NK4, a four-kringle antagonist of HGF, inhibits spreading and invasion of human pancreatic cancer cells

Because of the highly aggressive behaviour, i.e. invasive, disseminative and metastatic properties, the outcome for patients with pancreatic cancer is morbid. A better understanding and interference with the malignant behaviour of pancreatic cancer may provide new directions for treatment. We report here the induction of highly motile and invasive properties in human pancreatic cancer cells by hepatocyte growth factor (HGF) and blockage of these properties by NK4, a newly identified antagonist for HGF. In all of eight human pancreatic cancer cell lines we used (AsPC-1, BxPC-3, H-48N, KP-1N, KP-2, KP-3, MIA PaCa-2 and SUIT-2 cells), the c-Met/HGF receptor was expressed at varying levels. Although weak mitogenic activity of HGF was seen only in SUIT-2 and KP-3 cells, HGF strongly stimulated migration and invasion of these pancreatic cancer cells, except for BxPC-3 and MIA PaCa-2 cells. In contrast, migration and invasion potently induced by HGF in KP-1N, KP-3 and SUIT-2 cells were inhibited by NK4. The invasion of SUIT-2 cells was also potently stimulated with the influence of cocultured pancreatic fibroblasts and by ascitic fluid obtained after pancreatic cancer resection, however, invasiveness of the cancer cells in such conditions was practically abolished by NK4. Consistently, the ascitic fluid in patients who had undergone pancreatic cancer surgery contained high levels of HGF. These findings mean that HGF is probably involved in invasion, dissemination, and metastasis of pancreatic cancer, particularly through tumour-stromal interaction and after resection of the pancreatic cancer. NK4, an effective antagonist of HGF, may prove to have the potential for anti-invasion/metastasis. © 2001 Cancer Research Campaign http://www.bjcancer.co

Recording electrical activity from the brain of behaving octopus

: Octopuses, which are among the most intelligent invertebrates,1,2,3,4 have no skeleton and eight flexible arms whose sensory and motor activities are at once autonomous and coordinated by a complex central nervous system.5,6,7,8 The octopus brain contains a very large number of neurons, organized into numerous distinct lobes, the functions of which have been proposed based largely on the results of lesioning experiments.9,10,11,12,13 In other species, linking brain activity to behavior is done by implanting electrodes and directly correlating electrical activity with observed animal behavior. However, because the octopus lacks any hard structure to which recording equipment can be anchored, and because it uses its eight flexible arms to remove any foreign object attached to the outside of its body, in vivo recording of electrical activity from untethered, behaving octopuses has thus far not been possible. Here, we describe a novel technique for inserting a portable data logger into the octopus and implanting electrodes into the vertical lobe system, such that brain activity can be recorded for up to 12 h from unanesthetized, untethered octopuses and can be synchronized with simultaneous video recordings of behavior. In the brain activity, we identified several distinct patterns that appeared consistently in all animals. While some resemble activity patterns in mammalian neural tissue, others, such as episodes of 2 Hz, large amplitude oscillations, have not been reported. By providing an experimental platform for recording brain activity in behaving octopuses, our study is a critical step toward understanding how the brain controls behavior in these remarkable animals

Functional Coupling of Ca2+ Channels to Ryanodine Receptors at Presynaptic Terminals: Amplification of Exocytosis and Plasticity

Ca2+-induced Ca2+ release (CICR) enhances a variety of cellular Ca2+ signaling and functions. How CICR affects impulse-evoked transmitter release is unknown. At frog motor nerve terminals, repetitive Ca2+ entries slowly prime and subsequently activate the mechanism of CICR via ryanodine receptors and asynchronous exocytosis of transmitters. Further Ca2+ entry inactivates the CICR mechanism and the absence of Ca2+ entry for >1 min results in its slow depriming. We now report here that the activation of this unique CICR markedly enhances impulse-evoked exocytosis of transmitter. The conditioning nerve stimulation (10–20 Hz, 2–10 min) that primes the CICR mechanism produced the marked enhancement of the amplitude and quantal content of end-plate potentials (EPPs) that decayed double exponentially with time constants of 1.85 and 10 min. The enhancement was blocked by inhibitors of ryanodine receptors and was accompanied by a slight prolongation of the peak times of EPP and the end-plate currents estimated from deconvolution of EPP. The conditioning nerve stimulation also enhanced single impulse- and tetanus-induced rises in intracellular Ca2+ in the terminals with little change in time course. There was no change in the rate of growth of the amplitudes of EPPs in a short train after the conditioning stimulation. On the other hand, the augmentation and potentiation of EPP were enhanced, and then decreased in parallel with changes in intraterminal Ca2+ during repetition of tetani. The results suggest that ryanodine receptors exist close to voltage-gated Ca2+ channels in the presynaptic terminals and amplify the impulse-evoked exocytosis and its plasticity via CICR after Ca2+-dependent priming

Societal emotional environments and cross-cultural differences in life satisfaction: A forty-nine country study

In this paper, we introduce the concept of ‘societal emotional environment’: the emotional climate of a society (operationalized as the degree to which positive and negative emotions are expressed in a society). Using data collected from 12,888 participants across 49 countries, we show how societal emotional environments vary across countries and cultural clusters, and we consider the potential importance of these differences for well-being. Multilevel analyses supported a ‘double-edged sword’ model of negative emotion expression, where expression of negative emotions predicted higher life satisfaction for the expresser but lower life satisfaction for society. In contrast, partial support was found for higher societal life satisfaction in positive societal emotional environments. Our study highlights the potential utility and importance of distinguishing between positive and negative emotion expression, and adopting both individual and societal perspectives in well-being research. Individual pathways to happiness may not necessarily promote the happiness of others.info:eu-repo/semantics/publishedVersio

Stromal micropapillary pattern predominant lung adenocarcinoma - a report of two cases

Generally, adenocarcinomas with micropapillary pattern, featuring small papillary tufts lacking a central fibrovascular core, are thought to have poor prognosis. This pattern has been described in various organs. However, tumor cells with micropapillary pattern of lung adenocarcinoma are more often seen to float within alveolar spaces (aerogenous micropapillary pattern, AMP) than in fibrotic stroma like other organs (stromal micropapillary pattern, SMP) and SMP predominant lung adenocarcinoma (SMPPLA) has not been well described yet. We presented two cases of SMPPLA which were found in the last four years. Both the cases showed more than 50% of SMP in the tumor area. The majority of the stromal micropapillary clusters expressed MUC1 and epithelial membrane antigen along the outer surface of cell membrane. On the other hand, connective tissues surrounding stromal micropapillary clusters showed no reactivity for epithelial markers (thyroid transcription factor-1 and cytokeratin) or endothelial marker (D2-40 and CD34). It means clusters of SMP do not exist within air space or lymphatic or vessel lumens. The tumors with SMP often presented lymphatic permeation and vessel invasion, and intriguingly, one of the two cases showed metastasis to the mediastinal lymph node. Additionally, both the cases showed EGFR point mutations of exon 21. These results suggest that SMPPLA might be associated with poor prognosis and effective for EGFR tyrosine kinase inhibitors