Influence of Surgical Treatment and Neoadjuvant Therapy of Chemically Induced Breast Cancer on Correlation of Cytokine Concentrations in the Lymph with Structural Transformations in the Mesenteric Lymph Nodes.

We performed a correlation analysis of the morphometry of mesenteric lymph nodes and cytokines of the thoracic duct lymph in chemically induced breast cancer (BC) and after surgical treatment of BC and neoadjuvant chemotherapy for BC according to the CMF scheme. After surgical treatment, correlations were found between the level of cytokines in the thoracic duct lymph and morphological changes in the mesenteric lymph nodes. The observed correlations can be a result of total resection of the tumor and increased immunomodulatory and antitumor action of cytokines. Comparison of the effect of chemotherapy and surgical treatment revealed correlations between cytokine concentrations in the lymph and structural changes in the lymph nodes, which can be related to weakening of local immunity and antitumor effect of cytokines.

Cytokines of the Lymph and Blood Serum as Markers of Oncogenesis and Efficiency of Therapy in Chemically Induced Breast Cancer in Wistar Rats.

We studied the levels of serum and lymph cytokines involved in the pathogenesis of BC. BC was induced by injection of N-methyl-N-nitrosourea to Wistar rats. The animals underwent surgery, or received polychemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil), or surgical treatment was combined with polychemotherapy; in a special group, Panagen (fragmented DNA) was added to polychemotherapy. Cytokine concentration in the lymph was measured using Bio-Plex Pro Rat Cytokoness 24-Plex Assay test system (Bio-Rad). In rats with BC, the content of most studied cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-7, IL-12, IL-13, MIP-1α, MIP-3α, RANTES, TNFα, and MCP-1) in the lymph and blood was significantly higher, while the content of IL-10 and GRO/KC was lower than in intact animals. Surgical resection of the tumor led to a significant decrease in the content of both pro- and anti-inflammatory cytokines in the lymph. Polychemotherapy led to a significant decrease in the content of IL-1ß, IL-4, IL-6, IL-7, MIP-1α, MIP-3α, and RANTES in the serum and lymph. Comparison of the cytokine content in the serum and lymph of operated animals after polychemotherapy with and without Panagen showed that the content of most cytokines (IL-5, IL-6, IL-7, IL-10, IL-13, IL-17A , IL-18, GRO/KC, IFNγ, and MIP-3α) was higher after Panagen administration.

Correlation Analysis of Morphological Changes of Structural and Functional Areas of Mesenteric Lymph Nodes with Cytokines of Lymph of Thoracic Lymphatic Duct in Experimental Breast Cancer.

We performed a correlation analysis of the morphometric parameters of mesenteric lymph nodes and cytokine content in the lymph of thoracic duct in rats with chemically induced breast cancer. The study showed that activity of the local immune response in the lymph nodes in breast cancer is aimed at antitumor protection. In breast cancer, the area of the paracortical zone remained at the level of the intact group, while the area of lymphoid nodules with germinative centers and the area of medullary substance increased; the number of macrophages in the thymus-dependent zone and zone responsible for humoral immunity also increased. The following positive correlations were revealed: in germinative centers and medullary substance, number of mitotic cells correlated with cytokine IL-5 content and the number of medium lymphocytes correlated with the content of chemokine MIP-1α; in the germinative centers, the number of immunoblasts correlated with the level of cytokine GRO/KC, in the paracortical zone, the number of macrophages correlated with the level of chemokine MCP-1, the number of reticular cells correlated with IL-6 and M-CSF content; in medullary substance, the number of small lymphocytes and mature cells plasma cells (their content was reduced) correlated with the level of chemokine GRO/KC, which can be caused by their migration from the lymph node.

Relationships between Body Composition and Plasma Levels of Pancreatic, Gut, and Adipose Tissue Hormones in db/db Mice, a Model of Type 2 Diabetes Mellitus.

