Investigation of effect of paclitaxel on netrin 1 and factor 8 in Ehrlich solid tumors / Investigación del efecto del paclitaxel en netrina 1 y factor 8 en tumores sólidos de Ehrlich

SUMMARY: Cancer known as a malignant tumor, is a class of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. The Ehrlich tumor is a mammary adenocarcinoma of mice developed in solid and ascitic forms. This study was aimed to investigate the effects of paclitaxel on Netrin 1 and Factor 8 expression and also in tumor cell proliferation, apoptosis, angiogenesis, and development of tumor in Ehrlich solid tumors treated with paclitaxel. In this study, 26 adult Balb/C male mice were used. 6 of them were used as stock. Ehrlich ascites cells taken from animals in stock were injected subcutaneously from the neck area to all animals. The mice were randomly assigned to two groups of ten rats per group. Paclitaxel treatment group 10 mg/kg were administered to mice intraperitoneally (i.p.) 4,9, and 14th days. 15th day the animals were sacrificed and tumor tissues were taken. Paraffin-embedded solid tumor sections were stained Hematoxylin & Eosin, Masson's Trichrome. Also solid tumor sections were stained immunohistochemically with Netrin1 and Factor 8. Tunel method was applied to determine apoptosis. Paclitaxel applied as a therapeutic Ehrlich solid tumor reduced the volume of tumors in the treatment groups. At the end of the experiments, in the treatment groups' significantly reduced the Netrin 1 expression and microvessel density compared to the group control. Also paclitaxel in the treatment group increased the number of apoptotic cells. We suggest that decreasing the expression of Netrin 1 would be reduced vessel density and increased apoptosis.

RESUMEN: El cáncer, conocido como tumor maligno, es una clase de enfermedad que involucra un crecimiento celular anormal con potencial de invadir o diseminarse a otras partes del cuerpo. El tumor de Ehrlich es un adenocarcinoma mamario de ratones desarrollado en formas sólidas y ascíticas. Este estudio tuvo como objetivo investigar los efectos del paclitaxel en la expresión de Netrin 1 y Factor 8 y también en la proliferación de células tumorales, apoptosis, angiogénesis y desarrollo de tumores sólidos de Ehrlich tratados con paclitaxel. En esta investigación se utilizaron 26 ratones machos Balb / C adultos. Seis de ellos se utilizaron como stock. Se inyectaron por vía subcutánea células de ascitis de Ehrlich tomadas de animales en la zona del cuello. Los ratones se asignaron aleatoriamente a dos grupos de diez ratas por grupo. Se administraron 10 mg/kg del grupo de tratamiento con paclitaxel a ratones por vía intraperitoneal (i.p.) 4, 9 y 14 días. El día 15 se sacrificaron los animales y se extrajeron los tejidos tumorales. Las secciones de tumor sólido incluidas en parafina se tiñeron con hematoxilina y eosina y tricrómico de Masson. También se tiñeron inmunohisto-químicamente secciones de tumor sólido con Netrin1 y Factor 8. Se aplicó el método Tunel para determinar la apoptosis. El paclitaxel aplicado como tumor sólido terapéutico de Ehrlich redujo el volumen de tumores en los grupos de tratamiento. Al final de los experimentos, en los grupos de tratamiento se redujo significativamente la expresión de Netrin 1 y la densidad de microvasos en comparación con el grupo control. Además, el paclitaxel en el grupo tratamiento aumentó el número de células apoptóticas. Sugerimos que la disminución de la expresión de Netrin 1 reduciría la densidad de los vasos y aumentaría la apoptosis.

Enhancing Antitumor Efficacy of Cisplatin Low Dose by EDTA in Ehrlich Ascetic Carcinoma Bearing Mice

Abstract In a recent study, the treatment of different human cancer cell lines in vitro with ethylene diamine tetra-acetic acid (EDTA) showed a promising anticancer activity which could be a novel promising approach for cancer treatment. The aim of this study is to address the ability of EDTA to enhance the antitumor efficacy of the low dose of cisplatin (Cis) treatment in Ehrlich ascetic carcinoma (EAC) bearing mice. Sixty female albino mice were divided into six groups. The 1st group of mice was served as a negative control. 2nd - 6th groups were inoculated intraperitoneal (i.p) with 2×106 EAC cells/mouse. After one day of inoculation, the 2nd, 3rd and 4th groups were injected daily for 6 days (early treatment) with phosphate buffer saline, low dose of Cis and Cis/EDTA, respectively. After six days, the 5th and 6th groups were injected with the low dose of Cis and Cis/EDTA for 6 consecutive days (late treatment), respectively. At day 14, all groups of mice were sacrificed, sera were collected for biochemical assessment, then tumor volumes, counts, live and dead cells were determined from all groups. The results showed that EDTA co-treatment enhanced the efficacy of low dose of Cis at early and late time points. In addition, EDTA co-treatment potentially ameliorated the Cis-induced side effects on liver and kidney functions. In summary, co-therapy with EDTA could enhance the chemotherapeutic efficacy of low dose of Cis.

