Purpose: Tibolone is a selective tissue estrogenic activity regulator, approved for the treatment of vasomotor symptoms in postmenopausal women.We have done an exploratory, double-blind, randomized, placebo-controlled pilot trial to investigate the tissue-specific effects of 2.5 mg tibolone on breast cancer in postmenopausal women, in particular on tissue proliferation (STEM, Study of Tibolone Effects on Mamma carcinoma tissue). Experimental Design: Postmenopausal women with initially stage I/II, estrogen receptorp ositive (ER+) primary breast cancer, were randomly assigned to 14 days of placebo or 2.5 mg/d tibolone. Core biopsies of the primary tumor were obtained before and after treatment. Ki-67 and apoptosis index were analyzed in baseline and corresponding posttreatment specimen. Results: Of 102 enrolled patients, 95 had evaluable data. Baseline characteristics were comparable between both treatment groups. Breast cancer cases are mainly invasive (99%), stage I or II (42% and 50% respectively), and ER+ (99%). Median intratumoral Ki-67 expression at baseline was 13.0% in the tibolone group and 17.8% in the placebo group, and decreased to 12.0% after 14 days of tibolone while increasing to 19.0% in the placebo group.This change from baseline was not significantly different between tibolone and placebo (Wilcoxon test; P = 0.17). A significant difference was observed between the treatment groups when the median change from baseline apoptosis index was compared between the treatment groups (tibolone, 0.0%; placebo, +0.3%; Wilcoxon test; P = 0.031). The incidence of adverse effects was comparable. Conclusions: In ER+ breast tumors, 2.5 mg/d tibolone given for14 days has no significant effect on tumor cell proliferation.Vasomotor symptoms are a major side effect of adjuvant breast cancer treatment and it has been estimated that up to 96% of women who undergo chemotherapy or endocrine therapy suffer from hot flashes or night sweats (1). Although these symptoms are thought to result from systemic estrogen and progestin deprivation and can effectively be treated by hormone replacement therapy in patients who are not taking tamoxifen, such a therapeutic strategy is contraindicated, mainly because of a fear of the proliferative and tumorpromoting effects attributed to sex steroids (2). Unfortunately, the efficacy and safety of phytoestrogens as alternatives in the treatment of vasomotor symptoms is unproven and nonhormonal therapies with serotonin reuptake inhibitors and gabapentin are, at best, approximately half as effective as estrogen (3, 4). In addition, nonhormonal therapies have no effect on other postmenopausal symptoms such as bone loss or urogenital atrophy (5).Tibolone (Livial) is a selective tissue estrogenic activity regulator, approved for the treatment of climacteric symptoms in postmenopausal women. Following oral administration, it is converted into three primary metabolites, of which the 3a-hydroxymetabolite and the 3h-hydroxymetabolite only bind to the estrogen receptor a, whereas the parent...

Background. Various tumor control genes and microRNAs (miRNa) play an important role in the development and progression of colorectal cancer (CRC). the expression of these genes can differ significantly in tumor and adjacent healthy tissues. there is no exact data at what distance from the tumor the adjacent healthy tissue is located in terms of gene expression.The aim of the investigation was to study the tumor control genes (E2F3, TGFB, NFKB, KLF-12, EGFR and MMP9), as well as the microRNA genes (microRNA-15, -16, -21 and -210) expression profiles in tumor and adjacent healthy tissues.Material and methods. the study included 19 patients diagnosed with colorectal cancer. the tumor control genes (E2F3, TGFB, NFKB, KLF-12, EGFR and MMP9), as well as the miRNA genes (miRNA-15, -16, -21 and -210) expression levels were investigated in tumor and adjacent normal tissue samples taken during colonoscopy.Results. a decrease in the level of expression of E2F3 (median 3,73, Q1-Q3 2,64 Reu vs. median 6.5, Q1-Q3 6,39 REU, p=0,01) and miRNA-16 (median 2,83, Q1-Q3 4,74 REU vs. median 4,29, Q1-Q3 3,73 REU, p=0,027) and an increase in the expression level of miRNA-21 (median 2,64, Q1-Q3 1,38 REU vs. median 1,41, Q1-Q3 1,21 REU, p<0,001) were found in tumor tissue compared to normal tissue of patients with CRC.Conclusion. significant differences in the E2F3, miRNA-16 and miRNA-21 gene expressions were revealed. an increased level of E2F3 and miRNA-16 expressions at a distance of 1–2 cm from the tumor may be a predictor of tumor recurrence and progression, and an increased miRNA-21 expression in tumor tissue as compared to adjacent tissue may be a negative prognostic factor. this information can be used in further clinical research.

