Injectable extracellular matrix hydrogels contribute to native cell infiltration in a rat partial nephrectomy model.

Decellularized extracellular matrix (dECM) hydrogels have cytocompatibility, and are currently being investigated for application in soft tissues as a material that promotes native cell infiltration and tissue reconstruction. A dECM hydrogel has broad potential for application in organs with complex structures or various tissue injury models. In this study, we investigated the practical application of a dECM hydrogel by injecting a kidney-derived dECM hydrogel into a rat partial nephrectomy model. The prepared dECM hydrogel was adjustable in viscosity to allow holding at the excision site, and after gelation, had an elastic modulus similar to that of kidney tissue. In addition, the migration of renal epithelial cells and vascular endothelial cells embedded in dECM hydrogels was observed in vitro. Four weeks after injection of the dECM hydrogel to the partial excision site of the kidneys, infiltration of renal tubular constituent cells and native cells with high proliferative activity, as well as angiogenesis, were observed inside the injected areas. This study is the first to show that dECM hydrogels can be applied to the kidney, one of the most complex structural organs and that they can function as a scaffold to induce angiogenesis and infiltration of organ-specific renal tubular constituent cells, providing fundamental insights for further application of dECM hydrogels.

[Operational management in our hospice ward-from the viewpoint of supporting a patient's recuperation at home].

Although many terminally ill cancer patients desire to receive medical treatment in palliative care units(PCUs or hospices), very few patients are actually able to receive such treatment. Our aim is to provide palliative care to as many people as possible. We have practiced palliative care in general wards and prioritized care according to the patient's prognosis on admission to our hospice. From April 2007 to March 2011, 87% patients were admitted to our hospital in accordance with their wishes. By adequate management of hospital wards, including PCUs, and unitizing the health resources of the area, terminally ill cancer patients may be able to spend more time at home prior to hospitalization.

MM-1 facilitates degradation of c-Myc by recruiting proteasome and a novel ubiquitin E3 ligase.

We have reported that a novel c-Myc-binding protein, MM-1, repressed the E-box-dependent transcription activity of c-Myc by recruiting the HDAC1 complex via TIF1beta/KAP1, a transcriptional corepressor. We have also reported that a mutation of A157R in MM-1, which is often observed in patients with leukemia or lymphoma, abrogated all of the repressive activities of MM-1 toward c-Myc, indicating that MM-1 is a novel tumor suppressor. In this study, we found that MM-1 was bound to a component of proteasome and stimulated degradation of c-Myc in human cells. Knockdown of endogenous MM-1 in human HeLa cells by introduction of siRNA against MM-1 stabilized the endogenous c-Myc. To identify proteins that participate in c-Myc degradation by MM-1, in vivo and in vitro binding assays were carried out. The results showed that MM-1 directly bound to Rpt3, a subunit of 26S proteasome, and that c-Myc directly bound to Skp2, which recruited ElonginC, ElonginB and Cullin2, thereby forming a novel ubiquitin E3 ligase. Knockdown of endogenous Cullin2 stabilized the endogenous c-Myc. Thus, MM-1 is a factor that connects c-Myc to the ubiquitin E3 ligase and the proteasome.

Repression of the c-fms gene in fibroblast cells by c-Myc-MM-1-TIF1beta complex.

MM-1 has been reported to repress the E-box-dependent transcription activity of c-Myc by recruiting histone deacetylase 1 complex via TIF1beta/KAP1. In this study, to identify target genes for c-Myc-MM-1-TIF1beta, we established rat-1 cells harboring the dominant-negative form of TIF1beta to abrogate the pathway from TIF1beta to MM-1-c-Myc. This cell line, in which transcription activity of c-Myc was activated, was found to be tumorigenic. By DNA-microarray analysis of this cell line, expression and promoter activity of the c-fms oncogene were found to be upregulated. Of the two promoters, pE1 and pE2, in the c-fms gene, pE1 promoter activity was found to be activated in an E-box-dependent manner.