RESUMO
OBJECTIVES: Sleep deprivation is a growing public health hazard, yet it is still under-recognized. Sleep disorders and disruption of sleep patterns may compromise the immune function and adversely affect host resistance to infectious diseases. This is a particular risk in cancer patients, who report a high frequency of sleep disturbances. The present study investigated the effects of sleep deprivation on the development of Ehrlich ascitic tumors (EAT) in female BALB/c mice. Our study also evaluated whether EAT would induce alterations in sleep pattern. Spleen lymphocyte cell populations and mortality were also quantified. METHODS: Female BALB/c mice were intraperitoneally inoculated with EAT cells. Immediately after the inoculation procedure, animals were sleep deprived for 72 h. Ten or 15 days after inoculation, the number of tumoral cells was quantified and the lymphocytic cell population in the spleen was characterized by flow cytometry. In addition, the effect of sleep deprivation on EAT-induced mortality was quantified and the influence of EAT on sleep patterns was determined. RESULTS: Sleep deprivation did not potentiate EAT growth, but it significantly increased mortality. Additionally, both EAT and sleep deprivation decreased frequencies of splenic CD4+, CD8+ and CD19+ cells. With respect to sleep patterns, EAT significantly enhanced paradoxical sleep time. CONCLUSIONS: Although sleep deprivation did not potentiate EAT growth, it decreased the survival of female tumor-bearing mice.
Assuntos
Carcinoma de Ehrlich/mortalidade , Privação do Sono/complicações , Análise de Variância , Animais , Antígenos CD/metabolismo , Carcinoma de Ehrlich/imunologia , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Humanos , Linfócitos/imunologia , Linfócitos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias/métodos , Baço/patologiaRESUMO
BACKGROUND: Antineoplastic phospholipids (ALPs) represent a promising class of drugs with a novel mode of action undergoes rapid turnover in the cell membrane of tumors, interfering with lipid signal transduction, inducing cell death. The aim of this study was to investigate the synthetic phosphoethanolamine (Pho-s) as a new anticancer agent. MATERIALS AND METHODS: Cell viability and morphology were assessed by (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Hoechst and rhodamine staining. Apoptosis was assessed by Annexin V and propidium iodide (PI) staining, caspase-3 activity, mitochondrial membrane potential (ΔmΨ) and cell cycle analysis, combined with evaluation of tumor growth in Ehrlich Ascites Tumor (EAT) bearing mice. RESULTS: We found that Pho-s 2.30 mg/ml induced cytotoxicity in all tumor cell lines studied without affecting normal cells. In vitro studies with EAT cells indicated that Pho-s induced apoptosis, demonstrated by an increase in Annexin-V positive cells, loss of mitochondrial potential (ΔmΨ) and increased caspase-3 activity. It was also shown to increase the sub-G(1) apoptotic fraction and inhibit progression to the S phase of the cell cycle. Additionally, antitumor effects on the EAT-bearing mice showed that Pho-s, at a concentration of 35 and 70 mg/kg, inhibited tumor growth and increased the lifespan of animals without causing liver toxicity. CONCLUSION: These findings suggest that Pho-s is a potential anticancer candidate drug.
Assuntos
Apoptose/efeitos dos fármacos , Carcinoma de Ehrlich/tratamento farmacológico , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Etanolaminas/uso terapêutico , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Animais , Carcinoma de Ehrlich/mortalidade , Carcinoma de Ehrlich/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Citometria de Fluxo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Taxa de SobrevidaRESUMO
The objective of this work is to report the antiproliferative effect of P. cupana treatment in Ehrlich Ascites Carcinoma (EAC)-bearing animals. Female mice were treated with three doses of powdered P. cupana (100, 1000 and 2000 mg/kg) for 7 days, injected with 10(5) EAC cells and treated up to day 21. In addition, a survival experiment was carried out with the same protocol. P. cupana decreased the ascites volume (p = 0.0120), cell number (p = 0.0004) and hemorrhage (p = 0.0054). This occurred through a G1-phase arrest (p < 0.01) induced by a decreased gene expression of Cyclin D1 in EAC cells. Furthermore, P. cupana significantly increased the survival of EAC-bearing animals (p = 0.0012). In conclusion, the P. cupana growth control effect in this model was correlated with a decreased expression of cyclin D1 and a G1 phase arrest. These results reinforce the cancer therapeutic potential of this Brazilian plant.
