Monocarboxylate transporters (MCTs) support tumour growth by regulating the transport of metabolites in the tumour microenvironment. High MCT1 or MCT4 expression is correlated with poor outcomes in human patients with head and neck squamous cell carcinoma (HNSCC). Recently, drugs targeting these transporters have been developed and may prove to be an effective treatment strategy for HNSCC. Feline oral squamous cell carcinoma (OSCC) is an aggressive and treatment‐resistant malignancy resembling advanced or recurrent HNSCC. The goals of this study were to investigate the effects of a previously characterized dual MCT1 and MCT4 inhibitor, MD‐1, in OSCC as a novel treatment approach for feline oral cancer. We also sought to determine the potential of feline OSCC as a large animal model for the further development of MCT inhibitors to treat human HNSCC. In vitro, MD‐1 reduced the viability of feline OSCC and human HNSCC cell lines, altered glycolytic and mitochondrial metabolism and synergized with platinum‐based chemotherapies. While MD‐1 treatment increased lactate concentrations in an HNSCC cell line, the inhibitor failed to alter lactate levels in feline OSCC cells, suggesting an MCT‐independent activity. In vivo, MD‐1 significantly inhibited tumour growth in a subcutaneous xenograft model and prolonged overall survival in an orthotopic model of feline OSCC. Our results show that MD‐1 may be an effective therapy for the treatment of feline oral cancer. Our findings also support the further investigation of feline OSCC as a large animal model to inform the development of MCT inhibitors and future clinical studies in human HNSCC. 相似文献
Imbalanced fertilizer use with intensive cropping has threatened the sustainability of agroecosystems, especially on acid soils. An understanding of the long-term effects of fertilizers and amendments on soil health is essential for sustaining high crop yields. The effects of application of fertilizers, and amendments for 46 years on soil properties and maize yield in an acid Alfisol were investigated in this study. Ten fertilizer treatments comprising different amounts of NPK fertilizers, farmyard manure (FYM) and lime, and one control, were replicated three times in a randomized block design. At 0–15 cm soil depth, bulk density was least (1.20 t/m3), porosity (49.8%) and water holding capacity (61.7%) were greatest in 100% NPK + FYM, corresponding to the largest organic carbon content (13.93 g/kg). Microbial biomass C and dehydrogenase activity in 100% NPK + FYM were 42% and 13.7% greater than 100% NPK, respectively. Available nutrients were significantly more with 100% NPK + FYM and 100% NPK + lime than control and other fertilizer treatments. At 15–30 cm depth, the effect of various treatments was comparable to the surface layer. Grain yield declined by 55% and 53% in 100% NPK(-S) and 100% NP, respectively, compared with 100% NPK, whereas 100% N as urea alone eventually led to crop failure. Soil porosity recorded the greatest positive correlation (r = .933**), whereas bulk density recorded a negative significant correlation (r = −.942**) with grain yield. The results suggest that integrated use of FYM/lime with chemical fertilizers is a sustainable practice in terms of crop yield and soil health, whereas continuous application of urea alone is detrimental to the soil health. 相似文献
Biology and Fertility of Soils - Sorption is an important process for retention of organic carbon (C) in soils. The effect of Na+ and Ca2+ on sorption of organic C has been studied in salt-affected... 相似文献
Changes in the somatosensory evoked potentials (SEPs) and spontaneous electroencephalogram (EEG) in hens were investigated during stunning with a mixture of 30 per cent carbon dioxide in argon with 5 per cent residual oxygen. The results showed that the SEPs were lost on average in 17 seconds (maximum 28 seconds), which is similar to the 19 seconds (maximum 32 seconds) reported while stunning hens with a mixture of 30 per cent carbon dioxide in argon with 2 per cent residual oxygen. The spontaneous EEG showed suppression and a quiescent phase at 14 and 58 seconds, respectively. It is concluded that a mixture of 30 per cent carbon dioxide in argon with 2 per cent residual oxygen would be ideally suited for batch stunning chickens and any inadvertent increase in the residual oxygen level up to 5 per cent in the stunning atmosphere would not lead to inadequate stunning or recovery of consciousness before neck cutting. 相似文献
1. The aim of the experiment was to investigate the effect of gaseous stunning methods on the carcase and meat quality of broilers (dead weight 1.0 to 2.3 kg) in comparison with electrical stunning.
