Пути улучшения результатов лечения сарком тела матки

The choice of of ef ficient treatment of uterine sarcomas is challenge, due to the high malignancy and aggressiveness of the tumor, on the one hand, and the lack of a suf ficient amount for the treatment of uterine sarcomas studies on the other. The authors have shown to be promising, and the importance of choosing an adequate level of surgicaltreatment and the selectivity in the choice of additional methods of complex treatment. The ar ticle presents the results of treatment of sarcomas of the uterine body cancer (gynecologic) Department of Regional Oncology Center.Выбор тактики эффективного лечения сарком матки является актуальной задачей, в связи с высокой злокачественностью и агрессивностью данной опухоли, с одной стороны, и отсутствием достаточного количества исследований по лечению сарком матки, с другой.Авторами показана перспективность и важность выбора адекватного объема хирургического лечения и селективность в выборе дополнительных методов комплексного лечения. В статье представлены результаты лечения сарком тела матки онкологическим (гинекологическим) отделением областного онкологического диспансера

Sub-Telomere Directed Gene Expression during Initiation of Invasive Aspergillosis

Aspergillus fumigatus is a common mould whose spores are a component of the normal airborne flora. Immune dysfunction permits developmental growth of inhaled spores in the human lung causing aspergillosis, a significant threat to human health in the form of allergic, and life-threatening invasive infections. The success of A. fumigatus as a pathogen is unique among close phylogenetic relatives and is poorly characterised at the molecular level. Recent genome sequencing of several Aspergillus species provides an exceptional opportunity to analyse fungal virulence attributes within a genomic and evolutionary context. To identify genes preferentially expressed during adaptation to the mammalian host niche, we generated multiple gene expression profiles from minute samplings of A. fumigatus germlings during initiation of murine infection. They reveal a highly co-ordinated A. fumigatus gene expression programme, governing metabolic and physiological adaptation, which allows the organism to prosper within the mammalian niche. As functions of phylogenetic conservation and genetic locus, 28% and 30%, respectively, of the A. fumigatus subtelomeric and lineage-specific gene repertoires are induced relative to laboratory culture, and physically clustered genes including loci directing pseurotin, gliotoxin and siderophore biosyntheses are a prominent feature. Locationally biased A. fumigatus gene expression is not prompted by in vitro iron limitation, acid, alkaline, anaerobic or oxidative stress. However, subtelomeric gene expression is favoured following ex vivo neutrophil exposure and in comparative analyses of richly and poorly nourished laboratory cultured germlings. We found remarkable concordance between the A. fumigatus host-adaptation transcriptome and those resulting from in vitro iron depletion, alkaline shift, nitrogen starvation and loss of the methyltransferase LaeA. This first transcriptional snapshot of a fungal genome during initiation of mammalian infection provides the global perspective required to direct much-needed diagnostic and therapeutic strategies and reveals genome organisation and subtelomeric diversity as potential driving forces in the evolution of pathogenicity in the genus Aspergillus

Substrate Specifity Profiling of the Aspergillus fumigatus Proteolytic Secretome Reveals Consensus Motifs with Predominance of Ile/Leu and Phe/Tyr

The filamentous fungus Aspergillus fumigatus (AF) can cause devastating infections in immunocompromised individuals. Early diagnosis improves patient outcomes but remains challenging because of the limitations of current methods. To augment the clinician's toolkit for rapid diagnosis of AF infections, we are investigating AF secreted proteases as novel diagnostic targets. The AF genome encodes up to 100 secreted proteases, but fewer than 15 of these enzymes have been characterized thus far. Given the large number of proteases in the genome, studies focused on individual enzymes may overlook potential diagnostic biomarkers.As an alternative, we employed a combinatorial library of internally quenched fluorogenic probes (IQFPs) to profile the global proteolytic secretome of an AF clinical isolate in vitro. Comparative protease activity profiling revealed 212 substrate sequences that were cleaved by AF secreted proteases but not by normal human serum. A central finding was that isoleucine, leucine, phenylalanine, and tyrosine predominated at each of the three variable positions of the library (44.1%, 59.1%, and 57.0%, respectively) among substrate sequences cleaved by AF secreted proteases. In contrast, fewer than 10% of the residues at each position of cleaved sequences were cationic or anionic. Consensus substrate motifs were cleaved by thermostable serine proteases that retained activity up to 50°C. Precise proteolytic cleavage sites were reliably determined by a simple, rapid mass spectrometry-based method, revealing predominantly non-prime side specificity. A comparison of the secreted protease activities of three AF clinical isolates revealed consistent protease substrate specificity fingerprints. However, secreted proteases of A. flavus, A. nidulans, and A. terreus strains exhibited striking differences in their proteolytic signatures.This report provides proof-of-principle for the use of protease substrate specificity profiling to define the proteolytic secretome of Aspergillus fumigatus. Expansion of this technique to protease secretion during infection could lead to development of novel approaches to fungal diagnosis

