Advances in molecular oncology (E-Journal) / Успехи молекулярной онкологии
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РОЛЬ БЕЛКОВ NOTCH В ПРОЦЕССАХ КАНЦЕРОГЕНЕЗА
Get PDFNotch transmembrane receptors family in humans consists of 4 proteins (Notch1–4) which are activated upon direct contact of cells, carrying appropriate ligands of Jagged or Dll families. This interaction leads to certain proteolytic events resulting in Notch intracellular domain translocation to the nucleus, where it activates various signaling pathways regulating the balance between cellular proliferation, apoptosis or differentiation.Proteins of the Notch family influence intraand intercellular pathways and communications of the majority of cell types. These receptors regulate both embryogenesis and adult organs and tissues homeostasis sustenance. Dysregulation of Notch signaling result in various diseases, and carcinogenesis as well. These Notch alterations are better studied in various hemoblastoses but it ,s involvement in solid tumors car- cinogenesis has recently been shown. Notch proor antioncogenic action depends not only on the type of transformed cells but also on their microenvironment.This review is dedicated to canonical Notch signaling, as well as to non-canonical actions, epigenetic regulation and current proand antioncogenic functions in human malignancies. Special attention is drawn to interaction between Notch and other signaling pathways controlling epithelia-to-mesenchyma transition of cells, stem cells formation, sustention of specific niches, cellular differentiation, angiogenesis both during embryogenesis and in pathological conditions. Pharmacological regulation of Notch activation could be a promising way of anticancer therapy
Диагностическая значимость уровней ДНК и антител к капсидному антигену вируса Эпштейна–Барр в плазме крови больных раком носоглотки в неэндемическом регионе
Get PDFEpstein–Barr virus (EBV), a representative of the herpesvirus family, is the etiological agent for a number of benign and malignant human neoplasms. Among the latter, the nasopharyngeal carcinoma (NPC) occupies a special place. In NPC development EBV plays a key role stimulating the progression of the pathological process from precancerous lesions to the cancer development. For most NPC patients, elevated levels of humoral IgG and IgA antibodies against capsid and early EBV antigens are characteristic and their antibody titers rise to high levels long before the diagnosis of cancer. Using this phenomenon, virus-specific antibodies are used for many years as markers for NPC screening, especially in cases of undiagnosed primary lesion. In recent years, in endemic for NPC regions (South China, South-East Asia) a great attention has been paid to the use of quantitative determination of EBV DNA copies in the blood plasma of patients with NPC as a method of early cancer detection and monitoring.The aim of this study was to compare clinical significance of EBV DNA and humoral antibodies levels in blood plasma of NPC patients in non-endemic region, Russia. The results obtained indicate that both markers DNA / EBV and IgA antibodies against capsid EBV antigens can be successfully used for diagnosis of NPC in non-endemic region. However, in comparison with the virus-specific antibody titers, the viral DNA levels in the patients plasma are more sensitive and specific as NPC marker reflecting the efficacy of the therapy, and the state of remission or relapse
МикроРНК: половые гормоны, гормональный канцерогенез, гормоночувствительность опухолевой ткани
Get PDFSex hormones, regulating normal physiological processes of most tissues and organs, are considered to be one of the key factors in the development and progression of the reproductive system cancer. Recently, the importance of the system for post-transcriptional control of gene expression mediated by short single-stranded RNA molecules (microRNA) became evident. This system is involved in regulation of normal physiological processes and in the pathogenesis of many diseases, including cancer. In review we discuss the relationship between the two regulatory systems – sex hormones and microRNAs. The relationship of these systems is considered in the context of two tumors – breast and prostate cancer. In particular, the history of research on the role of sex hormones in the pathogenesis of breast cancer and prostate cancer is briefly covered. Additionally, modern scientific data on the biogenesis and biological role of microRNAs are presented in more detail. In the cells of the hormone-sensitive tissues, sex hormones regulate the microRNA-mediated machinery of gene expression control by two known ways: specifically, affecting the activity of individual microRNA molecules and non-specifically by altering the efficiency of microRNA biogenesis and activity of RNA-induced silencing complex. This downstream regulatory network substantially enhances biological effects of sex hormones at physiological conditions. Malignant transformation leads to a distortion of the regulatory effects of sex hormones that crucially influence the system of microRNA-regulated post-transcriptional control of gene expression. The most established and clinically significant example of such phenomenon is the loss of sensitivity of cells to the regulatory action of these hormones. As a consequence, cancer cells acquire the ability to active proliferation without stimulation with sex hormones. This effect is partly mediated by microRNAs. Also, relevant experimental data indicating the involvement of microRNAs in the phenomenon of breast cancer and prostate cancer cells hormone resistance are discussed in the review.Conception of the possible primary role of microRNAs in the process of malignant transformation and distortion of hormonal regulation is based on a smaller number of scientific reports. In general, in accordance with the main biological role of microRNAs, latter may affect sex hormones function via interaction with the mRNAs of hormone receptors and inhibition of their synthesis. As a result, the effect of many microRNA is converging on the single mRNA, results in suppression of corresponding protein function and, in the end, leads to inhibition of regulatory cascade downstream of sex steroids.Finally, the analysis of the fundamental aspects of sex hormones – microRNA interplay is supplemented by brief overview of clinically significant problems. The prospects for development and introduction into clinical practice innovative methods of diagnosis, prediction and optimization of therapy of breast and prostate cancers are discussed as well
Биохимические маркеры метастазирования в кости
Get PDFBone metastasis is one of the most frequent and dangerous complications of malignant tumors. The last years, achievements in the study of bone remodeling mechanisms promoted the search of sensitive and specific criteria reflecting the intensity of osteolysis and osteosynthesis in bone metastatic lesions. The most informative and clinically valid biochemical markers of bone formation and resorption are characterized in this review. The data on their possible implications in diagnostics, monitoring and prognosis of skeletal lesions by various malignant tumors are presented. The attention to biochemical markers of bone remodeling as noninvasive methods for oncologic patients examination is gradually increasing with adoption of modern laboratory technologies to clinical practice. The last years, publications suggest the possibility of their use both for monitoring, prognosis and early diagnostics of bone metastasis. We present the results of our own investigation of serum C-telopeptide of type I collagen (СТX) as bone resorption marker and bone-specific alkaline phosphatase (BAP) as formation marker in 238 breast cancer patients using ELISA methods. The elevation of studied biochemical parameters in breast cancer patients was significantly associated with the extent of skeletal metastases (р < 0.02–0.00001), pathological fractures (р < 0.005–0.0001) and the severity of pain (р < 0.01–0.00002). Elevated rate of bone turnover was associated with reduced overall survival of breast cancer patients. The significant difference of overall survival estimated on a base of cut-off values of CTX (0.74 ng/ml) and BAP (43.7 IU/L) was found both in the groups of breast cancer patients with and without bone metastases. Serum СТХ and BAP are of value in monitoring and predicting the status of breast cancer bone metastases