Role of Epigenetic Modification and Immunomodulation in a Murine Prostate Cancer Model

INTRODUCTION. Decreased expression of highly immunogenic cancer-testis antigens (CTA) might help tumor to achieve low immunogenicity, escape immune surveillance and grow unimpeded. Our aim was to evaluate CTA expression in tumor and normal tissues and to investigate possible means of improving the immune response in a murine prostate cancer (CaP) model by using the combination of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator lenalidomide. No study to date has examined the effect of this combination on the prostate cancer or its impact on antigen-presenting cells (APC). MATERIALS AND METHODS. Gene microarrays were performed to compare expression of several CTA in murine prostate cancer (RM-1 cells) and normal prostate. RM-1 cells were treated with 5-AzaC and real-time PCR was performed to investigate the expression of several CTA. Western blotting was used to determine whether expression of CTA-specific mRNA induced by 5-AzaC resulted in increase in the corresponding protein. Effect of the epigenetic agents and immunomodulators was assessed on dendritic cells (DC) using flow cytometry, ELISA and T-cell proliferation assay. RESULTS. Gene arrays demonstrated decreased expression of 35 CTA in CaP tissue compared to normal prostate. 5-AzaC treatment of RM-1 prostate cancer cells upregulated the expression of all 13 CTA tested in a dose-dependent fashion. DC were treated with 5-AzaC and lenalidomide and the expression of surface markers MHC Class I, MHC Class II, CD80, CD86, CD 205, and CD40 was increased. Combination of 5-AzaC and lenalidomide enhances the ability of DC to stimulate T-cell proliferation in mixed leukocyte reaction. Secretion of IL-12 and IL-15 by DC increased significantly with addition of 5-AzaC or 5-AzaC and lenalidomide. CONCLUSIONS. Decreased expression of CTA by prostate cancer may be a means of escaping immune monitoring. Combination of epigenetic modifications and immunomodulation by 5-AzaC and lenalidomide increased tumor immunogenicity and enhanced DC function and may be used in the treatment of advanced prostate cancer

(E)-3-(4-Chloro­phen­yl)-1-(2-fur­yl)prop-2-en-1-one

In the title mol­ecule, C13H9ClO2, the benzene and furyl rings are slightly twisted from each other with a dihedral angle of 5.1 (1)°. An intra­molecular C—H⋯O hydrogen-bond inter­action generates an S(5) ring motif. In the crystal structure, mol­ecules are stacked along the b axis and the crystal packing is stabilized by weak inter­molecular C—H⋯O hydrogen bonds

(E)-3-(2-Chloro­phen­yl)-1-(3-methoxy­phen­yl)prop-2-en-1-one

The title compound, C16H13ClO2, adopts an E configuration with respect to the double bond of the propenone unit. The two benzene rings are twisted slightly from each other, making a dihedral angle of 7.14 (5)°. The mol­ecules are arranged in stacks, in which adjacent mol­ecules are related by inversion symmetry and form π–π inter­actions with a centroid–centroid distance of 3.7098 (6) Å. C—H⋯O and C—H⋯π inter­actions are formed between neighbouring mol­ecules

The relationship of dielectric response and water activity in food

This study has deduced a correlation between points of inflection of water activity and loss factor with respect to moisture content. A point of inflection in loss factor with respect to moisture content was found to coincide with the sorption isotherm point of inflection that defines the transition from multilayer to solution in every instance analysed, with an average difference of just 0.01kg.kg-1. Food can support microbial growth and chemical reactions in water activity levels above this critical transition. This correlation was discovered using published dielectric and sorption data for specific foods at similar temperatures. It was found that low sugar foods containing high levels of hydrocolloids generally exhibited different behaviour from fruits. This shows that microwave heating behaviour will be different in fruits compared to low sugar foods with high hydrocolloid content when drying to achieve a certain water activity and therefore shelf life

Characterisation of potato crisp effective porosity using micro-CT

Background The effective porosity is an important quantitative parameter for food products that has a significant effect on taste and quality. It is challenging to quantify the apparent porosity of fried potato crisps as they have a thin irregularly shaped cross section containing oil and water. This study uses a novel micro-CT technique to determine the solid volume fraction and hence the effective porosity of three types of potato crisps: standard continuously fried crisps, microwaved crisps, and continuously fried ‘kettle’ crisps. Results It was found that continuously fried kettle crisps had the lowest effective porosity at 0.54, providing the desired crunchy taste and lower oil contents. Crisps produced using a microwave process designed to mimic the dehydration process of standard continuous fried crisps had an effective porosity of 0.65, which was very similar to the effective porosity of 0.63 for standard continuously fried crisps. The results were supported by the findings of a forced preference consumer test. Conclusion The effective porosity affects the product taste and is therefore a critical parameter. This study shows that micro-CT analysis can be used to characterise the change in effective porosity of a thin irregularly shaped food product, caused by a change of cooking procedure

4-Chloro-N′-[(Z)-4-(dimethyl­amino)benzyl­idene]benzohydrazide mono­hydrate

In the title compound, C16H16ClN3O·H2O, the dihedral angle between the two aromatic rings is 44.58 (11)°. The N atom of the dimethyl­amino group adopts a pyramidal configuration. In the crystal structure, mol­ecules are linked into a two-dimensional network parallel to the (001) plane by inter­molecular N—H⋯O, O—H⋯N and O—H⋯O hydrogen bonds involving the water mol­ecule and C—H⋯Cl hydrogen bonds. In addition, C—H⋯π inter­actions are observed

Enhanced 'In-situ' catalysis via microwave selective heating: catalytic chain transfer polymerisation

An extremely facile, single stage, ‘in-situ’, Catalytic Chain Transfer Polymerisation (CCTP) process has been identified, where the optimal polymerisation process was shown to depend upon a combination of catalyst characteristics (i.e. solubility, sensitivity, activity) and the method of heating applied. In comparison to the current benchmark catalyst, the preparation of which is only about 40 % efficient, this represents a significant increase in waste prevention/atom efficiency and removes the need for organic solvent. It was also shown possible to significantly reduce the overall ‘in-situ’ reaction cycle time by adopting different processing strategies in order to minimise energy use. The application of microwave heating was demonstrated to overcome system diffusion/dilution issues and result in rapid, ‘in-situ’ catalyst formation. This allowed processing times to be minimised by enabling a critical concentration of the species susceptible to microwave selective heating to dominate the heat and mass transfer involved

1-(2,4-Dichloro­phen­yl)-3-(4-methyl­phen­yl)prop-2-en-1-one

The mol­ecule of the title compound, C16H12Cl2O, adopts an E configuration. The dihedral angle between the two benzene rings is 42.09 (5)°. In the crystal structure, mol­ecules are linked into a three-dimensional framework by weak C—H⋯O inter­actions and by C—H⋯π inter­actions involving the methyl­phenyl ring

2,5-Dimethoxy­benzaldehyde thio­semicarbazone

In the title mol­ecule, C10H13N3O2S, the dihedral angle between benzene and –N—C(=S)—N—N=C– planes is 9.20 (6)°. The two meth­oxy groups are coplanar with the benzene ring [C—O—C—C torsion angles of −2.31 (18) and −6.45 (17)°]. In the crystal structure, mol­ecules are linked by inter­molecular N—H⋯S, N—H⋯O and C—H⋯O hydrogen bonds, forming a three-dimensional network