Protective and curative effect of thymoquinone on ehrlich solid carcinoma inoculated mice

Thymoquinone [TQ], the main constituents of the volatile oil from Nigella sativa seeds and it is reported to protect laboratory animals against chemical toxicity and induction of carcinogenesis. This study was undertaken to investigate the potential protective and curative effect of TQ on Ehrlich solid carcinoma cells [ESC] inoculated mice-induced carcinogenesis. [50] Swiss albino mice were divided into five groups. Control group, Thymoquonone group: animals of this group were orally treated with TQ [10 mg/kg/day] for 4 weeks, Ehrlich Carcinoma group: animals of this group were inoculated intramuscularly with 0.2mL Ehrlich Ascites Carcinoma [2.5×10[6] cells] in the right thigh of the lower limb, Thymoquinone and Ehrlich carcinoma group: animals of this group were pre-treated with TQ for 14 days then inoculated with [EAC] and Ehrlich Carcinoma and Thymoquinone group: in this group animals were inoculated with EAC then after 8 days received TQ orally for a month. Morphological, Molecular as well as histopathological and ultrastructural changes were examined. Our results revealed that TQ showed a significant anti-tumor activity in ESC bearing mice represented by a reduction in tumor weight and volume. Flow cytometric analysis illustrated that the level of apoptosis is significantly decreased in ESC inoculated group. Otherwise, TQ+ESC and ESC+TQ groups showed a highly significant increase in apoptosis G0/1 peak. The level of P53 protein expression showed a significant decrease in ESC inoculated group, and this decrease was ameliorated in TQ+ESC and ESC+TQ groups when compared to ESC inoculated group. Histopathological observations showed a reduction in tumor size after treatment with Thymoquinone and this tumor was found to be discontinuous and fragmented with slowly growing. Our results revealed that TQ has potential benefits in the prevention of the onset and progression of solid tumor model in mice

Histopathological evaluation of tumor necrosis and volume after cyanogenic chemotherapy

PURPOSE: To determine the percentage of tumoral necrosis and volume after cyanogenic chemotherapy. METHODS: Histopathological findings of 20 Swiss mice inoculated subcutaneously in the left abdominal wall with 0.05 ml of cell suspension containing 2.5 x 105 viable cells of the Ehrlich tumor were evaluated. The tumor response to cyanogenic chemotherapy was determined using a system that comprises two inhibition factors of tumor growth by calculating the percentage of necrosis in the tumor tissue and calculation of tumor volume in treated animals relative to that in control animals. The importance of this system has been validated by the correlation between tumor inhibition in the groups treated with the respective percentages of necrosis. RESULTS: While the control group presented an average of 13.48 ± 14.71% necrosis and average tumor volume of 16.18 ± 10.94, the treated group had an average of 42.02 ± 11.58 and 6.8 ± 3.57, respectively. The tumor inhibition was significantly associated with treatment (p=0.0189). The analysis of necrosis percentage showed a significant prognostic importance (p=0.0001). CONCLUSION: It is concluded that the effect of cyanogenic chemotherapy showed strong inhibitory action of tumor growth, as well as an increase in its area of necrosis. .

Avaliação da eficácia antitumoral e toxicidade de lipossomas pH-sensíveis de circulação prolongada contendo cisplatina no tratamento de camundongos portadores de tumor ascítico de Ehrlich

Cisplatina (CDDP) é um dos agentes ativos citotóxicos mais comumente usados notratamento da carcinomatose peritoneal. A inconveniência de seu uso clínico são os efeitoscolaterais sistêmicos, como nefrotoxicidade e mielotoxicidade. Lipossomas pH-sensíveis decirculação prolongada contendo CDDP (SpHL-CDDP) foram desenvolvidos por nosso grupode pesquisa com o objetivo de promover a liberação de CDDP mais próximo do tumor, bemcomo diminuir a toxicidade. O objetivo deste estudo foi avaliar a eficácia antitumoral etoxicidade de SpHL-CDDP, após a administração intraperitoneal em camundongos portadoresde tumor nas fases inicial ou avançada, com uma dose de 12 mg/Kg. A sobrevida foimonitorada e amostras de sangue foram coletadas para análises bioquímicas e hematológicas.Rins, fígado e baço foram removidos para exame histopatológico. As células tumorais foramavaliadas, segundo sua viabilidade e ciclo celular. Os resultados demonstraram que asobrevida de animais tratados com SpHL-CDDP foi maior do que aqueles tratados comCDDP livre