Assuntos
Carcinoma de Ehrlich/tratamento farmacológico , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Citostáticos/uso terapêutico , Paullinia , Fitoterapia , Preparações de Plantas/uso terapêutico , Animais , Carcinoma de Ehrlich/mortalidade , Carcinoma de Ehrlich/patologia , Citostáticos/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Preparações de Plantas/farmacologia , Análise de SobrevidaRESUMO
The aim of the present study was to examine the effect of a diet rich in synthetic PEtn on the metabolism macrophages of tumor-bearing mice. The results demonstrated that PEtn increased the animals' survival time. In addition, the treated animals released smaller amounts of hydrogen peroxide (H2O2) and nitric oxide (NO) than the non-treated animals, particularly after day 14. From the results it could be concluded that H2O2 and NO were important in the modulation of neoplastic growth, and pointed to a promising role of PEtn in the control of human neoplasms.
Assuntos
Animais , Camundongos , Fosfatidiletanolaminas , Carcinoma de Ehrlich/tratamento farmacológico , Animais de Laboratório , Macrófagos/efeitos dos fármacos , Carcinoma de Ehrlich/dietoterapia , Carcinoma de Ehrlich/mortalidadeRESUMO
The leaves of Chenopodium ambrosioides L. [Chenopodiaceae] ('mastruz') have been indicated for the treatment of several diseases, among which the cancer. There are no results focusing the effect of C. ambrosioides treatment on tumor development in vivo. The aim of this study was to investigate the effect of treatment with C. ambrosioides on Ehrlich tumor development. Swiss mice were treated by intraperitoneal route (i.p.) with hydroalcoholic extract from leaves of C. ambrosioides (5 mg/kg) or with PBS (control group) 48 h before or 48 h later the Ehrlich tumor implantation. The tumor cells were implanted on the left footpad (solid tumor) or in the peritoneal cavity (ascitic tumor). To determine the solid tumor growth, footpad was measured each 2 days until the fourteenth day, when the feet were weighed. Ascitic tumor development was evaluated after 8 days of tumor implantation by quantification of the ascitic fluid volume and tumor cell number. The i.p. administration of C. ambrosioides extract before or after the tumor implantation significantly inhibited the solid and ascitic Ehrlich tumor forms. This inhibition was observed in ascitic tumor cell number, in the ascitic volume, in the tumor-bearing foot size and foot weight when compared to control mice. The treatments also increased the survival of tumor-bearing mice. In conclusion, C. ambrosioides has a potent anti-tumoral effect which was evident with a small dose and even when the treatment was given two days after the tumor implantation. This effect is probably related with anti-oxidant properties of C. ambrosioides.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma de Ehrlich/tratamento farmacológico , Chenopodium ambrosioides/química , Animais , Carcinoma de Ehrlich/mortalidade , Carcinoma de Ehrlich/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Injeções Intraperitoneais , Longevidade/efeitos dos fármacos , Masculino , Camundongos , Transplante de Neoplasias , Fitoterapia , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Taxa de SobrevidaRESUMO
BACKGROUND: In vivo studies were conducted to quantify the effectiveness of low-level direct electric current for different amounts of electrical charge and the survival rate in fibrosarcoma Sa-37 and Ehrlich tumors, also the effect of direct electric in Ehrlich tumor was evaluate through the measurements of tumor volume and the peritumoral and tumoral findings. METHODS: BALB/c male mice, 7-8 week old and 20-22 g weight were used. Ehrlich and fibrosarcoma Sa-37 cell lines, growing in BALB/c mice. Solid and subcutaneous Ehrlich and fibrosarcoma Sa-37 tumors, located dorsolaterally in animals, were initiated by the inoculation of 5 x 10(6) and 