PubMed Health⌕ Search

Biomedical subjects

Taizo Tasaka

Publications and source records attributed to Taizo Tasaka.

17 recordsLinked to original sources
PubMed2006

The antitumor effects of sunitinib (formerly SU11248) against a variety of human hematologic malignancies: enhancement of growth inhibition via inhibition of mammalian target of rapamycin signaling.

We studied antitumor effects of receptor tyrosine kinase inhibitor sunitinib (formerly SU11248) against a variety of hematologic malignancies including the following leukemias: eosinophilic (EOL-1), acute myeloid (THP-1, U937, Kasumi-1), biphenotypic (MV4-11), acute lymphoblastic (NALL-1, Jurkat, BALL-2, PALL-1, PALL-2), blast crisis of chronic myeloid (KU812, Kcl-22, K562), and adult T-cell (MT-1, MT-2, MT-4), as well as non-Hodgkin's lymphoma (KS-1, Dauji, Akata) and multiple myeloma (U266). Thymidine uptake studies showed that sunitinib was active against EOL-1, MV4-11, and Kasumi-1 cells, which possessed activating mutations of the PDGFRalpha, FLT-3, and c-KIT genes, respectively, with IC(50)s of <30 nmol/L. In addition, sunitinib inhibited the proliferation of freshly isolated leukemia cells from patients possessing mutations in FLT3 gene. Annexin V staining showed that sunitinib induced apoptosis of these cells. Sunitinib inhibited phosphorylation of FLT3 and PDGFRalpha in conjunction with blockade of mammalian target of rapamycin signaling in MV4-11 and EOL-1 cells, respectively. Interestingly, rapamycin analogue RAD001 enhanced the ability of sunitinib to inhibit the proliferation of leukemia cells and down-regulate levels of mammalian target of rapamycin effectors p70 S6 kinase and eukaryotic initiation factor 4E-binding protein 1 in these cells. Taken together, sunitinib may be useful for treatment of individuals with leukemias possessing activation mutation of tyrosine kinase, and the combination of sunitinib and RAD001 represents a promising novel treatment strategy.

Adaptor Proteins, Signal Transducing↗
PubMed2006

[Cryotherapy is useful and safe in the prevention of oral mucositis after high-dose melphalan (L-PAM)].

We prospectively assessed the effectiveness of cryotherapy after high-dose L-PAM to prevent oral mucositis. Cryotherapy with ice tips was commenced 15 minutes before L-PAM administration, and continued until the end of administration. Twenty-six patients were enrolled in this study. Thirteen patients with myeloma were treated with 200 mg/m2 L-PAM followed by autologous peripheral blood stem cell transplantation, and 13 patients (4 AML, 4 MDS, 2 ALL, 2 lymphoma and 1 CML) were treated with 140 mg/m2 L-PAM followed by allogeneic stem cell transplantation. Grade 1 mucositis occurred in four of 13 patients (31%) with 200 mg/m2 L-PAM, and 2 of 13 patients (16%) with 140 mg/m2 L-PAM. Only one patient had grade 2 mucositis, and no grade 3 mucositis were observed. The procedure was well tolerated in all patients. These data suggest that cryotherapy is effective to minimize L-PAM-induced oral mucositis.

Adult↗
PubMed2004

Secondary acute monocytic leukemia with a translocation t(8;16)(p11;p13): case report and review of the literature.

Acute myeloblastic leukemia cases carrying the translocation t(8;16) (p11;p13) are characterized by the M4 and M5 subtypes, erythrophagocytosis by the blast cells and a poor prognosis, suggesting a new clinical entity. The t(8;16) fuses the MOZ gene which encodes a histone acetyltransferase, located on 8p11 with the CBP gene which also encodes a histone acetyltransferase, located on 16p13, and recent reports suggested that the chimeric transcription MOZ-CBP is essential for leukemogenesis. A 68-year-old woman who had been treated mainly with paclitaxel and carboplatin for preceding ovarian cancer was admitted to our hospital, complaining of right breast mass. She was diagnosed as having breast cancer and acute monocytic leukemia (M5b). Cytogenetic study with spectral karyotyping analysis revealed the development of 47 XX, + 8, t(8;16)(p11;p13). Eleven cases of therapy-related t(8;16) leukemia including the present case have been reported, but prior treatment with paclitaxel and carboplatin-based chemotherapy has never been reported. The relation of histone acetylase and therapy-related leukemia is discussed.

