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YAMAMOTO NobuyukiGraduate School of Medicine / Faculty of Medical SciencesAssociate Professor
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■ Paper- Accurate assessment of vital signs is important for reducing mortality. The aim of this study was to validate the effectiveness and safety of noncontact vital sign sensors. Interference tests were conducted with a noncontact vital sign sensor and medical devices. Inpatients' heart and respiratory rates were monitored via this sensor, and the measurements of this sensor were compared with those of reference medical equipment. Noncontact vital sign sensors and medical devices did not interfere with each other. A total of 21 patients (10 adults and 11 children, including 1 baby) were analysed. For all patients, the correlation coefficients for the HR and RR were 0.86 and 0.96, respectively. In adult patients, the correlation coefficients for the HR and RR were 0.75 and 0.96, respectively. In paediatric patients, the correlation coefficients for the HR and RR were 0.82 and 0.94, respectively. No effects of noncontact vital sign sensors on patients, surrounding patients or medical equipment were observed. Noncontact vital sign sensors are accurate and safe.May 2025, Scientific reports, 15(1) (1), 17269 - 17269, English, International magazineScientific journal
- Wiedemann-Steiner syndrome (WSS) is a congenital malformation syndrome characterized by intellectual disability, developmental delay, and distinctive facial features, caused by germline mutations in the KMT2A gene. Despite the key role of KMT2A in hematopoiesis, leukemia has not been previously reported in WSS patients. This report presents the first documented case of acute lymphoblastic leukemia (ALL) in a WSS patient. A 16-year-old boy with developmental delay, distinct facial features, and genital abnormalities was diagnosed with WSS following the identification of a heterozygous frameshift mutation in KMT2A. At age 17, he developed T-cell ALL harboring the KMT2A-CBL fusion gene, of which only nine cases have been reported so far. cDNA sequence analysis of the KMT2A-CBL transcript at the site of the germline KMT2A pathogenic variant revealed a wild-type sequence, indicating that the KMT2A-CBL fusion occurred on the wild-type allele. While this observation suggests a potential cooperative role of the KMT2A-CBL chimeric gene and the germline KMT2A pathogenic mutation in leukemogenesis, the rarity of leukemia in WSS underscores the need for cautious interpretation. This case provides preliminary insights into a possible mechanism of leukemogenesis in WSS, but further studies are required to clarify the relationship between WSS and ALL.Mar. 2025, International journal of hematology, English, Domestic magazineScientific journal
- The prognosis of patients with osteosarcoma who experience recurrence or progression (R/P) is extremely poor, and more effective and less toxic therapies are needed. In the current study, the clinical data of osteosarcoma patients who experienced R/P were retrospectively analyzed to verify the reliability of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression or MGMT promoter methylation for predicting the response to off-label temozolomide (TMZ)-containing chemotherapy. Of the 30 evaluable patients, 9 (30%) showed no/low MGMT protein expression, whereas all 16 evaluable patients had unmethylated MGMT promoter irrespective of MGMT protein expression levels. Twenty-three patients received TMZ-containing chemotherapy for measurable lesions (n = 14) or as adjuvant therapy following resection of recurrent lesions (n = 9). Among 14 patients with radiologically measurable lesions, the objective response rate was higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group with borderline significance (0%, p = 0.066). The 6-month progression-free survival (PFS) rate in patients with radiologically measurable lesions was significantly higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group (0%, p = 0.036). In the multivariate analysis of the 23 patients receiving TMZ-containing chemotherapy, MGMT expression and disease status before TMZ-containing chemotherapy were significantly associated with PFS. No severe adverse effects were observed during TMZ-containing chemotherapy. MGMT protein expression, but not MGMT promoter methylation, could predict a favorable outcome in patients receiving TMZ-containing chemotherapy.Oct. 2024, Cancer science, 115(10) (10), 3394 - 3402, English, International magazineScientific journal
- Abstract Hypomethylating agent treatment for myeloid leukemia associated with Down syndrome (ML‐DS) has been scarcely reported. Herein, we collected information on azacitidine treatment for ML‐DS in Japan. Forty‐eight cycles of azacitidine treatment were performed for 12 patients, including 11 relapsed or refractory (R/R) patients. In 40 cycles, azacitidine was used as monotherapy. No azacitidine‐related death was observed. One cycle concurrently administered with methotrexate‐based intrathecal therapy was discontinued due to toxicities. Only 4 of the 19 cycles given in non‐remission achieved complete or partial remission. In conclusion, although most toxicities were acceptable, azacitidine monotherapy might be insufficient for R/R ML‐DS cases.Wiley, Aug. 2024, Pediatric Blood & Cancer, 71(10) (10), e31244, English, International magazineScientific journal
- (一社)日本小児血液・がん学会, Jul. 2024, 日本小児血液・がん学会雑誌, 61(2) (2), 176 - 183, Japanese
- Non-high-risk (non-HR) neuroblastoma (NB) patients have excellent outcomes, with more than a 90% survival rate, whereas HR NB patients expect less than a 50% survival rate. Metastatic disease is the principal cause of death among both non-HR and HR NB patients. Previous studies have reported the significant but limited prognostic value of quantitative PCR (qPCR)-based assays, measuring overlapping but different sets of neuroblastoma-associated mRNAs (NB-mRNAs), to detect metastatic disease in both non-HR and HR patient samples. A droplet digital PCR (ddPCR)-based assay measuring seven NB-mRNAs (CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNAs) was recently developed and exhibited a better prognostic value for HR patient samples than qPCR-based assays. However, it remained to be tested on non-HR patient samples. In the present study, we employed the ddPCR-based assay to study peripheral blood (PB) and bone marrow (BM) samples collected at diagnosis from eight non-HR and eleven HR cases and characterized the expression profiles of NB-mRNAs. The most highly expressed NB-mRNAs in PB and BM differed between non-HR and HR cases, with the CRMP1 mRNA being predominant in non-HR cases and the GAP43 mRNA in HR cases. The levels of NB-mRNAs in PB and BM were 5 to 1000 times lower in non-HR cases than in HR cases. The PB to BM ratio of NB-mRNAs was 10 to 100 times higher in non-HR cases compared to HR cases. The present case series suggests that non-HR and HR NB patients have the distinct expression profiles of NB-mRNAs in their PB and BM.May 2024, Biology, 13(5) (5), English, International magazineScientific journal
- (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 631 - 632, Japanese国産手術支援ロボットhinotoriによるロボット支援下左副腎褐色細胞腫摘出術を行った1例
- (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 624 - 624, Japanese潰瘍性大腸炎の発症時に免疫性血小板減少症を合併した1例
- (一社)中部日本整形外科災害外科学会, Apr. 2024, 中部日本整形外科災害外科学会雑誌, 67(春季学会) (春季学会), 175 - 175, Japanese小児脛骨に発症したBCG骨髄炎の1例
- (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 631 - 632, Japanese国産手術支援ロボットhinotoriによるロボット支援下左副腎褐色細胞腫摘出術を行った1例
- Recently, heterozygous loss-of-function NFKB1 variants were identified as the primary cause of common variable immunodeficiency (CVID) in the European population. However, pathogenic NFKB1 variants have never been reported in the Japanese population. We present a 29-year-old Japanese woman with CVID. A novel variant, c.136 C > T, p.(Gln46*), was identified in NFKB1. Her mother and daughter carried the same variant, demonstrating the first Japanese pedigree with an NFKB1 pathogenic variant.Mar. 2024, Human Genome Variation, 11(1) (1), 15 - 15, English, International magazineScientific journal
- (一社)日本小児血液・がん学会, Mar. 2024, 日本小児血液・がん学会雑誌, 60(5) (5), 297 - 300, Japanese
- (一社)日本小児神経学会, Mar. 2024, 脳と発達, 56(2) (2), 152 - 152, Japanese
- (一社)日本小児血液・がん学会, Mar. 2024, 日本小児血液・がん学会雑誌, 60(5) (5), 297 - 300, Japanese
- (公社)日本小児科学会, Feb. 2024, 日本小児科学会雑誌, 128(2) (2), 238 - 238, EnglishMGMTタンパク発現は骨肉腫に対するテモゾロミド併用化学療法の治療効果予測に有用なバイオマーカーとなりうる(MGMT protein expression is a reliable predictive biomarker for temozolomide-containing chemotherapy against osteosarcoma)
- (公社)日本小児科学会, Feb. 2024, 日本小児科学会雑誌, 128(2) (2), 238 - 238, EnglishMGMTタンパク発現は骨肉腫に対するテモゾロミド併用化学療法の治療効果予測に有用なバイオマーカーとなりうる(MGMT protein expression is a reliable predictive biomarker for temozolomide-containing chemotherapy against osteosarcoma)
- More than half of patients with high-risk neuroblastoma (HR-NB) experience relapse/regrowth due to the activation of chemoresistant minimal residual disease (MRD). MRD in patients with HR-NB can be evaluated by quantitating neuroblastoma-associated mRNAs (NB-mRNAs) in bone marrow (BM) and peripheral blood (PB) samples. Although several sets of NB-mRNAs have been shown to possess a prognostic value for MRD in BM samples (BM-MRD), MRD in PB samples (PB-MRD) is considered to be low and difficult to evaluate. The present report describes an HR-NB case presenting higher PB-MRD than BM-MRD before 1st and 2nd relapse/regrowth. A 3-year-old female presented with an abdominal mass, was diagnosed with HR-NB, and treated according to the nationwide standard protocol for HR-NB. Following systemic induction and consolidation therapy with local therapy, the patient achieved complete remission but experienced a 1st relapse/regrowth 6 months after maintenance therapy. The patient partially responded to salvage chemotherapy and anti-GD2 immunotherapy but had a 2nd relapse/regrowth 14 months after the 1st relapse/regrowth. Consecutive PB-MRD and BM-MRD monitoring revealed that PB-MRD was lower than BM-MRD at diagnosis (100 times) and 1st and 2nd relapse/regrowth (1,000 and 3 times) but became higher than BM-MRD before 1st and 2nd relapse/regrowth. The present case highlights that PB-MRD can become higher than BM-MRD before relapse/regrowth of patients with HR-NB.Sep. 2023, Oncology letters, 26(3) (3), 369 - 369, English, International magazineScientific journal
- May 2023, American journal of hematology, 98(5) (5), E102-E105, English, International magazine
- (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 625 - 625, Japanese汎血球減少と斜指を契機に診断したMECOM関連症候群の女児
- (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 632 - 632, Japanese血性鼻汁をきっかけに診断したLCHの男児
- (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 625 - 626, Japanese一過性の細胞免疫不全所見を認めた超早期発症型炎症性腸疾患の1例
