Masataka Takeshita's research while affiliated with Tokyo-Kita Medical Center and other places

Publications (29)

Article
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Extramedullary disease (EMD) is known to be associated with chemoresistance and poor prognosis in multiple myeloma (MM); however, the mechanisms of its development are not fully understood. Elucidating the mechanism of EMD development and its therapeutic targeting would greatly contribute to further improvement of treatment outcome in MM patients....
Article
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Objective Currently, treatment of relapsed or refractory multiple myeloma is challenging. Although bortezomib-thalidomide-dexamethasone-cisplatin-doxorubicin-cyclophosphamide-etoposide (VTD-PACE), a potent combination of a proteasome inhibitor, immunomodulatory drug, and conventional chemotherapeutics, is a widely used regimen, its efficacy and saf...
Article
Autologous stem cell transplantation(ASCT)for newly-diagnosed multiple myeloma(NDMM)has underwent recent improvements in combination with novel agents-containing induction and post-ASCT therapy. Since the approval of bortezomib for NDMM in Japan, we conducted the following regimen(BD arm)in transplant-eligible patients with NDMM: BD (bortezomib and...
Article
Introduction The International Myeloma Working Group (IMWG)-frailty index (IMWG-FI) and revised myeloma comorbidity index (R-MCI) are multiple myeloma (MM)-specific frailty scoring systems, which the European Myeloma Network advocates to assess patient frailty, and to select goals and treatments including autologous stem cell therapy (ASCT). In Jap...
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Objective Although R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) is a standard therapy for diffuse large B-cell lymphoma (DLBCL), the optimal dose for elderly patients remains unclear. Methods and Patients We retrospectively verified our R-CHOP dose-attenuation system implemented from 2005 for DLBCL patients. Among...
Article
Two regimens are commonly used for peripheral blood hematopoietic stem cell harvesting (PBSCH) in multiple myeloma: high-dose cyclophosphamide (HD-CY) + granulocyte-colony stimulating factor (G-CSF), and G-CSF alone. The objective of the present study was to evaluate the anti-myeloma effect of the PBSCH regimen including HD-CY. We retrospectively a...
Article
background. High dose therapy and autogenic or allogeneic stem cell transplantation plays an important role in the treatment course of hematological malignancies. In some countries, major method of unrelated stem cell donation programs had shifted from bone marrow harvest (BM) to peripheral blood stem cell harvest (PBSCH). PBSCH is a heavy duty not...
Article
Background Kidney injury and/or renal failure are common complication in multiple myeloma. Well known mechanism is deposition of free immunoglobulin light chains in renal tubules leading to cast nephropathy and renal failure. In addition, not only cast nephropathy, but also invasion of myeloma cells is frequently found in autopsied cases of multipl...
Article
Background Autologous stem cell transplantation (ASCT) has been a part of the standard therapy for newly diagnosed multiple myeloma and several studies showed double ASCT improved the outcome in comparison with single ASCT, especially the patients who failed to achieve very good partial remission (VGPR). Recently, the introduction of novel agents s...
Article
3639 Background The combination therapy of RCHOP [rituximab (R), cyclophosphamide (CY), doxorubicin (DOX), vincristine (VCR), and prednisone (PSL)] is a standardized treatment for diffuse large B-cell lymphoma (DLBCL). However, its clinical outcome is worse in elderly patients because of comorbidities, age-related decrease in organ function, and i...
Article
2007 Background High-dose cyclophosphamide (HD-CY) + granulocyte-colony stimulating factor (G-CSF) and G-CSF alone have been used to mobilize hematopoietic stem cells (HSCs) for autologous SC transplantation (ASCT) in multiple myeloma (MM). However, which regimen is better is unknown; anti-myeloma effects of HD-CY + G-CSF have not been established...
Article
The p210Bcr/Abl and p190Bcr/Abl fusion oncoproteins are known to cause chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). Bcr/Abl phosphorylates several proteins that can lead to leukemogenesis. Crk-associated substrate lymphocyte type (Cas-L)/human enhancer of filamentation-1 (HEF1)/neural precursor cell expressed, developm...
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5001 Background Renal insufficiency is one of the main complications in myeloma patients. Various causes were reported to be responsible for renal damage. Through analysis of an autopsied cases we would show the diversity of the renal diseases in myeloma. Methods We studied 41 autopsied myeloma cases from 1979 to 2008 at the National Center for G...
