Apoptotic Cell Death and Inhibition of Wnt/β-Catenin Signaling Pathway in Human Colon Cancer Cells by an Active Fraction (HS7) from Taiwanofungus camphoratus

Aberrant activation of Wnt/β-catenin signaling plays an important role in the development of colon cancer. HS7 is an active fraction extracted from Taiwanofungus camphoratus, which had been widely used as complementary medicine for Taiwan cancer patients in the past decades. In this study, we demonstrated the effects of HS7 on the growth inhibition, apoptosis induction, and Wnt/β-catenin signaling suppression in human colon cancer cells. HS7 significantly inhibited proliferation of HT29, HCT116, and SW480 colon cancer cells in a dose- and time-dependent manner. The apoptosis induction was evidenced by DNA fragmentation and subG1 accumulation, which was associated with increased Bax/Bcl-2 ratio, activation of caspase-3 and cleavage of PARP. By using Tcf-dependent luciferase activity assay, HS7 was found to inhibit the β-catenin/Tcf transcriptional activities. In addition, HS7 strongly suppressed the binding of Tcf complexes to its DNA-binding site shown in electrophoretic mobility shift assay. This inhibition was further confirmed by the decreased protein levels of Tcf-4 and β-catenin. The β-catenin/Tcf downstream target genes, such as survivin, c-myc, cyclin D1, MMP7, and MT1-MMP involved in apoptosis, invasion, and angiogenesis were also diminished as well. These results indicate that Taiwanofungus camphoratus may provide a benefit as integrative medicine for the treatment of colon cancer

Honokiol Eliminates Human Oral Cancer Stem-Like Cells Accompanied with Suppression of Wnt/ β

Honokiol, an active compound of Magnolia officinalis, exerted many anticancer effects on various types of cancer cells. We explored its effects on the elimination of cancer stem-like side population (SP) cells in human oral squamous cell carcinoma SAS cells. The sorted SP cells possessed much higher expression of stemness genes, such as ABCG2, ABCC5, EpCAM, OCT-4, CD133, CD44, and β-catenin, and more clonogenicity as compared with the Non-SP cells. After 48 h of treatment, honokiol dose dependently reduced the proportion of SP from 2.53% to 0.09%. Apoptosis of honokiol-treated SP cells was evidenced by increased annexin V staining and cleaved caspase-3 as well as decreased Survivin and Bcl-2. Mechanistically, honokiol inhibited the CD44 and Wnt/β-catenin signaling of SP cells. The Wnt signaling transducers such as β-catenin and TCF-4 were decreased in honokiol-treated SP cells, while the β-catenin degradation promoting kinase GSK-3α/β was increased. Consistently, the protein levels of β-catenin downstream targets such as c-Myc and Cyclin D1 were also downregulated. Furthermore, the β-catenin-related EMT markers such as Slug and Snail were markedly suppressed by honokiol. Our findings indicate honokiol may be able to eliminate oral cancer stem cells through apoptosis induction, suppression of Wnt/β-catenin signaling, and inhibition of EMT

Surgical treatment and prognostic analysis for gastrointestinal stromal tumors (GISTs) of the small intestine: before the era of imatinib mesylate

BACKGROUND: Gastrointestinal stromal tumors (GISTs), the most common type of mesenchymal tumors of the gastrointestinal (GI) tract, demonstrate positive kit staining. We report our surgical experience with 100 small intestine GIST patients and identify predictors for long-term disease-free survival (DFS) and overall survival (OS) to clarify the difference between high- and low-risk patients. METHODS: The clinicopathologic and follow-up records of 100 small intestine GIST patients who were treated at Chung Gung Memorial Hospital between 1983 and 2002 were retrospectively reviewed. Clinical and pathological factors were assessed for long-term DFS and OS by using a univariate log-rank test and a multivariate Cox proportional hazard model. RESULTS: The patients included 52 men and 48 women. Their ages ranged from 27 to 82 years. Among the 85 patients who underwent curative resection, 44 (51.8%) developed disease recurrence (liver metastasis was the most common form of recurrence). The follow-up period ranged from 5 to 202 months (median: 33.2 months). The 1-, 3-, and 5-year DFS and OS rates were 85.2%, 53.8%, and 43.7%, and 91.5%, 66.6%, and 50.5%, respectively. Using multivariate analysis, it was found that high tumor cellularity, mitotic count >5/50 high-power field, and a Ki-67 index ≧10% were three independent factors that were inversely associated with DFS. However, absence of tumor perforation, mitotic count < 5/50 high power field, and tumor with low cellularity were predictors of long-term favorable OS. CONCLUSION: Tumors with low cellularity, low mitotic count, and low Ki-67 index, which indicate low risk, predict a more favorable DFS for small intestine GIST patients undergoing curative resection. Absence of tumor perforation with low mitotic count and low cellularity, which indicates low risk, can predict long-term OS for small intestine GIST patients who have undergone curative resection

Forward-Backward Asymmetry in Top Quark Production in ppbar Collisions at sqrt{s}=1.96 TeV

Reconstructable final state kinematics and charge assignment in the reaction ppbar->ttbar allows tests of discrete strong interaction symmetries at high energy. We define frame dependent forward-backward asymmetries for the outgoing top quark in both the ppbar and ttbar rest frames, correct for experimental distortions, and derive values at the parton-level. Using 1.9/fb of ppbar collisions at sqrt{s}=1.96 TeV recorded with the CDF II detector at the Fermilab Tevatron, we measure forward-backward top quark production asymmetries in the ppbar and ttbar rest frames of A_{FB,pp} = 0.17 +- 0.08 and A_{FB,tt} = 0.24 +- 0.14.Comment: 7 pages, 2 figures, submitted to Phys.Rev.Lett, corrected references and change of tex

