Biomedical subjects

Yoshio Honma

Publications and source records attributed to Yoshio Honma.

29 records · Page 2Linked to original sources

PubMed2002

Conjugate addition of organosiloxanes to alpha,beta-unsaturated carbonyl compounds catalyzed by a cationic rhodium complex.

[reaction: see text] A novel, additive-free, and clean conjugate addition reaction of organosiloxanes to alpha,beta-unsaturated carbonyl compounds catalyzed by a cationic rhodium complex in water-containing solvent has been developed. A plausible reaction mechanism involving the additive-free transmetalation step between the rhodium complex and the silicon reagent is proposed.

Journal Article↗

PubMed2002

Expression of cell surface NM23 proteins of human leukemia cell lines of various cellular lineage and differentiation stages.

Cell surface expression of NM23 protein is only observed on tumor cell lines, but not on normal cells. To examine what types of tumor cell line express the cell surface NM23 protein, we measured the cell surface NM23-H1 and NM23-H2 proteins of leukemia line cells on various cellular lineage and differentiation stages. The NM23-H1 was expressed on myeloid leukemia lines but not lymphoid lines, while NM23-H2 was only expressed on erythroleukemia lines. The complement-dependent cytolysis confirmed the expression of these proteins on the surface. Surface NM23-H1 and NM23-H2 proteins were decreased during in vitro erythroid and granulocyte differentiation. These results show that the surface expression of NM23 proteins is related to cellular lineage and differentiation stage of leukemia line cells.

Biomarkers, Tumor↗

PubMed2002

Human B-cell lymphoma cell lines are highly sensitive to apoptosis induced by all-trans retinoic acid and interferon-gamma.

When cells were incubated in the presence of both interferon-gamma (IFN-gamma) and all-trans retinoic acid (ATRA), the concentration of IFN-gamma required to induce apoptosis of B-cell lymphoma cells was much lower than that required for myeloid or erythroid cell lines. The concentration of IFN-gamma that effectively inhibited the proliferation of BALM-3 cells was 1/40 of that required for BALM-1 cells. STAT-1 phosphorylation, IRF-1 mRNA and protein expression and RAR-beta expression were enhanced to a greater degree in BALM-3 cells treated with IFN-gamma and ATRA than in BALM-1 cells treated with IFN-gamma and ATRA, suggesting that these IFN-gamma related genes were involved in the induction of apoptosis of BALM-3 cells.

Apoptosis↗

PubMed2002

Role of MmTRA1b/phospholipid scramblase1 gene expression in the induction of differentiation of human myeloid leukemia cells into granulocytes.

OBJECTIVE: We previously cloned a human normal counterpart (MmTRA1b/phospholipid scramblase 1) of the mouse leukemogenesis-associated gene MmTRA1a. MmTRA1b gene expression was increased during differentiation of human monoblastic leukemia U937 cells using some differentiation inducers but not 1alpha,25-dihydroxyvitamin D(3) (a typical monocytic differentiation inducer). To further elucidate the role of human MmTRA1b gene expression in the differentiation of myelogenous leukemia cells, we measured MmTRA1b gene expression in several myeloid leukemia cell lines and primary leukemia cells. MATERIALS AND METHODS: The expression of MmTRA1b mRNA was determined by semiquantitative reverse transcriptase polymerase chain reaction. RESULTS: Expression of the MmTRA1b gene was markedly induced during granulocytic differentiation of promyelocytic leukemia NB4 and HT93 cells induced by all-trans retinoic acid (ATRA). The level of MmTRA1b mRNA was significantly increased during differentiation toward granulocytes, but not monocytes/macrophages, in bipotential myeloid leukemia HL-60 cells. The level of MmTRA1 mRNA was not increased during erythroid differentiation induced by hemin in erythroid leukemia K562 and HEL cells or during megakaryocytic differentiation induced by 12-O-tetradecanoylphorbol-13-acetate in K562 cells. Expression of the MmTRA1b gene also was not induced when apoptosis of NB4 cells was induced by antileukemic drugs. ATRA-induced differentiation of antisense MmTRA1b-transfected NB4 cells was significantly suppressed. On the other hand, ATRA induced the differentiation of MmTRA1b-transfected NB4 cells more efficiently than that of mock-transfected cells. MmTRA1b mRNA also was clearly induced in ATRA-treated primary acute promyelocytic leukemia cells during granulocytic differentiation. CONCLUSION: MmTRA1b mRNA was specifically induced during granulocytic differentiation of acute promyelocytic leukemia cells and was associated with induction of their differentiation.

