Publications by authors named "Jinichi Mori"

57 Publications

Androgen-dependent and DNA binding-independent association of androgen receptor with chromatic regions coding androgen-induced non-coding RNAs.

Biosci Biotechnol Biochem 2021 Jul 23. Epub 2021 Jul 23.

Research Institute of Innovative Medicine, Tokiwa Foundation, Iwaki, Fukushima, Japan.

Androgen induces the binding of its receptor (AR) to androgen-responsive elements (AREs), while genome-wide studies showed that most androgen-induced AR binding sites on chromatin were unrelated to AREs. Enhancer RNAs (eRNAs), a class of non-coding RNAs(ncRNAs), are transcribed from super-enhancers (SEs), and trigger the formation of large ribonucleoprotein (RNP) condensates of transcription factors. By in silico search, an SE is found to be located on the locus of KLK3 that encodes prostate specific antigen (PSA). On the KLK3 SE, androgen-induced expression of ncRNAs was detected and designated as KLK3eRNAs in LNCaP cells, and androgen-induced association of AR and FOXA1 on the KLK3eRNA coding regions was detected. Such androgen-induced association of an AR mutant lacking DNA binding activity on the KLK3eRNA coding regions was undetectable on an exogenous ARE. Thus, the present findings suggest a molecular basis of androgen-induced association of AR with chromatin on ARE-unrelated sequences.
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http://dx.doi.org/10.1093/bbb/zbab135DOI Listing
July 2021

Idecabtagene Vicleucel in Relapsed Myeloma.

N Engl J Med 2021 Jun;384(24):2356-2357

Navitas Clinic, Kawasaki, Japan.

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http://dx.doi.org/10.1056/NEJMc2105069DOI Listing
June 2021

PET-guided omission of radiotherapy in Hodgkin lymphoma.

Lancet Oncol 2021 05;22(5):e181

Navitas Clinic Kawasaki, Kanagawa, Japan.

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http://dx.doi.org/10.1016/S1470-2045(21)00146-7DOI Listing
May 2021

Effect of allogeneic HCT from unrelated donors in AML patients with intermediate- or poor-risk cytogenetics: a retrospective study from the Japanese Society for HCT.

Ann Hematol 2020 Dec 17;99(12):2927-2937. Epub 2020 Sep 17.

Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan.

This study aimed to analyze the factors associated with outcomes of bone marrow transplantation (UR-BMT) or cord blood stem cell transplantation from unrelated donors (UR-CBT). We assessed the time from diagnosis to transplantation among acute myeloid leukemia (AML) patients with intermediate- or poor-risk cytogenetics to identify the potential clinical efficacy of transplantation. We retrospectively analyzed 5331 patients who received UR-BMT or UR-CBT between 2008 and 2017. Patients were divided into four groups according to time from diagnosis to transplantation: (1) UR-BMT and > 5 months (n = 2353), (2) UR-BMT and ≤ 5 months (n = 379), (3) UR-CBT and > 5 months (n = 1494), and (4) UR-CBT and ≤ 5 months (n = 1106). There was no difference in overall survival (OS) for transplantation at ≤5 months and > 5 months in patients with first complete remission for both UR-BMT and UR-CBT, but OS in patients with primary induction failure (PIF) and transplantation at ≤ 5 months was significantly higher in the UR-CBT group compared with that at >5 months (P < 0.001). Multivariate Cox regression analysis also showed that transplantation at >5 months in patients with PIF was an independent predictor of poorer OS. Therefore, UR-CBT at ≤ 5 months after diagnosis is an alternative option for AML patients with PIF.
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http://dx.doi.org/10.1007/s00277-020-04261-6DOI Listing
December 2020

Assessment of dysplasia in bone marrow smear with convolutional neural network.

Sci Rep 2020 09 7;10(1):14734. Epub 2020 Sep 7.

Department of Hemato-Oncology, International Medical Center, Saitama Medical University, Saitama, Japan.

