Characterisation and properties of a small cell lung cancer cell line and xenograft WX322 with marked sensitivity to alpha-interferon.

Controversy exists as to whether interferons usefully influence the growth of epithelial carcinomas. A small cell lung carcinoma (SCLC) cell line, WX322, has been derived which is greater than 1000-fold more sensitive to alpha-interferon (IFN) when grown in agar than other reported SCLC cell lines. The WX322 line has been characterised to prove its epithelial origin and its chemosensitivity compared with that of the NCI-H69 small cell line. The WX322 cell line expresses neuroendocrine and epithelial markers and possesses a morphology consistent with SCLC origin. A concentration of 5 IU ml-1 of IFN produced 50% inhibition of colony formation in agar in the WX322 line, whereas a concentration of greater than 10(5) IU ml-1 was required to produce a comparable effect with the NCI-H69 cell line. In contrast, WX322, possessed similar sensitivity to NCI-H69 cells when exposed to a range of cytotoxic agents. Analysis of the cell cycle indicated that IFN increased the percentage of cells in the G0/G1 phase for the WX322 cell line but increased the percentage in S phase for the NCI-H69 line. Growth of the xenograft, from which the cell line was derived, was also inhibited by IFN at doses greater than 10(5) IU/mouse/day. The WX322 cell line whether grown in agar or as a xenograft shows an unusually high sensitivity to IFN and provides an interesting model for studying mechanisms of IFN cytotoxicity to epithelial cells

Inhibition of transforming growth factor α (TGF-α)-mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868

The modulating effects of the epidermal growth factor (EGF) receptor-specific tyrosine kinase inhibitor ZM 252868 on cell growth and signalling have been evaluated in four ovarian carcinoma cell lines PE01, PE04, SKOV-3 and PE01CDDP. Transforming growth factor α (TGF-α)-stimulated growth was completely inhibited by concentrations ≥ 0.3 μM in the PE01 and PE04 cell lines and by ≥ 0.1 μM in SKOV-3 cells. TGF-α inhibition of PE01CDDP growth was reversed by concentrations ≥ 0.1 μM ZM 252868. TGF-α-stimulated tyrosine phosphorylation of both the EGF receptor and c-erbB2 receptor in all four cell lines. The inhibitor ZM 252868, at concentrations ≥ 0.3 μM, completely inhibited TGF-α-stimulated tyrosine phosphorylation of the EGF receptor and reduced phosphorylation of the c-erbB2 protein. EGF-activated EGF receptor tyrosine kinase activity was completely inhibited by 3 μM ZM 252868 in PE01, SKOV-3 and PE01CDDP cells. These data indicate that the EGF receptor-targeted TK inhibitor ZM 252868 can inhibit growth of ovarian carcinoma cells in vitro consistent with inhibition of tyrosine phosphorylation at the EGF receptor. © 1999 Cancer Research Campaig

Saturation-state sensitivity of marine bivalve larvae to ocean acidification

Ocean acidification results in co-varying inorganic carbon system variables. Of these, an explicit focus on pH and organismal acid-base regulation in has failed to distinguish the mechanism of failure in highly sensitive bivalve larvae. With unique chemical manipulations of seawater we show definitively that larval bivalve shell development and growth are dependent on seawater saturation state, and not on carbon dioxide partial pressure or pH. Although other physiological processes are affected by pH, mineral saturation state thresholds will be crossed decades to centuries ahead of pH thresholds due to the non-linear changes in the carbonate system variables as carbon dioxide is added. Our findings were repeatable for two species of larval bivalves, could resolve discrepancies in experimental results, are consistent with a previous model of ocean acidification impacts due to rapid calcification in bivalve larvae, and suggest a fundamental ocean acidification bottleneck at early life-history for some marine keystone species.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Nature Publishing Group, Macmillan Publishers Ltd., and can be found at: http://www.nature.com/nclimate/index.htmlKeywords: Biocalcification, Bivalve Larvae, Ocean Acidification, Larval Physiology, Carbonate ChemistryKeywords: Biocalcification, Bivalve Larvae, Ocean Acidification, Larval Physiology, Carbonate Chemistr

