TAS4464, a NEDD8-activating enzyme inhibitor, activates both intrinsic and extrinsic apoptotic pathways via c-Myc-mediated regulation in acute myeloid leukemia.

TAS4464, a potent, selective small molecule NEDD8-activating enzyme (NAE) inhibitor, leads to inactivation of cullin-RING E3 ubiquitin ligases (CRLs) and consequent accumulations of its substrate proteins. Here, we investigated the antitumor properties and action mechanism of TAS4464 in acute myeloid leukemia (AML). TAS4464 induced apoptotic cell death in various AML cell lines.

Ascl2-Dependent Cell Dedifferentiation Drives Regeneration of Ablated Intestinal Stem Cells.

Ablation of LGR5 intestinal stem cells (ISCs) is associated with rapid restoration of the ISC compartment. Different intestinal crypt populations dedifferentiate to provide new ISCs, but the transcriptional and signaling trajectories that guide this process are unclear, and a large body of work suggests that quiescent "reserve" ISCs contribute to regeneration. By timing the interval between LGR5 lineage tracing and lethal injury, we show that ISC regeneration is explained nearly completely by dedifferentiation, with contributions from absorptive and secretory progenitors.

Dynamic Reorganization of Chromatin Accessibility Signatures during Dedifferentiation of Secretory Precursors into Lgr5+ Intestinal Stem Cells.

Replicating Lgr5 stem cells and quiescent Bmi1 cells behave as intestinal stem cells (ISCs) in vivo. Disrupting Lgr5 ISCs triggers epithelial renewal from Bmi1 cells, from secretory or absorptive progenitors, and from Paneth cell precursors, revealing a high degree of plasticity within intestinal crypts. Here, we show that GFP cells from Bmi1 mice are preterminal enteroendocrine cells and we identify CD69CD274 cells as related goblet cell precursors.

Development of electrolyte-free ozone sensors using boron-doped diamond electrodes.

The electrochemical detection of dissolved ozone in water was examined using boron-doped diamond (BDD) electrodes. A well-defined reduction peak was observed at ~380 mV for H-terminated BDD, whereas it was observed at ~200 mV in the case of O-terminated BDD for an ozone solution in a 0.1 M phosphate buffer solution at pH 7.

Randomized controlled trial comparing antioxidant-enriched enteral nutrition with immune-enhancing enteral nutrition after esophagectomy for cancer: a pilot study.

Purpose: The objective of this study was to compare the effects of two types of enteral supplements, an antioxidant-enriched enteral nutrition (AeEN) and an immune-enhancing enteral nutrition (IeEN), on the nutrition, immunoinflammatory response, antioxidant capacity and clinical outcomes in patients after esophagectomy for cancer.

Methods: Patients (n = 20) undergoing esophagectomy for cancer were randomized in this single-center, open-label study. Two types of enteral supplements were used for 5 days before surgery and 7 days after surgery.

Proliferation and harvest of human mesenchymal stem cells using new thermoresponsive nanocomposite gels.

For tissue engineering and regenerative medicine, stem cells should be effectively cultured in vitro. New thermoresponsive nanocomposite gels (MD-NC gels), consisting of inorganic clay (hectorite) and copolymers composed of hydrophobic 2-methoxyethyl acrylate (MEA) and hydrophilic N,N-dimethylacrylamide (DMAA) units, could be applied in cell culture and cell harvesting without trypsinization, specifically using mesenchymal stem cells (MSCs). The composition of the MD-NC gel (the ratio of the two monomer types and the clay content) was found to determine its swelling properties in the culture medium, thermosensitivity, protein adsorption, and cell attachment and proliferation.

Esophagectomy for thoracic esophageal cancer with a double aortic arch: report of a case.

We report the case of a 50-year-old man with a double aortic arch who underwent esophagectomy for cancer in the middle thoracic esophagus at clinical Stage IIA (T3N0M0), based on the TNM classification (UICC 2002). The patient underwent esophagectomy with three-field lymphadenectomy following neoadjuvant chemotherapy. In such a case, it is important to recognize the anatomy in the upper mediastinum, especially the relationship between the right and left aortic arch, and the recurrent laryngeal nerves using computed tomography (CT) and three-dimensional CT.

Thermoresponsible cell adhesion/detachment on transparent nanocomposite films consisting of poly(2-methoxyethyl acrylate) and clay.

Soft, transparent and mechanically tough nanocomposite (M-NC) films composed of poly(2-methoxyethyl acrylate) (PMEA) and inorganic clay (hectorite) were studied as substrates for a living cell harvest system. It was found that five cell types could all be cultivated to confluence on the surface of M-NC n films with clay content (n = 10-23 wt%), although the cells hardly cultivated on the surface of chemically-cross-linked PMEA and linear PMEA films. Further, it was found that the cells cultured on the surfaces of M-NC films can be detached, without any enzymatic digestion, by decreasing the medium temperature and/or simultaneously using gentle pipetting.

Photodynamic therapy for large superficial squamous cell carcinoma of the esophagus.

Background: Photodynamic therapy (PDT) has been found to be safe and effective in patients with small early esophageal squamous cell carcinoma (SCC). However, its efficacy for widespread superficial SCC has not yet been confirmed.

Objective: To assess the long-term survival, complications, and recurrence of PDT for large superficial esophageal SCC.

Histone H3 lysine 4 methylation is associated with the transcriptional reprogramming efficiency of somatic nuclei by oocytes.

Background: When the nuclei of mammalian somatic cells are transplanted to amphibian oocytes in the first meiotic prophase, they are rapidly induced to begin transcribing several pluripotency genes, including Sox2 and Oct4. The more differentiated the donor cells of the nuclei, the longer it takes for the pluripotency genes to be activated after the nuclear transfer to oocytes. We have used this effect in order to investigate the role of histone modifications in this example of nuclear reprogramming.

A p53-dependent checkpoint pathway prevents rereplication.

Eukaryotic cells control the initiation of DNA replication so that origins that have fired once in S phase do not fire a second time within the same cell cycle. Failure to exert this control leads to genetic instability. Here we investigate how rereplication is prevented in normal mammalian cells and how these mechanisms might be overcome during tumor progression.

v-Crk activates the phosphoinositide 3-kinase/AKT pathway by utilizing focal adhesion kinase and H-Ras.

v-Crk, an oncogene product of avian sarcoma virus CT10, efficiently transforms chicken embryo fibroblasts (CEF). We have recently reported that constitutive activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway plays a critical role in the v-Crk-induced transformation of CEF. In the present study we investigated the molecular mechanism by which v-Crk activates the PI3K/AKT pathway.