In this study, we developed the world's first artificial intelligence (AI) system that assesses the dysplasia of blood cells on bone marrow smears and presents the result of AI prediction for one of the most representative dysplasia-decreased granules (DG). We photographed field images from the bone marrow smears from patients with myelodysplastic syndrome (MDS) or non-MDS diseases and cropped each cell using an originally developed cell detector. Two morphologists labelled each cell. The degree of dysplasia was evaluated on a four-point scale: 0-3 (e.g., neutrophil with severely decreased granules were labelled DG3). We then constructed the classifier from the dataset of labelled images. The detector and classifier were based on a deep neural network pre-trained with natural images. We obtained 1797 labelled images, and the morphologists determined 134 DGs (DG1: 46, DG2: 77, DG3: 11). Subsequently, we performed a five-fold cross-validation to evaluate the performance of the classifier. For DG1-3 labelled by morphologists, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 91.0%, 97.7%, 76.3%, 99.3%, and 97.2%, respectively. When DG1 was excluded in the process, the sensitivity, specificity, PPV, NPV, and accuracy were 85.2%, 98.9%, 80.6%, and 99.2% and 98.2%, respectively.
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http://dx.doi.org/10.1038/s41598-020-71752-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477564PMC
September 2020

Treatment of T-Cell Prolymphocytic Leukemia with Central Nervous System Involvement Using Intrathecal Alemtuzumab Administration.

Case Rep Hematol 2020 27;2020:8822172. Epub 2020 Jul 27.

Department of Hematology, Fukushima Medical University, Fukushima, Japan.

T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic cancer with a dismal prognosis. Although a small number of patients have central nervous system (CNS) involvement, a standard treatment approach for these patients has not been established. Herein, we present a case of T-PLL with CNS involvement that was treated with a higher dose of intrathecal alemtuzumab than that previously reported. A 66-year-old man who had T-PLL with CNS involvement was admitted to our hospital. Intravenously administered alemtuzumab, a monoclonal antibody against the CD52 antigen, successfully reduced leukemia cells in peripheral blood; however, intrathecal treatment with methotrexate, cytarabine, and prednisone had a limited effect on the CNS involvement. Therefore, we intrathecally injected alemtuzumab as an experimental treatment. Although we escalated the dose of intrathecal alemtuzumab up to 5 mg, no adverse reaction was noted; however, this treatment did not completely clear the leukemia cells from the patient's cerebrospinal fluid (CSF). We performed whole brain and whole spinal irradiation therapies and subsequently performed allogeneic transplantation from a human leukocyte antigen-matched sibling donor with a conditioning regimen containing total body irradiation. At 21 days after transplantation, leukemia cells remained in his CSF. Although intrathecal alemtuzumab did not eliminate the CNS-invading leukemia cells, it was well-tolerated in our case. Further accumulation of similar cases is needed to determine the benefits and safety of intrathecal alemtuzumab administration.
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http://dx.doi.org/10.1155/2020/8822172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403948PMC
July 2020

Cat Rearing: A Potential Risk of Fulminant Sepsis Caused by in a Hemodialysis Patient.

Case Rep Nephrol Dial 2020 May-Aug;10(2):51-56. Epub 2020 May 13.

Department of Hematology, Jyoban Hospital of Tokiwa Foundation, Fukushima, Japan.

is a commensal organism colonized in oral flora of dogs and cats and causes severe sepsis through bite wound in immunocompromised patients. To date, hemodialysis has not been reported as a risk of infection. A 75-year-old woman with end-stage renal disease secondary to hypertension suddenly developed septic shock. She reared 6 cats in her home, but no bite or scratch wound was found on her body. She was empirically treated with piperacillin-tazobactam and temporally received continuous hemodiafiltration. On the fifth day after sampling, blood culture revealed as the cause of sepsis. After 4 weeks of antibiotic therapy targeting this organism, she recovered from the sepsis and was discharged on the 109th hospitalization day. Hemodialysis patients may be vulnerable to invasion into the blood stream by due to the presence of punctures in their skin and the impaired immune function associated with uremia. Physicians should consider this organism as a cause of sepsis in hemodialysis patients who rear dogs or cats even in the absence of apparent bite wounds.
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http://dx.doi.org/10.1159/000507425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265706PMC
May 2020

Pharmacokinetics of dasatinib in a hemodialysis patient with chronic myeloid leukemia and chronic kidney disease.

Int J Hematol 2020 Jul 9;112(1):115-117. Epub 2020 Mar 9.

Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan.

