuriyama T., Tahara Y., Yoshida S., Ono N., Himeji D., Yamashita K., Shibata Y., Goto T., Inoue T., Yokota-Ikeda N., Uezono S., Yuge A., Nishiguchi T., Kinjo T., Ogura Y., Beppu K., Ueda Y., Kinoshita M., Moritake H., Shimoda K., Ochiai H., Ueda A.
Internal Medicine 53 ( 3 ) 205 - 213 2014.2
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Internal Medicine
Objective Disseminated intravascular coagulation (DIC) is a clinical condition with high mortality that is characterized by the systemic activation of coagulation pathways resulting in multiple organ failure. Although no standard treatment for DIC has been established, recent reports have indicated that recombinant human soluble thrombomodulin (rTM) is effective against DIC. Methods To elucidate the clinical characteristics and outcomes of DIC, we retrospectively analyzed 92 DIC patients who were treated with rTM at Miyazaki Prefectural Hospital over a 4-year period (62 patients had infectious diseases and 30 patients had hematological diseases). A diagnosis of DIC was made based on the diagnostic criteria of the Japanese Association for Acute Medicine (JAAM) and Japanese Ministry of Health and Welfare (JMHW) for infectious diseases and hematological diseases, respectively. In addition to treating the underlying disease, rTM was administered for six consecutive days. Results In this study, 49 of the 92 DIC patients (53.3%) experienced resolution of DIC seven days after administration (46.8% patients with infectious disease and 66.7% with hematological disease). A higher survival rate was observed after a 28-day observation period in 69 of the 92 patients (75.0%) (72.6% of the patients with infectious disease and 80.0% of the patients with hematological disease). A lower DIC score at the initiation of rTM treatment was closely related to a higher rate of resolution of DIC. Conclusion Our findings indicate that rTM therapy is an effective, safe and feasible treatment for DIC patients. Furthermore, making an accurate and early diagnosis of DIC and providing subsequent immediate treatment with rTM may improve the resolution of DIC. © 2014 The Japanese Society of Internal Medicine.
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Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: a Japanese retrospective study by the Kyushu-Yamaguchi Children's Cancer Study Group Reviewed
Hiroshi Moritake 1, Sachiyo Kamimura, Hiroyuki Nunoi, Hideki Nakayama, Aiko Suminoe, Hiroko Inada, Jiro Inagaki, Fumio Yanai, Yasuhiro Okamoto, Yuichi Shinkoda, Maiko Shimomura, Nobuyoshi Itonaga, Noriko Hotta, Yasufumi Hidaka, Osamu Ohara, Masakatsu Yanagimachi, Noriko Nakajima, Jun Okamura, Yoshifumi Kawano
Int J Hematol 2014.1
Authorship：Lead author Publishing type：Research paper (scientific journal)
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Excess treatment reduction including anthracyclins results in higher incidence of relapse in core binding factor acute myeloid leukemia in children. Reviewed
Tomizawa D., Tawa A., Watanabe T., Saito AM, Kudo K., Taga T, Iwamoto S., Shimads A., Terui K., Moritake H., Kinoshita A., Takahashi H., Nakayama H., Koh K., KIgasawa H., Kosaka Y., Miyachi H., Horibe K., Nakahata T., Adachi S
Leukemia 27 ( 12 ) 2413 - 2416 2013.12
Language：English Publishing type：Research paper (scientific journal)
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Appropriate dose reduction in induction therapy is essential for the treatment of infants with acute myeloid leukemia: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group Reviewed
Tomizawa D., Tawa A., Watanabe T., Saito AM, Kudo K., Taga T, Iwamoto S., Shimads A., Terui K., Moritake H., Kinoshita A., Takahashi H., Nakayama H., Kiyokawa N., Isoyama K., MIzutani S., Hara J., Horibe K., Nakahata T., Adachi S
Int J Hematol 98 ( 5 ) 578 - 588 2013.11
Language：English Publishing type：Research paper (scientific journal)
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Ewing Sarcoma Cells Secrete EWS/Fli-1 Fusion mRNA via Microvesicles Reviewed
Tsugita M., Yamada N., Noguchi S., Yamada K., Moritake H., Shimizu K., Akao Y., Ohno T.
