STRUCTURAL TRANSFORMATIONS IN AXILLARY AND MESENTERIC LYMPH NODES IN CHEMOTHERAPY AND SURGICAL TREATMENT OF EXPERIMENTAL MAMMARY TUMOR

Was conducted histological study axillary and mesenteric lymph nodes in breast cancer induced by intramammary administration of N-methyl-N-nitrosourea, chemotherapy according to the CMF scheme (cyclophosphamide, methotrexate, 5-fluorouracil), operative removal of breast tumors (6.5 months from the beginning of the experiment). The results of the study. At chemotherapy of breast cancer, compared with the group with breast cancer without treatment, there was a decrease in the number of tumor cells in the axillary lymph nodes in comparison with mesenteric lymph nodes. The decrease in the area of the paracortical zone and the area of secondary lymphoid nodes remain in the axillary lymph nodes, in comparison with breast cancer without treatment. The reduction of the paracortical zone square remains in mesenteric lymph nodes. The area of lymphoid nodules with germinative centers decreases. The number of postcapillary venules with high endothelium and the number of macrophages in structural zones grow down. In the axillary lymph nodes after surgical treatment of breast cancer and chemotherapy in comparison with the treatment of breast cancer only with cytostatics, there is decrease in the area of the paracortical zone (with an increase in the number of small lymphocytes) and medullare cords. The area of lymphoid nodules with germinative and without germinative centers increases. In mesenteric lymph nodes, drainage function is reduced, increased the area of the paracortical zone, reduced the areas of lymphoid nodules with germinative centers and medullare cords (increased proliferative activity of cells), macrophage reaction in the cortical substance was revealed. Conclusion. The severity of structural transformations in cytoarchitectonics of the axillary and mesenteric lymph nodes depends on the treatment method

CORRELATION BETWEEN CYTOKINE CONTENT IN LYMPH OF THORACIC LYMPH DUCT AND MESENTERIC LYMPH NODE STRUCTURAL TRANSFORMATIONS IN EXPERIMENTAL MAMMARY TUMOR AND CHEMOTHERAPY

The aim of the study was to fulfill correlation analysis of morphometry of the mesenteric lymph nodes and the concentration of cytokines in the lymph of the thoracic duct in breast cancer induced by intramammary administration of N-methyl-N-nitrosourea, chemotherapy according to the CMF scheme (cyclophosphamide, methotrexate, 5-fluorouracil). The results of the study. At breast cancer revealed positive correlation: in the germinative centers and medullary cords of cytokine IL-5 with mitotically dividing cells, chemokines MIP-1α with average lymphocytes, in the germinative centers of immunoblasts with cytokine GRO/KC, in the paracortical zone chemokine MCP-1 with macrophages, reticular cells with IL-6 and M-CSF, in the medullary sinuses chemokine GRO/KC with small lymphocytes and mature plasma cells (number which decreases). All this may indicate the activity of the local immune response in the lymph nodes aimed on the antitumor protection. After chemotherapy of breast cancer, compared with breast cancer without treatment, revealed positive relationship, which may indicate increased immunomodulatory and antitumor actions of cytokines: correlation of interferon IFNγ with small lymphocytes (number which increased) and macrophages in the germinative centers and mitotically dividing cells in the medullary cords, correlation in the germinative centers of immunoblasts with MIP-1α and increased of number small lymphocytes in T-dependent zone lymph nodes, correlation in medullary cords of interleukin IL-17 with mature plasma cells (number which increased) , correlation of interleukin IL-18 with mature plasma cells in medullary sinuses. Conclusion. Study of the correlation of the concentration of cytokines in the lymph of the thoracic duct with structural changes in the mesenteric lymph nodes revealed dependencies aimed at increasing the immunomodulating and antitumor effects of cytokines

Опухоль-ассоциированные мезенхимные стволовые клетки при химически-индуцированном раке молочной железы у крыс Wistar

