Faculty Profiles - MAEDA Yoshinobu

Histological and immunohistochemical features of gingival enlargement in a patient with AML

Norihiro Sonoi, Yoshihiko Soga, Hiroshi Maeda, Koichi Ichimura, Tadashi Yoshino, Kazutoshi Aoyama, Nobuharu Fujii, Yoshinobu Maeda, Mitsune Tanimoto, Richard Logan, Judith Raber-Durlacher, Shogo Takashiba

ODONTOLOGY 100 ( 2 ) 254 - 257 2012.7

Language：English Publisher：SPRINGER

Here, we discuss the pathophysiology of leukemia-associated gingival enlargement based on a case of acute myelomonocytic leukemia (AML-M4) with typical gingival enlargement. Uniquely, this patient was well enough to allow full periodontal examination and incisional gingival biopsy to be performed both before and after chemotherapy. The patient was a 39-year-old Japanese woman with AML-M4 showing gingival enlargement. Histological and immunohistochemical features of gingiva and bacterial counts in the periodontal pockets were examined before and after chemotherapy. The results were as follows: (1) infiltration of myelomonocytic blasts in enlarged gingiva; (2) resolution of gingival enlargement with complete remission of AML by anticancer chemotherapy; and (3) the numbers of bacteria in the periodontal pockets were not high and were not altered before or after chemotherapy. In patients with AML-M4, remarkable mucosal enlargement is not generally observed in the body except in the gingiva. We hypothesized that antigens derived from periodontal bacteria, even if they are not present in large numbers, could act as chemoattractants for myelomonocytic leukemic cells.

DOI： 10.1007/s10266-011-0051-0

中枢神経原発悪性リンパ腫に対する自己末梢血幹細胞移植併用大量化学療法

縦隔原発悪性リンパ腫に対しRituximab併用DA-EPOCH療法を施行した2症例

吉岡尚徳, 藤原英晃, 淺野豪, 廻勇輔, 黒井大雅, 長谷川詠子, 松岡賢市, 藤井伸治, 近藤英生, 前田嘉信, 品川克至, 吉野正, 谷本光音

日本リンパ網内系学会会誌 52 124 - 124 2012.5

近藤英生, 廻勇輔, 浅野豪, 吉岡尚徳, 松岡賢市, 淺田騰, 藤井敬子, 藤井伸治, 黒住和彦, 市川智継, 前田嘉信, 品川克至, 谷本光音

日本造血細胞移植学会総会プログラム・抄録集 34th 258 2012.2

同種移植後のサイトメガロウイルス抗原血症が急性骨髄性白血病の再発に及ぼす影響

吉田将平, 近藤英生, 浅野豪, 廻勇輔, 吉岡尚徳, 西之原正昭, 藤原英晃, 岡本幸代, 淺田騰, 西森久和, 藤井敬子, 松岡賢市, 藤井伸治, 前田嘉信, 品川克至, 谷本光音

日本造血細胞移植学会総会プログラム・抄録集 34th 208 2012.2

Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17 International journal

Hisakazu Nishimori, Yoshinobu Maeda, Takanori Teshima, Haruko Sugiyama, Koichiro Kobayashi, Yoshiko Yamasuji, Sachiyo Kadohisa, Hidetaka Uryu, Kengo Takeuchi, Takehiro Tanaka, Tadashi Yoshino, Yoichiro Iwakura, Mitsune Tanimoto

BLOOD 119 ( 1 ) 285 - 295 2012.1

Language：English Publisher：AMER SOC HEMATOLOGY

Chronic GVHD (cGVHD) is a main cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the roles of Th subsets in cGVHD with the use of a well-defined mouse model of cGVHD. In this model, development of cGVHD was associated with up-regulated Th1, Th2, and Th17 responses. Th1 and Th2 responses were up-regulated early after BM transplantation, followed by a subsequent up-regulation of Th17 cells. Significantly greater numbers of Th17 cells were infiltrated in the lung and liver from allogeneic recipients than those from syngeneic recipients. We then evaluated the roles of Th1 and Th17 in cGVHD with the use of IFN-gamma-deficient and IL-17-deficient mice as donors. Infusion of IFN-gamma(-/-) or IL-17(-/-) T cells attenuated cGVHD in the skin and salivary glands. Am80, a potent synthetic retinoid, regulated both Th1 and Th17 responses as well as TGF-beta expression in the skin, resulting in an attenuation of cutaneous cGVHD. These results suggest that Th1 and Th17 contribute to the development of cGVHD and that targeting Th1 and Th17 may therefore represent a promising therapeutic strategy for preventing and treating cGVHD. (Blood. 2012; 119(1): 285-295)

DOI： 10.1182/blood-2011-01-332478

合成レチノイドAm80はTh1とTh17を抑制することにより慢性移植片対宿主病を改善する

西森久和, 前田嘉信, 谷本光音

血液・腫瘍内科 124 ( 3 ) 197 - 201 2012

Am80による慢性GVHDの治療効果と作用機序.

