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ABSTRACT: To investigate the feasibility of double-balloon endoscopy (DBE) to detect jejunoileal lymphoma, compared with fluorodeoxyglucose positron emission tomography (FDG-PET).
Between March 2004 and January 2011, we histologically confirmed involvement of malignant lymphoma of the jejunoileum in 31 patients by DBE and biopsy. In 20 patients of them, we performed with FDG-PET. We retrospectively reviewed the records of these 20 patients. Their median age was 64 years (range 50-81). In the 20 patients, the pathological diagnosis of underlying non-Hodgkin's lymphoma (NHL) comprised follicular lymphoma (FL, n = 12), diffuse large B cell lymphoma (DLBCL, n = 4), mantle cell lymphoma (MCL, n = 2), enteropathy associated T cell lymphoma (ETL, n = 1) and anaplastic large cell lymphoma (ALCL, n = 1).
Ten cases showed accumulation by FDG-PET (50%). FDG-PET was positive in 3 of 12 FL cases (25%) while in 7 of 8 non-FL cases (88%, P < 0.05). Intestinal FL showed a significantly lower rate of positive FDG-PET, in comparison with other types of lymphoma. Cases with endoscopically elevated lesions (n = 10) showed positive FDG-PET in 2 (20%), but those with other type NHL did in 8 of 10 (80%, P < 0.05). When the cases having elevated type was compared with those not having elevated type lesion, the number of cases that showed accumulation of FDG was significantly smaller in the former than in the latter.
In a significant proportion, small intestinal involvement cannot be pointed out by FDG-PET. Especially, FL is difficult to evaluate by FDG-PET but essentially requires DBE.
World journal of gastrointestinal endoscopy. 03/2013; 5(3):111-6.
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Misaki Kawasoe,
Yasuko Yamamoto,
Katsuya Okawa,
Tadao Funato,
Mayu Takeda, Takeshi Hara,
Hisashi Tsurumi,
Hisataka Moriwaki,
Yuko Arioka,
Masao Takemura,
Hidetoshi Matsunami,
Sanford P Markey,
Kuniaki Saito
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ABSTRACT: The elucidation of drug resistance mechanisms is very important in the development of clinical therapies for the treatment of leukemia. To study the drug resistance mechanisms, protein expression profiles of 1-β-D-arabinofuranosylcytosine (AraC) sensitive K562 (K562S) cells and AraC resistant K562 (K562AC) cells were compared using two-dimensional fluorescence difference gel electrophoresis. In comparison of protein expression profiles, 2073 protein spots were found to be altered, 15 proteins of them were remarkably altered. These proteins were identified by mass spectrometry. The most differently expressed proteins were aldehyde dehydrogenase 1 family member A2 (ALDH1A2) and vimentin. Both proteins were verified using reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. ALDH1A2 protein was found to be effective in AraC resistance. ALDH1A2 knock down (KD) induced sensitivity to AraC treatment in K562AC cells, and ALDH1A2 overexpressed K562S cells acquired the AraC resistance. Further, the findings also suggest that ALDH1A2 expression is increased after the appearance of AraC resistance in clinical cases. These results will be helpful in understanding the mechanism of AraC resistance.
Experimental hematology 03/2013; · 3.11 Impact Factor
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Takashi Ibuka,
Hisashi Tsurumi,
Hiroshi Araki, Takeshi Hara,
Fumito Onogi,
Naoe Goto,
Yasushi Kojima,
Nobuhiro Kanemura,
Makoto Shiraki,
Senji Kasahara,
Masahito Shimizu,
Kengo Ogawa,
Soranobu Ninomiya,
Takayuki Nakanishi,
Tomohiro Kato,
Tsuyoshi Takami,
Hisataka Moriwaki
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ABSTRACT: Jejunoileal involvement of non-Hodgkin's lymphoma (NHL) is an important diagnostic factor in determining optimal treatment strategies. Here, we used double-balloon enteroscopy (DBE) to detect jejunoileal involvement of NHL and studied its clinical significance in a series of patients with NHL. Adults aged between 18 and 85 years with infiltration of the stomach, duodenum, or colon confirmed by gastrointestinal endoscopy or colonoscopy, suspected jejunoileal involvement determined by CT or FDG-PET, or any other gastrointestinal symptoms, were eligible for inclusion in the study. Among 428 patients with histologically confirmed NHL between 2004 and 2011, 83 were eligible for DBE, but 20 patients were excluded due to rejection or poor clinical status. Thus, 63 underwent DBE. The 3-year overall survival rate was significantly lower in patients with (n = 33), than without (n = 30) jejunoileal involvement of NHL confirmed by DBE (49 vs. 92 %, p < 0.005). Four participants developed aspiration pneumonia, but recovered after treatment with antibiotics.