- BACKGROUND: Preventing infection and managing febrile neutropenia (FN) is mandatory for children with cancer undergoing chemotherapy. However, the current situation in Japan is unknown. METHODS: We conducted a nationwide web-based questionnaire survey in 153 institutions treating childhood cancer in Japan. We asked about the type prophylaxis used to prevent infectious disease and manage FN. If patients with childhood cancer were managed by both pediatricians and surgeons at the same institution, we asked both to reply. RESULTS: We received replies from 117 departments at 111 centers: of these, 108 were from pediatricians. Laminar air flow for neutropenic patients, and frequent hand sanitization with ethanol, were widespread. Twenty-eight percent and forty percent of departments performed active surveillance by taking cultures from patients and the environment, respectively, before initiation of chemotherapy. Forty-four percent of departments administered prophylactic intravenous antibiotics according to patient status. Many departments measured serum (1,3)-β-D glucan, procalcitonin, and aspergillus galactomannan at the onset of FN. Twenty-eight percent of departments used carbapenem as empirical therapy for FN. Some departments used prophylactic granulocyte-colony stimulating factor for acute leukemia. Seventy-two percent of departments used prophylactic immunoglobulin for hypogammaglobinemia caused by chemotherapy. Palivizumab was administered widely for respiratory syncytial virus prophylaxis in immunocompromised infants. CONCLUSION: As a whole, intensive care for infectious prophylaxis or FN is applied in Japan; however, the methods vary among centers, and some are excessive or inadequate. Therefore, it is desirable to conduct clinical trials and establish adequate care protocols for infection in children with cancer in Japan.Feb. 2023, International journal of clinical oncology, 28(2) (2), 331 - 340, English, Domestic magazineScientific journal
- 兵庫県小児科医会, 2023, 兵庫県小児科医会報, (79) (79), 13 - 17, Japanese
- Mutations in the MECOM encoding EVI1 are observed in infants who have radioulnar synostosis with amegakaryocytic thrombocytopenia. MECOM-associated syndrome was proposed based on clinical heterogeneity. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for progressive bone marrow failure. However, data regarding allogeneic HSCT for this rare disease are limited. We retrospectively assessed overall survival, conditioning regimen, regimen-related toxicities and long-term sequelae in six patients treated with allogeneic HSCT. All patients received a reduced-intensity conditioning (RIC) regimen consisting of fludarabine, cyclophosphamide or melphalan, and rabbit anti-thymocyte globulin and/or low-dose total body/thoracic-abdominal/total lymphoid irradiation, followed by allogeneic bone marrow or cord blood transplantation from unrelated donors between 4 and 18 months of age. All patients survived and achieved stable engraftment and complete chimerization with the donor type. Moreover, no patient experienced severe regimen-related toxicities, and only lower grades of acute graft-versus-host disease were observed. Three patients treated with low-dose irradiation had relatively short stature compared to three patients not treated with irradiation. Therefore, allogeneic HSCT with RIC is an effective and feasible treatment for infants with MECOM-associated syndrome. Future studies are needed to evaluate the use of low-dose irradiation to avoid risks of other long-term sequelae.Dec. 2022, International journal of hematology, 117(4) (4), 598 - 606, English, Domestic magazineScientific journal
- Infantile fibrosarcoma (IFS) commonly harbors ETS variant transcription factor 6 (ETV6)-neurotrophic receptor tyrosine kinase 3 (NTRK3) fusion. However, the recent accessibility to clinical next-generation sequencing (NGS) has revealed ETV6-NTRK3 negative spindle cell sarcomas resembling IFS morphologically, involving NTRK1/2, MET, RET and BRAF. The present report describes a pediatric case of spindle cell sarcoma with KIAA1549-BRAF resembling IFS morphologically. A 20-month-old female patient was referred to Kobe Children's Hospital (Kobe, Japan) for the treatment of intrathoracic spindle cell sarcoma. Pathologically, the intrathoracic tumor cells were composed of spindle cells with focal hemagiopericytomatous pattern. In immunohistochemistry analysis, the intrathoracic tumor cells focally expressed desmin and WT-1 and were negative for pan-tropomyosin receptor kinase (TRK), S-100 and CD34. Fluorescence in situ hybridization analysis for ETV6 and capicua transcriptional repressor revealed negative split signals. Although the patient was initially diagnosed with IFS morphologically, KIAA1549-BRAF fusion transcript was detected by comprehensive genomic profiling with NGS using intrathoracic tumor tissues and confirmed by reverse transcription-PCR. Chemotherapy induced a reduction in the tumor size. At present, the patient is alive with the disease and has been receiving therapy for 8 months since the initiation of chemotherapy. Review of BRAF-altered spindle cell sarcomas resembling IFS morphologically revealed the inconsistency in immunohistochemical expression patterns and the diversity of BRAF fusion genes and mutations. Therefore, the elucidation of genomic profiling by NGS may assist in making an appropriate diagnosis and selecting novel alternative therapies in ETV6-NTRK3-negative spindle cell sarcomas resembling IFS morphologically.Dec. 2022, Oncology letters, 24(6) (6), 452 - 452, English, International magazineScientific journal
- More than half of high-risk neuroblastoma (NB) patients have experienced relapse due to the activation of chemoresistant minimal residual disease (MRD) even though they are treated by high-dose chemotherapy with autologous peripheral blood stem cell (PBSC) transplantation. Although MRD in high-risk NB patients can be evaluated by quantitative PCR with several sets of neuroblastoma-associated mRNAs (NB-mRNAs), the prognostic significance of MRD in PBSC grafts (PBSC-MRD) is unclear. In the present study, we collected 20 PBSC grafts from 20 high-risk NB patients and evaluated PBSC-MRD detected by droplet digital PCR (ddPCR) with 7NB-mRNAs (CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNA). PBSC-MRD in 11 relapsed patients was significantly higher than that in 9 non-relapsed patients. Patients with a higher PBSC-MRD had a lower 3-year event-free survival (P = 0.0148). The present study suggests that PBSC-MRD detected by ddPCR with 7NB-mRNAs has a prognostic impact on high-risk NB patients.Oct. 2022, Heliyon, 8(10) (10), e10978, English, International magazineScientific journal
- (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 557 - 557, Japanese小児科医の意識調査 大事にする価値観は?兵庫県で次に取り組むべき課題は?
- (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 547 - 547, Japanese兵庫県における治療可能となった難病に対する拡大新生児マススクリーニングの取り組み
- (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 547 - 547, Japanese5歳児検尿を契機に発見されたSchimke症候群の1例
- CONTEXT: Few instruments in Japanese assess health-related quality of life in pediatric cancer patients. OBJECTIVES: To translate the Memorial Symptom Assessment Scale (MSAS) into Japanese pediatric and proxy versions (MSAS-J 7-12, MSAS-J 13-18, and MSAS-J-Proxy) and assess validity and reliability. METHODS: Phase I comprised forward-backward translation and pilot testing in 13 children and 16 guardians. Phase II consisted of psychometric testing of the three MSAS-J versions in 164 children and 238 guardians. Internal consistency, test-retest reliability, and construct and known-group validity of the MSAS-J were assessed. RESULTS: Cronbach's alpha coefficients for the total and subscale scores were over 0.70, excluding the psychological symptom (PSYCH) subscale score of the MSAS-J 7-12. Most MSAS-J scores significantly inversely correlated with two versions of the Pediatric Quality of Life Inventory. A strong child-guardian correlation was shown in the total and subscale scores (ICC range 0.66-0.83). Kappa estimates showed acceptable child-guardian symptom agreement. MSAS-J 7-12 and proxy differentiated patients according to clinical status. CONCLUSION: MSAS-J is a reliable and valid instrument to assess symptoms among Japanese children with cancer.Jan. 2022, Journal of pain and symptom management, 63(5) (5), e495-e504, English, International magazineScientific journal
- BACKGROUND: An unprovoked seizure is a seizure or a cluster of seizures occurring within 24 h in a patient older than 1 month of age without precipitating factors. Recent studies have reported that extrinsic factors, such as meteorological conditions and air pollutants, may be important in seizure occurrence. Thus, this study aimed to examine the association between the number of visits to the emergency department (ED) by children for nighttime unprovoked seizures and exposure to multi-faceted factors, such as meteorological conditions and air pollution. METHODS: We conducted a clinical observational analysis and reviewed consecutive patients younger than 16 years of age who visited the primary ED center in Kobe City, Japan, during nighttime (7:30 p.m.-7:00 a.m.) between January 1, 2011 and December 31, 2015. We investigated the effects of meteorological factors and air pollutants on the number of patients with unprovoked seizures using multivariate analysis of Poisson regression estimates. RESULTS: In total, 151,119 children visited the ED, out of which 97 patients presented with unprovoked seizures. The mean age of the patients was 4.7 years (range, 1 month to 15.3 years), and 54.6% of them were boys. The total number of patients with unprovoked seizures showed no significant changes with the seasons; however, there were dominant peaks during the fall and fewer visits during the summer. The multivariate analysis of Poisson regression estimates revealed a significant positive relationship between the number of patients presenting with unprovoked seizures and precipitation (+1 patient/87 mm; p = 0.03) and methane (+1 patient/0.14 ppm; p = 0.03) levels and a negative relationship between the number of patients presenting with unprovoked seizures and nitrogen dioxide level (-1 patient/0.02 ppm; p = 0.04). CONCLUSIONS: The present study is the first to evaluate the association between the number of children who presented to the ED with nighttime unprovoked seizures and environmental factors after controlling for confounding factors.Dec. 2021, Epilepsy & behavior : E&B, 125, 108434 - 108434, English, International magazineScientific journal
- (一社)日本血液学会, Sep. 2021, 日本血液学会学術集会, 83回, PS - 2, English当科における小児造血細胞移植患者の精子保存(The sperm preservation in pediatric patients who underwent hematopoietic stem cell transplantation)