A morte celular causada pelo tratamento com SpHL-CDDP ocorreu através daindução de apoptose com a parada do ciclo celular na fase G0/G1. O tratamento decamundongos que apresentam câncer inicial com ambas as formulações provocou a supressãode granulócitos. Camundongos tratados com CDDP livre apresentaram também diminuição dacontagem de plaquetas, o que sugere alta mielotoxicidade. No modelo de câncer avançado, otratamento com SpHL-CDDP permitiu melhoria da resposta imune. Camundongos portadoresde câncer em estágio inicial e tratados com CDDP livre ou SpHL-CDDP apresentaram menoríndice de uréia/creatinina, em comparação ao grupo controle salina. Esses achados indicamque ambos os tratamentos foram capazes de reduzir o dano renal causado por carcinomatoseperitoneal. A análise microscópica dos rins de camundongos tratados com SpHL-CDDPmostrou alteração morfológica discreta, enquanto necrose tubular foi observada para animaistratados com CDDP livre. Em relação à hepatotoxicidade, nenhuma alteração nos parâmetros

de química clínica foi observada. Estes achados revelam que SpHL-CDDP pode melhorar aeficácia antitumoral e diminuir a toxicidade renal e da medula óssea. A dosagem de VEGF nolíquido ascítico mostrou que ambas as formulações contendo CDDP, em ambos os estágios detratamento, diminuíram a capacidade angiogênica do tumor de Ehrlich, apresentando efeitoantitumoral. O estudo imunológico mostrou que o tratamento com CDDP livre ou SpHLCDDPapresenta um perfil modulado de resposta imune, com diminuição das citocinas próinflamatóriase de citocinas reguladoras. Portanto, estes resultados abrem a possibilidade deuso futuro de SpHL-CDDP para o tratamento da carcinomatose peritoneal

Avaliação da eficácia antitumoral e toxicidade de lipossomas pH-sensíveis de circulação prolongada contendo cisplatina no tratamento de camundongos portadores de tumor ascítico de Ehrlich / Evaluation of antitumor efficacy and toxicity of pH-sensitive liposomes prolonged circulation containing cisplatin in the treatment of mice with Ehrlich ascites tumor

Cisplatina (CDDP) é um dos agentes ativos citotóxicos mais comumente usados notratamento da carcinomatose peritoneal. A inconveniência de seu uso clínico são os efeitoscolaterais sistêmicos, como nefrotoxicidade e mielotoxicidade. Lipossomas pH-sensíveis decirculação prolongada contendo CDDP (SpHL-CDDP) foram desenvolvidos por nosso grupode pesquisa com o objetivo de promover a liberação de CDDP mais próximo do tumor, bemcomo diminuir a toxicidade. O objetivo deste estudo foi avaliar a eficácia antitumoral etoxicidade de SpHL-CDDP, após a administração intraperitoneal em camundongos portadoresde tumor nas fases inicial ou avançada, com uma dose de 12 mg/Kg. A sobrevida foimonitorada e amostras de sangue foram coletadas para análises bioquímicas e hematológicas.Rins, fígado e baço foram removidos para exame histopatológico. As células tumorais foramavaliadas, segundo sua viabilidade e ciclo celular. Os resultados demonstraram que asobrevida de animais tratados com SpHL-CDDP foi maior do que aqueles tratados comCDDP livre. A morte celular causada pelo tratamento com SpHL-CDDP ocorreu através daindução de apoptose com a parada do ciclo celular na fase G0/G1. O tratamento decamundongos que apresentam câncer inicial com ambas as formulações provocou a supressãode granulócitos. Camundongos tratados com CDDP livre apresentaram também diminuição dacontagem de plaquetas, o que sugere alta mielotoxicidade. No modelo de câncer avançado, otratamento com SpHL-CDDP permitiu melhoria da resposta imune. Camundongos portadoresde câncer em estágio inicial e tratados com CDDP livre ou SpHL-CDDP apresentaram menoríndice de uréia/creatinina, em comparação ao grupo controle salina. Esses achados indicamque ambos os tratamentos foram capazes de reduzir o dano renal causado por carcinomatoseperitoneal. A análise microscópica dos rins de camundongos tratados com SpHL-CDDPmostrou alteração morfológica discreta, enquanto necrose tubular foi observada para animaistratados com CDDP livre. Em relação à hepatotoxicidade, nenhuma alteração nos parâmetros de química clínica foi observada. Estes achados revelam que SpHL-CDDP pode melhorar aeficácia antitumoral e diminuir a toxicidade renal e da medula óssea. A dosagem de VEGF nolíquido ascítico mostrou que ambas as formulações contendo CDDP, em ambos os estágios detratamento, diminuíram a capacidade angiogênica do tumor de Ehrlich, apresentando efeitoantitumoral. O estudo imunológico mostrou que o tratamento com CDDP livre ou SpHLCDDPapresenta um perfil modulado de resposta imune, com diminuição das citocinas próinflamatóriase de citocinas reguladoras. Portanto, estes resultados abrem a possibilidade deuso futuro de SpHL-CDDP para o tratamento da carcinomatose peritoneal.

