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1.
The PI3K/AKT/PTEN pathway is involved in the pathogenesis of several human cancers. This study investigated the biological and prognostic value of PI3K/AKT/PTEN pathway dysregulation in feline mammary tumours. Expression of p-AKT, HER2, PTEN and steroid receptors was assessed by immunohistochemistry (IHC) in 27 malignant and 12 benign mammary tumours from 39 female cats followed up over a 24-month period. Feline mammary carcinoma (FMC) cell lines were analyzed by Western blot and the feline AKT gene sequence was characterized. p-AKT expression statistically correlated with tumour malignancy, histological dedifferentiation and clinical recurrence. The animals with tumours expressing p-AKT had a shorter disease-free period than those with p-AKT-negative tumours. AKT activation was associated with HER2 expression and PTEN down-regulation, as occurs in human breast cancer, and feline AKT sequencing showed high homology with the human AKT gene. No AKT activation was observed in relation to either oestrogen receptor α (ERα) or progesterone receptor expression. Taken together, these data offer an explanation for AKT signalling and its role in FMC pathogenesis and prognosis, shedding new light on similarities between feline mammary tumours and hormone-independent breast cancer.  相似文献   

2.
The diversion of pancreatic juice and bile stimulates pancreatic exocrine secretion but the mechanism behind this process is still not clear. The present study investigates the influence of long lasting (10 h) bile diversion or pancreatic juice and bile diversion on the pancreatic secretion in conscious pigs. The experiments were performed on 4 weaned piglets, which had a catheter inserted to the accessory pancreatic duct and bile duct and two cannulas to the duodenum. The depletion of bile alone or both bile and pancreatic juice (PJ) resulted in an increased preprandial pancreatic juice outflow, as compared to controls. Bile diversion increased the pancreatic response to feeding. PJ volume, protein outflow, and trypsin activity values were significantly higher in bile diverted pigs than in control pigs during the prandial and postprandial periods. While in pancreatic juice and bile diverted piglets the PJ protein outflow and trypsin activity slightly increased in response to feeding, their values were lower than those of the control piglets. In conclusion, both pancreatic juice and bile present in the small intestine play an important role in the regulation of the pancreatic juice secretion.  相似文献   

3.
The methanol extract from the leaves of Petasites japonicus Maxim (PJ) was studied for its (anti-)mutagenic effect with the SOS chromotest and reverse mutation assay. The (anti-)carcinogenic effects were evaluated by the cytotoxicity on human cancer line cells and by the function and the expression of gap junctions in rat liver epithelial cell. PJ extracts significantly decreased spontaneous β-galactosidase activity and β-galactosidase activity induced by a mutagen, ICR, in Salmonella (S.) typhimurium TA 1535/pSK 1002. All doses of the extract (0.08-100 mg/plate) decreased the reversion frequency induced by benzo (α)pyrene (BaP) in S. typhimurium TA 98. It decreased not only the spontaneous reversion frequency but also that induced by BaP in S. typhimurium TA 100. PJ extract showed greater cytotoxic effects on human stomach, colon and uterus cancer cells than on other cancer cell types and normal rat liver epithelial cells. Dye transfers though gap junctions were significantly increased by PJ extracts at concentrations greater than 200 µg/mL and the inhibition of dye transfer by 12-O-tetradecanoylphorobol-13-acetate (TPA) was obstructed in all concentrations of PJ. PJ significantly increased the numbers of gap junction protein connexin 43, and increased the protein expression decreased by TPA in a dose-dependent manner. Based on these findings, PJ is suggested to contain antimutagenic and anticarcionogenic compounds.  相似文献   

4.
Effects of estrogen and progesterone on the first abdomino-inguinal mammary gland and the associated blood vessels in ovariectomized mice were investigated morphometrically, and light and electron microscopically. Although there were no significant differences in the area of the fat pad of the mammary gland among the experimental groups, the area of the mammary parenchyma and diameters of the blood vessels supplying the mammary gland, i.e., A. et V. circumflexa ilium profunda and A. et V. epigastrica caudalis superficialis, reached the maximal value in ovariectomized mice treated with estradiol (E) + progesterone (P). Similarly, the blood capillaries around buds and ducts of the mammary gland were most densely distributed in E + P treated mice. In the adipose tissues of the mammary stroma in intact mice, fat cells were of multilocular type in the peripheral regions around the main vessel, and of unilocular type in the other part. In E and E + P treated mice, however, fat cells were mostly of unilocular type. These findings suggest that the formation of mammary fat tissues may occur in advance of that of the mammary parenchyma. By TEM, epithelial cells of the mammary parenchyma contained a large number of mitochondria and ribosomes, well-developed Golgi apparatus and rER, and large lipid droplets. Endothelial cells of blood capillaries displayed numerous pinocytotic vesicles, longer marginal folds and microvillous processes. Each organelle in these two cell types increased in number or developed to a greater degree in E + P treated mice than the other experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

5.
In a closed pig breeding and finishing herd suffering from sarcoptic mange, two selected groups of pigs were filmed during a period of 10 days before and after treatment. The observation always commenced each hour and lasted for 15 min. Before treatment, observations was done round the clock, after treatment from 8:00 to 22:15.