- (一社)日本血液学会, Sep. 2021, 日本血液学会学術集会, 83回, PS - 2, EnglishThe sperm preservation in pediatric patients who underwent hematopoietic stem cell transplantation(和訳中)
- (一社)日本小児血液・がん学会, Aug. 2021, 日本小児血液・がん学会雑誌, 58(2) (2), 175 - 181, Japanese
- (一社)日本小児血液・がん学会, Aug. 2021, 日本小児血液・がん学会雑誌, 58(2) (2), 175 - 181, Japanese
- Neuroblastoma (NB) is the most common extracranial solid tumor in children and originates from sympathoadrenal or Schwann cell precursors derived from neural crest. These neural crest derivatives also constitute the hematopoietic and mesenchymal stem cells in bone marrow (BM) that is the most frequent site of NB metastasis and relapse. In NB patients, NB cells have been pathologically detected in BM and peripheral blood (PB), and minimal residual disease (MRD) in BM and PB (BM-MRD and PB-MRD) can be monitored by quantitating several sets of NB-associated mRNAs (NB-mRNAs). Although previous studies have shown varying degrees of correlation between BM-MRD and PB-MRD, the underlying factors and/or mechanisms remains unknown. In the present study, we determined the levels of BM-MRD and PB-MRD by quantitating seven NB-mRNAs in 133 pairs of concurrently collected BM and PB samples from 19 high-risk NB patients with clinical disease evaluation, and examined their correlation in overall and subgroups of sample pairs. The levels of BM-MRD and PB-MRD were moderately (r = 0.418, p < 0.001) correlated with each other in overall sample pairs. The correlation became strong (r = 0.725, p < 0.001), weak (r = 0.284, p = 0.008), and insignificant (p = 0.194) in progression, stable, and remission subgroups of sample pairs, respectively. It also became stronger in subgroups of sample pairs with poor treatment responses and poor prognostic factors. Present study suggests that MRD in high-risk NB shows a dynamic and disease burden-dependent correlation between BM and PB.Aug. 2021, Translational oncology, 14(8) (8), 101019 - 101019, English, International magazineScientific journal
- BACKGROUND: X-linked inhibitor of apoptosis protein (XIAP) deficiency is an infrequent inborn error of immunity that is often associated with refractory inflammatory bowel disease (IBD). The natural course of XIAP deficiency is typically associated with poor prognosis, and hematopoietic cell transplantation (HCT) is the only curative treatment. OBJECTIVE: To study (1) the effect of HCT on patients with XIAP deficiency undergoing HCT, (2) the status of XIAP deficiency-associated IBD after HCT, and (3) the gut microbiota of XIAP deficiency-associated IBD before and after HCT. METHODS: A nationwide survey of patients with XIAP deficiency was conducted. A spreadsheet questionnaire was collected from the physicians. Feces samples collected from the patients before and after HCT and their healthy family members were analyzed. RESULTS: Twenty-six patients with XIAP deficiency underwent HCT by the end of March 2020, and 22 patients (84.6%) survived. All the survivors underwent a fludarabine-based reduced-intensity condition regimen. Acute graft-versus-host disease was observed in 17 patients (65.4%). Nineteen patients experienced refractory IBD before undergoing HCT. IBD improved remarkably after HCT. After HCT, the colonoscopic and pathological symptoms were restored to normal, and the pediatric ulcerative colitis activity index improved significantly. Gut microbiota indicated dysbiosis before HCT; however, it was improved to resemble that of the healthy family members after HCT. CONCLUSIONS: This study revealed that HCT has a favorable outcome for XIAP deficiency. HCT rescues gut inflammation and dysbiosis in patients with XIAP deficiency.Jul. 2021, The journal of allergy and clinical immunology. In practice, 9(10) (10), 3767 - 3780, English, International magazineScientific journal
- Vanillylmandelic acid (VMA), homovanillic acid (HVA), neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) are classical tumor markers and are used as standard clinical evaluations for patients with neuroblastoma (NB). Minimal residual disease (MRD) can be monitored by quantifying several sets of NB-associated mRNAs in the bone marrow (BM) and peripheral blood (PB) of patients with NB. Although MRD in BM and PB has been revealed to be a strong prognostic factor that is independent of standard clinical evaluations, its interrelation with tumor markers remains uncharacterized. The present study determined the levels of tumor markers (VMA, HVA, NSE and LDH) and MRD (BM-MRD and PB-MRD) in 133 pairs of concurrently collected BM, PB and urine samples from 19 patients with high-risk NB. The patients were evaluated during the entire course of treatment, which included 10 diagnoses, 32 treatments, 36 post-treatment, 9 relapses and 46 post-relapse sample pairs. The level of BM-MRD and PB-MRD was determined by quantifying 7 NB-mRNAs (collapsin response mediator protein 1, dopamine beta-hydroxylase, dopa decarboxylase, growth-associated protein 43, ISL LIM homeobox 1, pairedlike homeobox 2b and tyrosine hydroxylase) using droplet digital PCR. In overall sample pairs, tumor markers (VMA, HVA, NSE and LDH) demonstrated weak but significant correlations (P<0.011) with BM-MRD and PB-MRD. In subgroups according to each patient evaluation, the degree of correlation between tumor markers and MRD became stronger in patients with adrenal gland tumors, BM metastasis at diagnosis and relapse/regrowth compared with overall sample pairs. In contrast, tumor markers demonstrated variable correlations with MRD in subgroups according to each sample evaluation (BM infiltration at sampling, collection time point and disease status). The results suggested that tumor markers may demonstrate limited correlation with MRD in patients with high-risk NB.Jul. 2021, Molecular and clinical oncology, 15(1) (1), 137 - 137, English, International magazineScientific journal
- 日本脳腫瘍病理学会, May 2021, Brain Tumor Pathology, 38(Suppl.) (Suppl.), 067 - 067, Japanese癌ゲノム医療 神戸大学医学部附属病院におけるがんゲノム医療の現状と課題
- (公社)日本小児科学会, Apr. 2021, 日本小児科学会雑誌, 125(4) (4), 681 - 681, Japanese多発乳児血管腫に対するプロプラノロール投与
- Diamond-Blackfan anemia (DBA) is mainly caused by pathogenic variants in ribosomal proteins and 22 responsible genes have been identified to date. The most common causative gene of DBA is RPS19 [NM_001022.4]. Nearly 180 RPS19 variants have been reported, including three deep intronic variants outside the splicing consensus sequence (c.72-92A > G, c.356 + 18G > C, and c.411 + 6G > C). We also identified one case with a c.412-3C > G intronic variant. Without conducting transcript analysis, the pathogenicity of these variants is unknown. However, it is difficult to assess transcripts because of their fragility. In such cases, in vitro functional splicing assays can be used to assess pathogenicity. Here, we report functional splicing analysis results of four RPS19 deep intronic variants identified in our case and in previously reported cases. One splicing consensus variant (c.411 + 1G > A) was also examined as a positive control. Aberrant splicing with a 2-bp insertion between exons 5 and 6 was identified in the patient samples and minigene assay results also identified exon 6 skipping in our case. The exon 6 skipping transcript was confirmed by further evaluation using quantitative RT-PCR. Additionally, minigene assay analysis of three reported deep intronic variants revealed that none of them showed aberrant splicing and that these variants were not considered to be pathogenic. In conclusion, the minigene assay is a useful method for functional splicing analysis of inherited disease.Feb. 2021, Pediatric hematology and oncology, 38(6) (6), 1 - 16, English, International magazineScientific journal
- (公社)日本小児科学会, Feb. 2021, 日本小児科学会雑誌, 125(2) (2), 250 - 250, English高リスク神経芽腫における微小残存病変(MRD)と腫瘍マーカーの相関に関する臨床的検討(Clinical analysis of the correlation between minimal residual disease and tumor markers in high-risk neuroblastoma)
- Rapidly growing nontuberculous mycobacteria should be considered if GPRs gram-positive rods are detected in blood cultures 2-3 days after the blood sample collection.Feb. 2021, Clinical case reports, 9(2) (2), 835 - 840, English, International magazineScientific journal
- Autoimmune enteropathy (AIE) is a rare disease, characterized by intractable diarrhea, villous atrophy of the small intestine, and the presence of circulating anti-enterocyte autoantibodies. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, and mutations in FOXP3, which is a master gene of regulatory T cells (Tregs), are major causes of AIE. Recent studies have demonstrated that mutations in other Treg-associated genes, such as CD25 and CTLA4, show an IPEX-like phenotype. We present the case of a 13-year-old girl with CTLA4 haploinsufficiency, suffering from recurrent immune thrombocytopenic purpura and intractable diarrhea. We detected an autoantibody to the AIE-related 75 kDa antigen (AIE-75), a hallmark of the IPEX syndrome, in her serum. She responded well to a medium dose of prednisolone and a controlled dose of 6-mercaptopurine (6-MP), even after the cessation of prednisolone administration. Serum levels of the soluble interleukin-2 receptor and immunoglobulin G (IgG) were useful in monitoring disease activity during 6-MP therapy. In conclusion, autoimmune-mediated mechanisms, similar to the IPEX syndrome, may be involved in the development of enteropathy in CTLA4 haploinsufficiency. Treatment with 6-MP and monitoring of disease activity using serum levels of soluble interleukin-2 receptor and IgG is suggested for such cases.Jan. 2021, Intestinal research, 20(1) (1), 144 - 149, English, International magazineScientific journal
- BACKGROUND: Patients with Ewing's sarcoma family of tumors (ESFT) who experience relapse or progression have a poor prognosis. AIM: This study aimed to identify the prognostic and therapeutic factors affecting overall survival (OS) of patients with recurrent or refractory localized ESFT. METHODS AND RESULTS: Thirty-eight patients with localized ESFT who experienced first relapse or progression between 2000 and 2018 were retrospectively reviewed. The 5-year OS rate of the entire cohort was 48.3% (95% confidence interval, 29.9%-64.5%). Multivariate analysis of OS identified time to relapse or progression, but not stem cell transplantation (SCT), as the sole independent risk factor (hazard ratio, 35.8; P = .002). Among 31 patients who received salvage chemotherapy before local treatment, 21 received chemotherapy regimens that are not conventionally used for newly diagnosed ESFT. The objective response rate to first-line salvage chemotherapy was 55.2% in the 29 evaluable patients. Time to relapse or progression was significantly associated with response to first-line salvage chemotherapy (P = .006). CONCLUSIONS: The present study fails to demonstrate significant clinical benefit of SCT for recurrent or refractory localized ESFT. Recently established chemotherapy regimens may increase the survival rate of patients with recurrent or refractory localized ESFT while attenuating the beneficial effect of SCT.Jan. 2021, Cancer reports (Hoboken, N.J.), 4(3) (3), e1329, English, International magazineScientific journal
