Introduction. The efficacy of anticancer treatment depends on biological factors of tumor. The aim of the study was to determine the activity of proteasomes and calpains and to  reveal their association with VEGF, HIF-1α and NF-κΒ expressions in normal, primary and metastatic renal cell carcinoma (RCC) tissues. Methods. Ninety-three patients with renal cell carcinoma were included into the study. The expression levels of transcription factor and VEGF were measured using ELISA kits. The  levels of proteasome subunits were measured by Western Blotting. Proteasome and calpain  activities were determined using specific fluorogenic  substrates. Results. We revealed inactivation of proteolysis in patients with kidney cancer. Disease advance was associated with a significant depression of cellular proteolysis and increase in  transcription and growth factor levels in primary kidney cancer tissues. The proteolysis  activation was found in metastatic tissues. Conclusions. Our results suggest that NF-κΒ, HIF-1α and VEGF transcription factors and intracellular proteolytic systems are involved in kidney cancer progression.

Introduction. The transcription factor Brn-3α (product of the POU4F1) plays a significant role in carcinogenesis. The purpose of the study was to investigate Brn-3α, AR, ERα expressions in tissues of benign prostatic hyperplasia and prostate cancer as well as to determine their association with AKT/mTOR signaling pathway activation. Material and methods . The study included 30 patients with locally advanced prostate cancer and 15 patients with benign prostatic hyperplasia. The expression levels of Brn-3α, AR, ERα and the components of AKT/m-TOR signaling pathway were determined using RT-PCR assay. Results. Overexpression of Brn-3α in prostate cancer tissues was found to be associated with high level of ERα mRNA. High expression of AR was revealed in tissues of benign prostatic hyperplasia and prostate cancer. High expression levels of AKT, m-TOR and PTEN were observed in prostate cancer tissues. However, no significant changes in PTEN mRNA level were found in tissues of prostatic hyperplasia. Conclusion. Brn-3α transcription factor was associated with prostate cancer and accompanied with high expression levels of ERα, AKT and m-TOR.

Introduction. The crosstalk between the estrogen and growth factor receptors signaling may play an important role in the resistance to endocrine therapy. The aim of the study was to examine the relationship between the protein and receptor gene expression of transforming growth factor β type I (TGF-βRI) and its polymorphism with progression of luminal breast cancer patients treated by adjuvant tamoxifen. Material and methods .  The study included 105 patients with luminal breast cancer (T 1-3 N 0–3 M 0 ), who had received adjuvant tamoxifen  at a dose of 20 mg/day for at least 5 years. Patients who developed distant metastasis or recurrence after tamoxifen therapy were defined as tamoxifen resistance (TR) group, while distant metastasis-free patients were analyzed as tamoxifen sensitive (TS) group. TGF-βRI expression level was evaluated using immunohistochemistry. TGF-BRI gene expression and genotypes for rs334354 SNP were detected by a Real-time PCR. Results. We found high TGF-βRI gene expression in patients with luminal A subtype compared with luminal B breast cancer (p=0.050). The Int7G24AA and Int 7G24A mutant carriers were more prevalent in luminal A breast cancer patients (p=0.019 and p=0.007, respectively). TGF-βRI protein expression level was significantly higher in the tamoxifen sensitive group compared to tamoxifen resistance breast cancer patients regardless of molecular subtypes (p=0.043). There was a trend for a tamoxifen sensitivity among luminal B breast cancer patients with a high TGF-βRI protein expression (p=0.090). Conclusion. TGF-βRI protein expression level can be a potential molecular marker of tamoxifen resistance in luminal breast cancer patients.

