Betamethasone inhibits tumor development, microvessel density and prolongs survival in mice with a multiresistant adenocarcinoma TA3

Tumor resistance to traditional cancer treatments poses an important challenge to modern science. Thus, angiogenesis inhibition is an important emerging cancer treatment. Many drugs are tested and corticosteroids have shown interesting results. Herein we investigate the effect on microvessel density, survival time and tumoral volume of mice with TA3-MTX-R tumors. Twenty six mice were inoculated with lxlO6 tumor cells, 4-5 days after injection, six mice were injected with PBS (group A) and twenty mice were treated with p-met (group B). All animals from Group A died on day 22. Group B was divided into Bl (treated discontinued) and B2 (treated daily) and observed until day 88. All mice were processed for histo-immunohistochemical analysis and the blood vessels were counted. A decrease in microvessel density and tumoral volume and longer survival times were observed in the treated group. We propose that the antiangiogenic p-met effect explains, at least partially, its tumor inhibitory properties. As an important perspective, we will experimentally combine these strategies with those recently described by us with regard to the important antiangiogenic-antitumor effects of Trypanosoma cruzi calreticulin. Since the molecular targets of these strategies are most likely different, additive or synergic effects are envisaged.

Expression of Angiopoietin 1, 2 and Their Common Receptor Tie2 in Human Gastric Carcinoma: Implication for Angiogenesis

Angiogenesis, formation of new microvessels providing oxygen and nutrient supply, is essential for tumor growth. It is dependent on the production of angiogenic growth factors by tumor cells. Angiopoietin 1 (Ang-1) and 2 (Ang-2) and their common receptor, Tie2, are thought to be critical regulators of tumor angiogenesis. We examined expression of Ang-1, Ang-2, and their common receptor Tie2 mRNAs and proteins in gastric cancers using in situ hybridization and immunohistochemistry. We also investigated the relationship between their expression and differentiation of cancer cells, lymph node metastasis, tumor size, depth of cancer cell invasion, TNM staging and microvessel density (MVD). The expression of Ang-1, Ang-2, and Tie2 mRNA in cancer cells significantly correlated with the MVD (p<0.001, <0.001 and =0.019, respectively). Ang-1 and Tie2 positivity correlated with advanced gastric cancers (p<0.05) and larger cancers had higher positive rates of Ang-1, Ang-2, and Tie2 mRNA expression (p<0.001, =0.010 and =0.039, respectively). Significant positive correlations were also found between mRNA expression of Tie2 and those of Ang-1 and Ang-2 (p<0.01 and <0.001, respectively). These findings indicate that the expression of Ang-1 and Ang-2 is important for tumor angiogenesis, and suggest a possible role of autocrine/paracrine function of angiopoietin/Tie2 system in gastric cancer progression.

Determination of carcinoembryonic antigen levels in peripheral and draining venous blood in patients with colorectal carcinoma

RACIONAL: O problema da relação entre os níveis de CEA no sangue e o conteúdo de CEA tissular no carcinoma colorretal e os mecanismos de liberação do CEA das células neoplásicas nos tecidos vizinhos à neoplasia e sua conseqüente entrada dentro do sangue periférico são importantes para o entendimento da biologia do carcinoma colorretal. Ainda não foi convenientemente elucidado se o CEA no sangue é drenado principalmente pelo sangue do sistema portal ou pelos linfáticos para o ducto torácico ou, ainda, por ambos os sistemas. OBJETIVO: Estudar o comportamento dos níveis do CEA no sangue periférico (CEA-p) e no sangue do efluente venoso (CEA-d) de doentes com tumores colorretais operados curativamente. MÉTODO: foram estudados 28 doentes, sendo 12 (42,9%) homens e 16 (57,1%) mulheres. A média de idade foi de 66,1 anos (43 a 84 anos). Imediatamente após a laparotomia, o sangue venoso periférico foi extraído por punção venosa antecubital e o sangue do efluente venoso coletado da veia principal de drenagem das lesões. Os valores de CEA-p, CEA-d e do gradiente entre o CEA-d e CEA-p abaixo de 5,0 ng/mL foram considerados normais. RESULTADOS: Oito (28,6%) doentes foram classificados no estádio A de Dukes, 9 (32,1%) no estádio B e 11 (39,3%) no estádio C. A neoplasia estava localizada no reto em 14 (50,0%), no cólon transverso em 5 (17,9%), no cólon sigmóide em 4 (14,3%), no ceco e/ou cólon ascendente em 3 (10,7%), e no cólon descendente em 2 (7,1%) enfermos. O exame histopatológico revelou adenocarcinoma bem diferenciado em todos os enfermos. Em apenas um (3,6%) doente a neoplasia, estadiada como Dukes C, exibia invasão venosa. O gradiente entre os níveis de CEA-p e de CEA-d estava normal em 25 (89,3%) doentes e elevado em 3 (10,7%). O valor médio do CEA-p foi de 3,8 ± 4,1 ng/mL (0,1 a 21,1 ng/mL) e do CEA-d foi de 4,5 ± 4,3 ng/mL (0,3 a 20,2 ng/mL), sem diferença significativa entre esses valores. Houve diferença significativa entre a média dos valores dos níveis do CEA-p e do CEA-d maiores que 5 ng/mL. CONCLUSAO: Os níveis de CEA-p e do CEA-d nos doentes com carcinoma colorretal não se mostraram diferentes. Os resultados deste estudo sugerem que, nas neoplasias colorretais sem invasão venosa, o CEA não é drenado expressivamente pelo sangue do efluente venoso portal do tumor.

Correlation between expression of matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) and angiogenesis in colorectal adenocarcinoma

Matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), which degrade extracellular matrix, are believed to play a crucial role in tumor invasion and metastasis. Angiogenesis is also perceived as an important step in tumor growth and metastasis. To investigate the expression of MMPs and the correlation between the expression of MMPs and angiogenesis in colorectal adenocarcinoma, we studied 72 cases of colorectal adenocarcinoma in Inha University Hospital from 1996 to 1997. We evaluated the expression of MMPs by immunohistochemistry and angiogenesis by counting the microvessels. The expression of MMP-2 was increased according to the Astler-Coller stage (p< 0.05). Angiogenesis in the metastatic group was higher than that of the localized one (p<0.05). The expression of MMP-2 positively correlated with angiogenesis (p<0.05), and marked expression of MMP-9 positively correlated with angiogenesis (p<0.05). The present results suggest that the expression of MMP-2 provides clues for tumor progression and angiogenesis provides significant information to predict whether metastasis is present in colorectal adenocarcinoma.