109 results on '"Takakazu Kawase"'
Search Results
2. Peripheral T cell profiling reveals downregulated exhaustion marker and increased diversity in lymphedema post-lymphatic venous anastomosis
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Hirofumi Imai, Takakazu Kawase, Shuhei Yoshida, Toshiro Mese, Solji Roh, Asuka Fujita, Toshio Uchiki, Ayano Sasaki, Shogo Nagamatsu, Atsushi Takazawa, Tatsuo Ichinohe, and Isao Koshima
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Health sciences ,Immunology ,Components of the immune system ,Science - Abstract
Summary: Lymphedema is a progressive condition accompanying cellulitis and angiosarcoma, suggesting its association with immune dysfunction. Lymphatic venous anastomosis (LVA) can provide relief from cellulitis and angiosarcoma. However, the immune status of peripheral T cells during lymphedema and post-LVA remains poorly understood. Using peripheral blood T cells from lymphedema, post-LVA, and healthy controls (HCs), we compared the profile of T cell subsets and T cell receptor (TCR) diversity. PD-1+ Tim-3 + expression was downregulated in post-LVA compared with lymphedema. IFN-γ levels in CD4+PD-1+ T cells and IL-17A levels in CD4+ T cells were downregulated in post-LVA compared with lymphedema. TCR diversity was decreased in lymphedema compared with HCs; such TCR skewing was drastically improved in post-LVA. T cells in lymphedema were associated with exhaustion, inflammation, and diminished diversity, which were relieved post-LVA. The results provide insights into the peripheral T cell population in lymphedema and highlight the immune modulatory importance of LVA.
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- 2023
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3. Prediction of mobilized hematopoietic stem cell yield in patients with multiple myeloma: Usefulness of whole-body MRI-derived indices.
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Miyuki Takasu, Ryo Higashino, Takahiro Sueoka, Saki Kawai, Nobuko Tanitame, Akihisa Tamura, Makoto Iida, Takakazu Kawase, Tatsuo Ichinohe, and Kazuo Awai
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Medicine ,Science - Abstract
IntroductionHigh-dose chemotherapy followed by autologous stem cell transplant is the mainstay of treatment for multiple myeloma (MM). The purpose of this study was to evaluate the ability of MRI-derived indices to predict mobilized hematopoietic stem cell yield.Materials and methodsIn this exploratory pilot work, we retrospectively analyzed 38 mobilization procedures for MM. Successful mobilization procedure was defined as a total yield of >4.0×106 CD34+ cells/kg. Univariate and multivariate analyses were performed to identify factors with a significant effect on successful mobilization from among clinical characteristics including number of prior lines of therapy, period from diagnosis to harvest, type of monoclonal protein (M protein); and radiological characteristics including total diffusion volume (tDV), median apparent diffusion coefficient (ADC) of tDV, and mean fat fraction of bone marrow calculated by MRI.ResultsUnivariate analyses showed that relatively poor mobilization was significantly associated with M protein of Bence-Jones type and with median ADC of tDV (P = 0.02 and P = 0.004, respectively). Multivariate analyses using these two indices showed that median ADC of tDV was a significant predictive factor for adequate mobilization (P = 0.01), with an area under the curve of 0.784 (cutoff value, 1.18×10-3 mm2/s; sensitivity, 72.7%; specificity, 87.5%).ConclusionThe present data indicate that median ADC of tDV is a predictive factor for relatively poor mobilization of hematopoietic stem cells in MM patients undergoing autologous stem cell transplant.
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- 2023
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4. Assessment of early treatment response on MRI in multiple myeloma: Comparative study of whole-body diffusion-weighted and lumbar spinal MRI.
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Miyuki Takasu, Shota Kondo, Yuji Akiyama, Yuji Takahashi, Shogo Maeda, Yasutaka Baba, Takakazu Kawase, Tatsuo Ichinohe, and Kazuo Awai
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Medicine ,Science - Abstract
OBJECTIVES:To compare remission status at completion of chemotherapy for multiple myeloma (MM) with changes in total diffusion volume (tDV) calculated from whole-body diffusion-weighted imaging (WB-DWI) and fat fraction (FF) of lumbar bone marrow (BM) by modified Dixon Quant (mDixon Quant) soon after induction of chemotherapy, and to assess the predictive value of MRI. METHODS:Fifty patients (mean age, 66.9 ± 10.5 years) with symptomatic myeloma were examined before and after two cycles of chemotherapy. From WB-DWI data, tDV was obtained with the threshold for positive BM involvement. Mean FF was calculated from lumbar BM using the mDixon Quant sequence. At the completion of chemotherapy, patients were categorized into a CR/very good PR (VGPR) group (n = 15; mean age, 67.6 ± 10.3 years) and a PR, SD or PD group (n = 35; mean age, 69.1 ± 8.6 years). ROC curves were plotted to assess performance in predicting achievement of CR/VGPR. RESULTS:At second examination, serum M protein, β2-microglobulin, and tDV were significantly decreased and hemoglobin, mean ADC, and FF were significantly increased in the CR/VGPR group and serum M protein was significantly increased in the PR/SD/PD group. The general linear model demonstrated that percentage changes in FF and M protein contributed significantly to achieving CR/VGPR (P = 0.02, P = 0.04, respectively). AUCs of ROC curves were 0.964 for FF and 0.847 for M protein. CONCLUSIONS:Early change in FF of lumbar BM and serum M protein soon after induction of chemotherapy contributed significantly to prediction of CR/VGPR.
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- 2020
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5. Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals
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Takahiko Miyama, Takakazu Kawase, Kazutaka Kitaura, Ren Chishaki, Masashi Shibata, Kumi Oshima, Hiroshi Hamana, Hiroyuki Kishi, Atsushi Muraguchi, Kiyotaka Kuzushima, Hiroh Saji, Tadasu Shin-I, Ryuji Suzuki, and Tatsuo Ichinohe
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Medicine ,Science - Abstract
Abstract To expand our knowledge of the ontogeny of the T-cell receptor (TCR) repertoire of antigen-specific T-cell subsets, we combined next-generation deep sequencing and single-cell multiplex clonotype analysis to evaluate the diversity and frequency of paired TCRs, their functions and whether clonotypic TCRs are shared among different individuals. Using an HLA-A*02-restricted cytomegalovirus (CMV) pp65-derived immunogenic peptide, we found that the more dominant pp65-specific TCR clonotypes in the blood of healthy donors have higher binding affinities for the CMV peptide and arise from clonotypes that are highly shared among individuals. Interestingly, these highly shared HLA-A*02-restricted CMV-specific TCRs were detected in a CMV-seronegative individual as well as in HLA-A*02-negative donors albeit at lower frequency. More intriguingly, these shared TCR clonotypes were abundant in the stem memory T-cell subset, and TCR diversity of the stem memory T-cell repertoire was significantly lower than in the central memory and effector memory T-cell repertoires. These results suggest that the stem memory T-cell subset may serve as a reservoir of highly shared and highly functional memory T-cells.
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- 2017
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6. Next-Generation Immune Repertoire Sequencing as a Clue to Elucidate the Landscape of Immune Modulation by Host–Gut Microbiome Interactions
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Tatsuo Ichinohe, Takahiko Miyama, Takakazu Kawase, Yasuko Honjo, Kazutaka Kitaura, Hiroyuki Sato, Tadasu Shin-I, and Ryuji Suzuki
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next-generation immune repertoire sequencing ,B-cell receptors ,T-cell receptors ,single-cell transcriptomics ,human microbiome ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The human immune system is a fine network consisted of the innumerable numbers of functional cells that balance the immunity and tolerance against various endogenous and environmental challenges. Although advances in modern immunology have revealed a role of many unique immune cell subsets, technologies that enable us to capture the whole landscape of immune responses against specific antigens have been not available to date. Acquired immunity against various microorganisms including host microbiome is principally founded on T cell and B cell populations, each of which expresses antigen-specific receptors that define a unique clonotype. Over the past several years, high-throughput next-generation sequencing has been developed as a powerful tool to profile T- and B-cell receptor repertoires in a given individual at the single-cell level. Sophisticated immuno-bioinformatic analyses by use of this innovative methodology have been already implemented in clinical development of antibody engineering, vaccine design, and cellular immunotherapy. In this article, we aim to discuss the possible application of high-throughput immune receptor sequencing in the field of nutritional and intestinal immunology. Although there are still unsolved caveats, this emerging technology combined with single-cell transcriptomics/proteomics provides a critical tool to unveil the previously unrecognized principle of host–microbiome immune homeostasis. Accumulation of such knowledge will lead to the development of effective ways for personalized immune modulation through deeper understanding of the mechanisms by which the intestinal environment affects our immune ecosystem.
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- 2018
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7. Analysis of outcomes following autologous stem cell transplantation in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia during first complete remission
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Harumi Kato, Takakazu Kawase, Shinichi Kako, Shuichi Mizuta, Mineo Kurokawa, Takehiko Mori, Kazuteru Ohashi, Koji Iwato, Koichi Miyamura, Michihiro Hidaka, Hisashi Sakamaki, Ritsuro Suzuki, Yasuo Morishima, and Junji Tanaka
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2014
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8. A genetic variant in the IL-17 promoter is functionally associated with acute graft-versus-host disease after unrelated bone marrow transplantation.
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J Luis Espinoza, Akiyoshi Takami, Katsuya Nakata, Makoto Onizuka, Takakazu Kawase, Hideki Akiyama, Koichi Miyamura, Yasuo Morishima, Takahiro Fukuda, Yoshihisa Kodera, Shinji Nakao, and Japan Marrow Donor Program
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Medicine ,Science - Abstract
Interleukin IL-17 is a proinflammatory cytokine that has been implicated in the pathogenesis of various autoimmune diseases. The single nucleotide polymorphism (SNP), rs2275913, in the promoter region of the IL-17 gene is associated with susceptibility to ulcerative colitis. When we examined the impact of rs2275913 in a cohort consisting of 438 pairs of patients and their unrelated donors transplanted through the Japan Marrow Donor Program, the donor IL-17 197A allele was found to be associated with a higher risk of acute graft-versus-host disease (GVHD; hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.00 to 2.13; P = 0.05). Next, we investigated the functional relevance of the rs2275913 SNP. In vitro stimulated T cells from healthy individuals possessing the 197A allele produced significantly more IL-17 than those without the 197A allele. In a gene reporter assay, the 197A allele construct induced higher luciferase activity than the 197G allele, and the difference was higher in the presence of T cell receptor activation and was abrogated by cyclosporine treatment. Moreover, the 197A allele displayed a higher affinity for the nuclear factor activated T cells (NFAT), a critical transcription factor involved in IL-17 regulation. These findings substantiate the functional relevance of the rs2275913 polymorphism and indicate that the higher IL-17 secretion by individuals with the 197A allele likely accounts for their increased risk for acute GVHD and certain autoimmune diseases.
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- 2011
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9. Genetic variants of human granzyme B predict transplant outcomes after HLA matched unrelated bone marrow transplantation for myeloid malignancies.
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Luis J Espinoza, Akiyoshi Takami, Katsuya Nakata, Kayoko Yamada, Makoto Onizuka, Takakazu Kawase, Hiroshi Sao, Hideki Akiyama, Koichi Miyamura, Shinichiro Okamoto, Masami Inoue, Takahiro Fukuda, Yasuo Morishima, Yoshihisa Kodera, Shinji Nakao, and Japan Marrow Donor Program
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Medicine ,Science - Abstract
Serine protease granzyme B plays important roles in infections, autoimmunity, transplant rejection, and antitumor immunity. A triple-mutated granzyme B variant that encodes three amino substitutions (Q48R, P88A, and Y245H) has been reported to have altered biological functions. In the polymorphism rs8192917 (2364A>G), the A and G alleles represent wild type QPY and RAH mutant variants, respectively. In this study, we analyzed the impact of granzyme B polymorphisms on transplant outcomes in recipients undergoing unrelated HLA-fully matched T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. The granzyme B genotypes were retrospectively analyzed in a cohort of 613 pairs of recipients with hematological malignancies and their unrelated donors. In patients with myeloid malignancies consisting of acute myeloid leukemia and myelodysplastic syndrome, the donor G/G or A/G genotype was associated with improved overall survival (OS; adjusted hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.41-0.89; P = 0.01) as well as transplant related mortality (TRM; adjusted HR, 0.48; 95% CI, 0.27-0.86, P = 0.01). The recipient G/G or A/G genotype was associated with a better OS (adjusted HR, 0.68; 95% CI, 0.47-0.99; P = 0.05) and a trend toward a reduced TRM (adjusted HR, 0.61; 95% CI, 0.35-1.06; P = 0.08). Granzyme B polymorphism did not have any effect on the transplant outcomes in patients with lymphoid malignancies consisting of acute lymphoid leukemia and malignant lymphoma. These data suggest that there is an association between the granzyme B genotype and better clinical outcomes in patients with myeloid malignancies after unrelated BMT.
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- 2011
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10. T cell receptor-engineered T cells derived from target human leukocyte antigen-DPB1-specific T cell can be a potential tool for therapy against leukemia relapse following allogeneic hematopoietic cell transplantation.