Article
5004 Background Despite recent progress in treatment, multiple myeloma is still uncurable disease. The impact of modern therapy on the causes of death and pathological feature of end-stage myeloma is not fully understood. Methods We studied autopsied cases with multiple myeloma between 1979 and 2009 at National Medical Center of Global Health and...
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Evi-1 is a zinc-finger transcriptional factor whose inappropriate expression leads to leukemic transformation in mice and humans. Recently, it has been shown that Evi-1 regulates proliferation of hematopoietic stem/progenitor cells at embryonic stage via GATA-2 up-regulation; however, detailed mechanisms underlying Evi-1-mediated early hematopoiesi...
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Transcription factor AML1/Runx1, initially isolated from the t(8;21) chromosomal translocation in human leukemia, is essential for the development of multilineage hematopoiesis in mouse embryos. AML1 negatively regulates the number of immature hematopoietic cells in adult hematopoiesis, whereas it is required for megakaryocytic maturation and lymph...
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The t(3;21) chromosomal translocation seen in blastic crisis of chronic myeloid leukemia and secondary leukemias results in a formation of a chimeric protein AML1-Evi-1, which suppresses wild-type AML1 function. Loss of AML1 function causes expansion of hematopoietic progenitor cells, whereas it is not sufficient for the development of leukemia. To...
Article
Transcription factor AML1/RUNX1, initially isolated from the t(8;21) chromosomal translocation in human leukemia, is essential for the development of multilineage hematopoiesis in mouse embryos. AML1 negatively regulates the number of immature hematopoietic cells in adult hematopoiesis, while it is required for megakaryocytic maturation and lymphoc...
Article
Cas-L (Crk-associated substrate lymphocyte type) which is also known as Hef1/Nedd9 was first identified as a protein tyrosine-phosphorylated upon stimulation of β1 integrin in peripheral T cells. Cas-L is a member of Cas family proteins, with a single Src homology (SH) 3 domain and multiple YXXP motifs (substrate domain) and functions as a docking...
Article
Transcription factor AML1 (also called Runx1), which was initially isolated from the t(8;21) chromosomal translocation frequently found in the acute myelogenous leukemia FAB M2 subtype, is essential for the development of multilineage hematopoiesis in mouse embryos. By analyzing conditional AML1 knockout mice, we have previously shown that AML1 neg...
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Constitutively active internal tandem duplication (ITD) in the juxtamembrane domain of Fms-like tyrosine kinase 3 (FLT3), a type III receptor tyrosine kinase, is the most common molecular defect associated with acute myeloid leukemia. Its presence confers a poor outcome in patients with acute myeloid leukemia who receive conventional chemotherapy....
Article
[Background] FLT3 is a class III receptor tyrosine kinase which is widely expressed on hematopoietic stem/progenitor cells. Two types of constitutively active FLT3 mutations have been reported to be expressed on a subset of leukemic cells; internal tandem duplications (ITD) and kinase domain mutations. The former are associated with poor prognosis...
Article
A male patient had a relapse of myelodysplastic syndrome (MDS) 2 years after BMT from a female matched unrelated donor. Conventional cytogenetics, FISH, and short-tandem repeat chimerism analysis proved a relapse of donor origin. He underwent reduced-intensity BMT after a conditioning with fludarabine and busulfan, since he had impaired renal, live...
Article
Polymerase chain reaction (PCR) is a sensitive method for detection of Aspergillus DNA in bronchoalveolar lavage fluid, but it has not yet been able to distinguish infection from contamination. We have established a technique to quantify Aspergillus DNA using a real-time PCR method to resolve this problem, and we report herein a successful applicat...
Article
Full-text available
Hepatitis B virus (HBV) reactivation in patients previously positive for hepatitis B surface antibody (HBsAb), so-called reverse seroconversion, has been considered to be a rare complication after hematopoietic stem cell transplantation (HSCT). We experienced two patients who developed reverse seroconversion among nine who were HBsAb positive and H...

Citations

... The quantitative data are expressed as photon units (photons/s). [25][26][27] We also used an orthotopic MM model, in which luciferase-expressing KMS26 cells were engrafted into the bone marrow of NOD/SCID mice via tail-vein injection. All animal studies were approved by the Institutional Animal Ethics Committee and performed in accordance with the Guide for the Care and Use of Lab-oratory Animals formulated by the National Academy of Sciences. ...
