The recurrences of cervical cancer: Possibilities of molecular prediction

The incidence of recurrence of cervical cancer ranges from 10 to 40 %. The 5-year survival rate for patients with recurrent cervical cancer is about 5–15 % against the background of current drug therapy. Clinical and morphological characteristics of the tumor process are known, which are used as markers of an unfavorable prognosis for the development of cervical cancer recurrence. The search for molecular prognostic markers of the course of cervical cancer continues.The aim. To determine the level of immune cycle proteins in patients with cervical cancer 0–IV stages, depending on the occurrence of a relapse of the disease.Materials and research methods. A retrospective analysis of previously obtained results of a study on the local level of immune cycle proteins in patients with cervical cancer was performed. Three years after follow-up, 2 groups were formed: group 1 – patients treated for cervical cancer without signs of disease progression (n = 83); group 2 – patients with cervical cancer with local or systemic recurrence (n = 18). Used statistical methods: non-parametric methods of statistics using the Kruskal – Wallis test; ROC-analysis for significant values in order to calculate threshold values; determination of the quality of the identified predictive markers by calculating the sensitivity, specificity, accuracy.Results. Local initial threshold values have a predictive value for predicting the occurrence of cervical cancer recurrence: B7.2 < 10.7 pg/ml (Se = 0.87; Sp = 0.73; Ac = 0.76; AUC = 0.78), PD-L1 ≤ 5.1 pg/ml (Se = 0.87; Sp = 0.68; Ac = 0.71; AUC = 0.76), sCD27 ≥ 32.0 pg/ml (Se = 0.75; Sp = 0.78; Ac = 0.78; AUC = 0.75).Conclusion. Determination of local levels of B7.2, PD-L1, sCD27 in patients with cervical cancer before treatment can be used to predict the development of disease recurrence during 3 years of follow-up

Role of viral infection in the etiopathogenesis of breast cancer

The viral nature of many female genital cancers is now beyond question; however, the role of viral infection in the pathogenesis of breast cancer (BC) has not been adequately investigated. The paper defines the importance of a number of viruses in the etiopathogenesis of on- cogynecological diseases. It presents the results of examining 60 patients with Stages I-IV BC and 30 patients with fibrocystic mastopathy, in whom the presence of DNA-containing virus genomes in tumor tissue was compared, and the data of polymerase chain reaction study of genital tract smears. It is shown that human papillomaviruses and cytomegaloviruses do not play a fundamental role in the develop- ment of BC; there is no valid evidence for Epstein–Barr virus

