Genome-wide combination profiling of copy number and methylation offers an approach for deciphering misregulation and development in cancer cells.

Copy number changes and DNA methylation alterations are crucial to gene regulation in mammals. Recently, a number of microarray studies have been based on copy number and DNA methylation alterations in order to find clinical biomarkers of carcinogenesis. In this study, we attempted to combine profiles of copy number and methylation patterns in four human cancer cell lines using BAC microarray-based approaches and we detected several clinically important genes which showed genetic and epigenetic relationships.

Cyclooxygenase-2 promotes cell proliferation, migration and invasion in U2OS human osteosarcoma cells.

Osteosarcoma is the most common primary bone tumor, but the pathogenesis is not well understood. While cyclooxygeanse-2 (COX-2) is known to be closely associated with tumor growth and metastasis in several kinds of human tumors, the function of COX-2 in osteosarcoma is unclear. Therefore, to investigate the function of COX-2 in osteosarcoma, we established stable cell lines overexpressing COX-2 in U2OS human osteosarcoma cells.

Relationship between parathyroid hormone and cardiac abnormalities in chronic dialysis patients.

Background: It has been shown that parathyroid hormone (PTH) influences cardiac abnormalities in dialysis patients. The purpose of this study was to evaluate the relationship between the plasma PTH level and cardiac abnormalities in these patients without overt cardiac disease.

Methods: A total of 81 of the 208 patients who received chronic dialysis treatment at our institution were included in this study.

p-Coumaric acid inhibits indoleamine 2, 3-dioxygenase expression in murine dendritic cells.

Indoleamine 2, 3-dioxygenase (IDO), a key enzyme that catalyses the initial and rate-limiting step in the degradation of the tryptophan, is simultaneously expressed in murine dendritic cells and macrophages stimulated with interferon-gamma (IFN-gamma). In the present study, we investigated whether p-Coumaric acid (CA), which is suggested to exhibit antioxidant properties, could suppress the functional expression of IDO in murine bone marrow-derived dendritic cells (BMDCs) stimulated with IFN-gamma. Treatment with CA reduced intracellular expression of IDO mRNA and protein levels in IFN-gamma-activated murine BMDCs in vitro and in CD11c(+)CD8alpha(+) DCs of tumor-draining lymph node (TDLN) of tumor-bearing mice in vivo.

Neuronal loss in primary long-term cortical culture involves neurodegeneration-like cell death via calpain and p35 processing, but not developmental apoptosis or aging.

Primary neuronal culture is a powerful tool to study neuronal development, aging, and degeneration. However, cultured neurons show signs of cell death after 2 or 3 weeks. Although the mechanism underlying this phenomenon has not been elucidated, several preventive methods have been identified.

Hypoxic condition- and high cell density-induced expression of Redd1 is regulated by activation of hypoxia-inducible factor-1alpha and Sp1 through the phosphatidylinositol 3-kinase/Akt signaling pathway.

Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. In the present study, we demonstrated that the expression of Redd1 in response to hypoxia (1% O(2)), hypoxia-mimetic agent, cobalt chloride (CoCl(2)) and high cell density (HCD) requires coactivation of HIF-1alpha and Sp1. CoCl(2) and HCD induced the activation of HIF-1alpha and Sp1 in HeLa cells, and siRNAs targeting HIF-1alpha and Sp1 abrogated Redd1 expression.

Rosmarinic acid inhibits indoleamine 2,3-dioxygenase expression in murine dendritic cells.

Indoleamine 2,3-dioxygenase (IDO), a key enzyme that catalyses the initial and rate-limiting step in the degradation of the tryptophan, is simultaneously expressed in murine dendritic cells and macrophages stimulated with interferon-gamma (IFN-gamma). In the present study, we investigated whether rosmarinic acid (RA), which is suggested to exhibit anti-oxidant and anti-cyclooxygenase properties, could suppress the functional expression of IDO in murine bone marrow-derived dendritic cells (BMDCs) stimulated with IFN-gamma. Treatment with RA reduced intracellular expression of IDO both in IFN-gamma-activated BMDCs in vitro and in CD11c(+)CD8alpha(+) DCs in vivo tumor-bearing mice model.

Hypoxia-induced cell death of HepG2 cells involves a necrotic cell death mediated by calpain.

To elucidate mechanism of cell death in response to hypoxia, we attempted to compare hypoxia-induced cell death of HepG2 cells with cisplatin-induced cell death, which has been well characterized as a typical apoptosis. Cell death induced by hypoxia turned out to be different from cisplatin-mediated apoptosis in cell viability and cleavage patterns of caspases. Hypoxia-induced cell death was not associated with the activation of p53 while cisplatin-induced apoptosis is p53 dependent.

