erbB-2 antisense oligonucleotides inhibit the proliferation of breast carcinoma cells with erbB-2 oncogene amplification.

Amplification and overexpression of the erbB-2 oncogene is an unfavourable prognostic marker in human breast cancer and occurs in approximately 25% of breast carcinomas. We used erbB-2 antisense oligonucleotides to inhibit the proliferation of human breast cancer cell lines. erbB-2 antisense oligonucleotides (20 microM) inhibited the growth and DNA synthesis of breast cancer cell lines with an amplified erbB-2 gene by up to 60%. Control complementary sense oligonucleotides did not inhibit cellular proliferation at the same concentration but showed inhibitory effects at higher concentrations. There was no specific effect of erbB-2 antisense oligonucleotides on breast cancer cell lines that had no amplification of erbB-2. erbB-2 antisense oligonucleotides reduced erbB-2 protein levels, measured by immunohistochemistry, in a dose-dependent manner. erbB-2 sense oligonucleotides did not decrease the levels of erbB-2 protein. These data indicate that erbB-2 antisense oligonucleotides induce a specific inhibition of erbB-2 protein expression and that erbB-2 gene overexpression is important for the proliferation of the breast cancer cells that have been selected for erbB-2 amplification

The efficacy of Herceptin therapies is influenced by the expression of other erbB receptors, their ligands and the activation of downstream signalling proteins

ErbB2 and EGFR are attractive oncology therapeutic targets as their overexpression in tumors predicts a poorer clinical outcome in a variety of epithelial malignancies. However, clinical results with therapeutic compounds targeting these receptors have been mixed. Therefore, there is a need for improved predictive biomarkers for these targeted therapeutics. In this study we analysed tissue microarrays of patients treated with combination chemotherapy and Herceptin for expression or phosphorylation of signalling proteins associated with erbB receptors to identify protein biomarkers that are predictive of breast cancer patient response. A comparison of expression or phosphorylation of these markers with patient outcome revealed that response to Herceptin depended not only on expression levels of erbB2 but also on expression of EGFR, expression of erbB ligands, expression of other receptors and phosphorylation of downstream proteins. Elucidating the biological effects of EGFR/erbB2 targeted therapeutics will enable patient tumor profiling to identify likely responders and the determination of biologically effective doses that allows chronic administration of these agents in order to maximise efficacy

Effective Operator Treatment of the Anharmonic Oscillator

We analyse the one dimensional quartic oscillator using the effective operator methodology of Lee and Suzuki. We reproduce known results for low lying energy eigenvalues.Comment: 9 Pages, Extended version with new references. To appear in Phys.ReV.

Asymptotic iteration method for eigenvalue problems

An asymptotic interation method for solving second-order homogeneous linear differential equations of the form y'' = lambda(x) y' + s(x) y is introduced, where lambda(x) \neq 0 and s(x) are C-infinity functions. Applications to Schroedinger type problems, including some with highly singular potentials, are presented.Comment: 14 page

A Guide to Precision Calculations in Dyson's Hierarchical Scalar Field Theory

The goal of this article is to provide a practical method to calculate, in a scalar theory, accurate numerical values of the renormalized quantities which could be used to test any kind of approximate calculation. We use finite truncations of the Fourier transform of the recursion formula for Dyson's hierarchical model in the symmetric phase to perform high-precision calculations of the unsubtracted Green's functions at zero momentum in dimension 3, 4, and 5. We use the well-known correspondence between statistical mechanics and field theory in which the large cut-off limit is obtained by letting beta reach a critical value beta_c (with up to 16 significant digits in our actual calculations). We show that the round-off errors on the magnetic susceptibility grow like (beta_c -beta)^{-1} near criticality. We show that the systematic errors (finite truncations and volume) can be controlled with an exponential precision and reduced to a level lower than the numerical errors. We justify the use of the truncation for calculations of the high-temperature expansion. We calculate the dimensionless renormalized coupling constant corresponding to the 4-point function and show that when beta -> beta_c, this quantity tends to a fixed value which can be determined accurately when D=3 (hyperscaling holds), and goes to zero like (Ln(beta_c -beta))^{-1} when D=4.Comment: Uses revtex with psfig, 31 pages including 15 figure

Arbitrarily Accurate Eigenvalues for General Anharmonic Potentials

We show that the Riccati form of the Schrodinger equation can be reformulated in terms of two linear equations depending on an arbitrary function G. When $G$ and the potential are polynomials, the solutions of these two equations are entire functions (L and K) and the zeroes of K are identical to those of the wave function. Requiring such a zero at a large but finite value of the argument yields the low energy eigenstates with exponentially small errors. Judicious choice of G can improve dramatically the numerical treatment. The method yields many significant digits with modest computer means.Comment: 10 pages, 8 figures, uses revtex; new section added, references adde

