Publications by authors named "Masayuki Mita"

7 Publications

  • Page 1 of 1

The BCR/ABL tyrosine kinase inhibitor, nilotinib, stimulates expression of IL-1β in vascular endothelium in association with downregulation of miR-3p.

Leuk Res 2017 07 5;58:83-90. Epub 2017 May 5.

Department of Hematology, Fukushima Medical University, Hikarigaoka-1, Fukushima 960-1295, Japan. Electronic address:

BCR/ABL tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis for in dividuals with chronic myeloid leukemia (CML). However, many patients treated with TKIs suffer from TKI-related complications. In particular, vascular events such as peripheral artery occlusive disease have become aserious clinical problem for patients who receive the TKI, nilotinib. At present, the molecular mechanisms by which TKIs cause vascular endothelial cell insults remain unknown.This study explored the effects of the TKIs, imatinib, nilotinib and dasatinib, on vascular endothelial cells in vitro, and found that only nilotinib induced expression of interleukin-1β (IL-1β) by vascular endothelial cells. Nilotinib-induced IL-1β expression stimulated the adhesion of monocytes to vascular endothelial cells in association with an increase in levels of adhesion molecules. MicroRNA database searching identified miR-3121-3p binding sites in the 3'-UTR of the IL-1β gene. Exposure of endothelial cells to nilotinib caused downregulation of miR-3121-3p in these cells. Importantly, forced-expression of miR-3121-3p counteracted nilotinib-induced expression of IL-1β. Importantly, serum levels if IL-1β were significantly elevated in CML patients receiving nilotinib (n=14) compared to those receiving other TKIs (n=16) (3.76±1.22pg/ml vs 0.27±0.77pg/ml, p<0.05). Taken together, our data suggest that nilotinib decreases levels of miR-3121-3p resulting in an increase in expression of IL-1β and adhesion molecules in vascular endothelial cells. The miR-3121-3p/IL-1β axis could be a potential target to prevent vascular events in CML patients with high risk of vascular events.
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http://dx.doi.org/10.1016/j.leukres.2017.05.005DOI Listing
July 2017

Serum Free Light Chain Only Myeloma with Cytoplasmic IgM.

Case Rep Hematol 2014 17;2014:676913. Epub 2014 Jun 17.

Division of Hematology/Oncology, Shirakawa Kosei General Hospital, 2-1 Toyochi Kamiyajirou, Shirakawa, Fukushima 961-0005, Japan.

In the past decade, the serum free light chain (FLC) immunoassays have become widely available enabling greater sensitivity in the diagnosis and management of monoclonal light chain diseases. Here, we describe a rare case of serum free light chain only myeloma with cytoplasmic IgM. A 75-year-old woman presented with a progressively worsening lumbosacral pain. FDG PET/CT images showed increased FDG uptake in the sacral mass, vertebral bodies, and ribs. Laboratory data found hypogammaglobulinemia and the bone marrow aspirate revealed only 2.2% of plasma cells. The serum and urine protein electrophoresis did not detect a monoclonal band. However, the serum FLC immunoassays reported an abnormal kappa/lambda ratio (0.001) indicating the presence of monoclonal lambda FLC. The sacral tumor biopsy revealed proliferation of plasma cells and immunohistochemical staining showed that the plasma cells were positive for CD138, IgM, and lambda light chain but negative for CD20. This case may have previously been described as a nonsecretory IgM myeloma but recently would be identified as free light chain only myeloma. The immunohistochemical and genetic features of the clonal plasma cells in free light chain only myeloma need to be further investigated to better understand the relevance and incidence of this myeloma type.
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http://dx.doi.org/10.1155/2014/676913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4084587PMC
July 2014

Multicenter phase II clinical trial of nilotinib for patients with imatinib-resistant or -intolerant chronic myeloid leukemia from the East Japan CML study group evaluation of molecular response and the efficacy and safety of nilotinib.

Biomark Res 2014 Mar 20;2(1). Epub 2014 Mar 20.

Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, 1-1-1 Hondo, 010-8543 Akita, Japan.

Background: Nilotinib is a second-generation tyrosine kinase inhibitor that exhibits significant efficacy as first- or second-line treatment in patients with chronic myeloid leukemia (CML). We conducted a multicenter Phase II Clinical Trial to evaluate the safety and efficacy of nilotinib among Japanese patients with imatinib-resistant or -intolerant CML-chronic phase (CP) or accelerated phase (AP).

Results: We analyzed 49 patients (33 imatinib-resistant and 16 imatinib-intolerant) treated with nilotinib 400 mg twice daily. The major molecular response (MMR) rate was 47.8% at 12 months among 35 patients who did not demonstrate an MMR at study entry. Somatic BCR-ABL1 mutations (Y253H, I418V, and exon 8/9 35-bp insertion [35INS]) were detected in 3 patients at 12 months or upon discontinuation of nilotinib. Although 75.5% of patients were still being treated at 12 months, nilotinib treatment was discontinued because of progressing disease in 1 patient, insufficient effect in 2, and adverse events in 9. There was no statistically significant correlation between MMR and trough concentrations of nilotinib. Similarly, no correlation was observed between trough concentrations and adverse events, except for pruritus and hypokalemia. Hyperbilirubinemia was frequently observed (all grades, 51.0%; grades 2-4, 29%; grades 3-4, 4.1%). Hyperbilirubinemia higher than grade 2 was significantly associated with the uridine diphosphate glucuronosyltransferase (UGT)1A9 I399C/C genotype (P = 0.0086; Odds Ratio, 21.2; 95% Confidence Interval 2.2-208.0).

Conclusions: Nilotinib was efficacious and well tolerated by patients with imatinib-resistant or -intolerant CML-CP/AP. Hyperbilirubinemia may be predicted before nilotinib treatment, and may be controlled by reducing the daily dose of nilotinib in patients with UGT1A9 polymorphisms.

Trial Registration: clinicaltrials.gov: UMIN000002201.
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http://dx.doi.org/10.1186/2050-7771-2-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994575PMC
March 2014

Identification of two novel mutations in adenine phosphoribosyltransferase gene in patients with 2,8-dihydroxyadenine urolithiasis.

Nucleosides Nucleotides Nucleic Acids 2004 Oct;23(8-9):1141-5

Institute of Rheumatology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.

Five mutations in the adenine phosphoribosyltransferase (APRT) gene have been described in Japanese patients with APRT deficiency. We investigated the APRT gene from three patients with APRT deficiency and two novel mutations, G133D and V84M, were determined.
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http://dx.doi.org/10.1081/NCN-200027393DOI Listing
October 2004

A 22-year-old woman with fulminant Chlamydia pneumoniae pneumonia.

Fukushima J Med Sci 2002 Jun;48(1):57-62

Department of Internal Medicine, Hoshi General Hospital, Koniyama, Japan.

Chlamydia pneumoniae (C. pneumoniae) is a common pathogen of community-acquired pneumonia. The clinical features of infection caused by C. pneumoniae are usually mild and it does not progress into respiratory failure in young people. We describe a healthy, immunologically intact, 22-year-old woman with severe respiratory failure caused by C. pneumoniae accompanied by aspergillosis. The infection rapidly progressed and required mechanical ventilation. C. pneumoniae infection should be taken into account when treating patients with rapidly progressive pneumonia even in immunocompetent young adults.
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http://dx.doi.org/10.5387/fms.48.57DOI Listing
June 2002
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