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Kiyoshi Hiruma

Publications and source records attributed to Kiyoshi Hiruma.

25 records · Page 2Linked to original sources
PubMed2003

Insights into the molecular basis of the hormonal control of molting and metamorphosis from Manduca sexta and Drosophila melanogaster.

This short review summarizes our current knowledge about the role of transcription factors regulated by ecdysteroids and juvenile hormone (JH) in larval molting and metamorphosis in the tobacco hornworm, Manduca sexta, and Drosophila melanogaster. We show new evidence that EcR-A/USP-2 and E75A contribute to the down-regulation of MHR3 after the peak of ecdysteroid. Also, there is suggestive evidence that both MHR4 and betaFTZ-F1 may regulate the expression of dopa decarboxylase as the ecdysteroid titer declines. We summarize the regulation by JH of the Broad transcription factor that normally appears in the epidermis in the final larval instar and specifies pupal cuticle formation at the metamorphic molt. Premature expression of different Broad isoforms also is shown to cause precocious degeneration of the prothoracic glands as well as to prevent ecdysteroid release during its presence.

Animals↗
PubMed2003

A novel gene in the takeout gene family is regulated by hormones and nutrients in Manduca larval epidermis.

A novel gene, moling, was cloned from epidermal RNA of the tobacco hornworm, Manduca sexta, using PCR-based suppression subtractive hybridization. moling belongs to a gene family that includes several lepidopteran hemolymph juvenile hormone (JH) binding proteins and takeout of Drosophila melanogaster. The mRNA first appears in the epidermis on day 0 of the fifth instar and rises to its peak expression by mid-day 2, then declines rapidly and is gone by the onset of wandering. moling is expressed exclusively in the last instar larval epidermis and not in the imaginal discs or any other tissues. Allatectomy early in the fourth instar induces precocious metamorphosis and causes the appearance of moling mRNA by 33 h. Allatectomy after the critical period for JH in the final larval molt had no effect on the timing of the onset of moling expression in the final instar but caused a more rapid up-regulation once begun. The JH mimic pyriproxifen given at the outset of the final instar suppressed the expression of moling mRNA to low levels, in both intact and allatectomized larvae. Starvation immediately after ecdysis to the fifth instar prevented the onset of expression. Thus, initiation of transcription requires both nutrient intake and decline in JH. Infusion of 20-hydroxyecdysone (20E) into ligated abdomens of day 2 fifth instar larvae and culture of the day 2 fifth instar larval abdominal epidermis with 20E in vitro both caused a rapid decline of moling mRNA. The slower and variable decline that occurred in mid-day 2 fifth instar larval epidermis in the ligated abdomens or when incubated in hormone-free medium indicated that the increase of 20E on day 2 had already initiated the decline of expression. The role of Moling may be to stabilize JH in the epidermal cell during the final intermolt when the JH esterase activity increases.

Abdomen↗
PubMed2003

[Sustained remission of MDS overt leukemia associated with abrupt discontinuation of immunosuppression following relapse after the second course of allogeneic hematopoietic stem cell transplantation].

The case of a 32-year-old female with relapsed myelodysplastic syndrome (MDS) after second course of allogeneic transplantation is described. The peripheral blood stem cell transplantation was performed as early as 3 months after the initial bone marrow transplantation because of rejection and relapse; however, the patient again relapsed 2 months later. Immediate discontinuation of cyclosporine resulted in the progression of pancytopenia and the development of high fever, liver dysfunction and skin eruption. The patient was then treated with dexamethasone, which successfully stabilized these symptoms. After these clinical events, a dramatic hematological response was obtained; the blast rate was reduced from 10.6 to 0% in bone marrow aspiration, and pancytopenia was restored to normal levels. Moreover, fluorescence in situ hybridization analyses with X and Y chromosome-specific probes revealed that hematopoietic precursor cells were predominantly of donor origin. The patient subsequently received donor lymphocyte infusion (DLI) from the original donor. Currently, 2 years after DLI, the patient continues to be in remission.

Adult↗
PubMedDate not supplied

Impact of vasculogenesis on solid tumor growth in a rat model.

Peripheral stem cells released from bone marrow (BM) are known to be incorporated into foci of neovascularization and to contribute to solid tumor development. In the present rat Walker256 tumor model, BM suppression induced by total body irradiation resulted in poor growth of the tumor with apparently poor vascularization, and BM transplantation restored tumor growth. Endothelial progenitor cells are considered to be crucial for vasculogenesis, but they are not yet well defined, and methodology for their purification has not been established. As a model to examine the significance of endothelial progenitor cells in tumor-specific vasculogenesis, we utilized an immortalized rat BM-derived endothelial cell line named TR-BME-2. Fluorescence-labeled TR-BME-2 cells injected systemically into rats were accumulated at the tumor site 4 days later. Another rat BM-derived cell line named C2-11, which does not have an endothelial profile, did not show tumor-specific accumulation. The tumor volume in rats treated with TR-BME-2 was significantly larger than that in rats treated with C2-11. Thus, our results suggest the importance of neovascularization by bone marrow-derived endothelial cells for the promotion of tumor growth.

Animals↗
PubMedDate not supplied

Study of cancer gene therapy using IL-12-secreting endothelial progenitor cells in a rat solid tumor model.

To test the hypothesis that genetically modified bone marrow-derived endothelial progenitor cells (EPCs) can be effective carriers of therapeutic agents to tumor sites, we utilized our conditionally immortalized endothelial progenitor cell line, TR-BME-2. In the syngenic rat, systemically injected TR-BME-2 cells were immediately distributed to the organs (lung, bone marrow, peripheral blood, liver, spleen). Trapped cells were cleared within 4 days, but selective accumulation in the Walker256 tumor was maintained for over 4 days. The tumor growth was enhanced by administration of TR-BME-2 cells. It is suggested that accumulated TR-BME-2 differentiated to tumor vasculature, increased the tumor blood supply, and thereby increased the tumor volume. We conducted IL-12 gene transfection of TR-BME-2 cells with a virus vector in vitro, and used the resultant IL-12-secreting TR-BME-2 to deliver IL-12, which strongly activates cytotoxic lymphocytes and natural killer cells, to the tumor site in vivo. However, the tumor-progressive character of TR-BME-2 offset the anti-tumor effect of IL-12. Nevertheless, our results suggest that gene-transfected EPCs could be useful as a tumor-specific drug delivery system, especially if the tumor vasculature-promoting effect of EPCs can be blocked.

Animals↗