ЦИРКУЛИРУЮЩИЕ ОПУХОЛЕВЫЕ КЛЕТКИ: КЛИНИЧЕСКОЕ ЗНАЧЕНИЕ ПРИ РАКЕ МОЛОЧНОЙ ЖЕЛЕЗЫ (ОБЗОР ЛИТЕРАТУРЫ)

Circulating tumor cells (CTCs) constitute a heterogeneous population. Some tumor cells are cancer stem cells (CSCs), while others are in the process of the epithelial-mesenchymal transition (EMT); however, most CTCs are neither stem cells nor participants in the EMT. There is increasing interest in the study of the molecular biological characteristics of CTCs. Many researchers consider circulating tumor cells (CTC) as one of the variants of «liquid biopsy in real time». In this review, we discuss the clinical significance of CTCs in breast cancer and in particular the prognostic and predictive significance both in early stage and metastatic breast cancer, as well as the pathogenetic role of CTCs in venous thromboembolism. Evaluation of various characteristics of CTCs is promising for the study of new biomarkers and targets for targeted therapies. The clinical importance involves the determination of the heterogeneity of the CТC and in particular of the stem subpopulation of these cells, cells with signs of EMТ, with no evidence of stem cells, and with a combination of these features.Многие исследователи рассматривают циркулирующие опухолевые клетки (ЦОК) в качестве одного из вариантов материала для «жидкостной биопсии в реальном времени». В данном обзоре обсуждаются клиническое значение ЦОК при раке молочной железы и, в частности, их прогностическая и предиктивная значимость при ранних стадиях и при метастатическом раке молочной железы, а также патогенетическая роль ЦОК в венозной тромбоэмболии. В настоящее время существует проблема широкого клинического использования детекции ЦОК в крови онкологических больных из-за отсутствия стандартизированных методов их обнаружения. Технологии, одобренные FDA, такие как CellSearch (Veridex, Warren, NJ, США), RCCT (Janssen Diagnostics, США), используют для детекции ЦОК в крови антитела к EpCam или к цитокератинам 8, 18 и 19. Недостатком данных технологий является отсутствие в панели маркеров стволовости и эпителиально-мезенхимального перехода опухолевых клеток и их переходных состояний, а также маркеров, позволяющих выявлять атипические субпопуляции ЦОК. Оценка различных характеристик ЦОК является перспективной для изучения новых биомаркеров и мишеней для таргетной терапии. Особое клиническое значение имеет определение гетерогенности ЦОК и, в частности, стволовой субпопуляции данных клеток, клеток с признаками эпителиально-мезенхимального перехода, без признаков стволовости и с сочетанием этих признаков. Следует отметить, что наличие опухолевых клеток в циркуляции и в местах метастазирования не является достаточным условием для развития макрометастаза. Процесс метастазирования определяется не только свойствами опухолевых клеток, но и условиями среды («почвы»), которые обеспечивают их выживание и пролиферацию в отдаленных органах и тканях

Comprehensive meta-analytical summary on human papillomavirus association with head and neck cancer

An etiological role of high risk human papillomavirus (HPV) in the development of cervical cancer has been well established. Hence, attention of researchers has been focused on the role of HPV in pathogenesis of other malignancies, such as head and neck cancers. An analysis of epidemiological data on the prevalence of HPV infection among healthy people and patients with precancerous lesions and/or cancer is an important step in understanding the role of HPV in head and neck carcinogenesis. More and more data demonstrate the impact of HPV infection on disease outcome. HPV­positive patients have been shown to have better responses to radiotherapy and better overall and disease­free survival than HPV­negative patients. This review presents data of the metaanalysis based on a large number of original studies on HPV prevalence in patients with precancerous lesions and in patients with oral, oropharyngeal and laryngeal cancers as well as findings on the impact of HPV infection on survival of these patients

Different morphological structures of breast tumors demonstrate individual drug resistance gene expression profiles

