ПРЕДИКТИВНОЕ ЗНАЧЕНИЕ МАРКЕРОВ КЛЕТОЧНОГО ЦИКЛА ПРИ РАКЕ СЛИЗИСТОЙ ОБОЛОЧКИ ПОЛОСТИ РТА

The aim of our study was to identify the most significant biological markers characterizing the behavior of the tumor and to forecast its clinical course and to specify an individual therapy regimen for each patient.Работа посвящена выявлению наиболее значимых биологических маркеров клеточного цикла, характеризующих поведение опухоли, с целью прогноза клинического течения опухолевого процесса и индивидуализации схем лечения

Оценка влияния экспрессии хемокиновых рецепторов CXCR4, ССR10 в опухолевой ткани на показатель безрецидивной выживаемости больных раком ободочной кишки

Considering a rise in colon cancer rates, searching for new treatment options remains highly relevant for this patient cohort. Determination of chemokine receptors in tumor tissue may become an additional prognostic tool that can be used for planning adjuvant therapy.Учитывая рост заболеваемости раком ободочной кишки, поиск новых вариантов лечения остается высоко актуальным для данной группы пациентов. Определение хемокиновых рецепторов в опухолевой ткани может стать дополнительным фактором прогноза и использоваться при планировании адъювантной терапии

Cистемное воспаление и иммунологическое микроокружение в прогнозе течения солидных опухолей

The purpose of the research. To study prognostic significance of indicators of systemic inflammation of peripheral blood and relative indicators: neutrophil‑lymphocytic and platelet‑lymphocytic ratio, the course of squamous cell carcinoma of the oral mucosa and gastric adenocarcinoma.Materials and methods. Prospective analysis of patients with squamous cell carcinoma of the oral mucosa and disseminated gastric adenocarcinoma was performed. Patients with verified diagnosis, without signs of inflammatory diseases in anamnesis, not receiving antibacterial and immunomodulatory therapy were selected. Overall survival and survival without progression were considered as the main estimated parameters.Results. The selection criteria were met by 32 patients with disseminated gastric adenocarcinoma and 60 patients with squamous cell carcinoma of the oral mucosa. The prognostic value of relative indicators is determined: overall survival of patients with gastric adenocarcinoma with a low value of the neutrophil‑lymphocytic index is significantly higher than that of the rest of the cohort of patients: 16 months vs. 8 and 7 months (95 % CI (confidence interval) from 12 to 23 months, p=0.0382). Overall survival of patients with low platelet‑lymphocytic index was also higher: 16 months vs. 8 months (95 % CI from 11 to 24 months, р=0,0026). Different relapse‑free survival was noted in the group of patients with squamous cell head and neck cancer: patients with low index value it is 7 months vs. 2 months (95 % CI from 5 to 9 months, p=0.0499).Conclusions. The results show the possibility of using immunological microenvironment of the tumor and indices, characterizing the systemic inflammation, for prognosis of gastric adenocarcinoma and squamous cell carcinoma of the oral mucosa.Цель исследования. изучить прогностическую значимость показателей системного воспаления периферической крови и относительных показателей: нейтрофильно-лимфоцитарное и тромбоцитарно-лимфоцитарное соотношение, на течение плоскоклеточного рака слизистой оболочки полости рта и аденокарциномы желудка.Материалы и методы. Произведен проспективный анализ больных плоскоклеточным раком слизистой оболочки полости рта и диссеминированной аденокарциномой желудка. Были отобраны пациенты с верифицированным диагнозом, без признаков воспалительных заболеваний в анамнезе, не получающие антибактериальную и иммуномодулирующую терапию. В качестве основных оцениваемых параметров рассматривали общую выживаемость и выживаемость без прогрессирования.Результаты. Критериям отбора соответствовали 32 больных диссеминированной аденокарциномой желудка и 60 больных плоскоклеточным раком слизистой оболочки полости рта. Определена прогностическая ценность относительных показателей: общая выживаемость пациентов с аденокарциномой желудка с низким значением нейтрофильно-лимфоцитарного индекса достоверно выше, чем у остальной когорты пациентов: 16 месяцев против 8 и 7 месяцев (95 % ДИ от 12 до 23 месяцев, р=0,0382). Общая выживаемость пациентов с низким уровнем тромбоцитарно-лимфоцитарным индексом также была выше: 16 месяцев против 8 месяцев (95% ДИ от 11 до 24 месяцев, р=0,0026). В группе больных плоскоклеточным раком головы и шеи достоверно отличалась безрецидивная выживаемость: у пациентов с низким значением показателя — 7 месяцев против 2 месяцев (95 % ДИ от 5 до 9 месяцев, р=0,0499).Выводы. Полученные результаты говорят о возможности использования показателей иммунологического микроокружения опухоли и индексов, характеризующих системное воспаление, для прогнозирования течения аденокарцином желудка и плоскоклеточного рака слизистой оболочки полости рта