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

Интерферон-γ и опухолевый рост

Purpose of the study: to analyze published data on the mechanisms of action of interferon gamma (IFN-γ) in tumor growth and to evaluate the possibility of its use in the treatment of solid tumors. Material and Methods. More than 200 publications were found in the Scopus, Pubmed, eLibrary and other databases, the search keywords were: interferon gamma, tumor growth, cancer therapy. This review includes 54 papers. Results. IFN-γ is a pleiotropic cytokine with antiviral, antitumor, and immunomodulatory functions and plays an important role in coordinating the innate and adaptive immune response. The success of immuno-oncology drugs and chemotherapy in the treatment of malignant tumors depends on the stimulation of the production and adequate signaling of IFN-γ. Suppression and loss of IFN-γ receptor and downstream signaling mediators, and amplifcation of molecules that inhibit the IFN-γ signaling pathway are common mechanisms for tumor cells to escape from the immune system. The development of malignant processes is accompanied by a change, more often a decrease, in the secretion of IFN-γ, which attracts the attention of researchers to its exogenous administration. Determination of the IFN-γ signature may be a predictive marker of clinical response to anticancer drug therapy. The antitumor properties of IFN-γ are largely dose-dependent, which has been clearly shown in clinical and experimental studies. Low doses of the drug often promote tumor growth. On the contrary, the use of high doses is usually accompanied by an antitumor effect. IFN-γ or its inducers remain promising agents for cancer therapy. Combinatorial strategies involving IFN-γ may be a rational option to overcome tumor resistance to blockade of immune checkpoints. Conclusion. It is necessary to continue fundamental and applied research to study the feasibility of using interferon gamma as a therapeutic agent in tumor growth.Цель исследования – проанализировать опубликованные данные о механизмах действия интерферона гамма (IFN-γ) при опухолевом росте и оценить возможности его применения для лечения солидных опухолей. Материал и методы. По теме найдено более 200 зарубежных и российских публикаций, представленных в базах данных Scopus, Pubmed, eLibrary и других; ключевые слова поиска: интерферон гамма, опухолевый рост, терапия рака. В данный обзор включено 54 работы. Результаты. IFN-γ – плейотропный цитокин, обладающий противовирусной, противоопухолевой и иммуномодулирующей функциями и играющий важную роль в координации врожденного и адаптивного иммунного ответа. Успешность применения в лечении злокачественных опухолей иммуноонкологических препаратов и химиотерапии зависит, в том числе, от стимулирования выработки и адекватной передачи сигналов IFN-γ. Подавление и потеря рецептора IFN-γ и нижестоящих сигнальных медиаторов, амплификация молекул, ингибирующих сигнальный путь IFN-γ, являются обычными механизмами ускользания опухолевых клеток от иммунной системы. Развитие злокачественных процессов сопровождается изменением (чаще снижением), секреции IFN-γ, что привлекает внимание исследователей к его экзогенному введению. Определение сигнатуры IFN-γ может являться прогностическим маркером клинического ответа на противоопухолевую лекарственную терапию. Противоопухолевые свойства IFN-γ во многом дозозависимы, что наглядно показано в клинических и экспериментальных исследованиях. Низкие дозы препарата чаще способствуют росту опухоли, напротив, использование высоких доз обычно сопровождается противоопухолевым действием. IFN-γ или его индукторы остаются многообещающими агентами для терапии злокачественных новообразований. Комбинаторные стратегии с включением IFN-γ могут быть рациональным вариантом для преодоления резистентности опухолей к блокаде иммунных контрольных точек. Заключение. Необходимо продолжать фундаментальные и прикладные исследования по изучению возможностей применения интерферона гамма в качестве лечебного агента при опухолевом росте

Proteome-metabolome profiling of ovarian cancer ascites reveals novel components involved in intercellular communication

© 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Ovarian cancer ascites is a native medium for cancer cells that allows investigation of their secretome in a natural environment. This medium is of interest as a promising source of potential biomarkers, and also as a medium for cell-cell communication. The aim of this study was to elucidate specific features of the malignant ascites metabolome and proteome. In order to omit components of the systemic response to ascites formation, we compared malignant ascites with cirrhosis ascites. Metabolome analysis revealed 41 components that differed significantly between malignant and cirrhosis ascites. Most of the identified cancer-specific metabolites are known to be important signaling molecules. Proteomic analysis identified 2096 and 1855 proteins in the ovarian cancer and cirrhosis ascites, respectively; 424 proteins were specific for the malignant ascites. Functional analysis of the proteome demonstrated that the major differences between cirrhosis and malignant ascites were observed for the cluster of spliceosomal proteins. Additionally, we demonstrate that several splicing RNAs were exclusively detected in malignant ascites, where they probably existed within protein complexes. This result was confirmed in vitro using an ovarian cancer cell line. Identification of spliceosomal proteins and RNAs in an extracellular medium is of particular interest; the finding suggests that they might play a role in the communication between cancer cells. In addition, malignant ascites contains a high number of exosomes that are known to play an important role in signal transduction. Thus our study reveals the specific features of malignant ascites that are associated with its function as a medium of intercellular communication

Possible pathogenetic types of sporadical ovarian cancer

This article in question dwells on a possible pathogenetic model ovarian cancer, it’s histogenesis speciality, the role of ovulation, chronic in- flammation and stem cells. The scheme of two variant of avarian cancer progress and possible ways of prevention it are represented as well

Molecular biological factors in the diagnosis of cervical intraepithelial neoplasias

The authors have made a complex analysis of the molecular biological factors associated with cervical intraepithelial neoplasia. They have revealed that infection by oncogenic human papillomavirus types is associated with suppressed apoptosis and enhanced cellular proliferative activity, which can be effectively used in the diagnosis and prediction of cervical neoplasias to optimize management tac- tics and to improve the results of treatment