Farnesyltransferase Inhibitor, ABT-100, Is a Potent Liver Cancer Chemopreventive Agent

Purpose: Treatment of hepatocellular carcinoma raised on cirrhotic liver represents a major endeavor because surgery and chemotherapeutic management fail to improve the clinical course of the disease. Chemoprevention could represent an important means to inhibit the process of hepatocarcinogenesis. Farnesyltransferase inhibitors are a class of drugs blocking the growth of tumor cells with minimal toxicity towards normal cells. Experimental Design: In the present study, we investigated the effects of a novel farnesyltransferase inhibitor, ABT-100, on human liver cancer cell lines, HepG2 and Huh7, and on an animal model of hepatocarcinogenesis. Results: ABT-100 inhibited HepG2 and Huh7 cell growth as well as the invading ability of Huh7 on Matrigel. In HepG2 and Huh7 cells, ABT-100 inhibited growth factor–stimulated phosphoinositide 3-kinase and Akt/protein kinase B activity. Furthermore, ABT-100 inhibited Akt-dependent p27 Kip1 phosphorylation and this event was associated with increased levels of p27 Kip1 in the nucleus and reduced activity of the cyclin-dependent kinase 2. Moreover, ABT-100 treatment resulted in a significant reduction in tumor incidence and multiplicity. Conclusions: Taken together, these findings identify a mechanism of ABT-100 function and show the efficacy of ABT-100 as a chemopreventive agent of hepatocellular carcinoma

Curvature driven acceleration : a utopia or a reality ?

The present work shows that a combination of nonlinear contribution from the Ricci curvature in Einstein field equations can drive a late time acceleration of expansion of the universe. The transit from the decelerated to the accelerated phase of expansion takes place smoothly without having to resort to a study of asymptotic behaviour. This result emphasizes the need for thorough and critical examination of models with nonlinear contribution from the curvature.Comment: 8 pages, 4 figure

Inverse bremsstrahlung contributions to Drell-Yan like processes

The contribution of the sub-process $\gamma q \to q' l_1\bar{l}_2$ in hadron-hadron interactions is considered. It is a part of one-loop electroweak radiative corrections for the Drell-Yan production of lepton pairs at hadron colliders. It is shown that this contribution should be taken into account aiming at the 1% accuracy of the Drell-Yan process theoretical description. Both the neutral and charged current cases are evaluated. Numerical results are presented for typical conditions of LHC experiments.Comment: 11 pages, 8 figure

Higher Order Curvature Theories of Gravity Matched with Observations: a Bridge Between Dark Energy and Dark Matter Problems

Higher order curvature gravity has recently received a lot of attention due to the fact that it gives rise to cosmological models which seem capable of solving dark energy and quintessence issues without using "ad hoc" scalar fields. Such an approach is naturally related to fundamental theories of quantum gravity which predict higher order terms for loop expansions of quantum fields in curved spacetimes. In this framework, we obtain a class of cosmological solutions which are fitted against cosmological data. We reproduce reliable models able to fit high redshift supernovae and WMAP observations. The age of the universe and other cosmological parameters are recovered in this context. Furthermore, in the weak field limit, we obtain gravitational potentials which differ from the Newtonian one because of repulsive corrections increasing with distance. We evaluate the rotation curve of our Galaxy and compare it with the observed data in order to test the viability of these theories and to estimate the scale-length of the correction. It is remarkable that the Milky Way rotation curve is well fitted without the need of any dark matter halo and similar results hold also for other galaxies.Comment: 8 pages, Proceedings of XVI SIGRAV conference, 13-16 September, Vietri (Italy

Non-minimally coupled scalar field cosmology on the phase plane

In this publication we investigate dynamics of a flat FRW cosmological model with a non-minimally coupled scalar field with the coupling term $\xi R \psi^{2}$ in the scalar field action. The quadratic potential function $V(\psi)\propto \psi^{2}$ is assumed. All the evolutional paths are visualized and classified in the phase plane, at which the parameter of non-minimal coupling $\xi$ plays the role of a control parameter. The fragility of global dynamics with respect to changes of the coupling constant is studied in details. We find that the future big rip singularity appearing in the phantom scalar field cosmological models can be avoided due to non-minimal coupling constant effects. We have shown the existence of a finite scale factor singular point (future or past) where the Hubble function as well as its first cosmological time derivative diverges.Comment: revtex4, 20 pages, 12 figs; (v2) title changed, analysis of critical points at infinity added, accepted to JCA

The hydrolysis mechanism of the anticancer ruthenium drugs NAMI-A and ICR investigated by DFT-PCM calculations

(ImH)[trans-RuCl4(DMSO-S)(Im)], (Im = imidazole, DMSO-S = S-bonded dimethylsulfoxide), NAMI-A, is the first anticancer ruthenium compound that successfully completed Phase I clinical trials. NAMI-A shows a remarkable activity against lung metastases of solid tumors, but is not effective in the reduction of primary cancer. The structurally similar (ImH)[trans-RuCl4(Im)(2)], ICR (or KP418), and its indazole analog (KP1019) are promising candidate drugs in the treatment of colorectal cancers, but have no antimetastatic activity. Despite the pharmacological relevance of these compounds, no rationale has been furnished to explain their markedly different activity. While the nature of the chemical species responsible for their antimetastatic/anticancer activity has not been determined, it has been suggested that the difference between reduction potentials of NAMI-A and ICR may be the key to the different biological responses they induce. In this work, Density Functional Theory calculations were performed to investigate the hydrolysis of NAMI-A and ICR in both Ru-III and Ru-II oxidation states, up to the third aquation. In line with experimental findings, our calculations provide a picture of the hydrolysis of NAMI-A and ICR mainly as a stepwise loss of chloride ligands. While dissociation of Im is unlikely under neutral conditions, that of DMSO becomes competitive with the loss of chloride ions as the hydrolysis proceeds. Redox properties of NAMI-A and ICR and of their most relevant hydrolytic intermediates were also studied in order to monitor the effects of biological reductants on the mechanism of action. Our findings may contribute to the identification of the active compounds that interact with biological targets, and to explain the different biological activity of NAMI-A and ICR

Cosmological dynamics of fourth order gravity with a Gauss-Bonnet term

We consider cosmological dynamics in fourth order gravity with both $f(R)$ and $\Phi(\mathcal {G})$ correction to the Einstein gravity ($\mathcal{G}$ is the Gauss-Bonnet term). The particular case for which both terms are equally important on power-law solutions is described. These solutions and their stability are studied using the dynamical system approach. We also discuss condition of existence and stability of de Sitter solution in a more general situation of power-law $f$ and $\Phi$.Comment: published version, references update