西森久和, 前田嘉信, 谷本光音

血液・腫瘍内科 65 ( 2 ) 223 - 230 2012

造血細胞移植による口腔粘膜障害のハイリスク因子の検討

佐桑奈々絵, 高橋郁名代, 村山夢乃, 西本仁美, 杉浦裕子, 曽我賢彦, 前田嘉信

日本造血細胞移植学会総会プログラム・抄録集 34th 2012

Germinal center B-cell-like diffuse large B-cell lymphoma of the duodenum is associated with t(14;18) translocation International journal

Maiko Tamura, Katsuyoshi Takata, Yasuharu Sato, Naoya Nakamura, Yara Yukie Kikuti, Koichi Ichimura, Takehiro Tanaka, Akira Tari, Yoshinobu Maeda, Mitsune Tanimoto, Hiroyuki Okada, Tadashi Yoshino

PATHOLOGY INTERNATIONAL 61 ( 12 ) 742 - 748 2011.12

Language：English Publisher：WILEY-BLACKWELL

Diffuse large B-cell lymphoma (DLBCL) rarely involves the duodenum, and its clinicopathological characteristics have not been well elucidated. We performed clinicopathological examinations and identified 15 patients with duodenal DLBCL using 18 gastric or colonic DLBCL as a control. Eleven of the 15 patients (73%) were subclassified by immunohistochemical analysis according to the Choi algorithm as germinal center B-cell-like (GCB) type, whereas the 18 control gastric and colonic DLBCL were predominantly subclassified as activated B-cell-like (ABC) type. The classifications according to organ involvement were statistically significant (P= 0.011 and P= 0.035). Macroscopically, the GCB lesions were varied, while all ABC lesions were ulcerative. Fluorescence in situ hybridization analysis revealed a higher frequency of t(14;18) translocation in patients with duodenal DLBCL (3 of 13) as compared with non-duodenal gastrointestinal tract DLBCL (0 of 18), however, the difference was not significant (P = 0.064). Furthermore, the three patients with t(14;18) translocations were classified as GCB. In addition, overall survival of patients was statistically different between those with and without t(14;18) translocation (P= 0.040). In conclusion, duodenal DLBCL predominantly exhibits GCB-type tumors and the frequency of t(14;18) translocation appears to be higher in duodenal GCB-type DLBCL compared to non-duodenal tumors.

DOI： 10.1111/j.1440-1827.2011.02748.x

Nodal follicular lymphoma without complete follicular dendritic cell networks is related to localized clinical stage International journal

Wei Cui, Lisha Che, Yasuharu Sato, Xingang Huang, Katsuyoshi Takata, Yorihisa Orita, Naoe Goto, Yoshinobu Maeda, Mitsune Tanimoto, Tadashi Yoshino

PATHOLOGY INTERNATIONAL 61 ( 12 ) 737 - 741 2011.12

Language：English Publisher：WILEY-BLACKWELL

Follicular lymphoma is the most common low-grade lymphoma and it frequently presents with a systemic disease, often showing advanced clinical stage (III/IV). The lymphoma cells are usually growing associated with follicular dendritic cell (FDC) networks. Abnormal FDC networks have been reported in duodenal follicular lymphoma, in which cases exhibit lower clinical stages than the nodal cases. In the present study, we analyzed the FDC network distribution pattern of 242 nodal follicular lymphomas by immunohistochemistry. Out of the 242 cases, 27 cases (11%) demonstrated an atypical pattern of FDC networks, in which the CD21 staining totally or partially disappeared in the neoplastic follicles. Furthermore, we compared the clinical data of these 27 cases and 58 typical FDC network cases of follicular lymphoma. We found that in the typical cases, 52 out of 58 patients (90%) showed advanced clinical stage (III or IV), whereas 10 of 27 (37%) atypical FDC network cases showed localized clinical stage (I or II) (P < 0.01). In conclusion, nodal follicular lymphoma with total loss or partially disrupted FDC networks therefore show a lower clinical stage.