Before treatment the pens were stocked with 11 (pen A) and 10 (pen B) growing pigs (Large White × Landrace sows; 5 months old) with an average weight of 70 kg examined for sarcoptic mange by skin scrapings and ELISA. The animals had never been treated with an acaricide or endectocide before.

After 10 days, the pigs were treated twice (18 days interval) with Dectomax® 1% solution for pigs (Pfizer, Austria) at a dose of 0.3 mg Doramectin i.m./kg body weight. After treatment, seven pigs were observed in both pens.

Most scratching actions both before (83.1%) and after (94.5%) treatment were of one to 10 s. After treatment, the 10 s-scratching episodes decreased by 67.3% (from 21.2 to 6.9 mean SRE/pig), and the scratching actions of longer than 10 s by 91.7% (from 4.3 to 0.4 mean SRE/pig), such that the latter could be observed only occasionally after treatment.

A distinct increase in scratching activity both before and after treatment could be observed primarily between 10:00 and 15:00. Significant differences of scratching and rubbing activity between before and after treatment could also be seen at midday.

The interpretation of the scratching index values before and after the treatment were carried out according to Cargill et al. [Cargill, C., Davies, P., Carmichael, I., Hooke, F., Moore, M., 1994. Treatment of pigs with doramectin to control sarcoptic mange. Proceedings of the 13th IPVS Congress, Bangkok, Thailand, p. 238] with the maximum and minimal limiting values specified in the literature, and compared with calculations using the method described by Hollanders et al. [Hollanders, W., Harbers, A.H.M., Huige, J.C.M., Monster, P., Rambags, P.G.M., Hendrikx, W.M.L., 1995. Control of Sarcoptes scabiei var. suis with ivermectin: influence on scratching behaviour of fattening pigs and occurence of dermatitis at slaughter. Vet. Parasitol. 58, 117–127].

Depending on the methods used and the limiting values set, 6.7–34.6% of the observations before and 2.0–17.3% of the observations after treatment revealed a “strong evidence of mange” or a “suspicion of mange”. All other observations indicated that the pigs were free from mange.  相似文献   


6.
7.
Introduction:  Mycobacterial cell wall‐DNA complex (MCC) is a bifunctional anticancer agent that induces cancer cell apoptosis and stimulates cytokine synthesis by immune cells. Intravesical MCC is currently being evaluated in humans with high‐grade urinary bladder cancer. Evaluation of MCC in dogs with transitional cell carcinoma (TCC) will allow mechanistic studies in a natural animal model of TCC, and a potentially beneficial therapy for dogs with this cancer. In this study, we have determined the anticancer activity of MCC against canine TCC cells in vitro .
Methods:  Canine TCC cells (K9TCC cell line) were incubated with MCC (0.05–100 μg/ml, 0.5–72 hours). Cellular proliferation was measured by MTT reduction. Cell cycle was analyzed by flow cytometry with propidium iodide. Apoptosis was identified by flow cytometry using anti‐active‐caspase‐3/PE and anti‐cleaved‐PARP/FITC antibodies. Apoptosis‐inducing activity of 100 μg/ml MCC in combination with piroxicam (0.1–1.0 uM) was evaluated.
Results:  MCC inhibited K9TCC cell proliferation in a concentration‐dependent manner (maximal activity – 45% at 100 μg/ml MCC) in association with the presence of activated caspase‐3 and cleaved PARP. Inhibition of proliferation and apoptosis‐inducing activities of MCC were independent of cell cycle phase. A thirty‐minute exposure of MCC was sufficient for optimal activity. Piroxicam (0.5 uM) enhanced apoptosis‐inducing activity of MCC.
Conclusions:  MCC induces apoptosis in K9TCC cells. This activity is potentiated by piroxicam. Following positive results in vitro , in vivo studies have been initiated. One dog, treated to date, has had a minor reduction in tumor volume following the first course of treatment with no treatment‐related toxicity.  相似文献   

