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Tumors of female reproductive system

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Vol 11, No 3 (2015)
View or download the full issue PDF (Russian)
https://doi.org/10.17650/1994-4098-2015-11-3

MAMMOLOGY. TOPICAL ISSUE

10-14 1261
Abstract

Despite progress in treating breast cancer (BC) using a combined approach in view of morphological findings, distant metastases may develop in 30–90 % of patients with primary BC even at its early stages. The cancer stem cell (CSC) theory is one of the versions that could at least partially explain therapeutic inefficiency. This theory suggests that cancer may occur and arise from a small proportion of stem cells that are able to induce tumor growth and to affect resistance to chemoand radiotherapy. CSCs were identified in different malignant tumors, including BC, cancer of the prostate, colon, pancreas, head and neck, melanoma, and multiple myelomas. 

This investigation analyzed aldehyde dehydrogenase type 1 (ALDH1) expression in patients with BC. Moreover, the investigators examined the relationship between this marker and the clinical and pathological features of BC. The investigation enrolled 83 locally advanced BC (T1–4N0–3M0) patients treated in 2005 to 2009. To detect CSCs, 83 histological specimens obtained at biopsy in BC patients treated at the Russian Research Center for Radiology and Surgical Technologies underwent immunohistochemical examination for ALDH1 according to the developed protocol. Analysis of a relationship between time to metastases and ALDH1 expression showed a statistically significant decrease in time to disease progression in BC patients with high ALDH1 expression versus those with low ALDH1 expression. The similar trend was observed in overall survival. The survival of patients with less than 1 % ALDH1 expression in the cancer cells was statistically higher than that in the patients with high ALDH1 expression (more than 1 %). 

15-21 755
Abstract

Breast cancer (ВС) is the most common form of cancer, leading to high mortality rates among women worldwide. Metastasis is the main cause of fatal outcomes in ВС. In this regard, of particular interest takes the study of molecular mechanisms of epithelial-mesenchymal transition (EMT). In the EMT processes involved in TGF-β1/SMAD-signaling pathway through the regulation of which can affect the processes of metastasis in ВС. 

In this study we have analyzed changes of mRNA expression of the mRNA SMADs, miR-21, and miR-155 of the tumor ВС cells with different metastatic potential MCF-7, BT-474, ZR-75-1. High expression of miR-21 was detected in all the tumor cell lines (MCF-7, ZR-75-1 and BT-474). In the ВС cell lines, the expression level of miR-155 was significantly lower than that of miR-21. Analysis of mRNA expression has clearly shown impairments of intracellular mechanisms of regulation of SMAD2, SMAD4, SMAD7 in ВС. 

Investigated the correlation of expression of miR-21 and miR-155 regulation of SMADs in TGF-β1/SMAD signaling pathway in three carcinomas lines of the human breast with different metastatic potential (MCF-7, ZR-75-1, BT-474). A significant inverse correlation was observed between SMAD4 and miR-155 in MCF-7 cells. Inverse correlation between the expression of SMAD2, SMAD4, SMAD7 and miR-155; miR21 was found in the BT-474 cells. 

The results obtained in this study showed that miR-21 and miR-155 regulate activity of several genes SMAD2, SMAD4, SMAD7 in the tumor cell ZR-75-1 and on some genes they exhibited a cumulative effect. It should be noted that the miR-155 and miR-21 in various degrees influenced the expression of SMAD2, SMAD4, SMAD7, blocking the work of these genes and, thereby exacerbating the progression and degree of malignancy of ВС cells human; in some cases their effects on individual genes were cumulative. 

MAMMOLOGY. ORIGINAL ARTICLE

22-29 2044
Abstract

Background. A clear relationship is now found between the activity of estrogen metabolites and the development of tumors in estrogen-dependent tissues. Many international and Russian studies could identify a number of compounds involved in the regulation of estrogen metabolites. Indole-3-carbinol is one of these compounds that correct a ratio of 2-hydroxyestrone (2-OHE1) to 16-OHE1. It is a phytonutrient that is contained in Cruciferous vegetables and has antitumor activity. Our investigations used highly purified indole-3-carbinol (Indinol). The ability to identify the role of metabolic syndrome, by applying the current methodological approaches, allowed us to study the effect of highly purified indole-3-carbinol on the level of expression of estrogen metabolites and to attempt to expand views on procedures to prevent and treat breast tumors.
Materials and methods. A total of 136 women were comprehensively examined; of them 44 patients formed a group of those with morphologically verified hormone-independent breast cancer (BC) and 42 patients were a group of those with hormone-dependent BC. A control group included 50 women without signs of breast disease. In all the patients, body mass index was calculated; the ratio of urinary estrogen metabolites (2-ОНЕ1/16α-ОНЕ1) was quantified; and biopsy specimens and operative material were histologically and immunohistologically studied.
Results. The BC patients were noted to have the high expression of 16α-OHE1 and the low values of 2-OHE1 (ratio, 0.42) as compared to the control group (2.09), which was an important component of metabolic syndrome. The BC patients had the high level of concomitant endocrine metabolic disturbances with the high body mass index, which reflected the clinical manifestation of metabolic syndrome. Indinol used to treat both hormone-dependent and hormone-independent BC showed an antimetabolic effect that was most pronounced 6 months later. Conclusion. Thus, early correction of metabolic disturbances with antimetabolites is one of the important, pathogenetically sound areas in the prevention of BC. 