Aged↗
PubMed2004

Diffuse large B-cell lymphoma presenting with hypercalcemia and multiple osteolysis.

Osteolysis and hypercalcemia are observed in 5-15%, and 10%, respectively, of malignant lymphoma patients during their clinical course. However, both osteolysis and hypercalcemia are uncommon at onset of the disease. We encountered a 24-year-old male non-Hodgkin's lymphoma patient who had multiple osteolytic lesion from the onset of the disease and repeated episodes of hypercalcemia during the clinical course. The patient died with refractory disease. We studied the expression of chemokines which might affect bone resorption using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Increased expressions of MIP-1alpha, MIP-1beta and RANKL, which are osteoclast-activating factors, were observed in the RNA derived from the patient's lymphoma cells. The secretion of osteoclast-activating factors such as MIP-1alpha by the tumor cells (and/or bone marrow stromal cells) might be involved in the etiology of osteolysis and hypercalcemia in some malignant lymphoma cases.

Acid Phosphatase↗
PubMed2003

High levels of hyaluronan production by a malignant lymphoma cell line with primary effusion lymphoma immunophenotype OHK.

We investigated whether hyaluronan (HA) was produced by a malignant lymphoma cell line with a primary effusion lymphoma immunophenotype, OHK. OHK secreted high levels of HA into the culture supernatant, and reverse transcription polymerase chain reaction showed mRNA for the HA synthases 2 and 3. HA binding protein-reactive HA was present in the plasma membrane and in the cytoplasm. The inoculation of OHK into severe combined immunodeficiency disease mice produced marked viscid ascites with concentrated HA and a vascular-rich mesenteric solid tumour. These results show that HA is produced and secreted by the malignant lymphoma cell line OHK.

Animals↗
PubMed2003

Peripheral T-cell lymphoma presenting with rapidly progressing myelofibrosis.

Myelofibrosis following peripheral T-cell lymphoma has rarely been reported. Described here is a case of peripheral T-cell lymphoma with myelofibrosis and elevated transforming growth factor beta (TGF-beta). A 69 years old male was admitted due to anemia and thrombocytopenia. His bone marrow showed fibrosis and was infiltrated with small lymphoid cells and a few residual normal hematopoietic cells. He had presented with hepatosplenomegaly and left inguinal lymph node swelling. Biopsy of the left inguinal lymph node revealed diffuse mature small lymphoid cells with atypical nuclei. Immunophenotyping of the small lymphoid cells were positive for CD3, CD8, TCR alphabeta and HLA-DR and were negative for CD4, CD19, CD20 and CD56. T-cell receptor beta-chain gene was rearranged in bone marrow cells. He was diagnosed as having peripheral T-cell lymphoma complicated with myelofibrosis. Chemotherapy was administrated which improved his pancytopenia and symptoms. Two years later, anemia and thrombocytopenia developed rather quickly, he died because of progression of myelofibrosis with severe pancytopenia.

Aged↗
PubMed2003

Increased expression of c-maf in pure red cell aplasia secondary to plasma cell dyscrasia.

Th2 dominancy in the peripheral T helper (Th) cell subsets were reported to be involved in the pathogenesis of pure red cell aplasia (PRCA). We encountered a PRCA case secondary to plasma cell dyscrasia that showed Th2 dominancy at the relapse of PRCA. Increased expression of c-maf, a transcriptional factor which induces Th2 differentiation of naive T-cells, and elevated expression of interleukin (IL)-4 were observed in the RNA derived from patient's bone marrow at relapse of PRCA. Following the administration of methylprednisolone which improved PRCA, normalization of Th1/Th2 ratio and decreased expression of c-maf and IL-4 were observed, which suggests that the upregulation of c-maf might have played a role in the pathogenesis of PRCA secondary to plasma cell dyscrasia.