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Naoya Katsuyama, Takakazu Kawase, Carolyne Barakat, Shohei Mizuno, Akihiro Tomita, Kazutaka Ozeki, Nobuhiro Nishio, Yoshie Sato, Ryoko Kajiya, Keiko Shiraishi, Yoshiyuki Takahashi, Tatsuo Ichinohe, Hiroyoshi Nishikawa, and Yoshiki Akatsuka
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T cells ,HLA histocompatibility antigens ,IMMUNOTHERAPY ,GRAFT versus host disease ,ANTIGEN presenting cells - Abstract
Human leukocyte antigen (HLA)-DPB1 antigens are mismatched in approximately 70% of allogeneic hematopoietic stem cell transplantations (allo-HSCT) from HLA 10/10 matched unrelated donors. HLADP-mismatched transplantation was shown to be associated with an increase in acute graft-versus-host disease (GVHD) and a decreased risk of leukemia relapse due to the graft-versus-leukemia (GVL) effect. Immunotherapy targeting mismatched HLA-DP is considered reasonable to treat leukemia following alloHCT if performed under non-inflammatory conditions. Therefore, we isolated CD4
+ T cell clones that recognize mismatched HLA-DPB1 from healthy volunteer donors and generated T cell receptor (TCR)- gene-modified T cells for future clinical applications. Detailed analysis of TCR-T cells expressing TCR from candidate clone #17 demonstrated specificity to myeloid and monocytic leukemia cell lines that even expressed low levels of targeted HLA-DP. However, they did not react to non-hematopoietic cell lines with a substantial level of targeted HLA-DP expression, suggesting that the TCR recognized antigenic peptide is only present in some hematopoietic cells. This study demonstrated that induction of T cells specific for HLA-DP, consisting of hematopoietic cell lineage-derived peptide and redirection of T cells with cloned TCR cDNA by gene transfer, is feasible when using careful specificity analysis. [ABSTRACT FROM AUTHOR]- Published
- 2023
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11. Supplementary Data from Myeloma Cells Are Activated in Bone Marrow Microenvironment by the CD180/MD-1 Complex, Which Senses Lipopolysaccharide
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Yusuke Furukawa, Tatsuo Ichinohe, Takakazu Kawase, Hiroshi Yasui, Tohru Izumi, Naoki Osada, Daisuke Koyama, Yoshiaki Kuroda, and Jiro Kikuchi
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Supplementary Materials and Methods, Tables S1-5, and Figures S1-9
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- 2023
12. Data from Folate Intake along with Genetic Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase in Patients with Advanced Gastric Cancer
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Keitaro Matsuo, Hideo Tanaka, Yasushi Yatabe, Kazuo Tajima, Miki Watanabe, Takakazu Kawase, Satoyo Hosono, Hidemi Ito, Takashi Ura, Takashi Shibata, Daisuke Takahari, Tomoya Yokota, Hiroki Kawai, Masahiro Tajika, Akira Sawaki, Seiji Ito, Kei Muro, and Kohei Shitara
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Background: A relationship between dietary folate intake and efficacy of fluorouracil (FU) is supported by preclinical data. Furthermore, there are several reports that evaluated genetic polymorphisms of MTHFR (methylenetetrahydrofolate reductase) or TYMS (thymidylate synthase) and efficacy of FU. However, to our knowledge, there are no reports that evaluate simultaneously the effects of folate intake and genetic polymorphisms on clinical outcome of gastric cancer patients.Methods: We retrospectively analyzed the survival impact of estimated folate intake by a food frequency questionnaire and MTHFR and TYMS polymorphisms in 132 patients with advanced gastric cancer who were treated with first-line FU-based chemotherapy.Results: Median overall survival was 11.3 months (95% confidence interval, 9.4-13.4 mo) and median progression-free survival was 5.2 months (95% confidence interval, 4.1-6.3 mo). Patients with folate intake of >260 μg/day (n = 88) showed longer overall survival compared with low folate intake (n = 44; overall survival, 12.2 versus 8.4 mo). In a multivariate Cox model, patients who had folate intake of >260 μg/day, MTHFR 677 TT polymorphism, and TYMS-3′ untranslated region 6-bp insertion were associated with better survival. Similar tendency was observed in progression-free survival. No interaction was observed between folate intake and favorable genotypes.Conclusion: Folate intake and genetic polymorphisms of MTHFR and TYMS were associated with better clinical outcome by FU-based chemotherapy in advanced gastric cancer.Impact: Our results suggested folate intake and folate-related genetic polymorphisms may play an important role in efficacy of FU-based chemotherapy in advanced gastric cancer. Cancer Epidemiol Biomarkers Prev; 19(5); 1311–9. ©2010 AACR.
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- 2023
13. Data from Impact of Multiple Alcohol Dehydrogenase Gene Polymorphisms on Risk of Upper Aerodigestive Tract Cancers in a Japanese Population
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Hideo Tanaka, Mitsune Tanimoto, Kazuo Tajima, Katsuyuki Kiura, Masayuki Shinoda, Yasuhisa Hasegawa, Yasuhi Yatabe, Shunzo Hatooka, Taijiro Ozawa, Satoyo Hosono, Hidemi Ito, Akio Hiraki, Miki Watanabe, Takakazu Kawase, Takeshi Suzuki, Keitaro Matsuo, and Isao Oze
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Alcohol intake is positively associated with the risk of upper aerodigestive tract (UAT) cancer. The genes that encode alcohol-metabolizing enzymes, primarily alcohol dehydrogenases (ADH) and aldehyde dehydrogenases (ALDH), are polymorphic. In Caucasians, significant associations between polymorphisms in ADH1B (rs1229984) and ADH1C (rs698 and rs1693482), and UAT cancer have been observed, despite strong linkage disequilibrium among them. Moreover, UAT cancer was significantly associated with rs1573496 in ADH7, and not with rs1984362 in ADH4. However, little evidence is available concerning ADH4 or ADH7 polymorphisms in Asian populations. We conducted a matched case-control study to clarify the role of ADH polymorphisms in a Japanese population. Cases and controls were 585 patients with UAT cancer and 1,170 noncancer outpatients. Genotyping for ADHs and ALDH2 was done using TaqMan assays. Associations between polymorphisms and UAT cancer were assessed by odds ratios and 95% confidence intervals using conditional logistic regression models that adjusted for age, sex, smoking, drinking, and ALDH2. Adjusted odds ratios were significant for rs4148887 and rs3805322 in ADH4, rs1229984 in ADH1B, rs698 and rs1693482 in ADH1C, and rs284787, rs1154460, and rs3737482 in ADH7. We also observed that ADH7 rs3737482 and ADH4 rs4148887 had independently and statistically significant effects on UAT cancer. The magnitude of effect of these ADH polymorphisms was greater in subjects who were heavy drinkers, heavy smokers, and had esophageal cancer. These findings show that multiple ADH gene polymorphisms were associated with UAT cancer in this Japanese population. Further studies in various ethnicities are required. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3097–102)
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- 2023
14. Supplementary Table and Figures 1-6 from Impact of Multiple Alcohol Dehydrogenase Gene Polymorphisms on Risk of Upper Aerodigestive Tract Cancers in a Japanese Population
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Hideo Tanaka, Mitsune Tanimoto, Kazuo Tajima, Katsuyuki Kiura, Masayuki Shinoda, Yasuhisa Hasegawa, Yasuhi Yatabe, Shunzo Hatooka, Taijiro Ozawa, Satoyo Hosono, Hidemi Ito, Akio Hiraki, Miki Watanabe, Takakazu Kawase, Takeshi Suzuki, Keitaro Matsuo, and Isao Oze
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Supplementary Table and Figures 1-6 from Impact of Multiple Alcohol Dehydrogenase Gene Polymorphisms on Risk of Upper Aerodigestive Tract Cancers in a Japanese Population
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- 2023
15. Supplementary Tables 1-3 from Folate Intake along with Genetic Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase in Patients with Advanced Gastric Cancer
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Keitaro Matsuo, Hideo Tanaka, Yasushi Yatabe, Kazuo Tajima, Miki Watanabe, Takakazu Kawase, Satoyo Hosono, Hidemi Ito, Takashi Ura, Takashi Shibata, Daisuke Takahari, Tomoya Yokota, Hiroki Kawai, Masahiro Tajika, Akira Sawaki, Seiji Ito, Kei Muro, and Kohei Shitara
- Abstract
Supplementary Tables 1-3 from Folate Intake along with Genetic Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase in Patients with Advanced Gastric Cancer
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- 2023
16. Peripheral T Cell Profiling Reveals Downregulation of Exhaustion Marker and Increased Diversity in Lymphedema Post-Lymphatic Venous Anastomosis
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Hirofumi Imai, Takakazu Kawase, Shuhei Yoshida, Toshiro Mese, Solji Roh, Asuka Fujita, Toshio Uchiki, Ayano Sasaki, Shogo Nagamatsu, Atsushi Takazawa, Tatsuo Ichinohe, and Isao Koshima
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- 2023
17. Effects of Haplotype Matching on Outcomes after Adult Single-Cord Blood Transplantation
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Toru Sakura, Satoko Morishima, Junya Kanda, Makoto Onizuka, Naoyuki Uchida, Hikaru Kobayashi, Junji Tanaka, Takakazu Kawase, Koji Nagafuji, Hidenori Tanaka, Yoshiko Matsuhashi, Hiroto Kojima, Shigesaburo Miyakoshi, Yasuo Morishima, Tetsuya Eto, Satoshi Takahashi, Tatsuo Ichinohe, Yoshiko Atsuta, and Takanori Ohta
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Transplantation ,medicine.medical_specialty ,Matching (statistics) ,Neutrophil Engraftment ,Multivariate analysis ,Platelet Engraftment ,business.industry ,Haplotype ,Hazard ratio ,Hematology ,Disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Cord blood ,medicine ,business ,030215 immunology - Abstract
It remains unclear whether the HLA haplotype of unrelated cord blood (UCB) should be matched to that of the patient in single UCB transplantation. Thus, using data from a Japanese registry, we analyzed the effect of haplotype matching on outcomes. Patients with hematologic diseases aged 16 years or older who had undergone their first transplant were included (N = 1347). The effects of haplotype matching and high-frequency HLA haplotype on outcomes were analyzed. Median patient age was 55 years. The cumulative incidences of neutrophil engraftment among groups with 0, 1, and 2 HLA haplotype matches were 79%, 82%, and 88%, respectively (P = .008). In a multivariate analysis, the group with 0 haplotype matches was marginally associated with worse neutrophil engraftment (P = .087) and significantly associated with platelet engraftment (P = .044) compared with the group with 1 haplotype match. Two-haplotype matches were associated with a higher risk of relapse. In the group with 1 haplotype match, the top 3 shared haplotypes were "A*24:02-B*52:01-C*12:02-DRB1*15:02" (HP-P1), "A*33:03-B*44:03-C*14:03-DRB1*13:02" (HP-P2), and "A*24:02-B*07:02-C*07:02-DRB1*01:01" (HP-P3). The presence of HP-P2 but not HP-P1 or HP-P3 was associated with a decreased risk of grades II to IV acute graft-versus-host disease (hazard ratio, .56; P = .001) but an increased risk of relapse (hazard ratio, 1.35; P = .045). HLA haplotype matching might be considered to improve engraftment. Two-haplotype matches should be avoided if the relapse risk is high. The haplotype itself may have an effect on the risk of acute graft-versus-host disease and relapse.
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- 2020
18. Impact of High-Frequency HLA Haplotypes on Clinical Cytomegalovirus Reactivation in Allogeneic Hematopoietic Stem Cell Transplantation
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Michihiro Hidaka, Minoko Takanashi, Hiroto Kojima, Takakazu Kawase, Naoyuki Uchida, Yoshiko Atsuta, Tatsuo Ichinohe, Yukiyasu Ozawa, Hidenori Tanaka, Kazuhiro Ikegame, Junya Kanda, Toshihiro Miyamoto, Tetsuya Eto, Yoshinobu Kanda, Takahiro Fukuda, Souichi Shiratori, Kazuteru Ohashi, and Takehiko Mori
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Adult ,Male ,Cytomegalovirus reactivation ,medicine.medical_treatment ,Cytomegalovirus ,Hematopoietic stem cell transplantation ,Lower risk ,03 medical and health sciences ,0302 clinical medicine ,HLA Antigens ,medicine ,Humans ,Transplantation ,Hla haplotypes ,business.industry ,Haplotype ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Heterozygote advantage ,Hematology ,Middle Aged ,Allografts ,Haplotypes ,Infectious disease (medical specialty) ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Cytomegalovirus Infections ,Immunology ,Female ,Virus Activation ,business ,030215 immunology - Abstract
Some studies support the hypothesis that HLA genes and haplotypes evolved by natural selection through their protective abilities against specific infectious pathogens. However, very little is known regarding the impact of high-frequency HLA haplotypes on the risk of relevant infectious diseases among a given ethnic group. We evaluated the impact of high-frequency HLA haplotypes on cytomegalovirus (CMV) reactivation and infection in allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a Japanese population as a model of infectious disease that has coexisted with humans. A total of 21,127 donor-patient pairs were analyzed. HLA-A-B-DRB1 haplotypes were estimated using the maximum probability algorithm. Seven haplotypes with1% frequency were defined as high-frequency haplotypes (HfHPs). Homozygotes of HfHP and heterozygotes had significantly lower risk of CMV reactivation and infection (hazard ratio [HR] = 0.88, P = .009 and HR = 0.93, P = .003, respectively) than homozygotes of low-frequency HLA haplotypes (LfHPs). In subgroup analyses of a different donor source, these associations were statistically significant in unrelated donor transplants. Finally, CMV risk for homozygotes and heterozygotes of each HfHP was compared with that of homozygotes of LfHPs. The 2 most predominant HfHP groups (A*24:02-B*52:01-DRB1*15:02 group and A*24:02-B*07:02-DRB1*01:01 group) had a significantly lower risk of CMV reactivation and infection (HR = 0.86, P.001 and HR = 0.91, P = .033, respectively). Our findings suggest that HfHPs may be protective against CMV reactivation and infection and that increased care regarding CMV reactivation and infection may be necessary for patients with LfHP after allo-HSCT.