- Jan. 2021, Haemophilia : the official journal of the World Federation of Hemophilia, 27(4) (4), e510-e512, English, International magazine
- Extranodal natural killer/T-cell lymphoma (ENKTL) is difficult to identify and diagnose appropriately. Positron emission tomography imaging is a crucial method that leads to precise diagnosis. A proper regimen including stem cell transplantation would possibly improve prognosis of advanced ENKTL.Dec. 2020, Clinical case reports, 8(12) (12), 3658 - 3660, English, International magazineScientific journal
- We herein describe soft tissue tumor arising in the lower extremity of a pediatric patient. The tumor displayed a unique and wide range of histological features, sheet-like and cohesive growth pattern consisting of enlarged round to epithelioid atypical cells with a large alveolar and pseudopapillary histological architecture, focally mimicking alveolar soft part sarcoma and MiT family translocation renal cell carcinoma. Tumor cells were focally immunoreactive for cytokeratin, S-100, and EMA. RNA sequencing identified a novel in-frame NR1D1 (exon 5)-MAML1 (exon 2) gene rearrangement resulting in the formation of a putative chimeric protein containing the N-terminal C4-type zing finger domains of NR1D1 and the C-terminal MAML1 protein, which was confirmed by subsequent RT-PCR, Sanger sequencing, and FISH assay. To the best of our knowledge, NR1D1-MAML1 fusion has not yet been described in any neoplasms, suggesting the emergence of a novel tumor entity.Dec. 2020, Virchows Archiv : an international journal of pathology, 477(6) (6), 891 - 895, English, International magazine[Refereed]Scientific journal
- (NPO)日本緩和医療学会, Aug. 2020, Palliative Care Research, 15(Suppl.) (Suppl.), S259 - S259, Japanese本邦小児がん患者における症状評価尺度開発のための調査研究
- (一社)日本頭頸部癌学会, Jul. 2020, 頭頸部癌, 46(2) (2), 168 - 168, Japanese小児・若年の上咽頭癌3例の治療経験
- This prospective observational study analyzed the pharmacokinetics of busulfan in Japanese children and evaluated the predicting accuracy of previous pediatric PPK models of busulfan. This study enrolled five patients (aged 2-12 years, BW 14-48 kg) receiving a busulfan-based conditioning regimen for hematopoietic stem cell transplantation at our hospital between January 2017 and December 2018. All patients received a 2-hour intravenous busulfan infusion four times daily for a total of 16 doses. After the infusions, 51 plasma samples were collected with the plasma busulfan concentration measured by liquid chromatography-tandem mass spectrometry. PPK model fitting was analyzed using the (%MPE) and the (%MAPE). Limited sampling strategies for estimating busulfan AUC were also evaluated. High interpatient variability was observed in the PK parameters. The most suitable PPK model that reflected our data was McCune's two-compartment model (%MPE -8.7, %MAPE 19.3). A combination sampling method using the busulfan concentration at 2 and 6 hours after the start of the first busulfan dose was found to be able to estimate AUC4 day . These results provide useful information on busulfan therapeutic drug monitoring in the Japanese pediatric population.Jun. 2020, Pediatric transplantation, 24(4) (4), e13696, English, International magazine[Refereed]Scientific journal
- 産業開発機構(株), May 2020, 映像情報Medical, 52(5) (5), 40 - 45, Japanese
- May 2020, Pediatric hematology and oncology, 37(4) (4), 337 - 343, English, International magazine[Refereed]Scientific journal
- (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 293 - 293, Japanese当院における小児がん患者の妊孕性温存について
- Monitoring of several sets of neuroblastoma-associated mRNAs (NB-mRNAs) by real-time quantitative PCR (qPCR) can be used to evaluate minimal residual disease in NB patients. Droplet digital PCR (ddPCR) is an adaption of qPCR that potentially provides simpler and more reproducible detection of low levels of mRNAs. However, whether minimal residual disease in NB patients can be monitored by ddPCR using a set of NB-mRNAs is not yet tested. In this study, 208 bone marrow (BM) and 67 peripheral blood samples were retrospectively collected from 20 high-risk NB patients with clinical disease evaluation at two Japanese centers between 2011 and 2018, and level of each NB-mRNA (CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNAs) was determined by ddPCR. Level of 7NB-mRNAs (defined as the combined signature of each NB-mRNA) was higher in BM than peripheral blood, but correlated significantly with each other. In accordance with disease burden, it varied with disease status (remission, stable, or progression) and collection time point (diagnosis, treatment, post-treatment, or relapse). In 73 post-treatment BM samples, it was significantly higher in 17 relapsed/regrown samples than in 56 nonrelapsed/nonregrown samples. Furthermore, ddPCR had a better prognostic value than qPCR in detecting 7NB-mRNAs in the same 73 post-treatment BM samples. This study suggests that ddPCR detection of 7NB-mRNAs is significantly associated with tumor relapse/regrowth in high-risk NB patients.Feb. 2020, The Journal of molecular diagnostics : JMD, 22(2) (2), 236 - 246, English, International magazine[Refereed]Scientific journal
- Dec. 2019, PEDIATRIC BLOOD & CANCER, 66, S73 - S74, EnglishVitB12 Deficiency Anemia in an Infant Born to Ileum-resected Mother[Refereed]
- Dec. 2019, Bone marrow transplantation, 54(12) (12), 1926 - 1929, English, International magazine[Refereed]
- Dec. 2019, PEDIATRIC BLOOD & CANCER, 66, S117 - S118Spontaneously Developed Undifferentiated Sarcoma and Rhabdomyosarcoma in mdx Mice[Refereed]
- Oct. 2019, Pediatrics and neonatology, 60(5) (5), 579 - 580, English, International magazine[Refereed]Scientific journal
- The dismal prognosis of patients with disseminated Ewing sarcoma necessitates the development of novel treatment strategies. Pazopanib is an oral multi-targeted tyrosine kinase inhibitor that is active against advanced soft tissue sarcoma. However, the clinical activity and feasibility of pazopanib for treating Ewing sarcoma remain poorly understood. Moreover, clinical information on the use of tandem high-dose chemotherapy for Ewing sarcoma is limited. A 14-year-old boy with Ewing sarcoma was transferred to our hospital for treatment. Magnetic resonance imaging, computed tomography scans, and bone scintigraphy revealed multiple lesions in the pubis, ilium, ischium, femur, rib, cranial bone, thoracic vertebrae, sacrum, obturator muscle, adductor magnus muscle, testicular cord, and lungs. Bone scintigraphy after intensive chemotherapies confirmed that multiple abnormal accumulations were still present in the cranial bone and pubis. Subsequently, the patient received tandem high-dose chemotherapy including topotecan, and radiotherapy. Abnormal accumulations have disappeared in bone scintigraphy. Subsequently, pazopanib maintenance therapy was initiated. Despite the presence of innumerable lesions at diagnosis, the patient has been in near-complete remission for the past 1 year with pazopanib administration. This confirms that adding pazopanib maintenance therapy after tandem high-dose chemotherapy is a therapeutic option for cases with disseminated Ewing sarcoma.Jul. 2019, International cancer conference journal, 8(3) (3), 95 - 100, English, International magazine[Refereed]
- 産業開発機構(株), May 2019, 映像情報Medical, 51(5) (5), 62 - 65, Japanese医療技術等国際展開推進事業の取り組み(後編) インドネシアにおける小児がん診療の現状と課題
- 産業開発機構(株), Apr. 2019, 映像情報Medical, 51(4) (4), 42 - 48, Japanese医療技術等国際展開推進事業の取り組み(前編) 開発途上国における小児がんの診療能力強化 国際的に注目されつつある課題である小児がんへの対応に関する研修
- Neuroblastoma is a common extracranial solid tumor of neural crest (NC) origin that accounts for up to 15% of all pediatric cancer deaths. The disease arises from a transient population of NC cells that undergo an epithelial-mesenchymal transition (EMT) and generate diverse cell-types and tissues. Patients with neuroblastoma are characterized by their extreme heterogeneity ranging from spontaneous regression to malignant progression. More than half of newly diagnosed patients present highly metastatic tumors and are stratified into a high-risk group with dismal outcome. As many as 20% of high-risk patients have residual disease that is refractory or progressive during induction chemotherapy. Although a majority of high-risk patients achieve remission, larger part of those patients has minimal residual disease (MRD) that causes relapse even after additional consolidation therapy. MRD is composed of drug-resistant tumor cells and dynamically presented as cancer stem cells (CSCs) in residual tumors, circulating tumor cells (CTCs) in peripheral blood (PB), and disseminated tumor cells (DTCs) in bone marrow (BM) and other metastatic sites. EMT appears to be a key mechanism for cancer cells to acquire MRD phenotypes and malignant aggressiveness. Due to the restricted availability of residual tumors, PB and BM have been used to isolate and analyze CTCs and DTCs to evaluate MRD in cancer patients. In addition, recent technical advances make it possible to use circulating tumor DNA (ctDNA) shed from tumor cells into PB for MRD evaluation. Because MRD can be detected by tumor-specific antigens, genetic or epigenetic changes, and mRNAs, numerous assays using different methods and samples have been reported to detect MRD in cancer patients. In contrast to the tumor-specific gene-rearrangement-positive acute lymphoblastic leukemia (ALL) and the oncogenic fusion-gene-positive chronic myelogenous leukemia (CML) and several solid tumors, the clinical significance of MRD remains to be established in neuroblastoma. Given the extreme heterogeneity of neuroblastoma, dynamics of MRD in neuroblastoma patients will hold a key to the clinical validation. In this review, we summarize the biology and detection methods of cancer MRD in general and evaluate the available assays and clinical significance of neuroblastoma MRD to clarify its dynamics in neuroblastoma patients.2019, Frontiers in oncology, 9, 455 - 455, English, International magazine[Refereed]Scientific journal
- Nov. 2018, PEDIATRIC BLOOD & CANCER, 65, S39 - S40, EnglishClinical Characteristics of Neuroblastoma with Central Nervous System Metastases at First Relapse[Refereed]
- Nov. 2018, PEDIATRIC BLOOD & CANCER, 65, S77 - S77, EnglishRe-Considering Old Strategies as Palliative Treatment for DIPG (Diffuse Intrinsic Pontine Glioma)[Refereed]
- Nov. 2018, PEDIATRIC BLOOD & CANCER, 65, S99 - S99, EnglishSuccessful Induction Therapy with Prednisolone and Maintenance Therapy with Cyclosporine for Subcutaneous Panniculitis-Like T-Cell Lymphoma: A Case Report[Refereed]
