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 intratracheal lung cancer development by systemic delivery of E1A

Amplification or overexpression of HER-2/neu in human lung cancer has been correlated with poor prognosis and chemoresistance. We have previously reported that the adenovirus type 5 early region 1A (E1A) gene product can suppress HER-2/neu-mediated transformation phenotypes through inhibition of HER-2/neu expression. To find an efficient way to treat HER-2/neu-overexpressing lung cancer with E1A, a replication-deficient adenovirus containing the E1A gene, Ad.E1A(+), was used to transduce E1A into HER-2/neu-overexpressing and low expressing human lung cancer cell lines. Tumour cell growth in vitro and colony formation in soft agarose were greatly inhibited by Ad.E1A(+) transduction in HER-2/neu-overexpressing lung cancer cell lines. In HER-2/neu low expressing cell lines, E1A could not inhibit cell growth in vitro but could reduce the colony formation ability in soft agarose, indicating different effects of E1A in these two types of cancer cells. To test the therapeutic efficacy of E1A to lung cancer by systemic delivery in vivo, tumor-bearing mice were established by intratracheal injection of lung cancer cells and treated by i.v. tail injections of Ad.E1A(+). As a result, Ad.E1A(+) suppressed HER-2/neu overexpression and inhibited intratracheal lung cancer growth. However, no significant tumor suppression effect of Ad.E1A(+) was observed in mice bearing HER-2/neu low expressing cell line when the same therapeutic procedure was followed. Thus, we conclude that systemic delivery of Ad.E1A(+) can efficiently achieve therapeutic effect in HER-2/neu-overexpressing lung cancer in vivo.     

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.     

Neurological complications of radiotherapy and chemotherapy

Neurological complications of radiotherapy and chemotherapy can affect the central or peripheral nervous system. Most are dose-dependent and constitute a limiting factor in the administration of treatments. Radiation-induced neurological complications are classified as acute, early-delayed or delayed. The most important are radionecrosis and cognitive dysfunction/leukoencephalopathy. Neurotoxicity of chemotherapy is frequent and depends upon dose, type of drugs (especially cisplatin and methotrexate) and their combination with radiotherapy.     

SCID-Hu mouse as a model for human lung HIV-1 infection

HIV induces a multi-organ infection with a dual tropism for both lymphocytes and monocytes/macrophages. The lung is a target both for HIV infection and HIV-related opportunistic infections. The SCID mouse has provided the opportunity to develop a small animal model for HIV infection. However, HIV-1 infection of the human fetal thymus and liver (SCID Liv/Thy) implanted in these mice occurred only after direct intraimplant injection of HIV-1 and the resultant HIV-1 infection was restricted to the human thymus. Here we report that human foetal lung can develop in SCID Liv/Thy mice resulting in the development of normal human alveolar and bronchiolar lung compartments which can be productively infected with cell-free HIV-1 virus, leading to a systemic and bifocal infection. This SCID-Hu model should be useful for studying AIDS physiopathology, human viruses with lung tropism and for helping to define gene therapy protocols in lung human cells in vivo.     

3-D shape from a shaded and textural surface image

A new 3D texture model is developed by considering the scene image as the superposition of a random texture image on a smooth shaded image. The whole image is analyzed using a patch-by-patch process. Each patch is assumed to be a tilted and slanted texture plane. A modified reflectance map function is applied to describe the deterministic part, and the fractional differencing periodic model is chosen to describe the random texture because of its good performance in texture synthesis and its ability to represent the coarseness and the pattern of the surface at the same time. An orthographical projection technique is developed to deal with this particular random model, which has a nonisotropically distributed texture pattern. For estimating the parameter, a hybrid method that uses both the least square and the maximum-likelihood estimates is applied directly to the given intensity function. By using these parameters, the synthesized image is obtained and used to reconstruct the original image     

Lysis of human monocytic leukemia cells by extracellular adenosine triphosphate: mechanism and characterization of the adenosine triphosphate receptor

The present study shows that extracellular adenosine triphosphate (ATP) has the capacity to mediate dose-dependent lysis of the monocytic leukemia cell line THP-1. The lysis, assessed by 51Cr release, was found to be selective for ATP, because adenosine diphosphate (ADP) or other nucleotides were less effective in their ability to lyse the cells. The amount of 51Cr released was particularly enhanced by the stimulation of the cells with 1,000 U/mL of interferon gamma (IFN-gamma) for 3 days, and the sensitivity was time and dose dependent. Analysis of the mechanism of lysis indicated that the fully ionized form, ATP4-, mediated the lysis, because the addition of cation chelators or the absence of the divalent cations, Ca2+ and Mg2+, in the culture medium of a 6-hour 51Cr release assay increased the percent specific lysis. Therefore, the ATP receptors on THP-1 cells were classified as P2Z purinoceptors. Moreover, it is shown here that the Ca2+/calmodulin complex plays a role in the regulation of the lysis by extracellular ATP of THP-1 cells, because antagonists of this complex, such as trifluoperazine or KN-62, were found to inhibit the ATP-mediated cell lysis.     

Effect of maturation on alpha-adrenoceptor activity in newborn piglet mesentery

To characterize the mesenteric alpha1- and alpha2-adrenoceptor populations in newborn piglets, an extracorporeal circuit was established to control intestinal blood flow in 0- to 2-day old and 10- to 14-day old animals. In both groups, alpha-adrenoceptor activation was first documented by observing dose-dependent increases in mesenteric perfusion pressure after intramesenteric arterial injection of alpha-adrenoceptor agonists. In the 10- to 14-day old piglets, mesenteric vasoconstrictor responses to alpha1-adrenoceptor agonists (methoxamine and norepinephrine) and an alpha2-adrenoceptor agonist (BHT-933) were each blunted (P < 0.05, analysis of variance) by peripheral intravenous injections of prazosin (an alpha1-adrenoceptor antagonist) and yohimbine (an alpha2-adrenoceptor antagonist), respectively. The mesenteric vasoconstrictor responses to those agonists were not significantly attenuated by prazosin or yohimbine in 0- to 2-day old animals, nor were they blunted by YM-12617 (alpha1-adrenoceptor antagonist) or idazoxan (alpha2-adrenoceptor antagonist)--compounds that are structurally unrelated to prazosin and yohimbine, respectively. In addition, mesenteric vasoconstrictor responses to other known vasoconstrictor agents--angiotensin II, neuropeptide Y, and a thromboxane A2 mimic (U-46619)--were not effected in either age group by prazosin or yohimbine, implying these agents act independently of alpha-adrenoceptor mechanisms. These data suggest that (1) there exists functional mesenteric alpha1- and alpha2-adrenoceptor-like activity in 10- to 14-day old piglets that, in 0- to 2-day old animals, is not specifically expressed; and (2) mesenteric alpha-adrenoceptor function becomes more selective as newborn piglets mature.