Expression of apoptosis-related markers and clinical outcome in patients with advanced colorectal cancer

The clinical relevance of bax and bcl-2 protein expression has been investigated in 84 patients with recurrent or metastatic colorectal cancer submitted to a chemotherapy regimen including methotrexate and fluorouracil/leucovorin. Cytoplasmic immunostaining of bax and bcl-2 was present in 65.5% and 38%, respectively, of the tumours. No association was found between bax and bcl-2 or between p53 and bax or bcl-2 protein expression. Moreover, the biomarkers were unrelated to patient and tumour characteristics known to affect the clinical outcome of colorectal cancer patients. In general, the apoptosis-related markers did not appear indicative of short- and long-term clinical response nor of prognosis. Bcl-2-negative lesions were more frequent among patients who reached an objective clinical response, which is in agreement with previously reported data regarding other tumour types. When the interrelationship between p53 and bax expression was examined, a better response rate (40%) was found for patients whose tumours did not express p53 and bax, and a better prognosis (2-year probability of overall survival 75%) for patients with p53-positive and bax-negative tumours. In the present series of patients with advanced colorectal cancer submitted to systemic chemotherapy we did not find a clear association between expression of apoptosis-related markers and clinical outcome, even in the subset of patients in which the apoptotic index as determined by the TUNEL approach was investigated. © 2001 Cancer Research Campaign http://www.bjcancer.co

Two-dimensional gapless spin liquids in frustrated SU(N) quantum magnets

A class of the symmetrically frustrated SU(N) models is constructed for quantum magnets based on the generators of SU(N) group. The total Hamiltonian lacks SU(N) symmtry. A mean field theory in the quasi-particle representation is developed for spin liquid states. Numerical solutions in two dimension indicate that the ground states are gapless and the quasi-particles are Dirac particles. The mechanism may be helpful in exploring the spin liquid phases in the spin-1 bilinear-biquadratic model and the spin-orbital model in higher dimensions.Comment: 9 pages, 3 figures, to appear in New Journal of Physic

Non-Hermitian Hamiltonians with real eigenvalues coupled to electric fields: from the time-independent to the time dependent quantum mechanical formulation

We provide a reviewlike introduction into the quantum mechanical formalism related to non-Hermitian Hamiltonian systems with real eigenvalues. Starting with the time-independent framework we explain how to determine an appropriate domain of a non-Hermitian Hamiltonian and pay particular attention to the role played by PT-symmetry and pseudo-Hermiticity. We discuss the time-evolution of such systems having in particular the question in mind of how to couple consistently an electric field to pseudo-Hermitian Hamiltonians. We illustrate the general formalism with three explicit examples: i) the generalized Swanson Hamiltonians, which constitute non-Hermitian extensions of anharmonic oscillators, ii) the spiked harmonic oscillator, which exhibits explicit supersymmetry and iii) the -x^4-potential, which serves as a toy model for the quantum field theoretical phi^4-theory.Comment: 14 pages, 3 figures, to appear in Laser Physics, minor typos correcte

Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients

The purpose of this work was to analyse the ability of p53 and thymidilate synthase (TS) primary tumour expression to retrospectively predict clinical response to chemotherapy and long-term prognosis in patients with advanced colorectal cancers homogeneously treated by methotrexate (MTX)-modulated–5-fluorouracil (5-FU-FA). A total of 108 advanced colorectal cancer patients entered the present retrospective study. Immunohistochemical p53 (pAb 1801 mAb) and TS (TS106 mAb) expression on formalin-fixed paraffin-embedded primary tumour specimens was related to probability of clinical response to chemotherapy, time to progression and overall survival. p53 was expressed in 53/108 (49%) tumours, while 54/108 (50%) showed TS immunostaining. No relationship was demonstrated between p53 positivity and clinical response to chemotherapy (objective response (OR): 20% vs 23%, in p53+ and p53– cases respectively) or overall survival. Percent of OR was significantly higher in TS-negative with respect to TS-positive tumours (30% vs 15% respectively;P< 0.04); simultaneous analysis of TS and p53 indicated 7% OR for p53-positive/TS-positive tumours vs 46% for p53-positive/TS-negative tumours (P< 0.03). Logistic regression analysis confirmed a significant association between TS tumour status and clinical response to chemotherapy (hazard ratio (HR): 2.91; 95% confidence interval (CI) 8.34–1.01; two-sided P< 0.05). A multivariate analysis of overall survival showed that only a small number of metastatic sites was statistically relevant (HR 1.89; 95% CI 2.85–1.26; two-sided P< 0.03). Our study suggests that immunohistochemical expression of p53 and TS could assist the clinician in predicting response of colorectal cancer patients to modulated MTX-5-FU therapy. © 2000 Cancer Research Campaig

Exact solutions for diluted spin glasses and optimization problems

We study the low temperature properties of p-spin glass models with finite connectivity and of some optimization problems. Using a one-step functional replica symmetry breaking Ansatz we can solve exactly the saddle-point equations for graphs with uniform connectivity. The resulting ground state energy is in perfect agreement with numerical simulations. For fluctuating connectivity graphs, the same Ansatz can be used in a variational way: For p-spin models (known as p-XOR-SAT in computer science) it provides the exact configurational entropy together with the dynamical and static critical connectivities (for p=3, \gamma_d=0.818 and \gamma_s=0.918 resp.), whereas for hard optimization problems like 3-SAT or Bicoloring it provides new upper bounds for their critical thresholds (\gamma_c^{var}=4.396 and \gamma_c^{var}=2.149 resp.).Comment: 4 pages, 1 figure, accepted for publication in PR