Evaluation of acetone cyanohydrin effect in "in vitro" inativation of the Ehrlich ascites tumor cells / Avaliação do efeito de acetona cianidrina na inativação de células do tumor ascítico de Ehrlich "in vitro"

PURPOSE: To evaluate the antitumor effect of acetone cyanohydrin in Ehrlich ascites tumor cells in vitro. METHODS: The Ehrlich ascites tumor cells and lymphocytes were incubated with different concentrations of acetone cyanohydrin (0, 0.5, 1.0, 2.0, 10.0, 20.0 and 30.0 μg.mL-1), After 1, 2, 3, 4, 18 and 24 hours cell viability tests were performed by the trypan blue method. RESULTS: The results demonstrated a dose-dependent cytotoxic effect against the cells of Ehrlich ascites tumor. The concentrations of 20 and 30 μg.mL-1 was 100 percent of cell death in only 1 and 2 hours respectively. In lower doses of 0.5, 1.0 and 2.0 μg.mL-1 the cytotoxic effect was less intense, increasing gradually with time. CONCLUSIONS: At low concentrations of 0.5, 1.0 and 2.0 μg.mL-1, more than 90 percent of cell death was observed only after 24 hours of incubation which is the evidence that the tumor cell has the ability to poison cumulatively and irreversibly itself with the acetone cyanohydrin when compared with the results presented by human lymphocytes that the same doses and at the same time of incubation reached a maximum of 30 percent of cell death, suggesting an activity of rhodanese differentiated between the two cells.

OBJETIVO: Avaliar o efeito antitumoral da acetona cinidrina em células do tumor ascítico de Ehrlich in vitro. MÉTODOS: Células do tumor ascítico de Ehrlich e linfócitos foram incubadas com diferentes concentrações de acetona cianidrina (0, 0,5, 1,0, 2,0, 10,0, 20,0 e 30,0 μg.mL-1), depois de 1, 2, 3, 4, 18 e 24 horas foi verificada a viabilidade celular atravéz do método de azul de trypan. RESULTADOS: Os resultados demonstraram um efeito citotóxico dose dependente frente as células do tumor ascítico de Ehrlich. Nas concentrações de 20 e 30 μg.mL-1 ocorreu 100 por cento de morte celular em apenas 1 e 2 horas respectivamente. Nas doses mais baixas de 0,5, 1,0 e 2,0 μg.mL-1 o efeito citotóxico foi menos intenso, aumentando gradativamente com o tempo. CONCLUSÕES: Nas concentrações baixas de 0,5. 1,0 e 2,0 μg.mL-1, foi observado mais de 90 por cento de morte celular somente após 24 horas de incubação o que evidência a capacidade da célula tumoral de se intoxicar de maneira irreversível e acumulativa com a acetona cianidrina, quando comparadas com os resultados apresentados pelos linfócitos humanos que nas mesmas doses e nos mesmos tempos de incubação atingiram um máximo de 30 por cento de morte celular, o que sugere uma atividade de rodanase diferenciada entre as duas células.