DOI： 10.1111/j.1440-1827.2011.02736.x

Successful Extracorporeal Life Support for Life-threatening Hypercapnia with Bronchiolitis Obliterans after Allogeneic Hematopoietic Stem Cell Transplantation

Koichi Waseda, Yasushi Tanimoto, Shingo Ichiba, Nobuaki Miyahara, Toshi Murakami, Nobuaki Ochi, Michihisa Terado, Osamu Nagano, Yoshinobu Maeda, Arihiko Kanehiro, Yoshihito Ujike, Mitsune Tanimoto

ACTA MEDICA OKAYAMA 65 ( 6 ) 403 - 406 2011.12

Language：English Publisher：OKAYAMA UNIV MED SCHOOL

Bronchiolitis obliterans (BO) is a disease with a poor prognosis, and a key factor that limits long-term survival after allogeneic hematopoietic stem cell transplantation (HSCT). We here report a case of a 31-year woman with acute lymphatic leukemia, which was treated by chemotherapy and HSCT, and consequently developed BO 2 years after HSCT. A non-tuberculous mycobacterial infection occurred and showed gradual exacerbation. She started taking anti-mycobacterial drugs, but lost appetite, felt tired and finally lost consciousness one month after beginning medication. Arterial blood gas revealed marked hypercapnia. Using extracorporeal life support (ECLS), the carbon dioxide concentration was reduced and her consciousness recovered. To our knowledge, this is the first case in which ECLS was successfully used for hypercapnia in a patient with BO.

Phase II Study of SMILE Chemotherapy for Newly Diagnosed Stage IV, Relapsed, or Refractory Extranodal Natural Killer (NK)/T-Cell Lymphoma, Nasal Type: The NK-Cell Tumor Study Group Study International journal

Motoko Yamaguchi, Yok-Lam Kwong, Won Seog Kim, Yoshinobu Maeda, Chizuko Hashimoto, Cheolwon Suh, Koji Izutsu, Fumihiro Ishida, Yasushi Isobe, Eisaburo Sueoka, Junji Suzumiya, Takao Kodama, Hiroshi Kimura, Rie Hyo, Shigeo Nakamura, Kazuo Oshimi, Ritsuro Suzuki

JOURNAL OF CLINICAL ONCOLOGY 29 ( 33 ) 4410 - 4416 2011.11

Language：English Publisher：AMER SOC CLINICAL ONCOLOGY

Purpose
To explore a more effective treatment for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer/T-cell lymphoma, nasal type (ENKL), we conducted a phase II study of the steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) regimen.
Patients and Methods
Patients with newly diagnosed stage IV, relapsed, or refractory disease and a performance status of 0 to 2 were eligible. Two cycles of SMILE chemotherapy were administered as the protocol treatment. The primary end point was the overall response rate (ORR) after the protocol treatment.
Results
A total of 38 eligible patients were enrolled. The median age was 47 years (range, 16 to 67 years), and the male: female ratio was 21:17. The disease status was newly diagnosed stage IV in 20 patients, first relapse in 14 patients, and primary refractory in four patients. The eligibility was revised to include lymphocyte counts of 500/mu L or more because the first two patients died from infections. No treatment-related deaths were observed after the revision. The ORR and complete response rate after two cycles of SMILE chemotherapy were 79% (90% CI, 65% to 89%) and 45%, respectively. In the 28 patients who completed the protocol treatment, 19 underwent hematopoietic stem-cell transplantation. The 1-year overall survival rate was 55% (95% CI, 38% to 69%). Grade 4 neutropenia was observed in 92% of the patients. The most common grade 3 or 4 nonhematologic complication was infection (61%).
Conclusion
SMILE chemotherapy is an effective treatment for newly diagnosed stage IV, relapsed or refractory ENKL. Myelosuppression and infection during the treatment should be carefully managed.

DOI： 10.1200/JCO.2011.35.6287

Cyclin D2 is overexpressed in proliferation centers of chronic lymphocytic leukemia/small lymphocytic lymphoma International journal

Takuro Igawa, Yasuharu Sato, Katsuyoshi Takata, Soichiro Fushimi, Maiko Tamura, Naoya Nakamura, Yoshinobu Maeda, Yorihisa Orita, Mitsune Tanimoto, Tadashi Yoshino