- Published
- 2019
19. Circulating T Cell Profiling of Lymphedema Reveals Upregulated Immune Checkpoint Molecules and Preserved Stem Cell-Like Memory T Cells
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Shuhei Yoshida, Isao Koshima, Tatsuo Ichinohe, Shogo Nagamatsu, Asuka Fujita, Toshiro Mese, Hirofumi Imai, Atsushi Takazawa, Solji Roh, Takakazu Kawase, Toshio Uchiki, and Ayano Sasaki
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body regions ,Lymphedema ,medicine.anatomical_structure ,Downregulation and upregulation ,Chemistry ,hemic and lymphatic diseases ,T cell ,Immune checkpoint molecules ,medicine ,Stem cell ,medicine.disease ,humanities ,Cell biology - Abstract
Lymphedema is a common complication seen in patients with cancer who undergo lymph node dissection. Lymphedema is a debilitating progressive condition that severely restricts the quality of life owing to the accompanying cellulitis and angiosarcoma, which suggest that immune dysfunction is associated with lymphedema. However, the immune status of peripheral T cells during lymphedema remains poorly understood. Using the peripheral blood T cells of patients with lymphedema and age-matched healthy controls (HC), we compared the profile of various functional T cell subsets in this study. Expression of PD-1, Tim-3, and Lag-3 increased in peripheral CD4 + but not CD8 + T cell populations, and the proportion of regulatory T cells was higher in lymphedema patients than in HC. The proportions of naïve CD4 + and CD8 + T cells were lower in lymphedema patients than in HC, although proportions of stem cell-like memory T cell subsets were constant. These observations suggest the distinct immunosuppressive status of patients with lymphedema, which might be related to the development of the accompanying cellulitis and angiosarcoma. This study might provide new insights into the late complication after undergoing lymph node dissection as a cancer treatment.
- Published
- 2021
20. Effect of Multiple HLA Locus Mismatches on Outcomes after Single Cord Blood Transplantation
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Junya Kanda, Shigeki Hirabayashi, Hisayuki Yokoyama, Takakazu Kawase, Hidenori Tanaka, Naoyuki Uchida, Shuichi Taniguchi, Satoshi Takahashi, Makoto Onizuka, Masatsugu Tanaka, Yasuhiro Sugio, Tetsuya Eto, Yoshinobu Kanda, Takafumi Kimura, Tatsuo Ichinohe, Yoshiko Atsuta, and Satoko Morishima
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Transplantation ,Adolescent ,HLA-A Antigens ,Histocompatibility Testing ,Graft vs Host Disease ,Cell Biology ,Hematology ,Middle Aged ,Leukemia, Myeloid, Acute ,HLA-B Antigens ,Recurrence ,Humans ,Molecular Medicine ,Immunology and Allergy ,Cord Blood Stem Cell Transplantation ,HLA-DRB1 Chains - Abstract
The effect of single or multiple mismatches at each HLA locus on outcomes after cord blood transplantation (CBT) is controversial. We analyzed the effects of single or multiple HLA locus mismatches on the outcomes after single CBT using Japanese registry data from the Japan Society for Hematopoietic Cell Transplantation. Patients age ≥16 years with acute leukemia and myelodysplastic syndromes who underwent their first CBT between 2003 and 2017 (n = 4074) were included. The effect of the number of HLA locus mismatches (0, 1, or 2 for the HLA-A, -B, -C, and -DRB1 loci) on outcomes was analyzed after adjusting for other significant variables. The patient cohort had a median age of 54 years. The median total nucleated and CD34 cell doses were 2.6 × 10
- Published
- 2022
21. CD56-positive B cell precursor acute lymphoblastic leukemia harboring KMT2A-AFF1 rearrangement developed in a pregnant woman successfully treated with allogeneic hematopoietic cell transplantation
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Hisao Nagoshi, Takakazu Kawase, Taro Edahiro, Kayo Toishigawa, Noriyasu Fukushima, Tatsuo Ichinohe, Mitsunori Noma, Hiromi Nakagawa, Tomoko Inoue, Teruhisa Fujii, Takahiko Miyama, Yoshiko Okikawa, Kyoko Kazihara, and Aiko Yamaoka
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medicine.medical_specialty ,Histology ,Hematology ,Hematopoietic cell ,biology ,business.industry ,Lymphoblastic Leukemia ,Pathology and Forensic Medicine ,Transplantation ,KMT2A ,medicine.anatomical_structure ,Internal medicine ,biology.protein ,Cancer research ,Medicine ,business ,B cell - Published
- 2020
22. Human leukocyte antigen (HLA) haplotype matching in unrelated single HLA allele mismatch bone marrow transplantation
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Akihisa, Kawajiri, Takakazu, Kawase, Hidenori, Tanaka, Takahiro, Fukuda, Junichi, Mukae, Yukiyasu, Ozawa, Tetsuya, Eto, Naoyuki, Uchida, Takehiko, Mori, Takashi, Ashida, Tadakazu, Kondo, Makoto, Onizuka, Tatsuo, Ichinohe, Yoshiko, Atsuta, Satoko, Morishima, and Junya, Kanda
- Subjects
Treatment Outcome ,Haplotypes ,HLA Antigens ,Histocompatibility Antigens Class I ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Humans ,Neoplasm Recurrence, Local ,Unrelated Donors ,Alleles ,Bone Marrow Transplantation - Abstract
The role of matching human leukocyte antigen (HLA) haplotypes in unrelated allogeneic bone marrow transplantation (allo-BMT) remains unclear. Here, we imputed the HLA haplotypes of 3657 patients who received unrelated single HLA allele-mismatched allo-BMT, included from the Transplant Registry Unified Management Program (TRUMP) database, the Japanese registry program for hematopoietic transplantation, using mathematical methods. We successfully imputed the HLA haplotypes of both patients and donors in 1365 cases (37.3%) with ≥90% probability. Of the patients, 1326 (97.1%) and 39 (2.9%) were categorized into one-haplotype-matched and no-haplotype-matched groups, respectively. Disease-free survival was significantly worse in the no-haplotype-matched group. Multivariate analyses revealed that no-haplotype-match was an independent risk factor for reducing disease-free survival (hazard ratio, 1.54 [95% confidence interval: 1.01-2.36]; p = 0.047). However, the overall survival did not significantly differ between the groups. The incidence of grade III-IV acute and chronic graft-versus-host disease did not significantly differ between the groups. Furthermore, there were no significant differences in the cumulative incidences of relapse and non-relapse mortality between the groups. Our findings suggest that imputing haplotypes using a mathematical approach can help to avoid transplanting patients with donors who do not share matching haplotypes, thereby improving the outcome of allo-BMT.
- Published
- 2021
23. Allogeneic hematopoietic cell transplantation using fludarabine plus myeloablative busulfan and melphalan confers promising survival in high-risk hematopoietic neoplasms: a single-center retrospective analysis
- Author
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Tatsuo Ichinohe, Keita Fujino, Masatoshi Nishizawa, Takahiko Miyama, Takehiko Morioka, Hisao Nagoshi, Teruhisa Fujii, Taro Edahiro, Yuji Hirata, Noriyasu Fukushima, Tatsuji Mino, Tetsumi Yoshida, Takakazu Kawase, Mitsunori Noma, and Kayo Toishigawa
- Subjects
Melphalan ,Oncology ,Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Graft vs Host Disease ,Single Center ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Recurrence ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Retrospective analysis ,Humans ,Transplantation, Homologous ,Hematopoietic Neoplasms ,Busulfan ,Aged ,Retrospective Studies ,Hematopoietic cell ,business.industry ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Myeloablative Agonists ,Combined Modality Therapy ,Survival Analysis ,Fludarabine ,Transplantation ,surgical procedures, operative ,Treatment Outcome ,030220 oncology & carcinogenesis ,Hematologic Neoplasms ,Female ,business ,Vidarabine ,030215 immunology ,medicine.drug - Abstract
Optimal selection of pretransplant conditioning is crucially vital for improving survival and quality-of-life of patients who receive allogeneic hematopoietic cell transplantation (allo-HCT), particularly in those with high-risk diseases. In this study, we evaluated the efficacy and safety of recently-developed reduced-toxicity myeloablative regimen that combines fludarabine, intravenous busulfan, and melphalan (FBM).We conducted a single-center retrospective analysis of 39 patients (23 with myeloid neoplasms and 16 with lymphoid neoplasms), with a median age of 50 (range, 17-68) years, who underwent their first allo-HCT using the FBM regimen. Graft types were bone marrow in 11, peripheral blood in 11, and cord blood in 17 patients. Cyclosporine- or tacrolimus-based graft-versus-host disease (GVHD) prophylaxis was administered. The primary end point of the study was the overall survival rate at 2-year after transplantation.After a median follow-up of 910 days for the surviving patients, 2-year overall survival was 62% for the entire cohort; 73% in the low-to-intermediate-risk group and 44% in the high-to-very high-risk group classified by the refined CIBMTR Disease Risk Index. Cumulative incidences of engraftment, grade II-IV acute GVHD, chronic GVHD, relapse, and non-relapse mortality were 95%, 56%, 56%, 31%, and 17%, respectively.These results suggest that our FBM regimen can be applied to allo-HCT using various graft types and yields acceptable outcomes with relatively low non-relapse mortality in both myeloid and lymphoid neoplasms. Also, we observed a promising survival in the group of patients with high-risk diseases, warranting more accumulation of patients and longer follow-up.
- Published
- 2021
24. Assessment of early treatment response on MRI in multiple myeloma: Comparative study of whole-body diffusion-weighted and lumbar spinal MRI
- Author
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Tatsuo Ichinohe, Shogo Maeda, Shota Kondo, Takakazu Kawase, Miyuki Takasu, Yuji Takahashi, Kazuo Awai, Yasutaka Baba, and Yuji Akiyama
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Male ,Serum Proteins ,Physiology ,medicine.medical_treatment ,Cancer Treatment ,Biochemistry ,030218 nuclear medicine & medical imaging ,Diagnostic Radiology ,Hematologic Cancers and Related Disorders ,Fats ,Cohort Studies ,0302 clinical medicine ,Bone Marrow ,Immune Physiology ,Medicine and Health Sciences ,Whole Body Imaging ,Multiple myeloma ,Aged, 80 and over ,Multidisciplinary ,medicine.diagnostic_test ,Pharmaceutics ,Radiology and Imaging ,Remission Induction ,Hematology ,Middle Aged ,Prognosis ,Blood proteins ,Magnetic Resonance Imaging ,Lipids ,Myelomas ,medicine.anatomical_structure ,Myeloma Proteins ,Oncology ,030220 oncology & carcinogenesis ,Medicine ,Female ,Multiple Myeloma ,Research Article ,Clinical Oncology ,Adult ,Myeloma protein ,Imaging Techniques ,Science ,Immunology ,Research and Analysis Methods ,03 medical and health sciences ,Cancer Chemotherapy ,Lumbar ,Drug Therapy ,Diagnostic Medicine ,medicine ,Chemotherapy ,Humans ,Myelomas and Lymphoproliferative Diseases ,Aged ,Retrospective Studies ,Receiver operating characteristic ,business.industry ,Lumbosacral Region ,Cancers and Neoplasms ,Biology and Life Sciences ,Proteins ,Magnetic resonance imaging ,medicine.disease ,Diffusion Magnetic Resonance Imaging ,Immune System ,Bone marrow ,Clinical Medicine ,Nuclear medicine ,business - Abstract
Objectives To compare remission status at completion of chemotherapy for multiple myeloma (MM) with changes in total diffusion volume (tDV) calculated from whole-body diffusion-weighted imaging (WB-DWI) and fat fraction (FF) of lumbar bone marrow (BM) by modified Dixon Quant (mDixon Quant) soon after induction of chemotherapy, and to assess the predictive value of MRI. Methods Fifty patients (mean age, 66.9 ± 10.5 years) with symptomatic myeloma were examined before and after two cycles of chemotherapy. From WB-DWI data, tDV was obtained with the threshold for positive BM involvement. Mean FF was calculated from lumbar BM using the mDixon Quant sequence. At the completion of chemotherapy, patients were categorized into a CR/very good PR (VGPR) group (n = 15; mean age, 67.6 ± 10.3 years) and a PR, SD or PD group (n = 35; mean age, 69.1 ± 8.6 years). ROC curves were plotted to assess performance in predicting achievement of CR/VGPR. Results At second examination, serum M protein, β2-microglobulin, and tDV were significantly decreased and hemoglobin, mean ADC, and FF were significantly increased in the CR/VGPR group and serum M protein was significantly increased in the PR/SD/PD group. The general linear model demonstrated that percentage changes in FF and M protein contributed significantly to achieving CR/VGPR (P = 0.02, P = 0.04, respectively). AUCs of ROC curves were 0.964 for FF and 0.847 for M protein. Conclusions Early change in FF of lumbar BM and serum M protein soon after induction of chemotherapy contributed significantly to prediction of CR/VGPR.
