e15508 Background: The most important stages of metastatic cascade are extravasation and invasion of malignant cells and their surviving in blood. The vast majority of circulating tumor cells (CTC) is destroyed by immune cells. The role of immune system which is able to play not only antitumor but also prooncogenic role is manifested both on local and systemic levels. We studied correlations between lymphocyte subsets` content in blood and in tumor of colorectal cancer patients (II, III, IV stages) with and without CTC. Methods: 60 colorectal cancer patients with II (n = 20), III (n = 20) and IV (n = 20) stages underwent surgery without previous chemotherapy. CTC were measured in blood by CellSearchSystem™ (JanssenDiagnostics, LLC), cell-mediated immunity was assessed in blood by flow cytometry (BD Canto II) and in tissue after surgery by immunohistochemistry; some markers of proliferation and epithelial-mesenchimal transition (EMT) in tumor cells (Ki-67, E- and N-cadherins) were also studied. Criteria of CTC-positive and CTC-negative samples were > 3 and ≤3 respectively. Correlative analysis was performed between the data of the patients with and without CTC in each stage, r was counted. Results: In CTC-positive patients with all the stages the number of strong and moderate correlations between system immunologic factors involving CD8+ appeared to be fewer than in CTC-negative ones (7 vs 19). On the contrary, the number of correlations with T regs in CTC-positive was increased: 5 vs 3 in CTC-negative patients. In patients with CTC > 3 fewer correlations were noted between factors of local and systemic immunity than in CTC-negative ones (9 vs 4 in II stage) and total disruption of all the correlations between system immunologic factors and proliferating tumor cells in III and IV stages was established. Some pathologic correlations appeared in CTC-positive patients like moderate direct one between activated T-lymphocytes` amount and Ki-67+ tumor cells. The number of correlations between intratumoral lymphocytes and tumor cells expressing proliferation and EMT markers in CTC-positive patients was decreased in comparison with CTC-negative ones (4 vs 10 in II stage, 1 vs 9 in III, 2 vs 9 in IV stage). Conclusions: The presence of CTC in colorectal cancer patients rather than tumor stage is associated with imbalance of their systemic and local immunologic factors. This provides some evidence that disruption of interactions in the immune system is at least partly due to CTC.
e15597 Background: Oncolytic virotherapy is developing intensively in modern oncology. Viruses demonstrate the ability to the direct oncolysis and to the stimulation of antitumor immune activity; this experiment was aimed at solving the question of the prevalence of one of them. Glial tumors are the most common brain tumors; oncolytic viruses show certain prospects in their treatment due to the ability to penetrate the blood-brain barrier. The aim of the study was to determine the possible oncolytic effect of new unclassified group K rotaviruses (RVK) on T98G and U87MG glioblastoma cells in vitro. Methods: T98G and U87MG cell cultures were received from Russian banks of cell lines of human and animal tissues. Standard culturing was performed with attenuated apatogenic RVK strains No. 100 and No. 228 at a concentration of 108, 107, 106 and 105 particles/mL. The cytotoxic effect was determined with MTT and Annexin V assays, cell morphology was evaluated by the light-optical method. Results: Both RVK strains demonstrated a dose-dependent cytotoxic activity; the maximal effect was observed in strain No.100 at a dose of 108 particles/mL on U87MG cells (predominantly apoptosis). Studies of cell morphology showed a pronounced effect of RVK on the cell culture: significant degenerative changes in cells, a tendency to a decrease in cluster size, a change in their shape and granularity. Cluster formation in culturing in the serum-free medium is considered in the literature as a property of cancer stem cells responsible in vivo for tumor recurrence and its chemo- and radio-resistance. T98G cells demonstrated morphological changes: nuclear segmentation, diffused cytoplasm, indistinct cell borders with signs of syncytium formation. Conclusions: The established oncolytic effect of RVK strain No. 100 in vitro on glioma cells, presumably with tumor stem cells, indicates a significant potential for the use of these rotaviruses in treatment of glial tumors.
Ростовский научно-исследовательский онкологический институт, г. Ростов-на-Дону, Россия Реферат Цель. Оценить результаты применения неоадъювантной химиоиммунотерапии у пациенток с неоперабельны-ми формами рака яичников. Методы. В исследование включены 72 пациентки с раком яичников стадии IIIС-IV, которые были разделены на три группы: с неоадъювантной химиотерапией и неоадъювантной химиоиммунотерапией с внутримышечным и внутрибрюшинным введением интерферона гамма. При оценке эффективности лечения изучали и сравнивали непосредственные и ближайшие результаты лечения. Дополнительно в свежем послеоперационном материале методом ДНК-проточной цитометрии проведены определение плоидности и анализ клеточного цикла. Выпол-нена оценка иммунного статуса до лечения и после окончания неоадъювантной терапии. Результаты. После проведения курсов неоадъювантной полихимиотерапии больным в группе с внутримышеч-ным введением интерферона гамма выполнена операция полного объёма у 81,8% женщин, в группе с внутри-брюшинным введением интерферона гамма -у 87,5% пациенток (р ≤0,05), в контрольной группе (без примене-ния интерферона гамма) операция полного объёма выполнена у 34,6% больных. Также выявлено, что в группах с применением интерферона гамма частота возникновения рецидива в группе с внутрибрюшинным введением интерферона гамма составила 25% (р <0,05) -против 59,09% в группе с внутримышечным введением и 76,9% в группе без применения интерферона гамма. Проведённое нами исследование позволило установить сниже-ние количества анеуплоидных опухолей в группе с внутрибрюшинным введением интерферона гамма. Анализ состояния иммунной системы показал положительную динамику иммунного статуса в группах с применени-ем интерферона гамма. Вывод. Применение интерферона гамма в комплексе с неоадъювантной химиотерапией позволяет улучшить непосредственные результаты лечения и увеличить срок до возникновения рецидива; внутрибрюшинное и вну-тримышечное введение интерферона гамма сопровождается сходными позитивными иммунологическими изме-нениями по ряду показателей клеточного иммунитета; количество анеуплоидных опухолей у больных с химио-иммунотерапией ниже, чем в контрольной группе, что свидетельствует о лучшем прогнозе течения заболевания. Ключевые слова: рак яичников, лечение, химиоиммунотерапия, интерферон гамма. Neoadjuvant chemoimmunotherapy for inoperable ovarian cancer G.A. Nerodo, E.Yu. Zlatnik, I.A. Novikova, A.Yu. Ardzha, E.V. Verenikina, V.P. Nikitina, O.E. Kravtsova, E.S. Bondarenko, E.I. Zolotareva Rostov Research Institute of Oncology, Rostov-on-Don, RussiaAim. To assess the results of neoadjuvant chemoimmunotherapy for patients with inoperable ovarian cancer. Methods. The study included 72 patients with stage IIIС-IV ovarian cancer divided into three groups: with neoadjuvant chemotherapy and with neoadjuvant chemoimmunotherapy with intramuscular and intraperitoneal interferon gamma. Direct and immediate results of the treatment were studied and compared to assess the efficacy of treatment. Besides, ploidy determination and cell cycle analy...
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