Системное воспаление в течении аденогенного рака слюнных желез

Relevance. The inflammatory process and endogenous intoxication of the patient’s body has a negative impact on the course of many malignant neoplasms, including salivary gland cancer.The objective of the study was to determine the influence of some factors of systemic inflammation and endogenous intoxication in salivary gland cancer.Methods and materials. A prospective study included the data of 59 patients with salivary gland cancer. The influence of peripheral blood parameters and relative indicators characterizing systemic inflammation on overall and disease-free survival was assessed.Results. As a result of the multivariate analysis, it was revealed that an increase in the level of the relative number of peripheral blood neutrophils by more than 60.08 % increases the risk of death in patients from salivary gland cancer by 3.90 times (p=0.0456; HR 3.90: 95 % CI 1.03–14.79). The level of the absolute number of peripheral blood lymphocytes, not exceeding 1.49x109 /l, increases the risk of disease progression by 8.72 times (p=0.0002, R 8.72: 95 % CI 2.78–27.28).Conclusion. Individual factors of systemic inflammation and endogenous intoxication, it is advisable to evaluate at the stage of planning the primary treatment of patients with salivary gland cancer, in order to determine the prognosis of the disease and optimize the choice of tactics for the primary treatment of patients. Введение. Воспалительный процесс и эндогенная интоксикация организма больного оказывает негативное влияние на течение многих злокачественных новообразований, в том числе и на течение аденогенного рака слюнных желез.Цель исследования – определение влияния некоторых факторов системного воспаления и эндогенной интоксикации на течение аденогенного рака слюнных желез.Методы и материалы. В проспективном исследовании проанализированы данные 59 больных с аденогенным слюнных желез. Оценено влияние показателей периферической крови и относительных показателей, характеризующих системное воспаление, на общую и безрецидивную выживаемость.Результаты. В результате проведенного многофакторного анализа выявлено, что, повышение уровня относительного числа нейтрофилов периферической крови выше 60,08 % увеличивает риск смерти больных от аденогенного рака слюнных желез в 3,90 раза (р=0,0456; ОР 3,90: 95 % ДИ 1,03–14,79). Уровень абсолютного числа лимфоцитов периферической крови, не превышающий 1,49∙109 /л, увеличивает риск прогрессирования заболевания в 8,72 раза: р=0,0002, ОР 8,72: 95 % ДИ 2,78–27,28.Заключение. Отдельные факторы системного воспаления и эндогенной интоксикации целесообразно оценивать на этапе планирования первичного лечения больных аденогенным раком слюнных желез с целью определения прогноза заболевания и оптимизации выбора тактики первичного лечения больных.

Application of the bacteriophage Mu-driven system for the integration/amplification of target genes in the chromosomes of engineered Gram-negative bacteria—mini review

The advantages of phage Mu transposition-based systems for the chromosomal editing of plasmid-less strains are reviewed. The cis and trans requirements for Mu phage-mediated transposition, which include the L/R ends of the Mu DNA, the transposition factors MuA and MuB, and the cis/trans functioning of the E element as an enhancer, are presented. Mini-Mu(LR)/(LER) units are Mu derivatives that lack most of the Mu genes but contain the L/R ends or a properly arranged E element in cis to the L/R ends. The dual-component system, which consists of an integrative plasmid with a mini-Mu and an easily eliminated helper plasmid encoding inducible transposition factors, is described in detail as a tool for the integration/amplification of recombinant DNAs. This chromosomal editing method is based on replicative transposition through the formation of a cointegrate that can be resolved in a recombination-dependent manner. (E-plus)- or (E-minus)-helpers that differ in the presence of the trans-acting E element are used to achieve the proper mini-Mu transposition intensity. The systems that have been developed for the construction of stably maintained mini-Mu multi-integrant strains of Escherichia coli and Methylophilus methylotrophus are described. A novel integration/amplification/fixation strategy is proposed for consecutive independent replicative transpositions of different mini-Mu(LER) units with “excisable” E elements in methylotrophic cells