Until now, no studies have addressed the use of dasatinib in hemodialysis patients. Herein, we report the case of a 73-year-old hemodialysis patient with chronic myeloid leukemia (CML) who was treated with dasatinib. For 5 years prior, the patient had received nilotinib for the treatment of CML. Regular hemodialysis was initiated due to progression of hypertensive nephrosclerosis, whereupon nilotinib was discontinued and the patient began receiving 100 mg dose of dasatinib once daily. On dialysis days, dasatinib was administered immediately after completion of dialysis. Four months after starting dasatinib, we performed a pharmacokinetic study. The plasma concentrations of dasatinib before, immediately, and 2 h after the completion of hemodialysis were 7.4, 6.1, and 59.5 ng/mL, respectively. Ultrasound cardiography revealed a gradual decline in ejection fraction during dasatinib therapy. Because the patient's dasatinib trough concentration was higher (6.1 ng/mL) than the target level (1.5 ng/mL), we suspected the development of dasatinib-related heart dysfunction; thus, dasatinib was discontinued 6 months after its initiation. We concluded that hemodialysis patients are potentially vulnerable to the cardiotoxic effects of dasatinib; monitoring of cardiac function and plasma drug concentration may thus be useful in assessing their condition.
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http://dx.doi.org/10.1007/s12185-020-02846-5DOI Listing
July 2020

Autologous hematopoietic cell transplantation for acute myeloid leukemia in adults: 25 years of experience in Japan.

Int J Hematol 2020 Jan 14;111(1):93-102. Epub 2019 Oct 14.

The Jikei University School of Medicine, Tokyo, Japan.

Autologous hematopoietic cell transplantation (HCT) has not gained universal popularity in the treatment of acute myeloid leukemia (AML), and its status remains unclear. To determine the implementation status and outcomes of autologous HCT for adults with AML in Japan, we analyzed data from 1,174 patients (including 446 with acute promyelocytic leukemia [APL]) who underwent autologous HCT between 1992 and 2016 consecutively reported to the Japanese nationwide transplantation registry. The annual number of transplantations peaked at 82 cases in 1997, and has recently remained at around 40 cases. The percentage of APL has increased sharply since 2004, and currently exceeds 70%. While most non-APL patients underwent autologous HCT during first complete remission (CR), transplantation during second CR has become mainstream for APL patients since the early 2000s. The 5-year survival, relapse, and non-relapse mortality rates were 55.3%, 42.1%, and 8.6% for non-APL patients, and 87.6%, 12.9%, and 3.4% for APL patients, respectively. Patients transplanted in the later period showed better survival than those transplanted in the earlier period, both for non-APL (P < 0.001) and APL (P = 0.036). These results clearly show the various changes in transplantation practice and post-transplant outcomes in Japan over the past 25 years.
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http://dx.doi.org/10.1007/s12185-019-02759-yDOI Listing
January 2020

Allogeneic hematopoietic cell transplantation for patients with a history of multiple relapses of acute myeloid leukemia.

Ann Hematol 2019 Sep 15;98(9):2179-2186. Epub 2019 Jun 15.

Jikei University School of Medicine, Tokyo, Japan.

The prognosis of patients with acute myeloid leukemia (AML) is dismal after experiencing multiple relapses. This study retrospectively analyzed outcomes of allogeneic hematopoietic cell transplantation (HCT) for 192 adults with AML in third or subsequent complete remission (CR3+), 300 in second relapse (REL2), and 50 in third or subsequent relapse (REL3+) who were enrolled in a Japanese nationwide transplantation registry. The study population included patients undergoing umbilical cord blood transplantation, but not those undergoing haploidentical HCT. Patients transplanted in CR3+ had better survival than those transplanted in REL2 and REL3+ (48%, 21%, and 12% at 4 years; P < 0.001), and this was due to a reduction in post-transplant relapse (23%, 57%, and 52%; P < 0.001). The corresponding cumulative incidence of non-relapse mortality was 33%, 26%, and 36% (P = 0.022). Multivariate analysis revealed significantly lower relapse and overall mortality for those in CR3+ and significantly lower non-relapse mortality for those in REL2. Hazard ratios (95% confidence intervals) for overall mortality were 2.02 (1.56-2.64) for REL2+ versus CR3+ (P < 0.001) and 2.12 (1.40-3.19) for REL3+ versus CR3+ (P < 0.001). Our analysis demonstrates the curative potential of allogeneic HCT for patients with a history of multiple AML relapses and suggests the potential benefits and risks of reinduction attempt before transplantation, highlighting the need for an individualized approach in determining whether to give reinduction therapy in this setting.
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http://dx.doi.org/10.1007/s00277-019-03736-5DOI Listing
September 2019

Role of alternative donor allogeneic hematopoietic stem cell transplantation in patients with intermediate- or poor-risk acute myeloid leukemia in first complete remission.