Aim: To identify gene expression profiles involved in drug resistance of different morphological structures (tubular, alveolar, solid, trabecular, and discrete) presented in breast cancer. Material and Methods: Ten patients with luminal breast cancer have been included. A laser microdissection-assisted microarrays and qRT-PCR were used to perform whole-transcriptome profiling of different morphological structures, to select differentially expressed drug response genes, and to validate their expression. Results: We found 27 differentially expressed genes (p < 0.05) encoding drug uptake (SLC1A3, SLC23A2, etc.) and efflux (ABCC1, ABCG1, etc.) transporters, drug targets (TOP2A, TYMS, and Tubb3), and proteins that are involved in drug detoxification (NAT1 and ALDH1B1), cell cycle progression (CCND1, AKT1, etc.), apoptosis (CASP3, TXN2, etc.), and DNA repair (BRCA1 and USP11). Each type of structures showed an individual gene expression profile related to resistance and sensitivity to anticancer drugs. However, most of the genes (19/27; p < 0.05) were expressed in alveolar structures. Functional enrichment analysis showed that drug resistance is significantly associated with alveolar structures. Other structures demonstrated the similar number (10–13 out of 27) of expressed genes; however, the spectrum of resistance and sensitivity to different anticancer drugs varied. Conclusion: Different morphological structures of breast cancer show individual expression of drug resistance genes. Key Words: breast cancer, tumor heterogeneity, gene expression, chemotherapy, drug resistance

Different morphological structures of breast tumors demonstrate individual drug resistance gene expression profiles

Aim: To identify gene expression profiles involved in drug resistance of different morphological structures (tubular, alveolar, solid, trabecular, and discrete) presented in breast cancer. Material and Methods: Ten patients with luminal breast cancer have been included. A laser microdissection-assisted microarrays and qRT-PCR were used to perform whole-transcriptome profiling of different morphological structures, to select differentially expressed drug response genes, and to validate their expression. Results: We found 27 differentially expressed genes (p < 0.05) encoding drug uptake (SLC1A3, SLC23A2, etc.) and efflux (ABCC1, ABCG1, etc.) transporters, drug targets (TOP2A, TYMS, and Tubb3), and proteins that are involved in drug detoxification (NAT1 and ALDH1B1), cell cycle progression (CCND1, AKT1, etc.), apoptosis (CASP3, TXN2, etc.), and DNA repair (BRCA1 and USP11). Each type of structures showed an individual gene expression profile related to resistance and sensitivity to anticancer drugs. However, most of the genes (19/27; p < 0.05) were expressed in alveolar structures. Functional enrichment analysis showed that drug resistance is significantly associated with alveolar structures. Other structures demonstrated the similar number (10–13 out of 27) of expressed genes; however, the spectrum of resistance and sensitivity to different anticancer drugs varied. Conclusion: Different morphological structures of breast cancer show individual expression of drug resistance genes. Key Words: breast cancer, tumor heterogeneity, gene expression, chemotherapy, drug resistance

THE POSITION OF THE WORLD HEALTH ORGANIZATION ON THE DEVELOPMENT OF NURSING AND MIDWIFERY

The article analyzes the current role of nurses in the world and presents the position of the World Health Organization concerning nursing on the basis of the basic documents on this issue over the last 10 years. Key words: nursing, nurses, public health organization, World Health Organization, policy documents

ПОЗИЦИЯ ВСЕМИРНОЙ ОРГАНИЗАЦИИ ЗДРАВООХРАНЕНИЯ ПО РАЗВИТИЮ СЕСТРИНСКОГО ДЕЛА И АКУШЕРСТВА

The article analyzes the current role of nurses in the world and presents the position of the World Health Organization concerning nursing on the basis of the basic documents on this issue over the last 10 years. Key words: nursing, nurses, public health organization, World Health Organization, policy documents.В статье проанализирована современная роль медсестер в мире и представлена позиция Всемирной организации здравоохранения в области сестринского дела на базе основных документов по этому вопросу за последние 10 лет. Ключевые слова: сестринское дело, медицинские сестры, организация здравоохранения, Всемирная организация здравоохранения, политические документы. (Педиатрическая фармакология. — 2011; 8 (5): 149–152