Search for Pair Production of Scalar Top Quarks Decaying to a tau Lepton and a b Quark in ppbar Collisions at sqrt{s}=1.96 TeV

We search for pair production of supersymmetric top quarks (~t_1), followed by R-parity violating decay ~t_1 -> tau b with a branching ratio beta, using 322 pb^-1 of ppbar collisions at sqrt{s}=1.96 TeV collected by the CDF II detector at Fermilab. Two candidate events pass our final selection criteria, consistent with the standard model expectation. We set upper limits on the cross section sigma(~t_1 ~tbar_1)*beta^2 as a function of the stop mass m(~t_1). Assuming beta=1, we set a 95% confidence level limit m(~t_1)>153 GeV/c^2. The limits are also applicable to the case of a third generation scalar leptoquark (LQ_3) decaying LQ_3 -> tau b.Comment: 7 pages, 2 eps figure

Observation of Bs-Bsbar Oscillations

We report the observation of Bs-Bsbar oscillations from a time-dependent measurement of the Bs-Bsbar oscillation frequency Delta ms. Using a data sample of 1 fb^-1 of p-pbar collisions at sqrt{s}=1.96 TeV collected with the CDF II detector at the Fermilab Tevatron, we find signals of 5600 fully reconstructed hadronic Bs decays, 3100 partially reconstructed hadronic Bs decays, and 61500 partially reconstructed semileptonic Bs decays. We measure the probability as a function of proper decay time that the Bs decays with the same, or opposite, flavor as the flavor at production, and we find a signal for Bs-Bsbar oscillations. The probability that random fluctuations could produce a comparable signal is 8 X 10^-8, which exceeds 5 sigma significance. We measure Delta ms = 17.77 +- 0.10 (stat) +- 0.07 (syst) ps^-1 and extract |Vtd/Vts| = 0.2060 +- 0.0007 (exp) + 0.0081 - 0.0060 (theor).Comment: 9 pages, 5 figures, submitted to Physical Review Letter

Search for the Higgs boson in events with missing transverse energy and b quark jets produced in proton-antiproton collisions at s**(1/2)=1.96 TeV

We search for the standard model Higgs boson produced in association with an electroweak vector boson in events with no identified charged leptons, large imbalance in transverse momentum, and two jets where at least one contains a secondary vertex consistent with the decay of b hadrons. We use ~1 fb-1 integrated luminosity of proton-antiproton collisions at s**(1/2)=1.96 TeV recorded by the CDF II experiment at the Tevatron. We find 268 (16) single (double) b-tagged candidate events, where 248 +/- 43 (14.4 +/- 2.7) are expected from standard model background processes. We place 95% confidence level upper limits on the Higgs boson production cross section for several Higgs boson masses ranging from 110 GeV/c2 to 140 GeV/c2. For a mass of 115 GeV/c2 the observed (expected) limit is 20.4 (14.2) times the standard model prediction.Comment: 8 pages, 2 figures, submitted to Phys. Rev. Let

Studying the Underlying Event in Drell-Yan and High Transverse Momentum Jet Production at the Tevatron

We study the underlying event in proton-antiproton collisions by examining the behavior of charged particles (transverse momentum pT > 0.5 GeV/c, pseudorapidity |\eta| < 1) produced in association with large transverse momentum jets (~2.2 fb-1) or with Drell-Yan lepton-pairs (~2.7 fb-1) in the Z-boson mass region (70 < M(pair) < 110 GeV/c2) as measured by CDF at 1.96 TeV center-of-mass energy. We use the direction of the lepton-pair (in Drell-Yan production) or the leading jet (in high-pT jet production) in each event to define three regions of \eta-\phi space; toward, away, and transverse, where \phi is the azimuthal scattering angle. For Drell-Yan production (excluding the leptons) both the toward and transverse regions are very sensitive to the underlying event. In high-pT jet production the transverse region is very sensitive to the underlying event and is separated into a MAX and MIN transverse region, which helps separate the hard component (initial and final-state radiation) from the beam-beam remnant and multiple parton interaction components of the scattering. The data are corrected to the particle level to remove detector effects and are then compared with several QCD Monte-Carlo models. The goal of this analysis is to provide data that can be used to test and improve the QCD Monte-Carlo models of the underlying event that are used to simulate hadron-hadron collisions.Comment: Submitted to Phys.Rev.

Global Search for New Physics with 2.0/fb at CDF

Data collected in Run II of the Fermilab Tevatron are searched for indications of new electroweak-scale physics. Rather than focusing on particular new physics scenarios, CDF data are analyzed for discrepancies with the standard model prediction. A model-independent approach (Vista) considers gross features of the data, and is sensitive to new large cross-section physics. Further sensitivity to new physics is provided by two additional algorithms: a Bump Hunter searches invariant mass distributions for "bumps" that could indicate resonant production of new particles; and the Sleuth procedure scans for data excesses at large summed transverse momentum. This combined global search for new physics in 2.0/fb of ppbar collisions at sqrt(s)=1.96 TeV reveals no indication of physics beyond the standard model.Comment: 8 pages, 7 figures. Final version which appeared in Physical Review D Rapid Communication