Gate Road Development in High Gas Content Coal Seams at Karaganda Basin Coal Mines, Kazakhstan

Most coal seams, currently mined in the Karaganda Coal Basin, are prone to outburst. The main thick D6 coal seam is considered as most prone to outburst risk. Trials of advance degassing from the surface have not given positive results because of low permeability. 100mm diameter inseam holes are subsequently drilled in almost all longwall blocks to facilitate preliminary degassing of the coal seams. Gas extraction quantities are however low, even the holes are placed on suction To facilitate the gas release during longwall block development, of the main seam, a method of development below the seam was used. This gave rise to increase in permeability of overlying thick seam with high gas content, achieving a local degasification of the overlying seam by up to 90%. The initial development roadway was driven under the seam, in rock, at a distance of between 8-12 m from seam floor in the same contour of the future development roadway in the coal seam. A relief area was created as a result of stress redistribution above the roadway. Degassing holes were drilled from the rock development, into the seam area of the future coal seam development heading. During traditional in seam development, outburst preventive measures were taken, which increased the labour intensiveness of development working, sharply decreasing the development rate. Application of these new techniques allowed increased development rates in seams to be realised, from 25-40 m per month to 120-150 m in the outburst prone areas

Isolation and characterization of a secreted metalloprotease of Aspergillus fumigatus.

A metalloprotease (MEP) secreted by Aspergillus fumigatus was isolated from an alkaline protease-deficient mutant after the fungus was cultivated in the presence of collagen as the sole nitrogen and carbon source. The enzyme was purified 50-fold from the culture supernatant after adsorption to hydroxylapatite and carboxy-methyl-Sephadex and after gel filtration. The molecular mass was determined to be 40 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isoelectric point was estimated at pH 5.5 by isoelectric focusing. Reducing agents and divalent cations strongly inhibited enzyme activity, whereas nonionic detergents had no effect. A. fumigatus MEP was totally inhibited by EDTA, 1,10-phenanthroline, and phosphoramidon but not by inhibitors specific for serine, aspartate, and cysteine proteases. MEP is not able to cleave elastin and is thermosensitive. Sera from patients suffering from aspergilloma reacted with MEP in Western blotting (immunoblotting) analyses, suggesting that MEP promotes an antigenic response in these patients

Clinical groups of dispensary observation in oncogynecology

Тhe article presents terms of dispensary, depending on the groups of patients (groups Ia, Ib; II, IIa; III) at all the times cancer patients sub- ject to dispensary observation, restorative and periodic treatment. This article also presents a classification used in dispensary observation

Role of oncomarkers in diagnosis of multiple primary neoplasms of female reproductive tract

Complex measurements of tumor markers help to improve the diagnosis of multiple primary neoplasms (MPN) significantly. For breast- ovarian MPN CA-125 was increased in 92.6 % and CA-153 — in 81.6 %. In patients with ovarian-colorectal MPN CA-125 was increased in 79.0 % and carcinoembryonic antigen — in 90.0 %

Overview of Aspergillus allergens

Fungi in general and, Aspergillus fumigatus (A. fumigatus) in particular, are able to produce complex patterns of IgE-binding molecules. Robotics-based high throughput screening of A. fumigatus cDNA libraries displayed on phage surfaces revealed at last 81 different sequences encoding structures potentially able to bind to serum IgE of sensitised individuals suffering from A. fumigatus-related complications. Although not all of these allergens have been characterised in detail, A. fumigatus still represents the best investigated allergenic source. A total of 23 A. fumigatus allergens are recorded by the official allergen list of the International Union of Immunological Societies (http://www.allergen.org) and this is by far the longest allergen list reported for a single allergenic source. The IgE-binding molecules include species-specific as well as phylogenetically highly conserved cross-reactive structures and such with unknown function. A subset of cDNAs have been used to produce and characterise the corresponding recombinant allergens which have proven to be useful diagnostic reagents allowing specific detection of A. fumigatus sensitisation and differential diagnosis of allergic bronchopulmonary aspergillosis. Structures highly conserved through different species like manganese-dependent superoxide dismutase, P2 acidic ribosomal protein, cyclophilins and thioredoxins induce, beyond sensitisation, IgE antibodies able to cross-react with the corresponding homologous self-antigens. The frequently observed cross-reactivity is traceable back to shared discontinuous B-cell epitopes as shown by detailed analyses of the crystal structures