MODERN TREATMENT OF METASTATIC MELANOMA: FROM STANDARDS TO AN INDIVIDUALIZED APPROACH IN REAL CLINICAL PRACTICE

The incidence and mortality of skin melanoma in the world and in Russia is growing every year. It should be noted that the proportion of patients with melanoma of late stages remains high. Until recently, only ineffective chemotherapy regimens were available for such patients. That is why the possibility of using modern drugs in real clinical practice for the treatment of this cohort of patients is an urgent issue of modern clinical oncology. The appearance in a real clinical practice of a new group of immunological drugs (anti-CTLA4 and anti-PD-1) for the treatment of patients with metastatic melanoma allows to increase both the time to progression and the life span of this cohort of patients.In this article, we present the experience of St. Petersburg Regional Clinical Hospital “City Clinical Oncology Clinic” in the treatment of patients with metastatic melanoma under the conditions of real clinical practice with the preparation of ipilimumab as part of the expanded access program from February 2014 to March 2017. In total, 31 patients with disseminated melanoma (12 men and 19 women) were treated with ipilimumab during this period. The average age was 57 years (from 39 to 81 years), in 8 patients there were metastases to the brain. Patients with ECOG status 1 at the time of initiation of treatment were the majority 28 patients (90%), three patients (10%) had ECOG status 2. All patients had previously received 1 to 4 lines of systemic chemotherapy. The median of the observation period is currently 12 (3-35) months. The median time to progression was 6 months. At 5 of 31 patients at the time of analysis, signs of progression were not identified. The median overall survival (OB) was 12 months 9 of 31 patients were alive at the time of the analysis. The annual OM was 56.5%, the 2-year period was 29.4%.The article presents a clinical case of treatment of a patient with metastatic melanoma, which will have an effect against the progression of the disease after four lines of therapy, including ipilimumab. The patient was included in the program of expanded access to the PD-1 inhibitor, nivolumab. In all, the patient received 65 nivolumab injections. The life expectancy of the patient from the moment of diagnosing the metastatic stage of the disease is 3.5 years, while 2.5 years on the background of nivolumab therapy. Patient monitoring continues

PROGNOSTIC ROLE OF LABORATORY AND IMMUNOHISTOCHEMICAL MARKERS IN THE RECURRENCE OF ORAL MUCOSAL SQUAMOUS CELL CARCINOMA

Twenty fifty-nine patients with oral mucosal squamous cell carcinoma (a study group) and 50 healthy volunteers (a control group) were followed up. The poor prognosis and occurrence of early recurrences correlated with the simultaneous high level of C-reactive protein (CRP), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA) (and an increase in their values over time), elevated WNC, ACN, and PLT levels, low Caspase-3 expression, high p53 and bcl-2 expression, and the absence of lower Ki-67 expression over time, and the presence of EBV and CMV in tumor tissue. Decreased Ki-67 index at the stages of treatment, high Caspase-3 expression, low bcl-2 and p53 expression, and low CRP, CEA, and SCCA levels, and tumor HPV-positive status were associated with the favorable prognosis of a tumor process

Survival of patients with salivary gland malignancies depending on the molecular profile of the tumor

Introduction. Standard methods of drug or radiation therapy administration for salivary gland cancer is the least successful for now. Therefore, the identification of new markers with morphological features is extremely necessary to improve the effectiveness of treatment and increase the survival rates of patients with this pathology.The study objective is to assess the prevalence of expression of HER2/neu, PD-L1, and RET mRNA in salivary gland malignancies and assess their impact on overall and disease-free survival.Materials and methods. Fifty-nine patients with a confirmed diagnosis of salivary gland cancer (stages II–IVA) were examined in the period from 2012 to 2014 at Saint Petersburg City Clinical Oncology Dispensary. All materials were subjected to immunohistochemical research to determine the expression of HER2, PD-L1 in tumor and immune cells, the CPS index was calculated, and the frequency of the mRNA gene RET expression using a real-time polymerase chain reaction was detected.Results. The overall survival of patients with mild and high HER2 expression was 41 months (95 % confidence interval (CI) 4.50–72.00), which is more than 4 time less than in patients with low or no expression (p = 0.00715). Significant differences were also received in the progression-free survival in the group of patients with negative or insignificant expression of HER2 receptors. The overall survival of patients with CPS >1 was 72 months (95 % CI 19.5–72.00) and significantly differed from the group of patients with CPS <1, where it was not yet achieved (p = 0.0124). mRNA expression of the RET gene was detected in 13 out of 48 cases, which was 27.08 %. The expression level ranged from 0 to 0.205. The progression-free survival in the group of patients with mRNA expression was 168 months (95 % CI 16.00–168.00) and tended to increase in the group of patients who did not have this expression.Conclusion. When analyzing the obtained data, it was proved that knowledge of the salivary glands malignant tumors receptor status become one of the factors in determining the prognosis of the disease, as well as a predictive factor of targeted drugs effectiveness (after сonducting prospective randomized studies)