Biomedical subjects

Kanji Sugita

Publications and source records attributed to Kanji Sugita.

24 records · Page 2Linked to original sources

PubMed2003

Effects of sodium in hydration solution on plasma methotrexate concentrations following high-dose methotrexate in children with acute lymphoblastic leukemia.

PURPOSE: To test whether a higher sodium dose in the hydration solution may facilitate faster methotrexate (MTX) elimination as compared with a lower sodium dose following high-dose MTX (HDMTX) treatment. METHODS: Intravenous solutions with alternate doses of sodium (regimen A 70 mEq/l, regimen B 100 mEq/l) were given to 30 children with acute lymphoblastic leukemia in two courses of HDMTX in a randomized crossover fashion. The plasma MTX concentrations every 24 h from the beginning of MTX administration and the adverse events associated with HDMTX were compared between the two hydration regimens. RESULTS: The plasma MTX concentrations were similar in the two hydration regimens at 24 h (A 50.9+/-7.4 vs B 40.9+/-5.4 microM, means+/- SE, P=0.17), but was significantly lower in regimen B at 48 and 72 h (A 0.65+/-0.17 vs B 0.27+/-0.03 microM, P=0.04; and A 0.14+/-0.03 vs B 0.05+/-0.01 microM, P=0.003). The time during which MTX plasma concentrations exceeded 0.1 microM was significantly longer in regimen A than in regimen B (A 3.83+/-0.18 vs B 3.13+/-0.06 days, P=0.001). The incidences of adverse events were similar between the two regimens ( P=0.78), and severe adverse events were not seen in either regimen. CONCLUSIONS: Hydration with a higher sodium dose facilitated faster MTX elimination following HDMTX. Sodium may have a beneficial effect on MTX-induced nephrotoxicity.

Adolescent↗

PubMed2003

Expression of pericyte, mesangium and muscle markers in malignant rhabdoid tumor cell lines: differentiation-induction using 5-azacytidine.

Malignant rhabdoid tumor (MRT) has been considered to have multiphenotypic diversity characteristics. Some MRTs exhibit a neural phenotype. However, it is still unclear whether MRT cells can display a skeletal muscle, smooth muscle or smooth muscle-like cell phenotype, like those of pericytes and mesangial cells. To determine if MRTs exhibit skeletal muscle cell or smooth muscle-like cell phenotypes, six MRT cell lines (TM87-16, STM91-01, TTC549, TTC642, YAM-RTK1 and TTC1240) were examined for markers of skeletal muscle (MyoD, myogenin, myf-5, myf-6, acetylcholine receptor-alpha, -beta and -gamma), smooth muscle (alpha-smooth muscle actin, SM-1 and SM22), and smooth muscle-like cells, such as pericytes (angiopoietin-1 and -2) and mesangial cells (megsin), using conventional RT-PCR, semi-quantitative PCR, western blotting and immunocytochemistry before and after differentiation-induction with 5-azacytidine. alpha-Smooth muscle actin and SM22 were detected in all six MRT cell lines, while MyoD and myf-5, crucial markers for skeletal myogenic determination, were not. The TM87-16 cell line expressed SM-1 and angiopoietin-1. TTC1240 also expressed angiopoietin-1. Interestingly, STM91-01 expressed megsin, a novel marker for mesangial cells, in addition to angiopoietin-1. Our results indicated that some MRTs exhibited smooth muscle and/or smooth muscle-like cell phenotypes and some renal MRTs might be of mesangial origin. Recently, smooth muscle and also smooth muscle-like cells have been considered to be of neuroectodermal origin. MRT can thus considered to belong to the category of primitive neuroectodermal tumors (PNETs) in the broad sense.

Antimetabolites, Antineoplastic↗

PubMed2003

[Development of severe aplastic anemia in a girl with Hashimoto's thyroiditis and papillary thyroid carcinoma].

A 14-year-old girl was admitted because of general fatigue and cervical lymphadenopathy. She showed bilateral struma (IInd degree) and enlargement of her left cervical lymph nodes. Laboratory data revealed neutropenia (219/microliter) and thrombocytopenia (Plt 5.1 x 10(4)/microliter) with mild anemia (Hb 11.1 g/dl), and the bone marrow aspirate and biopsy specimens showed hypocellularity. In addition, auto-antibodies against thyroid peroxidase (TPO) and thyroglobulin (TG) were highly elevated. Computed tomography of the neck showed a nodule in the left thyroid lobe with marked lymphadenopathy, and fine needle aspiration biopsy demonstrated papillary thyroid carcinoma with Hashimoto's thyroiditis and metastasis to the lymph nodes. One month after left thyroid lobectomy and cervical lymphadenectomy, the patient's condition progressed to very severe aplastic anemia, and she received immunosuppressive therapy consisting of cyclosporin A and anti-thymocyte globulin. Hematologically, partial and complete responses were obtained three and six months later, respectively. Of interest, anti-TPO and TG antibody titers remarkably decreased after immunosuppressive therapy. The patient had HLA-DR 2(DRB 1*1501) and DR 8(DRB 1*0802). The former is frequently found in patients with cyclosporin A-dependent aplastic anemia, and the latter is frequently found in Asian patients with Hashimoto's thyroiditis, suggesting an underlying autoimmune background for the simultaneous outbreak of aplastic anemia and Hashimoto's thyroiditis complicated by thyroid carcinoma.