Ca(2+) Mg(2+)-ATPase↗

PubMed2002

The catalytic DNA topoisomerase II inhibitor ICRF-193 and all-trans retinoic acid cooperatively induce granulocytic differentiation of acute promyelocytic leukemia cells: candidate drugs for chemo-differentiation therapy against acute promyelocytic leukemia.

OBJECTIVE: Although all-trans retinoic acid (ATRA) can bring about complete remission of acute promyelocytic leukemia (APL), the incidence of early recurrence is considerably high. Thus, chemotherapeutic agents, such as anthracycline agents or cytosine arabinoside (AraC), are generally co-administered with ATRA. The therapeutic outcome of APL patients has significantly improved by chemo-differentiation therapy. Late-phase toxicities, such as cardiotoxicity and secondary carcinogenesis, are becoming clinically important. Therefore, we must identify the most suitable chemotherapeutic agents for the treatment of APL. METHODS: We examined the effects of ICRF-193 and several other anticancer drugs on the growth and differentiation of APL cell lines (NB4 and HT-93) and other myeloid leukemia cell lines (HL-60 and U937). RESULTS: If anticancer agents were available that not only inhibited the proliferation of APL cells but also induced their differentiation, they would be very useful for the treatment of APL. DNR slightly induced the differentiation of APL cells. On the other hand, other DNA topoisomerase II inhibitors, such as ICRF-154 and ICRF-193, significantly induced the differentiation of APL cell lines and leukemia cells freshly isolated from APL patients. These drugs effectively cooperated with ATRA in inhibiting the growth and inducing the differentiation of APL cells, whereas DNR did not. The incidence of cardiotoxicity and secondary carcinogenesis associated with ICRF-193 are much lower than that with DNR. CONCLUSION: These results suggest that ICRF-193 may be useful in the treatment of patients with APL.

Antineoplastic Agents↗

PubMed2002

Differentiation of human myeloid leukemia cells by plant redifferentiation-inducing hormones.

Although differentiation therapy for patients with acute promyelocytic leukemia (APL) using all-trans retinoic acid (ATRA) has now been established, acute myeloid leukemia (AML) patients with other than APL only show a limited clinical response to ATRA. We must consider novel therapeutic drugs against other AML to develop a differentiation therapy for leukemia. Regulators that play an important role in the differentiation and development of plants may also affect the differentiation of human leukemia cells through a common signal transduction system, and might be clinically useful for treating AML. Cytokinins are important purine derivatives that serve as hormones that control many processes in plants. Cytokinins such as kinetin, isopentenyladenine (IPA) and benzyladenine were very effective at inducing nitroblue tetrazolium (NBT) reduction and morphological changes in human myeloid leukemia cells into mature granulocytes. On the other hand, cytokinin ribosides such as kinetin riboside, isopentenyladenosine (IPAR) and benzyladenine riboside were the most potent for inhibiting growth and inducing apoptosis. When the cells were incubated with cytokinin ribosides in the presence of an O2- scavenger, antioxidant or caspase inhibitor, apoptosis was significantly reduced and differentiation was greatly enhanced. These results suggest that both cytokinins and cytokinin ribosides can induce the granulocytic differentiation of HL-60 cells, but cytokinin ribosides also induce apoptosis prior to differentiation. Cotylenin A has been isolated as a plant growth regulator exhibits cytokinin-like activity. Although it has a different structure than cytokinins, it also induces the differentiation of human myeloid leukemia cells. These results suggest that there is an association between the action of plant redifferentiation-inducing hormones and the mechanism of the differentiation of human leukemia cells.