COMPREHENSIVE META-ANALYTICAL SUMMARY ON HUMAN PAPILLOMAVIRUS ASSOCIATION WITH HEAD AND NECK CANCER

An etiological role of high risk human papillomavirus (HPV) in the development of cervical cancer has been well established. Hence, attention of researchers has been focused on the role of HPV in pathogenesis of other malignancies, such as head and neck cancers. An analysis of epidemiological data on the prevalence of HPV infection among healthy people and patients with precancerous lesions and/or cancer is an important step in understanding the role of HPV in head and neck carcinogenesis. More and more data demonstrate the impact of HPV infection on disease outcome. HPV­positive patients have been shown to have better responses to radiotherapy and better overall and disease­free survival than HPV­negative patients. This review presents data of the metaanalysis based on a large number of original studies on HPV prevalence in patients with precancerous lesions and in patients with oral, oropharyngeal and laryngeal cancers as well as findings on the impact of HPV infection on survival of these patients

DIFFERENT MORPHOLOGICAL STRUCTURES OF BREAST TUMORS DEMONSTRATE INDIVIDUAL DRUG RESISTANCE GENE EXPRESSION PROFILES

Aim: To identify gene expression profiles involved in drug resistance of different morphological structures (tubular, alveolar, solid, trabecular, and discrete) presented in breast cancer. Material and Methods: Ten patients with luminal breast cancer have been included. A laser microdissection-assisted microarrays and qRT-PCR were used to perform whole-transcriptome profiling of different morphological structures, to select differentially expressed drug response genes, and to validate their expression. Results: We found 27 differentially expressed genes (p < 0.05) encoding drug uptake (SLC1A3, SLC23A2, etc.) and efflux (ABCC1, ABCG1, etc.) transporters, drug targets (TOP2A, TYMS, and Tubb3), and proteins that are involved in drug detoxification (NAT1 and ALDH1B1), cell cycle progression (CCND1, AKT1, etc.), apoptosis (CASP3, TXN2, etc.), and DNA repair (BRCA1 and USP11). Each type of structures showed an individual gene expression profile related to resistance and sensitivity to anticancer drugs. However, most of the genes (19/27; p < 0.05) were expressed in alveolar structures. Functional enrichment analysis showed that drug resistance is significantly associated with alveolar structures. Other structures demonstrated the similar number (10–13 out of 27) of expressed genes; however, the spectrum of resistance and sensitivity to different anticancer drugs varied. Conclusion: Different morphological structures of breast cancer show individual expression of drug resistance genes. Key Words: breast cancer, tumor heterogeneity, gene expression, chemotherapy, drug resistance

Development of novel monoclonal antibodies for evaluation of transmembrane prostate androgen-induced protein 1 (TMEPAI) expression patterns in gastric cancer.

Transmembrane prostate androgen-induced protein 1 (TMEPAI) is a single-span membrane protein, functionally involved in transforming growth factor beta signaling pathway. The particular protein presented in cells in three isoforms, which differs in the length of the soluble N-terminal extracellular domain, making it challenging for the immunochemical recognition. By using quantitative real-time polymerase chain reaction, we identified significant upregulation of PMEPA1 gene expression in malignant tissues of patients with gastric adenocarcinoma. The main part of commercially available anti-TMEPAI antibodies are having polyclonal nature or not suitable for immunocytochemical localization of target protein in tissue specimens. Hence, we decide to generate a set of novel rat monoclonal antibodies (mAb) directed against conservative C-terminal cytoplasmic epitope. Immunoblotting analysis showed that monoclonal antibodies, 2E1, 6C6, and 10A7 were able to recognize specifically target protein in transiently transfected HEK293T and CHO-K1 cells. Especially established mAb, named 10A7, showed the excellent binding ability to target protein in immunohistochemistry. By using developed antibodies, we observed pronounced expression of TMEPAI in normal gastric epithelial cells while tumor cells from gastric adenomas, and adenocarcinoma samples were mostly negative for target protein expression. Also, we found that gastric epithelium cells lose the TMEPAI expression concurrently with severe dysplasia progression, which probably caused by a mechanism involving specific microRNA