Cytokine net role in mechanisms of neuroimmune interaction (literature review)

This work deals with the literature review on the problems associated with the progress of the national and foreign authors in studying the role of the cytokine net in the pathogenetic mechanisms of forming the diseases of the nervous system. Studying the peculiarities in the functions of a number of the immune system indices as the targets of the combined exposure to the production and other factors are known to be the actual aspect of the works analyzed in the recent years. A special attention in the literature studied is paid to the intersystem interactions between the nervous and the immune systems and. the immune systems and. the value of their homeostasis. The literature deals with the causes of the injuries and/or the cellular death of the nervous system and, as the consequence, the function changes of other organism systems and the production of their activity products. The change regularities in the pro-inflammatory cytokines (IL-1β, TNF-α, IL-6 and IL-12) in the diseases of different etiology including those which were stipulated by the factors of the production environment and other factors on the example of the multiple sclerosis as the neurodegenerative disease are represented in this paper. The possibilities of the disease objectify of the nervous system and the determination of their process severity in the clinical praxis based on the immunological indices and the patient complaints are given in this work. The studies testifying the different mechanisms of the autoimmune response realization in exposure to the neuro toxicant of different etiology are represented in this paper as well as the direct correlation between the antibody content to the proteins of the nervous tissue and the production of the pro-inflammatory cytokines has been revealed. At the same time, the common morpho-functional regularities of the changes in the central nervous system of the albino rats in the post-contact period as a result of the exposure to the metallic mercury vapors and. sublimate including the persons examined working at the production were indicated. In the conclusion. the important actuality role of the molecular-genetic studies dealing with the gene polymorphism of the cytokine net in the ethiopathogenesis of the autoimmune disease and. the problems of the early diagnostics of the neurodegenerative disorders in the employees exposed to the neurotoxicants of different chemical nature is indicated

ПЛАНИРУЕМОЕ МНОГОЦЕНТРОВОЕ РАНДОМИЗИРОВАННОЕ КЛИНИЧЕСКОЕ ИССЛЕДОВАНИЕ II ФАЗЫ: НЕОАДЪЮВАНТНАЯ ХИМИОЛУЧЕВАЯ ТЕРАПИЯ С ПОСЛЕДУЮЩЕЙ ГАСТРЭКТОМИЕЙ D2 И АДЪЮВАНТНОЙ ХИМИОТЕРАПИЕЙ У БОЛЬНЫХ МЕСТНОРАСПРОСТРАНЕННЫМ РАКОМ ЖЕЛУДКА

