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Yoshio Honma

Publications and source records attributed to Yoshio Honma.

At least 19 recordsLinked to original sources
PubMed2006

Cotylenin A-induced differentiation is independent of the transforming growth factor-beta signaling system in human myeloid leukemia HL-60 cells.

Cotylenin A, which has been isolated as a plant growth regulator, potently induces the differentiation of human myeloid leukemia cells. Treatment of HL-60 cells with a combination of transforming growth factor (TGF)-beta and 1alpha, 25-dihydroxyvitamin D(3) (VD3) resulted in increased differentiation compared to separate treatments, but TGF-beta did not affect the cotylenin A-induced differentiation of HL-60 cells. It is possible that the signal transduction pathway used by cotylenin A for inducing the differentiation of leukemia cells is the same as that used by TGF-beta. However, cotylenin A did not affect the expression of TGF superfamily or Smad genes in HL-60 cells. Treatment with neutralizing anti-TGF-beta antibody or an inhibitor of TGF-beta signaling did not inhibit cotylenin A-induced differentiation, although VD3-induced differentiation was significantly suppressed by these treatments. The subcellular distribution of Smad3 was also unaffected by cotylenin A. These results suggest that the cotylenin A-induced differentiation of leukemia cells is independent of the TGF-beta signaling system, although TGF-beta acts as an autocrine mediator of the growth arrest and differentiation of leukemia cells induced by VD3 and other inducers.

Cell Differentiation↗
PubMed2005

Effects of combined treatment with rapamycin and cotylenin A, a novel differentiation-inducing agent, on human breast carcinoma MCF-7 cells and xenografts.

INTRODUCTION: Rapamycin, an inhibitor of the serine/threonine kinase target of rapamycin, induces G1 arrest and/or apoptosis. Although rapamycin and its analogues are attractive candidates for cancer therapy, their sensitivities with respect to growth inhibition differ markedly among various cancer cells. Using human breast carcinoma cell line MCF-7 as an experimental model system, we examined the growth-inhibitory effects of combinations of various agents and rapamycin to find the agent that most potently enhances the growth-inhibitory effect of rapamycin. METHOD: We evaluated the growth-inhibitory effect of rapamycin plus various agents, including cotylenin A (a novel inducer of differentiation of myeloid leukaemia cells) to MCF-7 cells, using either MTT assay or trypan blue dye exclusion test. The cell cycle was analyzed using propidium iodide-stained nuclei. Expressions of several genes in MCF-7 cells with rapamycin plus cotylenin A were studied using cDNA microarray analysis and RT-PCR. The in vitro results of MCF-7 cells treated with rapamycin plus cotylenin A were further confirmed in vivo in a mouse xenograft model. RESULTS: We found that the sensitivity of rapamycin to MCF-7 cells was markedly affected by cotylenin A. This treatment induced growth arrest of the cells at the G1 phase, rather than apoptosis, and induced senescence-associated beta-galactosidase activity. We examined the gene expression profiles associated with exposure to rapamycin and cotylenin A using cDNA microarrays. We found that expressions of cyclin G2, transforming growth factor-beta-induced 68 kDa protein, BCL2-interacting killer, and growth factor receptor-bound 7 were markedly induced in MCF-7 cells treated with rapamycin plus cotylenin A. Furthermore, combined treatment with rapamycin and cotylenin A significantly inhibited the growth of MCF-7 cells as xenografts, without apparent adverse effects. CONCLUSION: Rapamycin and cotylenin A cooperatively induced growth arrest in breast carcinoma MCF-7 cells in vitro, and treatment with rapamycin and cotylenin A combined more strongly inhibited the growth of MCF-7 cells as xenografts in vivo than treatment with rapamycin or cotylenin A alone, suggesting that this combination may have therapeutic value in treating breast cancer. We also identified several genes that were markedly modulated in MCF-7 cells treated with rapamycin plus cotylenin A.

Animals↗
PubMed2005

Antitumor effect of cotylenin A plus interferon-alpha: possible therapeutic agents against ovary carcinoma.