Purpose of work. To perform a genome-wide association study of loss of heterozygosity (LOH) with monoresistance genes expression during neoadjuvant chemotherapy (NAC) in breast cancer. Materials and methods. The study involved 68 patients with breast cancer. The tumour stages were IIAIIIB. RNA was extracted from tissue specimens (before and after NAC) using RNeasy Plus mini Kit (Qiagen, Germany). Expression profiling of the RRM1, ERCC1, TOP1, TOP2a, TUBB3, TYMS, BRCA1 genes was carried out using quantitative real-time PCR (qPCR). DNA was extracted from 68 biopsy specimens of tumour tissues using QIAamp DNA mini Kit (Qiagen, Germany). LOH status was detected using microarray analysis using high density DNA-chip manufactured by Affymetrix CytoScanTM HD Array company. Results. As a result of the study of loss of heterozygosity was evaluated in 13815 genes. The frequency of LOH varied from 0% to 63%. The highest incidence of heterozygosity loss events is characteristic for genes of 16, 17 and the X-chromosome. Our study established that the phenomenon of loss of heterozygosity in monoresistance genes (BRCA1, ERCC1, RRM1, TOP1, TOP2A, TUBB3 and TYMS), is not associated with their level of expression in the tumor. A statistical association has been found between LOH and level of expression of the studied genes in 54 genes. Among them it is necessary to note genes encoding miRNA and «zinc fingers» involved in the regulation of transcription of many genes, transmembrane drug transporters and ion channels, genes of the MAP kinase signaling pathway, and others. Conclusion. The results of this study allow for the more exact determination of the expression picture of monoresistance genes in the tumor and the indication of new candidate genes which are involved in the regulation of the expression of these genes. Evaluation of the loss of heterozygosity in tumor tissue can be used as an additional criterion for personalizing chemotherapy.

Background. Search for more informative prognostic parameters in patients with renal cell carcinoma is an actual problem of modern oncology. Purpose: to study the prognostic significance of expression of transcription factors, VEGF growth factors, its receptors, m-TOR protein kinase and the activity of intracellular proteinases in patients with disseminated renal cell carcinoma. Material and methods. Forty patients with metastatic renal cell carcinoma (T3–4N0–1M1) were included into the study. In accordance with the MSKCC scale, all patients were divided into 3 groups: with good prognosis (n=13), intermediate (n=26) and unfavorable prognosis (n=1). Further, the analysis included patients with good and intermediate prognosis (n=39). All patients received targeted therapy with pazopanib or everolimus. Palliative nephrectomy was performed after completion of preoperative treatment. The level of transcription and growth factors was studied using IFA method. The proteasome and calpain activities were assayed fluorometrically. Results. Initially high levels of the expression of HIF-1 transcription factor and VEGF growth factor in renal cell carcinoma were associated with good disease prognosis evaluated according to the MSKCC scale. The targeted therapy with pazopanib/ everolimus resulted in decrease in the expression of HIF-1, NF-κB р65, NF-κB and р50 transcription factors, VEGF growth factor and the proteasome activity. The increased calpain activity in patients with intermediate prognosis was associated with disease progression. Conclusion. Additional molecular parameters that increase the informative value of the MSKCC scale were identified, allowing for more precise prediction of the disease outcome in patients with metastatic renal cell carcinoma.

This review about the application of radiotherapy in breast cancer patients after radical mastectomy. Emphasizes the need for a differentiated approach to radiation therapy, which should be based on the definition of clinical morphological factors that determine the risk of loco-regional recurrence of breast cancer.

Capabilities of 199Tl-chloride and 99mTc-MIBI scintigraphy in the non-nonspecific indications of bone and soft tissue sarcomas in overall 31 patients (34 lesions) were studied. Sensitivity of these methods in the detections of neoplasms reached 96.0 % and 100.0 %, respectively. It described positive, negative and mixed types of sarcomas visualizations on the both 199Tl-chloride and 99mTc-MIBI scintigraphy. There are preconditions for the 199Tl-chloride scintigraphy in the successful differentiations between bone and soft tissue sarcomas and benign tumors or non-tumor diseases, primarily inflammations.