Introduction. The prognosis for surgical treatment of locally advanced gastric cancer remains disappointing. Neoadjuvant chemo-radiation therapy is relatively new and the least researched method of treatment, it is attracting more and more attention, mainly abroad in recent years. The aims of neoadjuvant therapy is the earliest start of systemic therapy, damage of the primary tumor and regional metastases, an increase in the percentage of radical operations, improving treatment outcome. Material and methods. The planning study is a multicenter, randomized clinical phase II trial. Patients of the first (experimental) group will be treated as the followes: neoadjuvant chemo-radiotherapy (total tumor dose of 46 Gy in 23 fractions with the concurrent modified CapOX scheme) followed by D2 gastrectomy and adjuvant chemotherapy. Patients of the second (control) group will be treated with D2 gastrectomy and adjuvant chemotherapy. Adjuvant chemotherapy will be carried out under the following schemes (optional for the researchers): CapOX or FOLFOX. Toxicity evaluation of neoadjuvant chemo-radiotherapy and adjuvant chemotherapy will be conducted with NCI CTC Toxicity Scale Version 3.0. The main objectives of the trial are to assess the safety and immediate effectiveness of neoadjuvant chemo-radiotherapy according to the criteria of the frequency and severity of postoperative complications and mortality, and tumor response. We are planning to include 80 patients with morphologically confirmed gastric cancer сT2–4N1–3, сT3–4N0–3; М0. The proposed trial will be carried out in accordance with the principles of the Helsinki Declaration, it has been approved by local ethic committees of the participated institutions. Results. As a result of this multicenter randomized trial it is planned to show the reproducibility of obtained in MRRC and a number of foreign centers results – that is, the safety and high immediate effectiveness of neoadjuvant chemo-radiotherapy in patients with locally advanced gastric cancer. Conclusion. If we reach the goals of the planning trial, the results would allow to reasonably recommend the start of large international phase III trials for the final evaluation of the proposed neoadjuvant treatment as a standard one in patients with locally advanced gastric cancer.Введение. Прогноз при хирургическом лечении местнораспространенного рака желудка остается неутешительным. Неоадъювантная химиолучевая терапия является относительно новым и наименее исследованным методом лечения, привлекающим к себе в последние годы все большее внимание, преимущественно за рубежом. Цели неоадъювантной терапии состоят в максимально раннем начале системной терапии, повреждении первичной опухоли и регионарных метастазов, увеличении процента выполнения радикальных операций, улучшении результатов лечения. Материал и методы. Исследование является многоцентровым рандомизированным клиническим исследованием II фазы. Больным первой (исследуемой) группы будет проведено лечение в составе: неоадъювантная химиолучевая терапия (СОД 46 Гр за 23 фракции на фоне модифицированного режима CapOX) с последующей гастрэктомией D2 и адъювантной химиотерапией. Больным второй (контрольной) группы будет выполнена гастрэктомия D2 и адъювантная химиотерапия. Адъювантная химиотерапия будет проводиться по следующим схемам (на выбор исследователя): САРОX или FOLFOX. Оценка токсичности неоадъювантной химиолучевой терапии и адъювантной химиотерапии будет проводиться с помощью шкалы токсичности NCI CTC, версия 3.0. Основные цели состоят в оценке безопасности и непосредственной эффективности неоадъювантной химиолучевой терапии по критерию частоты и степени выраженности послеоперационных осложнений и летальности, и терапевтического патоморфоза. Планируется включение 80 больных морфологически верифицированным раком желудка сT2–4N1–3, сT3–4N0–3; М0. Исследование выполняется в соответствии с принципами Хельсинкской декларации, оно одобрено локальными этическими комитетами учреждений-соисполнителей. Результаты. В результате проведения данного многоцентрового рандомизированного исследования планируется показать воспроизводимость полученных в МРНЦ и ряде зарубежных Центров результатов – то есть безопасность и высокую непосредственную эффективность неоадъювантной химиолучевой терапии у больных местнораспространенным раком желудка. Заключение. В случае достижения поставленных целей полученные результаты позволят обоснованно рекомендовать проведение крупных международных исследований III фазы для окончательного изучения предложенного метода в качестве стандартного у больных местнораспространенным раком желудка

PLANNING PHASE 2 MULTICENTER RANDOMIZED TRIAL OF NEOADJUVANT CHEMO-RADIOTHERAPY FOLLOWED BY D2 GASTRECTOMY AND ADJUVANT CHEMOTHERAPY FOR LOCALLY ADVANCED GASTRIC CANCER

Introduction. The prognosis for surgical treatment of locally advanced gastric cancer remains disappointing. Neoadjuvant chemo-radiation therapy is relatively new and the least researched method of treatment, it is attracting more and more attention, mainly abroad in recent years. The aims of neoadjuvant therapy is the earliest start of systemic therapy, damage of the primary tumor and regional metastases, an increase in the percentage of radical operations, improving treatment outcome. Material and methods. The planning study is a multicenter, randomized clinical phase II trial. Patients of the first (experimental) group will be treated as the followes: neoadjuvant chemo-radiotherapy (total tumor dose of 46 Gy in 23 fractions with the concurrent modified CapOX scheme) followed by D2 gastrectomy and adjuvant chemotherapy. Patients of the second (control) group will be treated with D2 gastrectomy and adjuvant chemotherapy. Adjuvant chemotherapy will be carried out under the following schemes (optional for the researchers): CapOX or FOLFOX. Toxicity evaluation of neoadjuvant chemo-radiotherapy and adjuvant chemotherapy will be conducted with NCI CTC Toxicity Scale Version 3.0. The main objectives of the trial are to assess the safety and immediate effectiveness of neoadjuvant chemo-radiotherapy according to the criteria of the frequency and severity of postoperative complications and mortality, and tumor response. We are planning to include 80 patients with morphologically confirmed gastric cancer сT2–4N1–3, сT3–4N0–3; М0. The proposed trial will be carried out in accordance with the principles of the Helsinki Declaration, it has been approved by local ethic committees of the participated institutions. Results. As a result of this multicenter randomized trial it is planned to show the reproducibility of obtained in MRRC and a number of foreign centers results – that is, the safety and high immediate effectiveness of neoadjuvant chemo-radiotherapy in patients with locally advanced gastric cancer. Conclusion. If we reach the goals of the planning trial, the results would allow to reasonably recommend the start of large international phase III trials for the final evaluation of the proposed neoadjuvant treatment as a standard one in patients with locally advanced gastric cancer