Ocean Acidification Has Multiple Modes of Action on Bivalve Larvae

Ocean acidification (OA) is altering the chemistry of the world’s oceans at rates unparalleled in the past roughly 1 million years. Understanding the impacts of this rapid change in baseline carbonate chemistry on marine organisms needs a precise, mechanistic understanding of physiological responses to carbonate chemistry. Recent experimental work has shown shell development and growth in some bivalve larvae, have direct sensitivities to calcium carbonate saturation state that is not modulated through organismal acid-base chemistry. To understand different modes of action of OA on bivalve larvae, we experimentally tested how pH, P[subscript]CO2, and saturation state independently affect shell growth and development, respiration rate, and initiation of feeding in Mytilus californianus embryos and larvae. We found, as documented in other bivalve larvae, that shell development and growth were affected by aragonite saturation state, and not by pH or P[subscript]CO2. Respiration rate was elevated under very low pH (~7.4) with no change between pH of ~ 8.3 to ~7.8. Initiation of feeding appeared to be most sensitive to P[subscript]CO2, and possibly minor response to pH under elevated P[subscript]CO2. Although different components of physiology responded to different carbonate system variables, the inability to normally develop a shell due to lower saturation state precludes pH or P[subscript]CO2 effects later in the life history. However, saturation state effects during early shell development will carry-over to later stages, where pH or P[subscript]CO2 effects can compound OA effects on bivalve larvae. Our findings suggest OA may be a multi-stressor unto itself. Shell development and growth of the native mussel, M. californianus, was indistinguishable from the Mediterranean mussel, Mytilus galloprovincialis, collected from the southern U.S. Pacific coast, an area not subjected to seasonal upwelling. The concordance in responses suggests a fundamental OA bottleneck during development of the first shell material affected only by saturation state

Forward Neutral Pion Transverse Single Spin Asymmetries in p+p Collisions at \sqrt{s}=200 GeV

We report precision measurements of the Feynman-x dependence, and first measurements of the transverse momentum dependence, of transverse single spin asymmetries for the production of \pi^0 mesons from polarized proton collisions at \sqrt{s}=200 GeV. The x_F dependence of the results is in fair agreement with perturbative QCD model calculations that identify orbital motion of quarks and gluons within the proton as the origin of the spin effects. Results for the p_T dependence at fixed x_F are not consistent with pQCD-based calculations.Comment: 6 pages, 4 figure

A comparison of machine learning techniques for survival prediction in breast cancer

<p>Abstract</p> <p>Background</p> <p>The ability to accurately classify cancer patients into risk classes, i.e. to predict the outcome of the pathology on an individual basis, is a key ingredient in making therapeutic decisions. In recent years gene expression data have been successfully used to complement the clinical and histological criteria traditionally used in such prediction. Many "gene expression signatures" have been developed, i.e. sets of genes whose expression values in a tumor can be used to predict the outcome of the pathology. Here we investigate the use of several machine learning techniques to classify breast cancer patients using one of such signatures, the well established <it>70-gene signature</it>.</p> <p>Results</p> <p>We show that Genetic Programming performs significantly better than Support Vector Machines, Multilayered Perceptrons and Random Forests in classifying patients from the NKI breast cancer dataset, and comparably to the scoring-based method originally proposed by the authors of the 70-gene signature. Furthermore, Genetic Programming is able to perform an automatic feature selection.</p> <p>Conclusions</p> <p>Since the performance of Genetic Programming is likely to be improvable compared to the out-of-the-box approach used here, and given the biological insight potentially provided by the Genetic Programming solutions, we conclude that Genetic Programming methods are worth further investigation as a tool for cancer patient classification based on gene expression data.</p

Projected Changes to Growth and Mortality of Hawaiian Corals over the Next 100 Years

BACKGROUND: Recent reviews suggest that the warming and acidification of ocean surface waters predicated by most accepted climate projections will lead to mass mortality and declining calcification rates of reef-building corals. This study investigates the use of modeling techniques to quantitatively examine rates of coral cover change due to these effects. METHODOLOGY/PRINCIPAL FINDINGS: Broad-scale probabilities of change in shallow-water scleractinian coral cover in the Hawaiian Archipelago for years 2000-2099 A.D. were calculated assuming a single middle-of-the-road greenhouse gas emissions scenario. These projections were based on ensemble calculations of a growth and mortality model that used sea surface temperature (SST), atmospheric carbon dioxide (CO(2)), observed coral growth (calcification) rates, and observed mortality linked to mass coral bleaching episodes as inputs. SST and CO(2) predictions were derived from the World Climate Research Programme (WCRP) multi-model dataset, statistically downscaled with historical data. CONCLUSIONS/SIGNIFICANCE: The model calculations illustrate a practical approach to systematic evaluation of climate change effects on corals, and also show the effect of uncertainties in current climate predictions and in coral adaptation capabilities on estimated changes in coral cover. Despite these large uncertainties, this analysis quantitatively illustrates that a large decline in coral cover is highly likely in the 21(st) Century, but that there are significant spatial and temporal variances in outcomes, even under a single climate change scenario