Bone Marrow Transplant 2019 12 31;54(12):2004-2012. Epub 2019 May 31.

Division of Hematology, Department of Internal Medicine, School of Medicine, Aichi Medical University, Nagakute, Japan.

Allogeneic hematopoietic stem cell transplantation (HCT) offers the most effective prevention of relapse and has significant overall survival (OS) benefits for patients with acute myeloid leukemia (AML) in first complete remission (CR1). We conducted a retrospective analysis of a cohort of patients with intermediate- or poor-risk AML. The purpose of the present study was to investigate the role of alternative donors for AML in CR1. We analyzed 1561 patients who underwent HCT from an HLA-matched related donor (MRD), HLA 8/8-matched unrelated donor (MUD), or umbilical cord blood (UCB). The results of a multivariate analysis showed that HCT from UCB (HR = 1.28, 95% CI: 1.07-1.52), age ≥50 years (HR = 1.36, 95% CI: 1.14-1.62), male (HR = 1.42, 95% CI: 1.21-1.66), PS > 1 (HR = 1.68, 95% CI: 1.17-2.42), and poor-risk cytogenetics (HR = 1.53, 95% CI: 1.29-1.81) had an inferior prognostic impact on OS. We conclude that an MUD is the best alternative to an HLA identical MRD for patients with AML in CR1. UCB is an alternative option if neither MRD nor MUD are available, or when patients need to receive urgent HCT for poor-risk AML in CR1.
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http://dx.doi.org/10.1038/s41409-019-0571-8DOI Listing
December 2019

Risk Stratification and Prognosticators of Acute Myeloid Leukemia with Myelodysplasia-Related Changes in Patients Undergoing Allogeneic Stem Cell Transplantation: A Retrospective Study of the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation.

Biol Blood Marrow Transplant 2019 09 2;25(9):1730-1743. Epub 2019 May 2.

Division of Clinical Oncology and Hematology, The Jikei University School of Medicine, Tokyo, Japan.

Although the prognosis of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is worse than that of AML not otherwise specified (AML-NOS), transplantation outcomes and prognosticators of AML-MRC patients undergoing allogeneic stem cell transplantation (allo-SCT) remain unclear. Transplantation outcomes of AML-MRC (n = 4091) were compared with those of AML-NOS (n = 3964) in patients who underwent allo-SCT between 2003 and 2016 using a nationwide registration database. The 3-year overall survival (OS; 35.5% versus 50.6%) was lower and the relapse (42.3% versus 32.1%) and nonrelapse mortality (26.3% versus 22.0%) rates were higher in the AML-MRC group than in the AML-NOS group. Based on the hierarchical AML-MRC classification, myelodysplasia as the sole criterion was associated with better OS compared with AML-NOS, whereas monosomal or complex karyotype and -5/del(5q) were associated with poor OS. A history of myelodysplastic syndrome and -7/del(7q) did not affect OS. Accordingly, AML-MRC with complex karyotype or -5/del(5q) and that with monosomal karyotype were classified as intermediate and high risks, respectively, whereas the remaining cases were classified as low risk. The 3-year OS rates were 50.7%, 36.9%, and 13.8% in the low-, intermediate-, and high-risk groups, respectively (P < .001). Risk classification, older age, and low performance status score were significant risk factors for survival in AML-MRC, independently of the disease status. Grades I to II acute graft-versus-host disease significantly reduced the 3-year relapse (24.7% versus 31.6%), leading to better survival (hazard ratio, .64). Our prognostic risk stratification can potentially aid in elucidating the diverse transplantation outcomes in patients with AML-MRC.
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http://dx.doi.org/10.1016/j.bbmt.2019.04.025DOI Listing
September 2019

Entrance examination misogyny in Japanese medical schools.