International journal of hematology 02/2013; · 1.17 Impact Factor
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ABSTRACT: We describe two patients with T cell prolymphocytic leukemia (T-PLL) who exhibited the same complex karyotype, including an additional segment at 1p36.1. One presented with secondary progression following an initial stable clinical course, and the other with typically progressive disease. Features of the cerebriform variant were identified in the peripheral blood of both patients. Aggressive symptoms, such as lymphocytosis, lymphadenopathy, pleural effusion, cutaneous involvement and hepatosplenomegaly, developed during the progressive phases. Levels of serum soluble interleukin 2 receptor increased when symptoms worsened. These patients did not have the karyotypic 14q11 abnormality and trisomy 8q that are features of non-Japanese patients. The prognoses of these patients were poor; one survived for 2 months and the other survived for 10 months after progression. A chromosomal abnormality may occur in other types of aggressive T-PLL, particularly when extramedullary infiltration is a feature.
International journal of hematology 10/2012; · 1.17 Impact Factor
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International Journal of Hematology 04/2012; 74(4):475-476. · 1.27 Impact Factor
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Ichiro Yasuda,
Naoe Goto,
Hisashi Tsurumi,
Masanori Nakashima,
Shinpei Doi,
Takuji Iwashita,
Nobuhiro Kanemura,
Senji Kasahara,
Seiji Adachi, Takeshi Hara,
Masahito Shimizu,
Tsuyoshi Takami,
Hisataka Moriwaki
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ABSTRACT: In addition to morphology, immunophenotype and genetic abnormalities should be assessed during diagnosis and subclassification of lymphoproliferative disorders. The objective of this study was to evaluate the yield of endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) using a standard 19-gauge needle for diagnosis and subclassification of lymphoma, assessing the feasibility of immunohistological, flow cytometric, and cytogenetic assessments.
Two hundred forty patients with suspected lymphoma were referred for EUS-FNAB to our quaternary EUS center between June 2005 and December 2010. EUS-FNAB using a conventional 19-gauge needle was attempted for all patients, followed by histological assessments including immunohistological staining, flow cytometry, and cytogenetic analysis (G-band karyotyping). Among the patients, 152 were ultimately diagnosed with lymphoma. The primary outcome measure of this study was the sensitivity of histological assessment, including immunohistological staining, flow cytometry, and G-band karyotyping, for diagnosis and subclassification of lymphoma.
Among the 152 patients ultimately diagnosed with lymphoma, 147 patients (96.7%) were diagnosed by EUS-FNAB, and classification in accordance with the WHO (World Health Organization) system was also possible for 135 patients (88.8%) on the basis of histological findings, including immunohistological staining. Flow cytometry showed abnormal or unusual cell populations in 121 (79.6%) of the 152 patients diagnosed with lymphoma, and in 114 (90.5%) of the 126 patients diagnosed with B-cell lymphoma. Specific cytogenetic abnormalities were detected in 21 (13.8%) of the lymphoma patients.
EUS-FNAB using a standard 19-gauge needle has high diagnostic value for lymphoma. Immunophenotyping is usually possible, while cytogenetic abnormalities can be identified in a relatively limited number of patients.
