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Author

Takako Miyamura

Other affiliations: Okayama University
Bio: Takako Miyamura is an academic researcher from Osaka University. The author has contributed to research in topics: Transplantation & Hematopoietic stem cell transplantation. The author has an hindex of 10, co-authored 54 publications receiving 447 citations. Previous affiliations of Takako Miyamura include Okayama University.


Papers
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Journal Article
TL;DR: The prostate cancer HERV-K gag-related NGO-Pr-54 antigen was identified by SEREX analysis using autologous patient serum and showed a strong reaction was constantly observed with clone ZH042, suggesting that it contained the sequence coding for the protein product.
Abstract: The prostate cancer HERV-K gag-related NGO-Pr-54 antigen was identified by SEREX analysis using autologous patient serum. NGO-Pr-54 mRNA was observed to be faintly expressed in normal prostate and strongly expressed in a variety of cancers, including ovarian cancer (5/8), prostate cancer (6/9), and leukemia (5/14). A phage plaque assay showed that a strong reaction was constantly observed with clone ZH042 in which the 5' end of NGO-Pr-54 is deleted, suggesting that it contained the sequence coding for the protein product. A TI-35 mAb was produced using a recombinant protein (438 aa) deduced from the sequence of ZH042. Transfection of clone ZH042 into 293T cells resulted in the production of an approximately 50-kDa molecule visualized by Western blotting. Natural production of the molecule was confirmed in a SK-MEL-23 melanoma cell line. An indirect immunofluorescence assay showed that NGO-Pr-54 protein was expressed on the cell surface as well as in the cytoplasm. Cell surface expression was confirmed by flow cytometry using the TI-35 mAb. The antibody response against NGO-Pr-54 was observed in patients with bladder (5.1%), liver (4.1%), lung (3.4%), ovarian (5.6%), and prostate (4.2%) cancer, as well as with malignant melanoma (13.2%).

76 citations

Journal ArticleDOI
TL;DR: This study was undertaken to explore the clinical relevance and molecular mechanisms underlying the activation of Akt (i.e., phosphorylated Akt, P‐Akt) in pediatric B‐pre ALL.
Abstract: Background Activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway, a pro-survival pathway, plays important roles in tumor cell growth. However, the role of Akt in the pathogenesis of pediatric B-precursor acute lymphoblastic leukemia (B-pre ALL) remains to be clarified. This study was undertaken to explore the clinical relevance and molecular mechanisms underlying the activation of Akt (i.e., phosphorylated Akt, P-Akt) in pediatric B-pre ALL. Procedure We evaluated the activation status of Akt in bone marrow samples from 21 children with newly diagnosed B-pre ALL and correlated the expression level of P-Akt with clinicopathologic and prognostic features. Additionally, we transfected the myristoylated Akt cDNA into the B-pre ALL cell line, Nalm-6, and examined the effect, in vitro, of Akt activation on the response to antitumor drugs. Results P-Akt expression in B-pre ALL blast cells at diagnosis was associated significantly with poor response to induction chemotherapy including prednisolone, dexamethasone, vincristine, and adriamycin in B-pre ALL patients. Both overall survival and relapse-free survival in patients with P-Akt expression were reduced significantly more than in patients without P-Akt expression. Activation of Akt reduced the extent of apoptosis induced by the antitumor drugs in Nalm-6 listed above. Activation of Akt did not induce expression of P-glycoprotein, a drug transporter that is capable of conferring multidrug resistance. Conclusion These results support the contention that Akt activation is a mechanism of chemotherapeutic resistance in B-pre ALL and suggest that Akt can be a therapeutic target for the treatment of relapsed or refractory pediatric B-pre ALL. Pediatr Blood Cancer 2012; 59: 83–89. © 2011 Wiley Periodicals, Inc.

73 citations

Journal ArticleDOI
15 Oct 2020-Blood
TL;DR: Risk stratification and introduction of intensive chemotherapy in the current study were effective and able to eliminate HSCT for a subset of infants with KMT2A-r ALL and should be incorporated into risk stratifications in future trials.