... Even in cases of relapse, treatment outcomes have improved with the use of novel agents [3]. However, in situations where novel agents have been exhausted or when the disease rapidly progresses, bortezomib (Velcade), thalidomide, dexamethasone, platinum (cisplatin), Adriamycin (doxorubicin), cyclophosphamide, and etoposide (VTD-PACE) have been frequently utilized, with reported effectiveness [4][5][6][7]. However, in the era of monoclonal antibodies, the outcome of VTD-PACE for patients with relapsed/refractory MM (RRMM) with anti-CD38 antibody resistance or triple-class refractory disease has not been fully evaluated. ...
... Accordingly, G-CSF alone may be an alternative method to collect autologous peripheral blood stem cells for elderly patients. On the other hand, a recent retrospective study (25) suggested that the CY regimen exhibits an anti-myeloma effect; therefore, the selection of mobilization methods should be balanced with regard to efficacy and toxicity, especially in elderly patients. ...
... Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), accounting for approximately 30% of NHL cases [1][2][3]. Although DLBCL has an aggressive disease course and poor prognosis, its clinical outcome and prognosis have improved since the era of rituximab therapy [1,4]. Over the past 10 years, six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combination chemotherapy (R-CHOP), administered every 3 weeks, have been the current standardof-care for previously untreated patients with DLBCL [5,6]. ...
... Stem cell mobilisation in MM is usually performed using a combination of granulocyte-colony stimulating factor (G-CSF) and cyclophosphamide (CY), or G-CSF alone. The former leads to higher CD34 + cell yields [4][5][6][7][8][9][10][11][12][13], but has been associated, particularly at CY doses ≥3 g/m 2 , with significant morbidity from febrile neutropenia and unplanned hospitalisations [10,11,[14][15][16]. Cytokine only mobilisation is less toxic [17,18] but is associated with a higher chance of mobilisation failure in heavily pre-treated individuals [19,20]. ...
... The overexpression of either fusion gene into Ctrl cells enabled hematopoietic colonies to be serially replated in methylcellulose culture with cytokines ( Figure 5C-E) as demonstrated previously. 42,43 In contrast, Kdm4b deficiency significantly reduced colony-forming activity in successive rounds of plating ( Figure 5D,E; Figure S3A), indicating a cell-intrinsic requirement of Kdm4b for robust clonogenic potential coupled with t(8;21). Supporting the compromised colony-forming properties in Kdm4b deficiency, AE-transduced Kdm4b Δ/Δ colony-forming cells displayed significantly decreased expression of HSCfingerprint genes, concurrently with increased expression of genes associated with differentiated states (monocyte and granulocyte fingerprints) 16 ( Figure 5F). ...
... 22 NEDD9-deficient p210-BCR/ABL transgenic mice show an increased number of granulocytes in peripheral blood, a hyperplasia of myeloid and megakaryocytic cells in the bone marrow and a diffuse myeloid infiltration in the spleen, lung and liver, leading to earlier progression and shorter mouse survival, which support NEDD9 capacity to block chronic myeloid leukaemia (CML) progression. 23 There are few studies on the association of NEDD9 and AML. 24 Herein, as far as known, we for the first time identified and verified that NEDD9 expression, among NEDD family members, was significantly increased in AML. ...
... [38,39] e. Polymerase chain reaction (PCR) test: Specific positive bands are amplified with the specific primers for the fungal 18S transfer ribonucleic acid (tRNA) and ribosomal deoxyribonucleic acid (rDNA). [40,41] ...
... Five of the nine patients received a second transplant, three of which died, and two were alive at 5 and 11 months after the second transplant, respectively [16]. In general, chemotherapy followed by a second allo-HCT from an alternative donor seems to be a preferable choice of treatment, though a second transplant from the same donor was also applied with success [39], and in some cases, donor lymphocyte infusion resulted in a transient response [40]. A more recent review of donor cell-derived leukemia by Wiseman et al. included outcome data available in 58 patients [19]. ...
... EPHB4 has an extracellular region containing an ephrin-binding domain, a cysteine-rich domain and two fibronectin type III repeats, and an intracellular region containing a tyrosine kinase domain, a sterile alpha motif and a PDZ-binding motif [4]. The extracellular region and tyrosine kinase domain represent excellent targets for developing high-affinity antagonistic compounds [5][6][7]. EPHB4 activation can promote cancer growth, migration and metastasis by activating downstream signaling pathways including the RAS/MEK/ERK and EPHB4/RHOA pathways [8,9]. Therefore, EPHB4 is a promising therapeutic target for the development of novel treatment for various types of cancers [10]. ...