AQP3 Increases Intercellular Cohesion in NSCLC A549 Cell Spheroids through Exploratory Cell Protrusions

Tumor cell aggregation is critical for cell survival following the loss of extracellular matrix attachment and dissemination. However, the underlying mechanotransduction of clustering solitary tumor cells is poorly understood, especially in non-small cell lung cancers (NSCLC). Here, we examined whether cell surface protrusions played an important role in facilitating the physical contact between floating cells detached from a substrate. We employed poly-2-hydroxyethyl methacrylate-based 3D culture methods to mimic in vivo tumor cell cluster formation. The suprastructural analysis of human NSCLC A549 cell spheroids showed that finger-like protrusions clung together via the actin cytoskeleton. Time-lapse holotomography demonstrated that the finger-like protrusions of free-floating cells in 3D culture displayed exploratory coalescence. Global gene expression analysis demonstrated that the genes in the organic hydroxyl transport were particularly enriched in the A549 cell spheroids. Particularly, the knockdown of the water channel aquaporin 3 gene (AQP3) impaired multicellular aggregate formation in 3D culture through the rearrangement of the actomyosin cytoskeleton. Moreover, the cells with reduced levels of AQP3 decreased their transmigration. Overall, these data indicate that cell detachment-upregulated AQP3 contributes to cell surface protrusions through actomyosin cytoskeleton remodeling, causing the aggressive aggregation of free-floating cells dependent on the property of the substratum and collective metastasis.     

Inhibition of 2-nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate

We observed that pretreatment of male F344 rats with benzyl selenocyanate, a versatile organoselenium chemopreventive agent in several animal model systems, decreases the levels of DNA and RNA modifications produced in the liver by the hepatocarcinogen 2-nitropropane. To clarify the mechanisms involved, we pretreated male F344 rats with either benzyl selenocyanate, its sulfur analog benzyl thiocyanate, phenobarbital or cobalt protoporphyrin IX; the latter is a depletor of P450. We then determined (1) the ability of liver microsomes to denitrify 2-nitropropane, (2) effects on 2-nitropropane-induced liver DNA and RNA modifications and (3) amount of nitrate excreted in rat urine following administration of the carcinogen. Pretreatment with benzyl selenocyanate or phenobarbital increased the denitrification activity of liver microsomes by 217 and 765%, respectively, increased liver P4502B1 by 31- and 435-fold, respectively, decreased the levels of 2-nitropropane-induced modifications in liver DNA (29-70% and 17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and increased the 24-h urinary excretion of nitrate by 157 and 209%, respectively. Pretreatment with benzyl thiocyanate had no significant effect on any of these parameters. Pretreatment with cobalt protoporphyrin IX decreased liver P4502B 1 by 87%, decreased the denitrification activity of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate by 88.5%, but increased the extent of 2-nitropropane-induced liver nucleic acid modifications by 17-67%. These results indicate that the metabolic sequence from 2-nitropropane to the reactive species causing DNA and RNA modifications does not involve the removal of the nitro group. Moreover, they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic acid modifications in part by increasing its detoxication through induction of denitrification, although it is evident that other mechanisms must also be involved.     

The organisational learning effects of management accounting information under advanced manufacturing technology

This study empirically examined the organisational learning effects of the nonfinancial performance information provided by management accounting information systems (MAISs) under advanced manufacturing technology (AMT). In this study, a target costing system and the frequent and quick reporting of information were considered the facilitators of learning. First, we examined the relationships between AMT level and the amount of nonfinancial performance information produced by MAISs. The empirical results showed that there are significant positive relationships between the level of AMT and nonfinancial performance information. With a systems approach, we also proved the impact of the relationships among AMT levels, nonfinancial performance information and learning facilitators on the organisational performance of a firm. The results of our research suggest that under a high level of AMT, for the provision of information to result in an increase of performance through organisational learning, a target costing system must be introduced and a large amount of information should be provided frequently and quickly. The results of this study also showed that although AMT level may be low, fairly well-arranged facilitators and a moderately large amount of information may be necessary for the improvement of performance. In conclusion, effective organisational learning depends on the provision of relevant information as well as efficient learning support mechanisms.     