The anti-proliferative effects of the ethanolic extract of Uncaria tomentosa in Ehrlich ascitic carcinoma / Efeitos antiproliferativos do extrato etanólico de Uncaria tomentosa sobre o tumor ascítico de Ehrlich

Objective: to evaluate the antineoplasic effect of ethanolic extract of the vine of Uncaria tomentosa (cat:.. claw) on cell viability and survivorship of Ehr/ich tumor-bearing mice. Methods: 2,8x107 Ehr/ich tumor cells were inoculated in the peritoneum of 30 Swiss male mice distributed on 3 groups of 10 animals, which were observed for 30 days and received the following solutions by gavage : CGcontrol group, which received NaCl 0,9%; EG 100 - experimental group that received the ethano/ic extract on a 100 mg/Kg dosage; and EG 200 - experimental group that received the ethano/ic extract on a 200 mg/Kg dosage. After eleven days oftreatment, 1ml of ascitic liquid was withdrawn of each animal and cellular counting was made on a Neubauer chamber by optic microscopy using the Trypan blue stain. Results: there were reduction on tumor proliferation on EG 100 and 200 of 39 and 43,5%, respectively, and a slightly increase on survivorship of EG 100 compared to control gro/lp. Conc/usion: the ethanolic extract of the vine of Uncaria tomentosa had a statistically significant and dose-dependant anti-proliferative action on Ehrlich tumor. However, on the dosages and routes studied, there was no significant increase on survi vorship of the animais.

Objetivo: avaliar os efeitos antineoplásicos do extrato etanólico (EA) do cipó de Uncaria tomentosa (Unha de gato) sobre a viabilidade celular e sobrevida de camundongos portadores do Tumor Ascítico de Ehrlich (TA E). Método: inoculadas 2,8 x 107 células do TA E, por via intraperitoneal, em 30 camundongos suíços, machos, distribuídos e.m três grupos de dez animais cada, sendo observados por 30 dias e recebendo as seguintes soluções por gavagem, por onze dias, após a inoculação do tumor: GC - GrttpO controle, que recebeu solução salina de NaCl a 0,9%; GE 100 - Grupo experimental que recebeu o EA na dose de 100 mglKg; e GE 200 - Grupo experimental, que recebeu o EA na dose de 200 mglKg. Após onze dias de tratamento, foi retirado 1 ml de líquido ascítico de cada animal e feita a contagem celular sob microscopia óptica em câmara de Neubauer, utilizando a coloração de azul de Trypan. Resultados: Houve redução na proliferação do tumor dos animais dos grupos GE 100 e GE 200 da ordem de 39 e 43,5%, respectivamente, e um ligeiro aumento da sobrevida dos animais do grupo GE /00 em cerca de três dias, comparado ao grupo controle. Conclusão: o extrato alcoólico do cipó de Uncaria tomentosa exerceu ação antiproliferativa do TA E, de forma estatisticamente significativa e dose dependente. Porém, nas doses e vias mencionadas o extrato não aumentou de forma significativa a sobrevida dos animais.

Cytotoxicity and antitumoral activity of dichloromethane extract and its fractions from Pothomorphe umbellata

The cytotoxicity of the dichloromethane crude extract (DCE), obtained from the aerial parts of Pothomorphe umbellata (L.) Miq (Piperaceae), was evaluated against nine human cancer cell lines (MCF-7, NCI-ADR/RES, OVCAR-3, PC-3, HT-29, NCI-H460, 786-O, UACC-62, K-562). The DCE presented antiproliferative activity with good potency against all cell lines at low concentrations (between 4.0 and 9.5 µg/mL) and with selectivity (1.55 µg/mL) for the leukemia cell line (K-652). DCE (100, 200, 300 and 400 mg/kg, ip) was also evaluated in the Ehrlich ascites tumor model. Both the survival number and the life span of the animals that died increased by at least 45 and 50 percent, respectively (8 animals per group), demonstrating P. umbellata extract potential anticancer activity. The results of the in vivo antitumor activity prompted the fractionation of the crude extract. The crude extract was submitted to dry column chromatography with dichloromethane-methanol (99:1). The column effluent fractions were extracted with methanol, dried under vacuum yielding fractions FR1 (less polar), FR2 (medium polarity), and FR3 (polar), which were analyzed for their growth inhibition or cytotoxic properties by a 48-h sulforhodamine B cell viability assay by measuring the total protein content. FR1 demonstrated high potency and cytotoxicity, a result compatible with the high toxicity of oxalic acid; FR2, containing 4-nerolidylcathecol, presented the lowest cytotoxic activity compared to the other two fractions but with selectivity for prostate cancer cell line; FR3, containing a mixture of steroids described in the literature as possessing various biological activities, also presented potent anticancer in vitro activity. These results suggest that P. umbellata DCE in vivo antitumor activity may be a consequence of the activity of different active principles.