Adolescent↗

PubMed2002

TNF-related apoptosis-inducing ligand (TRAIL) frequently induces apoptosis in Philadelphia chromosome-positive leukemia cells.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) have been implicated in antitumor immunity and therapy. In the present study, we investigated the sensitivity of Philadelphia chromosome (Ph1)-positive leukemia cell lines to TRAIL- or FasL-induced cell death to explore the possible contribution of these molecules to immunotherapy against Ph1-positive leukemias. TRAIL, but not FasL, effectively induced apoptotic cell death in most of 5 chronic myelogenous leukemia-derived and 7 acute leukemia-derived Ph1-positive cell lines. The sensitivity to TRAIL was correlated with cell-surface expression of death-inducing receptors DR4 and/or DR5. The TRAIL-induced cell death was caspase-dependent and enhanced by nuclear factor kappa B inhibitors. Moreover, primary leukemia cells from Ph1-positive acute lymphoblastic leukemia patients were also sensitive to TRAIL, but not to FasL, depending on DR4/DR5 expression. Fas-associated death domain protein (FADD) and caspase-8, components of death-inducing signaling complex (DISC), as well as FLIP (FLICE [Fas-associating protein with death domain-like interleukin-1-converting enzyme]/caspase-8 inhibitory protein), a negative regulator of caspase-8, were expressed ubiquitously in Ph1-positive leukemia cell lines irrespective of their differential sensitivities to TRAIL and FasL. Notably, TRAIL could induce cell death in the Ph1-positive leukemia cell lines that were refractory to a BCR-ABL-specific tyrosine kinase inhibitor imatinib mesylate (STI571; Novartis Pharma, Basel, Switzerland). These results suggested the potential utility of recombinant TRAIL as a novel therapeutic agent and the possible contribution of endogenously expressed TRAIL to immunotherapy against Ph1-positive leukemias.

Amino Acid Chloromethyl Ketones↗

PubMed2002

Aberrations of the hSNF5/INI1 gene are restricted to malignant rhabdoid tumors or atypical teratoid/rhabdoid tumors in pediatric solid tumors.

The hSNF5/INI1 gene, which encodes a subunit of the SWI/SNF family of chromatin-remodeling complexes and is located at 22q11.2, has been reported as a tumor suppressor gene inactivated in malignant rhabdoid tumors (MRTs). We analyzed this gene in varieties of pediatric solid tumors including MRTs, using the reverse transcription-polymerase chain reaction (PCR) and PCR-single strand conformation polymorphism method. We found 5 homozygous deletions, 2 truncated mutations, one missense mutation, and one silent mutation of the hSNF5/INI1 gene in 7 MRT cell lines, and one homozygous deletion, one microdeletion, one splicing acceptor site mutation, and one absence of expression in 7 fresh tumor tissues of MRT and atypical teratoid (AT)/rhabdoid tumors (RTs). Homozygous deletions were also found in one (KYM-1) of 8 rhabdomyosarcoma (RMS) cell lines. To investigate characteristics of the KYM-1 cell line, we have established KYM-1 tumors in nude mice into which KYM-1 cells were transplanted. Notably, we found that MyoD1, known as a marker for RMS, was not expressed in the KYM-1 cell line as well as MRT cell lines and fresh tumors. Histopathologic, cytogenetic, and molecular studies of the KYM-1 cell line and KYM-1 tumors in nude mice have revealed that this RMS cell line should be MRT rather than RMS. RMS-carrying aberrations of the hSNF5/INI1 gene should be reevaluated. No aberrations of this gene were found in the other 34 cell lines or 80 fresh tumor specimens except the single nucleotide polymorphisms in the 3' noncoding region. These results suggest that alterations of the hSNF5/INI1 gene were restricted to MRTs or AT/RTs in pediatric solid tumors.

Adult↗

PubMed2001

[Erythropoietin Receptor-Mediated Proliferative Signal Transduction in Leukemic Cell Line KOCL-33]

In order to investigate the expression of erythropoietin receptor(EPOR) in leukemic cell line and clarify the mechanism of proliferative signal transduction mediated by EPOR in the leukemic cell line KOCL-33, biotinylated EPO and flow cytometry were used for detection of EPOR expression, (3)H-TdR incoporation for cell proliferation, immunoprecipitation and Western blot analysis were used to investigate the tyrosine phosphorylation of signal transduction proteins as the causation of enhanced proliferation of KOCL-33 cells. There was EPOR expression and the cell proliferation could be stimulated by EPO in KOCL-33 cells. Dimerization and tyrosine phosphorylation of EPOR were found after 1 minute incubated with EPO. Coimmunoprecipitation of SHC and PLC-gamma and enhanced tyrosine phosphorylation following to the stimulation of EPO were found. Our results suggest that dimerization of EPOR and tyrosine phosphorylation were appeared under the stimulation of EPO, and SHC and PLC-gamma play a cooperative effect in EPOR mediated signal tranduction.

Journal Article↗