56 citations

Journal ArticleDOI
01 Feb 2015-Leukemia
TL;DR: The fact that substantial number of patients still relapsed even though transplanted in their first remission indicates the limited efficacy of allogeneic HSCT for infants with MLL-r ALL, and indications for HSCT should be restricted to specific subgroups with poor risk factors.
Abstract: Sixty-two infants with MLL gene-rearrangement-positive acute lymphoblastic leukemia (MLL-r ALL) were treated with the MLL03 protocol of the Japanese Pediatric Leukemia/Lymphoma Study Group: short-course intensive chemotherapy followed by early allogeneic hematopoietic stem cell transplantation (HSCT) within 4 months of the initial induction. The 4-year event-free survival and overall survival rates were 43.2% (95% confidence interval (CI)=30.7-55.1%) and 67.2% (53.8-77.4%), respectively. A univariate analysis showed younger age (<90 days at diagnosis), central nervous system disease and poor response to initial prednisolone therapy significantly associated with poor prognosis (P<0.05). In a multivariate analysis, younger age at diagnosis tended to be associated with poor outcome (hazard ratio=1.969; 95% CI=0.903-4.291; P=0.088). Although the strategy of early use of HSCT effectively prevented early relapse and was feasible for infants with MLL-r ALL, the fact that substantial number of patients still relapsed even though transplanted in their first remission indicates the limited efficacy of allogeneic HSCT for infants with MLL-r ALL. Considering the risk of severe late effects, indications for HSCT should be restricted to specific subgroups with poor risk factors. An alternative approach incorporating molecular-targeted drugs should be established.

50 citations

Journal ArticleDOI
TL;DR: A retrospective analysis of infants with recurrent or refractory ALL from two previous consecutive Japanese studies to clarify the characteristics and prognostic factors among these patients.
Abstract: Background Despite the poor outcome of recurrent or refractory acute lymphoblastic leukemia (ALL) in infants with MLL gene rearrangement, few studies have focused on this specific group. We conducted a retrospective analysis of infants with recurrent or refractory ALL from two previous consecutive Japanese studies to clarify the characteristics and prognostic factors among these patients Procedure All recurrent or refractory ALL infants with MLL gene rearrangement (MLL-R) who were registered in two consecutive Japanese nation-wide multicentric trials (MLL96 and MLL98; between 1995 and 2001) were eligible for the study. Results Among 80 MLL-R ALL infants, 34 cases of recurrence and 5 induction failures occurred. The median duration of first remission was 5 months (range, 0–28 months). All patients underwent various salvage chemotherapies; remission was achieved in 40.5% (15/37). A total of 23 patients received subsequent hematopoietic stem cell transplantations (HSCT): 9 in remission, 12 without remission, and 2 with unknown status. With median follow-up period of 5.5 years, the 5-year overall survival (OS) rate after the second-line treatment was 25.6% ± 6.9%. Young age (<3 months) and central nervous system involvement at initial diagnosis were associated with poor outcome; however, failure to achieve remission after salvage therapy was the sole independent poor prognostic factor in multivariate analysis (P = 0.01). Conclusions The prognosis of infants with recurrent or refractory MLL-R ALL is extremely poor despite alternative treatments including HSCT; therefore, it is necessary to develop novel treatment strategies. Pediatr Blood Cancer 2009;52:808–813. © 2009 Wiley-Liss, Inc.

37 citations


Cited by
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Journal ArticleDOI
TL;DR: The results suggest that Fgf23 acts downstream of Phex to cause both the renal and bone phenotypes in Hyp mice, and additional factors, associated with either osteocyte differentiation and/or extracellular matrix, are necessary for Phex deficiency to stimulate F gf23 gene transcription in bone.
Abstract: Inactivating mutations of the PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) endopeptidase, the disease-causing gene in X-linked hypophosphatemia (XLH), resu...

