RESUMO
We recently showed that a low-carbohydrate (CHO) diet containing soy protein and fish oil dramatically reduces lung nodules in a mouse model of lung cancer when compared to a Western diet. To explore the universality of this finding, we herein compared this low-CHO diet to a Western diet on in preventing breast and prostate cancer using a mouse model that expresses the SV40 large T-antigen specifically in breast epithelia in females and prostate epithelia in males. We found that breast cancer was significantly reduced with this low-CHO diet and this correlated with a reduction in plasma levels of glucose, insulin, IL-6, TNFα and prostaglandin E2 (PGE2). This also corresponded with a reduction in the Ki67 proliferation index within breast tumors. On the other hand, this low-CHO diet did not reduce the incidence of prostate cancer in the male mice. Although it reduced both blood glucose and insulin to the same extent as in the female mice, there was no reduction in plasma IL-6, TNFα or PGE2 levels, or in the Ki67 proliferation index in prostate lesions. Based on immunohistochemistry studies with antibodies to 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), carnitine palmitoyltransferase Ia (CPT1a) and fatty acid synthase (FAS), it is likely that this difference in response of the two cancer types to this low-CHO diet reflects differences in the glucose dependence of breast and prostate cancer, with the former being highly dependent on glucose for energy and the latter being more dependent on fatty acids.
Assuntos
Neoplasias da Mama , Dieta com Restrição de Carboidratos , Óleos de Peixe , Neoplasias da Próstata , Proteínas de Soja , Animais , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Dinoprostona , Feminino , Óleos de Peixe/administração & dosagem , Glucose , Insulina , Interleucina-6 , Antígeno Ki-67 , Masculino , Camundongos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/prevenção & controle , Proteínas de Soja/administração & dosagem , Fator de Necrose Tumoral alfaRESUMO
We recently found that a diet composed of 15% of total calories as carbohydrate (CHO), primarily as amylose, 35% soy protein and 50% fat, primarily as fish oil (FO) (15%Amylose/Soy/FO) was highly effective at preventing lung nodule formation in a nicotine-derived nitrosamine ketone (NNK)-induced lung cancer model. We asked herein whether adopting such a diet once cancers are established might also be beneficial. To test this, NNK-induced lung nodules were established in mice on a Western diet and the mice were then either kept on a Western diet or switched to various low CHO diets. Since we previously found that sedentary mice develop more lung nodules than active mice, we also compared the effect of exercise in this cancer progression model. We found that switching to a 15%Amylose/Soy/FO diet reduced lung nodules and slowed tumor growth with both 'active' and 'sedentary' mice. Ki67, cleaved caspase 3 and Terminal Deoxynucleotidyl Transferase-Mediated dUTP Nick End Labeling assays suggested that the efficacy of the 15%Amylose/Soy/FO in lowering tumor nodule count and size was not due to a reduction in tumor cell proliferation, but to an increase in apoptosis. The 15%Amylose/Soy/FO diet also significantly lowered liver fatty acid synthase and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 expression, pointing to a global metabolic switch from glycolysis to fatty acid oxidation. Mice fed the 15%Amylose/Soy/FO diet also had significantly reduced plasma levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor α. These results suggest that the 15%Amylose/Soy/FO diet may slow tumor growth by suppressing proinflammatory cytokines, inducing a metabolic switch away from glycolysis and inducing apoptosis in tumors.
Assuntos
Dieta com Restrição de Carboidratos/métodos , Óleos de Peixe , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/prevenção & controle , Proteínas de Soja , Amilose , Animais , Apoptose , Carcinógenos/toxicidade , Caspase 3/metabolismo , Citocinas/metabolismo , DNA Nucleotidilexotransferase , Ácido Graxo Sintases/metabolismo , Ácidos Graxos/metabolismo , Feminino , Glicólise , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/metabolismo , Fígado/enzimologia , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos , Neoplasias Experimentais , Nitrosaminas/toxicidade , Oxirredução , Fator de Necrose Tumoral alfa/metabolismoRESUMO
A 10-year-old female spayed German Shepherd dog, with a year-long history of recurrent left ear infections, was presented for progressive ataxia, head tilt, and pain on opening of the mouth. On physical examination, a large amount of ceruminous debris was present in the left ear and multiple neurologic defects localizing to the cerebellum and vestibular system were identified. Magnetic resonance imaging (MRI) demonstrated a minimally contrast-enhancing mass within the left bulla, an intracranial space-occupying, heterogeneously contrast-enhancing lesion at the level of the left cerebello-medullary junction, and contrast enhancement of the ipsilateral meninges. Cerebrospinal fluid analysis revealed a marked mixed cell pleocytosis (nucleated cell count 655 cells/µL). The mass was visualized within the horizontal ear canal by otoscopic examination and a biopsy was taken. Impression smears of the biopsy contained many anucleate keratinized squamous epithelial cells, mild mixed inflammation, and few presumptive fibroblasts. With the provided clinical history and MRI findings, a cytologic diagnosis of cholesteatoma was made. A ventral bulla osteotomy was performed, and histopathologic examination of resected tissue confirmed the cytologic diagnosis of cholesteatoma. The dog's clinical symptoms improved postoperatively, but the dog died of unrelated causes, 3.5 months later. To our knowledge, this is the first description of the cytologic features of a cholesteatoma, which is a nonneoplastic, but locally invasive epidermoid cyst, in the middle ear of dogs.
Assuntos
Colesteatoma/veterinária , Doenças do Cão/patologia , Meningoencefalite/veterinária , Otite Externa/veterinária , Animais , Colesteatoma/complicações , Colesteatoma/patologia , Doença Crônica , Cães , Meato Acústico Externo/patologia , Orelha Média/patologia , Feminino , Imageamento por Ressonância Magnética/veterinária , Meningoencefalite/complicações , Meningoencefalite/patologia , Osteotomia/veterinária , Otite Externa/complicações , Otite Externa/patologia , Período Pós-OperatórioRESUMO
The murine femoral intramedullary injection model is frequently used to examine the in vivo effects of biomaterials or cancer cells. The surgical technique includes a knee arthrotomy with patellar dislocation for intramedullary access. This study examined a less invasive surgical approach of direct injection of particles via the transpatellar tendon without patellar dislocation. By using polymethylmethacrylate injection and microCT scan, we found that, compared with the traditional technique, this new approach was more reproducible, less time consuming, and achieved identical volumes of intramedullary injections. Animal morbidity and the biomechanics of the joints were also improved as a result of the simplified procedure. Furthermore, our study suggested that an intramedullary volume in excess of 10 microL can lead to major vascular filling and so should be avoided.