Robust autoregressive predictive power control method for mobile CDMA systems

A closed-loop power control (CLPC) scheme with a multistep (indicating multiple prediction steps) linear autoregressive predictor is presented. The proposed CLPC relies on low-rate sample vector based autoregressive prediction. Compared to currently available predictive CLCP schemes, it demonstrates particularly robust performance in the presence of large loop delays and channel estimation errors.     

Colosplenic fistula in a patient treated with interleukin-2 for malignant melanoma

Interleukin-2 (IL-2) therapy often causes gastrointestinal side effects and at least 8 cases of bowel perforation have been reported. The patient reported here developed a colosplenic fistula, diagnosed by CT, with no neoplastic involvement of these organs. Awareness of these complications of IL-2 can help lead to earlier diagnosis.     

Immunostimulatory DNA: sequence-dependent production of potentially harmful or useful cytokines

Certain bacterial immunostimulatory (i.s.) DNA sequences containing unmethylated CpG motifs stimulate antigen-presenting cells (APC) to express a full complement of costimulatory molecules and to produce cytokines including interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha. While IL-12 is key to their T helper cell (Th)1-promoting adjuvant activity, secretion of toxic levels of TNF-alpha is harmful in that it promotes toxic shock. Given the beneficial as well as harmful consequences of i.s. DNA, we investigated the possibility of identifying DNA sequences, i.e. CpG oligodeoxynucleotides (ODN) which differentially activate IL-12 versus TNF-alpha cytokine production in APC. Here, we describe an i.s. DNA sequence with these characteristics. While its potential to induce IL-12 is preserved, its ability to trigger TNF-alpha release is strongly curtailed both in vitro and in vivo. I.s. DNA could be segregated into lethal and non-lethal in a mouse toxic shock model. The non-toxic i.s. DNA was useful as an adjuvant, thus allowing cytotoxic T cell responses to the soluble protein ovalbumin and conferring a resistant Th 1 phenotype to BALB/c mice lethally infected with Leishmania major. This i.s. CpG motif may thus be prototypic for a useful immunostimulating DNA sequence that lacks harmful side effects.     

Mutagenic and antimutagenic activities of human whole blood, plasma and albumin

The seeds of Crepis capillaris were used to examine the mutagenic und antimutagenic properties of human whole blood, plasma, serum albumin and gamma-globulin by recording chromosomal and chromatid aberrations. The antimutagenic activity was determined by preliminary, simultaneous, and subsequent biosubstrate treatments of the seeds. The whole and twice-diluted blood, as well as plasma, induced aberrations exceeding the level of self-arbitrary mutagenesis by 3.7-5.3 and 2.6-3.1 times, respectively. When the blood was diluted to its 20% concentration, the antimutagenic efficiency of biological fluids was recorded. Human serum albumin and gamma-globulin were found to have an antimutagenic effect. In the dilutions having no antimutagenic effect, blood, plasma, and albumin showed their ability to be effectively decrease the level of induced aberrations.     

The effects of treatment with PIXY321 (GM-CSF/IL-3 fusion protein) on human polymorphonuclear leukocyte function

During a phase I trial of the genetically engineered hematopoietic growth factor PIXY321 (granulocyte-macrophage colony-stimulating factor/interleukin-3 [IL-3] fusion protein), we examined the effects of PIXY321 treatment on human polymorphonuclear leukocyte (PMN) locomotive, respiratory burst, and phagocytic responses. PIXY321 treatment was associated with transient suppression of both unstimulated locomotion and chemotaxis responses to multiple stimuli, as well as significant transient enhancement of formyl peptide-stimulated H2O2 production. No effects on opsonic phagocytosis of Staphylococcus aureus were observed. In vitro exposure of control PMN to PIXY321 resulted in suppression of unstimulated locomotion/chemotaxis and enhancement of formyl peptide-stimulated H2O2 production but had no effects on phagocytosis. When patient cells were exposed in vitro to PIXY321 during treatment, suppression of chemotaxis and enhancement of H2O2 production were observed before PIXY321 treatment, but these effects diminished during treatment. The in vivo and in vitro exposure effects of PIXY321 treatment on PMN function are similar to those of the parent molecule, granulocyte-macrophage colony-stimulating factor (GM-CSF).