Tumour-amplified kinase BTAK is amplified and overexpressed in gastric cancers with possible involvement in aneuploid formation

Our recent analysis of gastric cancers using comparative genomic hybridization (CGH) revealed a novel high frequent copy number increase in the long arm of chromosome 20. Tumour-amplified kinase BTAK was recently cloned from breast cancers and mapped on 20q13 as a target gene for this amplification in human breast cancers. In the study presented here, we analysed BTAK copy-number and expression, and their relation to the ploidy pattern in 72 primary gastric cancers. Furthermore, wild-type BTAK and its deletion mutants were transfected to gastric cancers to examine changes in cell proliferation and DNA ploidy pattern. Evaluation of 72 unselected primary gastric cancers found BTAK amplification in 5% and overexpression in more than 50%. All four clinical samples with BTAK amplification showed aneuploidy and poor prognosis. Transfection of BTAK in near-diploid gastric cancers induced another aneuploid cell population. In contrast, the c-terminal-deleted mutant of BTAK induced no effect in DNA ploidy pattern and inhibited gastric cancer cell proliferation. These results suggest that BTAK may be involved in gastric cancer cell aneuploid formation, and is a candidate gene for the increase in the number of copies of the 20q, and thus may contribute to an increase in the malignant phenotype of gastric cancer. © 2001 Cancer Research Campaign http://www.bjcancer.co

Full order_alpha electroweak and order alpha_s corrections to e^+e^- --> t t H

We present the full ${{\cal O}}(\alpha)$ electroweak radiative corrections to associated Higgs top pair production in $e^+e^-$ collisions. We combine these results with a new calculation of the full one-loop QCD corrections. The computation is performed with the help of {\tt GRACE-loop}. We find that the ${{\cal O}}(\alpha)$ correction can be larger than the ${{\cal O}}(\alpha_s)$ corrections around the peak of the cross section especially for a light Higgs mass. At threshold these corrections are swamped by the QCD corrections which are enhanced by the gluon Coulomb contribution. We have also subtracted the complete QED corrections and expressed the genuine weak correction both in the $\alpha$-scheme and the $G_\mu$-scheme. This reveals that the genuine weak corrections are not negligible and should be taken into account for a precision measurement of this cross section and the extraction of the Yukawa $t \bar t H$ coupling.Comment: 20 pages, 2 figures. only change is the addition of one note stating that all our results have now been confirmed by an independent calculatio

Overexpression of SMYD2 in gastric cancer

Background: SET and MYND domain-containing protein 2 (SMYD2) is a lysine methyltransferase for histone H3, p53 and Rb and inhibits their transactivation activities. In this study, we tested whether SMYD2 (1q42) acts as a cancer-promoting factor by being overexpressed in gastric cancer. Methods: We analysed 7 gastric cancer cell lines and 147 primary tumor samples of gastric cancer, which were curatively resected in our hospital. Results: SET and MYND domain-containing protein 2 was detected in these cell lines (five out of seven cell lines; 71.4%) and primary tumor samples (fifty-six out of one hundred and forty-seven cases; 38.1%). Knockdown of SMYD2 using specific small interfering RNA inhibited proliferation, migration and invasion of SMYD2-overexpressing cells in a TP53 mutation-independent manner. Overexpression of SMYD2 protein correlated with larger tumor size, more aggressive lymphatic invasion, deeper tumor invasion and higher rates of lymph node metastasis and recurrence. Patients with SMYD2-overexpressing tumours had a worse overall rate of survival than those with non-expressing tumours (P=0.0073, log-rank test) in an intensity and proportion score-dependent manner. Moreover, multivariate analysis demonstrated that SMYD2 was independently associated with worse outcome (P=0.0021, hazard ratio 4.25 (1.69–10.7)). Conclusions: These findings suggest that SMYD2 has a crucial role in tumor cell proliferation by its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in gastric cancer

