MOLECULAR DESIGN OF SUGAR-FREE MIGRACIN ANALOG MIGRACINAL THAT INHIBITS OVARIAN CANCER CELL MIGRATION AND INVASION

Introduction. Cancer metastasis consists of several steps including detachment from the primary tumor, migration, invasion, transport in the blood or lymphatic vessels, attachment at the secondary site, and growth of secondary tumor. Migration and invasion areinvolved in the mechanism of all types of cancer metastasis. We previously isolated novel cellular migration inhibitor migracin A and B from a culture filtrate of Streptomyces sp. Migracin A was shown to inhibit IGF-1-mediated cellular migration and invasion in ovarian carcinoma cells. However, it is difficult to prepare large amount of migracin A. Migracin A consists of substituted benzene and an alkylated sugar moiety. In the present research, we have designed and synthesized a simplified dialdehydederivative of migracin called migracinal having no sugar moiety. Material and methods. Migracinal was purchased from Techno Chem Co., Ltd., Tokyo, Japan. Migracinal was prepared from 2,4-dihydroxybenzaldehyde (2,4-DHBA). The structure was confirmed by proton and carbon NMR spectra and ESI mass spectroscopy. The antitumor activity of the new derivative was studied by standard tests under conditions in vitro. Results. Migracinal inhibited cellular migration and invasion in ovarian clear cell carcinoma ES-2 cells. It also inhibited IGF-1 expression as migracin A. Moreover, it induced anoikis rather than apoptosis in ES-2 cells.Conclusions. Migracinal is easier to prepare than migracins, and it may be useful for the mechanistic study and suppression of metastasis. Введение. Процесс метастазирования рака состоит из нескольких этапов: отсоединение клеток от первичной опухоли, миграцию, инвазию, перемещение в крови или лимфатических сосудах, присоединение и рост вторичной опухоли. Механизмы миграции и инвазии универсальны для всех видов рака. Ранее из культуры Streptomyces SP мы выделили Migracin А и В - новые ингибиторы клеточной миграции. Было продемонстрировано как Migracin А ингибирует IGF-1-опосредованную миграцию и инвазию клеток рака яичников. Однако большое количество Migracin А, состоящего из замещенного бензола и алкилированного углеводного фрагмента, синтезировать трудоемко. В настоящем исследовании мы разработали и синтезировали упрощенное производное диальдегида Migracin, не имеющего углеводного компонента, названное Migracinal. Материалы и методы. Migracin приобретался у компании «ТехноХим Co., Лтд» (Токио, Япония). Производное Migracinal получали взаимодействием Migracin с 2,4-дигидроксибензалдегидом. Структура была подтверждена спектрами ЯМР и масс-спектроскопией. Противоопухолевая активность нового производного изучалась стандартными тестами в условиях in vitro. Результаты. Установлено, что Migracinal ингибирует клеточную миграцию и инвазию клеток ES-2 рака яичника и аналогично Migracin A ингибирует IGF-1 экспрессию. Кроме того, он индуцировал аноикис, а не апоптоз в клетках ES-2.Заключение. Синтез Migracinal легче в сравнении с Migracin, а спектр противоопухолевой активности идентичен, что может быть использовано для подавления процессов метастазирования.

Newly formated (tertiary) lymphoid structures in tumor growth

Aim to reproduce tertiary lymphoid structures and study their features in a malignant neoplasm in the experiment. Material and methods. Male white rats of the Wistar stress-resistant line were inoculated with the tumor strain sarcoma M1. Using the methods of microsurgical preparation, color lymphography and ultrasonic sonolipodestruction we isolated the lymph nodes without metastatic lesions (described as secondary in normal anatomy), the lymph nodes with metastases of M1 sarcoma, and the newly formed nodes (extrauterine or tertiary). Lymph nodes were examined macroscopically, micromorphometric studies were performed, histological and immunohistochemical signs of tertiary lymph nodes were determined. The obtained data were subjected to statistical analysis. Results. In 60% of rats, in the right axillary region, in addition to the secondary lymph nodes described in normal anatomy, the tertiary lymph nodes were found on the side of the tumor. They were located near the histologically verified metastatic lymph node. The studied parameters of the main structural and functional zones of the tertiary lymph nodes had the following features: the enlarged marginal sinuses; a fewer number of lymphoid follicles; the average total area of blood vessels increased by 92% in relation to the metastatic lymph nodes and by 78% in relation to the secondary lymph nodes. The significant differences were registered with CD3, CD4, CD20, CD30 markers. Conclusion. The study proved the possibility of reproducing tertiary lymphoid nodes in the experiment with malignant growth and revealed a number of their features

ВНУТРИАРТЕРИАЛЬНАЯ ХИМИОТЕРАПИЯ РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ

Introduction. Breast cancer is now the most common malignant tumor among women with annually increasing incidence. One of the new, advanced and minimally invasive breast cancer treatment directions is intra-arterial neoadjuvant chemotherapy. The main purpose of the project is to analyze the results of intraarterial chemotherapy in 30 patients with breast cancer during the period 2004-2006. Materials and methods. Intraarterial chemotherapy was carried out by selective internal thoracic artery catheterisation (a. Thoracica interna), supplying blood for the area of tumor lesions of the breast. Chemotherapy used the common scheme - Taxotere 75 mg/m2 + Doxorubicin 60 mg/m2, doses of chemotherapy are calculated on the basis of the nomogram in dosages for intravenous infusion, the speed of infusion was 8001000 ml/h. The sequential intraarterial injection of chemotherapeutic agents took 3-4 hours. Preoperative chemotherapy consisted of 4 courses. The interval between courses was 3 weeks. Results. As a result of treatment after 2-year chemotherapy a partial regression process is registered in 19 (63.3%) patients, 11 (36.7%) patients got stabilized. After 4 treatments a complete regression is registered in 15 (50%) patients, partial regression - in 12 (40%) patients, stabilization of the process - in 3 (10%) patients. As a result of the above kind of treatment, 27 (90%) patients have managed to undergo radical mastectomy. Conclusion. Application of intraarterial chemotherapy in patients during advanced IIIa, IIIb stages of cancer allows to achieve partial regression even after 2-year therapy. However, despite the effectiveness of the method the intra-arterial chemotherapy is only a step before radiotherapy or surgical treatment, so the method should be used as an initial, important link in the combined treatment of breast cancer.Введение. Рак молочной железы в настоящее время является наиболее часто встречающимся злокачественным новообразованием, с ежегодно увеличивающимися показателями заболеваемости. Одним из новых, перспективных и малоинвазивных направлений лечения рака молочной железы является селективная внутриартериальная химиотерапия. Основной целью данной работы является анализ результатов внутриартериальной химиотерапии у 30 пациенток с раком молочной железы за период 2004-2006 гг. Материалы и методы. Внутриартериальную химиотерапию проводили путем селективной катетеризации внутренней грудной артерии, кровоснабжающей зону опухолевого поражения молочной железы. Применялась общепринятая схема химиотерапии – Таксотер 75мг/м2 + Доксорубицин 60мг/м2 в дозировках для внутривенного введения, скорость инфузии составляла 800-1000 мл/ч. Последовательное внутриартериальное введение химиопрепаратов занимало 3-4 часа. Предоперационная химиотерапия состояла из 4 курсов. Интервал между курсами составлял 3 недели. Результаты. В результате лечения после 2-х курсов химиотерапии частичная регрессия процесса отмечена у 19 (63,3%), стабилизация у 11 (36,7%) больных. После 4-х курсов лечения полная регрессия отмечена у 15 (50%) больных, частичная регрессия у 12 (40%) больных, стабилизация процесса у 3 (10%) больных. В результате вышеуказанного вида лечения 27 (90%) больным удалось провести радикальную мастэктомию. Заключение. Применение внутриартериальной химиотерапии у пациентов в поздних IIIа, IIIб стадиях рака уже после 2-х курсов терапии способствует достижению частичной регрессии. Однако, несмотря на эффективность метода, внутриартериальная химиотерапия является лишь этапом, предшествующим лучевому или хирургическому лечению, поэтому данный метод должен применяться как начальное и важное звено комплексного лечения рака молочной железы

Experimental Substantiation of Autoplasma Application as a Haemostatic Agent in Endoscopic Operations in the Digestive Tract

Abstract Introduction. In endosurgery of the digestive tract, ‘cellular technologies’ are gaining popularity, including the use of blood components or blood cells with a haemostatic purpose. In this regard, the objective of the study is evaluation of the effectiveness of bleeding control and safety of resection of the hollow organs of the digestive tract in the experimental trauma models of the abdominal organs in laboratory animals. Materials and methods. The study was conducted in 20 mature male Chinchilla rabbits with the mean body mass of 2450 ± 210 g. All animals were divided into four experimental groups: the control group (without bleeding control); the group that received the infiltration of the wall of a hollow organ with saline; the group in which bleeding was controlled by argon plasma coagulation (APC), and the group wherein animals underwent haemostasis with autoplasma. Results. In the control group and the physiological saline group, no statistical difference was observed in the time of bleeding control. Autoplasma, due to preventive local administration, is more effective than APC and has a high haemostatic potential. Conclusion. Autoplasma has been found to be highly effective and safe for bleeding control in the gastrointestinal tract in the experimental model, which has paved the way for new possibilities for operations of various scales, including endoscopic operations.</jats:p