The American Journal of Gastroenterology 03/2012; 107(3):397-404. · 7.28 Impact Factor
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Naoe Goto,
Hisashi Tsurumi,
Masao Takemura,
Nobuhiro Kanemura,
Senji Kasahara, Takeshi Hara,
Ichiro Yasuda,
Masahito Shimizu,
Toshiki Yamada,
Michio Sawada,
Takeshi Takahashi,
Tetsuya Yamada,
Mitsuru Seishima,
Hisataka Moriwaki,
Tsuyoshi Takami
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ABSTRACT: Since the introduction of rituximab (R), the prognosis for diffuse large B-cell lymphoma (DLBCL) has markedly improved. We evaluated the prognostic significance of serum soluble CD27 (sCD27) in 143 patients with DLBCL treated with cyclophosphamide, doxorubicin, vincristine and prednisolone plus rituximab (R-CHOP). Five-year overall survival rates for patients with sCD27≥213 U/mL or <213 U/mL were 38.7% and 76.8%, respectively (p =0.0005). Multivariate analysis revealed that serum sCD27 was significantly correlated with OS (p =0.047). Immunohistochemical staining for CD27 in lymphoma tissues revealed positive lymphoma cells in 22 cases (18.5%) and positive microenvironment T-cells in 62 cases (52.1%) and was negative in the remaining patients. In these three subgroups, median sCD27 levels were 336 U/mL, 242.6 U/mL and 109.9 U/mL, respectively (p =0.004). Thus, serum sCD27 level is associated with CD27 expression on lymphoma cells, and may be a powerful prognostic factor for DLBCL.
Leukemia & lymphoma 03/2012; 53(8):1494-500. · 2.40 Impact Factor
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Kengo Ogawa, Takeshi Hara,
Masahito Shimizu,
Soranobu Ninomiya,
Junji Nagano,
Hiroyasu Sakai,
Masato Hoshi,
Hiroyasu Ito,
Hisashi Tsurumi,
Kuniaki Saito,
Mitsuru Seishima,
Takuji Tanaka,
Hisataka Moriwaki
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ABSTRACT: The escape of preneoplastic cells from the immune system, which is caused by immune tolerance, occurs during the development of several types of tumors. Indoleamine 2,3-dioxygenase (IDO) plays a critical role in the induction of immune tolerance. In the present study we investigated the effects of 1-methyltryptophan (1-MT), an IDO inhibitor, and (-)-epigallocatechin gallate (EGCG), the major catechin in green tea, on the development of azoxymethane (AOM)-induced colonic preneoplastic lesions by focusing on the inhibition of IDO. To induce colonic premalignant lesions, male F344 rats were injected with AOM (20 mg/kg body weight, s.c.) once a week for 2 weeks. They also received 0.2% 1-MT or 0.1% EGCG in their drinking water for 4 weeks, starting 1 week before the first dose of AOM. Both 1-MT and EGCG significantly decreased the total number of aberrant crypt foci and β-catenin-accumulated crypts, which overexpressed IDO protein. Treatment with EGCG decreased IDO mRNA expression in both the colonic epithelium and stroma of rats induced by AOM. The AOM-induced increase in cyclooxygenase-2 mRNA expression in the colonic stroma was significantly decreased by EGCG. Furthermore, AOM-induced increases in IDO activity in the serum and stroma were significantly inhibited by 1-MT and EGCG. Inhibition of IDO activity by 1-MT and EGCG was also observed in cell-free assays. These findings suggest that upregulation of IDO activity is observed in the early stages of colon carcinogenesis and that the use of IDO inhibitors, such as 1-MT and EGCG, which suppress the occurrence of colonic preneoplastic lesions, could be a novel strategy for the chemoprevention of colon cancer.