- Published
- 2020
25. Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals
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Kazutaka Kitaura, Masashi Shibata, Tadasu Shin-I, Atsushi Muraguchi, Kumi Oshima, Ren Chishaki, Ryuji Suzuki, Hiroshi Hamana, Tatsuo Ichinohe, Takahiko Miyama, Hiroh Saji, Hiroyuki Kishi, Takakazu Kawase, and Kiyotaka Kuzushima
- Subjects
0301 basic medicine ,Cellular immunity ,Science ,Receptors, Antigen, T-Cell ,Gene Expression ,T-Cell Antigen Receptor Specificity ,chemical and pharmacologic phenomena ,Immunogenetics ,Biology ,Lymphocyte Activation ,Deep sequencing ,Article ,Cell Line ,Immunophenotyping ,Viral Matrix Proteins ,03 medical and health sciences ,Antigen ,HLA Antigens ,Transduction, Genetic ,Humans ,Genetics ,Immunity, Cellular ,Precursor Cells, T-Lymphoid ,Multidisciplinary ,Effector ,Repertoire ,T-cell receptor ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Phosphoproteins ,030104 developmental biology ,Immunology ,Medicine ,Immunologic Memory ,Biomarkers - Abstract
To expand our knowledge of the ontogeny of the T-cell receptor (TCR) repertoire of antigen-specific T-cell subsets, we combined next-generation deep sequencing and single-cell multiplex clonotype analysis to evaluate the diversity and frequency of paired TCRs, their functions and whether clonotypic TCRs are shared among different individuals. Using an HLA-A*02-restricted cytomegalovirus (CMV) pp65-derived immunogenic peptide, we found that the more dominant pp65-specific TCR clonotypes in the blood of healthy donors have higher binding affinities for the CMV peptide and arise from clonotypes that are highly shared among individuals. Interestingly, these highly shared HLA-A*02-restricted CMV-specific TCRs were detected in a CMV-seronegative individual as well as in HLA-A*02-negative donors albeit at lower frequency. More intriguingly, these shared TCR clonotypes were abundant in the stem memory T-cell subset, and TCR diversity of the stem memory T-cell repertoire was significantly lower than in the central memory and effector memory T-cell repertoires. These results suggest that the stem memory T-cell subset may serve as a reservoir of highly shared and highly functional memory T-cells.
- Published
- 2017
26. Myeloma Cells Are Activated in Bone Marrow Microenvironment by the CD180/MD-1 Complex, Which Senses Lipopolysaccharide
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Tatsuo Ichinohe, Naoki Osada, Tohru Izumi, Hiroshi Yasui, Daisuke Koyama, Yoshiaki Kuroda, Jiro Kikuchi, Yusuke Furukawa, and Takakazu Kawase
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Lipopolysaccharides ,Transcriptional Activation ,Cancer Research ,Transplantation, Heterologous ,Bone Marrow Cells ,Mice, SCID ,Antibodies ,03 medical and health sciences ,Ikaros Transcription Factor ,Mice ,Downregulation and upregulation ,Antigen ,In vivo ,Antigens, CD ,Bone Marrow ,Mice, Inbred NOD ,Cell Line, Tumor ,medicine ,Cell Adhesion ,Animals ,Humans ,Immunologic Factors ,Cell adhesion ,Promoter Regions, Genetic ,Lenalidomide ,Cell Proliferation ,Gene knockdown ,Membrane Glycoproteins ,Chemistry ,Mesenchymal Stem Cells ,Cell Hypoxia ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Cellular Microenvironment ,Cell culture ,Antigens, Surface ,Cancer research ,Bone marrow ,Multiple Myeloma ,Neoplasm Transplantation - Abstract
Multiple myeloma (MM) cells acquire dormancy and drug resistance via interaction with bone marrow stroma cells (BMSC) in a hypoxic microenvironment. Elucidating the mechanisms underlying the regrowth of dormant clones may contribute to further improvement of the prognosis of MM patients. In this study, we find that the CD180/MD-1 complex, a noncanonical lipopolysaccharide (LPS) receptor, is expressed on MM cells but not on normal counterparts, and its abundance is markedly upregulated under adherent and hypoxic conditions. Bacterial LPS and anti-CD180 antibody, but not other Toll-like receptor ligands, enhanced the growth of MM cells via activation of MAP kinases ERK and JNK in positive correlation with expression levels of CD180. Administration of LPS significantly increased the number of CD180/CD138 double-positive cells in a murine xenograft model when MM cells were inoculated with direct attachment to BMSC. Knockdown of CD180 canceled the LPS response in vitro and in vivo. Promoter analyses identified IKZF1 (Ikaros) as a pivotal transcriptional activator of the CD180 gene. Both cell adhesion and hypoxia activated transcription of the CD180 gene by increasing Ikaros expression and its binding to the promoter region. Pharmacological targeting of Ikaros by the immunomodulatory drug lenalidomide ameliorated the response of MM cells to LPS in a CD180-dependent manner in vitro and in vivo. Thus, the CD180/MD-1 pathway may represent a novel mechanism of growth regulation of MM cells in a BM milieu and may be a therapeutic target of preventing the regrowth of dormant MM cells. Significance: This study describes a novel mechanism by which myeloma cells are regulated in the bone marrow, where drug resistance and dormancy can evolve after treatment, with potential therapeutic implications for treating this often untreatable blood cancer. Cancer Res; 78(7); 1766–78. ©2018 AACR.
- Published
- 2017
27. Effect of Haplotype Matching on Outcomes after Adult Single Cord Blood Transplantation
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Naoyuki Uchida, Takakazu Kawase, Makoto Onizuka, Yoshiko Atsuta, Yoshiko Matsuhashi, Koji Nagafuji, Tatsuo Ichinohe, Junji Tanaka, Junya Kanda, Yuji Ohno, and Hidenori Tanaka
- Subjects
medicine.medical_specialty ,Neutrophil Engraftment ,business.industry ,Immunology ,Haplotype ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Transplantation ,Calcineurin ,Graft-versus-host disease ,ABO blood group system ,Internal medicine ,medicine ,Cumulative incidence ,business ,Allele frequency - Abstract
Background: High incidence of graft failure is a major obstacle for successful unrelated cord blood transplantation (UCBT). To ensure engraftment, unrelated cord blood (UCB) unit with higher total nucleated cell (TNC) and CD34 cell doses and less HLA mismatches between UCB units and patients were usually selected. However, it remains unclear whether HLA haplotype between the UCB units and patients should be matched. Using data from Japanese registry, we analyzed the effect of haplotype matching on the outcomes after single UCBT. Methods: Patients with hematologic diseases, aged 16 years or more, and have undergone their first UCBT between 2005 and 2014 were included in the study. The effect of haplotype matching (0, 1, and 2 haplotype matches) on neutrophil engraftment, overall mortality, relapse, and non-relapse mortality was analyzed after adjusting for other significant variables. Haplotype was estimated based on HLA-A, -B, -C, and -DRB1 allele information and Japanese allele frequency data. The haplotypes of both the patient and UCB unit were determined in 1,347 cases. Cases with more than 4 allele mismatches (n = 96) were excluded from the study. Results: The median age of the patients included in the study was 55 years (range 16-79 years). Median TNC and CD34 doses were 2.7 x 107/kg (range, 1.4-8.1x107/kg) and 0.8 x 105/kg (range, 0.1-5.2x105/kg), respectively. The number of allele mismatches were 0 in 82, 1 in 154, 2 in 252, 3 in 565, and 4 in 294 patients. The graft-versus-host disease (GVHD) prophylaxes were calcineurin inhibitors in combination with methotrexate in 707, calcineurin inhibitors in combination with Mycophenolate mofetil in 430, and other prophylaxes in 208 patients. The cumulative incidence of neutrophil engraftment at day 42 among groups with 0, 1, and 2 HLA haplotype matches was 79%, 82%, and 88%, respectively (Gray test, P=0.008) (Figure 1). In the multivariate analysis, the group with no haplotype match was marginally associated with worse neutrophil engraftment compared to the group with 1 haplotype match group (0 match vs. 1 match, HR 0.88, P=0.087), whereas the group with 2 haplotype matches was significantly associated with better neutrophil engraftment (2 match vs. 1 match, HR 1.39, P=0.005). Other significant variables were recipient sex, CD34 cell dose, transplant year, performance status, ABO matching, GVHD prophylaxis, and disease status. Tendency of worse neutrophil engraftment in the group with no haplotype matches was more apparent in patients with double mismatches at the same locus (0 match + no double mismatch vs. 1 match, HR 0.93, P=0.429, 0 match + double mismatch vs. 1 match, HR 0.80, P=0.050). Haplotype matching did not have any effect on overall survival and non-relapse mortality. Group with 2 haplotype matches was significantly associated with higher risk of relapse than the group with 1 haplotype match, whereas, there was no difference in the risk of relapse between the groups with no match and 1 match. Conclusions: In addition to the CD34 cell dose and HLA matching, HLA haplotype matching might be considered to obtain better neutrophil engraftment. Two haplotype matches (8 of 8 allele matches) should be avoided if the relapse risk is high. Figure 1. Figure 1. Disclosures Tanaka: Pfizer: Honoraria; Otsuka: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Novartis Pharma: Honoraria. Ichinohe:Zenyaku Kogyo Co.: Research Funding; Celgene: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Taiho Pharmaceutical Co.: Research Funding; Mundipharma: Honoraria; Otsuka Pharmaceutical Co.: Research Funding; Nippon Shinyaku Co.: Research Funding; Sumitomo Dainippon Pharma Co.: Research Funding; MSD: Research Funding; Novartis.: Honoraria; JCR Pharmaceuticals: Honoraria; Alexion Pharmaceuticals: Honoraria; Repertoire Genesis Inc.: Research Funding; Bristol-Myers Squibb: Honoraria; Takeda Pharmaceutical Co.: Research Funding; Pfizer: Research Funding; Ono Pharmaceutical Co.: Research Funding; Kyowa Hakko Kirin Co.: Research Funding; Eisai Co.: Research Funding; CSL Behring: Research Funding; Chugai Pharmaceutical Co.: Research Funding; Astellas Pharma: Research Funding.
- Published
- 2018
28. Comparison of Unrelated Cord Blood Transplantation and HLA-Mismatched Unrelated Bone Marrow Transplantation for Adults with Leukemia
- Author
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Shunichi Kato, Satoshi Takahashi, Yoshihisa Kodera, Shunro Kai, Hiroshi Azuma, Yasuo Morishima, Masahiro Tsuchida, Takehiko Mori, Hisashi Sakamaki, Minoko Takanashi, Keisei Kawa, Takakazu Kawase, Ritsuro Suzuki, Yasushi Kouzai, Takahiro Fukuda, Yoshiko Atsuta, Naoki Kobayashi, Tokiko Nagamura-Inoue, and Shuichi Taniguchi
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Graft vs Host Disease ,Antineoplastic Agents ,Cord Blood Stem Cell Transplantation ,Human leukocyte antigen ,Disease-Free Survival ,HLA Antigens ,Recurrence ,Risk Factors ,Internal medicine ,Humans ,Medicine ,Aged ,Bone Marrow Transplantation ,Aged, 80 and over ,Transplantation ,Acute leukemia ,Leukemia ,business.industry ,Histocompatibility Testing ,Myelodysplastic syndromes ,Hematology ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Myelodysplastic Syndromes ,Acute Disease ,Immunology ,Female ,Bone marrow ,Unrelated Donors ,business ,HLA-mismatched unrelated bone marrow transplantation ,Unrelated cord blood transplantation - Abstract
Recent advances in unrelated cord blood transplantation (UCBT) and high-resolution typing of human leukocyte antigen (HLA) from an unrelated donor have increased choices in alternative donor/stem cell source selection. We assessed HLA-mismatched locus-specific comparison of the outcomes of 351 single-unit UCB and 1,028 unrelated bone marrow (UBM) adult recipients 16 years old or older at the time of transplantation who received first stem cell transplantation with myeloablative conditioning for acute leukemia or myelodysplastic syndromes. With adjusted analyses, HLA 0 to 2 mismatched UCBT showed similar overall mortality (relative risk [RR] = 0.85, 95% confidence interval [CI], 0.68-1.06; P = .149) compared with that of single-HLA-DRB1-mismatched UBMT. UCBT showed inferior neutrophil recovery (RR = 0.50, 95% CI, 0.42-0.60; P < .001), lower risk of acute graft-versus-host disease (RR = 0.55, 95% CI, 0.42-0.72; P < .001), and lower risk of transplantation-related mortality (RR = 0.68, 95% CI, 0.50-0.92; P = .011) compared with single-HLA-DRB1-mismatched UBMT. No significant difference was observed for risk of relapse (RR = 1.28, 95% CI, 0.93-1.76; P = .125). HLA 0 to 2 antigen-mismatched UCBT is a reasonable second alternative donor/stem cell source with a survival outcome similar to that of single-HLA-DRB1-mismatched or other 7 of 8 UBMT.