CANCER SCIENCE 102 ( 11 ) 2103 - 2107 2011.11

Language：English Publisher：WILEY-BLACKWELL

The D cyclins are important cell cycle regulatory proteins involved in the pathogenesis of some lymphomas. Cyclin D1 overexpression is a hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 have not been shown to be closely associated with any particular subtype of lymphoma. In the present study, we found that cyclin D2 was specifically overexpressed in the proliferation centers (PC) of all cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) examined (19/19). To examine the molecular mechanisms underlying this overexpression, we immunohistochemically examined the expression of nuclear factor (NF)-kappa B, p15, p16, p18, and p27 in the PC of six patients. Five cases showed upregulation of NF-kappa B expression, which is known to directly induce cyclin D2 by binding to the promoter region of CCND2. All six PC examined demonstrated downregulation of p27 expression. In contrast, upregulation of p15 expression was detected in five of six PC examined. This discrepancy suggests that unknown cell cycle regulatory mechanisms involving NF-kappa B-related pathways are also involved, because NF-kappa B upregulates cyclin D2 not only directly, but also indirectly through c-Myc, which is believed to downregulate both p27 and p15. In conclusion, cyclin D2 is overexpressed in the PC of CLL/SLL and this overexpression is due, in part, to the upregulation of NF-kappa B-related pathways. (Cancer Sci 2011; 102: 2103-2107)

DOI： 10.1111/j.1349-7006.2011.02046.x

Prevention of Idiopathic Pneumonia Syndrome by Intra-Bone Marrow Injection of Donor Cells

Yoshiko Yamasuji, Hisakazu Nishimori, Haruko Sugiyama, Koichiro Kobayashi, Sachiyo Okamoto, Eisei Kondo, Nobuharu Fujii, Katsuji Shinagawa, Takuro Kanekura, Mitsune Tanimoto, Yoshinobu Maeda

BLOOD 118 ( 21 ) 830 - 830 2011.11

非B非C肝炎ウイルスによる肝障害非B非C肝炎ウイルスによる急性肝障害の実態

高木章乃夫, 前田嘉信, 山下信子

肝臓 52 ( Suppl.2 ) A549 - A549 2011.9

同種造血細胞移植後の閉塞性細気管支炎岡山BMTグループ3施設での経験

藤井伸治, 中瀬浩一, 朝倉昇司, 原嘉孝, 松岡賢市, 近藤英生, 前田嘉信, 名和由一郎, 角南一貴, 品川克至, 池田和眞, 原雅道, 谷本光音

臨床血液 52 ( 9 ) 1108 - 1108 2011.9

中枢神経系悪性リンパ腫に対する自己末梢血幹細胞移植併用大量化学療法

近藤英生, 市川智継, 前田嘉信, 黒川和彦, 青山一利, 吉田将平, 原嘉孝, 新谷大悟, 西森久和, 藤井敬子, 藤井伸治, 品川克至, 谷本光音

臨床血液 52 ( 9 ) 1127 - 1127 2011.9

The utility of positron emission tomography/computed tomography in the staging of extranodal natural killer/T-cell lymphoma International journal

Hideaki Fujiwara, Yoshinobu Maeda, Yuichiro Nawa, Masayuki Yamakura, Daisuke Ennishi, Yukihiro Miyazaki, Katsuji Shinagawa, Masamichi Hara, Kosei Matsue, Mitsune Tanimoto

EUROPEAN JOURNAL OF HAEMATOLOGY 87 ( 2 ) 123 - 129 2011.8

Language：English Publisher：WILEY-BLACKWELL

Natural killer (NK)/T-cell lymphoma cases are rarely discovered using positron emission tomography/computed tomography (PET/CT). We compared the utility of PET/CT and that of conventional methods (CMs; CT with IV contrast, biopsies from primary sites, and bone marrow examinations) in the staging of extranodal NK/T-cell lymphoma. Nineteen untreated patients with extranodal NK/T-cell lymphoma at three institutions were analyzed. PET/CT and CMs were applied for initial workups following diagnosis. PET/CT and CMs were compared and evaluated for their ability to detect tumor lesions and their influence on the staging and treatment strategies. In total, 116 lesions were detected by CM and PET/CT. Using PET/CT, 108 lesions (93%) were discovered. The number of nodal lesions was 28: all were positive by PET/CT and 26 (93%) by CMs. The number of extranodal lesions was 89: 84 (94%) and 54 (61%) lesions were positive by PET/CT and CMs, respectively. PET/CT was superior to CMs in detecting cutaneous lesions [31/31 lesions (100%) vs. 20/31 lesions (65%), respectively; P = 0.042]. Bone marrow involvement was confirmed pathologically in only seven patients; four cases (57%) were positive by PET/CT. Using CMs, ten patients (53%) were stages I-II and nine (47%) were stages III-IV. Using PET/CT, eight patients (42%) were in stages I-II and 11 (58%) were in stages III-IV. PET/CT findings altered the stage and treatment strategy in two cases (11%). Our study demonstrated that PET/CT is a useful tool for detecting extranodal lesions in NK/T-cell lymphoma, particularly cutaneous lesions. PET/CT may therefore influence future staging and treatment strategies.

DOI： 10.1111/j.1600-0609.2011.01645.x