[Papillomatosis as a criteria for the formation of the group at risk of laryngeal cancer].

The objective of the present study was to determine the incidence of dysplastic pre-neoplastic alterations in the patients presenting with papillomatosis. The results of the clinical, endoscopic, and morphological examination of 42 patients presenting with laryngeal papillomas made it possible to diagnose grade II-III laryngeal cancer in 7 (16.7%) patients. Half of them exhibited pre-neoplastic changes in laryngeal mucosa. The following criteria for the formation of laryngeal cancer risk groups, besides grade II-III epithelial dysplasia, were identified: long (over 12 months) history of papillomatosis, human papilloma virus infection, the history of smoking over 20 years, professional contacts with petroleum, oil, and lubrication materials, and the male gender. An algorithm of observation and treatment for each group of patients differing in the degree of dysplastic changes in laryngeal mucosa was proposed. It is concluded that adequate clinical and endoscopic monitoring of the patients at risk of laryngeal cancer makes it possible to increase the frequency of detection of this condition at the early stages of its development.

MicroRNAs and human cancer.

MicroRNAs (miRNAs) are a recently discovered family of short non-coding RNA molecules of about 19-24 nucleotides in length that are involved in regulation of gene expression. These small molecules have been found to regulate genes involved in diverse biological processes such as cell proliferation, development, differentiation, apoptosis and others. MiRNAs regulate gene expression at the post-transcriptional level either by inhibition of the target (mRNA) or by its destruction. Recent studies have shown that mRNA deregulation is a basic problem in studying pathogenesis of many malignant tumors. It has been recently shown that miRNAs are able to regulate thousands of target genes simultaneously. Thus, the key role of miRNA in carcinogenesis reveals a new layer in the molecular architecture of cancer. Patterns of altered miRNA expression in cancer may serve as molecular biomarkers for tumor diagnosis, prognosis of disease-specific outcomes, and prediction of therapeutic responses. Furthermore, miRNAs may serve as specific targets of new gene therapies.

Cytogenetic effects of neutron therapy in patients with parotid gland tumors and relapse of breast cancer.

AIM: To assess the frequency and spectrum of chromosome aberrations and micronuclei in peripheral blood lymphocytes of patients with parotid salivary gland tumors and relapse of breast cancer during the course of neutron therapy. MATERIALS AND METHODS: Samples of peripheral blood were obtained from 9 patients with parotid salivary gland tumors (T3N0-3M0) and 8 patients with relapse of breast cancer before, after first fraction and at the end of neutron therapy. The treatment course specified 5.5-8.4 Gy (equivalent to 23-44 Gy of photon irradiation) with 1.3-2.2 Gy per fraction for patients with parotid salivary gland tumors and 4,8-8.0 Gy (equivalent to 30-40 Gy of photon irradiation) with 1.6 Gy per fraction for patients with relapse of breast cancer. Control group established for conventional cytogenetic analysis consisted of 15 healthy persons. Assessment of chromosome aberrations frequency was performed on routinely stained metaphase plates. Lymphocytes from the same patients were analyzed by micronucleus test in combination with fluorescent in situ hybridization (FISH) using pancentromeric DNA probe. RESULTS: Level of chromosome aberrations and micronuclei significantly increased in lymphocytes of patients from both groups during neutron therapy (P < 0.05). This increase was mainly due to chromosome-type aberrations and centromere-negative micronuclei. The prevalent types of aberrations are in agreement with theoretical mechanisms of neutron effects on cells. CONCLUSION: Cytogenetic effects of fast neutron therapy in lymphocytes of patients with parotid salivary gland tumors and relapse of breast cancer were observed. A positive dynamics of radiation-induced chromosomal damages formation during the course was denoted in lymphocytes of cancer patients in both groups.

Efficacy of natural L-asparagine in the complex therapy for malignant tumors in experimental studies.

