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Biomedical subjects

Tetsuro Nakazato

Publications and source records attributed to Tetsuro Nakazato.

7 recordsLinked to original sources
PubMed2007

Inhibition of heat shock protein-90 modulates multiple functions required for survival of human T-cell leukemia virus type I-infected T-cell lines and adult T-cell leukemia cells.

The molecular chaperone Hsp90 is involved in the stabilization and conformational maturation of many signaling proteins that are deregulated in cancers. The geldanamycin derivative 17-AAG is currently tested in clinical trials and known to inhibit the function of Hsp90 and promote the proteasomal degradation of its misfolded client proteins. ATL is a fatal malignancy of T lymphocytes caused by HTLV-I infection and remains incurable. Since Hsp90 is overexpressed in HTLV-I-infected T-cell lines and primary ATL cells, we analyzed the effects of 17-AAG on cell survival, apoptosis and expression of signal transduction proteins. HTLV-I-infected T-cell lines and primary ATL cells were significantly more sensitive to 17-AAG in cell survival assays than normal PBMCs. 17-AAG induced the inhibition of cell cycle and apoptosis. These effects could be mediated by inactivation of NF-kappaB, AP-1 and PI3K/Akt pathways, as well as reduction of expression of proteins involved in the G1-S cell cycle transition and apoptosis. Proteasome inhibition interfered with 17-AAG-mediated signaling proteins depletion. Collectively, our results indicate that 17-AAG suppresses ATL cell survival through, at least in part, destabilization of several client proteins and suggest that 17-AAG is a potentially useful chemotherapeutic agent for ATL.

Adult↗
PubMed2004

Very late central nervous system relapse in a patient with B cell lymphoblastic lymphoma.

Very late relapse of lymphoblastic lymphoma (LBL) is very rare. We report a case of a patient who developed central nervous system (CNS) relapse of LBL 16 years after the onset of the primary disease. An 8-year-old girl was hospitalized with a skin tumor in the occipital region on November 27, 1984. Examination of a biopsy of the skin tumor showed typical features of non-Hodgkin's lymphoma (diffuse medium-sized cell type). She received multiagent chemotherapy and went into remission. On July 4, 2000, she was hospitalized with persistent headache. Cranial magnetic resonance imaging showed a cerebellar lesion, which was hypointense on T1-weighted images and of heterogeneous intensity on T2-weighted images. A midline suboccipital craniotomy was performed and pathological examination revealed a diffuse proliferation of lymphoid cells, which were positive for terminal deoxynucleotidyl transferase, but negative for CD45RO, CD3 and CD20. Tumor cells stained positively for CD10, CD22, CD38 and HLA-DR. Revised immunohistochemistry of the primary specimens of skin tumor obtained 16 years earlier revealed a phenotype similar to that of the CNS disease. Polymerase chain reaction products for the immunoglobulin gene from both the skin and cerebellar specimens were an identical size. Thus, the original diagnosis of diffuse medium-sized lymphoma was revised to B cell LBL. An isolated CNS relapse of LBL was apparent in the present case. After salvage chemotherapy, the patient underwent high-dose chemotherapy with autologous peripheral blood stem cell support and subsequent craniospinal irradiation. She went into a lasting complete remission.

Cell Proliferation↗
PubMed2003

[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↗
PubMed2002

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↗