Identification of novel PTEN-binding partners: PTEN interaction with fatty acid binding protein FABP4.

PTEN is a tumor suppressor with dual protein and lipid-phosphatase activity, which is frequently deleted or mutated in many human advanced cancers. Recent studies have also demonstrated that PTEN is a promising target in type II diabetes and obesity treatment. Using C-terminal PTEN sequence in pEG202-NLS as bait, yeast two-hybrid screening on Mouse Embryo, Colon Cancer, and HeLa cDNA libraries was carried out. Isolated positive clones were validated by mating assay and identified through automated DNA sequencing and BLAST database searches. Sequence analysis revealed a number of PTEN-binding proteins linking this phosphatase to a number of different signaling cascades, suggesting that PTEN may perform other functions besides tumor-suppressing activity in different cell types. In particular, the interplay between PTEN function and adipocyte-specific fatty-acid-binding protein FABP4 is of notable interest. The demonstrable tautology of PTEN to FABP4 suggested a role for this phosphatase in the regulation of lipid metabolism and adipocyte differentiation. This interaction was further studied using coimmunoprecipitation and gel-filtration assays. Finally, based on Biacore assay, we have calculated the K(D) of PTEN-FABP4 complex, which is around 2.8 microM.

Solution to the bioheat equation for hyperthermia with La(1-x)Ag(y)MnO(3-delta) nanoparticles: the effect of temperature autostabilization.

This work aimed to analyze the possibility and performance of the temperature controlled hyperthermia based on AC heating of magnetic nanoparticles with low Curie temperature. Temperature dependence of dynamic magnetic susceptibility has been studied experimentally on fine powders of La(0.8)Ag(0.15)MnO(2.95) in the frequency range of 0.5-2.0 MHz. Critical drop of the AC magnetic losses was found in the vicinity of the Curie point, T(C) = 42 degrees C. The obtained data was used in the numerical analysis of the bioheat equations under typical conditions of the hyperthermia treatment. The mathematical model includes a spherical tumor containing magnetic particles and surrounded by concentric healthy tissue, with account made for the blood perfusion. The calculations performed for various AC power, tumor sizes and doping geometries predict effective autostabilization of the temperature at T congruent with T(C) inside the tumor and steep temperature profile at the interface with the healthy tissue.

Ag-doped manganite nanoparticles: new materials for temperature-controlled medical hyperthermia.

The purpose of this study was to introduce newly synthesized nanomaterials as an alternative to superparamagnetic ironoxide based particles (SPIO) and thus to launch a new platform for highly controllable hyperthermia cancer therapy and imaging. The new material that forms the basis for this article is lanthanum manganite particles with silver ions inserted into the perovskite lattice: La(1-x)Ag(x)MnO(3+delta). Adjusting the silver doping level, it is possible to control the Curie temperature (T(c)) in the hyperthermia range of interest (41-44 degrees C). A new class of nanoparticles based on silver-doped manganites La(1-x)Ag(x)MnO(3+delta) is suggested. New nanoparticles are stable, and their properties were not affected by the typical ambient conditions in the living tissue. It is possible to monitor the particle uptake and retention by MRI. When these particles are placed into an alternating magnetic field, their temperature increases to the definite value near T(c) and then remains constant if the magnetic field is maintained. During the hyperthermia procedure, the temperature can be restricted, thereby preventing the necrosis of normal tissue. A new class of nanoparticles based on silver-doped manganites La(1-x)Ag(x)MnO(3+delta) was suggested. Ag-doped perovskite manganites particles clearly demonstrated the effect of adjustable Curie temperature necessary for highly controllable cellular hyperthermia. The magnetic relaxation properties of the particles are comparable with that of SPIO, and so we were able to monitor the particle movement and retention by MRI. Thus, the new material combines the MRI contrast enhancement capability with targeted hyperthermia treatment.

Content of proinflammatory cytokine in patients with clinical remission of chronic herpes infection during immunocorrection.

The concentrations of cytokines (interleukin-1beta, interleukin-6, and interferon-gamma) in blood plasma from patients with remission of chronic herpes infection were measured during immunocorrective therapy. Our results indicate that immunocorrection is pathogenetically substantiated and immunologically effective. It was manifested in reduction of inflammation and activation of antiviral protection.

Laser with rapid tuning of the spectrum shape.

We have studied a laser system with quick electronic tuning of the spectrum shape and continuous distribution. The proposed method is based on separate control of phase and amplitude spatial distributions of resonator transmittance. Evolution of the spectral function of the diffractively coupled dispersive resonators and the model for the formation of the resonator with the spectral function given by its moments are studied theoretically. The synthesis of continuous spectra is investigated experimentally in the laser with a novel control element including a spatial acousto-optic modulator and a tunable lens telescope.