OBJECTIVE: Recently, we found that cotylenin A and IFNalpha synergistically inhibited growth both in vitro and in vivo, and induced apoptosis in human cancer cells. For the clinical application of this combined treatment, suitable cancer targets should be selected. METHODS: We examined the combined effects of these compounds on various types of cancer cells by a human cancer cell line panel assay, and on cancer cells that had been freshly isolated from patients in three-dimensional cultures embedded in collagen gel. RESULTS: In the analysis of 39 cancer cell lines, ovarian cancer cells were highly sensitive to combined treatment with cotylenin A and IFNalpha in inhibiting cell growth. This treatment was also effective toward ovarian cancer cells that were refractory to CDDP, and significantly inhibited the growth of ovarian cancer cells as xenografts without apparent adverse effects. Ovarian cancer cells from the patients were also sensitive to the combined treatment in primary cultures. CONCLUSION: Combined treatment with cotylenin A and IFNalpha may have therapeutic value in treating ovarian cancer.

Adult↗
PubMed2005

Nuclear DNA but not mtDNA controls tumor phenotypes in mouse cells.

Recent studies showed high frequencies of homoplasmic mtDNA mutations in various human tumor types, suggesting that the mutated mtDNA haplotypes somehow contribute to expression of tumor phenotypes. We directly addressed this issue by isolating mouse mtDNA-less (rho(0)) cells for complete mtDNA replacement between normal cells and their carcinogen-induced transformants, and examined the effect of the mtDNA replacement on expression of tumorigenicity, a phenotype forming tumors in nude mice. The results showed that genome chimera cells carrying nuclear DNA from tumor cells and mtDNA from normal cells expressed tumorigenicity, whereas those carrying nuclear DNA from normal cells and mtDNA from tumor cells did not. These observations provided direct evidence that nuclear DNA, but not mtDNA, is responsible for carcinogen-induced malignant transformation, although it remains possible that mtDNA mutations and resultant respiration defects may influence the degree of malignancy, such as invasive or metastatic properties.

Animals↗
PubMed2005

Immediate up-regulation of the calcium-binding protein S100P and its involvement in the cytokinin-induced differentiation of human myeloid leukemia cells.

Cytokinins are important purine derivatives that act as redifferentiation-inducing hormones to control many processes in plants. Cytokinins such as isopentenyladenine (IPA) and kinetin are very effective at inducing the granulocytic differentiation of human myeloid leukemia HL-60 cells. We examined the gene expression profiles associated with exposure to IPA using cDNA microarrays and compared the results with those obtained with other inducers of differentiation, such as all-trans retinoic acid (ATRA), 1 alpha,25-dihydroxyvitamin D3 (VD3) and cotylenin A (CN-A). Many genes were up-regulated, and only a small fraction were down-regulated, upon exposure to the inducers. IPA and CN-A, but not ATRA or VD3, immediately induced the expression of mRNA for the calcium-binding protein S100P. The up-regulation of S100P was confirmed at the protein expression level. We also examined the expression of other S100 proteins, including S100A8, S100A9 and S100A12, and found that IPA preferentially up-regulated S100P at the early stages of differentiation. IPA-induced differentiation of HL-60 cells was suppressed by treatment with antisense oligonucleotides against S100P, suggesting that S100P plays an important role in cell differentiation.

Adenine↗
PubMed2005

Clinical significance of serum NM23-H1 protein in neuroblastoma.

We have previously reported that NM23 genes are overexpressed in various hematological malignancies and that serum NM23-H1 protein levels are useful for predicting patient outcomes. In this study we assessed the clinical implications of serum NM23-H1 protein on neuroblastoma. We examined serum NM23-H1 protein levels in 217 patients with neuroblastoma, including 131 found by mass-screening and 86 found clinically by an enzyme-linked immunosorbent assay, and determined the association between levels of this protein, and known prognostic factors or the clinical outcome. The serum NM23-H1 protein level was higher in neuroblastoma patients than in control children (P < 0.0001). Patients with MYCN amplification had higher serum NM23-H1 levels than those with a single copy of MYCN. Overall survival was assessed in the 86 patients found clinically, and was found to be worse in patients with higher serum MN23-H1 levels (> or = 250 ng/mL) than in those with lower levels (< 250 ng/mL; P = 0.034). The higher level of NM23-H1 was correlated with a worse outcome in patients with a single MYCN copy, or in those younger than 12 months of age. Serum NM23-H1 protein levels may contribute to predictions of clinical outcome in patients with neuroblastoma.