Cancer Science 02/2012; 103(5):951-8. · 3.33 Impact Factor
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Naoe Goto,
Hisashi Tsurumi,
Hideko Goto,
Yoriko Ino Shimomura,
Senji Kasahara, Takeshi Hara,
Ichiro Yasuda,
Masahito Shimizu,
Nobuo Murakami,
Takeshi Yoshikawa,
Kenji Fukuno,
Takeshi Takahashi,
Yusuke Kito,
Tsuyoshi Takami,
Hisataka Moriwaki
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ABSTRACT: Serum concentration of soluble interleukin-2 receptor (sIL-2R) predicts the clinical outcome of patients with aggressive non-Hodgkin's lymphoma treated with the cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) regimen without rituximab. In the present study, we aim to re-assess the prognostic significance of serum sIL-2R for diffuse large B cell lymphoma (DLBCL) patients treated with CHOP plus rituximab and to assess sIL-2R with subtype of DLBCL, such as GCB type and non-GCB type. Two hundred and thirty-three patients with DLBCL were enrolled between December 2002 and March 2008. To evaluate serum levels of sIL-2R, venous blood samples were drawn from patients immediately before initiation of treatment. Serum sIL-2R was determined by sandwich enzyme-linked immunosorbent assay. The 5-year overall survival (OS) rates for patients with sIL-2R levels of ≥2,000 (110 cases) and <2,000 U/mL (123 cases) were 54.2% and 89.0% (P < 0.0001), respectively. Multivariate analysis using the proportional-hazards model revealed that serum sIL-2R (P = 0.0099) and extranodal involvement sites (P = 0.0392) were independent prognostic factors for OS and that clinical stage (P = 0.0168), performance status (P = 0.0181), sIL-2R (P = 0.0232), and LDH (P = 0.0316) were independent prognostic factors for progression-free survival in sIL-2R and every factor of the International Prognostic Index. Serum sIL-2R might be a useful prognostic factor for DLBCL patients in the rituximab era.
Annals of Hematology 12/2011; 91(5):705-14. · 2.62 Impact Factor
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ABSTRACT: Indoleamine 2,3-dioxygenase (IDO) catalyses tryptophan degradation in the kynurenine pathway, and plays an important role in immune tolerance by regulating antigen-presenting cells. We introduce the results of our investigations of IDO for hematological malignancies. Serum L-kynurenine (KYN) for diffuse large B cell lymphoma (DLBCL): The Complete remission (CR) rates of patients with lower KYN and higher KYN were 83% and 61%, respectively (p < 0.05). The 3-year overall survival (OS) rates for patients with lower KYN and higher KYN were 89% and 58%, respectively (p < 0.005). IDO expression for DLBCL: CR rates in patients with IDO-positive DLBCL and IDO-negative DLBCL were 55.3% and 79.0% (p = 0.008), while 3-year overall survival rates were 49.8% and 78.8%, respectively (p = 0.0003). Serum KYN and IDO expression for DLBCL: Three-year OS rates were 55% and 78% for patients with higher KYN and lower KYN, respectively (p = 0.027), and 44% and 75% for patients with IDO-positive and IDO-negative DLBCL, respectively (p = 0.0017). Patients with low KYN and IDO-negative showed the best outcomes, while patients with high KYN and IDO-positive showed the poorest outcome. Serum KYN for T-cell lymphoma: The 5-year OS rates for patients with lower KYN and higher KYN were 77% and 38%, respectively (p < 0.005). Serum KYN and IDO expression for AML: The 5-year OS rates for patients with lower KYN and higher KYN were 68% and 11%, respectively (p < 0.05). The 5-year OS rates for patients with IDO mRNA expression and without IDO mRNA expression were 64% and 41%, respectively (p < 0.05). IDO activity might play an important role in the disease activity of hematological malignancies.
Rinsho byori. The Japanese journal of clinical pathology 12/2011; 59(12):1133-43.