- Published
- 2012
29. Impact of graft-versus-host disease on outcomes after allogeneic hematopoietic cell transplantation for adult T-cell leukemia: a retrospective cohort study
- Author
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Shuichi Taniguchi, Minoko Takanashi, Ryuji Tanosaki, Masakatsu Hishizawa, Yasushi Miyazaki, Jun Okamura, Koji Nagafuji, Atae Utsunomiya, Takakazu Kawase, Tetsuya Eto, Ritsuro Suzuki, Junya Kanda, Yoshiko Atsuta, Tokiko Nagamura-Inoue, Yukiyoshi Moriuchi, Yasuo Morishima, Keitaro Matsuo, Tatsuo Ichinohe, Fumio Kawano, Shunichi Kato, Masato Masuda, Masamichi Hara, Takashi Uchiyama, Shunro Kai, and Hisashi Sakamaki
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Transplantation Conditioning ,Immunology ,T-cell leukemia ,Graft vs Host Disease ,Disease ,Lower risk ,Biochemistry ,Cohort Studies ,Young Adult ,immune system diseases ,Internal medicine ,medicine ,Humans ,Leukemia-Lymphoma, Adult T-Cell ,Transplantation, Homologous ,Aged ,Retrospective Studies ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Retrospective cohort study ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Survival Analysis ,Transplantation ,Leukemia ,Treatment Outcome ,surgical procedures, operative ,Graft-versus-host disease ,Female ,business - Abstract
Allogeneic hematopoietic cell transplantation (HCT) is an effective treatment for adult T-cell leukemia (ATL), raising the question about the role of graft-versus-leukemia effect against ATL. In this study, we retrospectively analyzed the effects of acute and chronic graft-versus-host disease (GVHD) on overall survival, disease-associated mortality, and treatment-related mortality among 294 ATL patients who received allogeneic HCT and survived at least 30 days posttransplant with sustained engraftment. Multivariate analyses treating the occurrence of GVHD as a time-varying covariate demonstrated that the development of grade 1-2 acute GVHD was significantly associated with higher overall survival (hazard ratio [HR] for death, 0.65; P = .018) compared with the absence of acute GVHD. Occurrence of either grade 1-2 or grade 3-4 acute GVHD was associated with lower disease-associated mortality compared with the absence of acute GVHD, whereas grade 3-4 acute GVHD was associated with a higher risk for treatment-related mortality (HR, 3.50; P < .001). The development of extensive chronic GVHD was associated with higher treatment-related mortality (HR, 2.75; P = .006) compared with the absence of chronic GVHD. Collectively, these results indicate that the development of mild-to-moderate acute GVHD confers a lower risk of disease progression and a beneficial influence on survival of allografted patients with ATL.
- Published
- 2012
30. Outcome of medium-dose VP-16/CY/TBI superior to CY/TBI as a conditioning regimen for allogeneic stem cell transplantation in adult patients with acute lymphoblastic leukemia
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Yoichi M. Ito, Heiwa Kanamori, Junji Tanaka, Takahiro Fukuda, Takakazu Kawase, Ritsuro Suzuki, Yasuo Morishima, Akio Shigematsu, Naoki Kobayashi, Takashi Fukuhara, Fumiaki Yoshiba, Takuya Yamashita, Masahiro Imamura, Keiki Kumano, Koji Iwato, and Yoshiko Atsuta
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Cyclophosphamide ,Adolescent ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Acute lymphoblastic leukemia ,Medium-dose VP/CY/TBI ,Young Adult ,Conditioning regimen ,Internal medicine ,Acute lymphocytic leukemia ,medicine ,Humans ,Transplantation, Homologous ,Survival rate ,Etoposide ,Retrospective Studies ,business.industry ,Hazard ratio ,Stem cell transplantation ,Hematology ,Total body irradiation ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,nervous system diseases ,Surgery ,Transplantation ,Survival Rate ,Regimen ,Treatment Outcome ,Female ,business ,Immunosuppressive Agents ,Whole-Body Irradiation ,medicine.drug - Abstract
The choice of conditioning regimen before allogeneic stem cell transplantation (SCT) in patients with acute lymphoblastic leukemia (ALL) is important. We retrospectively compared outcomes of medium-dose VP-16/cyclophosphamide/total body irradiation (VP/CY/TBI) regimen and CY/TBI. Five hundred and twenty-nine patients (VP/CY/TBI: n = 35, CY/TBI: n = 494) who met all of the following criteria were compared: first time for SCT, aged 15-59 years; first or second complete remission at SCT; bone marrow or peripheral blood as stem cell source; and HLA phenotypically matched donor. Median age of the patients was 34 years, and patients who received VP/CY/TBI were younger (28 years vs. 34 years, P = 0.02). Cumulative incidences of relapse and non-relapse mortality (NRM) were higher for patients who received CY/TBI (P = 0.01 for relapse, P < 0.01 for NRM). After a median follow-up period of 36.9 months, 5-year overall survival (OS) rates were 82.2% in the VP/CY/TBI group and 55.2% in the CY/TBI group. OS, and disease-free survival (DFS) in the VP/CY/TBI group were shown to be significantly better by multivariate analysis [hazard ratio: 0.21 (95% confidence interval: 0.06-0.49) for DFS, hazard ratio: 0.25 (95% confidence interval: 0.08-0.59) for OS]. VP/CY/TBI was associated with a lower relapse rate and no increase in NRM, resulting in better survival than that in CY/TBI for adult ALL patients.
- Published
- 2011
31. Acceptable HLA-mismatching in unrelated donor bone marrow transplantation for patients with acquired severe aplastic anemia
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Seiji Kojima, Hiroshi Yagasaki, Hisato Kigasawa, Koji Kato, Yoshihisa Kodera, Hisashi Sakamaki, Takakazu Kawase, Yasuo Morishima, Shunichi Kato, Hiromasa Yabe, and Masahiro Tsuchida
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Bone marrow transplantation ,Immunology ,Human leukocyte antigen ,Multiple alleles ,Severity of Illness Index ,Biochemistry ,Gastroenterology ,Young Adult ,HLA Antigens ,Unrelated Donor ,Internal medicine ,medicine ,Humans ,Sibling Relations ,Significant risk ,Allele ,Child ,HLA-DP beta-Chains ,Bone Marrow Transplantation ,business.industry ,Histocompatibility Testing ,Infant, Newborn ,Anemia, Aplastic ,Infant ,Cell Biology ,Hematology ,Middle Aged ,Severe Aplastic Anemia ,Tissue Donors ,Molecular Typing ,Transplantation ,Child, Preschool ,Female ,business - Abstract
We retrospectively analyzed the effect of HLA mismatching (HLA-A, -B, -C, -DRB1, -DQB1) with molecular typing on transplantation outcome for 301 patients with acquired severe aplastic anemia (SAA) who received an unrelated BM transplant through the Japan Marrow Donor Program. Additional effect of HLA-DPB1 mismatching was analyzed for 10 of 10 or 9 of 10 HLA allele-matched pairs (n = 169). Of the 301 recipient/donor pairs, 101 (33.6%) were completely matched at 10 of 10 alleles, 69 (23%) were mismatched at 1 allele, and 131 (43.5%) were mismatched at ≥ 2 alleles. Subjects were classified into 5 subgroups: complete match group (group I); single-allele mismatch group (groups II and III); multiple alleles restricted to HLA-C, -DRB1, and -DQB1 mismatch group (group IV); and others (group V). Multivariate analysis indicated that only HLA disparity of group V was a significant risk factor for poor survival and grade II-IV acute GVHD. HLA-DPB1 mismatching was not associated with any clinical outcome. We recommend the use of an HLA 10 of 10 allele-matched unrelated donor. However, if such a donor is not available, any single-allele or multiple-allele (HLA-C, -DRB1, -DQB1) mismatched donor is acceptable as an unrelated donor for patients with severe aplastic anemia.
- Published
- 2011
32. Association analysis of the NOD2 gene with susceptibility to graft-versus-host disease in a Japanese population
- Author
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Yoshinobu Eishi, Keisei Kawa, Takakazu Kawase, Natsu Yamaguchi, Yusuke Nakamura, Makoto Onizuka, Kazutoshi Koike, Yasuo Morishima, Masamichi Hara, Keiko Yamazaki, Hideki Akiyama, Hiroki Amano, Shigetaka Asano, Tsuyoshi Tanabe, Jun Ishikawa, Koichi Matsuda, Mikiko Kobayashi-Miura, Arinobu Tojo, Takehiko Mori, Yasuyuki Fujita, Satoshi Takahashi, and Takeyasu Kakamu
- Subjects
Genotype ,Nod2 Signaling Adaptor Protein ,Graft vs Host Disease ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Crohn Disease ,Japan ,NOD2 ,medicine ,Humans ,Genetic Predisposition to Disease ,Alleles ,Leukemia ,Donor selection ,Hematology ,Odds ratio ,medicine.disease ,digestive system diseases ,HEK293 Cells ,medicine.anatomical_structure ,Graft-versus-host disease ,Gene Expression Regulation ,Immunology ,Cytokine secretion ,Bone marrow - Abstract
Members of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family participate in the innate immune system, exerting widespread effects on cytokine secretion, autophagy, and apoptosis. Recent studies in Caucasians revealed the association between mutants of NOD2, a member of the NLR family, and severity of acute graft-versus-host disease (GVHD). NOD2 polymorphism screening has been recommended for donor selection and risk assessment at bone marrow transplantation. To investigate whether NOD2 plays a role in the pathogenesis of GVHD in a Japanese population, we examined DNA from 142 bone marrow transplant patient/donor pairs to detect genetic variation in the NOD2 gene. No genetic variants of NOD2 were associated with the severity of acute GVHD in our patients. However, a weak association between a single nucleotide polymorphism in the NOD2 gene (R471C) and acute myeloid leukemia in the bone marrow patients (p = 0.029, odds ratio 4.08, 95% CI 1.22-13.67) was detected. This polymorphism was not prevalent in 479 Crohn's disease (CD) patients in Japan. These results suggest that, in the Japanese population, unlike the Caucasian, NOD2 is not a major contributor to susceptibility to severe acute GVHD.
- Published
- 2011
33. Profile of Participants and Genotype Distributions of 108 Polymorphisms in a Cross-Sectional Study of Associations of Genotypes With Lifestyle and Clinical Factors: A Project in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study
- Author
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Ryoichi Takayanagi, Satoyo Hosono, Kokichi Arisawa, Megumi Hara, Tatsuhiko Sakamoto, Aya Yoshikawa, Kenji Matsui, Miwa Yamaguchi, Kenji Wakai, Hidenobu Takami, Hidemi Ito, Kazuyo Nakamura, Kazuo Tajima, Miki Watanabe, Hinako Nanri, Takeshi Suzuki, Yasuki Higaki, Keitaro Matsuo, Shinkan Tokudome, Noriko Tsunematsu, Naoto Taguchi, Kazuyo Hirasada, Masako Shigeta, Nami Hattori, Yoshikuni Kita, Akihiro Hosono, Haruo Mikami, Ryosuke Ando, Keitaro Tanaka, Shin Ogawa, Rieko Okada, Etsuko Ozaki, Satoko Mitani, Asahi Hishida, Guang Yin, Nahomi Imaeda, Emi Morita, Hideo Takeda, Kazuko Nishio, Yasuyuki Nakamura, Takakazu Kawase, Michiaki Kubo, Mitsuru Fukatsu, Hideo Tanaka, Nagato Kuriyama, Mineyoshi Hiyoshi, Hirokazu Uemura, Sayo Kawai, Tanvir Chowdhury Turin, Mikako Horita, Mariko Naito, Daisuke Matsui, Isao Watanabe, Kiyoshi Shibata, Toshiro Takezaki, Hirotsugu Ueshima, Hideshi Niimura, Keizo Ohnaka, Yatami Asai, Takeshi Imaizumi, Suminori Kono, Shirabe Chiba, Chiho Goto, Mariko Nakamoto, Naoyuki Takashima, Kotaro Ozasa, Tamaki Yamada, Koichi Shinchi, Kaoru Inoue, Sadao Suzuki, Nobuyuki Hamajima, Masaya Tatebo, Nahid Rumana, Akihiko Nakamura, Yoshiyuki Watanabe, and Katsuyuki Miura
- Subjects
Gerontology ,Adult ,Male ,Genotype ,Epidemiology ,Cross-sectional study ,Population ,cross-sectional studies ,Environment ,polymorphism ,Cohort Studies ,Gene Frequency ,Japan ,Genetics ,Medicine ,Humans ,Study Profile ,education ,Allele frequency ,Life Style ,Aged ,education.field_of_study ,Polymorphism, Genetic ,business.industry ,Significant difference ,General Medicine ,Middle Aged ,gene–environment interactions ,Minor allele frequency ,Japan Multi-institutional Collaborative Cohort Study ,Cohort ,Population study ,Female ,business ,allele frequency ,Demography - Abstract
Background: Most diseases are thought to arise from interactions between environmental factors and the host genotype. To detect gene–environment interactions in the development of lifestyle-related diseases, and especially cancer, the Japan Multi-institutional Collaborative Cohort (J-MICC) Study was launched in 2005.Methods: We initiated a cross-sectional study to examine associations of genotypes with lifestyle and clinical factors, as assessed by questionnaires and medical examinations. The 4519 subjects were selected from among participants in the J-MICC Study in 10 areas throughout Japan. In total, 108 polymorphisms were chosen and genotyped using the Invader assay.Results: The study group comprised 2124 men and 2395 women with a mean age of 55.8 ± 8.9 years (range, 35–69 years) at baseline. Among the 108 polymorphisms examined, 4 were not polymorphic in our study population. Among the remaining 104 polymorphisms, most variations were common (minor allele frequency ≥0.05 for 96 polymorphisms). The allele frequencies in this population were comparable with those in the HapMap-JPT data set for 45 Japanese from Tokyo. Only 5 of 88 polymorphisms showed allele-frequency differences greater than 0.1. Of the 108 polymorphisms, 32 showed a highly significant difference in minor allele frequency among the study areas (P < 0.001).Conclusions: This comprehensive data collection on lifestyle and clinical factors will be useful for elucidating gene–environment interactions. In addition, it is likely to be an informative reference tool, as free access to genotype data for a large Japanese population is not readily available.
