Investigation of the structure of poly(p-chlorophenyl glycidyl ether) by the 13C n.m.r. technique: tacticity and addition isomerism

The p-chlorophenyl glycidyl ether was polymerized in the presence of Al(OiPr)₃, ZnCl₂, SnCl₄, BuOK, KOH and by the Al(OiPr)₃ZnCl₂ 1:1 initiator system. Analysis of the ¹³C n.m.r. spectra of the poly(p-chlorophenyl glycidyl ethers) obtained has made it possible to determine their tacticity and the content of the head-to-tail and head-to-head linkages in the polymer chain.     

Monte Carlo simulation of radiation-induced solid state polymerization

A Monte Carlo method was used for a computer simulation of radiation-induced solid state polymerization. The propagation of polymer chains was simulated by means of self-avoiding random walks on a tetrahedral lattice. The initiation and termination of the chains were modelled by pseudorandom processes. The influence of conditions of the in-source process on the post-polymerization kinetics and on the degree of polymerization of the polymers was studied.     

Determination of the ash yield and the mineral matter content of brown coals by density measurements

A method of measuring the density of bed-moist brown coals based on their plastic properties is described and the feasibility of using the method for determination of the ash yield of the coal is evaluated.     

Integrated instrumental analysis of soft brown coals

A method for the simultaneous determination of calorific value Q^r, ash yieldA^r and total water content W^r_t of soft brown coals is described. The method involves instrumental analysis of brown coal samples using neutron thermalization and gamma back-scattering techniques. Over 80 coal samples (1.1 kg) were analysed, having Q^rvalues up to 15.5 MJ kg^?1,A^r ranging from 3.6 to 76.1 wt% and W^r_t ranging from 11.4 to 61.7 wt%. A comparison of the results from the instrumental method with those of standard laboratory analyses is given, followed by a discussion of the accuracy of the method and of possible ways for improving it.     

Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models

1,25-Dihydroxycholecalciferol, the hormonally active vitamin D₃ metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)₂D₃ analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR.     

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses.     

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.     

Stiffness alterations of single cells induced by UV in the presence of nanoTiO2

Nanocrystalline titanium dioxide (nanoTiO2) has been reported to generate reactive oxygen species (ROS) under UV illumination. In our studies, changes in mechanical properties of human skin fibroblasts, exposed to the oxidative stress induced in the presence of nanoTiO2 and UV light, were studied using atomic force microscopy (AFM). The exposure of cells to the action of ROS was performed at low TiO2 concentration (4 microg/mL) and under illumination with low-intensity UVA (8 and 20 mW/cm2) or UVC (0.1 mW/ cm2). AFM measurements of the cell stiffness were carried out immediately after exposure of cells to the oxidative stress. The data suggest that under illumination with low-intensity UVA nanoTiO2 generates ROS, which, in turn, damage cellular and subcellular structures. This process was detected by AFM as a marked drop in the cellular stiffness of ca. 30-75%, which occurred rapidly, in the time frame of 1 min. The photo-oxidative stress inducing the decrease of cell stiffness was cancelled in the presence of a well-established antioxidant, beta-carotene. The results highlight the sensitivity of AFM to detect early changes in mechanical properties of cells exposed to oxidative stress.     

Formation of mesoglobules in aqueous media from thermo-sensitive poly(ethoxytriethyleneglycol acrylate)

A series of six poly(ethoxytriethyleneglycol acrylate) (PETEGA) homopolymers were synthesized by atom transfer radical polymerization, reversible addition-fragmentation transfer polymerization, and anionic polymerization in order to cover a molecular weight range from 7,000 to 40,000 Da. The polymers exhibited a lower critical solution temperature (LCST) behavior in water, which was observed by the occurrence of a cloud point (CP) at around 35 °C. The transmittance of visible light versus temperature dependence overlapped during the cooling and the heating cycles, showing almost a complete lack of hysteresis. Moreover, instead of the occurrence of an uncontrolled macroscopic phase separation, stable colloidal aggregates (mesoglobules) of narrow distribution in particle size were formed in water at temperatures above the LCST of PETEGA at 1 g L⁻¹ solutions. The dimensions of the mesoglobules ranged from 91 to 235 nm, and particle size was not influenced by the molecular weight of PETEGA. Temperature changes caused considerable variations of the mesoglobules dimensions, which were smaller at higher temperatures. The addition of an anionic surfactant simultaneously increased the CP values by 4–6 °C and lowered the dimensions of the mesoglobules.