Metalloproteinase-2 (MMP-2) and -14 (MMP-14) and the tissue inhibitor of metalloproteinases type 2 (TIMP-2) participate in epithelial-mesenchymal transition and tumor progression in many cancers. However, the correlation between these enzymes in gastric cancer and the metastatic potential to their respective lymph node needs to be determined. Here, we evaluated the expression of these enzymes in gastric carcinoma and lymph node metastases and their possible involvement in tumor progression. Histological samples from 83 patients with gastric cancer and their respective lymph nodes were used. MMP-2, MMP-14 and TIMP-2 immunoexpression was scored. TIMP-2 expression in tumor-associated macrophages occurred more frequently than in normal mucosa (P = 0.0128). Female tumor samples presented higher MMP-2 expression (P = 0.0248), while TIMP-2 occurred mainly in patients over 50 years old (P = 0.0034). MMP-2 was higher expressed in primary tumor macrophages than in neoplastic cells (P = 0.0118), and was also seen in macrophages from metastatic-affected lymph nodes of intestinal and diffuse histotypes (P = 0.0006). MMP-2, MMP-14 and TIMP-2 expression in mononuclear cells might be correlated with progression of gastric cancer. MMP-14 production by macrophages appears to be more involved in diffuse gastric cancer progression.

-ORIGINAL ARTICLEEXPERIMENTAL ABSTRACT PURPOSE:To determine the effects of green propolis extracted in L-lysine (WSDP) and of L-lysine for 40 weeks on induced rat bladder carcinogenesis. METHODS:The animals (groups I, II, III, IV, V and VI) received BBN during 14 weeks. Group I was treated with propolis 30 days prior received BBN, and then these animals were treated daily with propolis; Groups II and III was treated with subcutaneous and oral propolis (respectively) concurrently with BBN. The animals of Group IV were treated L-lysine; Group V received water subcutaneous;and Group VI received only to BBN. Among the animals not submitted to carcinogenesis induction, Group VII received propolis, Group VIII received L-lysine and Group IX received water. RESULTS:The carcinoma incidence in Group I was lower than that of control (Group VI). The carcinoma multiplicity in Group IV was greater than in Group VI. All animals treated with L-lysine developed carcinomas, and they were also more invasive in Group IV than in controls. On the other hand, Group VIII showed no bladder lesions. CONCLUSION:The WSDP is chemopreventive against rat bladder carcinogenesis, if administered 30 days prior to BBN , and that L-lysine causes promotion of bladder carcinogenesis.

PURPOSE:To determine the effects of water-soluble derivative of green propolis in bladder cancer angiogenesis in rats given N-butyl-(-4-hydroxybutyl) nitrosamine (BBN). METHODS:Nine groups were established, where six of them (Groups 1 to 6), the animals received 0.05% BBN in their drinking water for 14 weeks. From the 32nd to the 40th week, Groups 1, 2, 3 and 4 were treated respectively with water, L-lysine (300 mg/kg/ day), celecoxib (30 mg/kg/day) and propolis (300 mg/kg/day). Groups 5 and 6 were given propolis and L-lysine from the 1st to the 40th week (150 mg/kg/day). Microvascular density was determined by histological sections stained for the marker CD-31 and analyzed with specific software. RESULTS:The microvascular density in bladder carcinomas was lower (p<0.01) in rats receiving propolis than in controls given carcinogen only. On the other hand, the microvascular density of tumors in rats receiving carcinogen and L-lysine for 40 weeks from the beginning of carcinogen treatment was significantly higher (p<0.01) than in the corresponding controls. -Acta Cirúrgica Brasileira -Vol. 27 (8) 2012de beber por 14 semanas. Na 32ª semana das 40 semanas, os grupos 1, 2, 3 e 4 foram tratados respectivamente com água, L lisina (300 mg/kg/dia), celecoxibe (30 mg/kg/dia) e própolis (300 mg/kg/dia). Os grupos 5 e 6 receberam própolis e L lisina da 1ª a 40ª semana (150 mg/ kg/dia). A densidade microvascular foi determinada por cortes histológicos corados pelo CD-31 e analisados por programa de computador específico. RESULTADOS:A densidade microvascular em carcinomas de bexiga foi menor com p<0,01 nos ratos que receberam própolis do que nos carcinomas do grupo controle que recebeu apenas carcinógeno. Por outro lado, a densidade microvascular de tumores de ratos que receberam carcinógeno e L-Lisina por 40 semanas desde o início do carcinógeno foi significantemente maior com p<0,01 que a densidade microvascular dos tumores de seu respectivo grupo controle. CONCLUSÃO:A própolis verde solúvel em água inibiu a angiogênese em câncer de bexiga induzido pelo BBN, enquanto a L-lisina estimulou a angiogênese quando iniciada juntamente com o BBN.

Purpose To evaluate red propolis, gum arabic and L-lysine activity on colorectal preneoplastic lesions induced by azoxymethane (AOM). Methods The study featured 4 control groups (I-IV) and 4 experimental groups (V-VIII), totaling 48 rats. Once a week for 2 weeks, animals on control groups received saline, while animals in experimental groups received azoxymethane (15 mg/kg i.p.). The follow up along 16 weeks included daily oral gavage to administer water (I and V), L-lysine (150 mg/kg)(II and VI), própolis (100mg/5ml/kg)(III and VII), or gum arabic (5ml/kg)(IV and VIII). Was performed surgery on the animals in the end of this time in order to collect blood for biological assays (TBARS, GSH), followed by their sacrifice to tissue extract. Results Oxidative stress (TBARS) and the number of aberrant crypt foci (ACF) in distal colon were lower using própolis (p<0.01 for both parameters). Gum arabic reduced preneoplastic lesions (ACF ≤ 4 crypts) on distal colon and on the entire colon (p<0.05). Conclusions Red propolis reduced AOM-induced oxidative stress (TBARS) and total number of ACF in the distal colon. L-lysine neither protected against nor enhanced AOM-induced ACF. Gum arabic reduced the number of ACF.