Background. The paper has been devoted to the study of clinical and morphological features of bilateral breast cancer (BC). Despite the increased interest in the lateral BC, pathogenesis of this type of cancer have been little studied. М aterials and methods. Clinical and morphological parameters were studied in 600 patients with unilateral and bilateral breast carcinoma. Results. Synchronous and metachronic bilateral breast cancer is characterized by more pronounced heterogeneity of the morphological structure with the frequent presence of discrete groups of tumor cells and ductal structures in the tumor node as compared to unilateral breast cancer. Synchronous bilateral breast cancer has a favorable clinical course and is mainly represented by the luminal A molecular genetic type. Metachronous bilateral breast cancer is often characterized as a triple negative and luminal B type with high proliferative activity and is associated with poor prognosis. There is a difference in prognostic parameters of lymphogenous and hematogenous metastasis between synchronous and metachronous breast cancer. For synchronous bilateral breast cancer, morphological parameters can serve as prognostic factors of hematogenous and lymphogenous metastasis. For metachronous breast cancer, prognosis of hematogenous metastasis is associated with severity of lymphogenous metastasis. Conclusion. The data obtained allow us to determine the typical clinical and morphological features of synchronous and metachronous bilateral breast cancers, as well as to identify additional prognostic parameters of tumor progression.

New and original values (coefficient of phosphorylation and coefficient of intracellular distribution) proposed. They are reflecting a functional state of the heat shock protein 27 kDa (Hsp27) in tumor cells of breast cancer. These coefficients are more clearly reflect the functional state of Hsp27, than classical evaluation of chaperone expression only in the cytoplasm. It has been shown that in tumors with high expression of receptor Her2/neu on the membrane in the absence of gene amplification cerb2/neu (Her2/neu (3+) FISH (-)) there are low coefficients of phosphorylation and intracellular distribution as compared with Her2/neu-positive (Her2/neu (2+/3+) FISH (+)) and Her2/neu-negative tumors (Her2/neu (0/1+) FISH (-)). The possible molecular mechanisms of the phenomenon of dissonance cerb2 / neu gene amplification and receptor Her2/neu expression on the membrane of tumor cells breast cancer are discussing.

The mechanism of regulation of ABC transporter gene expression, which is related to individual characteristics of the tumor-bearing organism and its tumor, defined by gene single nucleotide polymorphisms (SNP – Single Nucleotide Polymorphism) has not been extensively studied. We conducted large-scale genome studies of association of SNP with the level of ABC transporter gene expression. The study involved 68 patients with morphologically verified diagnosis of breast cancer treated with neoadjuvant chemotherapy (NAC). Using a quantitative Real-time PCR, the expression of 4 multidrug resistence (MDR) genes ( ABCB1, ABCC1, ABCC2, ABCG2) was studied in surgical samples after NAC. Microarray analysis was performed using high density DNA microarrays, which contain more than 750.000 SNPs. Six SNPs significantly associated with postoperative expression levels of multidrug resistance genes, ABCB1, ABCC1, ABCC2, ABCG2 , were identified. It was shown that in carriers of a rare genotype, the expression levels of all 4 examined genes in tumors after chemotherapy were either decreased (rs2680835, rs1951366 and rs12018988), or increased (rs4676478, rs6896596, rs1154121) compared to those observed in carriers of frequent and heterozygous genotypes of the SNP. The possible mechanisms of the effect of the identified SNPs and their genes on the expression of ABC transporters were discussed.

The development of castration-resistant prostate cancer is an important problem of modern oncology. The review is focused on the system of growth factors – neuregulins and hepatocyte growth factor (HGF), direct pathligands of ErbB tyrosine protein kinases and hepatocyte growth factor receptor, c-Met, the activation of which triggers a cascade of signaling pathways, ending by the stimulation of proliferation of cancer cells, their migration under conditions of the development of tolerance to the treatment of castration.

