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Biomedical subjects

Masato Masuda

Publications and source records attributed to Masato Masuda.

32 records · Page 2Linked to original sources

Childhood blastic NK cell leukemia successfully treated with L-asparagenase and allogeneic bone marrow transplantation.

Blastic NK cell lymphoma/leukemia is a rare and highly malignant neoplasia in both adults and children. It is characterized by lymphoblastoid morphology without cytoplasmic granules and immature NK cell immunophenotypes (CD56+, CD57-, CD16-). It has predilection for extranodal organ involvement, and the prognosis of affected patients is extremely poor under the current chemotherapy. We present a 14-year-old girl who was diagnosed as having blastic NK cell leukemia with mediastinal, pleural, and pericardial involvement. Immunophenotyping of her leukemic cells showed positive for CD2, CD5, CD7, CD34, CD56, HLA-DR, and cytoplasmic CD3. T cell receptor (TCR) and Immunoglobulin heavy chain genes were not rearranged. She received chemotherapy for acute lymphoblastic leukemia incorporating L-asparaginase (L-asp) which successfully induced complete remission. Bone marrow transplantation (BMT) from her HLA-identical sibling was conducted after two courses of consolidation therapy. Expression of aspargine synthetase (AS) protein in the leukemic cells at diagnosis was examined by an immunocytochemical method. She remains in hematological remission for over 36 months after BMT. The expression of AS protein was negative, suggesting that the leukemic cells were sensitive to L-asp. Induction and consolidation therapy incorporating L-asp followed by allo-BMT might be a promising treatment for child hood blastic NK cell leukemia, but more samples of the rare leukemia need to be studied before any definitive conclusions can be drawn.

Adolescent↗

Adult T-cell leukemia: future prophylaxis and immunotherapy.

A small population of human T-cell leukemia virus Type I (HTLV-I) carriers develop adult T-cell leukemia after a long incubation period. The results of a series of experiments using animal models suggest that insufficiency of HTLV-I-specific T-cell response induced by vertical HTLV-I infection allows enlargement of the HTLV-I-infected cell reservoir in vivo, a crucial risk factor of adult T-cell leukemia. In this review it is proposed that prophylactic Tax-targeted vaccines for the high-risk group of adult T-cell leukemia, which is characterized by low HTLV-I-specific T-cell response and high proviral load, can reduce the risk. Immunological studies on adult T-cell leukemia patients after hematopoietic stem cell transplantation also suggest that Tax-targeted immunotherapy may be effective against full-blown disease, although its indication may be limited.

Animals↗

Phase II study of cladribine (2-chlorodeoxyadenosine) in relapsed or refractory adult T-cell leukemia-lymphoma.

Adult T-cell leukemia-lymphoma (ATL) is a retrovirus-associated T-cell malignancy with an extremely poor prognosis; the median survival time of ATL patients with the acute or lymphoma type is less than 1 year with various combination chemotherapies. Cladribine (2-chlorodeoxyadenosine; 2-CdA), a purine analog resistant to degradation by adenosine deaminase, has shown definitive clinical activity against various lymphoid malignancies, including hairy cell leukemia, indolent lymphoma, and cutaneous T-cell lymphoma. An in vitro study showed the sensitivity of T-lymphoblastoid cell lines to cladribine, and a preceding Japanese phase I study of cladribine showed that 1 refractory patient with ATL achieved an objective response. To evaluate the therapeutic efficacy of cladribine in treating ATL, we conducted a multicenter phase II study. The plan was to administer cladribine to 30 ATL patients as 0.09 mg/kg per day by 7-day continuous intravenous infusion every 4 weeks for up to 3 courses. Before the planned interim analysis, 16 patients with relapsed or refractory ATL were enrolled, 15 of whom were eligible. Only 1 of the 15 eligible patients showed an objective response (overall response rate, 7%; 90% confidence interval, 0% to 28%), and 11 patients (73%) showed progressive disease, mostly during the first course of treatment. Because the upper limit of the 90% confidence interval of the overall response rate did not reach 30% in the interim analysis, the Independent Monitoring Committee advised us to discontinue patient enrollment. In conclusion, cladribine is not worthy of further investigation for the treatment of ATL.