AIM: To study the influence of natural L-asparagine on the efficacy of cytostatic therapy for malignant tumors in experimental investigations. MATERIALS AND METHODS: Female C57B1/6 mice weighing 18-20 g were selected for the experiments. Lewis' lung carcinoma (LLC) and melanoma B16 cells were used in the study. Animals were inoculated with tumor cells intramuscularly. Solution of L-asparagine in a volume of 0.2 ml per mouse (in appropriate doses) was administered to the animals using gastric probe, daily, for 14 days. Cyclophosphane was administered intraperitoneally in total doses of 180 mg/kg and 90 mg/kg on days 3 and 7 after tumor implantation. The percentage of tumor growth inhibition was calculated and inhibition index and frequency of metastasis were assessed. RESULTS: It has been shown that despite low activity of L-asparagine with regard to primary tumor, the level of metastasis inhibition is rather high (up to 91% depending on experimental model, therapy regimen and follow-up period). The analysis of previously obtained data and our studies indicate that L-asparagine derived from burdock (Arctium lappa) root has not only its own antimetastatic activity but it is also able to increase antimetastatic activity of cyclophosphane partially reducing toxic effect of cyclophosphane on the organism without decreasing its antitumor and antimetastatic activities. CONCLUSION: L-asparagine derived from burdock (Arctium lappa) root can be effective in the complex anticancer therapy with the use of appropriate chemotherapy doses and regimens.

Influence of venezuelan equine encephalitis, influenza and mumps vaccine viral strains on morphological patterns and viability of human tumor cells in vitro.

PURPOSE: To study the cytolytic and cytostatic effects in some human tumor cells lines after their infection with vaccine viral stains. MATERIALS AND METHODS: Cultures of human tumor cell lines (Hep-2, P3HR-1 and K-562) were exposed to vaccine viral strains of mumps, influenza and venezuelan equine encephalitis (VEE) to determine the impact of these strains on cell mitotic activity, nuclear abnormalities in interphase, extent of cell vacuole dystrophy and cell viability. RESULTS: Vaccine strains of the VEE and mumps viruses induced definite cytolytic effect in all studied cell lines, whereas the influenza virus showed such ability only in the Hep-2 cell line. Moreover, the VEE virus induced cytostatic effect in Hep-2, K-562, P3HR-1 cell lines; the mumps virus in Hep-2 and P3HR-1; and the influenza virus in Hep-2 and K- 562 cell lines. CONCLUSION: Vaccine strains of both the VEE and mumps viruses were able to induce definite cytolytic effect in all studied cell lines. However, further investigations are required to develop novel immunological methods for human tumor treatment.

[Clinical and morphologic aspects of cervical papillomavirus infection]. / Kliniko-morfologicheskie aspekty tservikal'noi papillomavirusnoi infektsii.

415 female residents of the City of Tomsk and Tomsk Region (patients with cervical carcinoma--22, dysplasia stage I-III--23 and healthy subjects--71) were screened for HPV16/18 infection, which was diagnosed in 18.3%. In the cervical carcinoma group, infection was detected in 27.4%, among patients with advanced cervical dysplasia--25.7%, and in those with background pathologies and healthy females--12.3 and 38%, respectively. Infection peaks were reported for the age brackets of 31-40 years (19.7%) and 51-60 years (19.6%). HPV-infection showed a wide range of colposcopic symptoms: areas of atypical blood vessels, leukoplakia, atypical epithelium and iodine-negative patches. Papillomavirus-related morphological changes in endometrial cells were typical of those associated with any viral infection and showed no specific features.

[Biotherapy of experimental tumors with vaccines of Venezuelan encephalomyelitis virus, parotitis and influenza viruses and cytologic evaluation of effectiveness]. / Bioterapiia éksperimental'nykh opukholei virusnymi vaktsinami Venesuél'skogo éntsefalomielita, parotita, grippa i otsenka eë éffektivnosti s ispol'zovaniem tsitologicheskikh pokazatelei.

Inhibition of experimental tumor growth, life-span, mitotic activity and cytologic damage have been studied in cells of ascitic and solid carcinoma of Ehrlich in the course of biotherapy with vaccines of Venezuelan encephalomyelitis virus, mumps and influenza viruses. Summing up, it is concluded that the vaccine of Venezuelan encephalomyelitis virus looks most promising as far as further research in development of an antitumor viral drug is concerned.

[Features of immunologic and virusologic indicators in oncology patients]. / Osobennosti immunologicheskikh i virusologicheskikh pokazatelei u onkologicheskikh bol'nykh.

Specific immunological indices have been compared in patients with head and neck tumors. It was found that the EBV-specific antibody levels in such patients were almost one order of magnitude higher than similar indices in healthy humans. The study identified profound changes in the T-cell chain of the immune system which is responsible for intercellular interaction regulation and cell killing. Altered number of lymphocytes and proportion of their main regulatory subpopulations were founded in cancer patients.