- Published
- 2011
34. A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT
- Author
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K Miyamura, Masami Inoue, Takakazu Kawase, M Onizuka, Nakao S, Hiroshi Sao, Tetsuya Fukuda, Yasuo Morishima, J. L. Espinoza, Akiyoshi Takami, Shigeki Ohtake, Yoshihisa Kodera, H Akiyama, and Shinichiro Okamoto
- Subjects
Adult ,Transplantation Conditioning ,Adolescent ,Graft vs Host Disease ,Single-nucleotide polymorphism ,Human leukocyte antigen ,Polymorphism, Single Nucleotide ,Cohort Studies ,Asian People ,Genotype ,Humans ,Medicine ,Child ,Bone Marrow Transplantation ,Retrospective Studies ,Transplantation ,business.industry ,Interleukin-17 ,Hazard ratio ,Infant ,Retrospective cohort study ,Hematology ,Middle Aged ,Pathophysiology ,Child, Preschool ,Immunology ,Unrelated Donors ,business ,Cohort study - Abstract
IL-17 has an important role in the host defense against extracellular pathogens and the pathophysiology of autoimmune diseases. This study retrospectively examined the impact of a single-nucleotide polymorphism (rs2275913, G197A) in the IL-17 gene of a total 510 recipients with hematologic malignancies and their unrelated donors on the clinical outcomes in HLA-matched myeloablative (discovery study) and nonmyeloablative (validation study) BMT through the Japan Marrow Donor Program (JMDP). In the discovery study, the presence of a 197A genotype in the recipient resulted in a higher incidence of grades II-IV acute GVHD (hazard ratio (HR), 1.87; 95% confidence interval (CI), 1.23-2.85; P=0.004). The donor IL-17A genotype did not significantly influence the transplant outcomes. The validation study showed a trend toward an association of the recipient 197A genotype with an increased risk of grades III-IV acute GVHD (HR, 5.84; 95% CI, 0.75-45.72; P=0.09), as well as a significantly increased risk for chronic GVHD (HR, 3.86; 95% CI, 1.29-11.59; P=0.02). These results suggest an association of the 197A genotype in the recipient side with the development of acute GVHD.
- Published
- 2011
35. Weight Gain During Adulthood and Body Weight at Age 20 Are Associated With the Risk of Endometrial Cancer in Japanese Women
- Author
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Hidemi Ito, Takakazu Kawase, Hideo Tanaka, Kaoru Hirose, Miki Watanabe, Satoyo Hosono, Takeshi Suzuki, Toru Nakanishi, Kazuo Tajima, and Keitaro Matsuo
- Subjects
Adult ,medicine.medical_specialty ,Epidemiology ,case-control study ,Body Mass Index ,Young Adult ,Japan ,Risk Factors ,Statistical significance ,medicine ,Humans ,Obesity ,Young adult ,Risk factor ,Cancer ,Gynecology ,business.industry ,Obstetrics ,Endometrial cancer ,Body Weight ,Age Factors ,Case-control study ,weight gain ,General Medicine ,medicine.disease ,Endometrial Neoplasms ,Case-Control Studies ,endometrial cancer ,Female ,Original Article ,medicine.symptom ,business ,Weight gain ,Body mass index - Abstract
Background Current obesity is an established risk factor for endometrial cancer; however, the roles of weight gain during adulthood and obesity in early adulthood on endometrial cancer have not been elucidated. Here, we conducted a case-control study comprising 222 histologically diagnosed incident endometrial cancer cases and 2162 age- and menstrual-status matched non-cancer controls. Methods Information on current body weight, weight and height at age 20 years, and lifestyle/environmental factors was obtained from a self-administered questionnaire. Subjects were classified into 3 groups according to change in body mass index (BMI, kg/m2) from age 20 years to enrollment (≤0 [reference], 0–3, and >3 kg/m2). The effects of adult BMI change and obesity in early adulthood were evaluated using an unconditional logistic regression model adjusted for potential confounders. Results A high BMI at age 20 (BMI ≥25, BMI 3 BMI change, OR = 2.02, 95% CI = 1.38–2.96; P-trend < 0.001). Parity and BMI at age 20 appeared to modify the effect of weight gain on cancer risk, albeit without statistical significance. This positive association of weight gain with risk was observed only for endometrioid adenocarcinoma. Conclusions The results show that endometrial cancer is positively associated with obesity at age 20 and weight gain during adulthood among Japanese women.
- Published
- 2011
36. Analysis of outcomes following autologous stem cell transplantation in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia during first complete remission
- Author
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Michihiro Hidaka, Koji Iwato, Hisashi Sakamaki, Shuichi Mizuta, Junji Tanaka, Mineo Kurokawa, Harumi Kato, Koichi Miyamura, Ritsuro Suzuki, Shinichi Kako, Kazuteru Ohashi, Takakazu Kawase, Yasuo Morishima, and Takehiko Mori
- Subjects
Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Philadelphia Chromosome Negative ,Lymphoblastic Leukemia ,Hematopoietic stem cell transplantation ,Philadelphia chromosome ,Transplantation, Autologous ,Autologous stem-cell transplantation ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Philadelphia Chromosome ,Online Only Articles ,Adult patients ,business.industry ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Complete remission ,Treatment options ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Prognosis ,medicine.disease ,Treatment Outcome ,business - Abstract
The optimal treatment for adult Philadelphia chromosome-negative acute lymphoblastic leukemia [Ph(−)ALL] during first complete remission (CR1) remains a matter of debate. One treatment option for Ph(−)ALL is autologous hematopoietic stem cell transplantation (auto-SCT).[1][1],[2][2] Previous
- Published
- 2014
37. Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospective study
- Author
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Koji Nagafuji, Minoko Takanashi, Junya Kanda, Yasushi Miyazaki, Tokiko Nagamura-Inoue, Fumio Kawano, Ryuji Tanosaki, Takakazu Kawase, Ritsuro Suzuki, Yoshiko Atsuta, Tatsuo Ichinohe, Masamichi Hara, Atae Utsunomiya, Keitaro Matsuo, Shuichi Taniguchi, Yukiyoshi Moriuchi, Shunichi Kato, Masato Masuda, Tetsuya Eto, Masakatsu Hishizawa, Jun Okamura, Yasuo Morishima, Takashi Uchiyama, Shunro Kai, and Hisashi Sakamaki
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,Graft vs Leukemia Effect ,Hematopoietic stem cell transplantation ,Biochemistry ,Japan ,Internal medicine ,Humans ,Leukemia-Lymphoma, Adult T-Cell ,Transplantation, Homologous ,Medicine ,Survival rate ,Retrospective Studies ,Human T-lymphotropic virus 1 ,Hematology ,business.industry ,Umbilical Cord Blood Transplantation ,Graft Survival ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,Middle Aged ,medicine.disease ,Surgery ,Survival Rate ,Transplantation ,Leukemia ,medicine.anatomical_structure ,Cord blood ,Disease Progression ,Female ,Bone marrow ,business ,Follow-Up Studies - Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is increasingly used as a curative option for adult T-cell leukemia (ATL), an intractable mature T-cell neoplasm causally linked with human T-cell leukemia virus type I (HTLV-I). We compared outcomes of 386 patients with ATL who underwent allogeneic HSCT using different graft sources: 154 received human leukocyte antigen (HLA)–matched related marrow or peripheral blood; 43 received HLA-mismatched related marrow or peripheral blood; 99 received unrelated marrow; 90 received single unit unrelated cord blood. After a median follow-up of 41 months (range, 1.5-102), 3-year overall survival for entire cohort was 33% (95% confidence interval, 28%-38%). Multivariable analysis revealed 4 recipient factors significantly associated with lower survival rates: older age (> 50 years), male sex, status other than complete remission, and use of unrelated cord blood compared with use of HLA-matched related grafts. Treatment-related mortality rate was higher among patients given cord blood transplants; disease-associated mortality was higher among male recipients or those given transplants not in remission. Among patients who received related transplants, donor HTLV-I seropositivity adversely affected disease-associated mortality. In conclusion, allogeneic HSCT using currently available graft source is an effective treatment in selected patients with ATL, although greater effort is warranted to reduce treatment-related mortality.
- Published
- 2010
38. Impact of highly conserved HLA haplotype on acute graft-versus-host disease
- Author
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Yasuo Morishima, Masahiro Satake, Hidetoshi Inoko, Hiroo Saji, Aiko Matsubara, Shunichi Kato, Satoko Morishima, Yasuhito Nannya, Seishi Ogawa, Takehiko Sasazuki, Takakazu Kawase, Yoshihisa Kodera, and Koichi Kashiwase
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Immunology ,Graft vs Host Disease ,Single-nucleotide polymorphism ,Human leukocyte antigen ,Hematopoietic stem cell transplantation ,Biology ,Polymorphism, Single Nucleotide ,Biochemistry ,Asian People ,Japan ,Risk Factors ,Internal medicine ,Immunopathology ,medicine ,Humans ,Transplantation, Homologous ,Allele ,Child ,Aged ,Retrospective Studies ,Aged, 80 and over ,Hematology ,Histocompatibility Antigens Class I ,Haplotype ,Hematopoietic Stem Cell Transplantation ,Infant, Newborn ,Infant ,Cell Biology ,Middle Aged ,medicine.disease ,Graft-versus-host disease ,Haplotypes ,Genetic Loci ,Child, Preschool ,Hematologic Neoplasms ,Acute Disease ,Female ,Genome-Wide Association Study - Abstract
Although the effects of human leukocyte antigen (HLA) locus matching on clinical outcome in unrelated hematopoietic stem cell transplantations have been characterized, the biologic implications of HLA haplotypes have not been defined. We demonstrated the genetic fixity of Japanese conserved extended haplotypes by multi–single nucleotide polymorphism analysis in 1810 Japanese donor-recipient pairs matching with HLA-A, -B, -C, -DRB1, and -DQB1 alleles. Three major Japanese conserved extended haplotypes (named HP-P1, HP-P2, and HP-P3) were essentially completely conserved at least in the 3.3-Mb HLA region from HLA-A to -DPB1, and extended far beyond HLA-A. The risk of acute graft-versus-host disease (GVHD) of these HLA haplotypes was assessed with multivariate Cox regression in 712 patients transplanted from HLA fully (HLA-A, B, C, DRB1, DQB1, and DPB1) matched unrelated donors. HP-P2 itself reduced the risk of grade 2 to 4 acute GVHD (hazard ratio [HR] = 0.63; P = .032 compared with HP-P2-negative), whereas HP-P3 tended to increase the risk (HR = 1.38; P = .07). Among 381 patients with HP-P1, HP-P1/P3 (HR = 3.35; P = .024) significantly increased the risk of acute GVHD compared with homozygous HP-P1. This study is the first to demonstrate that a genetic difference derived from HLA haplotype itself is associated with acute GVHD in allogeneic hematopoietic stem cell transplantation.
- Published
- 2010
39. Comparison between self-reported facial flushing after alcohol consumption and ALDH2 Glu504Lys polymorphism for risk of upper aerodigestive tract cancer in a Japanese population
- Author
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Satoyo Hosono, Yasushi Yatabe, Hideo Tanaka, Hidemi Ito, Kazuo Tajima, Keitaro Matsuo, Shunzo Hatooka, Masayuki Shinoda, Takakazu Kawase, Takeshi Suzuki, Yasuhisa Hasegawa, Isao Oze, and Miki Watanabe
- Subjects
Adult ,Male ,Risk ,Cancer Research ,medicine.medical_specialty ,Pathology ,Alcohol Drinking ,Esophageal Neoplasms ,Gastroenterology ,Internal medicine ,Genotype ,Flushing ,medicine ,Humans ,Genetic Predisposition to Disease ,Laryngeal Neoplasms ,Genotyping ,Aged ,ALDH2 ,Polymorphism, Genetic ,Surrogate endpoint ,business.industry ,Aldehyde Dehydrogenase, Mitochondrial ,digestive, oral, and skin physiology ,Head and neck cancer ,Cancer ,Pharyngeal Neoplasms ,General Medicine ,Odds ratio ,Aldehyde Dehydrogenase ,Middle Aged ,medicine.disease ,Confidence interval ,Oncology ,Female ,Mouth Neoplasms ,business - Abstract
Some Japanese exhibit facial flushing after drinking alcohol. Facial flushing was considered to be caused by acetaldehydemia. The concentration of blood acetaldehyde was concerned with the catalytic activity of acetaldehyde dehydrogenase (ALDH). Acetaldehyde dehydrogenase (ALDH)-2 polymorphism (rs671, Glu504Lys) was known to be associated with upper aerodigestive tract (UAT) cancer due to modulation of ALDH2 enzyme activity. It remains controversial whether facial flushing is useful in predicting UAT cancer risk as a surrogate marker of ALDH2 polymorphism. We conducted a case-control study to assess the risk of UAT cancer and facial flushing and ALDH2 polymorphism. Cases and controls were 585 UAT cancer patients and matched 1170 noncancer outpatients of Aichi Cancer Center Hospital. Information on facial flushing and other lifestyle factors was collected via a self-administered questionnaire. Association between facial flushing, polymorphism, and UAT cancer was assessed by odds ratios and 95% confidence intervals by using conditional logistic regression models. The facial flushing had no significant association with UAT cancer, although ALDH2 Lys allele was significantly associated with UAT cancer. No significant interaction between facial flushing and alcohol consumption was observed in this study, whereas ALDH2 Lys allele had significant association with UAT cancer. The misclassification between facial flushing and ALDH2 genotype was observed in 18% of controls with ALDH2 Glu/Glu genotype and in 16% of controls with ALDH2 Glu/Lys genotype. Facial flushing was less useful to predict UAT cancer risk than genotyping ALDH2 polymorphism.