Adult↗

[A case of primary malignant lymphoma of the duodenum successfully treated with dose escalating chemotherapy].

A 65-year-old woman with diabetes mellitus was hospitalized for heart failure and anemia in August 2001, and recovered with conservative treatment. An endoscopic examination revealed an ulcerative mass located in the duodenal bulb to the 2nd portion. Abdominal CT scan demonstrated tumor involvement in the pancreas head. The diagnosis of a diffuse large B-cell lymphoma, clinical stage IIE, was made by endoscopic biopsy. Although surgical resection of the localized intestinal tumor would have been a common choice for initial treatment, polychemotherapy was selected; the patient had diabetes mellitus and preferred polychemotherapy to surgical operation. Because of bulky intestinal mass, transmural disease and sensitive histological type, standard-dose chemotherapy was considered to include a high risk of intestinal perforation. We performed dose-escalating chemotherapy: A half dose of THP-COP (pirarubicin, cyclophosphamide, vincristine) was given at the start in October 2001, 60% THP-COP as the next cycle, 80% THP-COP as the 3rd cycle and thereafter. Without serious complications of the intestine, she received a total of 6 cycles of chemotherapy and subsequent involved field radiation. There has been no evidence of recurrence of disease 14 months from the start of chemotherapy. When conditions make surgical treatment difficult, dose-escalating chemotherapy in a treatment cycle may be considered as an alternative.

Aged↗

Detection of Epstein-Barr virus and human T-cell lymphotropic virus type 1 in malignant nodal lymphoma, studied in Okinawa, a subtropical area in Japan.

Formalin-fixed paraffin-embedded lymph node samples were collected from 100 cases of malignant nodal lymphoma documented in Okinawa in the period from 1973 through 1998. According to the new World Health Organization classification, 12 cases were Hodgkin's lymphoma (HL). Eighty-eight cases of non-Hodgkin's lymphoma (NHL) included 54 cases of T-cell type and 34 cases of B-cell type. Using polymerase chain reaction (PCR), Epstein-Barr virus (EBV) was detected in 11 cases (91.7%) of HL and in 57 cases (64.8%) of NHL, and human T-cell lymphotropic virus type 1 (HTLV-1) was detected in 23 cases (26.1%) of NHL. Clonal integration of HTLV-1 was detected in 10 (43.5%) of 23 HTLV-1 PCR-positive cases by the inverse PCR technique. The EBV-infected cells were detected by EBER-1 in situ hybridization in 11 (91.7%) of 12 HL cases and in 64 (72.7%) of 88 NHL cases. Irrespective of phenotype and tissue type of the malignant lymphoma, the rate of EBV-positive infection in Okinawa was higher than that in any other districts reported in Japan. This characteristic high rate of EBV-positive infection in Okinawa can be ascribed to various factors, such as racial and geographical differences.

Clone Cells↗

Establishment of a primary effusion lymphoma cell line (RM-P1) and in vivo growth system using SCID mice.