Background. BRCA-associated triple negative breast cancer (TNBC) is considered one of the most aggressive subtypes of breast cancer with high sensitivity to chemotherapy, which leads to increased interest in finding new treatment options for patients with this subtype of breast cancer.   Aim. To determine the role of adding a platinum drug to standard systemic neoadjuvant therapy (NAC) for patients with primary BRCA-associated TNBC with clinical stage T1–3N0–3M0, and to evaluate the effect of platinum-based drugs on recurrence-free survival in patients of this category.   Materials and methods. The study included 75 patients diagnosed with primary BRCA-associated TNBC. They were divided into 2 groups depending on the NAC provided, and then they were subdivided depending on the completion of the course of ongoing NAC, the final pathomorphological result and the presence of recurrence.   Results. Group I included 48 (64 %) patients who received the AC–T regimen; in group II (n = 27 (36 %)) patients received NAC according to the AC–TCarb regimen. Patients of group II showed a higher frequency of achieving pathological complete response (pCR) compared with patients of group I (73.7 % versus 41.2 %, respectively, p = 0.0433). Taking into account the NAC regimens being carried out, patients of group I had a slightly higher risk of recurrence compared to patients of group II (p = 0.099).   Conclusion. In patients with primary BRCA-associated TNBC, the addition of platinum compounds to the systemic NAC resulted in achieving of pCR in 73.7 % cases compared with 41.2 % pCR after the standard anthracycline-taxane NAC, which entails a reduced risk recurrence in this category of patients. Performing a full course of planned NAC has a positive trend in achieving pCR in patients of this category.

BACKGROUND: Surgical treatment of breast cancer plays a major role in the combined and complex treatment of patients. The purity of the examined edges of the resected breast tissue is the main indicator of the reliability of the breast-conserving surgery and one of the main factors in the development of local recurrence. Neoadjuvant (preoperative) systemic therapy allows evaluating the effectiveness of therapy in vivo and reducing the size of the initial formation, both in locally advanced and resectable forms of breast cancer. The main advantage of this treatment is the ability for surgeons to perform breast-conserving surgery to improve patients quality of life and aesthetic outcomes without compromising disease-free and overall survival. AIM: To study the clinical and pathological characteristics and analyze of the breast-conserving surgery in patients with breast cancer after neoadjuvant chemotherapy. MATERIALS AND METHODS: 156 performed breast-conserving surgery after neoadjuvant chemotherapy were analyzed. Breast-conserving resection implied radical removal of the residual tumor node within healthy breast tissues with the achievement of negative resection margins. If pathologists detected stained invasive cells/cancer in situ in a formalin-fixed preparation, a second surgical intervention was performed. RESULTS: Of the 156 studied anatomical preparations after breast-conserving surgery, a positive margin was found in 4 (2.56%) cases. In 4 patients, positive margin was represented by ductal carcinoma in situ. According to the results of trephine biopsy, no intraductal component was found before neoadjuvant chemotherapy. The greatest length of the ductal carcinoma in situ section is 2.2 mm. In 3 cases, the distance to the stained resection margin of the micropreparation was 1 mm. As a result of repeated pathomorphological examination of pre-cut margins after surgical intervention, cancer in situ was not found. CONCLUSIONS: The ongoing neoadjuvant systemic therapy for breast cancer with a partial or complete response of the tumor increases the percentage of breast-conserving surgery performed in patients who initially belong to the group of radical mastectomy, but who want to save breast tissue.

Glial cerebral tumors (GCT) are primary tumors of the central nervous system that develop from glial tissue. Despite the use of combination treatment, the overall median survival rate in patients with glioblastoma, the most malignant form of HCC, is low. MicroRNA is a large class of endogenous small RNA molecules that inhibit mRNA translation of target genes involved in the evolution of GCT. It was shown that miRNA-21 has antiapoptotic and invasive functions by means of silencing of the PTEN tumor suppressor. MicroRNA-128 can activate a number of genes that are responsible for the mechanisms of suppression of tumor growth. MicroRNA-342, modulating PAK4 gene expression, is involved in the control of tumor cell proliferation, invasion and apoptosis.The aim of the work was to study the feasibility of using the assessment of miRNA-21, -128 and -342 expressions in the blood plasma and saliva of patients to monitor GCT progression or stabilization during combined modality treatment.Material and Methods. The main group consisted of 56 patients with GCTs. (34 men and 22 women), aged 25 to 72 years (average age 48.5 years) GCTs. The control group consisted of 50 people (45 volunteers and 5 neurosurgical patients with extracerebral meningiomas). The study of miRNA-21, -128, and -342 expressions was carried out according to the semiquantitative StemLoopRealTime protocol, using small U6 RNA as a reference gene. Data was processed using the STATISTICA for Windows computer system.Results. In 70 % of patients with disease progression assessed by magnetic resonance imaging, without progression in cerebral and focal neurological signs, the expression level of miRNA21 exceeded the control values both in blood plasma and saliva, and the expression levels of miRNA-128 and -342 were significantly reduced. In patients with GCT stabilization, the expression levels of miRNA-21, -128, and -342 did not go beyond the reference values. The diagnostic significance of miRNA-128, -342 for GCT was 69 %; therefore these miRNAs can be used in a clinical setting. Thus, the increased expression of miRNA-21 and decreased expressions of miRNA-128 and -342 in both blood plasma and saliva indicate cerebral glioma progression.