Objective: to compare the morphological and functional properties of mesenchymal stem cells from mammary tissues and chemically-induced mammary tumor tissues. material and methods. The study included 25 female Wistar rats. In 20 rats, mammary carcinoma was induced by intramammary injection of N-methyl-N-nitrosourea after estrus synchronization with chorionic gonadotropin. The control group consisted of 5 rats. Mammary carcinoma was verified histologically and immunohistochemically. To examine, whether the cells isolated from normal tissue and tumor tissue belonged to mesenchymal stem cells, FACS Canto II flow cytofluorometer was used. The functional properties of mesenchymal stem cells were evaluated in MTT assay by the level of nitric oxide production in normal and by hydrogen peroxide-induced hypoxia. The levels of prolactin, luteinizing hormone and estradiol E2 in urine were studied using solid-phase enzyme-linked immunosorbent assay. results. Chemically-induced mammary tumor according to histological and immunohistochemical studies corresponded to luminal B type breast cancer in humans. In rats that developed mammary tumors, the urine prolactin levels after synchronization of estrus were increased. In rats that did not develop tumors, the levels of prolactin and luteinizing hormone were decreased, but the levels of estradiol E2 were increased. More mesenchymal stem cells with CD45-/CD90+phenotype were obtained from the breast tumor tissue. Mesenchymal stem cells from tumor tissue showed increased proliferative potential and were more resistant to hypoxia. conclusion. Tumor- associated mesenchymal stem cells having high proliferative potential and resistance to hypoxia were obtained from chemically-induced mammary tumor tissue. Morphologic and functional differences in mesenchymal stem cells obtained from mammary breast tissue and tumor tissue require further studies.Цель исследования – сравнить морфофункциональные свойства мезенхимных стволовых клеток из тканей молочной железы и ткани химически-индуцированной опухоли молочной железы. материал и методы. У 20 крыс-самок Wistar после синхронизации эструса хорионическим гонадотропином, интрамаммарным введением N-метил-N-нитрозомочевины индуцирована аденокарцинома молочной железы, контрольную группу составили 5 крыс. Верификацию опухоли проводили гистологически и иммуногистохимически. Принадлежность выделенных клеток из ткани молочной железы и опухоли молочной железы к мезенхимным стволовым клеткам верифицировали на основании морфологии и фенотипирования на проточном цитофлуориметре FACS Canto II. Функциональные свойства мезенхимных стволовых клеток оценивали в МТТ-тесте и по уровню продукции оксида азота в норме и при индукции перекисью водорода окислительного стресса. Уровни пролактина, лютеинизирующего гормона и эстрадиола Е2 в моче исследовали твердофазным иммуноферментным анализом. Результаты. Химически индуцированная опухоль молочной железы по данным гистологического и иммуногистохимического исследования соответствовала люминальному В1 типу рака молочной железы у человека. Уровни пролактина в моче после синхронизации эструса у животных с развившейся опухолью были повышены, а у животных с неразвившейся опухолью молочной железы снижены уровни пролактина и лютеинизирующего гормона, но повышены уровни эстрадиола Е2. Из ткани опухоли молочной железы получено большее количество мезенхимных стволовых клеток с фенотипом CD45-/CD90+. Мезенхимные стволовые клетки из ткани опухоли проявляли повышенный пролиферативный потенциал и были более устойчивы к окислительному стрессу. заключение. Из ткани химически индуцированной опухоли молочной железы получены опухоль-ассоциированные мезенхимные стволовые клетки, которые имеют высокий пролиферативный потенциал и устойчивы к окислительному стрессу. Выявленные морфофункциональные различия мезенхимных стволовых клеток из тканей молочных желез и ткани опухоли молочной железы требуют дальнейшего исследования

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences

COMPARATIVE ANALYSIS OF THE CONTENT IN LYMPH OF HORMONES DRAWING IN PATHOGENESIS OF BREAST CANCER IN RATS WISTAR

The aim of the research was to study the levels of hormones involved in the pathogenesis of BC in the lymph of the thoracic duct. Methods. BC induced by the introduction of n-methyl-N-nitrosourea rats of Wistar breed. The animals underwent only surgery chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil). In some animals combined surgery followed by a course of chemotherapy, and in some animals advanced therapy fragmented DNA. In the lymph examined the contents of the follicle-stimulating hormone (FSH), prolactin, luteinizing hormone (LH), estradiol (E2 ) and thyroglobulin (TG). Results. It is shown that surgical removal of tumors in the mammary gland leads to lower levels in the lymph LH and E2 . The combination of surgery with a course of chemotherapy leads to lower levels in the lymph FSH. Chemotherapy without surgical removal of tumors in the mammary gland leads to a decrease in the concentration of E2 in the lymph. Conclusion. The concentration of sex hormones and thyroglobulin in the lymph of the thoracic duct in breast cancer in rats depends on the type of treatment

Tumor-associated mesenchymal stem cells in chemically-induced breast cancer in Wistar rats

Objective: to compare the morphological and functional properties of mesenchymal stem cells from mammary tissues and chemically-induced mammary tumor tissues. material and methods. The study included 25 female Wistar rats. In 20 rats, mammary carcinoma was induced by intramammary injection of N-methyl-N-nitrosourea after estrus synchronization with chorionic gonadotropin. The control group consisted of 5 rats. Mammary carcinoma was verified histologically and immunohistochemically. To examine, whether the cells isolated from normal tissue and tumor tissue belonged to mesenchymal stem cells, FACS Canto II flow cytofluorometer was used. The functional properties of mesenchymal stem cells were evaluated in MTT assay by the level of nitric oxide production in normal and by hydrogen peroxide-induced hypoxia. The levels of prolactin, luteinizing hormone and estradiol E2 in urine were studied using solid-phase enzyme-linked immunosorbent assay. results. Chemically-induced mammary tumor according to histological and immunohistochemical studies corresponded to luminal B type breast cancer in humans. In rats that developed mammary tumors, the urine prolactin levels after synchronization of estrus were increased. In rats that did not develop tumors, the levels of prolactin and luteinizing hormone were decreased, but the levels of estradiol E2 were increased. More mesenchymal stem cells with CD45-/CD90+phenotype were obtained from the breast tumor tissue. Mesenchymal stem cells from tumor tissue showed increased proliferative potential and were more resistant to hypoxia. conclusion. Tumor- associated mesenchymal stem cells having high proliferative potential and resistance to hypoxia were obtained from chemically-induced mammary tumor tissue. Morphologic and functional differences in mesenchymal stem cells obtained from mammary breast tissue and tumor tissue require further studies