- Published
- 2010
40. Impact of Multiple Alcohol Dehydrogenase Gene Polymorphisms on Risk of Upper Aerodigestive Tract Cancers in a Japanese Population
- Author
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Satoyo Hosono, Miki Watanabe, Katsuyuki Kiura, Keitaro Matsuo, Hidemi Ito, Shunzo Hatooka, Takeshi Suzuki, Hideo Tanaka, Kazuo Tajima, Yasuhi Yatabe, Masayuki Shinoda, Takakazu Kawase, Akio Hiraki, Yasuhisa Hasegawa, Mitsune Tanimoto, Isao Oze, and Taijiro Ozawa
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Linkage disequilibrium ,Alcohol Drinking ,Genotype ,Epidemiology ,Population ,Biology ,Cohort Studies ,Asian People ,Risk Factors ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,education ,Aged ,Neoplasm Staging ,ALDH2 ,Genetics ,education.field_of_study ,Polymorphism, Genetic ,Aldehyde Dehydrogenase, Mitochondrial ,Alcohol Dehydrogenase ,Case-control study ,ADH1B ,Cancer ,Odds ratio ,Aldehyde Dehydrogenase ,Middle Aged ,Prognosis ,medicine.disease ,Head and Neck Neoplasms ,ADH7 ,Case-Control Studies ,Female - Abstract
Alcohol intake is positively associated with the risk of upper aerodigestive tract (UAT) cancer. The genes that encode alcohol-metabolizing enzymes, primarily alcohol dehydrogenases (ADH) and aldehyde dehydrogenases (ALDH), are polymorphic. In Caucasians, significant associations between polymorphisms in ADH1B (rs1229984) and ADH1C (rs698 and rs1693482), and UAT cancer have been observed, despite strong linkage disequilibrium among them. Moreover, UAT cancer was significantly associated with rs1573496 in ADH7, and not with rs1984362 in ADH4. However, little evidence is available concerning ADH4 or ADH7 polymorphisms in Asian populations. We conducted a matched case-control study to clarify the role of ADH polymorphisms in a Japanese population. Cases and controls were 585 patients with UAT cancer and 1,170 noncancer outpatients. Genotyping for ADHs and ALDH2 was done using TaqMan assays. Associations between polymorphisms and UAT cancer were assessed by odds ratios and 95% confidence intervals using conditional logistic regression models that adjusted for age, sex, smoking, drinking, and ALDH2. Adjusted odds ratios were significant for rs4148887 and rs3805322 in ADH4, rs1229984 in ADH1B, rs698 and rs1693482 in ADH1C, and rs284787, rs1154460, and rs3737482 in ADH7. We also observed that ADH7 rs3737482 and ADH4 rs4148887 had independently and statistically significant effects on UAT cancer. The magnitude of effect of these ADH polymorphisms was greater in subjects who were heavy drinkers, heavy smokers, and had esophageal cancer. These findings show that multiple ADH gene polymorphisms were associated with UAT cancer in this Japanese population. Further studies in various ethnicities are required. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3097–102)
- Published
- 2009
41. Association of Alcohol Intake and Smoking with Malignant Lymphoma Risk in Japanese: A Hospital-Based Case-Control Study at Aichi Cancer Center
- Author
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Takeshi Suzuki, Masao Seto, Tatsuo Ichinohe, Kazuo Tajima, Keitaro Matsuo, Takakazu Kawase, Hideo Tanaka, Junya Kanda, and Yasuo Morishima
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Adolescent ,Alcohol Drinking ,Lymphoma ,Epidemiology ,Young Adult ,Japan ,Risk Factors ,Internal medicine ,medicine ,Humans ,Risk factor ,Young adult ,Aged ,Aged, 80 and over ,business.industry ,Smoking ,Case-control study ,Cancer ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Oncology ,Case-Control Studies ,Female ,business - Abstract
Given the lower incidence and differences in distribution of malignant lymphoma in Asian than western populations, the association of alcohol intake and smoking with malignant lymphoma risk in Asian populations merits investigation. Here, we conducted a sex- and age-matched case-control study of a Japanese population using two data sets, the first and second versions of the Hospital-based Epidemiological Research Program at Aichi Cancer Center Hospital (HERPACC-I and HERPACC-II, respectively), in 452 and 330 cases of histologically diagnosed malignant lymphoma and 2,260 and 1,650 noncancer controls, respectively. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using a conditional logistic regression model that incorporated smoking exposure and alcohol intake. Compared with nondrinking, consumption of ≥50 g/d by frequent drinkers was associated with significantly decreased risk in both data sets [OR (95% CI), 0.70 (0.53-0.93) for HERPACC-I and 0.40 (0.23-0.68) for HERPACC-II]. Given similar findings among groups, we used pooled data sets in subsequent analyses. For any alcohol intake versus nondrinking, point estimates of OR were less than unity for all four malignant lymphoma subtypes. In contrast, pack-years of smoking were associated with increased malignant lymphoma risk: relative to the reference (0-4 pack-years), OR (95% CI) were 1.32 (1.02-1.71), 1.39 (1.07-1.80), and 1.48 (1.12-1.95) for 5 to 19, 20 to 39, and ≥40 pack-years, respectively. This association with smoking was less apparent for all subtypes, except Hodgkin's lymphoma. In conclusion, we found that alcohol had an inverse association with malignant lymphoma risk across all malignant lymphoma subtypes in our Japanese subjects. Smoking appeared to be positively associated with malignant lymphoma risk, but this finding may vary by subtype.(Cancer Epidemiol Biomarkers Prev 2009;18(9):2436–41)
- Published
- 2009
42. Interaction of the Effects of Alcohol Drinking and Polymorphisms in Alcohol-Metabolizing Enzymes on the Risk of Female Breast Cancer in Japan
- Author
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Takakazu Kawase, Hiroji Iwata, Takeshi Suzuki, Kazuo Tajima, Keitaro Matsuo, Akio Hiraki, Hideo Tanaka, and Miki Watanabe
- Subjects
Oncology ,Adult ,Pathology ,medicine.medical_specialty ,Alcohol Drinking ,Epidemiology ,Health Status ,Breast Neoplasms ,medicine.disease_cause ,polymorphisms in alcohol-metabolizing enzyme genes ,Breast cancer ,breast cancer ,Japan ,Risk Factors ,Internal medicine ,medicine ,Humans ,Risk factor ,ALDH2 ,Alcohol dehydrogenase ,Cancer ,Aged ,Polymorphism, Genetic ,biology ,Ethanol ,business.industry ,Aldehyde Dehydrogenase, Mitochondrial ,Case-control study ,Alcohol Dehydrogenase ,ADH1B ,case–control study ,General Medicine ,Aldehyde Dehydrogenase ,Middle Aged ,medicine.disease ,Case-Control Studies ,biology.protein ,Original Article ,Female ,business ,Carcinogenesis ,acetaldehyde - Abstract
Background: Epidemiological studies consistently indicate that alcoholic beverages are an independent risk factor for female breast cancer. Although the mechanism underlying this effect remains unknown, the predominant hypothesis implicates mutagenesis via the ethanol metabolite acetaldehyde, whose impact on the carcinogenesis of several types of cancer has been shown in both experimental models and molecular epidemiological studies. Many of the epidemiological studies have investigated genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) His48Arg and aldehyde dehydrogenase-2 (ALDH2) Glu504Lys, because of the strong impact these polymorphisms have on exposure to and accumulation of acetaldehyde. With regard to breast cancer, however, evidence is scarce.Methods: To clarify the impact on female breast cancer risk of the interaction of the effects of alcohol consumption and polymorphisms in the alcohol-metabolizing enzymes ADH1B and ALDH2, we conducted a case–control study of 456 newly and histologically diagnosed breast cancer cases and 912 age- and menopausal status-matched noncancer controls. Gene–gene and gene–environment interactions between individual and combined ADH1B and ALDH2 gene polymorphisms and alcohol consumption were evaluated.Results: Despite sufficient statistical power, there was no significant impact of ADH1B and ALDH2 on the risk of breast cancer. Neither was there any significant gene–environment interactions between alcohol drinking and polymorphisms in ADH1B and ALDH2.Conclusions: Our findings do not support the hypothesis that acetaldehyde is the main contributor to the carcinogenesis of alcohol-induced breast cancer.
- Published
- 2009
43. Alcohol Drinking and One-Carbon Metabolism-Related Gene Polymorphisms on Pancreatic Cancer Risk
- Author
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Takeshi Suzuki, Miki Watanabe, Takakazu Kawase, Tsuneya Nakamura, Hideo Tanaka, Nobumasa Mizuno, Keitaro Matsuo, Akira Sawaki, Kenji Yamao, Kazuo Tajima, and Akio Hiraki
- Subjects
Adult ,Male ,Risk ,medicine.medical_specialty ,Pancreatic disease ,Alcohol Drinking ,Genotype ,Epidemiology ,5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ,Gastroenterology ,Japan ,Internal medicine ,Pancreatic cancer ,medicine ,Humans ,Methylenetetrahydrofolate Reductase (NADPH2) ,Aged ,Chi-Square Distribution ,Polymorphism, Genetic ,biology ,business.industry ,Cancer ,Thymidylate Synthase ,Odds ratio ,(Methionine synthase) reductase ,Middle Aged ,medicine.disease ,MTRR ,Ferredoxin-NADP Reductase ,Pancreatic Neoplasms ,Logistic Models ,Endocrinology ,Oncology ,Case-Control Studies ,Methylenetetrahydrofolate reductase ,biology.protein ,Female ,business - Abstract
Effect of alcohol consumption on pancreatic cancer risk has been investigated in many studies, but results have been inconsistent. We conducted a case-control study to assess the effect of alcohol on pancreatic cancer in conjunction with polymorphisms in one-carbon metabolism enzymes, methylenetetrahydrofolate reductase (MTHFR C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), and thymidylate synthase (TS) variable number of tandem repeat. A total of 157 pancreatic cancer patients and 785 age- and sex- matched control subjects were genotyped for polymorphisms. Odds ratios (OR) with 95% confidence intervals (95% CI) were estimated using unconditional logistic models adjusted for potential confounders. Heavy alcohol drinking was marginally associated with an increased risk of pancreatic cancer (OR, 1.90; 95% CI, 1.00-3.62). None of the polymorphisms showed any significant effect on pancreatic cancer risk by genotype alone. In stratified analysis, effect of alcohol consumption on pancreatic cancer was observed in individuals with the MTHFR 667 CC, MTR 2756 AA, or MTRR 66 G allele. OR (95% CI) of pancreatic cancer for heavy drinkers compared with never drinkers was 4.50 (1.44-14.05) in the MTHFR 667 CC genotype, 2.65 (1.17-6.00) in the MTR 2756 AA genotype, and 3.35 (1.34-8.36) in the MTRR 66 G allele carriers. These results suggest that the folate-related enzyme polymorphism modifies the association between drinking habit and pancreatic cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2742–7)
- Published
- 2008
44. Anthropometric factors at age 20 years and risk of thyroid cancer
- Author
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Yasuhisa Hasegawa, Hideo Tanaka, Keitaro Matsuo, Akio Hiraki, Takakazu Kawase, Kazuo Tajima, and Takeshi Suzuki
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Weight Gain ,Body Mass Index ,Young Adult ,Risk Factors ,Surveys and Questionnaires ,Internal medicine ,Adenocarcinoma, Follicular ,Confidence Intervals ,Odds Ratio ,medicine ,Humans ,Thyroid Neoplasms ,Young adult ,Thyroid cancer ,Body surface area ,Obstetrics ,business.industry ,Body Weight ,Reproducibility of Results ,Odds ratio ,Anthropometry ,medicine.disease ,Body Height ,Carcinoma, Papillary ,Confidence interval ,Logistic Models ,Endocrinology ,Oncology ,Case-Control Studies ,Female ,medicine.symptom ,business ,Body mass index ,Weight gain - Abstract
Effect of anthropometric factors at adolescence and the change since young age on thyroid cancer risk is unclear. Here, we conducted a case-control study to investigate the association between anthropometric factors at the time of diagnosis and age 20 years and risk of thyroid cancer. A total of 173 patients with thyroid cancer (papillary carcinoma, n = 167 and follicular carcinoma, n = 6) and 865 age- and sex-matched controls were included. Anthropometric factors were assessed using a validated self-administered questionnaire and categorized into three groups. Odd ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional logistic models adjusted for potential confounders. Results showed a positive association between current weights, weight at age 20 years and height, and thyroid cancer risk. Adjusted ORs in the top tertiles were 2.46 (95% CI, 1.54-3.94; trend p \ 0.001) for current weight, 2.69 (95% CI, 1.71-4.25; trend p \ 0.001) for weight at age 20 years and 2.44 (95% CI, 1.52-3.93; trend p \ 0.001) for height compared with the lowest tertile. A positive association with current body surface area (BSA), BSA at age 20 years, and current body mass index was also observed, with respective adjusted ORs in the top tertile of 1.96 (95% CI, 1.23-3.11; trend p = 0.007), 1.82 (95% CI, 1.15-2.88; trend p = 0.007) and 1.71 (95% CI, 1.06-2.78; trend p = 0.034). In contrast, no association with risk was seen for a change in anthropometric factors since age 20 years. These findings suggested that body size in early life as well as in adult is associated with an increased risk of thyroid cancer.