In vivo anti-tumour activity of Wrightia tomentosa in Ehrlich ascites carcinoma bearing mice

Anti-tumour activity of ethanolic extracts of leaf and bark of Wrightia tomentosa [Fam: Apocynaceae] in the mice transplanted with Ehrlich ascites carcinoma [EAC] were investigated. The EAC mice receiving 100 and 200 mg/kg ethanolic leaf and bark extract showed a dose dependent elevation in tumour-free survival and a highest number of survivors were observed at 200 mg/kg for leaf extract of ethanol. which was considered as an optimum dose for its neoplastic action. The Median survival time [MST] for this dose was approximately 44 days when compared with 23 days of non-drug treated controls. Statistical analysis also indicates that the leaf extract showed highly significant anti-tumour potency [p<0.00l] when compared with control

Immunomodulatory and antitumor activity of Biophytum sensitivum extract.

An alcoholic extract of Biophytum sensitivum was studied for its immunomodulatory and antitumor activity. The extract was 100% toxic at a concentration of 0.5 mg/ml to Dalton's lymphoma ascites (DLA) and Ehrlich ascites carcinoma (EAC) cells. B. sensitivum extract was also found to be cytotoxic towards L929 cells in culture at a concentration of 0.1 mg/ml. Administration of B. sensitivum extract (500 microg/dose/animal) could inhibit the solid tumor development in mice induced with DLA cells and increase the lifespan of mice bearing Ehrlich ascites carcinoma tumors by 93.3%. B. sensitivum treatment significantly (p<0.001) reduced the tumor cell glutathione (GSH) levels as well as serum gamma glutamyl transpeptidase (GGT) and nitric oxide (NO) levels in ascites tumor bearing animals. The total WBC count was also increased to 14,087 cells/mm(3) on the 12th day in BALB/c mice. The number of plaque forming cells also enhanced significantly (p<0.001), and bone marrow cellularity and beta-esterase positive cells were also increased by the administration of B. sensitivum extract.

Cytotoxic activity of the dichloromethane fraction from Vernonia scorpioides (Lam.) Pers. (Asteraceae) against Ehrlich's tumor cells in mice

Vernonia scorpioides has been widely used in Brazil to treat skin problems and chronic wounds, such as ulcers of the lower limbs and diabetic lesions. In the present study, we investigated the effect of a dichloromethane (DCM) fraction of V. scorpioides leaf extract on Ehrlich ascitic and solid tumor-bearing mice. The animals were treated once a day with the DCM fraction at a concentration of 5 mg/kg, administered ip during and after the development of the tumor. The lifespan, weight, number and type of leukocytes, number of tumor cells, volume of solid and ascitic tumors were measured. The development of the tumor with pre-treated tumor cells in vitro with the DCM fraction (5 mg/kg) was analyzed and the animals were sacrificed after 7 days. The DCM fraction (5 mg/kg) totally inhibited tumor development when in direct contact with tumor cells, and also ascitic tumor development with in vitro treatment or when administered ip, in loco (after 7 days). Animals treated with the DCM fraction increased their lifespan ca. 2 weeks and maintained their body weight for 30 days. When applied immediately after the inoculation of the tumor cells in vivo, it totally abolished tumor development, with tumor development only decreasing when treatment was started 3 days after the tumor challenge. These data suggest an antineoplastic activity of the fraction. Oral or ip administration of DCM fraction (5 mg/kg) for 7 days did not reduce the solid tumor volume. The cytotoxic activity described here differs from the conventional immune suppressing profile of standard chemotherapy because it increases neutrophil influx to the peritoneal cavity. These results show that, besides exhibiting a tumoricidal activity, the DCM fraction also exhibits inflammatory activity.

Anti-tumour activity of Ruta graveolens extract.

An extract of Ruta graveolens was found to be cytotoxic to Dalton's lymphoma ascites (DLA), Ehrlich ascites carcinoma (EAC) and L929 cells in culture (IC100=16 mg/ml) and also to increase the lifespan of tumour bearing animals. The extract further decreased solid tumours developing from DLA and EAC cells when given simultaneously with elongation of the lifespan of tumour-bearing animals. A homeopathic preparation of Ruta graveolens (200 c) was equally effective. Neither was effective for reducing already developed tumours. The Ruta graveolens extract was found to scavenge hydroxyl radicals and inhibit lipid peroxidation at low concentrations. However, at higher concentrations the extract acted as a prooxidant as inhibition of lipid peroxidation and scavenging of hydroxyl radical was minimal. These data indicates that the prooxidant activity of Ruta graveolens may be responsible for the cytocidal action of the extract and its ability to produce tumour reduction.

