Monosialoganglioside GM1 reduces toxicity of Ptx and increase anti-metastasic effect in a murine mammary cancer model.

Having demonstrated the ability of monosialoganglioside GM1 micelles as oncology drug transporter, this work focuses on evaluating its application in an in vivo system, studying the toxicity and antitumoral effect of GM1-Ptx micellar formulation. The maximum tolerated dose (MTD) obtained after intravenous administration of GM1-Ptx in mice was 55 mg/kg and the 50% lethal dose (LD50) was 70 mg/kg. This value is higher than those described for the commercial formulations TAXOL and ABRAXANE, with LD50 of 30 and 45 mg/kg respectively. The antitumor activity, mortality and incidence of metastasis were studied on a murine model of mammary gland cancer. The GM1-Ptx formulation was administered i.v. at different doses for 9 weeks using empty GM1 micelles and saline as treatment controls. Once the treatments were completed, biochemical markers were quantified and histological tissue tests were performed. The most promising results were obtained with the treatment at a dose of 15 mg/kg/twice a week, condition in which a longer survival and significant reduction in the incidence of animals with metastasis, since only one 25% of the mice showed presence of pulmonary micro metastases.

High Concentrations of Sodium Chloride Improve Microbicidal Activity of Ibuprofen against Common Cystic Fibrosis Pathogens.

Ibuprofen (IBU-H), a widely used anti-inflammatory, also shows a marked antimicrobial effect against several bacterial species, including those involved in cystic fibrosis such as Pseudomona aeruginosa, methicillin resistant Staphylococcus aureus and Burkholderia cepacia complex. Additionally, our results show significant synergy between water soluble Na-ibuprofen (IBU-Na) and ionic strength. Salt concentrations above 0.5 M modify the zeta potential promoting the action of Na-IBU; thus, with 1 M sodium chloride, IBU-Na is ten times more efficient than in the absence of ionic strength, and the minimum effective contact time is reduced from hours to minutes. In short time periods, where neither IBU-Na nor controls with 1 M NaCl show activity, the combination of both leads to a reduction in the bacterial load. We also analyzed whether the changes caused by salt on the bacterial membrane also promoted the activity of other microbicide compounds used in cystic fibrosis like gentamicin, tobramycin and phosphomycin. The results show that the presence of ionic strength only enhanced the bactericidal activity of the amphipathic molecule of IBU-Na. In this respect, the effect of saline concentration was also reflected in the surface properties of IBU-Na, where, in addition to the clear differences observed between 145 mM and 1 M, singular behaviors were also found, different in each condition. The combination of anti-inflammatory activity and this improved bactericidal effect of Na-IBU in hypertonic solution provides a new alternative for the treatment of respiratory infections of fibrotic patients based on known and widely used compounds.

Influence of diets varying in lipid and protein content on the histopathologic variety of murine salivary gland tumors induced by 9,10-dimethyl-1,2-benzanthracene (DMBA).

The purpose of this study was to analyze the influence of diets varying in lipids and proteins on the histopathologic variety of murine salivary tumors induced by DMBA. 117 BALB/c mice were assigned to experiments one (E1: lipids, males) and two (E2: proteins, males and females), E1 comprising Soy oil (SO); Corn oil (CO, control); Fish oil (FO) and Olein (O) groups and E2, soy protein (SP) and casein (C) groups. Tumors were induced by DMBA and the animals were sacrificed at week 13- post-induction. Tumor volume was calculated. Tumor sections were stained with H-E for histopathologic evaluation. No significant association was found between tumor volume and dietary condition (p > 0.05). In E1, FO animals developed mainly carcinomas (C) (58.8%), the sarcomas (S) and carcinosarcomas (CS) being especially of high-grade type (tumors < 600 mm3). In E2, SP animals developed mainly C (55.6%). Although no significantly different (p > 0.05), S and C were more frequent in female and male mice, respectively. In both E1 and E2, the biggest tumors (> 600 mm3) were mainly high-grade S (87.5%-80%). Dietary fat and soy protein appear to influence the tumor histopathology and thus its prognosis.

