[Viral co-infection with head and neck tumors]. / Virusnaya koinfektsiya pri opukholyakh golovy i shei.

The review is devoted to assessing the prevalence of human papillomavirus (HPV) in combination with other viral agents for head and neck tumors (HNT). HPV is recognized as an etiological factor in the development of cervical cancer, but there is evidence that it may be involved in carcinogenesis in other locations, in particular the upper respiratory tract. However, HPV is not the most important factor in tumor growth and progression. Recently, many researchers have reported the presence of concomitant co-infection, affecting tumor progression. Of all the studies analyzed, only 3 studies showed the absence or low rates of co-infection in HNT: from the Czech Republic (0%), China (0.6%) and Japan (3%). Most often, HPV infection was detected together with the Epstein-Barr virus (EBV) - from 12.5 to 34.1% of cases. In Russia, the prevailing combination of viral co-infection was a combination of EBV and cytomegalovirus (9.5%) and a combination of EBV and herpes simplex virus (6.7%). Thus, the degree of incidence of HPV in HNT varies greatly, and the mechanisms of coinfection are poorly understood, which raises the question of whether HPV and concomitant infection can be involved in tumor progression. This makes further research in this direction relevant and promising.

Regenerative Potential of Spermatogonial Stem Cells, Endothelial Progenitor Cells, and Epithelial Progenitor Cells of C57Bl/6 Male Mice with Metabolic Disorders.

The properties of spermatogonial stem cells, endothelial progenitor cells, and the epithelial progenitors of C57Bl/6 mice under conditions of metabolic disorders were studied using the model of busulfan-induced suppression of spermatogenesis and in vitro culture technique. Spermatogonial stem cells CD117-CD90+ and epithelial progenitors CD45-CD31-Sca-1+CD49f+ derived from the testes of mice with metabolic disturbances demonstrated 17- and 28-fold increase in the respective cell mass and generated cell colonies in vitro. In contrast, spermatogonial stem cells with immune phenotype CD51-CD24+CD52+ had reduced selfrenewal capacity. Spermatogonial stem cells CD117-CD90+ and CD117+CD90+ as well as endothelial progenitors CD45-CD31+ derived from the testes of donor mice with metabolic disorders demonstrated high transplantation capacity in C57Bl/6 mouse testes damaged by cytostatic busulfan.

[The clinical aspects of HPV-positive cancer of the oral cavity and oropharynx].

This review was designed to focus on the prevalence and the magnitude of infection with human papilloma virus (HPV) among healthy subjects and patients presenting with cancer of the oral cavity and oropharynx. We compare the data on the relative frequency of HPV-positive and HPV-negative cancer of the oral cavity and oropharynx in different populations, peculiarities of the clinical course of this pathology, and methods of its treatment. Much emphasis is placed on the specific clinical and morphological features of HPV-positive cancer of the oral cavity and oropharynx. The general and relapse-free survival rates are considered with special reference to the outcome and prognosis of this disease. The currently accepted approaches to the treatment of HPV-positive cancer of the oral cavity and oropharynx are discussed. It is concluded that HPV-positive cancer of the oral cavity and oropharynx should be regarded as an autonomous pathological condition requiring specific approaches to its management, such as the application of adequate treatment schemes and algorithms.

[Clinical studies of ABC-transporters contribution to the multidrug resistance of breast cancer].

This review summarizes the clinical trials of the relationship of gene expression and protein ABC-transporters in breast cancer with the response to neoadjuvant chemotherapy (NAC) and survival of patients. In a large clinical material is considered the pre-treatment multidrug resistance (MDR) and adaptive MDR, that occurs in tumor cells during chemotherapy. Association pre-treatment MDR with NAC efficiency and survival is highly variable and not well-established. In all clinical trials, adaptive MDR showed a good association with NAC efficiency and survival of patients. The own results showed that 5-year distant metastasis-free survival was 73-78% and good response to NAC in patients with a decrease in ABC- expression. The up-regulation of these genes during NAC was related to a significant decrease (up to 50-55%) in metastasis-free survival and poor response to NAC. In the development of strategies to overcome MDR phenotype it is concluded based on the submitted clinical data.

[Substantiation of Expressive Markers Use to Personalize Lung Cancer Chemotherapy].

Surgery results of II-III stage lung cancer remain unsatisfactory and the chemotherapy does not improve the survival. The main obstacle is the use of the standard clinical parameters for the treatment strategy and not sufficiently effective selection of regimens for the chemotherapy. Monoresistance genes defining the tumor cells sensitivity to the chemotherapeutic drugs play a significant role in development of the lung tumor resistance. The review examines the mechanisms of transport, activation and targets of the chemotherapeutic drugs, identifies the key markers for predicting their effectiveness and possible use in the clinical practice. Monoresistance genes, such as ABCC5, RRM1, ERCC1, TOP1, TOP2a, TUBB3 and TYMS are characteristic of lung cancer. Clinical trials demonstrating the efficiency of their use as predictive markers for the lung cancer chemotherapy are described. A prospective study with a personalized adjuvant chemotherapy for lung cancer patients will be performed.

Age-related function of tumor suppressor gene TP53:contribution to cancer risk and progression.

AIM: To examine the influence of combined genotypes of TP53 (exon 4, intron 3, intron 6) and XRCC1 (codon 10) on lung cancer age of onset. METHODS: TP53 polymorphisms in codon 72 of exon 4 (Arg72Pro), in intron 3 (16 bp duplication), in intron 6 (G/A transition) and XRCC1 polymorphism in codon 10 (Arg399Gln) were analyzed in blood cells of 177 lung cancer patients and 196 healthy donors with Restriction Fragment Lenth Polymorphism PCR. RESULTS: We showed that combination of TP53 variant genotypes and XRCC1 variant genotype is associated with the increased lung cancer risk in younger, but not elderly, smokers. In contrast, wild allele combination increases lung cancer risk for individuals over the age of 60. CONCLUSION: Our data confirm antagonistic pleiotropy hypothesis indicating that p53 protects the organism against cancer early in life, but promoting aging phenotype, including late life cancer in older persons.