1 x 10(5) viable tumor cells, respectively. For each type of tumor four groups (one control group and three treated groups) consisting of 10 mice randomly divided were formed. When the tumors reached approximately 0.5 cm3, four platinum electrodes were inserted into their bases. The electric charge delivered to the tumors was varied in the range of 5.5 to 110 C/cm3 for a constant time of 45 minutes. An additional experiment was performed in BALB/c male mice bearing Ehrlich tumor to examine from a histolological point of view the effects of direct electric current. A control group and a treated group with 77 C/cm3 (27.0 C in 0.35 cm3) and 10 mA for 45 min were formed. In this experiment when the tumor volumes reached 0.35 cm3, two anodes and two cathodes were inserted into the base perpendicular to the tumor long axis. RESULTS: Significant tumor growth delay and survival rate were achieved after electrotherapy and both were dependent on direct electric current intensity, being more marked in fibrosarcoma Sa-37 tumor. Complete regressions for fibrosarcoma Sa-37 and Ehrlich tumors were observed for electrical charges of 80 and 92 C/cm3, respectively. Histopathological and peritumoral findings in Ehrlich tumor revealed in the treated group marked tumor necrosis, vascular congestion, peritumoral neutrophil infiltration, an acute inflammatory response, and a moderate peritumoral monocyte infiltration. The morphologic pattern of necrotic cell mass after direct electric current treatment is the coagulative necrosis. These findings were not observed in any of the untreated tumors. CONCLUSION: The data presented indicate that electrotherapy with low-level DEC is feasible and effective in the treatment of the Ehrlich and fibrosarcoma Sa-37 tumors. Our results demonstrate that the sensitivity of these tumors to direct electric current and survival rates of the mice depended on both the amount of electrical charge and the type of tumor. Also the complete regression of each type of tumor is obtained for a threshold amount of electrical charge.
Assuntos
Carcinoma de Ehrlich/terapia , Terapia por Estimulação Elétrica/métodos , Fibrossarcoma/terapia , Animais , Carcinoma de Ehrlich/mortalidade , Carcinoma de Ehrlich/patologia , Linhagem Celular Tumoral , Terapia por Estimulação Elétrica/instrumentação , Terapia por Estimulação Elétrica/mortalidade , Eletrodos Implantados , Desenho de Equipamento , Estudos de Viabilidade , Fibrossarcoma/mortalidade , Fibrossarcoma/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Taxa de SobrevidaRESUMO
Rhodium (II) trifluoroacetate (TFARh), rhodium (II) trifluoroacetate adduct with sulfadiazine (TFARh.Sd) and rhodium (II) acetate adduct with sulfisoxazole (RhSx) were tested in mice for acute toxicity, antitumoral activity against Ehrlich ascites carcinoma and for viability of Ehrlich tumor cells in culture. At ip doses up to 60 mumol/kg (40-70 and 59 mg/kg, respectively), these compounds had no toxic effects up to 14 days. At ip doses of 10 mumol kg-1 day-1 for 5 days, TFARh and TFARh.Sd significantly increased the survival rate of mice bearing Ehrlich ascites cells (probability of survival to the end of 34th day, controls = 0.23, TFARh = 0.85, TFARh.Sd = 0.74). No significant effect was observed for RhSx. In vitro, these rhodium complexes at 40 microM significantly increased the number of dead cells in cultured Ehrlich tumor cells.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Ehrlich/tratamento farmacológico , Ródio/farmacologia , Acetatos/administração & dosagem , Animais , Carcinoma de Ehrlich/mortalidade , Ensaios de Seleção de Medicamentos Antitumorais , Camundongos , Camundongos Endogâmicos BALB C , Sulfadiazina/administração & dosagem , Sulfisoxazol/administração & dosagem , Taxa de Sobrevida , Fatores de Tempo , Ácido Trifluoracético/administração & dosagemRESUMO