- Nov. 2018, PEDIATRIC BLOOD & CANCER, 65, S103 - S104, EnglishSecondary Thyroid Carcinoma After Irradiation for Hematopoietic Stem Cell Transplantation in Childhood[Refereed]
- Nov. 2018, PEDIATRIC BLOOD & CANCER, 65, S60 - S60, EnglishClinical Characteristics and Risk Factors of Hypertension in the Early Phase After Allogeneic Stem Cell Transplantation[Refereed]
- Nov. 2018, PEDIATRIC BLOOD & CANCER, 65, S102 - S102, EnglishDermal Mucormycosis with Blood Stream Infection During High-Dose Chemotherapy (HDC) with BCOR-ITD Positive Undifferentiated Sarcoma: A Case Report[Refereed]
- Nov. 2018, BLOOD, 132, English[Refereed]
- Nov. 2018, PEDIATRIC BLOOD & CANCER, 65, S50 - S51, EnglishMediastinal Yolk Sac Tumor in a Patient with Concurrent 8p23.1 Duplication and 8p23.2-pter Deletion[Refereed]
- Nov. 2018, PEDIATRIC BLOOD & CANCER, 65, S95Spontaneous Development of Spindle Cell Sarcoma in mdx Mice[Refereed]
- Disseminated fusariosis is a fatal infection in immunocompromised hosts. However, the optimal antifungal treatment for disseminated fusariosis has not yet been established. We report a case of disseminated fusariosis after chemotherapy for acute lymphoblastic leukemia, presenting with multiple skin, lung and kidney lesions and cerebrospinal fluid invasion. The combination therapy of liposomal amphotericin B and caspofungin resolved disseminated fusariosis successfully.Oct. 2018, The Pediatric infectious disease journal, 37(10) (10), e251-e253, English, International magazine[Refereed]Scientific journal
- The dismal prognosis of pediatric acute myeloid leukemia (AML) relapsing after hematopoietic stem cell transplantation (HSCT) requires exploration of novel strategies to prevent relapse. Azacitidine (AZA) maintenance therapy could potentially reduce the recurrence rate post HSCT. Here, we presents the cases of three children with high-risk AML post HSCT who were treated with low-dose AZA maintenance therapy, demonstrating the feasibility of this therapy. Currently, all three are in complete remission for 13-41 months despite their high-risk characteristics. Our encouraging data warrant larger prospective studies to assess the efficacy and safety of low-dose AZA maintenance therapy post HSCT for pediatric patients with high-risk AML.Oct. 2018, Pediatric blood & cancer, 65(10) (10), e27284, English, International magazine[Refereed]Scientific journal
- (一社)日本血液学会-東京事務局, Sep. 2018, 臨床血液, 59(9) (9), 1698 - 1698, English経時的なRT-qPCRにより、急性GVHD出現後に初めてMRDの消失を確認したNUP98-NSD1陽性AML例(Monitoring RT-qPCR revealed the elimination of MRD after the onset of aGVHD in the NUP98-NSD1(+) AML)
- 日本癌学会, Sep. 2018, 日本癌学会総会記事, 77回, 2012 - 2012, EnglishデジタルPCRによる高リスク神経芽腫患者の微小残存病変(MRD)の検出(Detection of minimal residual disease in high-risk neuroblastoma patients by digital PCR)
- ETV6-ABL1 fusion is a rare but recurrent oncogenic lesion found in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), without an established chromosomal abnormality, and is associated with poor outcome. In ETV6-ABL1-positive cases, an in-frame fusion produced by a complex rearrangement results in constitutive chimeric tyrosine kinase activity. Monosomy 7 is also a rare and unfavorable chromosomal abnormality in childhood BCP-ALL. Here, we report a 14-year-old female BCP-ALL patient with ETV6-ABL1 fusion combined with monosomy 7. She was admitted to our hospital because of persistent fever. Bone marrow nuclear cell count on admission was 855,000/µL with 90.0% blastic cells of lymphoid morphology. Blasts were positive for CD10, CD19, CD20, CD34, cyCD79a, cyTdT, HLA-DR, and CD66c, had a karyotype of 45, XX, - 7 [18/20] and a split signal for ABL1 FISH probe (92.7%), and were sensitive to tyrosine kinase inhibitors, imatinib and dasatinib, in vitro. ETV6-ABL1 fusion transcript was identified by whole transcriptome sequencing and confirmed by RT-PCR. She was treated with the high-risk protocol based on ALL-BFM 95, achieved complete remission (CR) after induction chemotherapy, and maintained CR for 4 months. To our knowledge, this is the first report of ETV6-ABL1 fusion combined with monosomy 7 in childhood BCP-ALL.May 2018, International journal of hematology, 107(5) (5), 604 - 609, English, Domestic magazine[Refereed]Scientific journal
- Background: X-linked lymphoproliferative disease type 1 (XLP1) is a rare primary immune deficiency, which is caused by SH2D1A gene mutations. XLP1 is commonly associated with Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis, hypogammaglobulinemia, and/or lymphoma. The only curative treatment for XLP1 is allogeneic hematopoietic cell transplantation. However, published data detailing the clinical course of, and indications for, allogeneic hematopoietic cell transplantation in asymptomatic patients with XLP1 is lacking. Although relevant family history could be useful in identifying patients with XLP1 before disease onset, no guidelines have been established on the management of asymptomatic patients with XLP1. Therefore, clinicians and families face dilemmas in balancing between the risk of waiting for the disease onset, and the risk of transplant-related mortality associated with allogeneic hematopoietic cell transplantation, which is often performed at a very young age. We first describe the detailed clinical course of an asymptomatic patient with XLP1 who successfully underwent allogeneic hematopoietic cell transplantation. Case presentation: A boy was born at 39 weeks of gestation, weighing 3016 g at birth. He appeared fine, but he underwent genetic testing because his maternal cousin had XLP1. He was found to have a novel c.207_208insC (p.Pro70ProfsX4) mutation in exon 3 of SH2D1A, which was also found in his cousin. There was no HLA-identical donor in his family. Immunoglobulin was administered monthly to prevent EBV infection while searching for an alternative donor. He underwent allogeneic bone marrow transplantation (BMT) from an allele HLA 8/8 fully matched, unrelated donor with a reduced-intensity conditioning (RIC) regimen consisting of fludarabine, melphalan, and low-dose total body irradiation (TBI) at 20 months of age. The patient has been doing well for 2 years post transplantation and maintaining complete donor chimerism without any evidence of chronic graft versus host disease. Conclusions: We describe a case of an asymptomatic patient with XLP1, who successfully underwent unrelated BMT with RIC regimen consisting of fludarabine, melphalan, and 3 Gy TBI. That was well tolerated and successfully generated complete chimerism in every subpopulation. This case delineates the option of allogeneic hematopoietic cell transplantation even in asymptomatic patients with XLP1.2018, Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology, 14, 82 - 82, English, International magazine[Refereed]
- Dec. 2017, BLOOD, 130, EnglishMolecular Diagnosis of Hemophilia B Leyden in Japanese Brothers Reveals Spontaneous Amelioration in Early Childhood with c.-35 G > A Onecut Binding Site Mutation[Refereed]
- Nov. 2017, PEDIATRIC BLOOD & CANCER, 64, S39 - S40, EnglishTreatment Results and Prognostic Factors of Retinoblastoma: A Single Institution Experience[Refereed]
- Nov. 2017, PEDIATRIC BLOOD & CANCER, 64, S107 - S107, EnglishPathological Fracture in Children with Nonosteogenic Malignant Tumor[Refereed]
- Nov. 2017, PEDIATRIC BLOOD & CANCER, 64, S115 - S115, EnglishEpidemiology of Factor VIII Inhibitor Development in Patients with Severe Hemophilia A Treated in our Institution[Refereed]
- (一社)日本血液学会-東京事務局, 2017, [Rinsho ketsueki] The Japanese journal of clinical hematology, 58(2) (2), 143 - 149, Japanese, Domestic magazine[Refereed]Scientific journal
- Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients.Neuroblastoma is an aggressive pediatric tumor accounting for ~15% of cancer-associated mortalities in children. Despite the current intensive therapy, >50% of high-risk patients experience tumor relapse or regrowth caused by the activation of minimal residual disease (MRD). Although several MRD detection protocols using various reverse transcription-quantitative polymerase chain reaction (RT-qPCR) markers have been reported to evaluate the therapeutic response and disease status of neuroblastoma patients, their clinical significance remains elusive. The present study reports two high-risk neuroblastoma patients, whose MRD was consecutively monitored using 11 RT-qPCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment. The two patients initially responded to the induction therapy and reached MRD-negative status. The patients' MRD subsequently became positive with no elevation of their urinary homovanillic acid, urinary vanillylmandelic acid and serum neuron-specific enolase levels at 13 or 19 weeks prior to the clinical diagnosis of tumor relapse or regrowth. The present cases highlight the possibility of consecutive MRD monitoring using 11 markers to enable an early detection of tumor relapse or regrowth in high-risk neuroblastoma patients.Aug. 2016, Oncology letters, 12(2) (2), 1119 - 1123, English, International magazine[Refereed]Scientific journal
- May 2016, Pediatrics international : official journal of the Japan Pediatric Society, 58(5) (5), 429 - 30, English, International magazine[Refereed]Scientific journal
- (公社)日本小児科学会, Feb. 2016, 日本小児科学会雑誌, 120(2) (2), 316 - 316, Japanese神経芽腫患者の微小残存病変モニタリング
- Nov. 2015, Oncology letters, 10(5) (5), 3228 - 3232, English, International magazine[Refereed]Scientific journal
- Nov. 2015, International journal of hematology, 102(5) (5), 594 - 601, English, Domestic magazine[Refereed]Scientific journal
- (一社)日本小児血液・がん学会, Oct. 2015, 日本小児血液・がん学会雑誌, 52(4) (4), 257 - 257, EnglishDENNドメイン蛋白質DENND2Aによる神経芽腫の制御機構(DENN domain protein DENND2A mediates the progression of neuroblastoma)
- (一社)日本小児血液・がん学会, Oct. 2015, 日本小児血液・がん学会雑誌, 52(4) (4), 257 - 257, English高リスク神経芽腫患者の骨髄と末梢血における微小残存病変の発現についての検討(Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients)
- (公社)日本小児科学会, Sep. 2015, 日本小児科学会雑誌, 119(9) (9), 1374 - 1379, Japanese海綿状血管腫と鑑別を要した右下腿原発乳児線維肉腫
- Mar. 2015, International journal of oncology, 46(3) (3), 1089 - 98, English, International magazine[Refereed]Scientific journal
- Dec. 2014, European journal of pediatrics, 173(12) (12), 1615 - 8, English, International magazine[Refereed]Scientific journal
- Jun. 2014, BMC pediatrics, 14, 139 - 139, English, International magazine[Refereed]Scientific journal
- (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, Nov. 2013, 日本小児血液・がん学会学術集会,日本小児がん看護学会,公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号55回・11回・18回, 55回・11回・18回, 338 - 338, Japaneseメソトレキセート大量療法後の急性腎不全に対し血液浄化療法を施行した若年成人急性リンパ性白血病の1例
- (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, Nov. 2013, 日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号55回・11回・18回, 55回・11回・18回, 275 - 275, Japanese初診時に血管腫と鑑別を要した右下腿原発乳児線維肉腫の新生児例
- (一社)日本小児血液・がん学会, Oct. 2013, 日本小児血液・がん学会雑誌, 50(3) (3), 489 - 489, Japanese大量化学療法後早期に再発し終末期を迎えたユーイング肉腫の青年期男性例 終末期の予後告知をめぐる本人・家族との関わりについて