PLoS ONE 8 ( 10 ) 2013.10
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：PLoS ONE
Tumours defined as Ewing sarcoma (ES) constitute a group of highly malignant neoplasms that most often affect children and young adults in the first 2 decades of life. The EWS/Fli-1 fusion gene, a product of the translocation t(11;22) (q24; 12), is detected in 95% of ES patients. Recently, it was validated that cells emit a heterogeneous mixture of vesicular, organelle-like structures (microvesicles, MVs) into their surroundings including blood and body fluids, and that these MVs contain a selected set of tumor-related proteins and high levels of mRNAs and miRNAs. In this present study, we detected the Ewing sarcoma-specific EWS/Fli-1 mRNA in MVs from the culture medium of ES cell lines carrying t(11;22) (q24; 12). Also, we detected this fusion gene in approximately 40% of the blood samples from mice inoculated with xenografts of TC135 or A673 cells. These findings indicate the EWS/Fli-1 mRNA in MVs might be a new non-invasive diagnostic marker for specific cases of Ewing sarcoma. © 2013 Tsugita et al.
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YAMADA Ai, MORITAKE Hiroshi, SAWA Daisuke, SHIMONODAN Hidemi, KOJIMA Hitomi, KAMIMURA Sachiyo, NUNOI Hiroyuki
Rinsho Ketsueki 54 ( 4 ) 383 - 387 2013.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Hematology
We here report a 2-year-old female with relapsed acute myeloid leukemia (AML) with MLL gene rearrangement in the bone marrow and central nervous system. The 3'-RACE (Rapid Amplification of cDNA Ends) method identified the MLLT10 gene as a fusion partner of the MLL gene. The patient was complicated with hemophagocytic lymphohistiocytosis (HLH) and invasive aspergillosis (IPA) after re-induction treatment with FLAG-IDA following etoposide, cytarabine, and mitoxantrone. Although treatment with systemic anti-fungal drugs was effective for IPA, HLH did not improve. We considered tumor-associated HLH to be initiated from leukemic stem cells (LSCs) in the bone marrow niche because reverse transcription-polymerase chain reaction (RT-PCR) analysis of a bone marrow biopsy sample was positive for MLL-MLLT10. Gemtuzumab ozogamicin and sorafenib had no major effect on acquiring complete remission, and the patient died of progressive AML with an exacerbation of HLH and aspergillosis. LSCs are known to be resistant to conventional chemotherapy due to their quiescence in the cell cycle. Novel therapeutic concepts are important to eradicate LSCs in order to cure AML patients.
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小児急性前骨髄球性白血病に対する三酸化ヒ素による治療 Reviewed
高橋浩之、盛武 浩、照井君典、井上彰子、落合秀匡、金井理恵、豊田秀実、松野良介、塩原正明、中尾朋平、富澤大輔、多賀崇、多和昭雄、足立壮一
日本小児血液・がん学会誌 50 ( 1 ) 32 - 37 2013.4
Language：Japanese Publishing type：Research paper (scientific journal)
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Yamada A., Moritake H., Sawa D., Shimonodan H., Kojima H., Kamimura S., Nunoi H.
[Rinshō ketsueki] The Japanese journal of clinical hematology 54 ( 4 ) 383 - 387 2013.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：[Rinshō ketsueki] The Japanese journal of clinical hematology
We here report a 2-year-old female with relapsed acute myeloid leukemia (AML) with MLL gene rearrangement in the bone marrow and central nervous system. The 3'-RACE (Rapid Amplification of cDNA Ends) method identified the MLLT10 gene as a fusion partner of the MLL gene. The patient was complicated with hemophagocytic lymphohistiocytosis (HLH) and invasive aspergillosis (IPA) after re-induction treatment with FLAG-IDA following etoposide, cytarabine, and mitoxantrone. Although treatment with systemic anti-fungal drugs was effective for IPA, HLH did not improve. We considered tumor-associated HLH to be initiated from leukemic stem cells (LSCs) in the bone marrow niche because reverse transcription-polymerase chain reaction (RT-PCR) analysis of a bone marrow biopsy sample was positive for MLL-MLLT10. Gemtuzumab ozogamicin and sorafenib had no major effect on acquiring complete remission, and the patient died of progressive AML with an exacerbation of HLH and aspergillosis. LSCs are known to be resistant to conventional chemotherapy due to their quiescence in the cell cycle. Novel therapeutic concepts are important to eradicate LSCs in order to cure AML patients.
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Boron neutron capture therapy (BNCT) selectively destroys human clear cell sarcoma in mouse model Reviewed
Fujimoto T., Andoh T., Sudo T., Fujita I., Moritake H., Sugimoto T., Sakuma Y., Akisue T., Kawabata S., Kirihara M., Suzuki M., Sakurai Y., Ono K., Fukumori Y., Kurosaka M., Ichikawa H.
Applied Radiation and Isotopes 73 96 - 100 2013.3
Language：English Publishing type：Research paper (scientific journal)