Age Factors↗
PubMed2005

Induction of CCAAT/enhancer binding protein-delta by cytokinins, but not by retinoic acid, during granulocytic differentiation of human myeloid leukaemia cells.

Cytokinins, purine derivatives that act as hormones to control many processes in plants, are very effective at inducing the granulocytic differentiation of human myeloid leukaemia cells. Isopentenyladenine (IPA), a potent cytokinin, significantly induced the expression of CCAAT/enhancer-binding protein (C/EBP)delta, but not C/EBP alpha protein, whereas all-trans retinoic acid, a well-known inducer of granulocytic differentiation, induced C/EBP alpha but not C/EBP delta protein. Antisense oligonucleotide for C/EBP delta, but not C/EBP alpha or C/EBP beta, effectively suppressed IPA-induced differentiation, suggesting that the expression of C/EBP delta protein is necessary for cytokinin-induced differentiation. Although C/EBP alpha is known to be crucial for granulocytic differentiation, the function of C/EBP delta has not been well documented in the regulation of haematopoiesis. The role of C/EBP delta in the granulocytic differentiation of myeloid leukaemia cells is discussed.

Adenine↗
PubMed2004

Selective activation of vitamin D receptor by lithocholic acid acetate, a bile acid derivative.

The vitamin D receptor (VDR), a member of the nuclear receptor superfamily, mediates the biological actions of the active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3). It regulates calcium homeostasis, immunity, cellular differentiation, and other physiological processes. Recently, VDR was found to respond to bile acids as well as other nuclear receptors, farnesoid X receptor (FXR) and pregnane X receptor (PXR). The toxic bile acid lithocholic acid (LCA) induces its metabolism through VDR interaction. To elucidate the structure-function relationship between VDR and bile acids, we examined the effect of several LCA derivatives on VDR activation and identified compounds with more potent activity than LCA. LCA acetate is the most potent of these VDR agonists. It binds directly to VDR and activates the receptor with 30 times the potency of LCA and has no or minimal activity on FXR and PXR. LCA acetate effectively induced the expression of VDR target genes in intestinal cells. Unlike LCA, LCA acetate inhibited the proliferation of human monoblastic leukemia cells and induced their monocytic differentiation. We propose a docking model for LCA acetate binding to VDR. The development of VDR agonists derived from bile acids should be useful to elucidate ligand-selective VDR functions.

Animals↗
PubMed2004

Clinical significance of intracytoplasmic nm23-H1 expression in diffuse large B-cell lymphoma.

PURPOSE: Recently, we established an ELISA technique for measuring nm23-H1 protein in serum and found that the serum nm23-H1 level is a potential prognostic factor for patients with non-Hodgkin's lymphoma. EXPERIMENTAL DESIGN: We used immunohistochemistry to examine the expression of nm23-H1 by the lymphoma cells in patients with diffuse large B-cell lymphoma (DLBCL). RESULTS: By analyzing a consecutive series of 172 untreated DLBCL patients, we found that 100 (58.1%) were strongly positive. The cytoplasmic nm23 expression in lymphoma cells correlated significantly with the serum nm23-H1 level. There was a significant correlation between patients with cytoplasmic nm23-positive lymphoma and those with performance status 2-4, stage III/IV, bulky mass, B symptoms, elevated serum level of soluble interleukin 2 receptor, and elevated serum level of C-reactive protein. Overall and progression-free survival rates were significantly lower in patients with nm23-H1-positive lymphomas than in those with nm23-H1-negative lymphomas. Similar difference was seen between patients with high and low serum levels of nm23-H1. Thus, the correlation between presence or absence of cytoplasmic nm23-H1 expression and serum nm23-H1 levels suggests that serum nm23-H1 is produced directly by lymphoma cells. CONCLUSION: We suggest that nm23-H1 expression is a prognostic factor for DLBCL, and that it is as important as serum nm23-H1, both of which are useful for planning a treatment strategy.