- Minimal residual disease (MRD) is derived from tumor-initiating cells (TICs) and is responsible for tumor relapse. Neuroblastoma is characterized by extreme tumor heterogeneity, and more than half of high-risk patients experience tumor relapse. To overcome tumor heterogeneity and achieve more sensitive detection of MRD, several sets of real-time RT-PCR markers have been reported for MRD monitoring in neuroblastoma patients from different centers. However, these markers vary across centers and are still being validated. In the present study, we validated the ability of 14 commonly used real-time RT-PCR markers to detect MRD based on their expression in neuroblastoma TICs, and we developed a novel MRD detection protocol, which scored the samples as MRD-positive when the expression of one of the 11 real-time RT-PCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) exceeded the normal range. By using this protocol, we prospectively monitored MRD in 73 bone marrow (BM), 12 peripheral blood stem cell and 8 peripheral blood samples from 14 neuroblastoma patients treated at a single center. We scored 100, 56, 56 and 57% BM cytology-positive, elevated vanillylmandelic acid (VMA), elevated homovanillic acid (HVA) and elevated neuron-specific enolase (NSE) samples as MRD-positive, respectively. MRD was also positive in 48, 45, 46 and 43% of the BM cytology-negative and normal VMA, normal HVA and normal NSE samples, respectively. These results suggest that the present MRD detection protocol based on the expression of a set of 11 real-time RT-PCR markers in neuroblastoma TICs achieves sensitive MRD monitoring in neuroblastoma patients.Apr. 2013, Oncology reports, 29(4) (4), 1629 - 36, English, International magazine[Refereed]Scientific journal
- (一社)日本検査血液学会, Feb. 2013, 日本検査血液学会雑誌, 14(1) (1), 57 - 63, Japanese初診時、播種性血管内凝固(DIC)を合併、急性白血病が疑われた胞巣型横紋筋肉腫の一症例
- BACKGROUND: Ewing sarcoma family of tumors is the second most common primary bone tumor of childhood. Extraosseous Ewing sarcoma family of tumors is rare. We present a pediatric case of primary endobronchial Ewing sarcoma family of tumors. CASE REPORT: A 12-year-old boy presented with dyspnea and chest radiography showed right pulmonary atelectasis. Chest computed tomography demonstrated tumor in the right main bronchus. Histopathological examination of the resected tumor demonstrated Ewing sarcoma family of tumors. No other lesions were detected throughout the body and the right main bronchus was thought to be the primary site. As of 1 year and 6 months after further resection of residual tumor followed by chemotherapy and radiotherapy, the patient remains disease-free. CONCLUSIONS: Extraosseous Ewing sarcoma family of tumors arises in soft tissues of the trunk or extremities, but primary endobronchial Ewing sarcoma family of tumors has rarely been reported. Although quite rare, Ewing sarcoma family of tumors should be considered among the differential diagnoses for pediatric bronchial tumor.2013, The American journal of case reports, 14, 67 - 9, English, International magazine[Refereed]Scientific journal
- Place of death of pediatric cancer patients in a single institute during 7 years.Place of death is an important issue at the end-of-life. It is poorly understood in pediatric cancer patients in Japan. This study aimed to clarify place of death of children with cancer as well as variables associated with place of death. Study population was pediatric cancer patients who died in the Department of Pediatrics at Kobe University Hospital during the last 7 years. The medical records were retrospectively reviewed regardless of cause of death to derive data relating to patients' characteristics and disease. 18 patients were included. Median age at death was 12.2 years old. 6 patients including 5 children in complete remission had hematological disease and 12 patients suffered from solid tumors. 4 patients (22.2%) died at home, whereas 14 patients (77.8%) died in the hospital including 6 ICU deaths. No one died in hospices. Preference of patients was unavailable due to the lack of inquiry. Factors influencing place of death (home, ICU, non-ICU) were disease (hematological disease vs. solid tumor, p=0.010, brain tumor vs. non-brain tumor, p=0.023), disease status (complete remission vs. non-complete remission, p=0.0014) and preference of families (p=0.029). Among 6 families who expressed preference, no disparity was observed between actual and preferred place of death. This is the first English publication of place of death of pediatric cancer patients in Japan. The low percentage of home death, factors influencing place of death and the lack of disparity between actual and preferred place of death were indicated. Further studies are required to better understand place of death.Jun. 2012, The Kobe journal of medical sciences, 58(2) (2), E33-40 - 40, English, Domestic magazine[Refereed]Scientific journal
- Jun. 2012, Oncology reports, 27(6) (6), 2045 - 9, English, International magazine[Refereed]Scientific journal
- (一社)日本小児血液・がん学会, May 2012, 日本小児血液・がん学会雑誌, 49(1-2) (1-2), 115 - 120, Japaneseタンデム自家造血細胞移植併用大量化学療法を施行後3年寛解を維持している初診時全身骨髄転移陽性Ewing肉腫ファミリー腫瘍の1例
- OBJECTIVES: A growing number of epidemiological studies have demonstrated that the consumption of green tea inhibits the growth of a variety of cancers. Epigallocatechin gallate (EGCG), the most abundant catechin in green tea, has been shown to have an anti-cancer effect against many cancers. Most cancers are believed to be initiated from and maintained by a small population of tumor-initiating cells (TICs) that are responsible for chemotherapeutic resistance and tumor relapse. In neuroblastoma, an aggressive pediatric tumor that often relapses and has a poor prognosis, TICs were recently identified as spheres grown in a serum-free non-adherent culture used for neural crest stem cell growth. Although EGCG has been reported to induce growth arrest and apoptosis in neuroblastoma cells, its effect on neuroblastoma TICs remains to be defined. METHODS: Gene expression was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). The effects of EGCG on cell proliferation, apoptosis, and sphere formation were determined by cell counting, propidium iodide staining, and sphere (>100 μm in diameter) counting, respectively. RESULTS: Neuroblastoma BE(2)-C cells showed increased expression of stem cell markers (nanog homeobox [NANOG] and octamer-binding transcription factor 4 [OCT4]), as well as decreased expression of neuronal differentiation markers (Cu(2+)-transporting ATPase alpha polypeptide [ATP7A] and dickkopf homolog 2 [DKK2]) in spheres grown in serum-free non-adherent culture, compared to parental cells grown in conventional culture. Although EGCG induced growth arrest and apoptosis in the parental cells in a dose-dependent manner, it was not effective against spheres. However, EGCG potently inhibited sphere formation in the BE(2)-C cells. CONCLUSIONS: The present results suggest that EGCG may inhibit the development of TICs in BE(2)-C cells.May 2012, Environmental health and preventive medicine, 17(3) (3), 246 - 51, English, International magazine[Refereed]Scientific journal
- Neuroblastoma is the most common extracranial solid tumor in children and accounts for 15% of pediatric cancer deaths. Although retinoic acid (RA) is currently used to treat high-risk neuroblastoma patients in the clinic, RA-responsiveness is variable and unpredictable. Since no alterations in the RA-signaling pathway have been found in neuroblastoma cells, molecules correlated with RA-induced differentiation will provide predictive markers of RA-responsiveness for clinical use. The Rab family of small G proteins are key regulators of membrane traffic and play a critical role in cell differentiation and cancer progression. Although an increasing number of cancer-associated alternative splicing events have been identified, alternative splicing of Rab proteins remains to be characterized in neuroblastoma. In the present study, we focused on Rab15 that was originally identified as a brain-specific Rab protein and regulates the endocytic recycling pathway. We identified alternatively spliced Rab15 isoforms designated as Rab15CN and Rab15AN in neuroblastoma cells. Rab15CN was composed of 7 exons encoding 212 amino acids and showed brain-specific expression. Alternative splicing of exon 4 generated Rab15AN that was predicted to encode 208 amino acids and was predominantly expressed in testis. RA induced neuronal differentiation of neuroblastoma BE(2)-C cells and specifically up-regulated Rab15CN expression. Reciprocally, RA-induced differentiation was observed in Rab15CN-expressing BE(2)-C cells in preference to Rab15AN-expressing BE(2)-C cells. Furthermore, Rab15CN expression was also specifically up-regulated during RA-induced differentiation of newly established neuroblastoma cells from high-risk patients. These results suggest that Rab15 expression correlates with RA-induced differentiation of neuroblastoma cells.Jul. 2011, Oncology reports, 26(1) (1), 145 - 51, English, International magazine[Refereed]Scientific journal
- 2024, 近畿小児科学会プログラム・抄録集, 37th副腎皮質腫瘍を合併したBeckwith-Wiedemann症候群の一例
- 2023, 日本小児血液・がん学会雑誌(Web), 60(5) (5)Bio-absorbable polyglycolic acid spacer placement surgery for malignant abdominal tumor treatment: Clinical observations at Kobe University
- Dec. 2020, PEDIATRIC BLOOD & CANCER, 67, EnglishPrognostic Values of Tumor Markers and Minimal Residual Disease Detected by 7NB-mRNAs ddPCR Assay for High-Risk Neuroblastoma PatientsSummary international conference
- (公社)日本整形外科学会, Jul. 2020, 日本整形外科学会雑誌, 94(6) (6), S1453 - S1453, Japanese
- 産業開発機構(株), May 2020, 映像情報Medical, 52(5) (5), 40 - 45, Japanese医療技術等国際展開推進事業 小児がんの診療能力強化(前編) 開発途上国における小児がん診療能力強化事業5年間のまとめ
- Dec. 2019, PEDIATRIC BLOOD & CANCER, 66, S50 - S51, EnglishThree Cases of Nasopharyngeal Carcinoma in a Single InstituteSummary international conference
- Dec. 2019, PEDIATRIC BLOOD & CANCER, 66, S81 - S82, EnglishLevel of Seven Neuroblastoma-Associated mRNAs Analyzed by ddPCR is Correlated Between Bone Marrow and Peripheral Blood in High-risk NeuroblastomaSummary international conference
- (一社)日本小児血液・がん学会, Sep. 2019, 日本小児血液・がん学会雑誌, 56(2) (2), 256 - 257, Japanese血友病未治療例(PUPs)に対する半減期延長凝固因子製剤(EHL)の使用経験
- (一社)日本小児血液・がん学会, Sep. 2019, 日本小児血液・がん学会雑誌, 56(2) (2), 258 - 258, Japanese集学的治療を行った転移性ユーイング肉腫(ESFT)の2例
- 日本癌学会, Sep. 2019, 日本癌学会総会記事, 78回, E - 1060, English神経芽腫の七つのmRNA発現に関する骨髄と末梢血サンプルの相関(Expression of seven neuroblastoma-associated mRNAs is correlated between bone marrow and peripheral blood samples)
- (一社)日本血栓止血学会, May 2019, 日本血栓止血学会誌, 30(2) (2), 450 - 450, Japanese治療歴のない血友病患者(PUPs)に対する半減期延長凝固因子製剤(EHL)の使用経験
- (公社)日本小児科学会, Mar. 2019, 日本小児科学会雑誌, 123(3) (3), 621 - 621, Japanese兵庫県がん・生殖医療ネットワークを通じた小児がん患者における卵巣凍結保存の取り組み
