P148 CD68 expression in inflammatory cell infiltration of nonspecific invasive breast cancer

BackgroundTumor-associated macrophages play a main role in tumor progression and dissemination. Taking into account the high heterogeneicity of tumor the different clinical impact of macrophages, infiltrating different sites of tumor, could be expected. The aim was to detect the level of CD68+ cells (macrophages) in the different site of stroma in breast tumor in comparison to clinical course.Materials and methodsOne thirty-six women with nonspecific invasive breast cancer T1-4N0-3M0, who were treated in General Oncology Department of Tomsk Cancer Research Institute (Tomsk, Russia), were included in the present study. Patients did not receive preoperative treatment. The material was fixed in 10–12% neutral formalin. Preparation of the histological material was carried out according to standard procedures. Morphological examination of the surgical specimens was performed by the standard method using a light microscope “Carl Zeiss Axio Lab.A1” (Germany) and slidescanner “MiraxMidiZeiss” (Germany). Metastatic lesion was detected in regional lymph nodes. Immunohistochemical study was performed according to standard procedures. Cytoplasmic expression of these markers was determined in the inflammatory cell infiltrate of different tumor segments: (1) in areas with soft fibrous stroma; (2) in areas with coarse fibrous stroma; (3) in the areas of the so-called “maximum stromal-and-parenchymal relationship” where the individual tumor cells, short strands and groups of tumor cells arranged in soft fibrous stroma; (4) among parenchymal elements; (5) in gaps of ductal tumor structures. Double-stained immunofluorescence was performed according to standard procedures using Leica TCS SP2 laser-scanning spectral confocal microscope (Germany). The following primary antibodies were used: mouse monoclonal anti-human CD68 (BD Biosciences) and rabbit polyclonal anti-stabilin-1 or RS1 (marker of M2 macrophages).ResultsThe highest expression of CD68 in the inflammatory cell infiltrate was detected more frequently in areas with soft fibrous stroma (54%) or the so-called “maximum stromal-and-parenchymal relationship” (79%) in patients with breast cancer. The lowest expression of CD68 was observed in areas with coarse fiber stroma (23%). The CD68-positive cells of the inflammatory infiltrate were located between parenchymal elements of tumor (88%). Inverse correlation (R=−0.67; p=0.02) observed between tumor size and the expression of CD68 in the cells of the inflammatory infiltrate in gaps of tubular tumor structures. The CD68 expression in cells of the inflammatory tumor infiltrate was correlated with the presence of metastatic regional lymph nodes. It was found that in the case of the lymph node metastases the average score of CD68 expression in cells of ductal gaps tumor structures was lower (1.4±0.5) in comparison with the negative lymph nodes case (3.1±1.0; F=10.9; p=0.007). Same time no correlation between the CD68 expression in the inflammatory cell tumor infiltrate and the rate of tumor malignancy was found. Using confocal microscopy domination of CD68+/RS1+ cells were found.ConclusionSo, low CD68 expression level in ductal gaps tumor structures is associated with the presence of metastatic regional lymph nodes

The molecular aspects of personalized anticancer treatment

Only 25% of cancer patients, on average, benefit from therapy. Even in the cases of complete clinical response the tumor progression is an event of high level expectation. The main reasons for tumor progression are: intratumor heterogeneity resulted from clonal evolution, drug resistance, and tumor-promoting microenvironment. The reprogramming of microenvironmental stromal-inflammatory components is expected to allow tumor phenotype reversion. So, to find the new effective markers of tumor progression, drug response and targets for therapy, it could be promising to take into account the tumor-microenvironment heterogeneity and tumor clonal evolution

Comparison of titanium mesh implants with PLA-hydroxyapatite coatings for maxillofacial cancer reconstruction