Adolescent↗
PubMed2004

MmTRA1b/phospholipid scramblase 1 gene expression is a new prognostic factor for acute myelogenous leukemia.

We previously found that expression of the Mm-1 cell-derived transplantability-associated gene 1b (MmTRA1b)/phospholipid scramblase 1 gene was markedly induced during the granulocytic differentiation of human myeloid leukemia cells. To evaluate the role of MmTRA1b expression in human myeloid leukemia, we investigated the relative levels of MmTRA1b transcripts in 81 patients with acute myelogenous leukemia (AML) by the reverse transcriptase polymerase chain reaction. The expression of MmTRA1b in AML-M1, -M5a and -M5b was significantly lower than that in normal bone marrow cells. The levels of MmTRA1b expression in AML-M2 and -M4 varied among patients. Higher MmTRA1b mRNA levels were associated with significantly longer overall survival in AML, especially in AML-M4 patients, independent of chromosomal aberrations such as t(8;21) and inv(16). The present results suggest that the MmTRA1b mRNA level is a new prognostic factor for AML, especially the AML-M4 subtype.

Adult↗
PubMed2004

Granulocytic differentiation of leukemic cells with t(9;11)(p22;q23) induced by all-trans-retinoic acid.

Acute leukemia patients with MLL (mixed linage leukemia) rearrangements tend to respond poorly to conventional therapies. We examined differentiation of human myeloid leukemia cells displaying the MLL-AF9 gene, using several differentiation agents. When MOLM-14 cells were treated with all-trans retinoic acid (ATRA) or 1beta,25-dihydroxyvitamin D3, significant induced differentiation was observed. Trichostatin A (TSA), an inhibitor of histone deacetylase, demonstrated enhance effects with ATRA in regard to growth inhibition and differentiation induction in MOLM-14 cells. Pretreatment with TSA before exposure to ATRA displayed increased effect. Based on these findings, combined treatment with ATRA and TSA may be clinically useful in therapy for acute leukemia displaying MLL-AF9 fusion gene.

Acute Disease↗
PubMed2003

Cytokinin-induced differentiation of human myeloid leukemia HL-60 cells is associated with the formation of nucleotides, but not with incorporation into DNA or RNA.

Cytokinins are important purine derivatives that act as hormones to control many processes in plants. Cytokinins such as isopentenyladenine (IPA), kinetin and benzyladenine were very effective at inducing the granulocytic differentiation of human myeloid leukemia HL-60 cells. The metabolism of cytokinins to their nucleotides was closely associated with cytokinin-induced differentiation and growth inhibition. When the cells were incubated with [14C]-benzyladenine, radioactivity was significantly incorporated into RNA and DNA. However, the radioactive nucleotides in RNA or DNA were adenine nucleotides, not benzyladenine nucleotides, suggesting that cytokinins were not incorporated into RNA and DNA. The benzyladenine nucleotides were not stably released into the medium in intact form. Cytokinins effectively induced a phosphorylated (active) form of mitogen-activated protein kinase (MAPK). MAPK activation was necessary for cytokinin-induced differentiation, because PD98059, an inhibitor of MAPK kinase, suppressed the differentiation induced by cytokinins. These results suggest that cytokinin nucleotides themselves play an important role in inducing the differentiation of HL-60 cells.

Adenine↗
PubMed2003

Cotylenin A, a differentiation-inducing agent, and IFN-alpha cooperatively induce apoptosis and have an antitumor effect on human non-small cell lung carcinoma cells in nude mice.

Cotylenin A, a novel inducer of the differentiation of leukemia cells, and IFN-alpha synergistically inhibited the growth of and induced apoptosis in several human non-small cell lung carcinoma cell lines. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor DR5 were the early genes induced by the combination of cotylenin A and IFN alpha in lung carcinoma cells. Neutralizing antibody to TRAIL inhibited apoptosis, suggesting that cotylenin A and IFN alpha cooperatively induced apoptosis through the TRAIL signaling system. This combined treatment preferentially induced apoptosis in human lung cancer cells while sparing normal lung epithelial cells and significantly inhibited the growth of human lung cancer cells as xenografts without apparent adverse effects, suggesting that this combination may have therapeutic value in treating lung cancer.

