Complex ultrasound diagnostic assessment of the results of neoadjuvant chemotherapy for locally advanced cervical cancer (Stages IIB–IIIB)

Background. Current complex ultrasound diagnosis using novel imaging techniques can assess, to a high accuracy, different tumor parameters during neoadjuvant chemotherapy (NCT) for locally advanced cervical cancer (CC) (Stages IIB–IIB). This assessment is very important and necessary to define further treatment policy.Materials and methods. A total of 199 patients diagnosed with Stages IIB–IIIB CC, including 60 patients with Stage IIB (T2bN0M0), 4 with Stage IIIА (T3aN0M0), and 135 with Stage IIIВ (T2bN1M0, T3aN1M0, T3bN0–1M0) (according to the International Federationof Gynecology and Obstetrics (FIGO) classification), who received NCT at Stage 1 of treatment, were examined. Complex ultrasound study was conducted before treatment initiation and after each NCT cycle. The therapeutic pathomorphism of a tumor was evaluated in surgically treated patients.Results. The criteria have been determined for evaluating the efficiency of NCT for locally advanced CC, which are based on current ultrasonographic techniques including B-mode, Doppler ultrasound (power, spectral, three-dimensional ones), as well as on the results of therapeutic pathomorphism.Conclusion. The criteria for evaluating the efficiency of NCT for CC should be based on current complex ultrasonographic techniques

SCREENING FOR OVARIAN CANCER: REALITY AND PROSPECTS. REVIEW OF THE LITERATURE

A review article presents the modern methods of screening and early diagnosis of primary ovarian cancer (OC). This issue is still relevant in view of the continuing upward trend in incidence rate ratios along with a slight decrease in mortality and 5-year survival rate, as well as the lack of clear definition of the concept of pathogenesis. The diagnostic value of tumor markers and their potential, advantages and disadvantages are discussed. In light of this the need becomes evident for combination of tumor markers with radiological method of imaging, such as transvaginal sonography as the most affordable, safe and multi-reproducible method enabling to most accurately determine the nature of the process, its nosology belonging, as well as to carry out the required dynamic monitoring within a short time. More advanced imaging techniques such as computer tomography or magnetic resonance imaging proved too expensive for widespread use in view of their limited sensitivity and specificity. Attempt to assess the performance of marker screening on the base of CA-125 in groups, divided by clinical and pathogenic way of OC development also proved to be ineffective. Currently, none of the presented algorithms can meet the criteria of economic efficiency, even in the most developed countries. In view of the above, possible options to enhance their performance by developing reliable multimarker panels, the use of ultrasound color power doppler mapping, and others are considered. In addition, the feasibility and application prospects of ultrasound elastometry, mass-spectrometry, IVDMIA tests, OVA dx-test as part of screening programs are discussed. The data of recent studies on the direct comparison of diagnostic tests is given. The importance of genetic counseling for persons at high risk of cancer development process is noted. In case of mutation detection in the BRCA1, BRCA2 genes, in some countries a wide range of preventive activities is recommended: from regular «targeted» preventive examinations to the prophylactic oophorectomy and mastectomy. Increased survival rate of patients with OC is the main aim of all scientific research

The balance of estrogen metabolites in breast cancer and the ways of its correction

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

Current principles of effective therapy for ovarian cancer

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

Molecular biological and ultrasonic methods in the evaluation of the effectiveness of drug therapy in patients with cervical cancer and ovarian cancer

We explored the complex of modern ultrasound technology for dynamic monitoring to assess the effectiveness of drug therapy. This paper analyzes the data of complex clinical, ultrasound and pathological study of 86 patients, was 2 groups of patients – 58 women with locally advanced cervical cancer (IIb–IIIb stages) and 28 patients with ovarian cancer (IIa−IV stages).During the morphological and ultrasonic parallels found a direct correlation between the degree of drug and the amount pathomorphism tumor focus, a reduction of vascularization and blood flow velocity