2. Two replicates of broilers (age 54 and 59 d respectively) were stunned in carbon dioxide, in argon or by electric current, and the carcases were plucked either by a mechanical plucker or by hand.
3. Carcase and meat quality were evaluated to determine the effect of these stunning treatments and plucking methods. The quality factors measured included pH at 20 min post‐mortem, ultimate pH, texture and colour of the pectoralis major muscle, and the incidence of carcase appearance defects, cooking loss, broken bones and bruises in the breast and leg muscles.
4. Stunning method had a significant effect on pH at 20 min, ultimate pH, texture and colour of breast meat. Plucking method had a significant effect on the cooking loss and texture.
5. Argon stunning resulted in fewer muscle haemorrhages, a more rapid early post‐mortem fall in pH and more tender breast meat than in the electrically stunned broilers; carbon dioxide stunned broilers had intermediate values for pH decline and meat tenderness but were not significantly different from argon stunning regarding muscle haemorrhages.
6. Appearance defects occurred to a similar extent in all the stunning methods and mechanical plucking resulted in 4 times as many defects compared with hand plucking; the incidence of broken bones was higher in mechanically plucked broilers than in hand plucked carcases.
7. Gaseous stunning of broilers produced relatively better quality carcases and meat than electrical stunning, and therefore may have commercial advantages. 相似文献
1. Twenty four 22 week‐old large stags were stunned using one of two methods, argon‐induced anoxia (2% residual oxygen) or an electric current (150 mA per bird, 50 Hz). The birds were processed under commercial conditions and carcasses held at 3°C until the breast muscles were filleted at either 3 h after killing or after overnight maturation.
2. The meat samples were frozen at — 40° C and stored at — 20°C until they were thawed at 1°C and cooked at 85°C. They were subjected to sensory evaluation by 10 experienced assessors and instrumental texture measurements were made.
3. Only stunning method had significant effects on the sensory profile and instrumental texture. Breast meat from anoxia‐stunned turkeys was less firm on cutting, more tender and had a more powdery residue on eating than that from electrically‐stunned turkeys. The instrumental texture values confirmed that breast meat from anoxia‐stunned turkeys was more tender than that from the electrically‐stunned turkeys.
4. There was no significant correlation between the subjective tenderness rating and the instrumental texture value.
5. Principal components analysis showed that 59% of total variation was explained by the first two dimensions, the first being a contrast between turkeys that were tender and powdery and those that were firmer and fibrous. When values from individuals were plotted, this dimension was related to the differences between anoxia and electrical stunning, with anoxia‐stunned turkeys at the tender end of the first dimension. 相似文献
1. Eighty broilers were stunned with anoxia (< 2% oxygen) induced by argon and after evisceration, at 20 min post‐mortem, the carcases were chilled in slushed ice for 30 min. Twenty breasts were filleted at each time 1, 2, 3 and 24 h post‐mortem and aged overnight at 1°C.
2. An additional 40 broilers were stunned either by anoxia or by constant current electrical stunning (107 mA 50Hz) and their eviscerated carcases held overnight at 1°C prior to filleting at 24 h postmortem.
3. All the breast muscles (pectoralis major) were cooked at 24 h postmortem and their texture measured. The results indicated that the mean texture of breasts from the different stunning and filleting time treatments were similar, and there were no significant differences between them.
4. It is concluded that stunning with anoxia followed by a rapid chilling would enable the broiler carcases to be filleted at 1 h postmortem with no adverse effect on the texture of the meat. 相似文献