Rhodium (II) trifluoracetate (TFARh), rhodium (II) trifluoracetate adduct with sulfadiazine (TFARh.Sd) and rhodium (II) acetate adduct with sulfisoxazole (RhSx) were tested in mice for acute toxicity, antitumoral activity against Ehrlich ascites carcinoma and for viability of Ehrlich tumor cells in culture. At ip doses up to 60 µmg/kg (40-70 and 59 mg/kg, respectively), these coumpounds had no toxic effects up to 14 days. At ip doses of 10 µmol Kg-1 day-1 for 5 days, TFARh and TFARh.Sd significantly increased the survival rate of mice bearing Ehrlich ascites cells (probability of survival to the end of 34th day, controls = 0.23, TFARh = 0.85, TFARh.Sd = 0.74). No significant effect was observed for RhSx. In vitro, these rhodium complexes at 40 µM significantly increased the number of dead cells in cultured Ehrlich tumor cells
Assuntos
Camundongos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Ehrlich/tratamento farmacológico , Técnicas In Vitro , Ródio/farmacologia , Acetatos/administração & dosagem , Carcinoma de Ehrlich/mortalidade , Camundongos Endogâmicos BALB C , Sulfadiazina/administração & dosagem , Sulfisoxazol/administração & dosagem , Fatores de Tempo , Ácido Trifluoracético/administração & dosagemRESUMO
OBJECTIVE--to verify the effects of Listeria monocytogenes (LM) inoculation in the survival of animals bearing Ehrlich's tumor. KIND OF STUDY--experimental. Animals-isogenic mice, Balb/c, female, 19-21 g. Tumor-Ascitic Ehrlich's tumor, dilution of 5 x 10(5) cells/0.1 ml. Bacteria-LM serotype 4a, solution with 7 x 10(3) bacteria (standard sub-lethal dose). Intervention-a) inoculation of LM in mice bearing Ehrlich tumor at the same time as ascitic cells transplantation. b) inoculation of LM seven days before and, again, seven and fourteen days after ascitic cells transplantation. c) to study the effect of using ampicillin 100 mg/kg, im, simultaneously with the inoculation of Ehrlich tumor and LM organisms and, again, 3, 5, 7, 14, 21 and 30 days after the ascitic cells transplantation. ANALYSIS--Chi-square test; p < 0.05 RESULTS AND CONCLUSION--LM increases significantly the survival of mice bearing Ehrlich tumor even when only one inoculum of viable LM was used, seven days before or seven days after the ascitic cells transplantation. The use of ampicillin after the inoculation of LM and tumor transplantation does not alter the survival of mice
Assuntos
Animais , Feminino , Carcinoma de Ehrlich/imunologia , Listeria monocytogenes/patogenicidade , Ampicilina/uso terapêutico , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/mortalidade , Distribuição de Qui-Quadrado , Avaliação Pré-Clínica de Medicamentos , Listeriose/tratamento farmacológico , Listeriose/imunologia , Listeriose/mortalidade , Camundongos , Camundongos Endogâmicos BALB CRESUMO
OBJECTIVE: to verify the effects of Listeria monocytogenes (LM) inoculation in the survival of animals bearing Ehrlich's tumor. KIND OF STUDY: experimental. Animals-isogenic mice, Balb/c, female, 19-21 g. Tumor-Ascitic Ehrlich's tumor, dilution of 5 x 10(5) cells/0.1 ml. Bacteria-LM serotype 4a, solution with 7 x 10(3) bacteria (standard sub-lethal dose). Intervention-a) inoculation of LM in mice bearing Ehrlich tumor at the same time as ascitic cells transplantation. b) inoculation of LM seven days before and, again, seven and fourteen days after ascitic cells transplantation. c) to study the effect of using ampicillin 100 mg/kg, im, simultaneously with the inoculation of Ehrlich tumor and LM organisms and, again, 3, 5, 7, 14, 21 and 30 days after the ascitic cells transplantation. ANALYSIS: Chi-square test; p < 0.05 RESULTS AND CONCLUSION: LM increases significantly the survival of mice bearing Ehrlich tumor even when only one inoculum of viable LM was used, seven days before or seven days after the ascitic cells transplantation. The use of ampicillin after the inoculation of LM and tumor transplantation does not alter the survival of mice.