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Leukemia & lymphoma 11/2011; 53(6):1143-5. · 2.40 Impact Factor
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ABSTRACT: Obesity and related metabolic abnormalities, including adipocytokine dysbalance, are risk factors for hepatocellular carcinoma (HCC). Visfatin, an adipocytokine that is highly expressed in visceral fat, is suggested to play a role in the progression of human malignancies. Branched-chain amino acids (BCAA) reduce the incidence of HCC in obese patients with liver cirrhosis and prevent obesity-related liver carcinogenesis in mice. In this study, we investigated the possible role of visfatin on HCC progression and the effects of BCAA on visfatin-induced proliferation of HCC cells. In patients with HCCs, serum visfatin levels were significantly correlated with stage progression and tumor enlargement. Visfatin preferentially stimulated the proliferation of HepG2, Hep3B, and HuH7 human HCC cells compared with Hc normal hepatocytes. Visfatin phosphorylated extracellular signal-regulated kinase (ERK), Akt, and GSK-3β proteins in HepG2 cells. LY294002 [a phosphoinositide-3-kinase (PI3K) inhibitor], PD98059 [a MAP/ERK 1 kinase (MEK1) inhibitor], CHIR99021 (a GSK-3β inhibitor), and BCAA significantly inhibited visfatin-induced proliferation in HepG2 cells. BCAA also inhibited phosphorylation of GSK-3β, increased cellular levels of p21(CIP1), caused cell-cycle arrest in G(0)/G(1) phase, and induced apoptosis in HCC cells in the presence of visfatin. These findings suggest that visfatin plays a critical role in the proliferation of HCC cells and may be associated with the progression of this malignancy. In addition, BCAA might inhibit obesity-related liver carcinogenesis by targeting and, possibly, by overcoming the stimulatory effects of visfatin.
Cancer Prevention Research 09/2011; 4(12):2092-100. · 4.91 Impact Factor
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Hisashi Tsurumi, Takeshi Hara,
Naoe Goto,
Jun-Ichi Kitagawa,
Nobuhiro Kanemura,
Takeshi Yoshikawa,
Senji Kasahara,
Hideko Goto,
Kenji Fukuno,
Toshiki Yamada,
Michio Sawada,
Masahito Shimizu,
Takeshi Takahashi,
Tsuyoshi Takami,
Hisataka Moriwaki
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ABSTRACT: The anthracycline drug pirarubicin (tetrahydropyranyl-adriamycin [THP]) apparently has been reported to show fewer cardiotoxic effects than doxorubicin. We have previously described the effectiveness of the R-THP-COP regimen comprising rituximab, cyclophosphamide, pirarubicin, vincristine and prednisolone in patients with diffuse large B-cell lymphoma. We conducted a phase II study to determine the effectiveness of a regimen incorporating rituximab (R-THP-COP) for patients with previously untreated advanced-stage indolent CD20-positive B-cell lymphoma according to the Working Formulation and World Health Organization classification. Four to six courses of the regimen were administered every 3 weeks in 50 patients. The complete remission rate was 57%, while the 3-year overall survival rate was 92%. Regimen-related death was not observed. The R-THP-COP regimen appears very effective for patients with previously untreated advanced-stage indolent CD20-positive B-cell lymphoma. The present results indicate the need for randomized trials of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) and R-THP-COP among patients with CD20-positive indolent lymphoma.
Leukemia & lymphoma 08/2011; 53(2):247-53. · 2.40 Impact Factor
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ABSTRACT: A 63-year-old woman presented with leukocytosis (278 × 10(9)/L) with 72% blasts. Bone marrow blast cells showed cytogenetic abnormality with 46,XX, t(9;22), inv(16). Despite achievement of hematological remission by induction chemotherapy, Philadelphia chromosome did not disappear; chronic myeloid leukemia (CML) in blast crisis (BC) was thus diagnosed. The P190 BCR/ABL fusion transcript was detected. Imatinib mesylate introduced a hematological remission of short duration; however, infiltration into the central nervous system occurred, and the patient died 7 months after presentation. Coexistence of inv(16) and t(9:22) has been described in CML-BC and de novo AML, and CML-BC patients always carry P210 BCR/ABL, while de novo AML patients usually have P190 BCR/ABL. To the best of our knowledge, this is the first report of CML-BC with inv(16) and P190 BCR/ABL. We discuss this case with reference to the literature.
