RS4673 and pon1 level in blood plasma - new prospects in prediction and early diagnostics of anthracycline-mediated cardiotoxicity.

The purpose of this study was to research the effectiveness of molecular genetic tests based on the determination of the rs4673 CYBA polymorphism (c.242C>T) and the level of paraoxonase 1 (PON1) in the blood plasma of patients with breast cancer (BC) for predicting and diagnosing anthracycline-mediated cardiotoxicity (AMC). The genotyping of rs4673 CYBA (c.242C>T) and the study of the PON1 level in the blood plasma of 280 patients of the Caucasian type with a histologically verified diagnosis of breast cancer, who received complex treatment on the basis of the National Medical Research Center of Oncology, were carried out. Based on the results of observation for at least 8 months, two groups were identified: group 1 (257 people) without diagnosed cardiovascular changes; group 2 (23 people) - patients with subacute and early chronic AMC. It was found that carriers of the rs4673 polymorphism increase the likelihood of developing AMC by 6.8 times (p = 0.001). In the blood plasma of both groups of patients, an increase in the level of PON1 was described after the fourth course compared to the initial level (group 1 - p = 0.036, group 2 - p = 0.048). The level of the studied enzyme was higher in the blood plasma of patients with diagnosed AMC compared with patients without cardiovascular complications (before chemotherapy - p = 0.001, after the fourth course - p = 0.023). The test based on the measurement of the concentration of PON1 in the blood plasma of patients after the fourth course of chemotherapy was distinguished by high quality metrics: sensitivity - 100%, specificity - 70.8%, area under the ROC-curve (AUC) - 0.825 with a threshold level of PON1 equal to 2, 9 ng/µL. The presence of the T/T genotype caused a high level of PON1 in the blood plasma after the fourth course of chemotherapy (p = 0.012). The results of our work are of undoubted practical importance, since they allow us to obtain data on the prognosis and diagnosis of a patient in a short time, which can later be verified using clinical and instrumental methods.

[Anti-EGFR monoclonal antibodies in locally advanced head and neck squamous cell cancer].

The article presents immediate results of neoadjuvant treatment of patients with locally advanced head and neck squamous cell cancer and an evaluation of the toxicity of cetuximab. Standard chemotherapy in combination with targeted therapy with cetuximab showed its high effectiveness and satisfactory tolerance.

[Experience with the use of palonosetron (onicit) in patients with solid tumors receiving cytostatic therapy].

Nausea and vomiting are among adverse effects of chemotherapy that significantly worsen quality of life of patients. 5-HT3 receptor antagonists have been used in recent decades to prevent and arrest these complications. Palonosetron is the most modern drug in this group. Palonosetron application during highly and moderately emetogenic chemotherapy showed its high effectiveness for nausea and vomiting prevention.

[The role of assessing UGT1A1 gene polymorphism in the prediction of irinotecan-induced toxicity in the course of chemotherapy for colorectal cancer].

There was performed a molecular genetic study of UGTlAl gene allelic variants polymorphism in patients with colorectal cancer who had had chemotherapy irinotecan-containing regimens FOLFIRI. Comparison of toxicity and the results of polymorphism of UGTlAl showed that dose-limiting hematologic and non-hematologic toxicities in patients with moderate and high risk of toxicity were higher (p = 0.050- 0.061) and the frequency of thrombocytopenia (p = 0.0257) and hyperbilirubinemia (p = 0.0439) were significantly higher compared to the low-risk group. Molecular genetic study of a complex examination of patients, which was planned to irinotecan should be performed to select the optimal dose and reduce the risk of toxicity of chemotherapy.

[The relationship between EGFR mutation and clinico-pathological features of lung adenocarcinoma in residents of southern Russia].

The study was designed to analyse the relationship between EGFR mutation and clinico-pathological features of lung adenocarcinoma in residents of southern Russia taking account oftheir age and sex, localization of the primary tumour, its cell differentiation, regional metastases, stage of disease and smoking status of the patients with mutant and wild-type EGFR genes. The frequency analysis included 29 somatic mutations in EGFR exones 18-21. The study revealed statistically significant associations of EGFR gene mutations with gender, smoking and stage of disease.

[State of collective immunity against poliomyelitis in some regions of Russia].