Stellar Rotation in Young Clusters. II. Evolution of Stellar Rotation and Surface Helium Abundance

We derive the effective temperatures and gravities of 461 OB stars in 19 young clusters by fitting the H-gamma profile in their spectra. We use synthetic model profiles for rotating stars to develop a method to estimate the polar gravity for these stars, which we argue is a useful indicator of their evolutionary status. We combine these results with projected rotational velocity measurements obtained in a previous paper on these same open clusters. We find that the more massive B-stars experience a spin down as predicted by the theories for the evolution of rotating stars. Furthermore, we find that the members of binary stars also experience a marked spin down with advanced evolutionary state due to tidal interactions. We also derive non-LTE-corrected helium abundances for most of the sample by fitting the He I 4026, 4387, 4471 lines. A large number of helium peculiar stars are found among cooler stars with Teff < 23000 K. The analysis of the high mass stars (8.5 solar masses < M < 16 solar masses) shows that the helium enrichment process progresses through the main sequence (MS) phase and is greater among the faster rotators. This discovery supports the theoretical claim that rotationally induced internal mixing is the main cause of surface chemical anomalies that appear during the MS phase. The lower mass stars appear to have slower rotation rates among the low gravity objects, and they have a large proportion of helium peculiar stars. We suggest that both properties are due to their youth. The low gravity stars are probably pre-main sequence objects that will spin up as they contract. These young objects very likely host a remnant magnetic field from their natal cloud, and these strong fields sculpt out surface regions with unusual chemical abundances.Comment: 50 pages 18 figures, accepted by Ap

N-acetylaspartate supports the energetic demands of developmental myelination via oligodendroglial aspartoacylase

Breakdown of neuro-glial N-acetyl-aspartate (NAA) metabolism results in the failure of developmental myelination, manifest in the congenital pediatric leukodystrophy Canavan disease caused by mutations to the sole NAA catabolizing enzyme aspartoacylase. Canavan disease is a major point of focus for efforts to define NAA function, with available evidence suggesting NAA serves as an acetyl donor for fatty acid synthesis during myelination. Elevated NAA is a diagnostic hallmark of Canavan disease, which contrasts with a broad spectrum of alternative neurodegenerative contexts in which levels of NAA are inversely proportional to pathological progression. Recently generated data in the nur7 mouse model of Canavan disease suggests loss of aspartoacylase function results in compromised energetic integrity prior to oligodendrocyte death, abnormalities in myelin content, spongiform degeneration, and motor deficit. The present study utilized a next-generation “oligotropic” adeno-associated virus vector (AAV-Olig001) to quantitatively assess the impact of aspartoacylase reconstitution on developmental myelination. AAV-Olig001-aspartoacylase promoted normalization of NAA, increased bioavailable acetyl-CoA, and restored energetic balance within a window of postnatal development preceding gross histopathology and deteriorating motor function. Long-term effects included increased oligodendrocyte numbers, a global increase in myelination, reversal of vacuolation, and rescue of motor function. Effects on brain energy observed following AAV-Olig001-aspartoacylase gene therapy are shown to be consistent with a metabolic profile observed in mild cases of Canavan disease, implicating NAA in the maintenance of energetic integrity during myelination via oligodendroglial aspartoacylase

Klebsiella pneumoniae is able to trigger epithelial-mesenchymal transition process in cultured airway epithelial cells

The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells

Virtual Compton Scattering and the Generalized Polarizabilities of the Proton at Q^2=0.92 and 1.76 GeV^2

Virtual Compton Scattering (VCS) on the proton has been studied at Jefferson Lab using the exclusive photon electroproduction reaction (e p --> e p gamma). This paper gives a detailed account of the analysis which has led to the determination of the structure functions P_LL-P_TT/epsilon and P_LT, and the electric and magnetic generalized polarizabilities (GPs) alpha_E(Q^2) and beta_M(Q^2) at values of the four-momentum transfer squared Q^2= 0.92 and 1.76 GeV^2. These data, together with the results of VCS experiments at lower momenta, help building a coherent picture of the electric and magnetic GPs of the proton over the full measured Q^2-range, and point to their non-trivial behavior.Comment: version 2: modified according to PRC Editor's and Referee's recommendations. Archival paper for the E93-050 experiment at JLab Hall A. 28 pages, 23 figures, 5 cross-section tables. To be submitted to Phys.Rev.

Study of the a_0(980) meson via the radiative decay phi->eta pi^0 gamma with the KLOE detector

We have studied the phi->a_0(980) gamma process with the KLOE detector at the Frascati phi-factory DAPhNE by detecting the phi->eta pi^0 gamma decays in the final states with eta->gamma gamma and eta->pi^+ pi^- pi^0. We have measured the branching ratios for both final states: Br(phi->eta pi^0 gamma)=(7.01 +/- 0.10 +/- 0.20)x10^-5 and (7.12 +/- 0.13 +/- 0.22)x10^-5 respectively. We have also extracted the a_0(980) mass and its couplings to eta pi^0, K^+ K^-, and to the phi meson from the fit of the eta pi^0 invariant mass distributions using different phenomenological models.Comment: 17 pages, 6 figures, submitted to Physics Letters B. Corrected typos in eq.