- Published
- 2008
45. Teeth Loss and Risk of Cancer at 14 Common Sites in Japanese
- Author
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Keitaro Matsuo, Takakazu Kawase, Takeshi Suzuki, Kazuo Tajima, and Akio Hiraki
- Subjects
Adult ,Male ,medicine.medical_specialty ,Lung Neoplasms ,Esophageal Neoplasms ,Epidemiology ,Dentistry ,Tooth Loss ,Japan ,Risk Factors ,Neoplasms ,Internal medicine ,Tooth loss ,Humans ,Medicine ,Aged ,Chi-Square Distribution ,business.industry ,Incidence ,Incidence (epidemiology) ,Confounding ,Case-control study ,Cancer ,Confounding Factors, Epidemiologic ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Logistic Models ,Oncology ,Head and Neck Neoplasms ,Case-Control Studies ,Female ,medicine.symptom ,business ,Chi-squared distribution - Abstract
Background: Tooth loss has been associated with a higher risk of several types of cancer. To clarify the significance of tooth loss to the risk of 14 common cancers, we conducted a large-scale, case-control study based on the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Methods: A total of 5,240 cancer subjects and 10,480 age- and sex-matched noncancer controls were recruited. Patients with 14 types of cancer newly diagnosed from 2000 to 2005 were eligible as case subjects, and new outpatients without cancer in the same time period were eligible as controls. Tooth loss was categorized into four groups: group 1, number of remaining teeth, ≥21; group 2, 9 to 20; group 3, 1 to 8; and group 4, 0. The effect of tooth loss was assessed as odds ratios (OR) with 95% confidence intervals (95% CI) calculated with conditional logistic regression models, with adjustment for potential confounders. Results: A decreased number of remaining teeth was associated with increased OR of head and neck (OR, 1.68; 95% CI, 0.88-1.93; Ptrend = 0.055), esophageal (OR, 2.36; 95% CI, 1.17-4.75; Ptrend = 0.002), and lung (OR, 1.54; 95% CI, 1.05-2.27; Ptrend = 0.027) cancers. Conclusions: We showed a significant positive association between tooth loss and the risk of head and neck, esophageal, and lung cancers after adjustment for potential confounding factors. The findings indicate that preventive efforts aimed at the preservation of teeth may decrease the risk of these cancers. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1222–7)
- Published
- 2008
46. One-carbon metabolism-related gene polymorphisms and risk of breast cancer
- Author
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Takeshi Suzuki, Keitaro Matsuo, Akio Hiraki, Kaoru Hirose, Miki Watanabe, Hiroji Iwata, Takakazu Kawase, Toshinari Yamashita, and Kazuo Tajima
- Subjects
Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Genotype ,Breast Neoplasms ,5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ,Folic Acid ,Breast cancer ,Japan ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Methylenetetrahydrofolate Reductase (NADPH2) ,Aged ,Polymorphism, Genetic ,biology ,Cancer ,Thymidylate Synthase ,General Medicine ,(Methionine synthase) reductase ,Environmental exposure ,Middle Aged ,medicine.disease ,MTRR ,Ferredoxin-NADP Reductase ,Endocrinology ,Methylenetetrahydrofolate reductase ,biology.protein ,Female ,Breast disease - Abstract
Environmental exposures and/or genetic background in Japanese population, which might contribute to the relatively low breast cancer incidence rates in Japan, have not been clarified in detail. Folate plays an essential role in DNA methylation and synthesis, and thus may be involved in the development of breast cancer. Functional polymorphisms in genes encoding one-carbon metabolism enzymes, methylenetetrahydrofolate reductase (MTHFR C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G) and thymidylate synthase (TS), influence folate metabolism, but epidemiological studies have yielded inconsistent findings. We therefore conducted a case-control study to clarify their associations with breast cancer risk. A total of 456 breast cancer cases and 912 age-matched and menopausal status-matched non-cancer controls were genotyped for the polymorphisms. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional logistic models adjusted for potential confounders and gene-environment interactions between the polymorphisms and folate consumption were also evaluated. We observed an increased risk of postmenopausal breast cancer with the MTHFR 677TT genotype (OR = 1.83, 95% CI: 1.08-3.11) with a menopausal status-based analysis. In combination analysis, a significantly elevated OR was found among postmenopausal women with the MTHFR 677TT genotype and lower intake of dietary folate compared with those with 677CC genotype and adequate folate consumption (OR = 2.80, 95% CI: 1.11-7.07). In addition, interaction between the MTRR A66G polymorphism and folate intake for risk of postmenopausal breast cancer was observed (interaction P = 0.008). Our findings indicated that the MTHFR and MTRR polymorphisms were associated with individual susceptibility to breast cancer among postmenopausal women.
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- 2008
47. High-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease and implication for its molecular mechanism
- Author
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Koichi Kashiwase, Yasuo Morishima, Takehiko Sasazuki, Yoshihisa Kodera, Takakazu Kawase, Shunichi Kato, Hidetoshi Inoko, Keitaro Matsuo, Hiroh Saji, and Takeo Juji
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Adult ,Male ,Models, Molecular ,medicine.medical_specialty ,Immunology ,Graft vs Host Disease ,Disease ,Human leukocyte antigen ,Biology ,Biochemistry ,HLA Antigens ,Risk Factors ,immune system diseases ,Immunopathology ,Internal medicine ,medicine ,Humans ,Amino Acids ,Allele ,Alleles ,Genetics ,Hematology ,Cell Biology ,medicine.disease ,Protein Structure, Tertiary ,Histocompatibility ,Survival Rate ,Transplantation ,Graft-versus-host disease ,Acute Disease ,Female - Abstract
In allogenic hematopoietic stem-cell transplantation, an effect of HLA locus mismatch in allele level on clinical outcome has been clarified. However, the effect of each HLA allele mismatch combination is little known, and its molecular mechanism to induce acute graft-versus-host disease (aGVHD) remains to be elucidated. A total of 5210 donor-patient pairs who underwent transplantation through Japan Marrow Donor Program were analyzed. All HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles were retrospectively typed in all pairs. The impacts of the HLA allele mismatch combinations and amino acid substitution positions in 6 HLA loci on severe aGVHD were analyzed. A total of 15 significant high-risk HLA allele mismatch combinations and 1 HLA-DRB1-DQB1 linked mismatch combinations (high-risk mismatch) for severe aGVHD were identified, and the number of high-risk mismatches was highly associated with the occurrence of severe aGVHD regardless of the presence of mismatch combinations other than high-risk mismatch. Furthermore, 6 specific amino acid substitution positions in HLA class I were identified as those responsible for severe aGVHD. These findings provide evidence to elucidate the mechanism of aGVHD on the basis of HLA molecule. Furthermore, the identification of high-risk mismatch, that is, nonpermissive mismatch, would be beneficial for the selection of a suitable donor.
- Published
- 2007
48. Alternative splicing due to an intronic SNP in HMSD generates a novel minor histocompatibility antigen
- Author
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Koichi Miyamura, Hiroki Torikai, Mikinori Miyazaki, Kunio Tsujimura, Satoko Morishima, Yoshihisa Kodera, Yasuo Morishima, Toshitada Takahashi, Kiyotaka Kuzushima, Takakazu Kawase, Akane Tsujimura, Yoshiki Akatsuka, Akira Oka, Hidetoshi Inoko, and Seishi Ogawa
- Subjects
DNA, Complementary ,Immunology ,Epitopes, T-Lymphocyte ,Mice, SCID ,Human leukocyte antigen ,Biology ,Polymorphism, Single Nucleotide ,Biochemistry ,Epitope ,HLA-B44 Antigen ,Minor Histocompatibility Antigens ,Mice ,Antigen ,Mice, Inbred NOD ,Cell Line, Tumor ,Minor histocompatibility antigen ,Animals ,Humans ,Cytotoxic T cell ,Myeloid leukemia ,Cell Biology ,Hematology ,Molecular biology ,Alternative Splicing ,Haematopoiesis ,CTL ,HLA-B Antigens ,Leukemia, Myeloid ,Neoplastic Stem Cells ,Immunotherapy ,RNA Splice Sites ,T-Lymphocytes, Cytotoxic - Abstract
Here we report the identification of a novel human leukocyte antigen (HLA)-B44–restricted minor histocompatibility antigen (mHA) with expression limited to hematopoietic cells. cDNA expression cloning studies demonstrated that the cytotoxic T lymphocyte (CTL) epitope of interest was encoded by a novel allelic splice variant of HMSD, hereafter designated as HMSD-v. The immunogenicity of the epitope was generated by differential protein expression due to alternative splicing, which was completely controlled by 1 intronic single-nucleotide polymorphism located in the consensus 5′ splice site adjacent to an exon. Both HMSD-v and HMSD transcripts were selectively expressed at higher levels in mature dendritic cells and primary leukemia cells, especially those of myeloid lineage. Engraftment of mHA+ myeloid leukemia stem cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID)/γcnull mice was completely inhibited by in vitro preincubation with the mHA-specific CTL clone, suggesting that this mHA is expressed on leukemic stem cells. The patient from whom the CTL clone was isolated demonstrated a significant increase of the mHA-specific T cells in posttransplantation peripheral blood, whereas mHA-specific T cells were undetectable in pretransplantation peripheral blood and in peripheral blood from his donor. These findings suggest that the HMSD–v–encoded mHA (designated ACC-6) could serve as a target antigen for immunotherapy against hematologic malignancies.
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- 2007
49. Primary Hepatic Follicular Lymphoma: A Case Report and Discussion of Chemotherapy and Favorable Outcomes
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Yoshitoyo Kagami, Takashi Oyama, Harumi Kato, Hirofumi Taji, Aya Ohshiro, Shigeo Nakamura, Yoshikazu Kamiya, Yasuo Morishima, Takakazu Kawase, Hiroshi Gomyo, and Michinori Ogura
- Subjects
Adult ,medicine.medical_specialty ,Vincristine ,Pathology ,Cyclophosphamide ,medicine.medical_treatment ,Follicular lymphoma ,Antibodies, Monoclonal, Murine-Derived ,immune system diseases ,Prednisone ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Cholecystitis ,medicine ,Humans ,Lymphoma, Follicular ,Aged ,Chemotherapy ,business.industry ,Liver Neoplasms ,Remission Induction ,Antibodies, Monoclonal ,General Medicine ,medicine.disease ,Immunohistochemistry ,Magnetic Resonance Imaging ,Lymphoma ,Doxorubicin ,Female ,Rituximab ,Radiology ,business ,Generalized lymphadenopathy ,medicine.drug - Abstract
This report concerns a rare case of follicular lymphoma with features suggestive of primary hepatic lymphoma. At the disease onset, multiple nodular lesions in the liver and small para-aortic nodes were detected by abdominal magnetic resonance imaging without generalized lymphadenopathy. After careful observation for three months, lymphadenopathy was observed in the right occipital, para-aortic, and bilateral inguinal regions. The patient was treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) and achieved complete remission for more than 2 years. To the best of our knowledge, this is the ninth report of primary hepatic follicular lymphoma. Insufficient cases have been reported to determine the long-term outcome and clinical characteristics of primary hepatic follicular lymphoma. However, it seems that patients with primary hepatic follicular lymphoma that are treated with appropriate chemotherapy with or without surgical resection have favorable outcomes.
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- 2007
50. Allogeneic Bone Marrow Transplantation from Unrelated Human T-Cell Leukemia Virus-I–negative Donors for Adult T-Cell Leukemia/Lymphoma: Retrospective Analysis of Data from the Japan Marrow Donor Program
- Author
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Yasuo Morishima, Tsuyoshi Muta, Yoshihisa Kodera, Atae Utsunomiya, Mine Harada, Tetsuya Eto, Hisashi Gondo, Takakazu Kawase, Koji Kato, Tsunefumi Shibuya, Shuichi Taniguchi, Yoshinobu Kanda, and Shunichi Kato
- Subjects
Oncology ,Adult ,Male ,Unrelated donor ,medicine.medical_specialty ,medicine.medical_treatment ,Graft vs Host Disease ,Graft vs Leukemia Effect ,Hematopoietic stem cell transplantation ,Adult T-cell leukemia/lymphoma ,Japan ,Graft-versus-adult T-cell leukemia/lymphoma ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Humans ,Leukemia-Lymphoma, Adult T-Cell ,Transplantation, Homologous ,Cumulative incidence ,Survival analysis ,Bone Marrow Transplantation ,Retrospective Studies ,Human T-lymphotropic virus 1 ,Transplantation ,biology ,business.industry ,Graft Survival ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,biology.organism_classification ,Survival Analysis ,Lymphoma ,Leukemia ,Allogeneic hematopoietic stem cell transplantation ,Immunology ,Female ,business - Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an HLA-matched related donor has been suggested to improve the poor prognosis of adult T-cell leukemia/lymphoma (ATLL). However, the infusion of HTLV-I–infected cells from HTLV-I–positive related donors could lead to the development of donor-derived ATLL under immunosuppressive conditions. Although most ATLL patients lack a suitable HLA-matched related donor and require an HTLV-I–negative unrelated donor, little information is currently available regarding the outcome of unrelated bone marrow transplantation (UBMT) for ATLL. To evaluate the role of UBMT in treating ATLL, we retrospectively analyzed data from 33 patients with ATLL treated by UBMT through the Japan Marrow Donor Program (JMDP). Overall survival (OS), progression-free survival, and cumulative incidence of disease progression and progression-free mortality at 1 year after UBMT were 49.5%, 49.2%, 18.6%, and 32.3%, respectively. Multivariate analysis identified recipient age as an independent prognostic factor for OS (P = .044). Patients age ≥50 years who showed nonremission at transplantation tended to have higher rates of treatment-related mortality. Our observations suggest that UBMT could represent a feasible treatment option for ATLL patients and warrant further investigation based on these risk factors.
- Published
- 2007
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