International journal of hematology 06/2011; 93(6):806-10. · 1.17 Impact Factor
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Naoe Goto,
Hisashi Tsurumi,
Senji Kasahara,
Nobuhiro Kanemura, Takeshi Hara,
Ichiro Yasuda,
Masahito Shimizu,
Nobuo Murakami,
Michio Sawada,
Toshiki Yamada,
Masao Takemura,
Mitsuru Seishima,
Yusuke Kito,
Tsuyoshi Takami,
Hisataka Moriwaki
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ABSTRACT: We have previously reported that serum interleukin-18 (IL-18) concentration predicted the clinical outcome of patients with aggressive non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). When rituximab (R) was added to this regimen, the prognosis of diffuse large B-cell lymphoma (DLBCL) was markedly improved.
In this study, we re-evaluated the prognostic significance of serum IL-18 in 227 DLBCL patients. Seventy-three patients received CHOP before R-era, and 154 patients received rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) recently.
Four-year overall survival (4-yr OS) rates for patients in CHOP group with IL-18 ≥720 pg/mL and <720 pg/mL were 8.2% and 67.3% (P<0.0001), respectively, and 4-yr OS rates with IL-18 ≥590 and <590 pg/mL in R-CHOP group were 53.4% and 77.8% (P=0.0008), respectively. Multivariate analysis revealed that serum IL-18 correlated most significantly with OS and progression-free survival (PFS) in both groups (OS: P<0.0001, PFS: P<0.0001, in CHOP group; OS: P=0.0147, PFS: P=0.0084 in R-CHOP group). The high serum IL-18 patients with poor prognostic group in revised IPI or with non-germinal center B-cell phenotype had a very poor prognosis.
Serum IL-18 might be a powerful prognostic factor for DLBCL in R-era.
European Journal Of Haematology 05/2011; 87(3):217-27. · 2.61 Impact Factor
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ABSTRACT: The aim of this study was to assess the effects of acyclic retinoid (ACR) and vitamin K(2) (VK(2)) in HL-60 cells.
We used HL-60 cells, and the Trypan Blue dye exclusion method was used for cell proliferation assays. For detection of apoptosis, the Annexin V-binding capacity of treated cells was examined by flow cytometry. To evaluate the cell cycle, we used a FITC BrdU Flow KIT and flow cytometry. Total extracted and equivalent amounts of protein were examined by Western blotting using specific antibodies.
ACR and VK(2) dose dependently inhibited the proliferation of HL-60 cells. These two agents in combination synergistically inhibited cell growth and induced apoptosis. VK(2) inhibited activation of the Ras/MAPK signaling pathway, and ACR plus VK(2) cooperatively inhibited phosphorylation of RXRα and the growth of HL-60 cells. Moreover, ACR and VK(2) induced increases in G0/G1 phase HL-60 cells, alone and synergistically in combination.
The synergistic effects of ACR and VK(2) on HL-60 cells may provide a novel strategy for treating leukemia.
Journal of Cancer Research and Clinical Oncology 05/2011; 137(5):779-87. · 2.56 Impact Factor
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Naoe Goto,
Hisashi Tsurumi,
Michio Sawada,
Nobuhiro Kanemura, Takeshi Hara,
Senji Kasahara,
Yusuke Kito,
Katsuyoshi Takada,
Yasuharu Sato,
Tadashi Yoshino,
Hisataka Moriwaki,
Tsuyoshi Takami
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ABSTRACT: Peripheral T-cell lymphoma (PTCL) with a follicular growth pattern is very rare. Herein, a case of follicular variant of PTCL in a 50-year-old man who complained of tonsillar and generalized lymph node swelling is reported. The resected tonsil revealed a vague nodular growth pattern of atypical cells, medium to large in size, with abundant pale cytoplasm. The lymphoma cells were CD3(+) CD4(+) CD5(+) CD8(-) CD10(+) CD56(-) CD57(-) BCL6(+) PD-1(+) CXCL13(+) and were associated with a meshwork of CD21(+) follicular dendritic cells. Molecular studies revealed clonal rearrangement of the T-cell receptor gamma chain gene but not of the immunoglobulin gene. Cytogenetic analysis disclosed a complex abnormality in 18 of 20 cells with the exclusion of t(5; 9). These findings suggest that the present case is a follicular variant of PTCL derived from follicular T-helper cells.