AIM: Study the state of collective immunity against poliomyelitis in 7 regions of Russia in the last 3 years. MATERIALS AND METHODS: 2579 sera were studied for antibodies against poliomyelitis virus. Antibodies (AT) against 3 types of viruses were determined in neutralization reaction in RD cell culture, the state of collective immunity in the examined individuals was evaluated by the percent of individuals with AT against a type of poliovirus and geometric mean AT titer. The circulation of wild polioviruses was judged by the presence of strain specific AT against wild and vaccine viruses in the examined children (311 sera were studied). RESULTS: The indicators of collective immunity against poliomyelitis in both select examined regions and select age groups were generally high. The data obtained allow to make a conclusion that the quality of vaccine prophylaxis in the examined regions is good. Introduction of wild poliovirus type 1 from Tajikistan in 2010 caused disease in 7 residents of Russia whereas an epidemic that had affected more than 700 individuals emerged in Tajikistan. CONCLUSION: The studies carried out confirmed the necessity to continue qualitative poliomyelitis vaccine prophylaxis in the country despite the lack of circulation of wild polioviruses that can be introduced at any time.

[Sweat gland polyneoplasia with extensive metastases].

The paper describes a case of sweat gland polyneoplasia with extensive metastases in a 47-year-old woman, which is indicative of extreme malignancy of this tumor.

[Peculiarities of diagnosis and treatment of patients with hyposialosis].

33 patients with complaints of hyposalivation (21 in a 33 with syaloadenopatya and 12 in a 33 with syalosis out of the acute stage of disease) were examined. Complex examination of the saliva glands, analysis of the haemokynes in the various mediums of organism and thyoles compounds in the blood plasma was carried out. Tendency to increase in contents of haemokynes in the mixed saliva and in the tissue samples (from low in the syaloadenopatya to expressed in the syalosis) was revealed. Reduction of thyosulfide index in the blood plasma of these patients was determined. Use of antioxidant remedy in complex treatment of syaloadenopatya and syalosis was substanciated in this paper.

[Optimal conditions for producing immunomodulating effect of epithalamine as component of neoadjuvant chemotherapy using autoplasma and autoblood in patients with locally advanced breast cancer]. / Usloviia optimal'noi realizatsii immunomoduliruiushchego deistviia preparata épitalamina u bol'nykh mestorasprostranennym rakom molochnoi zhelezy pri ad''iuvantnoi khimioterapii na estestvennykh sredakh organizma.

Neoadjuvant chemotherapy was given to 105 patients with locally advanced breast cancer after incubation of cytostatics with autoplasma (APCT) and autoblood (AHCT). Most of them also received epithalamine after incubation with AHCT. That significantly improved such parameters of cellular immunity as T-cell content, their subset distribution and function. The most favorable changes were observed when epithalamine was used in conjunction with AHCT. A similar immuno-modulating effect was exerted when epithalamine was used irrespective of either CMAV or CMFV regimens.

[Effect of epithalamin on free-radical reactions in the formed elements of blood from breast cancer patients]. / Vliianie épitalamina na aktivnost' svobodnoradikal'nykh protsessov v formennykh élementakh krovi bol'nykh rakom molochnoi zhelezy.

Translocation of cytomedins into the cell is determined by their interaction with cellular membranes. The investigation concerned membrane-associated free-radical reactions in the formed elements of blood incubated with epithalamin. The antioxidative effect of epithalamin on such elements as red blood cells and lymphocytes sampled from breast cancer patients manifested itself as enhanced activity of antioxidative enzymes and elevated concentrations of fat-soluble antioxidative vitamins in the membranes. These changes are likely to be brought about by the intensification of their regeneration from the oxidized forms. It is suggested that the stimulating effect of epithalamin on immunocompetent cells is due to its modulating influence on free-radical reactions. This effect gives epithalamin significant advantage over many immunotropic drugs and makes a case for its large-scale application for immunological rehabilitation of cancer patients.

[Effect of new chemotherapeutic methods on the biologic tissue environment and on the immune status of patients with breast cancer]. / Vliianie novykh metodov khimioterapii na biologicheskikh sredakh organizma na immunnyi status bol'nykh rakom molochnoi zhelezy.

