Preclinical evaluation of microRNA-34b/c delivery for malignant pleural mesothelioma.

The microRNA-34s (miR-34s) have p53 response elements in their 5'-flanking regions and demonstrate tumor-suppressive functions. In malignant pleural mesothelioma (MPM), we previously reported that expression of miR-34b and miR-34c (miR-34b/c) was frequently downregulated by methylation in MPM cell lines and primary tumors. The forced overexpression of miR-34b/c showed significant antitumor effects with the induction of apoptosis in MPM cells.

Anti-cancer effects of REIC/Dkk-3-encoding adenoviral vector for the treatment of non-small cell lung cancer.

Objectives: REIC/Dkk-3 is down-regulated in a broad range of human cancer cells and is considered to function as a tumor suppressor. We previously reported that REIC/Dkk-3-expressing adenovirus vector (Ad-REIC) induced endoplasmic reticulum (ER) stress and cancer-specific apoptosis in human prostate cancer. In this study, we examined the therapeutic impact of Ad-REIC on non-small cell lung cancer (NSCLC).

Large-scale somatotopic refinement via functional synapse elimination in the sensory thalamus of developing mice.

Functional synapse elimination and strengthening are crucial developmental processes in the formation of precise neuronal circuits in the somatosensory system, but the underlying alterations in topographical organization are not yet fully understood. To address this issue, we generated transgenic mice in which afferent fibers originating from the whisker-related brain region, called the maxillary principal trigeminal nucleus (PrV2), were selectively visualized with genetically expressed fluorescent protein. We found that functional synapse elimination drove and established large-scale somatotopic refinement even after the thalamic barreloid architecture was formed.

Behavioral palatability of dietary fatty acids correlates with the intracellular calcium ion levels induced by the fatty acids in GPR120-expressing cells.

We recently reported that G-protein-coupled receptor 120 (GPR120) is expressed on taste buds, and that rodents showed preference for long-chain fatty acids (LCFA) at a low concentration. We also showed that the LCFA (1% linoleic acid) increased the extracellular dopamine (DA) level in the nucleus accumbens (NAc), which participates in reward behavior. However, the mechanism underlying the involvement of the GPR120-agonistic activity of LCFA in the palatability of dietary fat remains elusive.

CD133 is a positive marker for a distinct class of primitive human cord blood-derived CD34-negative hematopoietic stem cells.

The identification of human CD34-negative (CD34(-)) hematopoietic stem cells (HSCs) provides a new concept for the hierarchy in the human HSC compartment. Previous studies demonstrated that CD34(-) severe combined immunodeficiency (SCID)-repopulating cells (SRCs) are a distinct class of primitive HSCs in comparison to the well-characterized CD34(+)CD38(-) SRCs. However, the purification level of rare CD34(-) SRCs in 18 lineage marker-negative (Lin(-)) CD34(-) cells (1/1000) is still very low compared with that of CD34(+)CD38(-) SRCs (1/40).

The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma.

Objectives: Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. microRNA-34b/c (miR-34b/c), which plays an important role in the pathogenesis of MPM, is frequently downregulated by DNA methylation in approximately 90% of MPM cases. In this study, we estimated the degree of miR-34b/c methylation in serum-circulating DNA using a digital methylation specific PCR assay (MSP).

Identification of two novel Shank3 transcripts in the developing mouse neocortex.

SHANK3 is a synaptic scaffolding protein enriched in the post-synaptic density of excitatory synapses. Since several SHANK3 mutations have been identified in a particular phenotypic group of patients with autism spectrum disorder (ASD), SHANK3 is strongly suspected of being involved in the pathogenesis and neuropathology of ASD. Several SHANK3 isoforms are known to be produced in the developing brain, but they have not been fully investigated.

Identification of a glutamic acid repeat polymorphism of ALMS1 as a novel genetic risk marker for early-onset myocardial infarction by genome-wide linkage analysis.

Background: Myocardial infarction (MI) is a leading cause of death worldwide. Given that a family history is an independent risk factor for coronary artery disease, genetic variants are thought to contribute directly to the development of this condition. The identification of susceptibility genes for coronary artery disease or MI may thus help to identify high-risk individuals and offer the opportunity for disease prevention.