Comparison of DNA histograms by standard flow cytometry and image cytometry on sections in Barrett's adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to compare DNA histograms obtained by standard flow cytometry (FC) and high fidelity image cytometry on sections (ICS) in normal gastrointestinal mucosa and Barrett's adenocarcinoma (BAC).</p> <p>Methods</p> <p>Archival formalin-fixed paraffin-embedded tissue blocks of 10 normal controls from 10 subjects and 42 BAC tissues from 17 patients were examined. DNA FC was performed using standard techniques and ICS was carried out by Automated Cellular Imaging System (ACIS). DNA ploidy histograms were classified into diploid with peak DNA index (DI) at 0.9–1.1, and aneuploid with peak DI > 1.1. DI values of aneuploid peaks were determined. Additionally, for DNA ICS, heterogeneity index (HI) representing DNA content heterogeneity, and histograms containing cells with DI > G2 were also identified.</p> <p>Results</p> <p>All control samples were diploid by both FC and ICS analyses. In BAC, FC showed diploid peaks in 29%, diploid peaks with additional aneuploid or tetraploid peaks in 57%, and 14% of the samples, respectively. In contrast, ICS showed aneuploid peaks in all the cases with peak DI > 1.25; 37 cases had peak DI between 1.25 and 2.25; and 5 cases had peak DI > 2.25. HI values (mean ± SD) were 11.3 ± 1.1 in controls and 32.4 ± 8.5 in BAC (p < 0.05). Controls had no G2 exceeding cells. However, 19/37 (51%) of the cases with primary peak DI < 2.25 had cells exceeding 9N.</p> <p>Conclusion</p> <p>ICS detects DNA aneuploidy in all BAC samples while FC missed the diagnosis of aneuploidy in 29%. In addition, ICS provides more information on HI and G2 exceeding rates.</p

Conformal mappings versus other power series methods for solving ordinary differential equations: illustration on anharmonic oscillators

The simplicity and the efficiency of a quasi-analytical method for solving nonlinear ordinary differential equations (ODE), is illustrated on the study of anharmonic oscillators (AO) with a potential $V(x) =\beta x^{2}+x^{2m}$ ($m>0$). The method [Nucl. Phys. B801, 296 (2008)], applies a priori to any ODE with two-point boundaries (one being located at infinity), the solution of which has singularities in the complex plane of the independent variable $x$. A conformal mapping of a suitably chosen angular sector of the complex plane of $x$ upon the unit disc centered at the origin makes convergent the transformed Taylor series of the generic solution so that the boundary condition at infinity can be easily imposed. In principle, this constraint, when applied on the logarithmic-derivative of the wave function, determines the eigenvalues to an arbitrary level of accuracy. In practice, for $\beta \geq 0$ or slightly negative, the accuracy of the results obtained is astonishingly large with regards to the modest computing power used. It is explained why the efficiency of the method decreases as $\beta$ is more and more negative. Various aspects of the method and comparisons with some seemingly similar methods, based also on expressing the solution as a Taylor series, are shortly reviewed, presented and discussed.Comment: 32 pages, 7 figures, 8 table

Identification of a potent herbal molecule for the treatment of breast cancer

<p>Abstract</p> <p>Background</p> <p>Breast cancer (BCa)-related mortality still remains the second leading cause of cancer-related deaths worldwide. Patients with BCa have increasingly shown resistance and high toxicity to current chemotherapeutic drugs for which identification of novel targeted therapies are required.</p> <p>Methods</p> <p>To determine the effect of PDBD on BCa cells, estrogen-receptor positive (ER⁺)-MCF-7 and estrogen-receptor negative (ER^-)-MDA 231 cells were treated with PDBD and the cell viability, apoptotic, cell cycle, Western blot and Promoter assays were performed.</p> <p>Results</p> <p>PDBD inhibits cell viability of ER⁺and ER^-BCa cells by inducing apoptosis without causing significant toxicity in normal breast epithelial cells. While dissecting the mechanism of action of PDBD on BCa, we found that PDBD inhibits Akt signaling and its downstream targets such as NF-κB activation, IAP proteins and Bcl-2 expression. On the other hand, activation of JNK/p38 MAPK-mediated pro-apoptotic signaling was observed in both ER⁺and ER^-BCa cells.</p> <p>Conclusion</p> <p>These findings suggest that PDBD may have wide therapeutic application in the treatment of BCa.</p