466 citations

Book ChapterDOI
01 Jan 2003
TL;DR: In this chapter, the evidence for an effect of such treatment on long-term outcome is considered, and it is attempted to distinguish changes that are simply a part of the natural history of the disorder from those that are truly associated with therapeutic intervention.
Abstract: The prognosis in West syndrome is poor overall, although a small number of individuals recover, with both resolution of seizures and achievement of normal mental development. While the natural history of this disorder is, in general, well documented, major questions remain unanswered regarding the factors that influence, or predict, outcome, and the long-term benefits of various therapeutic modalities. As discussed in the preceding chapter, a number of therapies have demonstrated efficacy for the control of spasms and improvement of the EEG characteristics. In this chapter, the evidence for an effect of such treatment on long-term outcome is considered, and we attempt to distinguish changes that are simply a part of the natural history of the disorder from those that are truly associated with therapeutic intervention.

372 citations

Journal ArticleDOI
TL;DR: Unraveling the components of this hormone/enzyme/extracellular matrix pathway will not only lead to a better understanding of phosphate homeostasis and mineralization but may also improve the diagnosis and treatment of hypo- and hyperphosphatemic disorders.
Abstract: There is evidence for a hormone/enzyme/extracellular matrix protein cascade involving fibroblastic growth factor 23 (FGF23), a phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX), and a matrix extracellular phosphoglycoprotein (MEPE) that regulates systemic phosphate homeostasis and mineralization. Genetic studies of autosomal dominant hypophosphatemic rickets (ADHR) and X-linked hypophosphatemia (XLH) identified the phosphaturic hormone FGF23 and the membrane metalloprotease PHEX, and investigations of tumor-induced osteomalacia (TIO) discovered the extracellular matrix protein MEPE. Similarities between ADHR, XLH, and TIO suggest a model to explain the common pathogenesis of renal phosphate wasting and defective mineralization in these disorders. In this model, increments in FGF23 and MEPE, respectively, cause renal phosphate wasting and intrinsic mineralization abnormalities. FGF23 elevations in ADHR are due to mutations of FGF23 that block its degradation, in XLH from indirect actions of inactivating mutations of PHEX to modify the expression and/or degradation of FGF23 and MEPE, and in TIO because of increased production of FGF23 and MEPE. Although this model is attractive, several aspects need to be validated. First, the enzymes responsible for metabolizing FGF23 and MEPE need to be established. Second, the physiologically relevant PHEX substrates and the mechanisms whereby PHEX controls FGF23 and MEPE metabolism need to be elucidated. Finally, additional studies are required to establish the molecular mechanisms of FGF23 and MEPE actions on kidney and bone, as well as to confirm the role of these and other potential "phosphatonins," such as frizzled related protein-4, in the pathogenesis of the renal and skeletal phenotypes in XLH and TIO. Unraveling the components of this hormone/enzyme/extracellular matrix pathway will not only lead to a better understanding of phosphate homeostasis and mineralization but may also improve the diagnosis and treatment of hypo- and hyperphosphatemic disorders.

309 citations

Journal ArticleDOI
TL;DR: The normal biological roles of MLL1 and its fusion partners are discussed, how these roles are hypothesized to be dysregulated in the context of M LL1 rearrangements, and the clinical manifestations of this group of leukemias are discussed.
Abstract: The Mixed-lineage leukemia 1 (MLL1) gene (now renamed Lysine [K]-specific MethylTransferase 2A or KMT2A) on chromosome 11q23 is disrupted in a unique group of acute leukemias. More than 80 different partner genes in these fusions have been described, although the vast majority of leukemias result from MLL1 fusions with one of about six common partner genes. Approximately 10% of all leukemias harbor MLL1 translocations. Of these, two patient populations comprise the majority of cases: patients younger than one year of age at diagnosis (primarily acute lymphoblastic leukemias), and young- to-middle-aged adults (primarily acute myeloid leukemias). A much rarer subgroup of patients with MLL1 rearrangements develop leukemia that is attributable to prior treatment with certain chemotherapeutic agents – so-called “therapy related leukemias”. In general, outcomes for all of these patients remain poor when compared to patients with non-MLL1 rearranged leukemias. In this review we will discuss the normal biological roles of MLL1 and its fusion partners, how these roles are hypothesized to be dysregulated in the context of MLL1 rearrangements, and the clinical manifestations of this group of leukemias. We will go on to discuss the progress in clinical management and promising new avenues of research which may lead to more effective targeted therapies for affected patients.

283 citations