[Continuation of chemotherapy with bevacizumab for advanced and recurrent colorectal cancer].

We evaluated the association between the number of treatment courses with the concomitant use of bevacizumab(BV) and the reasons for discontinuation of the regimen in patients who received FOLFOX with or without BV as first-line chemotherapy and FOLFIRI with or without BV as second-line chemotherapy for advanced and recurrent colorectal cancer. In first-line treatment, 12 (2-46) and 10 (2-60) treatment courses were administered with and without BV, respectively, and this difference was not significant (p=0.60).

Association between obesity and Barrett's esophagus in a Japanese population: a hospital-based, cross-sectional study.

Background: The association between obesity and Barrett's esophagus (BE) in the Japanese population remains unclear. The prevalence of BE and its associated risk factors was examined.

Methods: A cross-sectional study of 1581 consecutive individuals who underwent upper gastrointestinal endoscopy was conducted.

Induction of beige-like adipocytes in 3T3-L1 cells.

There are two types of brown adipocytes: classical brown adipocytes that form the brown fat depots and beige adipocytes that emerge in the white fat depots. Beige adipocytes have a low level of uncoupling protein 1 (Ucp1) expression in the basal state, but Ucp1 expression is increased in response to β adrenergic receptor activation. The present study explored the factors responsible for the differentiation of 3T3-L1 white preadipocytes to beige adipocytes.

Role of type II pneumocyte senescence in radiation-induced lung fibrosis.

Background: Radiation is a commonly delivered therapeutic modality for cancer. The causes underlying the chronic, progressive nature of radiation injury in the lung are poorly understood.

Methods: C57Bl/6NCr mice were exposed to thoracic irradiation (n = 3 per dose and time point for tissue collection).

[A search for the risk factors for hiccups and evaluation of antiemetic therapy in CDDP-based chemotherapy, using cluster analysis].

Hiccups are often observed in patients treated with cisplatin(CDDP)-based chemotherapy. It has been reported that gender and specific dosages of CDDP and antiemetic drugs(e.g.

Identification of stable cytotoxic factors in the gas phase extract of cigarette smoke and pharmacological characterization of their cytotoxicity.

Smoking is a major risk factor for atherosclerotic vascular diseases, but the mechanism for its genesis is unknown. We have recently shown that the gas phase of cigarette smoke (nicotine- and tar-free cigarette smoke extract; CSE) likely to reach the systemic circulation contains stable substances which cause cytotoxicity like plasma membrane damage and cell death in cultured cells, and also that the plasma membrane damage is caused through sequential activation of protein kinase C (PKC) and NADPH oxidase (NOX) and the resulting generation of reactive oxygen species (PKC/NOX-dependent mechanism), whereas cell death is caused through PKC/NOX-dependent and -independent mechanisms. To identify these stable substances, the CSE was prepared by passing the main-stream smoke of 10 cigarettes through a Cambridge glass fiber filter, trapping of the smoke in a vessel cooled at -80°C, and subsequent dissolution in 10ml of water.

Theophylline-dependent riboswitch as a novel genetic tool for strict regulation of protein expression in Cyanobacterium Synechococcus elongatus PCC 7942.

The cyanobacterium Synechococcus elongatus PCC 7942 is a major model species for studies of photosynthesis. It is are also a potential cell factory for the production of renewable biofuels and valuable chemicals. We employed engineered riboswitches to control translational initiation of target genes in this cyanobacterium.

Bmp4 expressed in preadipocytes is required for the onset of adipocyte differentiation.

We previously revealed that endogenous bone morphogenetic protein (Bmp) activity is required for lipid accumulation in 3T3-L1 adipocytes. The present study characterized the role of endogenous Bmp activity in preadipocytes. Endogenous Bmp activity was monitored by analyzing the level of phosphorylation of Smad1/5/8, downstream molecules in the Bmp pathway.

Medium modification of jet fragmentation in Au+Au collisions at √[s(NN)]=200 GeV measured in direct photon-hadron correlations.

The jet fragmentation function is measured with direct photon-hadron correlations in p+p and Au+Au collisions at √[s(NN)]=200 GeV. The p(T) of the photon is an excellent approximation to the initial p(T) of the jet and the ratio z(T)=p(T)(h)/p(T)(γ) is used as a proxy for the jet fragmentation function. A statistical subtraction is used to extract the direct photon-hadron yields in Au+Au collisions while a photon isolation cut is applied in p+p.