Aged↗
PubMed2003

Aberrant methylation in promoter-associated CpG islands of multiple genes in therapy-related leukemia.

Methylation profile was analyzed in eleven cases of therapy-related leukemia (t-leukemia) for p14, p15, p16, Rb, hMLH1, hMSH2, MGMT, APC, RAR beta, DAPK, RIZ1, FHIT, and SOCS-1 genes by using methylation specific polymerase chain reaction (MSP) analysis. Six (55%) of eleven cases showed methylation of at least one gene. The average time to the development of t-leukemia after the treatment of the primary tumor was significantly shorter in patients with methylation than those without methylation (49.3 months vs. 133.2 months, P=0.044). These results suggest that hypermethylation might be involved in the development of t-leukemia.

Aged↗
PubMed2003

Huge post-operative ulcer following hydroxyurea therapy in a patient with polycythemia vera.

A 75-year old woman was referred to our hospital due to a worsening post-operative cutaneous ulcer. She had a history of polycythemia vera and had been treated with a daily dose of 500mg hydroxyurea (HU) for six years. She underwent a right hernioplasty in another hospital in September 2002. Two days after the hernioplasty, the skin around the wound became erythematous and necrosis was observed. Even with the administration of antibiotics and debridment was performed three times, her condition deteriorated and she was referred to our hospital. On admission, a 22x15cm ulcer was observed on the lower abdomen. With termination of HU, the cutaneous ulcer became smaller and with the withdrawal of other medication, the ulcer size continued to decrease. Although post-operative cutaneous ulcer complicated by HU administration has rarely been reported, our case clearly indicates that early termination of HU should be considered when patients develop symptoms preceding cutaneous ulcer.

Aged↗
PubMed2002

Establishment and characterization of a Kaposi's sarcoma-associated herpesvirus- and Epstein-Barr virus-negative malignant lymphoma cell line (OHK) with primary effusion lymphoma immunophenotype.

A novel cell line, designated OHK, was established from ascites of a 59-year-old Japanese woman with diffuse large B-cell lymphoma showing a peculiar serosal tropism, as seen in primary effusion lymphomas (PEL). OHK exhibited a large pleomorphic morphology with irregular nuclei and distinct nucleoli, and included immunoblastic and Reed-Sternberg-like giant cells. On ultrastructural examination, rich intermediate filaments, and well-developed Golgi apparati and rough endoplasmic reticulum, were seen. Immunophenotypically, OHK lacked T and B cell-associated antigens, and had CD10, CD30, CD33 and CD138 antigens. Although OHK cells did not express immunoglobulin (Ig) protein, Southern blot analysis demonstrated clonal rearrangements of Ig heavy and light chain genes. These observations suggest that OHK cells are derived from preterminally differentiated B cells, and that they have features of PEL. Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus were not detected. OHK displayed hyperploid karyotypes with multiple structural abnormalities, and produced some cytokines such as macrophage-colony-stimulating factor (M-CSF), granulocyte-CSF, interleukin 6 and transforming growth factor beta 1. In particular, vascular endothelial growth factor (VEGF), whose stimulation of vascular permeability is thought to be critical to the pathogenesis of PEL, was also produced in large quantities. These results indicate that OHK may be a useful tool for the investigation of PEL.

Ascitic Fluid↗
PubMed2002

Marked thrombocytosis following relapse of acute myeloblastic leukemia associated with development of translocation (2;14) (p13;q32).

Thrombocytosis is a rare finding in acute myeloblastic leukemia (AML). Here, we describe a patient with AML who relapsed with marked thrombocytosis. The patient was initially diagnosed as having AML (M4) with a low platelet count. The patient was started on combination chemotherapy including high-dose etoposide and achieved complete remission. However, the patient relapsed six months later with an extremely high platelet count (72.5 x 10(4)/microl). Cytogenetic analysis at relapse revealed the development of t(2;14)(p13;q32). Despite the repeated combination chemotherapy, the patient died with progressive disease. This case suggests that the additional chromosomal aberration t(2;14)(p13;q32) may be related to abnormal thrombocytosis in AML.