D-pinitol regulates Th1/Th2 balance via suppressing Th2 immune response in ovalbumin-induced asthma.

D-pinitol has been demonstrated to exert insulin-like and anti-inflammatory activities. However, its anti-allergic effect in the Th1/Th2 immune response is poorly understood. Recently, it was shown that T-bet and GATA-3 are master Th1 and Th2 regulatory transcription factors.

Enhanced lung cancer cell killing by the combination of selenium and ionizing radiation.

Selenium has been associated with anticancer activity by affecting multiple cellular processes. We reasoned that the simultaneous modulation of multiple radioresponse regulators by selenium should increase radiosensitivity if selenium is combined with radiation in cancer therapy. Therefore, we explored the possibility of whether we could obtain an enhancement of radiosensitivity by the combination of selenium and ionizing radiation.

Analysis of double stranded DNA-dependent activities of Deinococcus radiodurans RecA protein.

In this study, the double-stranded DNA-dependent activities of Deinococcus radiodurans RecA protein (Dr RecA) were characterized. The interactions of the Dr RecA protein with double-stranded DNA were determined, especially dsDNA-dependent ATP hydrolysis by the Dr RecA protein and the DNA strand exchange reaction, in which multiple branch points exist on a single RecA protein-DNA complex. A nucleotide cofactor (ATP or dATP ) was required for the Dr RecA protein binding to duplex DNA.

Decomposition of biological macromolecules by plasma generated with helium and oxygen.

In this study, we attempted to characterize the biomolecular effects of an atmospheric pressure cold plasma (APCP) system which utilizes helium/oxygen (He/O(2)). APCP using He/O(2) generates a low level of UV while generating reactive oxygen radicals which probably serve as the primary factor in sterilization; these reactive oxygen radicals have the advantage of being capable to access the interiors of the structures of microbial cells. The damaging effects of plasma exposure on polypeptides, DNA, and enzyme proteins in the cell were assessed using biochemical methods.

Synergistic induction of apoptosis by sulindac and arsenic trioxide in human lung cancer A549 cells via reactive oxygen species-dependent down-regulation of survivin.

Survivin, a member of the inhibitor of apoptosis protein (IAP) family, may be a good target for cancer therapy because it is expressed in a variety of human tumors but not in differentiated adult tissues. In the present study, we show that a combination of sulindac and arsenic trioxide (ATO) induces more extensive apoptosis than either drug alone in A549 human non-small cell lung carcinoma (NSCLC) cells. Treatment with sulindac/ATO reduced the expression of survivin and promoted major apoptotic signaling events, namely, collapse of the mitochondrial membrane potential, release of cytochrome c, and activation of caspases.

Implication of ADAM-8, -9, -10, -12, -15, -17, and ADAMTS-1 in implantational remodeling of a mouse uterus.

In the present study, whether the ADAM-8, -9, -10, -12, -15, -17, and ADAMTS-1 proteins might play a role in mouse uterus during periimplantation period was investigated. Immunoblotting analyses demonstrated that all ADAM proteins consistently appeared throughout days 1 to 8 of pregnancy but with a variation depending on the species of ADAM gene, the progression of pregnancy, and the site of the uterus. Immunohistochemical analyses indicated that ADAM proteins were localized in the luminal or glandular epithelial layers with a varying intensity depending on the species of ADAM and the progression of pregnancy.

Inhibitory effect of insulin on vasopressin-induced intracellular calcium response is blunted in hyperinsulinemic hypertensive patients: role of membrane fatty acid composition.

Impaired insulin-mediated vasodilation has been implicated in hypertension that is associated with the metabolic syndrome. The aim of this study was to determine whether an abnormality in membrane fatty acid composition was related to a weakening of insulin's inhibitory effect on agonist-stimulated intracellular free calcium elevation. Mild to moderate hypertensive patients (n = 27) and normotensive controls (n = 11) were studied.

The role of tonicity responsive enhancer sites in the transcriptional regulation of human hsp70-2 in response to hypertonic stress.

The inducible 70 kDa heat shock proteins (Hsp70) in mice are encoded by two almost identical genes, hsp70.1 and hsp70.3.

Intestinal protozoan infections and echinococcosis in the inhabitants of Dornod and Selenge, Mongolia (2003).