- (公社)日本小児科学会, Feb. 2019, 日本小児科学会雑誌, 123(2) (2), 266 - 266, JapaneseAtraumatic needle使用による腰椎穿刺後合併症の出現頻度
- (公社)日本小児科学会, Feb. 2019, 日本小児科学会雑誌, 123(2) (2), 317 - 317, Japanese高リスク神経芽腫患者における化学療法中の筋肉量減少
- Nov. 2018, PEDIATRIC BLOOD & CANCER, 65, S71 - S71, EnglishImmunohistochemical Analysis for Predicting Prognosis in HepatoblastomaSummary international conference
- Nov. 2018, PEDIATRIC BLOOD & CANCER, 65, S38 - S39, EnglishQuantitation of Minimal Residual Disease by Droplet Digital PCR in High-Risk Neuroblastoma PatientsSummary international conference
- Oct. 2018, CANCER RESEARCH, 78(19) (19), EnglishSummary international conference
- (一社)日本小児血液・がん学会, Oct. 2018, 日本小児血液・がん学会雑誌, 55(4) (4), 312 - 312, JapaneseAYA世代ALLの寛解導入療法中に発症した脳静脈血栓症
- (一社)日本小児血液・がん学会, Oct. 2018, 日本小児血液・がん学会雑誌, 55(4) (4), 325 - 325, Japanese早期に遺伝子診断が得られ治療介入できた先天性葉酸吸収不全の一例
- (一社)日本血液学会-東京事務局, Sep. 2018, 臨床血液, 59(9) (9), 1685 - 1685, EnglishELANE遺伝子変異を有する重症感染症を合併しない好中球減少症の1例(Long-term severe infection free survival with neutropenia due to ELANE mutation without G-CSF)
- (一社)日本小児血液・がん学会, Jun. 2018, 日本小児血液・がん学会雑誌, 55(1) (1), 61 - 61, Japanese兵庫県がん・生殖医療ネットワークにおける小児がん患者に対する卵巣組織凍結保存の試み
- (公社)日本小児科学会, Apr. 2018, 日本小児科学会雑誌, 122(4) (4), 815 - 815, Japanese小児がん患者に対する粒子線治療の試み
- (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 230 - 230, Japanese小児がん患者における聴力障害発症頻度とリスク因子についての後方視的検討
- (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 231 - 231, Japanese再発神経芽腫の臨床的検討
- (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 231 - 231, Japanese本邦における小児がん治療時の深在性真菌症対策の現状 JCCG施設調査より
- (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 232 - 232, Japanese小児急性白血病に対する化学療法の好中球減少期における予防的抗菌薬投与
- (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 233 - 233, Japanese5年以上のromiplostim投与後に無治療経過観察に至った幼児慢性免疫血小板減少性紫斑病
- (株)東京医学社, Dec. 2017, 小児内科, 49(12) (12), 1761 - 1764, Japanese【プライマリ・ケア医が知っておくべき小児悪性疾患】オンコロジック・エマージェンシー 乏尿・無尿
- (一社)日本小児血液・がん学会, Oct. 2017, 日本小児血液・がん学会雑誌, 54(4) (4), 370 - 370, Japanese本邦の小児がん化学療法における感染症対策の現状(第一報) 環境と検査 JCCG施設調査より
- (一社)日本小児血液・がん学会, Oct. 2017, 日本小児血液・がん学会雑誌, 54(4) (4), 370 - 370, Japanese本邦における小児がん化学療法に対する感染症対策の現状(第二報) 予防と治療 JCCG施設調査より
- (一社)日本小児血液・がん学会, Oct. 2017, 日本小児血液・がん学会雑誌, 54(4) (4), 370 - 370, Japanese本邦における小児がん患者の食事管理に関する現状調査 JCCG施設調査より
- (一社)日本小児血液・がん学会, Oct. 2017, 日本小児血液・がん学会雑誌, 54(4) (4), 371 - 371, Japanese本邦における小児がん患者に対する口腔ケアの現状 JCCG施設調査より
- (公社)日本小児科学会, May 2017, 日本小児科学会雑誌, 121(5) (5), 914 - 914, Japanese胸部CTにより速やかに診断し得たX連鎖性重症複合型免疫不全症の乳児
- (一社)日本小児血液・がん学会, Nov. 2016, 日本小児血液・がん学会雑誌, 53(4) (4), 349 - 349, JapanesePET-MRI所見に基づく肺・下鼻甲介・腎生検が原疾患の診断に有効であった二次性血球貪食性リンパ組織球症の1例
- (一社)日本小児血液・がん学会, Nov. 2016, 日本小児血液・がん学会雑誌, 53(4) (4), 298 - 298, JapaneseG-CSF投与と自家末梢血幹細胞移植を併用しbi-weekly VDC-IE療法を完遂し得た切除不能ユーイング肉腫例
- 日本小児放射線学会, Jun. 2016, 日本小児放射線学会雑誌, 32(Suppl.) (Suppl.), 23 - 23, JapaneseSpectral shaping+高ピッチ二重らせん撮影による低線量胸部CT
- (一社)日本TDM学会, May 2016, TDM研究, 33(2) (2), 172 - 172, Japaneseメチルプレドニゾロンの吸収不良により造血細胞移植後急性移植片対宿主病のコントロールに難渋した小児急性リンパ性白血病の1症例
- (一社)日本小児血液・がん学会, Apr. 2016, 日本小児血液・がん学会雑誌, 53(1) (1), 31 - 31, Japanese化学療法後の好中球減少期に血栓性静脈炎によりメチシリン耐性表皮ブドウ球菌の持続菌血症を呈した急性骨髄性白血病の1例
- 2016, 日本小児血液・がん学会雑誌(Web), 53(1) (1)化学療法後の好中球減少期に血栓性静脈炎によりメチシリン耐性表皮ブドウ球菌の持続菌血症を呈した急性骨髄性白血病の1例
- 2016, 日本小児血液・がん学会雑誌(Web), 53(4) (4)G-CSF投与と自家末梢血幹細胞移植を併用しbi-weekly VDC-IE療法を完遂し得た切除不能ユーイング肉腫例
- (公社)日本小児科学会, Jan. 2016, 日本小児科学会雑誌, 120(1) (1), 84 - 84, Japanese左鎖骨部腫瘤を呈した生後6ヵ月の乳児例
- (一社)日本小児血液・がん学会, Oct. 2015, 日本小児血液・がん学会雑誌, 52(4) (4), 342 - 342, Japanese外来化学療法中(ALL B12臨床試験)の中心静脈カテーテルの管理についての検討
- 日本癌学会, Oct. 2015, 日本癌学会総会記事, 74回, J - 1346, English神経芽腫の発症・進展におけるRab6BとRab28の役割
- 日本癌学会, Oct. 2015, 日本癌学会総会記事, 74回, P - 3035, EnglishDENNドメイン蛋白質DENND2Aによる神経芽腫発の発症・進展の制御機構
- (一社)日本小児血液・がん学会, Aug. 2015, 日本小児血液・がん学会雑誌, 52(2) (2), 176 - 176, Japanese骨髄移植後のKaufmann療法中に肝腫瘤を認めた1例
- (一社)日本小児救急医学会, Jun. 2015, 日本小児救急医学会雑誌, 14(2) (2), 305 - 305, Japanese神戸こども初期急病センターにおける同日複数回受診患児についての検討
- (公社)日本小児科学会, Feb. 2015, 日本小児科学会雑誌, 119(2) (2), 410 - 410, Japanese化学療法中に血液培養陽性となった急性リンパ球白血病症例の臨床的検討
- 2015, 日本小児血液・がん学会雑誌(Web), 52(2) (2)骨髄移植後のKaufmann療法中に肝腫瘤を認めた1例
- Oct. 2014, CANCER RESEARCH, 74(19) (19), EnglishSummary international conference
- (一社)日本小児血液・がん学会, Oct. 2014, 日本小児血液・がん学会雑誌, 51(4) (4), 250 - 250, English神経芽腫がん幹細胞の発生・分化における細胞内小胞輸送の制御因子Rab6Bの役割(Role of a membrane traffic regulator Rab6B in the development of cancer stem cells in neuroblastoma)Meeting report
- (一社)日本小児血液・がん学会, Oct. 2014, 日本小児血液・がん学会雑誌, 51(4) (4), 233 - 233, English化学療法中に虫垂炎を発症した小児悪性腫瘍症例の検討(Acute appendicitis of cancer children during chemotherapy: A single center experience)Meeting report
- (公社)日本小児科学会, Jun. 2014, 日本小児科学会雑誌, 118(6) (6), 959 - 959, Japanese顔貌と胆汁うっ滞をきっかけとして診断に至ったAlagille症候群の1例Meeting report
- 2014, 日本造血細胞移植学会総会プログラム・抄録集, 36th骨髄移植後の卵巣機能障害に対するKaufmann療法中に肝線維腫を発症したALLの一例
- 日本小児科学会, Oct. 2013, 日本小児科学会雑誌, 117(10) (10), 1640 - 1644, JapaneseRomiplostim Therapy in a Child with Refractory Chronic Immune Thrombocytopenia
- 日本医療薬学会, 28 Aug. 2013, 日本医療薬学会年会講演要旨集, 23rd, 218 - 218, Japanese乳児血管腫に対するプロプラノロール内服療法の有用性について
- (一社)日本小児救急医学会, May 2013, 日本小児救急医学会雑誌, 12(2) (2), 195 - 195, Japanese積極的治療にて救命し長期間寛解を維持している頭蓋内出血合併急性前骨髄球性白血病の1例
- (一社)日本小児救急医学会, May 2013, 日本小児救急医学会雑誌, 12(2) (2), 276 - 276, Japanese哺乳不良・体重増加不良にて発症し著明な高カルシウム血症を呈した悪性腎腫瘍の1乳児例
- (一社)日本輸血・細胞治療学会, Apr. 2013, 日本輸血細胞治療学会誌, 59(2) (2), 330 - 330, Japanese抗Jka自己抗体を検出したIgA欠損症を伴うEvans症候群の一例Meeting report
- (公社)日本小児科学会, Feb. 2013, 日本小児科学会雑誌, 117(2) (2), 369 - 369, JapaneseビタミンB12欠乏性貧血を発症したDown症候群の乳児例Meeting report
- (公社)日本小児科学会, Jan. 2013, 日本小児科学会雑誌, 117(1) (1), 145 - 145, Japanese乳児血管腫に対するβ遮断薬の治療経験
- (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, Nov. 2012, 日本小児血液・がん学会学術集会、日本小児がん看護学会、公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号54回・10回・17回, 54回・10回・17回, 374 - 374, Japanese電撃性紫斑病にて発症した先天性Protein C欠損症の新生児例Meeting report
- (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, Nov. 2012, 日本小児血液・がん学会学術集会,日本小児がん看護学会,公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号54回・10回・17回, 54回・10回・17回, 334 - 334, Japanese初診時に高Ca血症を認めた小児悪性腫瘍3例の臨床的検討Meeting report
- (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, Nov. 2012, 日本小児血液・がん学会学術集会・日本小児がん看護学会・がんの子供を守る会公開シンポジウムプログラム・総会号, 54回・10回・17回, 291 - 291, Japanese神経芽腫症例におけるmultiple real‐time RT‐PCR markerを用いた微小残存病変(MRD)解析
- 日本小児呼吸器学会, Aug. 2012, 日本小児呼吸器疾患学会雑誌, 23(Suppl.) (Suppl.), 120 - 120, Japanese免疫性血小板減少症治療中の重症肺炎・ARDSに対しECMOを2回長期導入し救命し得た幼児例
- (公社)日本小児科学会, Feb. 2012, 日本小児科学会雑誌, 116(2) (2), 273 - 273, JapaneseヒトパルボウイルスB19感染症により血液学的異常を呈した6例の臨床的検討
- 01 Feb. 2012, 日本造血細胞移植学会総会プログラム・抄録集, 34th, 298, Japanese非血縁者間同種骨髄移植後にEBV関連リンパ増殖症および血球貪食症候群を合併し致死的経過をとった未分化大細胞性リンパ腫の1例
- (公社)日本小児科学会, Dec. 2011, 日本小児科学会雑誌, 115(12) (12), 1937 - 1937, Japaneseバルガンシクロビル内服治療により聴性脳幹反応異常が改善した先天性サイトメガロウィルス感染症の2例
- (NPO)日本小児がん学会, Nov. 2011, 日本小児血液・がん学会学術集会・日本小児がん看護学会・がんの子供を守る会公開シンポジウムプログラム・総会号, 48(プログラム・総会号) (プログラム・総会号), 341 - 341, Japanese初診時急性白血病様所見を呈した胞巣型横紋筋肉腫の1例
- (一社)日本血液学会-東京事務局, Sep. 2011, 臨床血液, 52(9) (9), 1242 - 1242, Japanese小児同種造血幹細胞移植におけるGFRの指標としての血清シスタチンCの有用性の検討
- (一社)日本検査血液学会, Jun. 2011, 日本検査血液学会雑誌, 12(学術集会) (学術集会), S93 - S93, Japanese初診時、播種性血管内凝固症候群(DIC)を発症、急性白血病が疑われた胞巣型横紋筋肉腫の一症例
- (公社)日本小児科学会, Mar. 2011, 日本小児科学会雑誌, 115(3) (3), 611 - 615, Japanese全身性けいれんと意識障害で発症した中枢神経系ループスの6歳例
- (公社)日本小児科学会, Feb. 2011, 日本小児科学会雑誌, 115(2) (2), 493 - 493, Japanese当院におけるユーイング肉腫ファミリー腫瘍の治療成績
- (公社)日本小児科学会, Dec. 2010, 日本小児科学会雑誌, 114(12) (12), 1939 - 1939, Japanese一児が臍帯ヘルニアであった一絨毛膜二羊膜性双胎の2例
- (公社)日本小児科学会, Dec. 2010, 日本小児科学会雑誌, 114(12) (12), 1941 - 1941, Japanese精神症状を主訴とした14歳女児のBasedow病の1例
- (公社)日本小児科学会, Dec. 2010, 日本小児科学会雑誌, 114(12) (12), 1942 - 1942, Japanese生来健康な児に発症したサイトメガロウイルス肝炎の1例
- (NPO)日本小児がん学会, Dec. 2010, 日本小児血液学会・日本小児がん学会・日本小児がん看護学会・財団法人がんの子供を守る会公開シンポジウムプログラム・総会号, 47(プログラム・総会号) (プログラム・総会号), 302 - 302, Japaneseタンデム自家末梢血幹細胞移植後2年間寛解維持している初診時骨髄転移陽性Ewing肉腫の1例
- (一社)日本血液学会-東京事務局, Sep. 2010, 臨床血液, 51(9) (9), 1279 - 1279, Japanese経口鉄キレート療法後のRISTにて速やかな生着と造血の回復を認めたDiamond‐Blackfan Anemiaの16歳女児例
- 姫路赤十字病院図書学術委員会, Jul. 2010, 姫路赤十字病院誌, 34, 13 - 18, Japanese全身性痙攣で発症しステロイドパルス療法が奏功したCNSループスの1例
- (公社)日本小児科学会, Dec. 2009, 日本小児科学会雑誌, 113(12) (12), 1894 - 1894, JapaneseBasedow病の診断時に僧帽弁逸脱を認めた2歳女児の1例
- (公社)日本小児科学会, Dec. 2009, 日本小児科学会雑誌, 113(12) (12), 1896 - 1896, Japanese当院における胃食道逆流症例の検討
- 姫路赤十字病院図書学術委員会, Jun. 2009, 姫路赤十字病院誌, 33, 136 - 136, Japanese小児疾患の身近な漢方治療 インフルエンザ・感冒性嘔吐下痢症を中心に
- 姫路赤十字病院図書学術委員会, Jun. 2009, 姫路赤十字病院誌, 33, 11 - 14, Japanese当院における髄膜炎起炎菌と抗生剤感受性に関する検討
- (公社)日本小児科学会, Mar. 2009, 日本小児科学会雑誌, 113(3) (3), 604 - 604, Japanese低血糖と意識障害をきっかけに診断されたプロピオン酸血症の1例
- (公社)日本小児科学会, Mar. 2009, 日本小児科学会雑誌, 113(3) (3), 604 - 604, Japanese新生児におけるくも膜下出血と初期嘔吐の臨床像の比較
- (公社)日本小児科学会, Mar. 2009, 日本小児科学会雑誌, 113(3) (3), 605 - 605, Japanese発熱を主訴に当院に入院した新生児74例の検討
- (公社)日本小児科学会, Mar. 2009, 日本小児科学会雑誌, 113(3) (3), 605 - 606, Japanese当科における腹腔鏡下鼠径ヘルニア手術(LPEC法)の導入
- (公社)日本小児科学会, Mar. 2009, 日本小児科学会雑誌, 113(3) (3), 608 - 608, Japanese当院における髄膜炎起炎菌と抗生剤感受性に関する検討
- (公社)日本小児科学会, Mar. 2009, 日本小児科学会雑誌, 113(3) (3), 608 - 608, Japanese抗SS-B抗体陽性であったエルシニア感染症の1例
- 日本赤十字社医学会, Sep. 2008, 日赤医学, 60(1) (1), 241 - 241, Japanese当院での川崎病におけるIVIG療法不応症例の検討
- 日本赤十字社医学会, Sep. 2008, 日赤医学, 60(1) (1), 242 - 242, Japaneseシクロフォスファミドが有効であった小児難治性ネフローゼ症候群の2例
- 第58回日本小児血液・がん学会学術集会, Dec. 2016, Japanese, 日本小児血液・がん学会, 東京, Domestic conferencePET-MRI所見に基づく肺・下鼻甲介・腎生検が原疾患の診断に有効であった二次性血球貪食リンパ組織球症の1例Poster presentation
- 第58回日本小児血液・がん学会学術集会, Dec. 2016, Japanese, 日本小児血液・がん学会, 東京, Domestic conferenceG-CSF投与と自家末梢血幹細胞移植を併用しbi-weekly VDC-IE療法を完遂し得た切除不能ユーイング肉腫例Oral presentation
- 第79回日本血液学会学術集会, Oct. 2016, Japanese, 日本血液学会, 横浜, Domestic conferenceReemergence of a translocation t(11;19)(q23;p13.1) in the absence of leukemiaPoster presentation
- 第78回日本血液学会学術集会, Oct. 2016, Japanese, 日本血液学会, 横浜, Domestic conferenceAggressive double-hit leukemia/lymphoma with t(14;18)(q32;q21) and t(8;21)(q24;q11.2)Poster presentation
- 第52回小児放射線学会学術集会, Jun. 2016, Japanese, 日本小児放射線学会, 東京, Domestic conferenceSpectral shaping+高ピッチ二重らせん撮影による低線量胸部CTOral presentation
- Advances in Neuroblastoma Research Conference 2016, Jun. 2016, English, Advances in Neuroblastoma Research Conference, Cairns, Australia, International conferenceRab6B mediates the progression of neuroblastoma through the interaction with MTMR5Poster presentation
- Advances in Neuroblastoma Research Conference 2016, Jun. 2016, English, Advances in Neuroblastoma Research Conference, Cairns, Australia, International conferenceDENN domain protein DENND2A regulates the progression of neuroblastoma.Poster presentation
- The 119th Annual Meeting of the Japan Pedeatric Society, May 2016, Japanese, Japan Pediatric Society, 札幌, Domestic conferenceMinimal residual disease monitoring in neuroblastoma patients.Oral presentation
- 第33回日本TDM学会学術大会, May 2016, Japanese, 日本TDM学会, 栃木, Domestic conferenceメチルプレドニゾロンの吸収不良により造血細胞移植後急性移植片対宿主病のコントロールに難渋した小児急性リンパ性白血病の1症例Poster presentation
- 第33回日本TDM学会・学術大会, May 2016, Japanese, 日本TDM学会, 宇都宮, Domestic conferenceメチルプレドニゾロンの吸収不良により造血細胞移植後急性移植片対宿主病のコントロールに難渋した急性リンパ性白血病の1症例Poster presentation