Regulation of brown adipogenesis by the Tgf-β family: involvement of Srebp1c in Tgf-β- and Activin-induced inhibition of adipogenesis.

Background: Brown adipocytes generate heat through the expression of mitochondrial Ucp1. Compared with the information on the regulatory differentiation of white preadipocytes, the factors affecting brown adipogenesis are not as well understood. The present study examined the roles of the Tgf-β family members Bmp, Tgf-β and Activin during differentiation of HB2 brown preadipocytes.

Phase-locking of oscillating images using laser-induced spin-polarized pulse TEM.

Pulse-mode operation was realized in spin-polarized transmission electron microscopy (SP-TEM) using a laser-driven electron gun with a GaAs-GaAsP strained-layer-superlattice photocathode. TEM images were acquired with a pulsed electron beam with a 5-μs pulse duration. Phase locking of wobbling TEM images was demonstrated using a pulsed beam with a 1-kHz repetition frequency, which matched the image wobbling frequency.

Anomalous systemic arterial supply to the Basal segments of the lung: feasible thoracoscopic surgery.

Background: Anomalous systemic arterial supply to the basal segments of the lung is a rare anomaly. This study aimed to evaluate the outcomes of thoracoscopic surgery for this anomaly.

Methods: We reviewed patients who underwent thoracoscopic surgery for anomalous systemic arterial supply to the basal segments of the lung between October 2007 and September 2012 at our institution.

Clinical outcomes and risk factors for perforation in gastric endoscopic submucosal dissection: A prospective pilot study.

Aim: To evaluate clinical outcomes and risk factors for endoscopic perforation during endoscopic submucosal dissection (ESD) in a prospective study.

Methods: We investigated the clinical outcomes and risk factors for the development of perforation in 98 consecutive gastric neoplasms undergoing ESD regarding. Demographic and clinical parameters including patient-, tumor-, and treatment-related factors, clinical parameters, and duration of hospital stay were analyzed for risk factors for perforation.

Oncological outcomes of thoracoscopic thymectomy for the treatment of stages I-III thymomas.

Objectives: Thoracoscopic thymectomy has gradually replaced conventional sternotomy for resection of thymoma; however, a thoracoscopic approach for thymoma remains controversial. We evaluated the oncological outcomes of thoracoscopic thymectomy for the treatment of stages I-III thymomas.

Methods: Sixty-two patients who underwent thoracoscopic thymectomy for the treatment of thymoma were retrospectively reviewed between July 2005 and September 2011 at Jikei University Hospital.

MEK1/2 inhibition enhances the radiosensitivity of cancer cells by downregulating survival and growth signals mediated by EGFR ligands.

The inhibition of the Ras/mitogen-activated protein kinase (Ras/MAPK) pathway through the suppression of mutated Ras or MAPK/extracellular signal-regulated kinase 1/2 (MEK1/2) has been shown to sensitize tumor cells to ionizing radiation (IR). The molecular mechanisms of this sensitization however, are not yet fully understood. In this study, we investigated the role of transforming growth factor-α (TGF-α) in the radiosensitizing effects of selumetinib, a selective inhibitor of MEK1/2.

Acquired resistance to EGFR inhibitors is associated with a manifestation of stem cell-like properties in cancer cells.

Acquired resistance to EGF receptor (EGFR) tyrosine kinase inhibitor (TKI) is a critical problem in the treatment of lung cancer. Although several mechanisms have been shown to be responsible for acquired resistance, all mechanisms have not been uncovered. In this study, we investigated the molecular and cellular profiles of the acquired resistant cells to EGFR-TKI in EGFR-mutant lung cancers.

Downregulation of microRNA-34 induces cell proliferation and invasion of human mesothelial cells.

Malignant mesothelioma (MM) is an aggressive tumor with a dismal prognosis, and the molecular alterations involved in this disease remain unknown. We previously reported that microRNA-34s (miR-34s) are methylated and downregulated in MM and may play an important role in the carcinogenesis of MM. In this study, we downregulated miR-34s in human mesothelial cells to investigate the cellular effect of miR-34 knockdown.