Lancet 2019 Apr 4;393(10179):1416. Epub 2019 Apr 4.

Department of Internal Medicine, Jyoban Hospital, Tokiwa Foundation, Fukushima 972-8322, Japan.

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http://dx.doi.org/10.1016/S0140-6736(18)33180-5DOI Listing
April 2019

The Function of the Vitamin D Receptor and a Possible Role of Enhancer RNA in Epigenomic Regulation of Target Genes: Implications for Bone Metabolism.

J Bone Metab 2019 Feb 28;26(1):3-12. Epub 2019 Feb 28.

Center for Regional Cooperation, Iwaki Meisei University, Iwaki, Japan.

Vitamin D (VD) is essential for bone health, and VD or its analogues are widely used in clinics to ameliorate bone loss. The targets and mode of VD anti-osteoporotic actions appear to be different from those of other classes of drugs modulating bone remodeling. VD exerts its biological activities through the nuclear VD receptor (VDR)-mediated transcriptional regulation of target mRNA and non-coding RNA genes. VD-induced gene regulation involves epigenetic modifications of chromatin conformation at the target loci as well as reconfiguration of higher-order chromosomal organization through VDR-mediated recruitment of various regulatory factors. Enhancer RNAs (eRNA), a class of non-coding enhancer-derived RNAs, have recently emerged as VDR target gene candidates that act through reorganization of chromatin looping to induce enhancer-promoter interaction in activation of mRNA-encoding genes. This review outlines the molecular mechanisms of VD actions mediated by the VDR and suggests novel function of eRNAs in VDR transactivation.
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http://dx.doi.org/10.11005/jbm.2019.26.1.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416145PMC
February 2019

Patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation: trends in survival during the past two decades.

Bone Marrow Transplant 2019 04 14;54(4):578-586. Epub 2018 Aug 14.

Jikei University School of Medicine, Tokyo, Japan.

It remains unclear how specific innovations in allogeneic hematopoietic cell transplantation (HCT) attained over the past decades have contributed to improvement in transplantation outcomes. To address this question, we conducted a registry-based study of adults with acute myeloid leukemia in first or second complete remission who underwent allogeneic HCT between 1994 and 2013 from a sibling (N = 1600) or unrelated (N = 2113) donor matched at the antigen level for HLA-A, -B, and -DR. Preliminary analysis led us to focus on comparisons between the 1994-2006 and 2007-2013 periods. Significant improvement in survival was observed in the later cohort compared to the earlier cohort for unrelated HCT (P = 0.004), but not for related HCT (P = 0.767). The improvement in unrelated HCT was solely due to diminished non-relapse mortality (P = 0.001), while incidence of relapse did not change over time (P = 0.934). The percentage of patients receiving transplants from 8/8-matched unrelated donors was significantly higher in the later cohort (P < 0.001), and their survival was significantly better than that of those undergoing mismatched unrelated HCT (P = 0.022). These findings suggest that advances in HLA-typing technology have been vital for improvement in transplantation outcomes.
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http://dx.doi.org/10.1038/s41409-018-0301-7DOI Listing
April 2019

Predictive gene-expression score for follicular lymphoma.

Lancet Oncol 2018 06 1;19(6):e281. Epub 2018 Jun 1.

Jyoban Hospital of Tokiwa Foundation, 972-8322 Fukushima, Japan.

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http://dx.doi.org/10.1016/S1470-2045(18)30324-3DOI Listing
June 2018

A model-based estimation of inter-prefectural migration of physicians within Japan and associated factors: A 20-year retrospective study.

Medicine (Baltimore) 2018 Jun;97(22):e10878

Keio University Navitas Clinic, Tokyo Jyoban Hospital of Tokiwa Foundation Soma Central Hospital, Fukushima Medical Governance Research Institute, Tokyo National Cancer Center Hospital East, Chiba National Center for Child Health and Development, Tokyo Kyoto University, Kyoto Ohmachi Hospital, Fukushima Graduate School of Public Health, Teikyo University, Tokyo Kanagawa Cancer Center, Kanagawa Institute of Medical Sciences, University of Tokyo, Tokyo, Japan.