- The 57th Annual Meeting of the Japanese Society of Pediatric Hematology / Oncology, Nov. 2015, Japanese, The Japanese Society of Pediatric Hematology / Oncology, 甲府市, Domestic conferenceDifferential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patientsOral presentation
- 第57回日本小児血液がん学会学術集会, Nov. 2015, Japanese, 日本小児血液がん学会, 山梨, Domestic conference外来化学療法中(ALL B12臨床試験)の中心静脈カテーテルの管理についての検討Poster presentation
- 第57回日本小児血液がん学会学術集会, Nov. 2015, Japanese, 日本小児血液がん学会, 山梨, Domestic conferenceDifferential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients.Oral presentation
- The 57th Annual Meeting of the Japanese Society of Pediatric Hematology / Oncology, Nov. 2015, Japanese, The Japanese Society of Pediatric Hematology / Oncology, 甲府市, Domestic conferenceDENN domain protein DENND2A mediates the progression of neuroblastomaOral presentation
- 第57回日本小児血液がん学会学術集会, Nov. 2015, Japanese, 日本小児血液がん学会, 山梨, Domestic conferenceDENN domain protein DENND2A mediates the progression of neuroblastoma.Oral presentation
- 第74回日本癌学会学術総会, Oct. 2015, Japanese, 日本癌学会, 名古屋, Domestic conference神経芽腫の発症・進展におけるRab6BとRab28の役割Oral presentation
- 第77回日本血液学会学術集会, Oct. 2015, Japanese, 日本血液学会, 金沢, Domestic conferencePersistent MRSE infection and CV line-related thrombosis in AML patient in neutropenic phase.Oral presentation
- 第74回日本癌学会学術総会, Oct. 2015, Japanese, 日本癌学会, 名古屋, Domestic conferenceDENNドメイン蛋白質DENND2Aによる神経芽腫発の発症・進展の制御機構Oral presentation
- European Academy of Paediatrics, Sep. 2015, English, EAP, Oslo, ノルウェー, International conferenceClinical differences between Anaphylaxis children with prehospital remission and exacerbation.Oral presentation
- 第16回日本検査血液学会学術集会, Jul. 2015, Japanese, 日本検査血液学会, 名古屋, Domestic conference骨髄像にて腫瘍細胞の集簇を認め診断に難渋した急性巨核芽性白血病の1例Oral presentation
- 第29回日本小児救急医学会学術集会, Jun. 2015, Japanese, 日本小児救急医学会, 大宮, Domestic conference神戸こども初期急病センターにおける同日複数回受診患児についての検討Poster presentation
- 第265 回 日本小児科学会兵庫県地方会, May 2015, Japanese, 日本小児科学会兵庫県地方会, 神戸, Domestic conference左鎖骨部腫瘤を呈した生後6ヶ月の乳児例Oral presentation
- The 11th Asian Society for Pediatric Research, Apr. 2015, English, Asian Society for Pediatric Research, 大阪, International conferenceNeuroblastoma minimal residual disease markers are differentially expressed in peripheral blood and bone marrow samples.Poster presentation
- The 56th Annual Meeting of the Japanese Society of Pediatric Hematology/Oncology, Nov. 2014, Japanese, the Japanese Society of Pediatric Hematology/Oncology, 岡山, Domestic conferenceRole of a membrane traffic regulator Rab6B in the development of cancer stem cells in neuroblastomaOral presentation
- 第56回日本小児血液・がん学会学術総会, Nov. 2014, Japanese, 日本小児血液・がん学会, 岡山, Domestic conference化学療法中に虫垂炎を発症した小児悪性腫瘍症例の検討Oral presentation
- The 56th Annual Meeting of the Japanese Society of Pediatric Hematology/Oncology, Nov. 2014, English, the Japanese Society of Pediatric Hematology/Oncology, 岡山, Domestic conferenceAldehyde dehydrogenase ALDH1A2 regulates cancer stem cell properties in neuroblastoma.Oral presentation
- 第76回日本血液学会学術集会, Oct. 2014, English, 日本血液学会, 大阪, Domestic conferencePrognostic impact of absolute lymphocyte counts at the end of induction in pediatric non-T cell ALL.Oral presentation
- AACR Annual Meeting 2014 (American Association for Cancer Research), Apr. 2014, English, American Association for Cancer Research, San Diago, アメリカ, International conferenceInduction of ALDH1A2 expression is critical for cancer stem cell properties in neuroblastoma.Poster presentation
- 第36回近畿小児がん研究会, Feb. 2014, Japanese, 近畿小児がん研究会, 滋賀, Domestic conference開腹下腫瘍生検時にDamage control手術を行い、術後腹部コンパートメント症候群に対して血液透析下に化学療法を施行した神経芽腫破裂の1例Oral presentation
- 第55回日本小児血液・がん学会学術集会, Nov. 2013, Japanese, 日本小児血液・がん学会, 福岡, Domestic conference初診時に血管腫と鑑別を要した右下腿原発乳児線維肉腫の新生児例Poster presentation
- 第55回日本小児血液・がん学会学術集会, Nov. 2013, Japanese, 日本小児血液・がん学会, 福岡, Domestic conferenceメソトレキセート大量療法後の急性腎不全に対し血液浄化療法を施行した若年成人急性リンパ性白血病の1例Poster presentation
- Pediatric Cancer at The Crossroad, Nov. 2013, English, American Association for Cancer Research, San Diego, USA, Purpose: Neuroblastoma is the most common extra-cranial solid tumor that accounts for ~15% of all cancer-related deaths in children. Despite current aggressive therapies, more than half of high-risk neuroblastoma patients have experienced a tumor relapse leading to mostly cancer-related deaths. As in most cancers, recurrent neuroblastoma is primarily driven by chemoresistant ca, International conferenceIdentification of ALDH1A2 as a critical ALDH isoform in neuroblastoma cells with cancer stem cell phenotypePoster presentation
- 第75回日本血液学会学術集会, Oct. 2013, Japanese, 日本血液学会, 札幌, Domestic conferenceCytokine changes in a juvenile case with rapidly progressive multicentric Castleman disease.Poster presentation
- 第23回日本医療薬学会年会, Sep. 2013, Japanese, 日本医療薬学会, 仙台, Domestic conference乳児血管腫に対するプロプラノロール内服療法の有用性についてOral presentation
- 第27回日本小児救急医学会学術集会, Jun. 2013, Japanese, 日本小児救急医学会, 沖縄, Domestic conference哺乳不良・体重増加不良にて発症し著明な高カルシウム血症を呈した悪性腎腫瘍の1乳児例Oral presentation
- 第27回日本小児救急医学会学術集会, Jun. 2013, Japanese, 日本小児救急医学会, 沖縄, Domestic conference積極的治療にて救命し長期間寛解を維持している頭蓋内出血合併急性前骨髄球性白血病の1例Oral presentation
- 第61回日本輸血・細胞治療学会, May 2013, Japanese, 日本輸血・細胞治療学会, 横浜, Domestic conference抗Jka自己抗体を検出したIgA欠 損症を伴うEvans症候群の一例Poster presentation
- 第116回日本小児科学会学術集会, Apr. 2013, Japanese, 日本小児科学会, 広島, Domestic conferenceビタミンB12欠乏性貧血を発症したDown症候群の乳児例Oral presentation
- 第35回日本造血細胞移植学会総会, Mar. 2013, Japanese, 日本造血細胞移植学会, 石川, Domestic conference骨髄移植後の造血機能不全に対して同一の非血縁ドナーからの前処置なしで骨髄液再輸注を行い、有効であった慢性活動性EBV感染症の一例Poster presentation
- 第 258 回 日本小児科学会兵庫県地方会, Feb. 2013, Japanese, 尼崎, Domestic conference顔貌と胆汁うっ滞をきっかけとして診断に至った Alagille 症候群の1例Oral presentation
- 第258回日本小児科学会兵庫県地方会, Feb. 2013, Japanese, 日本小児科学会兵庫県地方会, 尼崎, Domestic conference顔貌と胆汁うっ滞をきっかけとして診断に至ったAlagille症候群の1例Oral presentation
- 第54回日本小児血液・がん学会学術集会, Dec. 2012, Japanese, 日本小児血液・がん学会, 横浜, 【諸言】神経芽腫の予後は全体的には改善したが、進行例の長期予後は未だ不良であり、微小残存病変 (MRD) の正確 な評価が予後改善には不可欠である。今回我々は、MRD 検索の感度向上のため、multiple real-time RT-PCR marker を 用いた MRD 測定系を樹立し、各マーカーの感度、臨床情報との相関について解析を行った。【方法】既報の 11 の MRD マーカー (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B, TH) について、神経芽腫 tumor initiating cells を段階的に希釈して検量線を作成し 、基準値を設定した。倫理委員会の 承認の下、2011 年 2 月から 2012 年 6 月までに当科で経験した, Domestic conference神経芽腫症例におけるmultiple real-time RT-PCR markerを用いた微小残存病変(MRD)解析Oral presentation
- 第54回日本小児血液・がん学会学術集会, Nov. 2012, Japanese, 横浜, Domestic conference電撃性紫斑病にて発症した先天性Protein C欠損症の新生児例Poster presentation
- 第54回日本小児血液・がん学会学術集会, Nov. 2012, Japanese, 横浜, Domestic conference初診時に高Ca血症を認めた小児悪性腫瘍3例の臨床的検討Poster presentation
- 第74回日本血液学会学術集会, Oct. 2012, Japanese, 東京, Domestic conference当院における造血幹細胞移植後のリンパ球回復とその予後の検討Poster presentation
- 第45回日本小児呼吸器疾患学会, Sep. 2012, Japanese, 旭川, Domestic conference免疫性血小板減少症治療中の重症肺炎・ARDSに対しECMOを2回長期導入し救命し得た幼児例Oral presentation
- 2012ASCO meeting, Jun. 2012, English, American Society of Clinical Oncology, Chicago, Background: IP is the standard treatment for ED-SCLC, however often cause severe diarrhea. AP have shown promising activity in SCLC with fewer diarrhea. We conducted a phase III trial comparing AP with IP. Methods: Eligibility criteria included patients (, International conferenceA phase III study comparing amrubicin and cisplatin (AP) with irinotecan and cisplatin (IP) for the treatment of extended-stage small cell lung cancer (ED-SCLC): JCOG0509.Keynote oral presentation
- 第256回日本小児科学会兵庫県地方会 神戸 2012.5.26, May 2012, Japanese, 神戸, Domestic conference乳児血管腫に対するβ遮断薬の治療経験Oral presentation
- 第53回日本小児血液・がん学会学術集会, Nov. 2011, Japanese, 日本小児血液・がん学会, 前橋, Domestic conferenceA case of alveolar rhabdomyosarcoma mimicking acute leukemia of admissionPoster presentation
- 第73回日本血液学会学術集会, Oct. 2011, Japanese, 日本血液学会, 名古屋, Domestic conference小児同種造血幹細胞移植におけるGFRの指標としての血清シスタチンCの有用性の検討Others
- the 43rd Congress of the International Society of Pediatric Oncology, Oct. 2011, English, オークランド, ニュージーランド, International conferencePlace of Death of Pediatric Cancer Patients in JapanOthers
- 第114回日本小児科学会学術集会, Aug. 2011, Japanese, 日本小児科学会, 東京, Domestic conference当院におけるユーイング肉腫ファミリー腫瘍の治療成績Others
- 第253回日本小児科学会兵庫県地方会, May 2011, Japanese, 日本小児科学会兵庫県地方会, 神戸, Domestic conferenceバルガンシクロビル内服治療により聴性脳幹反応異常が改善した先天性サイトメガロウィルス感染症の2例Oral presentation
- 第25回近畿小児科学会, Mar. 2011, Japanese, 近畿小児科学会, 京都, Domestic conferenceトロンボポエチン受容体作動薬が有効であった何時性慢性ITPの1歳男児例Others
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2021 - 31 Mar. 2024神経芽腫のがん微小環境制御における間葉系幹細胞の役割に関する研究神経芽腫は、神経堤細胞が交感神経系へ分化する過程で発生する代表的な小児難治性固形がんで、小児がん死亡の約1/6を占めている。特に、高リスク神経芽腫患者の大部分は、一旦は治療に反応して寛解を達成するが、その半数以上が再発して極めて治療困難になり、その長期生存率は未だ50%に達していない。これには、治療後に微小残存病変(MRD)として体内に残存したがん細胞が再活性化し、異なる形質を示すようになることが重要だと考えられる。化学療法や放射線療法は、治療後に亜致死となったがん細胞および微小環境中の間質細胞に細胞老化を誘導(治療誘発細胞老化:TIS)し、エクソソームやサイトカイン等の分泌(細胞老化随伴分泌現象:SASP)を促していることが明らかになり、治療困難のメカニズムを理解するためには、がん細胞の異なる形質の発現を担う分泌因子の同定が必須だと考えられる。これまでに申請者らは、MRDの新規評価法を開発してその動態を明らかにすると共に、神経芽腫細胞と微小環境の主要な構成細胞で分泌活性の高い間葉系幹細胞(MSC)との相互作用を明らかにしてきた。そこで本研究では、MSCのSASPによって分泌される分子を同定し、その機能を明らかにすることを試みる。本年度の研究では、高リスク神経芽腫治療に用いられるシスプラチン(CDDP)やテモゾロミド(TMZ)によるMSCのSASPによって分泌される分子群を同定した。
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2017 - 31 Mar. 2020High-risk neuroblastoma causes more than 50% relapse and shows therapy resistance. This is mainly due to tumor heterogeneity that is induced by tumor microenvironment and therapy stress and controlled by Rab family small G proteins (Rabs), key regulators of membrane traffic. In the present study, we have identified some members of Rabs, which potentially control the secretion of growth factors and tumor markers in neuroblastoma microenvironment.Competitive research funding
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), Kobe University, 01 Apr. 2016 - 31 Mar. 2018, Principal investigatorNeuroblastoma is a typical recurrent and refractory tumor in children and its long-term survival remains less than 40%. Neuroblastoma relapse is caused by activation of chemo-resistant cancer stem cells (CSCs). Key regulators of intracellular vesicle trafficking, DENN domain proteins, were implicated in this process. In this study, a member of DENND domain proteins DENND2A and its target Rab family small G protein Rab9B were found to be involved in the development and progression of neuroblastoma.Competitive research funding
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), Kobe University, 01 Apr. 2014 - 31 Mar. 2016, Principal investigatorMore than half of high-risk neuroblastoma patients experience tumor relapses and less than 40% can expect a long-term survival. Intracellular vesicle transport seems to play an important role on the development of neuroblastoma cancer stem cells that are responsible for tumor relapses. In this study, we focused on DENN domain proteins, regulators of intracellular vesicle transport, and revealed that a member of DENN domain proteins is involved in the progression of neuroblastoma.Competitive research funding