The review aimed to assess the role of local hyperthermia in combined modality treatment of soft tissue sarcoma. The recent randomized trials have shown significant benefits from local hyperthermia in patients with soft tissue sarcoma. When combined with radiotherapy, hyperthermia has a complementary and additive effect. Extensive researches have also shown that hyperthermia improves the efficacy of many chemotherapeutic agents. Besides the increased effectiveness of radiotherapy and chemotherapy, hyperthermia has many anti-cancer effects and improves treatment results in patients with soft tissue sarcomas.

The purpose of the present research was influence studyingneoadjuvantMVAC (cisplatin, methotrexate, vinblastin, doxorubicin) on efficacy of treatment muscleinvasive bladder cancer. Neoadjuvant chemotherapy in patients with muscle invasive bladder cancer reduces quantity of local recurrence, enlarges lifetime and reduces quantity of carried out radical cystectomy.

The article is devoted to the study the characteristics of hematogenous metastasis in bilateral synchronous and metachronous breast cancer. The comparison of the obtained expression and morphological characteristics of primary tumor nodules with features of hematogenous metastasis to identify prognostically significant parameters. The study included surgical material from 566 patients with invasive carcinoma of the non-specific type of breast cancer. The study found that in patients with synchronous bilateral breast cancer tended to have a lower incidence of hematogenous metastasis in comparison with two-sided and one-sided defeat of metachronous breast cancer. On the basis of studies performed in synchronous and metachronous bilateral breast cancer for predicting hematogenous metastasis is recommended to use different prognostic parameters. The risk of hematogenous metastasis in patients synchronous bilateral cancer associated with fibrosis of the stroma of the tumor, monomorphic structure infiltrative component comprising a smaller number of different types of structures. When metachronous bilateral lesions in the case of the presence of hematogenous metastasis was detected more severe fibrosis of the stroma of the tumor was determined a lower percentage rate and the expression of receptors for estrogen, as well as more and larger percentage of the affected lymph node metastases.

The purpose of the study was to assess immediate response to preoperative external beam radiotherapy in patients with soft tissue sarcomas. The study comprised 55 patients with primary and recurrent soft tissue sarcomas. All patients underwent external beam radiotherapy at a total dose of 38-44 Gy in 5 fractions of 3 Gy daily, followed by surgery with 10-15 Gy intraoperative radiotherapy. The objective tumor response to preoperative external beam radiotherapy was assessed using RECIST criteria. Partial response to preoperative radiotherapy was achieved in 9.1% of patients and disease stabilization in 90.9% of cases. Grade I pathological tumor response was observed in 25 (46.5 %) patients, grade II tumor response in 19 (34.5 %) patients and grade III tumor response in 11 (20 %) cases. A 3-week interval between radiotherapy and surgery was the most optimal time. Pathological tumor response with RECIST criteria is an additional parameter in assessment of immediate tumor response.

Luminal A breast cancer has been shown to be characterized by the marked morphological heterogeneity. It is manifested by the variety of the infiltrative component structure of the primary tumor in which different structure types vary widely. The frequency of metastatic involvement of lymph nodes has appeared to associate with a variety of infiltrative component of the tumor and the presence of microalveolar structures in it. Neither morphological patterns of the lesion nor parameters of lymphogenic metastasis were associated with hematogenous dissemination, thus allowing no them to be considered as prognostic criteria.

The present study has found significant heterogeneity of luminal A breast cancer group, which is manifested by differences in relationship between the frequency of lymphogenic metastasis and morphologic and molecular-biological parameters of the primary tumor. The frequency of regional metastases has appeared to relate to the presence of microalveolar structures in infiltrating component of invasive ductal breast cancer and to its phenotypic variety only in menopausal patients. It can be evidence of differences in tumor pathogenesis in patients with different state of menstrual function even within one molecular-genetic tumor group. It is important to emphasize that the different variants of clinical behavior of luminal A breast cancer are associated with morphological parameters of the tumor, allowing one to easily obtain the additional information during histological examination of bioptic material for predicting clinical course of luminal-type A breast cancer.