A low-carbohydrate diet containing soy protein and fish oil reduces breast but not prostate cancer in C3(1)/Tag mice.

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.

Low carbohydrate diets containing soy protein and fish oil slow the growth of established NNK-induced lung tumors.

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.

Cholesteatoma and meningoencephalitis in a dog with chronic otitis externa.

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.

Mouse femoral intramedullary injection model: technique and microCT scan validation.

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.

Modulation of allograft incorporation by continuous infusion of growth factors over a prolonged duration in vivo.

Morselized cancellous allograft bone is frequently used in the reconstruction of bone defects in cases of revision total joint replacement, trauma, spine fusion and treated infection. However, the initial lack of viable bone cells in morselized allograft bone significantly slows the process of graft incorporation compared to autograft bone. This study examined the effects of prolonged local infusion of the growth factors bone morphogenic protein-7 (BMP-7 or OP-1) and fibroblast growth factor-2 (FGF-2 or basic FGF) in the process of allograft incorporation using a rabbit tibial chamber model. New bone formation was evaluated by two indices, the activity of alkaline phosphatase and the level of birefringence. The markers of osteoclast-like cells were also measured. Without the infusion of the growth factors, lower levels of new bone formation were observed in the allograft group, compared to the autograft group. Infusion of growth factors FGF-2 and OP-1, singly or in combination, for 4 weeks, diminished this difference. The numbers of osteoclast-like cells were much higher in the allograft group before the growth factors were delivered. The infusion of FGF, singly, diminished this difference. However, the infusion of OP-1 or the combination of FGF and OP-1 did not decrease the number of osteoclast-like cells to a level comparable to autograft only. Local infusion of growth factors appears to be a useful adjunct to promote the incorporation of allograft bone in vivo.