Influence of diets varying in lipid and protein content on the histopathologic variety of murine salivary gland tumors induced by 9, 10-dimethyl-1, 2-benzanthracene (DMBA) / Influencia de dietas de diferente contenido lipídico y proteico sobre variantes histopatológicas de tumores de glándulas salivares murinos inducidos con 9, 10-dimethyl-1, 2-benzathraceno (DMBA)

The purpose of this study was to analyze the influence of diets varying in lipids and proteins on the histopathologic variety of murine salivary tumors induced by DMBA. 117 BALB/c mice were assigned to experiments one (E1: lipids, males) and two (E2: proteins, males and females), E1 comprising Soy oil (SO); Corn oil (CO, control); Fish oil (FO) and Olein (O) groups and E2, soy protein (SP) and casein (C) groups. Tumors were induced by DMBA and the animals were sacrificed at week 13- post-induction. Tumor volume was calculated. Tumor sections were stained with H-E for histopathologic evaluation. No significant association was found between tumor volume and dietary condition (p > 0.05). In E1, FO animals developed mainly carcinomas (C) (58.8%), the sarcomas (S) and carcinosarcomas (CS) being especially of high-grade type (tumors < 600 mm3). In E2, SP animals developed mainly C (55.6%). Although no significantly different (p > 0.05), S and C were more frequent in female and male mice, respectively. In both E1 and E2, the biggest tumors (> 600 mm3) were mainly high-grade S (87.5%-80%). Dietary fat and soy protein appear to influence the tumor histopathology and thus its prognosis.

El objetivo de este estudio fue analizar la influencia de dietas con diferente contenido de lípidos y proteínas sobre la variedad histopatológica de tumores salivares murinos inducidos por DMBA. Se asignaron 117 ratones BALB/c a los experimentos uno (E1: lípidos, machos) y dos (E2: proteínas, machos y hembras). E1 comprendió a los grupos aceite de soja (AS), aceite de maíz (AM, control), aceite de pescado (AP) y oleína (O), en tanto E2 incluyó a los grupos preteína de soja (PS) y caseína (C). Los tumores fueron inducidos por DMBA y los animales fueron sacrificados a la 13ª semana post-inducción. Se calculó el volumen tumoral. Los cortes de tumor fueron coloreados con Hematoxilina-Eosina para su evaluación histopatológica. No se encontró asociación entre volumen tumoral y condición dietaria (p>0.05). En E1, los animales del grupo AP desarrollaron principales carcinomas (C) (58,8%), en tanto que los sarcomas (S) y carcinosarcomas (CS) fueron de alto grado (tumores<600 mm³). En el E2, los animales del grupo PS desarrollaron principalmente C (55.6%). Aunque la diferencia no fue significativa (p>0.05), S y C fueron más frecuentes en ratones hembras y machos, respectivamente. Tanto el E1 com en E2, los tumores más voluminosos (> 600 mm³) fueron principalmente de alto grado (87.5%-80%) Los lípidos y la proteína de soja de la dieta parecen influenciar la histopatología de los tumores y, en consecuencia, su pronóstico.

Effects of soy oil on murine salivary tumorigenesis.

Dietary fat influences dimethylbenzanthracene (DMBA)-induced tumorigenesis of several organs, including the salivary glands. There is not enough evidence to suggest that soy oil could also affect growth of salivary tumors. The main purpose of this work therefore was to study the effects of dietary soy oil on macroscopic parameters of chemically induced murine salivary gland tumors. Eighty BALB/c male mice were assigned to four groups: soy oil (SO), corn oil (CO, control), fish oil (FO) and olein (O). Two weeks later, tumors were induced by 9,10-dimethyl-1,2-benzanthracene (DMBA). At the 13th post-injection week, the animals were sacrificed. In vivo tumor diameter, gland volume (total resected mass), tumor volume (microscopically measured), tumor remission and tumor histopathology were analyzed. The initial in vivo tumor diameter, gland and tumor volume were significantly greater in soy oil than in fish oil group. 26.7% of animals on the soy oil diet showed tumor remission. Sarcomas were more often found in the SO group, carcinomas in FO and the mixed-type tumors both in SO and CO groups. This study shows that the soy oil treatment resulted in larger tumors, some of which later became undetectable. It is necessary to further investigate these divergent results.