MAMMOLOGY. TREATMENT

30-34 1093
Abstract

Tumor progression (distant metastases, local-regional recurrences, contralateral cancer) is a main cause of death in patients with breast cancer (BC). The occurrence of local recurrences is associated mainly with the nonradicality of surgery. Patient age, tumor subtype, and personalized systemic therapy have a statistically significant impact on the prediction of recurrence. It is most likely that the disease can come back as a local recurrence in the subgroups of nonluminal tumors with HER-2 overexpression and in those of triple negative cancer.
The paper presents the data available in the literature and the authors’ observations concerning the role and place of surgical treatment for locally recurrent BC. It gives major predictors of local and local-regional recurrences and defines main indications for different types of surgical interventions, including plastic surgery. 

35-42 1804
Abstract

The use of tamoxifen is conventional adjuvant hormone therapy in premenopausal patients with receptor-positive breast cancer. Clinical trials demonstrating the benefits of ovarian function suppression as adjuvant treatment had an ambiguous interpretation. There is no scientific evidence favoring the empiric use of ovarian suppression for these patients. The members of the American Society of Clinical Oncology consider that ovarian ablation or suppression should be used during adjuvant hormone therapy only in certain cases. Irreversible ovarian function ablation may improve time to relapse, by simultaneously deteriorating the quality of life in patients. Irreversible fertility loss in the patients who have experienced breast cancer may become a leading stressful factor for these patients. Many investigators believe that chemotherapy-induced amenorrhea reduces the risk of recurrence. The paper discusses the usage of gonadotropin-releasing hormone agonists in combination with tamoxifen and aromatase inhibitors during adjuvant hormone therapy for early breast cancer. Whether ovarian suppression is needed during hormone therapy is considered, it is the reversible ovarian function suppression that must be standard treatment in premenopausal patients. 

GYNECOLOGY. PROBLEM

61-66 1240
Abstract

This paper analyzes large amounts of literature data on studies of the efficiency of neoadjuvant chemotherapy (NCT) for advanced ovarian cancer (OC), which is performed prior to standard surgery. Clinical trials have demonstrated that a NCT regimen followed by cytoreductive surgery is less effective than primary cytoreductive one; however, evidence for the benefit of NCT is lacking so far. The authors conducted investigations using the intraoperative material obtained from 17 patients with T3a–cNxM0 OC, who were divided for a comparative examination into 2 groups. Group 1 included OC patents who received NCT; Group 2 comprised OC patients who did not. The tumor cells obtained from the intraoperative material of both groups were able to generate a well-proliferating culture in in vitro experiments. The cultured OC cells were characterized, by analyzing cytological specimens and the functional activity of these cells. It was ascertained that 35 % of the cultured tumor cells from OC retained their resistance to the cytotoxic action of effector cells (autologous lymphocytes) at a target cell/effector cell ratio of 1:5. Thus, both the literature and the experiment provide no unambiguous evidence supporting the fact that NCT before cytoreductive surgery is a better approach than primary surgical treatment. The optimal regimen of NCT, which would be able to enhance its efficiency, remains important. 

GYNECOLOGY. DIAGNOSIS

67-71 856
Abstract

Ovarian carcinoma is one of the most aggressive cancer in women, and one of the leading causes of death from cancer of the reproductive system. Despite enhancement methods of prevention, early diagnosis, treatment, such as surgery, radiation, drugs, including targeted and hormone therapy, long-term results remain unsatisfactory. In this connection, much attention is paid to the search for molecular biological mechanisms involved in carcinogenesis and the development of laboratory tests for detecting patients at early stages of tumor process, to differentiate malignant and benign tumors, to determine the tactics of treatment of a particular patient, to assess the prognosis. One of the key aspects of the pathogenesis of ovarian cancer is the interaction of tumor tissue extracellular matrix, the protein degradation of which in most cases is controlled by proteolytic enzymes. Matrix metalloproteinase 7 (MMP-7), also known as matrilysin, like other members of the matrix metalloproteinase` family, demonstrates proteolytic activity against components of the extracellular matrix, the degradation of which is the basis of cancer invasion and metastasis. Matrilysin is also involved in the regulation of activities of bioactive molecules associated with cell physiology. The overview briefly highlights the role of MMP-7 in ovarian cancer. 

