Рак шейки матки: проблемы профилактики и скрининга в Российской ФедерацииЛ.А

In spite of all of modern medicine»s advances, ovarian cancer (OC) mortality remains to be incommensurably high and to hold the lead among gynecological cancers. The initial cause of this deplorable statistics is the absence of a clear concept of the pathogenesis of OC and hence the justified prevention and methodology of early diagnosis of the disease; in this connection, therapy that proves to be ineffective is frequently used by medical oncologists in their daily practice. As a consequence, there is a high proportion of its further progression: the rates of early and late recurrences were about 30 and 60–65 %, respectively; most of which are drug resistant to further chemotherapy cycles. By taking into account these strikingly modest statistics, it becomes apparent that oncologists desire to make changes in the existing treatment regimen to achieve meaningful results. To use target drugs is one of these promising areas owing to new views on the concept of the pathogenesis of OC.Nevertheless, considering a wide variety of the signaling cascades and molecules, which are involved in the process of carcinogenesis, even target compounds, if they have only one point of application, cannot always produce their desirable therapeutic effect and their co-administration is responsible for high toxicity. In this light, the most effective drugs are indole-3-carbinol and epigallocathechin-3-gallate, which virtually cause no adverse reactions and can block various molecular targets at different levels of the mechanism of malignant transformation. Based on L. A. Ashrafyan, s concept of two pathogenetic variants of sporadic OC (2009) and on the recent findings in molecular biology and epigenetics, the incorporation of the above medications into the standard treatment regimen for OC should increase survival rates and change the nature of recurrence by that of more locally advanced forms. On this basis, a clinical trial was carried out to study the efficiency of using antitumor drugs based on indole-3-carbinol and epigallocathechin-3-gallate as part of combination therapy for OC. The results of the clinical trial performed are suggestive of considerably higher survival rates in the groups receiving the above drugs than in the control groups. In addition, the multitarget effect of indole-3-carbinol and epigallocathechin-3-gallate can effectively remodel the function of a cancer stem cell, the main source of recurrences and metastases, and may be considered as an important adjunct to the existing strategy of antitumor therapy.

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.