The status of intestinal parasitic infections and seroprevalence of cystic echinococcosis in the inhabitants in Dornod and Selenge, Mongolia, was observed with stool and serum samples from 165 and 683 residents from August 9 to August 15, 2003. A total of 10 inhabitants (6.1%) were found to be infected with protozoan cysts or oocysts by stool examinations; 7, 1 and 2 cases with Entamoeba coli, Giardia lamblia and Cryptosporidium parvum, respectively.

Transforming growth factor-beta1 regulates macrophage migration via RhoA.

Brief treatment with transforming growth factor (TGF)-beta1 stimulated the migration of macrophages, whereas long-term exposure decreased their migration. Cell migration stimulated by TGF-beta1 was markedly inhibited by 10 mug/mL Tat-C3 exoenzyme. TGF-beta1 increased mRNA and protein levels of macrophage inflammatory protein (MIP)-1alpha in the initial period, and these effects also were inhibited by 10 mug/mL Tat-C3 and a dominant-negative (DN)-RhoA (N19RhoA).

Heat shock protein 25 or inducible heat shock protein 70 activates heat shock factor 1: dephosphorylation on serine 307 through inhibition of ERK1/2 phosphorylation.

The expression of heat shock proteins (HSPs) is known to be increased via activation of heat shock factor 1 (HSF1), and excess expression of HSPs exerts feedback inhibition of HSF1. However, the molecular mechanism to modulate such relationships between HSPs and HSF1 is not clear. In the present study, we show that stable transfection of either Hsp25 or inducible Hsp70 (Hsp70i) increased expression of endogenous HSPs such as HSP25 and HSP70i through HSF1 activation.

Downstream components of RhoA required for signal pathway of superoxide formation during phagocytosis of serum opsonized zymosans in macrophages.

Rac1 and Rac2 are essential for the control of oxidative burst catalyzed by NADPH oxidase. It was also documented that Rho is associated with the superoxide burst reaction during phagocytosis of serum- (SOZ) and IgG-opsonized zymosan particles (IOZ). In this study, we attempted to reveal the signal pathway components in the superoxide formation regulated by Rho GTPase.

Effects of acupuncture on potential along meridians of healthy subjects and patients with gastric disease.

The purpose of this study was to investigate the differences in bio-potential in the stomach meridians of 20 normal healthy control subjects (NHC) and 20 patients with gastric disease (PGD). We measured changes in potential between ST-39 and ST-37 on the stomach meridian in response to invasive insertion of a needle at ST-36. The response patterns of NHC were regular in both the left and right meridians, whereas the response patterns of PGD were irregular.

HSP90 protects apoptotic cleavage of vimentin in geldanamycin-induced apoptosis.

Heat shock protein (HSP) 90 is of interest as an anticancer drug target because of its importance in maintaining the conformation, stability and function of the client proteins involved in signal transduction pathways leading to proliferation, cell cycle progression, and apoptosis. Geldanamycin, a specific antagonist of HSP90, binds directly to HSP90 and promotes proteolytic degradation of client proteins of HSP90. The aim of the present study was to identify novel client proteins of HSP90 and to elucidate HSP90 function through inhibition of HSP90 binding to its client proteins, by using of geldanamycin.

p21WAF/CIP1/SDI1 is upregulated due to increased mRNA stability during hydroxyurea-induced senescence of human fibroblasts.

Hydoxyurea induces senescence-like growth arrest in normal human fibroblasts. p21(WAF/CIP1/SDI1), a cyclin dependent kinase inhibitor, was found to be upregulated during this growth arrest. Levels of p21(WAF/CIP1/SDI1) protein and mRNA were increased nine-fold by hydroxyurea in these cells.

COX-2 inhibits anoikis by activation of the PI-3K/Akt pathway in human bladder cancer cells.

Cyclooxygenase-2 (COX-2) has been reported to be associated with tumor development and progression as well as to protect cells from apoptosis induced by various cellular stresses. Through a tetracycline-regulated COX-2 overexpression system, we found that COX-2 inhibits detachment-induced apoptosis (anoikis) in a human bladder cancer cell line, EJ. We also found that the inhibition of anoikis by COX-2 results from activation of the PI-3K/Akt pathway as evidenced by suppression of the COX-2 effect on anoikis by a PI-3K inhibitor, LY294002.

Characterization of calcium-activated bifunctional peptidase of the psychrotrophic Bacillus cereus.

The protease purified from Bacillus cereus JH108 has the function of leucine specific endopeptidase. When measured by hydrolysis of synthetic substrate (N-succinyl-Ala-Ala-Pro-Leu-p-nitroanilide), the enzyme activity exhibited optimal activity at pH 9.0, 60 degrees C.