We studied the relationships between body composition parameters and plasma levels of pancreatic, gut, and adipose tissue hormones regulating energy balance and glucose metabolism in diabetic db/db mice (BKS.Cg-Dock7m+/+Leprdb/J). The body composition parameters in mice aged 8, 12, and 16 weeks were assessed by magnetic resonance imaging. The concentrations of insulin, glucagon, ghrelin, glucagon-like peptide-1, glucose-dependent immunotropic peptide, leptin, resistin, and plasminogen activator-1 were measured by multiplex analysis at the age of 8 and 16 weeks. In comparison with non-diabetic control (db/+), db/db mice demonstrated high fat mass and reduced lean body mass and water content. In 8- and 16-week-old db/db mice, the levels of leptin (p<0.001), insulin (p<0.01), and glucagon-like peptide-1 (p<0.05) were elevated and the concentration of ghrelin (p<0.05) was reduced. The body weight and fat mass positively correlated with the levels of leptin, insulin, plasminogen activator-1, and glucagon-like peptide-1 and negatively correlated with ghrelin concentration. The results provide further details for characteristics of db/db mice, a widely used model of obesity and type 2 diabetes mellitus.

[Ghrelin deficiency in patients with type 2 diabetes: the relationships with obesity, adipose tissue dysfunction and glucose variability].

AIM: Ghrelin, a peptide hormone mostly produced by stomach, plays an important role in regulation of feeding behavior, energy balance and glucose homeostasis. THE AIM: to determine the relationships between fasting serum levels of ghrelin, body composition, adipose tissue endocrine function and glucose variability (GV) in type 2 diabetic subjects with and without obesity. MATERIALS AND METHODS: We observed 124 individuals with type 2 diabetes, including 42 non - obese subjects and 82 patients with obesity. Thirty non - obese healthy subjects were acted as control. The concentrations of ghrelin, leptin, resistin, and visfatin in the fasting serum were determined by Multiplex analysis. Body composition was assessed with DEXA. The 24-hour and nocturnal GV parameters were derived from continuous glucose monitoring. RESULTS AND DISCUSSION: Ghrelin levels in patients with diabetes were decreased significantly as compared to control (p.

Blood Serum Levels of Proinflammatory Cytokines (IL-1ß, IL-6, TNFα, IL-8, IL-12p70, and IFNγ) in Patients with Uterine Myoma.

We analyzed cytokine profile in blood serum of patients with uterine myoma and revealed significantly reduced level of IFNγ and a tendency towards a decrease in the levels of IL-1ß and TNFα; the levels of IL-6, IL-8, and IL-12p70 did not differ from those in healthy women. The drop in the concentrations of factors responsible for inflammation and angiogenesis in tissues are unfavorable for proliferation and differentiation of the uterine tissues.

[Association of Serum Levels and Gene Polymorphism of Vascular Endothelium Growth Factor With Ischemic Heart Disease in Type 2 Diabetic Patients].

AIM: to study serum levels of vascular endothelium growth factor family peptides (VEGF-A, VEGF-C and VEGF-D) and functional gene polymorphisms of VEGFA gene (rs699947 and rs3025039) in patients with type 2 diabetes (T2D) depending on the presence of ischemic heart disease (IHD). MATERIALS AND METHODS: The study involved 196 Caucasian patients with T2D (age 43-70 years, 76 with IHD). The concentrations of VEGF-A, VEGF-C and VEGF-D in blood serum were determined by Multiplex assay. Twenty-four persons without diabetes and IHD served as controls. The genotyping of VEGFA polymorphism -2578A/C (rs699947) and +936C/ (rs3025039) was performed by TaqMan. RESULTS: Concentrations of VEGF-A and VEGF-C in patients with T2D were significantly lower than those in controls (p=0.03 and p=0.006, respectively). The level of VEGF-D showed a tendency to decrease (p=0.14). Patients with IHD, as compared to other patients, had higher levels of VEGF-A (p=0.04) and a tendency to VEGF-D increase (p=0.06). The concentration of VEGF-C was not different between groups. No relationships were found between VEGF-A, VEGF-C and VEGF-D levels, HbA1c or glucose variability parameters. C-allele and CC-genotype at +936 position of VEGFA were more frequent among patients with IHD (odds ratio 2.14 and 2.41, respectively, p=0.02). The rs699947 polymorphism was not related to IHD and VEGF-A levels. CONCLUSION: Patients with T2D have decreased serum levels of angiogenic factors VEGF-A and VEGF-C. VEGFA rs3025039 polymorphism is associated with presence of IHD and levels of circulating VEGF-A in these patients.