Despite an increase in the number of physicians in Japan, misdistribution of physicians within the 47 prefectures remains a major issue. Migration of physicians among prefectures might partly explain the misdistribution. However, geographical differences and the magnitude of physicians' migration are unclear. The aim of this study was to estimate the extent of migration of physicians among prefectures and explore possible factors associated with physicians' migration patterns.Using a publicly available government database from 1995 to 2014, a quantitative estimation of physicians' migration after graduation from a medical school was performed. The inflow and outflow of physicians were ostensibly calculated in each prefecture based on the differences between the number of newly licensed physicians and the actual number of practicing physicians after an adjustment for the number of deceased or retired physicians. Simple and multiple linear regression analyses were conducted to examine socio-demographic background factors.During the 20-year study period, the mean annual numbers of newly licensed physicians, deceased or retired physicians, and increase in practicing physicians in the whole country were 7416, 3382, and 4034, respectively. Among the 47 prefectures, the median annual number of newly licensed physicians to 100,000 population ratio (PPR) was 6.4 (range 1.5-16.5), the median annual adjusted number of newly licensed physicians was 61 (range, -18 to 845; the negative and positive values denote outflow and inflow, respectively), whereas the median annual number of migrating physicians was 13 (range, -171 to 241). The minimum and maximum migration ratios observed were -68% and 245%, respectively. In the final regression model of the 8 variables examined, only "newly licensed PPR" remained significantly associated with physician's migration ratios.A significant inequality in the proportion of the migration of physicians among prefectures in Japan was observed. The multivariate analyses suggest that the newly licensed PPRs, and not from-rural-to-urban migration, might be one of the keys to explaining the migration ratios of physicians. The differences and magnitude of physicians' migration should be factored into mitigate misdistribution of physicians.
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http://dx.doi.org/10.1097/MD.0000000000010878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392712PMC
June 2018

Letermovir Prophylaxis for Cytomegalovirus.

N Engl J Med 2018 03;378(10):964

Jyoban Hospital, Iwaki, Japan

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http://dx.doi.org/10.1056/NEJMc1800572DOI Listing
March 2018

Carfilzomib for relapsed or refractory multiple myeloma.

Lancet Oncol 2018 01;19(1):e1

Jyoban Hospital of Tokiwa Foundation, Fukushima 9728322, Japan.

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http://dx.doi.org/10.1016/S1470-2045(17)30859-8DOI Listing
January 2018

Targeted-release budesonide therapy for IgA nephropathy.

Lancet 2017 12;390(10113):2625

Teikyo University Chiba Medical Center, Chiba 299-0111, Japan.

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http://dx.doi.org/10.1016/S0140-6736(17)32145-1DOI Listing
December 2017

Characteristics of Novel Therapeutics and Postmarket Safety Events.

JAMA 2017 09;318(11):1067

Institute of Medical Sciences, University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1001/jama.2017.11513DOI Listing
September 2017

Rituximab and autologous stem-cell transplantation for high-risk diffuse large B-cell lymphoma.

Lancet Oncol 2017 10;18(10):e557

Department of Urology, Jyoban Hospital of Tokiwa Foundation, 9728322 Fukushima, Japan.

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http://dx.doi.org/10.1016/S1470-2045(17)30706-4DOI Listing
October 2017

Effect of cytogenetic risk status on outcomes for patients with acute myeloid leukemia undergoing various types of allogeneic hematopoietic cell transplantation: an analysis of 7812 patients.

Leuk Lymphoma 2018 03 28;59(3):601-609. Epub 2017 Jul 28.

q Jikei University School of Medicine , Tokyo , Japan.

This study aimed at determining how cytogenetic risk status affects outcomes for patients with acute myeloid leukemia (AML) after undergoing various types of allogeneic hematopoietic cell transplantation (HCT). Of 7812 patients eligible for analysis, cytogenetic risk was classified as favorable for 1088, intermediate for 5025, and poor for 1699. Overall, multivariate analysis showed significant intergroup differences in terms of relapse and survival, with the difference between poor- and intermediate-risk groups being greater than that between favorable- and intermediate-risk groups. Non-relapse mortality was identical for the three groups. Significant effects of cytogenetic risk status on survival were documented irrespective of donor type (related, unrelated, and umbilical cord blood), disease status at the time of transplantation (first or second complete remission, and more advanced disease status), and conditioning intensity (myeloablative and reduced-intensity). Our findings demonstrate robust and constant effects of cytogenetic risk status on survival after allogeneic HCT for patients with AML.
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http://dx.doi.org/10.1080/10428194.2017.1357173DOI Listing
March 2018

Temporal Changes in Subsequent Malignancies Among Childhood Cancer Survivors.

