Down-regulation of PPARgamma1 suppresses cell growth and induces apoptosis in MCF-7 breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear hormone receptor superfamily and is highly expressed in many human tumors including breast cancer. PPARγ has been identified as a potential target for breast cancer therapy based on the fact that its activation by synthetic ligands affects the differentiation, proliferation, and apoptosis of cancer cells. However, the controversial nature of current studies and disappointing results from clinical trials raise questions about the contribution of PPARγ signaling in breast cancer development in the absence of stimulation by exogenous ligands. Recent reports from both <it>in vitro </it>and <it>in vivo </it>studies are inconsistent and suggest that endogenous activation of PPARγ plays a much more complex role in initiation and progression of cancer than previously thought.</p> <p>Results</p> <p>We have previously demonstrated that an increase in expression of PPARγ1 in MCF-7 breast cancer cells is driven by a tumor-specific promoter. Myc-associated zinc finger protein (MAZ) was identified as a transcriptional mediator of PPARγ1 expression in these cells. In this study, using RNA interference (RNAi) to inhibit PPARγ1 expression directly or via down-regulation of MAZ, we report for the first time that a decrease in PPARγ1 expression results in reduced cellular proliferation in MCF-7 breast cancer cells. Furthermore, we demonstrate that these changes in proliferation are associated with a significant decrease in cell transition from G₁to the S phase. Using a dominant-negative mutant of PPARγ1, Δ462, we confirmed that PPARγ1 acts as a pro-survival factor and showed that this phenomenon is not limited to MCF-7 cells. Finally, we demonstrate that down-regulation of PPARγ1 expression leads to an induction of apoptosis in MCF-7 cells, confirmed by analyzing Bcl-2 expression and PARP-1 cleavage.</p> <p>Conclusion</p> <p>Thus, these findings suggest that an increase in PPARγ1 signaling observed in breast cancer contributes to an imbalance between proliferation and apoptosis, and may be an important hallmark of breast tumorigenesis. The results presented here also warrant further investigation regarding the use of PPARγ ligands in patients who are predisposed or already diagnosed with breast cancer.</p

Next-to-Next-to-Leading Order Higgs Production at Hadron Colliders

The Higgs boson production cross section at pp and p\bar{p} colliders is calculated in QCD at next-to-next-to-leading order (NNLO). We find that the perturbative expansion of the production cross section is well behaved and that scale dependence is reduced relative to the NLO result. These findings give us confidence in the reliability of the prediction. We also report an error in the NNLO correction to Drell-Yan production.Comment: 5 pages, 4 figures, minor change

Prevalence of rotavirus diarrhea among hospitalized under-five children

Objective: To estimate the prevalence of rotavirus diarrhea among hospitalized children less than 5 years of age in Kerala State and to determine the circulating strains of rotavirus in Kerala. Desigh: Multicenter, cross-sectional study. Setting: Eight representative hospitals in Kunnathunadu Thaluk, Ernakulam district, Kerala. Participants: Children in the age group under 5 years. Methods: Hospitalized children admitted with acute diarrhea were examined and standardized case report form was used to collect demographic, clinical and health outcome. Stool specimens were collected and ELISA testing was done. ELISA rotavirus positive samples were tested by reverse transcription PCR for G and P typing (CMC Vellore). Results: Among the 1827 children, 648 (35.9%) were positive for rotavirus by the Rotaclone ELISA test. The prevalence of rotavirus diarrhea in infants less than 6 months of age was 24.7%; 6- 11 months 31.9%; 12- 23 months 41.9%; 24- 35 months 46.9%; and 33.3% in 36- 59 months. Rotavirus infections were most common during the dry months from January through May. G1P[8] (49.7%) was the most common strain identified followed by G9P[8] (26.4%), G2P[4] (5.5%), G9P[4] (2.6%) and G12P[6] (1.3%). Conclusions: The prevalence of rotavirus diarrhea among hospitalized children less than 5 years is high in Ernakulam district, Kerala State

Chronic Hepatitis B and C Co-Infection Increased All-Cause Mortality in HAART-Naive HIV Patients in Northern Thailand

A total of 755 highly active antiretroviral therapy (HAART)-naive HIV-infected patients were enrolled at a government hospital in Thailand from 1 June 2000 to 15 October 2002. Census date of survival was on 31 October 2004 or the date of HAART initiation. Of 700 (92.6%) patients with complete data, the prevalence of hepatitis B virus (HBV) surface antigen and anti-hepatitis C virus (HCV) antibody positivity was 11.9% and 3.3%, respectively. Eight (9.6%) HBV co-infected patients did not have anti-HBV core antibody (anti-HBcAb). During 1166.7 person-years of observation (pyo), 258 (36.9%) patients died [22.1/100 pyo, 95% confidence interval (CI) 16.7–27.8]. HBV and probably HCV co-infection was associated with a higher mortality with adjusted hazard ratios (aHRs) of 1.81 (95% CI 1.30–2.53) and 1.90 (95% CI 0.98–3.69), respectively. Interestingly, HBV co-infection without anti-HBc Ab was strongly associated with death (aHR 6.34, 95% CI 3.99–10.3). The influence of hepatitis co-infection on the natural history of HAART-naive HIV patients requires greater attention

On the Rational Terms of the one-loop amplitudes

The various sources of Rational Terms contributing to the one-loop amplitudes are critically discussed. We show that the terms originating from the generic (n-4)-dimensional structure of the numerator of the one-loop amplitude can be derived by using appropriate Feynman rules within a tree-like computation. For the terms that originate from the reduction of the 4-dimensional part of the numerator, we present two different strategies and explicit algorithms to compute them.Comment: 14 pages, 3 figures, uses axodraw.st

Tevatron-for-LHC Report of the QCD Working Group

The experiments at Run 2 of the Tevatron have each accumulated over 1 inverse femtobarn of high-transverse momentum data. Such a dataset allows for the first precision (i.e. comparisons between theory and experiment at the few percent level) tests of QCD at a hadron collider. While the Large Hadron Collider has been designed as a discovery machine, basic QCD analyses will still need to be performed to understand the working environment. The Tevatron-for-LHC workshop was conceived as a communication link to pass on the expertise of the Tevatron and to test new analysis ideas coming from the LHC community. The TeV4LHC QCD Working Group focussed on important aspects of QCD at hadron colliders: jet definitions, extraction and use of Parton Distribution Functions, the underlying event, Monte Carlo tunes, and diffractive physics. This report summarizes some of the results achieved during this workshop.Comment: 156 pages, Tevatron-for-LHC Conference Report of the QCD Working Grou

Summary: Working Group on QCD and Strong Interactions

In this summary of the considerations of the QCD working group at Snowmass 2001, the roles of quantum chromodynamics in the Standard Model and in the search for new physics are reviewed, with empahsis on frontier areas in the field. We discuss the importance of, and prospects for, precision QCD in perturbative and lattice calculations. We describe new ideas in the analysis of parton distribution functions and jet structure, and review progress in small-$x$ and in polarization.Comment: Snowmass 2001. Revtex4, 34 pages, 4 figures, revised to include additional references on jets and lattice QC

Applications of QCD

Talk given at XIXth International Symposium on Lepton and Photon Interactions at High Energies (LP 99), Stanford, California, 9-14 August 1999.Comment: latex, 26 page