Adenine↗

PubMed2002

Cotylenin A--a plant growth regulator as a differentiation-inducing agent against myeloid leukemia.

Acute myeloid leukemia (AML) is characterized by the arrest of differentiation leading to the accumulation of immature cells. This maturation arrest can be reversed by certain agents. Although differentiation therapy for patients with acute promyelocytic leukemia (APL) using all-trans retinoic acid (ATRA) has been established, the clinical response of AML patients other than those with APL to ATRA is limited. We must consider novel therapeutic drugs against other forms of AML for the development of a differentiation therapy for leukemia. Regulators that play an important role in the differentiation and development of plants or invertebrates may also affect the differentiation of human leukemia cells through a common signal transduction system, and might be clinically useful for treating AML. Cotylenin A, a plant growth regulator, is a potent and novel inducer of the monocytic differentiation of human myeloid leukemia cell lines and leukemia cells freshly isolated from AML patients.

Animals↗

PubMed2002

Effects of hibarimicins and hibarimicin-related compounds produced by Microbispora on v-Src kinase activity and growth and differentiation of human myeloid leukemia HL-60 cells.

We studied the effects of hibarimicins and hibarimicin-related compounds produced by Microbispora rosea subsp. hibaria [glycosides (hibarimicins A, B, C, D, E, G, H and I) and aglycon (hibarimicinone)] or compounds produced by its mutants [glycosides (HMP-P4 and -Y6), aglycons (HMP-P1 and -Y1) and shunt products (HMP-M1, M2, M3 and -M4)] on v-Src tyrosine kinase and growth and differentiation of human myeloid leukemia HL-60 cells. Among them, hibarimicin B was a strong and the most selective v-Src kinase inhibitor with differentiation inducing activity of HL-60 cells. Hibarimicin E similarly induced HL-60 cell differentiation but had no v-Src kinase inhibitory activity. Hibarimicinone was the most potent v-Src kinase inhibitor, although less selective, and did not induce differentiation of HL-60 cells. Hibarimicin B competitively inhibited ATP binding to the v-Src kinase, but hibarimicinone showed noncompetitive inhibition. These two compounds, however, showed similar mixed types of inhibition against a Src substrate binding to the v-Src kinase. Altogether, these results suggest that signaling molecules other than Src might be more important in the differentiation induction of HL-60 cells.

Actinomycetales↗

PubMed2002

Androgen-dependent hereditary mouse keratoconus: linkage to an MHC region.

PURPOSE: To better understand the pathogenesis of hereditary keratoconus, an inbred line of spontaneous mutant mice with keratoconus-affected corneas (SKC mice) was established and studied with a multidisciplinary approach. METHODS: Using a mutant mouse with corneas having a keratoconical appearance as the progenitor, an inbred line of SKC mouse was established by repeated sibling mating. Morphology, cell growth, apoptosis and protein expression of SKC mouse corneas were examined. Castration of males and androgen treatment for females were conducted to determine any androgen dependency of the phenotype. Linkage analysis was conducted to reveal the responsible or predisposing gene of SKC mouse keratoconus. RESULTS: Corneas of the SKC mouse resemble those of human eyes with keratoconus. Both are conical and show similar corneal changes, including apoptosis of keratocytes and increased expression of c-fos protein. The SKC mouse phenotype was transmitted in an autosomal recessive manner, although it was observed almost exclusively in males. Intriguingly, female mice showed the phenotype when injected with testosterone, whereas male incidence of the phenotype diminished drastically when mice were castrated. Linkage analysis localized a predisposition locus to an MHC region on mouse chromosome 17, which includes a locus for the gene for sex-limited protein (Slp). CONCLUSIONS: SKC mouse keratoconus is a potential model for a subset of human keratoconus, which is a disease entity with heterogeneous pathogeneses. Alternatively, SKC mouse keratoconus could be a model for other human or mouse-specific keratopathies.