[Proliferation and apoptosis in tongue epithelium of mice bearing salivary tumors induced by dimetilbenzantraceno (DMBA) and modulated by dietary lipids]. / Proliferación y apoptosis en epitelio lingual de ratones con tumores salivales inducidos por dimetilbenzantraceno (DMBA) y modulados por lípidos dietarios.

INTRODUCTION: According to the concept of field defects during the carcinogenesis process, excessive epithelial proliferation/apoptosis may exist in areas near tumors. Proliferation or apoptosis could be modified by dietary lipids. PURPOSE: The present study was designed to analyze proliferation and apoptosis in tongue epithelium of mice fed diets based on different lipids followed by induction of salivary tumors with DMBA. MATERIALS AND METHODS: Forty-five days after weaning, ten BALB/c mice were assigned to two diets: corn oil (CO) and fish oil (cod liver, FO). Two weeks later, DMBA was injected in the submandibular area. Animals were sacrificed at the 13th post-injection week. Samples of tongue were fixed in formalin-ethanol and immunohistochemically stained for proliferation (Ki-67) and apoptosis (Bax). By light microscopy, the number of nuclei positive for these markers were counted out of three-hundred total interphase cells both in dorsal and in ventral tongue surfaces. Results were analyzed through Analysis of Variance and t Test. RESULTS: Cell proliferation was greater in dorsal than in ventral tongue surfaces (p < 0.0001) with no diet difference. Apoptosis was significantly greater in mice fed FO than CO, particularly in tongue dorsal epithelia (p < 0.018). CONCLUSIONS: This study shows that FO diet induces higher levels of apoptosis in tongue epithelia suggesting a tissue defensive mechanism when exposed to a carcinogenic-tumoral agent.

Proliferación y apoptosis en epitelio lingual de ratones con tumores salivales inducidos por dimetilbenzantraceno (DMBA) y modulados por lípidos dietarios. / [Proliferation and apoptosis in tongue epithelium of mice bearing salivary tumors induced by dimetilbenzantraceno (DMBA) and modulated by dietary lipids]

INTRODUCTION: According to the concept of field defects during the carcinogenesis process, excessive epithelial proliferation/apoptosis may exist in areas near tumors. Proliferation or apoptosis could be modified by dietary lipids. PURPOSE: The present study was designed to analyze proliferation and apoptosis in tongue epithelium of mice fed diets based on different lipids followed by induction of salivary tumors with DMBA. MATERIALS AND METHODS: Forty-five days after weaning, ten BALB/c mice were assigned to two diets: corn oil (CO) and fish oil (cod liver, FO). Two weeks later, DMBA was injected in the submandibular area. Animals were sacrificed at the 13th post-injection week. Samples of tongue were fixed in formalin-ethanol and immunohistochemically stained for proliferation (Ki-67) and apoptosis (Bax). By light microscopy, the number of nuclei positive for these markers were counted out of three-hundred total interphase cells both in dorsal and in ventral tongue surfaces. Results were analyzed through Analysis of Variance and t Test. RESULTS: Cell proliferation was greater in dorsal than in ventral tongue surfaces (p < 0.0001) with no diet difference. Apoptosis was significantly greater in mice fed FO than CO, particularly in tongue dorsal epithelia (p < 0.018). CONCLUSIONS: This study shows that FO diet induces higher levels of apoptosis in tongue epithelia suggesting a tissue defensive mechanism when exposed to a carcinogenic-tumoral agent.