JAMA 2017 06;317(23):2451

Jyoban Hospital of Tokiwa Foundation, Fukushima, Japan.

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http://dx.doi.org/10.1001/jama.2017.6020DOI Listing
June 2017

Blinatumomab for Acute Lymphoblastic Leukemia.

N Engl J Med 2017 06;376(23):e49

Navitas Clinic, Tokyo, Japan

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http://dx.doi.org/10.1056/NEJMc1704012DOI Listing
June 2017

The Transcriptional Landscape of p53 Signalling Pathway.

EBioMedicine 2017 Jun 18;20:109-119. Epub 2017 May 18.

Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Laboratory of Clinical Genome Sequence, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan. Electronic address:

Although recent cancer genomics studies have identified a large number of genes that were mutated in human cancers, p53 remains as the most frequently mutated gene. To further elucidate the p53-signalling network, we performed transcriptome analysis on 24 tissues in p53 or p53 mice after whole-body X-ray irradiation. Here we found transactivation of a total of 3551 genes in one or more of the 24 tissues only in p53 mice, while 2576 genes were downregulated. p53 mRNA expression level in each tissue was significantly associated with the number of genes upregulated by irradiation. Annotation using TCGA (The Cancer Genome Atlas) database revealed that p53 negatively regulated mRNA expression of several cancer therapeutic targets or pathways such as BTK, SYK, and CTLA4 in breast cancer tissues. In addition, stomach exhibited the induction of Krt6, Krt16, and Krt17 as well as loricrin, an epidermal differentiation marker, after the X-ray irradiation only in p53 mice, implying a mechanism to protect damaged tissues by rapid induction of differentiation. Our comprehensive transcriptome analysis elucidated tissue specific roles of p53 and its signalling networks in DNA-damage response that will enhance our understanding of cancer biology.
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http://dx.doi.org/10.1016/j.ebiom.2017.05.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478243PMC
June 2017

Essential medicines for universal health coverage.

Lancet 2017 05 11;389(10082):1880-1881. Epub 2017 May 11.

Jyoban Hospital of Tokiwa Foundation, Fukushima 9728322, Japan.

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http://dx.doi.org/10.1016/S0140-6736(17)31211-4DOI Listing
May 2017

Outcomes of Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Patients with Abnormalities of the Short Arm of Chromosome 17.

Biol Blood Marrow Transplant 2017 Aug 25;23(8):1398-1404. Epub 2017 Apr 25.

Division of Clinical Oncology and Hematology, Jikei University School of Medicine, Tokyo, Japan.

We retrospectively analyzed a Japanese nationwide database to elucidate the impact of abnormalities in the short arm of chromosome 17 (abnl[17p]) on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia. Of 10,923 patients, 262 (2.4%) had abnl(17p), 235 of whom were classified into the poor cytogenetic risk group according to the National Comprehensive Cancer Network criteria. The median follow-up period was 1425 days. In abnl(17p) versus non-abnl(17p) patients of poor cytogenetic risk group, overall survival (OS), disease-free survival, cumulative incidence of disease relapse, and nonrelapse mortality rates at 5 years after allo-HSCT were 9.2% versus 27.4%, 7.8% versus 25.0%, 66.6% versus 49.4%, and 25.6% versus 25.6%, respectively. In contrast to the other types of abnl(17p), isochromosome 17q rarely encompassed the poor cytogenetic risk traits and did not adversely affect OS. Among the abnl(17p) patients, male sex, nonremission disease status at transplantation, and poor cytogenetic risk group were significantly associated with shorter OS. In conclusion, the presence of an abnl(17p) negatively affects allo-HSCT outcomes, which are influenced by the type of abnormality. Prompt initiation of allo-HSCT during complete remission may improve outcomes.
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http://dx.doi.org/10.1016/j.bbmt.2017.04.020DOI Listing
August 2017
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