Qa-2 expression levels is related with tumor-infiltrating lymphocytes profile during solid Ehrlich tumor development.

The Qa-2 has been described as Human Leucocyte Antigen G (HLA-G) murine homolog. This homology is well accepted to gene and protein structure, in different pathology process and embryos implantation. However, in some neoplasm, this homology is questioned, where Qa-2 has been proposed as an immunogenic molecule, associated to tumor rejection. In this way, the aim of this study was to describe the pattern of Qa-2 expression and its relationship with the profile of tumor-infiltrating lymphocytes in solid Ehrlich tumor. The Ehrlich tumor growth was evaluated in Balb/c female mice in different tumor stages. The inflammatory infiltration features were determined by histopathology and, both lymphocyte type and tissue Qa-2 expression by immunohistochemistry. ELISA kit was used to determine soluble Qa-2 in the serum from the animals. We observed that Qa-2 in neoplastic cells increases in intermediate tumor development stages, while, serum Qa-2 increases in the late stage. Qa-2 increasing is correlated with CD3+ increase. Our results suggest that Qa-2 has a role opposite to HLA-G in Ehrlich solid carcinoma, and may be modulating the immune response by attracting the inflammatory infiltrate, especially T CD8+ Lymphocytes.

Effect of cyhalothrin on Ehrlich tumor growth and macrophage activity in mice

Cyhalothrin, a pyrethroid insecticide, induces stress-like symptoms, increases c-fos immunoreactivity in the paraventricular nucleus of the hypothalamus, and decreases innate immune responses in laboratory animals. Macrophages are key elements in cellular immune responses and operate at the tumor-host interface. This study investigated the relationship among cyhalothrin effects on Ehrlich tumor growth, serum corticosterone levels and peritoneal macrophage activity in mice. Three experiments were done with 10 experimental (single gavage administration of 3.0 mg/kg cyhalothrin daily for 7 days) and 10 control (single gavage administration of 1.0 mL/kg vehicle of cyhalothrin preparation daily for 7 days) isogenic BALB/c mice in each experiment. Cyhalothrin i) increased Ehrlich ascitic tumor growth after ip administration of 5.0 x 106 tumor cells, i.e., ascitic fluid volume (control = 1.97 ± 0.39 mL and experimental = 2.71 ± 0.92 mL; P < 0.05), concentration of tumor cells/mL in the ascitic fluid (control = 111.95 ± 16.73 x 106 and experimental = 144.60 ± 33.18 x 106; P < 0.05), and total number of tumor cells in the ascitic fluid (control = 226.91 ± 43.22 x 106 and experimental = 349.40 ± 106.38 x 106; P < 0.05); ii) increased serum corticosterone levels (control = 200.0 ± 48.3 ng/mL and experimental = 420.0 ± 75.5 ng/mL; P < 0.05), and iii) decreased the intensity of macrophage phagocytosis (control = 132.3 ± 19.7 and experimental = 116.2 ± 4.6; P < 0.05) and oxidative burst (control = 173.7 ± 40.8 and experimental= 99.58 ± 41.7; P < 0.05) in vitro in the presence of Staphylococcus aureus. These data provide evidence that cyhalothrin simultaneously alters host resistance to Ehrlich tumor growth, hypothalamic-pituitary-adrenocortical (HPA) axis function, and peritoneal macrophage activity. The results are discussed in terms of data suggesting a link between stress, HPA axis activation and resistance to tumor growth.

Effect of cyhalothrin on Ehrlich tumor growth and macrophage activity in mice.

Cyhalothrin, a pyrethroid insecticide, induces stress-like symptoms, increases c-fos immunoreactivity in the paraventricular nucleus of the hypothalamus, and decreases innate immune responses in laboratory animals. Macrophages are key elements in cellular immune responses and operate at the tumor-host interface. This study investigated the relationship among cyhalothrin effects on Ehrlich tumor growth, serum corticosterone levels and peritoneal macrophage activity in mice. Three experiments were done with 10 experimental (single gavage administration of 3.0 mg/kg cyhalothrin daily for 7 days) and 10 control (single gavage administration of 1.0 mL/kg vehicle of cyhalothrin preparation daily for 7 days) isogenic BALB/c mice in each experiment. Cyhalothrin i) increased Ehrlich ascitic tumor growth after ip administration of 5.0 x 106 tumor cells, i.e., ascitic fluid volume (control = 1.97 +/- 0.39 mL and experimental = 2.71 +/- 0.92 mL; P < 0.05), concentration of tumor cells/mL in the ascitic fluid (control = 111.95 +/- 16.73 x 106 and experimental = 144.60 +/- 33.18 x 106; P < 0.05), and total number of tumor cells in the ascitic fluid (control = 226.91 +/- 43.22 x 106 and experimental = 349.40 +/- 106.38 x 106; P < 0.05); ii) increased serum corticosterone levels (control = 200.0 +/- 48.3 ng/mL and experimental = 420.0 +/- 75.5 ng/mL; P < 0.05), and iii) decreased the intensity of macrophage phagocytosis (control = 132.3 +/- 19.7 and experimental = 116.2 +/- 4.6; P < 0.05) and oxidative burst (control = 173.7 +/- 40.8 and experimental= 99.58 +/- 41.7; P < 0.05) in vitro in the presence of Staphylococcus aureus. These data provide evidence that cyhalothrin simultaneously alters host resistance to Ehrlich tumor growth, hypothalamic-pituitary-adrenocortical (HPA) axis function, and peritoneal macrophage activity. The results are discussed in terms of data suggesting a link between stress, HPA axis activation and resistance to tumor growth.

