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

Microarray research of allelic imbalance in breast cancers during neoadjuvant chemotherapy

For single nucleotide polymorphism – SNP (SNP – Single Nucleotide Polymorphism) is characterized by phenomenon of allelic imbalance (AI). The phenomenon of allelic imbalanced (AI) is typical of many genes in different malignancies. Allelic imbalanced may result allelic deletions (loss of one copy of the locus) or amplification of one allele, resulting in only a single allelic variant of SNP is determined in the tumor in the PCR. Phenomenon of AI in tumors of breast cancer (BC) is considered in one or more genes. The phenomenon of AI during chemotherapy (CT) and especially in the longer format of the gene had not previously been studied. Thus, the aim of this work was to study microarray imbalanced allele in mammary tumors during neoadjuvant chemotherapy (NCT). Materials and methods: The study included 26 breast cancer patients with stage IIA – IIIC. The patients in the neoadjuvant mode received 2–4 courses of chemotherapy regimens FAC or CAX. DNA from 26 paired samples before treatment and operational samples were isolated by dialing QIAampDNA miniKit (Qiagen, Germany). Microarray analysis was performed on DNA chips of high density company Affymetrix (USA) CytoScanTM HD Array, which contains more than 750 thousand SNP. Microarray analysis was performed on SNP genotypes DNA tumor tissue before and after treatment for each patient and recorded as change occurring allelic imbalanced tumor tissue genotype (AA > AB > AB AA BB > AB > AB BB) during therapy. Results: The frequency of the AI in breast tumor during NCT was highly variable (within 0.9–66.5%) of the studied SNP (6850 – 497,979 SNP). For each patient, frequency shift genotype (homozygous in heterozygous genotype, and vice versa) was calculated as a percentage of all the shifts. Changes in the wild or mutant heterozygous genotypes (AA or BB > AB) were combined into one group; the second group was the sum of the change in the heterozygous genotype homozygous wild genotype or the mutant (AB > AA or BB). We have found that the direction of the AI was significantly associated effect of NCT. In the group of patients with partial regression, the direction of AI change from homozygous to heterozygous genotype often occurs (AA or BB > AB) (9/14, 64%), whereas patients with no response to the NCT (with stabilization or progression) have the opposite effect. All these patients (12/12 cases) have the direction of the change of AI from heterozygous genotype to homozygous (AA or AB > BB) (p = 0.00071). AI during chemotherapy at the level of the marked tendency (Log-rank test, p = 0.062) is associated with 5-year metastasis-free survival. Low metastasis-free survival rate is observed in patients with AI in the direction of the change from the heterozygous to homozygous genotype, while 100% survival is noted in patients with change from homozygous to heterozygous genotypes, and this imbalanced t allele is a favorable prognostic factor. Conclusion: Allelic imbalanced in breast tumor during NCT phenomenon is massive and may affect up to 67% of SNP. AI may occur in the direction of change from homozygous to heterozygous genotype, and it is associated with a good response to treatment and 100% metastasis-free survival. Apparently, this can be explained by the fact that the change from homozygous genotypes to heterozygous occur due to partial destruction of tumor cells by chemotherapy, resulting in the increase of stromal elements. In contrast, AI in the direction change from heterozygous to homozygous genotype during NCT is associated with no response to chemotherapy due to metastasis and occurring of new mutant clones in the tumor

Multidimensional visualization for the immune system state presentation in breast cancer patients

The immune system is a complex organization system possessing its hierarchical structure of morphological and functional elements united into an integral unity. Therefore the immune system state should be characterized as an integral unity. The use of the NovoSpark Visualisation approach (Canada) to multidimensional data visualization provides the visual image representing the immune system state as an integral unity. This uniform visual characteristic is formed by values of individual immunological parameters in every person. The curves appropriating the immune system states in breast cancer patients with and without cancer progression (hematogenous metastases) during a 3-year follow-up are located in disjoint areas of the multidimensional data space. The obtained data suggest that the immune system greatly influences the course and outcome of breast cancer. In prospect this approach can be useful for a breast cancer outcome prognosis

Circulating tumor cells in breast cancer: functional heterogeneity, pathogenetic and clinical aspects

Each patient has a unique history of cancer ecosystem development, resulting in intratumor heterogeneity. In order to effectively kill the tumor cells by chemotherapy, dynamic monitoring of driver molecular alterations is necessary to detect the markers for acquired drug resistance and find the new therapeutic targets. To perform the therapeutic monitoring, frequent tumor biopsy is needed, but it is not always possible due to small tumor size or its regression during the therapy or tumor inaccessibility in advanced cancer patients. Liquid biopsy appears to be a promising approach to overcome this problem, providing the testing of circulating tumor cells (CTC) and/or tumor-specific circulating nucleic acids. Their genomic characteristics make it possible to assess the clonal dynamics of tumors, comparing it with the clinical course and identification of driver mutation that confer resistance to therapy. The main attention in this review is paid to CTC. The biological behavior of the tumor is determined by specific cancer-promoting molecular and genetic alterations of tumor cells, and by the peculiarities of their interactions with the microenvironment that can result in the presence of wide spectrum of circulating tumor clones with various properties and potentialities to contribute to tumor progression and response to chemotherapy and prognostic value. Indeed, data on prognostic or predictive value of CTC are rather contradictory, because there is still no standard method of CTC identification, represented by different populations manifesting various biological behavior as well as different potency to metastasis. Circulating clasters of CTC appear to have essentially greater ability to metastasize in comparison with single CTC, as well as strong association with worse prognosis and chemoresistance in breast cancer patients. The Food and Drug Administration (USA) has approved the CTC-based prognostic test for clinical application in patients with advanced breast cancer. Prospective clinical trials have demonstrated that measuring changes in CTC numbers during treatment is useful for monitoring therapy response in breast cancer patients. Molecular and genetic analysis of CTC gives the opportunity to have timely information on emergence of resistant tumor clones and may shed light on the new targets for pathogenetic antitumor therapy

The influence of cisplatin on transcriptional profile of tumor-associated macrophages of breast cancer and colon cancer

In the present study we demonstrated the whole transcriptome analysis of model tumor-associate

Application of repetitively pulsed X-ray radiation in experimental oncology

Development of new technologies in the field of radiation required new approaches and strategies for their application. Power radiation when one continued pulsed divided to serial pulses with different specific repetition rate could provide more complicated and expressed reaction of the biological objects. We used different normal and tumor cell lines in vivo and in vitro to compare efficacy of different pulse repetition rate of X-ray radiation when the total absorbed dose didn’t exceed 1 Gy. We observed strong dependent of tumor cell reaction to repetition rate. Using this parameter we can stimulate or inhibit tumor growth up to 90% compare to control group. Irradiation of tumor-bearing mice inhibited growth of primary tumor up to 60% with the total absorbed dose 0.4 Gy. Moreover same experimental conditions allowed to reduce number of metastasis in mouse lung at 70%. That resulted in longer survival of experimental animals compare to control group. Thus we can conclude that pulsed radiation with nanosecond pulse duration has a potential for application in oncology

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