[Combined therapy of experimental tumors with the vaccinal strain of Venezulean encephalomyelitis virus]. / Kombinirovannaia terapiia éksperimental'nykh opukholei vaktsinnym shtammom virusa venesuél'skogo éntsefalomielita.

The potential of therapy with vaccinal strain of Venezuelan encephalomyelitis virus (VEL) in conjunction with cytostatics (cyclophosphamide) or immunomodulators (T-activin) has been studied. It was found that VEL in conjunction with cyclophosphamide inhibited the antitumor action of the drugs while T-activin potentiated the same effects of the virus and its oncolysate.

Assessment of the relationship of chronic opisthorchiasis to Epstein-Barr virus infection as well as some cytogenetical and immunological parameters in two comparable Siberian regions.

Previous studies have shown an increase in the frequency of chromosomal abnormalities in the peripheral blood lymphocytes from opisthorchiasis patients. Some evidence suggests that there is an association between chronic opisthorchiasis and certain herpes viruses. To study the relationship of opisthorchiasis to the reactivation of Epstein-Barr virus (EBV) infection as well as the influence of opisthorchis infection on some cytogenetical and immunological parameters, we used the indirect immunofluorescence for measuring some virus specific antibodies, the cytokinesis-block lymphocyte micronucleus assay, and the quantitative immunodiffusion method for measuring immunoglobulin concentrations in serum. A total of 1,580 people were monitored in two comparable Siberian regions: in the Ob River region which is endemically related to opisthorchiasis caused by Opisthorchisfelineus and in the nonendemic control Yenisey River region. There was no significant difference in each of the tested parameters between two uninfected controls from the endemic Ob and nonendemic Yenisey regions. We have found significant difference (p < 0.01) in the frequency of micronucleated cytokinesis-block lymphocytes and the antibody levels against certain EBV antigens between the examined inhabitants of the opisthorchis-infected Ob and uninfected Yenisey regions. Furthermore, there were a good correlation (r = + 0.72) between the increase in titres of antibody to the EBV capsid antigen and the high frequency of micronucleated lymphocytes in the opisthorchis-infected Ob population. Also, levels of both IgG and IgM were increased in opisthorchiasis patients. This study confirms an association between chronic opisthrochiasis and reactivation of EBV which may be implicated in the development of cancer in opisthorchiasis patients.

[The level of antibodies to Epstein-Barr virus antigens in the blood serum of the inhabitants of southern Siberia and the Far East]. / Uroven' antitel k antigenam virusa Epshteina--Barr v syvorotke krovi zhitelei iuga Sibiri i Dal'nego Vostoka.

Antibodies to Epstein-Barr virus have been detected in sera from 1538 healthy adult persons living in the south of Siberia and Far East. It has been shown that the virus infectivity varied from 77% in Russians of the Yakutsk ASSR to 100% in Orochi and Russians residing in the territory of the Gorno-Altai Autonomous Province. Antibody levels to the Epstein-Barr virus for inhabitants of the south regions were higher than those for inhabitants of the north regions.

[Diagnostic significance of determining antibodies to antigens of the Epstein-Barr virus in infectious mononucleosis]. / Diagnosticheskoe znachenie opredeleniia antitel k antigenam virusa Epshteina-Barr pri infektsionnom mononukleoze.

Infectious mononucleosis may be differentiated from clinically similar diseases by the detection of classes M and A antibodies to Epstein-Barr virus capsid antigen. The authors emphasize the high specificity of this test vs. the detection of the Paul-Bunnell-Davidson heterophilic antibodies.

[Human acute lymphoblastic leukemia associated with HTLV-I virus and its infection in healthy populations from various regions of the USSR]. / Ostryi limfoblastnyi leikoz cheloveka, assotsiirovannyi s virusom HTLV-I, i infitsirovannost' im zdorovogo naseleniia nekotorykh regionov SSSR.

Patients with various forms of hemoblastoses (328) and clinically healthy persons (530) were examined for antibodies to HTLV-I. The presence of antibodies was detected in 3 out of 40 patients with acute lymphoblastic leukemia and only in 1 of 70 patients with lymphosarcoma. These data indicate that sporadic cases of T-cell leukemia associated with HTLV-I were detected in the USSR. Out of 530 healthy persons only 4 contained antibodies to HTLV-I antigens.