Effect of red propolis on hamster cheek pouch angiogenesis in a new sponge implant model 1 Abstract Purpose: To evaluate the effects of red propolis on cheek pouch angiogenesis in a hamster new model sponge implant. Methods: Forty eight animals divided into eight groups. (Groups I-IV), the animals were treated for 15 days before and 10 days after sponge implantation. (Groups V-VIII), the animals were treated for 10 days after sponge implantation (GI and GV: red propolis 100 mg/kg, GII and GVI: celecoxib 20 mg/kg, GIII and GVII: 1% gum arabic 5 mL/kg, GIV and GVIII: distilled water 5 mL/kg). On the 11th day of implantation, the animals were anesthetized for stereoscopic microscopic imaging and morphometric quantification of angiogenesis (SQAN), followed by histopathological evaluation (H&E). Results: In the SQAN analysis, no significant difference was found between the groups. However, on histology, propolis was found reduce the population of mastocytes in the qualitative analyses (p = 0,013) in the quantitative analyses to reduce the number of blood vessels (p = 0,007), and increase the macrophage count (p = 0,001). Conclusion: Red propolis inhibited inflammatory angiogenesis when administered before andcontinuously after sponge implant, and was shown to have immunomodulating effects on inflammatory cells (mastocytes and macrophages) in a new sponge implant hamster model.

Chemical investigation of the ethanol extract of propolis allowed the isolation of 2'-hydroxy-4',7-dimethoxyisoflavan (1) 2',7-dihydroxy-4'-methoxyisoflavan (2) 2',4'-dihydroxy-7-methoxyisoflavan (3), 4',7-dihydroxy-2'-methoxyisoflavan (4) 2',4',4-trihydroxychalcone (5) and lup-20(29)-en-3-ol (6). The structures of compounds were identified based on their spectral data and by comparison with the literature. It was performed test to evaluate antioxidant activity by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method of the ethanol extract and its fractions obtaining significant results similar to Vitamin C. It was also evaluated anticholinesterase activity, observing promising results with the extract and fractions. Being the red propolis of these activities, it can be used in the treatment of degenerative diseases such as Alzheimer. There are already records of propolis as an antioxidant, however, the activity of anticholinesterase is being cited for the first time.

-Context -Non-alcoholic fatty liver disease is characterized by lipid deposits in the hepatocytes and has been associated with obesity, dyslipidemia and type-2 diabetes. It is considered a hepatic manifestation of the metabolic syndrome, of which the main component is insulin resistance leading to hyperinsulinemia and increased production of inflammatory cytokines. Saturated fat promotes hypertriglyceridemia and hyperinsulinemia, reduces levels of high-density cholesterol and increases levels of low-density cholesterol, while polyunsaturated fat is associated with hypolipidemic, antiinflammatory and imunoregulating action. ObjectiveTo evaluate the hepatic and biochemical repercussions of a polyunsaturated fat-rich diet in Wistar rats. Methods -Twenty-two rats were distributed equally in two groups: GI -standard diet (Biobase Bio-tec Ratos e Camundongos ® ) providing 3.000 kcal/kg and GII -hypercaloric and hyperlipidic diet providing 4.250 kcal/kg (ω-6:ω-3 = 3:1). The animals were euthanized after 23 weeks of experiment. The weight, biochemical parameters and hepatohistological changes were registered. Results -Findings were submitted to variance analysis with the level of statistical significance at 5%. The average weight did not differ significantly between the groups at baseline (P = 0.711), but was greater in Group II by the end of the experiment (P = 0.000). The levels of triglycerides (P = 0.039), total cholesterol (P = 0.015) and HDL (P = 0.005) were higher in Group I than in Group II. Macrovesicular steatosis was significantly more common in Group II than in Group I (P = 0.03). Conclusion -Hypercaloric and hyperlipidic diet rich in polyunsaturated fat promotes weight gain and favors the development of hepatic steatosis while reducing serum levels of triglycerides, total cholesterol and HDL.

PURPOSE: To determine whether a hypercaloric and hyperlipidic diet enriched with polyunsaturated fatty acids influences the formation of aberrant crypt foci (ACF) in colonic mucosa of Wistar rats treated with azoxymethane (AOM). METHODS: At eight weeks of life, the rats were assigned to four groups: Group I―standard diet (STD) not treated with AOM; Group II―hypercaloric and hyperlipidic diet (FED), not treated with AOM; Group III―STD, treated with AOM; Group IV―FED, treated with AOM. At 16 weeks, the animals were injected intraperitoneal with 0.9% saline solution (Group I and II) or AOM at 15mg/Kg (Groups III and IV) once a week for two weeks. Fifteen weeks later, the animals were euthanized. RESULTS: FED promoted weight gain in Groups II and IV compared to Groups I and III, respectively. The groups did not differ with regard to the total number of ACF. The Chi-square test revealed no predominance of the presence of foci with <4 crypts. However, foci with ≥5 crypts were proportionally more prevalent in Group III than in Group IV (p=0.043). CONCLUSION: The administration of polyunsaturated fatty acids did not interfere with the formation of aberrant crypt foci, but reduced ACF multiplicity, exercising an attenuating effect on carcinogenesis.