[Acute-phase serum proteins and adipocytokines in women with type 2 diabetes mellitus: Relationships with body composition and blood glucose fluctuations]. / Belki ostroi fazy vospaleniya i adipotsitokiny v syvorotke krovi u zhenshchin s sakharnym diabetom 2-go tipa: vzaimosvyazi s sostavom tela i kolebaniyami urovnya glyukozy v krovi.

AIM: To estimate the relationships between the serum concentrations of acute-phase proteins (APPs) and adipocytokines, body composition (BC), and blood glucose (BG) fluctuations in women with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: A total of 165 women with T2DM and 22 with a normal body mass index (BMI) at the age of 40 to 70 years were examined. The concentrations of high-sensitivity C-reactive protein (hs-CRP) and acid α1-glycoprotein (α1-AGP) were determined by ELISA. The levels of interleukins 6, 8, and 18 (IL-6, IL-8, IL-18), tumor necrosis factor-α (TNF-α), and plasminogen activator inhibitor type 1 (PAI-1) were measured by a multiplex analysis. Dual energy X-ray absorptiometry was used to estimate BC parameters. BG fluctuations were estimated via continuous glucose monitoring. RESULTS: The levels of hs-CRP, α1-AGP, IL-6, IL-8, IL-18, TNF-α, and PAI-1 were significantly higher in the obese women with T2DM than those in the control group. In the diabetic normal weight women, only hs-CRP, α1-AGP, and IL-8 concentrations exceeded those in the controls. The level of hs-CRP (other than α1-AGP) correlated positively with BMI, the mass of adipose tissue, body trunk (android), and gynoid fats. A multivariate regression analysis showed that adipose tissue mass and trunk fat proportion were independent predictors of hs-CRP levels. The concentrations of IL-6, IL-8, IL-18, PAI-1, and TNF-α correlated positively with waist-to-hip ratio, but demonstrated no associations with BMI and BC. Only the serum α1-AGP level showed a positive association with mean BG and its variability parameters. CONCLUSION: In the women with T2DM, the serum concentrations of APPs and adipocytokines correlate differently with the mass of adipose tissue, its distribution, and BG fluctuations. The findings indicate the multifactorial genesis of chronic inflammation in these patients.

Lymph cytokines as markers oncogenesis and effective treatment of experimental breast cancer Wistar rat.

The purpose of this paper is to examine the levels of cytokines in the lymph involved in the pathogenesis of breast cancer. Methods: Breast cancer was induced by introducing n-methyl-N-nitrosourea rats Wistar breed. Some of the animals subjected to surgery alone or chemotherapy alone (cyclophosphamide, methotrexate, 5-fluorouracil). Some animals combine both types of therapy, as well as a separate group to the administration of chemotherapy added Panagene drag presenting a fragmented DNA. To investigate the concentration of cytokines used in lymph test system Bio-Plex Pro Rat Cytokoness 24-Plex Assay (Bio-Rad, USA). Results: In rats with breast cancer content of most studied cytokines such as, IL-1b, IL-2, IL-4, IL-6, IL-7, IL-12, IL-13, IL-17A, MIP-1a, MIP-3a, RANTES, TNF-a, MCP-1 was significantly higher than in intact animals. Surgical removal of the tumor resulted in a significant decrease in the content in the lymph as a pro-inflammatory cytokine. Comparative performance study cytokine content in the lymph after tumor removal from intact animals showed that the content of cytokines such as IL-10, IL-18, GRO / KC, RANTES were significantly higher in the control animals group. Conducting chemotherapy has led to a significant decrease in the content of IL-1b, IL-4, IL-6, IL-7, IL-10, MIP-1a, MIP-3a, RANTES in rat breast cancer lymph. Comparative study of cytokine content in the lymph operated animals after the administration of chemotherapy and Panagene revealed that most of the content indicators cytokines such as IL-5, IL-6, IL-7, IL-10, IL-13, IL-17A, IL- 18, GRO / KC, IFNg, MIP-3a in the lymph was higher after administration of the drug Panagene. Conclusion: In a comparative study cytokine profile lymph Wistar rats found that cytokine content depended on the therapy in animals with induced breast cancer. Lymph cytokine levels may serve as a diagnostic criterion for tumor growth, as well as the predictor of the effectiveness of the therapy and the risk of metastasis of breast cancer.