Comparative studies of the effects of Tabebuia avellanedae bark extract and beta-lapachone on the hematopoietic response of tumour-bearing mice.

The effects of Tabebuia avellanedae (TACE), traditionally prescribed in the treatment of cancer, and the naphtoquinone beta-lapachone (beta-lap) on the growth and differentiation of granulocyte and macrophage progenitor cells (CFU-GM) were studied in Ehrlich ascites tumour-bearing mice. Myelosuppression concomitant with increases in spleen CFU-GM and in serum colony-stimulating activity (CSA) were observed in these animals. Treatment with TACE (30-500 mg/kg) and beta-lap (1-5mg/kg) reversed these effects in a dose-dependent manner. The optimal biologically active doses of 120 mg/kg TACE and 1mg/kg beta-lap prolonged life span of tumour-bearing mice, both producing the same rate of extension in the duration of survival. Toxic manifestations were produced by the higher doses of beta-lap in normal and tumour-bearing mice. In spite of similarities between treatments, TACE concentrations used to treat the animals presented no traces of beta-lap, as measured by TLC and HPLC analyses. Our findings suggest that the antitumour effect of TACE and beta-lap, acting synergistically with other factors, such as specific cytokines, may result from enhanced macrophage activation against tumour cells. In addition, it is clear from our results that hematopoietic disorders produced by tumours are an important pathological condition that must be considered in drug development.

Antitumor activities of iodoacetate and dimethylsulphoxide against solid Ehrlich carcinoma growth in mice.

Treatment of tumor-bearing mice with LD12.5 values of iodoacetate; IAA (1.84 mg/100 g b.w.) and/or dimethylsulphoxide; DMSO (350 mg/100 g b.w.) significantly increased the cumulative mean survival time and percentage of survivors and reduced the mean tumor weight, compared to tumor-bearing controls, however, a more pronounced effect is recorded in the combined treatment. Also, an increase in the life span (ILS%) and tumor growth inhibition ratio (T/C%) are reported and amounted to 145.78 and 43.80%, 195.54 and 61.30% and 220.77 and 78.40% in IAA, DMSO and combined-treated groups, respectively. Results obtained from biochemical studies reveal that a single IAA treatment of tumor-bearing mice significantly increased the levels of plasma lactate dehydrogenase (LDH) activity, while it also significantly decreased the levels of plasma glucose and liver total protein, RNA and DNA, compared to normal controls. On the other hand, a single DMSO treatment significantly elevated the activities of blood antioxidant enzymes, i.e. glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PDH) and decreased the liver RNA and DNA levels. Combined treatment increased significantly the levels of plasma LDH and erythrocytes G6PDH activities, as well as liver glycogen, and in contrast it decreased the levels of liver total protein, RNA and DNA, compared to normal controls.

The effect of a Titanocene Dichloride derivative, Ti IV (C5H5)(2) NCS(2), on the haematopoietic response of Ehrlich tumour-bearing mice.

The effects of the [Ti IV (C(5)H(5))(2) NCS(2)] metallocene (BCDT), a Titanocene Dichloride derivative, on the growth and differentiation of granulocyte-macrophage progenitor cells [colony-forming unit-granulocyte-macrophage (CFU-GM)] and bone marrow cellularity in normal and Ehrlich ascites tumour-bearing mice were studied. As expected for the Ehrlich ascites tumour-model, concomitant myelosuppression, increased number of spleen CFU-GM and changes in bone marrow cellularity were observed. The treatment of Ehrlich ascites tumour-bearing mice with BCDT (10-30 mg/kg/day) produced a dose-dependent increase in myelopoiesis, a reduction in splenic colonies and a restoration in the total and differential marrow cell counts. We also observed an increase in CFU-GM number when bone marrow cells obtained from normal mice were incubated in vitro with serum from normal mice treated with BCDT. In addition, BCDT prolonged, in a dose-dependent manner, the survival of mice inoculated with Ehrlich ascites tumour. Although it has been previously reported that substitutions in the two halides of the titanocene do not interfere with antitumoural effect, our results with BCDT demonstrated a reduction in antitumour efficacy when compared to previous results with the original titanocene produced in our laboratory.