Pathology International 05/2011; 61(5):326-30. · 1.62 Impact Factor
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Senji Kasahara, Takeshi Hara,
Hisashi Tsurumi,
Naoe Goto,
Jun-Ichi Kitagawa,
Nobuhiro Kanemura,
Takeshi Yoshikawa,
Hideko Goto,
Kenji Fukuno,
Toshiki Yamada,
Michio Sawada,
Takeshi Takahashi,
Tsuyoshi Takami,
Hisataka Moriwaki
[show abstract]
[hide abstract]
ABSTRACT: The anthracycline drug pirarubicin (tetrahydropyranyl adriamycin; THP) apparently has fewer cardiotoxic effects than doxorubicin. We previously described the benefit of the THP-COP regimen comprising cyclophosphamide, THP, vincristine, and prednisolone for elderly patients with diffuse large B-cell lymphoma (DLBCL). However, that study was completed before rituximab (R) was introduced into clinical practice. Here we report a phase II study of the THP-COP regimen combined with R (R-THP-COP) every 3 weeks. The complete response and 3-year overall survival rates was 63% and 53%, respectively, and no deaths were related to the regimen. We conclude that the R-THP-COP regimen is safe and effective for patients with DLBCL. Based on these results, a randomized controlled trial of rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) and R-THP-COP as a phase III study is ongoing.
Leukemia & lymphoma 04/2011; 52(4):629-34. · 2.40 Impact Factor
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ABSTRACT: Pachydermoperiostosis (PDP) is a rare disorder of bone and connective tissue growth. A 21-year-old man was referred to our hospital with anemia. He showed characteristics of PDP. Bone marrow biopsy showed myelofibrosis. Chromosomal abnormalities or JAK2 mutation were not found. Anemia gradually progressed, and he became transfusion-dependent. Oral prednisolone was initiated; it gradually improved his anemia and rendered the patient free of transfusion. However, other clinical symptoms such as clubbed fingers and skin hypertrophy remained unimproved. In this case, the serum concentration of vascular endothelial growth factor and transforming growth factor-β levels were increased. Further investigation will be necessary to establish appropriate treatment strategies for this disease.
Internal Medicine 01/2011; 50(19):2207-11. · 0.94 Impact Factor
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Soranobu Ninomiya, Takeshi Hara,
Hisashi Tsurumi,
Masato Hoshi,
Nobuhiro Kanemura,
Naoe Goto,
Senji Kasahara,
Masahito Shimizu,
Hiroyasu Ito,
Kuniaki Saito,
Yoshinobu Hirose,
Tetsuya Yamada,
Takeshi Takahashi,
Mitsuru Seishima,
Tsuyoshi Takami,
Hisataka Moriwaki
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ABSTRACT: Indoleamine 2,3-dioxygenase (IDO) exerts immunomodulatory effects due to enzymatic activities catalyzing the essential amino acid L-tryptophan. IDO activity might play an important role in regulating immune responses exerted by antigen-presenting cells as a potent tool to help escape from assault by the immune system. In this study, we performed immunohistochemical analysis for IDO expression using mouse anti-human IDO monoclonal antibody in 119 tissue samples of diffuse large B-cell lymphoma (DLBCL) obtained before treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Not only the lymphoma cells themselves but also dendritic cells (DCs) expressed IDO. Positive IDO expression in lymphoma cells was found in 38 cases (32%). Complete remission rates in patients with IDO-positive DLBCL and IDO-negative DLBCL were 55.3% and 79.0% (p=0.008), while 3-year overall survival rates were 49.8% and 78.8%, respectively (p=0.0003). IDO activity might thus play an important role in DLBCL and cells that express IDO appear important for determining outcomes after R-CHOP treatment. IDO might represent a candidate therapeutic target for DLBCL patients who show resistance to chemotherapy.
Annals of Hematology 10/2010; 90(4):409-16. · 2.62 Impact Factor