Since 2013 physics of TPU and oncologists from the TCRI with participation of the “ConMet” company (Moscow) and the “Sintel” company (Tomsk Special Economic Zone resident) have been working on the theme entitled “Development of the composite implants for reconstructive surgery of a craniofacial areas of the traumatological and oncological patients” supported with the Federal Program ”R&D, part 1.3”. The goal was to develop the maxillo-facial implants on the basis of the transformable titanium mesh with PLA & hydroxyapatite coating. According to the Contract No. 14.578.21.0031, the team of developers had to start supplying these advanced implants to the industrial partners up to 2017. This research was supported with the preliminary market researches by the ISPMS SB RAS and the TP “MF”. The stages of preliminary market researches were: 1) research of the Worldwide CMF market; 2) forecasting the BRIC CMF market up to 2020; 3) the total Russian market (epidemiology) estimation as a sum of official calculations and statistics; 4) looking for the best foreign analogue prices, comparing their and our implant properties; 5) search for the best Russian analogues; 6) the investigation of the world patent databaseEspacenet for the last years, and finding the owners and applicants of patents of CMF osteosynthesis plates on the basis of titanium coated with PLA & hydroxyapatite; 7) comparison of the domestic implants, and making conclusions. Several variants of the meshes have got the equal quality with the best foreign and Russian implants. The closest analogues were titanium, polyethylene, PEEK composite meshes suited to the patient shape by the Synthes company in 2014, and the only hybrid titanium "Grey" implant with layers of gelatin, dextran, collagen, HAP & BMP-2 was found. This implant was produced by Russian institution, and it was mentioned in the report on clinical trials by L.A. Pavlova et al., 2014 [1]. There are no manufacturers of the coated implants in Russia. The average price of the similar foreign implants varies from 12 up to 4

Prognostic significance of TGF-B-associated proteins in breast cancer patients treated with adjuvant tamoxifen

We investigated the effect of 3 TGF-β-associated signaling components (TGF-β1, TGF-βR1

X-ray film chamber with carbon target of Tien-Shan complex array

X-ray films were exposed inside the ionization calorimeter under 74g/sq cm of carbon and 5 cm of lead. The X-ray film chamber area is 35 sq. m. Moving X-ray films were used, 50% of the events, which succeeded to determine incidence time, were identified with corresponding extensive air showers (EAS). For such events the size spectrum of associated EAS was derived. Two methods of energy measurement using X-ray films and ionization calorimeter were compared. The energy transfer from selected hadron to electromagnetic component is illustrated. It is found that in cascades with high energy release into electromagnetic components the hadron component is practically absent

Search for potential gastric cancer markers using miRNA databases and gene expression analysis

Aim: The aim of this study was to identify genes that are differentially expressed in gastric tumors and to analyze the association of their expression level with tumor clinicopathologic features. Methods: In the present research, we used bioinformatic-driven search to identify miRNA that are down-regulated in gastric tumors and to find their potential targets. Then, the expression levels of some of the target mRNAs were investigated using reverse transcription polymerase chain reaction (RT-PCR) analysis. Results: As a result of the bioinformatics analysis, fifteen genes were found to be potentially differentially expressed between the tumors and normal gastric tissue. Five of them were chosen for the further analysis (WNT4, FGF12, EFEMP1, CTGF, and HSPG2) due to their important role in cell proliferation and differentiation. Expression levels of these genes were evaluated in our collection of frozen tissue samples of gastric tumor and paired normal stomach epithelia. Increased FGF12 expression was observed in diffuse type of gastric cancer while WNT4 mRNA was found to be down-regulated in intestinal type of gastric cancer. Besides, CTGF gene overexpression was revealed in diffuse type of stomach cancer in comparison with that in intestinal type. Up-regulation of CTGF was also associated with lymph node metastasis. Conclusions: The findings show its expedient to perform further investigations in order to clarify diagnostic and prognostic value of CTGF, FGF12, and WNT4’s in stomach cancer as well as the role of these genes in carcinogenesis

Macrophage polarization markers of blood monocytes in patients with breast cancer

Polarized monocytes can have diagnostic value in breast cancer, including a triple negativ

Effect of atmospheric-pressure plasma jet on normal and tumor cells in vitro

The purpose of this work is to investigate the effect of low-temperature plasma on tumor and normal cells. As a result of in vitro experiments, plasma-exposed tumor and normal cells demonstrate several effects such as cell detachment, apoptosis or necrosis according to cell type and exposure parameters (power, time of exposure, frequency). In experiments, the inhibition of tumor cell growth was observed up to 70% on the 5th day after exposure. The effect of gas discharge plasma on normal cells was the opposite, and by 5 days there was a stimulation of cell proliferation. The obtained data demonstrate the prospects of using this atmospheric-pressure plasma jet in biomedical research aimed at the treatment of cancer