Animals↗
PubMed2003

Asymmetric 1,4-addition of organosiloxanes to alpha,beta-unsaturated carbonyl compounds catalyzed by a chiral rhodium complex.

Highly enantioselective 1,4-addition of organosiloxanes to alpha,beta-unsaturated carbonyl compounds was found to be catalyzed by a chiral rhodium complex generated from [Rh(cod)(MeCN)(2)]BF(4) and (S)-BINAP. Both (E)- and (Z)-1-alkenyl groups as well as aryl groups can be introduced enantioselectively into the beta-position of a variety of ketones, esters, and amides. [reaction--see text]

Journal Article↗
PubMed2003

Treatment of human promyelocytic leukemia in the SCID mouse model with cotylenin A, an inducer of myelomonocytic differentiation of leukemia cells.

Cotylenin A has differentiation-inducing activity in human myeloid leukemia cell lines and leukemic cells that were freshly isolated from acute myeloid leukemia (AML) patients in primary culture. Injection of the human promyelocytic leukemia cell line NB4 into SCID mice resulted in the death of all mice due to leukemia. Administration of cotylenin A significantly prolonged the survival of mice inoculated with NB4 cells. In an in vivo analysis, cotylenin A induced the differentiation of leukemia cells in a retinoid-resistant leukemia model. Cotylenin A may be useful for differentiation therapy of retinoid-resistant leukemia.

Animals↗
PubMed2003

Elevated levels of cyclin A1 and A (A2) mRNA in acute myeloid leukaemia are associated with increased survival.

Cyclin A (A2) and cyclin A1 are members of the G2 cyclins, which are involved in the control of G2/M and G1/S transitions as well as mitosis. Human cyclin A1 was cloned as an A-type cyclin that is highly expressed in acute myeloid leukaemia (AML). The clinical significance of these cyclins in myeloid leukaemia remains to be clarified. We investigated the relative levels of these transcripts in 80 patients with de novo AML. Correlations with clinical parameters showed that the initial white blood cell count and serum lactate dehydrogenase levels were inversely associated with cyclin A (A2) mRNA levels (r = -0.276, P = 0.019) and cyclin A1 mRNA levels (r = -0.241, P = 0.042) respectively. They were independently associated with increased overall survival [P = 0.035 for cyclin A (A2) and P = 0.016 for cyclin A1]. Multivariate analysis using Cox's proportional hazard model showed that elevated cyclin A1 mRNA levels contributed significantly to the better prognosis of patients with AML. Furthermore, the analysis of survival probability showed that the group with high levels of both cyclin A (A2) and A1 survived significantly longer than the group with low expression of both these cyclins (P = 0.002). These data indicate that high expression levels of both cyclin A (A2) and A1 are associated with good prognosis in AML patients.

Acute Disease↗
PubMed2003

Expression of nm23-H1 is associated with poor prognosis in peripheral T-cell lymphoma.

We have reported previously that the serum nm23-H1 level is a prognostic factor for non-Hodgkin's lymphoma. In this study, we examined nm23-H1 expression in T- and natural killer (NK)-cell lymphoma in order to evaluate whether lymphoma cells produce the protein. The clinical significance of the cytotoxic molecules, T-cell intracellular antigen-1 (TIA-1) and granzyme B and nm23-H1 expression were also examined. Expression of nm23-H1, TIA-1, or granzyme B was examined by immunohistochemistry in 137 previously untreated lymphoma patients. The relationship between the results and clinical outcome was examined in 81 patients with angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, or peripheral T-cell lymphoma, unspecified. The neoplastic cells of some lymphomas produced nm23-H1 and the expression rates of nm-23-H1, TIA-1 and granzyme B were 36.5%, 78.8% and 32.8% respectively. The nm23-H1-positive or TIA-1-positive groups had significantly shorter overall and disease-free survivals. Multivariate analysis confirmed nm23-H1 expression to be an independent prognostic factor. The nm23-H1 protein can be an important prognostic factor in the lymphomas studied here. New treatments that target nm23 overexpression could be developed as a result of nm23-HI production by lymphoma cells.

Adult↗