Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

Histone deacetylase inhibitors (HDIs) are promising anti-cancer agents that inhibit proliferation of many types of cancer cells including breast carcinoma (BC) cells. In the present study, we investigated the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two HDIs, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), in luminal-like BC cells. The type of drug–drug interaction between CDDP and HDIs was determined by isobolographic analysis. MCF7 cells were genetically modified to express differential levels of Notch1 activity. The cytotoxic effect of SAHA or VPA was higher on cells with decreased Notch1 activity and lower for cells with increased Notch1 activity than native BC cells. The isobolographic analysis demonstrated that combinations of CDDP with SAHA or VPA at a fixed ratio of 1:1 exerted additive or additive with tendency toward synergism interactions. Therefore, treatment of CDDP with HDIs could be used to optimize a combined therapy based on CDDP against Notch1-altered luminal BC. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of luminal-type BC with altered Notch1 activity.     

Experimental and Computational Chemistry Studies on the Inhibition Efficiency of Phthalic Acid (PHA) for the Corrosion of Aluminum in Hydrochloric and Tetraoxosulphate (VI) Acids

Protection of Metals and Physical Chemistry of Surfaces - In this work, phthalic acid is investigated for its corrosion inhibition properties (for aluminum in solutions of HCl and H2SO4) through...     

Development of a Nb3Sn multifilamentary composite conductor for a.c. use

A Nb₃Sn composite conductor with ≈ 10 000 submicron diameter filaments has been manufactured using the external diffusion process. A.c. losses were greatly reduced by the use of a fine filament size (0.53 μm, design value), a tight twist pitch (0.87 mm) and a small wire diameter (0.153 mm) with a bronze matrix. In an a.c. field with a frequency of 50 Hz and amplitude of 2.0 T, the hysteresis loss and the coupling current loss were observed to be 465 kW m⁻³ and 26 kW m⁻³, respectively. A triplex conductor was constructed by cabling three strands at a twisting pitch of 3 mm, and a small coil was wound from this cable (i.d. 11 mm, o.d. 33 mm, axial length 19 mm). With d.c. the coil generated a field of 1.3 T at the critical current, l_c of 37.4 A. When the coil was operated at 50 Hz, with an exciting current of I_c, the observed loss averaged over the windings was 240 kW m⁻³. The quenching current for 50 Hz operation was 53 A at a maximum field of 1.8 T. This was considerably higher than the critical values under d.c. conditions. Preliminary studies have shown that, if this conductor is used in superconducting armature windings of rotating machines, economical benefits are obtained compared with the use of conventional armatures.     

Potential integrals associated with quadratic distributions in a triangular domain

Exact expressions are presented for the potentials, at an arbitrary point in space, due to two quadratic distributions in a triangular disc. These expressions are obtained by means of extensions of the analytical techniques previously developed for evaluating the potential integrals for constant and linear distributions. It is shown that the potential due to any quadratic distribution in a triangle may be obtained by using the two expressions derived here, together with an expression for the potential corresponding to a linear distribution. This latter expression was presented in an earlier paper.¹ Numerical values obtained through the use of the two expressions are compared with those which result from the numerical evaluation of the potential integrals by triangle quadratures.     

The potential integral for a linear distribution over a triangular domain

In this paper an exact expression is derived for the potential at an arbitrary point due to a linear distribution of source over a triangular domain. The integral which gives the potential is evaluated by means of an extension of an analytical procedure previously evolved for a constant distribution. Numerical values of the potential are obtained for several field points by evaluating the above analytical expression, and are compared with those calculated by using triangle quadratures.     

Antagonistic Interaction between Histone Deacetylase Inhibitor: Cambinol and Cisplatin—An Isobolographic Analysis in Breast Cancer In Vitro Models

Breast cancer (BC) is the leading cause of death in women all over the world. Currently, combined chemotherapy with two or more agents is considered a promising anti-cancer tool to achieve better therapeutic response and to reduce therapy-related side effects. In our study, we demonstrated an antagonistic effect of cytostatic agent-cisplatin (CDDP) and histone deacetylase inhibitor: cambinol (CAM) for breast cancer cell lines with different phenotypes: estrogen receptor positive (MCF7, T47D) and triple negative (MDA-MB-231, MDA-MB-468). The type of pharmacological interaction was assessed by an isobolographic analysis. Our results showed that both agents used separately induced cell apoptosis; however, applying them in combination ameliorated antiproliferative effect for all BC cell lines indicating antagonistic interaction. Cell cycle analysis showed that CAM abolished cell cycle arrest in S phase, which was induced by CDDP. Additionally, CAM increased cell proliferation compared to CDDP used alone. Our data indicate that CAM and CDDP used in combination produce antagonistic interaction, which could inhibit anti-cancer treatment efficacy, showing importance of preclinical testing.     

Cytophotometric determination of non-heme iron in hepatocytes. II. Effect of fixation on the cell iron content

The study deals with the effect of different fixatives, such as absolute methanol, 96% ethanol, 10% buffered neutral formalin, as well as mixtures: methanol-formalin-acetic acid and ethanol-formalin-acetic acid (Tellesnitsky's solution) on preservation of iron in isolated hepatocytes of rats on a diet with addition of 2% carbonyl iron. The iron preservation in cells, on application of different fixatives and performance of Perls' reaction, was evaluated by the intensity of cell staining that was measured using cytospectrophotometer. The best preservation of iron in cells has been achieved when using alcohol fixatives only. Fixation of preparations with the methanol-formalin-aceticacid mixture also produced no decrease in the iron content in hepatocytes, however, morphology of the stained cells was much worse than after methanol and ethanol fixation. Fixation with Tellesnitsky's solution resulted in a 36% reduction of the cellular iron content, whereas fixation with 10% neutral formalin reduced iron content by 58%, as compared with methanol fixation. A prolongation formalin fixation from 10 min to 24 hr had no effect on the intensity of Perls' reaction.