Atmospheric Muon Flux at Sea Level, Underground, and Underwater

The vertical sea-level muon spectrum at energies above 1 GeV and the underground/underwater muon intensities at depths up to 18 km w.e. are calculated. The results are particularly collated with a great body of the ground-level, underground, and underwater muon data. In the hadron-cascade calculations, the growth with energy of inelastic cross sections and pion, kaon, and nucleon generation in pion-nucleus collisions are taken into account. For evaluating the prompt muon contribution to the muon flux, we apply two phenomenological approaches to the charm production problem: the recombination quark-parton model and the quark-gluon string model. To solve the muon transport equation at large depths of homogeneous medium, a semi-analytical method is used. The simple fitting formulas describing our numerical results are given. Our analysis shows that, at depths up to 6-7 km w. e., essentially all underground data on the muon intensity correlate with each other and with predicted depth-intensity relation for conventional muons to within 10%. However, the high-energy sea-level data as well as the data at large depths are contradictory and cannot be quantitatively decribed by a single nuclear-cascade model.Comment: 47 pages, REVTeX, 15 EPS figures included; recent experimental data and references added, typos correcte

Production and Decay of Scalar Stoponium Bound States

In this paper we discuss possible signatures for the production of scalar \stst\ (stoponium) bound states \sigst\ at hadron colliders, where \st\ is the lighter scalar top eigenstate. We first study the decay of \sigst; explicit expressions are given for all potentially important decay modes. If \st\ has unsuppressed two--body decays, they will always overwhelm the annihilation decays of \sigst. Among the latter, we find that usually either the $gg$ or $hh$ final state dominates, depending on the size of the off--diagonal entry of the stop mass matrix; $h$ is the lighter neutral scalar Higgs boson of the minimal supersymmetric model. If \msig\ happens to be close to the mass of one of the neutral scalar Higgs bosons, $Q \bar{Q}$ final states dominate ($Q=b$ or $t$). \ww\ and $ZZ$ final states are subdominant. We argue that \sigst \rightarrow \gamgam decays offer the best signal for stoponium production at hadron colliders. The tevatron should be able to close the light stop window left open by LEP searches, but its mass reach is limited to \msig \leq 90 GeV. In contrast, at the LHC one should ultimately be able to probe the region \msig \leq 700 GeV, if the $hh$ partial width is not too large. We also comment on the feasibility of searching for \sigst\ production at hadron colliders in the $ZZ, \ Z \gamma$ and \fourtau\ final states, and briefly mention \sigst\ production at \gamgam\ colliders.Comment: 31 pages plus 10 figures (available from DREES@WISCPHEN); LaTeX with equation.sty; MAD/PH/808, KEK-TH-37

Lepton Fluxes from Atmospheric Charm

We reexamine the charm contribution to atmospheric lepton fluxes in the context of perturbative QCD. We include next-to-leading order corrections and discuss theoretical uncertainties due to the extrapolations of the gluon distributions at small-x. We show that the charm contribution to the atmospheric muon flux becomes dominant over the conventional contribution from pion and kaon decays at energies of about 10^5 GeV. We compare our fluxes with previous calculations.Comment: 19 pages, latex, revtex, psfi

Stop and Sbottom Searches in Run II of the Fermilab Tevatron

We estimate the Tevatron Run II potential for top and bottom squark searches. We find an impressive reach in several of the possible discovery channels. We also study some new channels which may arise in non-conventional supersymmetry models. In each case we rely on a detailed Monte Carlo simulation of the collider events and the CDF detector performance in Run I.Comment: 30 pages, LaTeX, 10 figure

Genetic analysis of multifocal superficial urothelial cancers by array-based comparative genomic hybridisation

The purpose of this study was to investigate the accumulation of genetic alterations during metachronous and/or synchronous development of multifocal low-grade superficial urothelial tumours in the same patient, by using array-based comparative genomic hybridisation (array-CGH) and FGFR mutation analysis. We analysed 24 tumours (pTa-1 G1-2) from five patients. We had previously identified a clonal relationship among the tumours of each patient by microsatellite analysis. This time, unsupervised hierarchical cluster analysis revealed that the tumours from each patient were clustered together independently of the tumours from the other patients. All of the tumours from a single patient showed a set of 2–7 identical regional or whole-arm chromosomal changes. In addition, several individual alterations were also found. Cladistic diagrams revealed that the accumulation of genetic alterations could not be explained by a linear model, and the existence of a hypothetical precursor cell was assumed in four patients. In some cases, FGFR mutation seemed to occur later during multifocal tumour development. Taken together, these findings suggest that low-grade superficial urothelial tumours accumulate minor genetic alterations during multifocal development, although these tumours are genetically stable