Animals↗

PubMed2002

Control of differentiation and apoptosis of human myeloid leukemia cells by cytokinins and cytokinin nucleosides, plant redifferentiation-inducing hormones.

We examined the effects of various adenine analogues on the growth and differentiation of human myeloid leukemia HL-60 cells. Some of these analogues inhibit growth and induce nitroblue tetrazolium reducing activity in HL-60 cells. Cytokinins such as kinetin, isopentenyladenine, and benzyladenine were very effective in inducing nitroblue tetrazolium reduction and morphological changes in the cells into mature granulocytes. On the other hand, cytokinin ribosides such as kinetin riboside, isopentenyladenosine, and benzylaminopurine riboside were the most potent for growth inhibition and apoptosis. Cytokinin ribosides greatly reduced the intracellular ATP content and disturbed the mitochondrial membrane potential and the accumulation of reactive oxygen species, whereas cytokinins did not. When the cells were incubated with cytokinin ribosides in the presence of O(2)(-) scavenger, antioxidant or caspase inhibitor, apoptosis was significantly reduced and differentiation was greatly enhanced. These results suggest that both cytokinins and cytokinin ribosides can induce granulocytic differentiation of HL-60 cells, but cytokinin ribosides also induce apoptosis prior to the differentiation process.

Adenosine↗

PubMedDate not supplied

Induction of apoptosis by combined treatment with differentiation-inducing agents and interferon-alpha in human lung cancer cells.

BACKGROUND: Differentiation-inducing agents for myeloid leukemic cells, such as dimethyl sulfoxide (DMSO), Na-butyrate and hexamethylene-bis-acetamide (HMBA), barely induce irreversible differentiation or growth inhibition in solid tumors when used alone. However, we previously reported that combined treatment with differentiation-inducing agents and interferon (IFN)-alpha effectively suppressed the growth of human lung cancer cell lines in vitro and in vivo. We show here that combined treatment-induced cell death is caused by apoptosis. MATERIALS AND METHODS: Induction of apoptosis was examined by expression of several apoptotic markers. RESULTS: Combined treatment-induced cell death is caused by apoptosis, which is characterized by the induction of apoptotic morphological changes and the activation of caspase-3-like protease. The expression of Apo2.7, an early apoptotic change, is also induced by this combined treatment, and is suppressed by the addition of Z-Asp-CH2-DCB, a pan caspase inhibitor. The signal transduction pathway of IFN-alpha is rapidly observed in lung cancer cells, although it does not induce significant growth inhibition when used alone. We analyzed the effect of IFN-alpha on the apoptotic pathway and found that IFN-alpha but not DMSO induces the expression of caspase-4. The combination of IFN-alpha and DMSO did not cause further increase in the expression of caspase-4. In many cases of the induction of apoptosis, cytochrome c is released from mitochondria, which induces the formation of large caspase-activating complexes. Caspase-3-like-activities induced by the combination of DMSO or Na-butyrate with IFN-alpha were analyzed by gel filtration and detected equally in fractions with molecular weights of 200-300 kDa, suggesting that caspase-3 is activated in large complexes in lung cancer cells. However, Na-butyrate and HMBA, when used alone, induced the release of cytochrome c and enhanced the loss of mitochondrial membrane potential, whereas DMSO had no effect. CONCLUSION: These results suggest that the combination of differentiation-inducing agents with IFN-alpha effectively induces apoptosis in lung cancer cells whereas the mechanism of such induction varies depending on the differentiation-inducing agent used.

Acetamides↗