Very high dilutions of dexamethasone inhibit its pharmacological effects in vivo.

We evaluated the interaction of dexamethasone 10(-17) and 10(-33) M (equivalent to 7cH and 15cH) with dexamethasone in pharmacological concentrations, using as experimental models: acute inflammation induced by carrageenan, Ehrlich ascitic tumour, and migration of tumour infiltrating leukocytes (TIL). Male adult BALB/c mice (n=7 per group) were used in all experiments. Carrageenan (1%) was injected into the footpad for oedema evaluation and into the peritoneal cavity (i.p.), for differential counting of inflammatory cells. Ehrlich ascitic tumour cells (10(7) viable cells/ml) were injected i.p. and tumour cells were counted after 6 days, by the Trypan blue exclusion method. The differential TIL was counted using smears stained by hematoxylin-eosin. Treatments were made immediately after carrageenan inoculation or once a day, during Ehrlich tumour development, until the animals were killed. Animals were treated with the following preparations: (1) phosphate buffer saline (PBS) solution; (2) dexamethasone (0.5 mg/kg for inflammation model or 4mg/kg for tumour model) mixed with dexamethasone 7cH or 15cH; (3) dexamethasone (same doses) mixed in PBS. Homeopathic dexamethasone partially blocked the anti-inflammatory effect of pharmacological dexamethasone with regard to paw oedema (two-way ANOVA, P < 0.0008) and polymorphonuclear cell migration (chi2, P=0.0001). No important differences were observed between experimental and control groups, in relation to Ehrlich tumour cells viability or count, or bodyweight, but potentised dexamethasone restored control levels of TIL viability, compared to mice treated with pharmacological doses of dexamethasone (chi2, P< or = 0.001). The results demonstrate that a potentised substance may change its own pharmacological effects and suggest that ultradilutions effects act mostly on host response.

Electrochemical treatment of mouse Ehrlich tumor with direct electric current.

Electrochemical treatment of cancer utilizes direct electric current (DEC) to produce direct alterations and chemical changes in tumors. However, the DEC treatment is not established and mechanisms are not well understood. In vivo studies were conducted to evaluate the effectiveness of DEC on animal tumor models. Ehrlich tumors were implanted subcutaneously in sixty male BALB/c mice. When the tumor volumes reached 850 mm(3), four platinum electrodes were inserted into the tumors. DEC of 4 mA was applied for 21 min to the treated group; the total charge was 5 C. The healthy and sick control groups were subjected to the same conditions but without DEC. Hematological and chemical parameters as well as histopathological and peritumoral findings were studied. After the electrochemical therapy it was observed that both tumor volume decrease and necrosis percentage increase were significant in the treated group. Moreover, 24 h after treatment an acute inflammatory response, as well as sodium ion decrease, and potassium ion and spleen weight increase were observed in this group. It was concluded that both electrochemical reactions (fundamentally those in which reactive oxygen species are involved), and immune system stimulation induced by cytotoxic action of the DEC could constitute the most important antitumor mechanisms.

Evoluçäo do carcinoma mamário: novos parâmetros imunopatológicos de avaliaçäo; estudo experimental em camundongos (MuMT), II. Alteraçöes hematológicas / Course of mammary carcinoma: new immunopathologic parameters of evaluation; experimental study in mice (MuMT), II. Hematological changes

Foram comparados perfis hematológicos do sangue periférico de camundongos normais com os de camundongos inoculados, intraperitonialmente, com carcinomas de Ehrlich (MuMT). Esses animais foram sacrificados em grupos de dez, diariamente, até o 20§ dia de experimentaçäo. durante esse período de observaçäo constatou-se uma queda gradual do número de hemácias e uma inversäo dos porcentuais dos polimorfonucleares com os linfócitos, os primeiros aumentando progressivamente enquanto que os segundos decresciam da mesma forma. Os monícitos e eosinófilos aumentaram, em termos porcentuais nos primeiros dias e em seguida na metade do período de observaçäo, decresceram progressivamente até 50% dos valores iniciais. As plaquetas aumentaram ligeiramente até o 2§ dia de observaçäo e decresceram gradualmente chegando no vigésimo dia a 25% do percentual inicial

Alteraçöes da hemostasia em alguns tumores experimentais / Hemostatic changes in some experimental tumors

As alteraçöes hemostásicas em animais portadores de tumores de Ehrlich, Krebs e do carcinoma Walker-256 foram avaliadas pelo tempo de protrombina de Quick e pelo tempo de tromboplastina parcial ativada. Nos animais portadores da forma sólida desses tumores, o tempo de protombina foi sempre igual aos dos grupos-controles. Nos animais portadores das formas ascíticas, o tempo de protombina esteve aumentado, enquanto o tempo de tromboplastina parcial esteve normal nos tumores de Krebs e Ehrlich e aumentado no tumor de Walker-256