Investigação dos efeitos do extrato bruto de Tabebuia avellanedae e do principio ativo isolado 'beta'-Lapachona sobre alguns parametros imunologicos em camundongos portadores do tumor ascitico de Ehrlich / Tabebuia avellanedae crude extract and 'beta-Lapachone induced anti-tumor response in Erhrlich tumor-bearing mice

Com os recentes progressos na compreensão dos complexos mecanismos moleculares relacionados a diferentes aspectos da modulação imunológica, cada vez mais vem se tornando possível ampliar os conhecimentos acerca das potenciais interferências do ponto de vista imunopatogênico induzidas pela presença e evolução tanto de processos infecciosos quanto tumorais. Modelos experimentais vêm sendo desenvolvidos e aprimorados com a finalidade de criar condições controladas para avaliações de diferentes aspectos relativos a potenciais modificações no comportamento imunológico de linhagens celulares frente à ação de novos agentes. O modelo do Tumor Ascítico de Erlich apresentou-se como uma opção de interesse, uma vez que os conhecimentos experimentais sobre diferentes aspectos relativos a sua manipulação já fazem parte de consagrada linha de pesquisa nacional. Um dos comportamentos mais recentemente estudados a seu respeito se refere a condições onde ocorre a migração do fenótipo Th1 para Th2, relacionadas ao agravamento da doença. A busca de fontes naturais para conhecimento e aplicação de novos princípios ativos vem se caracterizando como uma das mais promissoras soluções do ponto de vista farmacêutico, e pode corresponder a uma importante área de exploração da biodiversidade nacional. Dessa forma, a proposta do presente estudo foi, unindo linhas de pesquisa bastante consolidadas e conhecimentos relativos à nossa biodiversidade, avaliar o potencial terapêutico, com foco em abordagens imunopatológicas, do extrato da planta Tabebuia avellanedae (ETA) através do modelo experimental Tumor ascítico de Ehrlich. Neste trabalho investigamos os efeitos do ETA e...

In accordance with the recent progress in the understanding of immunological and molecular mechanisms related to the different aspects of immunological modulation, the improvement of knowledge about the potential interferences, at the immunopathogenic point of view, induced by the presence and evolution of infectious diseases or neoplastic process has increased. Experimental models have been developed and refined in order to create appropriate conditions to evaluate different aspects related to potential changes in the immunological behaviors of determinate cell lines with the presence of new pharmacological agents. The Ehrlich ascites tumor (EAT) model is an option of interest, since the accumulated experimental knowledge about its manipulation is part of a consolidated research line. One of its more recently studied behaviors is concerned with situations where the migration from Th1 to Th2 phenotype occurs, at the same time with the disease impairment. The search for new natural sources of pharmaceutical active principles and the careful and detailed studies about them, has been characterized as one of most promising therapeutic solutions at the moment, and would be seen as a strategic way to explore the national biodiversity. Therefore, the aim of the present study was to combine the well known techniques related to the Ehrlich ascites tumor changing behavior with a potential active principle from our botanical biodiversity, the Tabebuia avellanedae extract (TACE), in order to evaluate its immunological therapeutic potential. The effects of TACE and its isolated naphtoquinone...

Efeito do tratamento com isoflavona no crescimento do tumor sólido de Ehrlich / Effect of Isoflavone treatment on Solid Ehrlich Tumor growth

Estudos epidemiológicos revelam que o consumo regular de soja reduz ou suprime o câncer de mama, sendo esse fato associado à presença de isoflavonas, fitoestrógenos contidos nesses grãos. Atribui-se ao estrogênio a facilitação do crescimento de neoplasias mamárias humanas e, por conseqüência, o uso do fitoestrogênio vem se mostrando uma terapia alternativa ao uso de estrogênio. Neste estudo, avaliou-se a ação das isoflavonas sobre o crescimento do tumor de Ehrlich, baseando-se nas determinações de peso, área e proliferação celular. Para tanto, administrou-se uma suspensão de isoflavona, via intraperitoneal, na dose de 20 mg/kg de peso, por 20 dias. Constatou-se que o tratamento com isoflavona é capaz de interferir no ciclo de divisão celular, pois o número de figuras de mitose foi significativamente reduzido no grupo tratado. O peso e as dimensões da massa tumoral não apresentaram dife renças significativas entre os grupos, fato que merece investigação futura...