Standard (SCT), autoplasmochemotherapy using cytostatics preincubation with autoplasma (APCT) and autoblood (autohemochemotherapy--AHCT) were compared to evaluate their effects on locally advanced breast tumors. SCT showed marked immunosuppressor effect while APCT and, particularly, AHCT--a sparing one. The use of the latter modalities involved significantly higher levels of active T-, NK- and cytotoxic CD+ 8 cells. A comparison of the latter methods also showed ABCT to yield a better subset balance between T- and B-cells and a higher level of their mitogen response.

[Effect of chemotherapeutical agents on the structure and function of blood serum albumin in breast cancer]. / Vliianie khimiopreparatov na strukturu i funktsional'nye svoistva al'bumina syvorotki krovi bol'nykh rakom molochnoi zhelezy.

Superoxide-removing activity, the number of sulfo-hydryl NH2-groups and groups, mean mass molecular concentration, free and antioxidant activity of albumin were determined in blood serum and its albumin fraction in 20 patients with breast cancer T3-4N1-2Mo, before and after incubation with cyclophosphamide, adriablastin, methotrexate and vincristine at concentrations used in clinic. Our data suggested that, following incubation with blood plasma, chemotherapeutic drugs bound to albumin fraction and protein fragmentation took place. Preincubation of blood plasma with the drugs and their immobilization on albumin molecules caused protein fragmentation to occur. Fragments having pro-oxidant properties might have been absorbed and fixed by both tumor tissues and any others thus creating a pool of fast-dividing cells and organs. Therefore, cytostatic drugs can exert enhanced antitumor action and, at the same time, a highly toxic effect when administered with autoplasma during chemotherapy.

LDL-receptor gene polymorphism in patients with early-onset coronary artery disease.

Simultaneous amplification of the promoter and 17 (out of 18) exons of the LDL-R gene (along with flanking intron sequences) was performed in 36 patients with hypercholesterolemia and early-onset coronary artery disease. The identification of the PCR-products on denaturing gradient gel electrophoresis (DGGE) revealed 34 cases of heteroduplexes in 24 patients. The heteroduplexes in exons 12, 10, and 2 (31%, 28% and 22%, respectively) probably reflect common polymorphism of LDL-R gene, while heteroduplexes in exons 6, 4 and 13 are less frequent (5.6%, 5.6%, and 2.8%, respectively). Significant association between the genetic variants, or polymorphism with clinical manifestations, could not be established.

[A clinical and experimental validation of the use of Stimuloss in patients with chronic generalized periodontitis]. / Kliniko-éksperimental'noe obosnovanie primeneniia u bol'nykh khronicheskim parodontitom "Stimulossa".

The pharmacological effect of hydroxyapatite and a composition based on it in the form of Stimulos sponge has been studied in human osteogenic tissue culture. Hydroxyapatite stimulated the biosynthetic processes in the cells. Addition of chlorohexidine and thymogen to the composition in order to increase its antibacterial activity did not decrease the osteoinductive properties of the drug. Trials of Stimulos in 66 patients with chronic generalized periodontitis demonstrated its high efficacy, particularly of the compositions containing immunostimulants: inflammation disappeared and the height of alveolar osseous tissue increased, as did bone compactness.

[An experimental and clinical study of Ossocol, a compound of hydroxylapatite and collagen]. / Izuchenie v éksperimente i klinike kompozitsii gidroksilapatita c kollagenom--"Ossokola".

Experiments on white rats revealed that introduction of Ossocol, a sponge with a composition of hydroxyl apatite with collagen, into a removed tooth well prevented mandibular atrophy and was conducive to a more smooth defect filling with better compact bone tissue. Ossocol use in 214 patients with bone tissue defects developing after tooth removal, of odontogenic cysts, sequestra, and after radical surgery for periodontal diseases demonstrated a positive effect of this agent on the course of the postoperative period: the defect was more rapidly replaced by bone tissue. No unfavorable local or general reactions to Ossocol implantation were observed.

[The effect of hydroxylapatite on the experimental healing of the tooth socket]. / Vliianie gidroksilapatita na zazhivlenie lunki zuba v éksperimente.

Synthetic hydroxylapatite, a drug made in this country, enhanced reparative osteogenesis if introduced in the dental well of a white rat. The regenerate represented solid bone structure in 4 months after tooth removal.