GYNECOLOGY. TREATMENT

72-75 2878
Abstract

The paper discusses the results of studies conducted in international clinics and the authors’ data on approaches to treating borderline ovarian tumors. It analyzes and comparatively assesses groups of patients who have received chemotherapy and those who have not. The authors mainly state the view that chemotherapy for borderline ovarian tumors affects their prognosis in no way, but makes it even worse in a number of investigations. They also give the data of their observations, which show that attitudes towards chemotherapy for borderline ovarian tumors change in different decades. If in the 1980s chemotherapy was a mandatory treatment stage, it is nowadays prescribed only in exceptional cases in the author’s clinic. Different predictors, such as microinvasion, the micropapillary pattern of borderline tumors, invasive implants, their impact on the probability of recurrences and survival are being investigated. Whether chemotherapy against unfavorable factors, such as invasive implants, may be used is considered. There is evidence that conservative and ultraconservative surgeries for borderline ovarian tumors may be performed. Ultraconservative operations that can spare ovarian tissue as much as possible demonstrate the best pregnancy and labor outcomes as compared with conservative surgical approaches.
Thus, this paper considers whether it is expedient to use chemotherapy in patients with borderline ovarian tumors. It also discusses scientists’ views and the authors’ data on neoadjuvant and adjuvant treatments, predictors in borderline ovarian tumors, and survival rates in different international clinics. 

GYNECOLOGY. CLINICAL LECTURE

76-86 982
Abstract

The paper covers the most important topographic-anatomic and histological characteristics of the vagina, gives general information on the epidemiology of primary vaginal cancer (VC), on the rules of its staging, describes the frequently encountered morphological types of this tumor, and indicates the properties and features of the course of neuroendocrine tumors (NETs), including the most common manifestations of carcinoid syndrome and the symptoms of tumor hypersecretion of a number of biologically active substances. It also indicates the most common sites of NETs, the rules of their classification according to the grade and mitotic activity of tumor cells, as well as major methods for biochemical and radiological diagnosis. The immunohistochemical NET markers that can diagnose VC, their physiological role, sensitivity, and specificity, as well as the possibility of determining them in the body’s biological environments in order to increase physicians’ awareness are described in detail and the main aspects of tumor immunohistochemical staining are denoted. The role of circulating tumor cells as a promising method to specify the extent of NETs is defined. The paper gives epidemiological information on the development of vaginal NET and summarizes the available data by their clinical course and treatment results. It provides current guidelines on the required treatment volume and specifies the role of surgical intervention and the necessary volume if the intervention is expedient. It sets forth the up-to-date guidelines for chemotherapy for small cell tumors, as well as VC, which includes the specific features of managing patients with tumor recurrences depending on the time of their development. 

GYNECOLOGY. REGIONAL EXPERIENCE

87-96 994
Abstract

The world marked increase in the incidence of cervical cancer in young women, especially from 29 to 45 years old. Analysis showed that in patients with preserved ovarian function, not only the effectiveness of the treatment, but also the quality of life. It is associated with the acceleration, earlier puberty and the onset of sexual activity. In recent years more and more widely used radical surgery with preservation of the ovaries and the abduction of the radiation castration and preservation of reproductive function. In the National Cancer Research Centre of the Ministry of Health of the Republic of Uzbekistan analyzed the results of surgical treatment of 204 patients with cervical cancer younger. Age of patients from 23 to 45 years, that is, in the most hard-working, reproductive period. In our study patients met principally with exophytic – 82 (40.2 %) and 68 (33.3 %) еndophytic growth cervical tumors. Histological in 197 (96.6 %) patients with squamous cervical cancer patients with 7 (3.4%). Adenocarcinoma of cervical cancer. Handard examination of the patient are further adapted to determine the level of sex hormones (estradiol, progesterone), determination of the tumor marter CA-125 levels of calcium and phosphate in the blood. 112 patients from the main group and the combined complex therapy surgical treatment with organ-component (conservation and ovarian transposition). The first group included 112 (55.1 %) patients, who as part of combination therapy was performed and complex surgical treatment of ovarian transposition. The second group included 92 (44.9%) patients who as part of combination therapy and complex surgery performed without ovarian transposition. Each group was divided into 3 subgroup included patients with stage process T1b–2aN0M0. Which performs the combined radiotherapy. The second subgroups included patients with stage process that runs systemic chemotherapy, surgery, combined radiotherapy. The third group included patients with stage process that runs endoarterial regional prolonged chemotherapy + surgery + combined radiotherapy. In phases of dynamic monitoring of patient evaluated the effectiveness of treatment as well as studied T2bN0–1M0 the quality of life of a young body. Quality of life of patient in the dynamics of observation was determined by the American system MENQOL. 



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ISSN 1994-4098 (Print)
ISSN 1999-8627 (Online)