Antitumor and biochemical effects of Echis coloratus crude venom on Ehrlich ascites carcinoma cells in vivo

The search for snake venom antitumor efficacy has attracted the interest of scientists since the beginning of last century. Snake venom possesses a wide spectrum of biological activities. In this study, we evaluated the effect of Echis coloratus crude venom on the evolution of Ehrlich ascites carcinoma cells (EAC). Normal and EAC-bearing mice were treated with 0.2 mg/kg body weight of crude venom. Crude venom was seen to suppress tumor growth by significantly decreasing EAC cell count and cell viability (p<0.01). There was also a significant increase in survival time of the venom-treated tumor-bearing mice (52.3 percent, p<0.05) in comparison to the non-treated tumor-bearing counterparts. The study of venom effect and/or tumor inoculation on some important biochemical parameters and enzyme activities showed that the expected venom toxic effect disappeared due to the low (sublethal) dose; treatment of the tumor-bearing mice with this low dose could correct and restore biochemical parameters to normal levels which had been altered due to tumor growth. It can be concluded that Echis coloratus crude venom antitumor efficiency exceeded or camouflaged its toxic effect.

Investigation of lipids, mucilage and cytotoxic activity of the leaves of abutilon hirtum lam. Growing in Egypt

Lipid content of the leaves of Abutilon hirtum Lam. was studied. GLC analysis of the unsaponifiable matter revealed the presence of a series of hydrocarbons C10-C34, cholesterol, stigmasterol and beta- sitosterol. Stigmasterol was also isolated from the unsaponifiable matter. GLC analysis of the fatty acids revealed the presence of 11 identified components. Palmitic, linoleic, oleic and linolenic acids constituted about 81% of the total acids in the leaves. Chromatographic analysis of mucilage hydrolyzate prepared from the leaves by cold water methods, showed that it contained L-rhamnose, L- arabinose, mannose, glucuronic acid and galacturonic acid. Screening of the cytotoxic activity of the petroleum ether extract [100, 50 mug/ml] showed 100% inhibition of Ehrlich ascites carcinoma [EAC] tumor cells [in vitro]

Evaluation of anti-tumor efficacy of injectable Centchroman in mice bearing Ehrlich ascites carcinoma.

Anti-tumor efficacy of Centchroman formulated as niosomes and gel implant was evaluated in Swiss albino mice bearing Ehrlich ascites carcinoma at 10 mg/kg body weight dose given subcutaneously. Median day of death, percentage increase in host life span and changes in body weight were studied. Centchroman significantly (P < 0.05) increased the median day of death both in free and formulated systems. Also, injectable formulations exhibited a significant (P < 0.05) increase in host life span compared to free drug, hence, enhanced anti-tumor efficacy against Ehrlich ascites carcinoma.

Effect of plumbagin on the radiation induced cytogenetic and cell cycle changes in mouse Ehrlich ascites carcinoma in vivo.

The effect of plumbagin, a naphthoquinone from the roots of the Indian medicinal plant Plumbago rosea, and Cobalt-60 gamma radiation was studied on Ehrlich ascites carcinoma in vivo, taking cytogenetic damage and cell cycle changes as experimental endpoints. Plumbagin (5 mg/kg body wt, P1) administered intraperitoneally produced a significant increase in the percentage of S-phase as well as G2-M cells with a corresponding decrease in the G1 phase at different post-treatment times. Radiation (7.5 Gy, RT) alone produced the classical G2 block at 1 hr, which persisted with a continuous increase throughout the post-treatment observation period. The combination treatment produced a similar effect as that of RT on G2-M cells, but its effect on the G1 phase was more pronounced than the latter. While P1 treatment produced a small increase in the percentage of labeled S-phase cells, combination treatment significantly reduced the labeled S-phase cells with a corresponding increase in the unlabeled fraction. Drug or radiation alone significantly increased micronuclei induction at various post-treatment times and the combination of the two further enhanced this effect additively. The mechanism of interaction of P1 with radiation in bringing about this effect is not clear.

Antitumor activity of Hygrophila spinosa on Ehrlich ascites carcinoma and sarcoma-180 induced mice.

Petroleum ether extract from H. spinosa root exhibited antitumor activity in Ehrlich ascites carcinoma and Sarcoma-180 bearing mice Processed extract suppressed significantly the tumor fluid volume at the end of 3 weeks experiment. It decreased about 50% of packed cell volume and increased life span of EAC/S-180 bearing mice in a day dependent manner. Red blood cell count, hemoglobin content and white blood cell count were more or less normal after processed extract treatment of the tumor bearing mice. In tumor control animals, neutrophils increased (273.7% in EAC and 263.4% in S-180 bearing mice respectively with respect to normal mice) whereas lymphocytes decreased (60.0% in EAC and 56.5% in S-180 bearing mice respectively with respect to normal mice). It also inhibited the rapid increase of body weight of tumor bearing mice.