Adult↗
PubMed2002

EBV associated hemophagocytic syndrome accompanied by central pontine myelinolysis.

The development of central pontine myelinolysis (CPM) has rarely been reported in association with hemophagocytic syndromes (HPS). Here we report a unique case of Epstein-Barr Virus (EBV)-related HPS which was accompanied with CPM. A 72-year-old man who had no significant medical history was admitted to our hospital due to high fever and progressing dysphasia and dysarthria. Physical examination revealed anisocoria of the right pupil, fixed reaction to light, and paralysis of the left vagus nerves. Magnetic resonance imaging revealed low signal intensity on T1-weighted images and high signal intensity T2-weighted images in the patient's central midpontine lesion. Initial work-up showed anemia and thrombocytopenia with elevated levels of serum ferritin, lactate dehydrogenase, and soluble IL-2 receptor. Bone marrow aspiration revealed hemophagocytosis. The EBV genome was detected in the peripheral blood using the polymerase chain reaction method. He was diagnosed as having EBV-related HPS and CPM. Despite intensive treatment with methylpredonisolone, immunoglobulin, and etoposide, he died due to progressive disease and fungal septicemia. The etiology and relation between CPM and HPS are discussed.

Aged↗
PubMed2002

[Reversible cardiomyopathy secondary to interferon-alpha in chronic myelogenous leukemia].

Interferon-alpha (IFN-alpha) has been accepted as an effective agent in the treatment of chronic myelogenous leukemias (CML). Cardiac toxicity of IFN-alpha has rarely been reported in cases of CML. A 62-year-old woman with a two-year history of chronic myelogenous leukemia who had been treated with IFN-alpha (10 million U/3 days/week) given subcutaneously with oral hydroxycarbamide 500 mg, presented with chest pain, dyspnea and subconsciousness. Chest X-ray revealed cardiomegaly and congestion, and ultrasonography showed diffuse hypokinesis of the heart with decreased left ventricular ejection fraction (LVEF) 34%. She was diagnosed cardiomyopathy caused by IFN-alpha administration. She was treated with furosemide, dobutamine hydrochloride, milrinone and carperitide. The administration of IFN-alpha was terminated. LVEF was improved to 50% within one month from the onset of events, and the patient was discharged. We discuss herein the cardiomyopathy caused by IFN-alpha in CML.

Cardiomyopathies↗
PubMed2002

[Lupus cystitis in the course of Evans syndrome].

A 50-year-old woman with a 4-year history of Evans syndrome was admitted to our hospital because of progressive nausea, appetite loss, body weight loss, diarrhea and abdominal pain. Abdominal ultrasonography revealed pleural effusion, ascites, bilateral hydronephrosis, dilatation of the bilateral ureter, and irregular wall thickness of the urinary bladder. Immunological studies revealed decreased complement components (C3; 72 mg/dl, C4; 7 mg/dl, CH50; 28.8 mg/dl), a x 80 antinuclear antibody titer (homogeneous pattern), antibody against single-stranded DNA 19 U/ml, anti-SS-A antibody over 500 U/ml and negativity for antibody against double-stranded DNA (anti-dsDNA Ab). Although the patient did not fulfill the criteria for systemic lupus erythematosus (SLE), we diagnosed her as having lupus cystitis. Bolus methylprednisolone (mPSL) therapy (1,000 mg mPSL over 3 days, div) was administered, followed by 60 mg PSL, and this led to immediate improvement of the patient's symptoms and laboratory data. Later, anti-dsDNA Ab became positive, and the patient thereby fulfilled the criteria for SLE. Lupus cystitis following Evans syndrome has rarely been reported. The present such case was treated successfully with bolus mPSL therapy.

Anemia, Hemolytic, Autoimmune↗