Local tissue interleukine profile in breast cancer

Breast cancer ranks first in the structure of oncological diseases in women in Russia and in the World. In recent years there have been numerous reports that the growth and progression of breast cancer and other tumors depend not only on their malignant potential, but also on stromal factors presented in the tumor microenvironment and intercellular interactions. The aim of our study was to evaluate intercellular interactions of the tissues surrounding the tumor, by means of determination of the locally interleukine profile. We have identified interleukine profiles of the axillary fatty tissue from the lesions and subcutaneous fat of the anterior chest wall, located at a maximum distance from the tumors, in stage IIa-IIIb breast cancer patients. As a result we came to a conclusion: the method based on the measurement of IL-1, IL-2, IL-6, IL-10 and а-TNF levels in the tissues and in the blood allows to evaluate the immune processes occurring in the tissues surrounding the tumor; adipose tissue of various areas of breast cancer patients differs significantly according to the level of interleukines, which indicates that different involvement of adipose tissue in various areas of the immune response; there is a dependence of the local immune status of armpit adipose tissue on the expression of ER, PgR, Her2/neu on the surface of breast cancer cells.</jats:p

Anticancer Activity of Novel NF-B Inhibitor DHMEQ by Intraperitoneal Administration

There have been great advances in the therapy of cancer and leukemia. However, there are still many neoplastic diseases that are difficult to treat. For example, it is often difficult to find effective therapies for aggressive cancer and leukemia. An NF-B inhibitor named dehydroxymethylepoxyquinomicin (DHMEQ) was discovered in 2000. This compound was designed based on the structure of epoxyquinomicin isolated from a microorganism. It was shown to be a specific inhibitor that directly binds to and inactivates NF-B components. Until now, DHMEQ has been used by many scientists in the world to suppress animal models of cancer and inflammation. Especially, it was shown to suppress difficult cancer models, such as hormone-insensitive breast cancer and prostate cancer, cholangiocarcinoma, and multiple myeloma. No toxicity has been reported so far. DHMEQ was administered via the intraperitoneal (IP) route in most of the animal experiments because of its simplicity. In the course of developmental studies, it was found that IP administration never increased the blood concentration of DHMEQ because of the instability of DHMEQ in the blood. It is suggested that inflammatory cells in the peritoneal cavity would be important for cancer progression, and that IP administration, itself, is important for the effectiveness and safety of DHMEQ. In the present review, we describe mechanism of action, its in vivo anticancer activity, and future clinical use of DHMEQ IP therapy.</jats:p

Experimental Substantiation of Autoplasma Application as a Haemostatic Agent in Endoscopic Operations in the Digestive Tract

Abstract In endosurgery of the digestive tract, ‘cellular technologies’ are gaining popularity, including the use of blood components or blood cells with a haemostatic purpose. In this regard, the objective of the study is evaluation of the effectiveness of bleeding control and safety of resection of the hollow organs of the digestive tract in the experimental trauma models of the abdominal organs in laboratory animals. The study was conducted in 20 mature male Chinchilla rabbits with the mean body mass of 2450 ± 210 g. All animals were divided into four experimental groups: the control group (without bleeding control); the group that received the infiltration of the wall of a hollow organ with saline; the group in which bleeding was controlled by argon plasma coagulation (APC), and the group wherein animals underwent haemostasis with autoplasma. In the control group and the physiological saline group, no statistical difference was observed in the time of bleeding control. Autoplasma, due to preventive local administration, is more effective than APC and has a high haemostatic potential. Autoplasma has been found to be highly effective and safe for bleeding control in the gastrointestinal tract in the experimental model, which has paved the way for new possibilities for operations of various scales, including endoscopic operations.</jats:p

INTRA-ATERIAL CHEMOTHERAPY OF THE BREAST CANCER

Introduction. Breast cancer is now the most common malignant tumor among women with annually increasing incidence. One of the new, advanced and minimally invasive breast cancer treatment directions is intra-arterial neoadjuvant chemotherapy. The main purpose of the project is to analyze the results of intraarterial chemotherapy in 30 patients with breast cancer during the period 2004-2006. Materials and methods. Intraarterial chemotherapy was carried out by selective internal thoracic artery catheterisation (a. Thoracica interna), supplying blood for the area of tumor lesions of the breast. Chemotherapy used the common scheme - Taxotere 75 mg/m2 + Doxorubicin 60 mg/m2, doses of chemotherapy are calculated on the basis of the nomogram in dosages for intravenous infusion, the speed of infusion was 8001000 ml/h. The sequential intraarterial injection of chemotherapeutic agents took 3-4 hours. Preoperative chemotherapy consisted of 4 courses. The interval between courses was 3 weeks. Results. As a result of treatment after 2-year chemotherapy a partial regression process is registered in 19 (63.3%) patients, 11 (36.7%) patients got stabilized. After 4 treatments a complete regression is registered in 15 (50%) patients, partial regression - in 12 (40%) patients, stabilization of the process - in 3 (10%) patients. As a result of the above kind of treatment, 27 (90%) patients have managed to undergo radical mastectomy. Conclusion. Application of intraarterial chemotherapy in patients during advanced IIIa, IIIb stages of cancer allows to achieve partial regression even after 2-year therapy. However, despite the effectiveness of the method the intra-arterial chemotherapy is only a step before radiotherapy or surgical treatment, so the method should be used as an initial, important link in the combined treatment of breast cancer