ULTRASOUND CRITERIA OF EARLY DIAGNOSTICS OF OVARIAN CARCINOMA

Introduction. Ovarian cancer (OC) in Russia is ranked the seventh within the structure of general cancer diseases and the third within the gynecological tumors, due to such reasons the problem of early diagnostics is still actual. New technologies, such as color Doppler ultrasonography,3D power Doppler ultrasonography contribute to increasing of opportunities of ultrasound analysis to detect any malignancy signs.Materials and methods. The paper sets out the results of comprehensive ultrasound study of 68 patients with morphologically verified OC at stages IА–В, IIА–В. The control group was made of 100 female patients with morphologically verified ovarian tumors (serosal cystadenomas, thecomas, fibromas). A complex of the following ultrasound methods was used during the study: 2D and 3D ultrasonography in B mode, in color Doppler and power mapping mode, 3D angiography, spectrum Doppler imaging.Results. Maximum size of tumor varied within a range between 37 and 300 mm (108 ± 61.2 mm). It worth noting that no direct dependence between the size of neoplasm and process phase was established. When assessing the echostructure, all ovarian tumors were divided into 3 structure types: cystic type (57.8 % of cases), cystic and solid type (33.3 % of cases), solid type (8.9 % of cases). The conducted analysis of types of small pelvis neoplasm echostructures enabled to evolve the sonographic types of ovarian tumors, more or less associated with the malignant transformation. The most relevanl Doppler ultrasonography exponents characteristic for benignant and malignant processes: resistance index in benignant tumors was 0.56, at OC – 0.32 (р < 0.001); average arterial blood velocity in benignant tumors – 7.8 cm/s, at OC – 20.1 cm/s (р < 0.001); average maximum venous flow velocity in benignant tumors – 3.2 cm/s, at OC – 9.3 cm/s (р < 0.001).Conclusion. Therefore modern ultrasonography can detect and differentiate rather efficiently the localized variants of OC, provided that the main part of diagnosis is formed in mode of color and power Doppler mapping, which shall be taken into consideration during the primary diagnostics of OC

Table1_Deeper insights into transcriptional features of cancer-associated fibroblasts: An integrated meta-analysis of single-cell and bulk RNA-sequencing data.XLSX

Cancer-associated fibroblasts (CAFs) have long been known as one of the most important players in tumor initiation and progression. Even so, there is an incomplete understanding of the identification of CAFs among tumor microenvironment cells as the list of CAF marker genes varies greatly in the literature, therefore it is imperative to find a better way to identify reliable markers of CAFs. To this end, we summarized a large number of single-cell RNA-sequencing data of multiple tumor types and corresponding normal tissues. As a result, for 9 different types of cancer, we identified CAF-specific gene expression signatures and found 10 protein markers that showed strongly positive staining of tumor stroma according to the analysis of IHC images from the Human Protein Atlas database. Our results give an insight into selecting the most appropriate combination of cancer-associated fibroblast markers. Furthermore, comparison of different approaches for studying differences between cancer-associated and normal fibroblasts (NFs) illustrates the superiority of transcriptome analysis of fibroblasts obtained from fresh tissue samples. Using single-cell RNA sequencing data, we identified common differences in gene expression patterns between normal and cancer-associated fibroblasts, which do not depend on the type of tumor.</p

Table3_Deeper insights into transcriptional features of cancer-associated fibroblasts: An integrated meta-analysis of single-cell and bulk RNA-sequencing data.XLSX

Cancer-associated fibroblasts (CAFs) have long been known as one of the most important players in tumor initiation and progression. Even so, there is an incomplete understanding of the identification of CAFs among tumor microenvironment cells as the list of CAF marker genes varies greatly in the literature, therefore it is imperative to find a better way to identify reliable markers of CAFs. To this end, we summarized a large number of single-cell RNA-sequencing data of multiple tumor types and corresponding normal tissues. As a result, for 9 different types of cancer, we identified CAF-specific gene expression signatures and found 10 protein markers that showed strongly positive staining of tumor stroma according to the analysis of IHC images from the Human Protein Atlas database. Our results give an insight into selecting the most appropriate combination of cancer-associated fibroblast markers. Furthermore, comparison of different approaches for studying differences between cancer-associated and normal fibroblasts (NFs) illustrates the superiority of transcriptome analysis of fibroblasts obtained from fresh tissue samples. Using single-cell RNA sequencing data, we identified common differences in gene expression patterns between normal and cancer-associated fibroblasts, which do not depend on the type of tumor.</p

DataSheet1_Deeper insights into transcriptional features of cancer-associated fibroblasts: An integrated meta-analysis of single-cell and bulk RNA-sequencing data.pdf

Cancer-associated fibroblasts (CAFs) have long been known as one of the most important players in tumor initiation and progression. Even so, there is an incomplete understanding of the identification of CAFs among tumor microenvironment cells as the list of CAF marker genes varies greatly in the literature, therefore it is imperative to find a better way to identify reliable markers of CAFs. To this end, we summarized a large number of single-cell RNA-sequencing data of multiple tumor types and corresponding normal tissues. As a result, for 9 different types of cancer, we identified CAF-specific gene expression signatures and found 10 protein markers that showed strongly positive staining of tumor stroma according to the analysis of IHC images from the Human Protein Atlas database. Our results give an insight into selecting the most appropriate combination of cancer-associated fibroblast markers. Furthermore, comparison of different approaches for studying differences between cancer-associated and normal fibroblasts (NFs) illustrates the superiority of transcriptome analysis of fibroblasts obtained from fresh tissue samples. Using single-cell RNA sequencing data, we identified common differences in gene expression patterns between normal and cancer-associated fibroblasts, which do not depend on the type of tumor.</p