Primary effusion lymphoma (PEL) is recognized as a unique lymphoma entity, which occurs exclusively in body cavities as a serous lymphomatous effusion without tumor formation or organ infiltration. We established a cell line of B-cell origin from a pericardial effusion of a 63-year-old Japanese PEL patient who did not have human immunodeficiency virus infection. This PEL cell line had human herpesvirus-8 (HHV-8) and Epstein-Barr virus (EBV) infection. We named this cell line RM-P1. This cell line showed complex chromosomal abnormalities that could not be identified by G-banding. However, spectral karyotyping analysis determined the origin and organization of all unidentified chromosomal abnormalities. When inoculated into the peritoneal cavity of 8 severe combined immunodeficiency (SCID) mice depleted of natural killer cells, RM-P1 cells induced solid tumor with ascites in all animals tested. These tumor and ascitic cells had the same immunogenotypic features as those of the original RM-P1. These 2 types of cells were positive for both HHV-8 and EBV as demonstrated using polymerase chain reaction. Fluorescence-activated cell sorting analyses showed that neither tumors nor ascitic cells grown in SCID mice expressed leukocyte function-associated antigen (LFA)-1alpha (CD11a), LFA-1lbeta (CD18), LFA-2 (CD2), LFA-3 (CD58), intercellular adhesion molecule (ICAM)-1 (CD54), ICAM-2 (CD102), ICAM-3 (CD50), or leukocyte endothelial adhesion molecule (LECAM)-1 (CD62L), suggesting that these cytoadhesion molecules are not involved in tumor formation of RM-P1 cells in vivo. The establishment of the RM-P1 cell line and the animal model of PEL may provide insights for understanding the relationship between these viruses and PEL and for understand the mechanism for PEL.

Animals↗

Acute myeloid leukemia (FAB-M2) with a masked type of t(8;21) translocation revealed by spectral karyotyping.

We report a case of acute myeloid leukemia (AML), M2 subtype according to the French-American-British (FAB) classification, with extramedullary myeloblastoma of the uterus and a masked type of variant translocation of t(8;21)(q22;q22). A 45-year-old Japanese woman presented with metrorrhagia, and AML (M2) with uterine invasion was diagnosed. The patient received an allogeneic peripheral blood stem cell transplantation after remission, and her pelvis was irradiated locally. Cytogenetic study at first showed t(8;17)(q22;p13) by G-banding. Spectral karyotyping (SKY) analysis modified this interpretation to a 3-way translocation involving chromosomes 8,17, and 21 and identified a masked type of variant t(8;21)(q22;q22) translocation. Results of fluorescence in situ hybridization using the AML1/ETO probe, and of detection of the AML1/ETO fusion transcript by reverse transcriptase-polymerase chain reaction were consistent with the karyotyping result. SKY analysis is useful to compensate for the limitations of cytogenetic studies.

Chromosomes, Human, Pair 21↗

Cytotoxic T-lymphocyte antigen-4 gene polymorphisms and human T-cell lymphotrophic virus-1 infection: their associations with Hashimoto's thyroiditis in Japanese patients.

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) decreases the immune response of T cells by inactivating the signal that occurs with interaction between CD28 on T cells and B7 on antigen-presenting cells. Gene polymorphisms involving CTLA-4 promoter (-318 C/T), exon 1 (49 A/G), and exon 4 (microsatellite (AT)n) have been linked to Hashimoto's thyroiditis (HT) and other autoimmune diseases. HT also has a reported association with human T-cell lymphotrophic virus-1 (HTLV-1) infection. We investigated the occurrence of CTLA-4 polymorphisms in Japanese patients with HT with and without anti-HTLV-1 antibodies (HTLV-1 Ab). DNA samples from 143 patients with HT and 199 controls were subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis using the restriction enzymes, Bbv 1, Tse 1, and Mse 1. In the HTLV-1 Ab-positive group the exon 1 G allele was more frequent in patients with HT than in controls (67% vs. 53%, p = 0.0377), and in HTLV-1 Ab-negative group it was also frequent in patients with HT than in controls (68% vs. 53%, p = 0.0041). Frequency of the G allele in HT with HTLV-1 Ab was comparable to those without HTLV-1 Ab. Frequency of polymorphism in the promoter did not differ between patients with HT and controls, nor between controls with and without HTLV-1 Ab. HTLV-1 infection is not associated with CTLA-4 polymorphisms in either HT or controls. HTLV-1 infection is not regulated by genetic factor such as CTLA-4, and may affect occurrence of HT as an independent purely environmental factor.

Abatacept↗