8.
Lactoferrin (Lf) is a multifunctional iron-binding protein that was first identified in mammary secretions, but is synthesized by most mammalian tissues. The protein has a signal sequence that dictates secretion; it also has a nuclear localization sequence that facilitates entry into the cell nucleus. The mechanism of the latter action is currently unknown, but is thought to occur via a Lf receptor. Lactoferrin content of mammary tissue and secretions varies with developmental state; it is synthesized in mammary tissue at high levels during both pregnancy and involution, and during mammary infections. Using fluorescent (FITC)-labeled holo-bLf, we show that bovine primary epithelial cells and MCF-7 breast cancer cells do not translocate the exogenously added Lf to the nucleus after culture in serum free media (SFM). However, the supplementation of SFM with 1 μM all-trans retinoic acid (atRA) caused breast cancer cells to gain the capacity to take up labeled bLf into the cell nucleus. Primary bovine mammary cells (MeBo) exhibited similar capacity in culture. This suggests that in addition to Lf, one or more components modulated by atRA, are necessary for nuclear translocation to occur. Transfection experiments with atRA treated MCF-7 cells containing retinoic acid response element reporter constructs showed that the extracellular application of lactoferrin alters reporter gene expression. Lactoferrin increased a DR5 luciferase response element in a dose-dependent manner only when atRA was applied. Immunocytochemical markers for the cell cycle (Ki67) and apoptotic events (Caspase-3 and PARP-85) showed that lactoferrin alters the atRA-induced phenotype, blocking apoptosis and maintaining cell cycle activity in both MCF-7 and MeBo cells in the presence of 1 μM atRA. We propose that nuclear lactoferrin interacts with retinoic acid signaling pathways in cells and alters/blocks the signals so that cells remain in the cell cycle and/or do not enter the apoptotic pathway.  相似文献   

9.
Silymarin, a naturally acknowledged hepatoprotector used in humans to treat liver diseases has been tested in murine (HC11) and bovine (BME‐UV) mammary epithelial cell lines to evaluate a possible direct effect on cell growth and differentiation in mammary gland. Silymarin enhanced cell proliferation (p < 0.05) from 10 to 1000 ng/ml in association with growth factors, (up to 20%) or alone (up to 15%) versus controls. Furthermore, silymarin (100 ng/ml) was able to increase (p < 0.05) β‐casein gene expression alone or in association with prolactin (5 μg/ml). These effects may be related with protein kinase B (AKT) activation induced by silymarin treatment (p < 0.05) and/or by a dose‐related inhibitory effect (p < 0.05) on caspase‐3 activity related to a protective role in cell apoptosis. These data suggest that silymarin should be considered a candidate to support mammary gland activity during a lactogenetic state.  相似文献   

10.
Introduction   Cowpea (Vigna unguiculata) is a valuable protein source that can contribute towards overcoming a predicted protein deficit equivalent to more than 1 000 000 t oilcake in Southern Africa by the year 2000 (N ell et al. 1992). However, like most other legumes, cowpeas contain antinutritional factors (ANFs) (M akinde et al. 1996). It has also been shown that feeding raw cowpea causes reduced growth and histomorphometric changes in the various segments of the intestine (M akinde et al. 1997) attributable to ANFs. The major ANFs in the cowpea are trypsin inhibitors, tannins and phytates (A letor and A ladetimi 1989). Although the protease inhibitors are found in most legumes, only soybean inhibitors have been thoroughly investigated (L iener and K akade 1980), and trypsin inhibitors in other legumes have received little attention.  相似文献   

11.
12.
Invasive micropapillary carcinoma (IMC) is a variant of infiltrating ductal carcinoma of the breast associated with poor outcome. In this study, we report 16 carcinomas of the feline mammary gland displaying histologic features that correspond to IMC of the breast in women. The clinicopathologic findings, overall survival time, disease-free survival time, and nuclear DNA content of these cats were compared with 65 more common invasive mammary carcinomas (other feline mammary carcinoma [FMC]) of nonspecified type. IMC was associated with larger tumor size, higher histologic grade (P < .0001), deeper muscle invasion (P = .004), and more frequent lymphovascular invasion and nodal metastases (P = .009 and P = .001, respectively) than other FMCs. The aneuploid pattern was more frequent in IMC lesions. IMCs were also associated with lower survival rates. In summary, all cases of feline IMC were associated with clinicopathologic features of high biologic aggressiveness and should be classified as independent histologic types of FMC.  相似文献   

13.
Routine examination of milk was performed on five herds of lactating goats in northern Italy as part of a milk quality-monitoring program in the year 2000. As part of the study, aseptic samples of foremilk were collected monthly from both half udders during the entire lactation for 305 goats, resulting in a total of 4571 samples. The samples were tested with cytological and bacteriological analyses to evaluate the relationship between mammary infections and somatic-cell count (SCC; Fossomatic (TM) method). Prevalence of intramammary infection (IMI) was 40.2% (n = 1837) of all udder-half samples examined. The most-prevalent mastitis agents were coagulase-negative Staphylococci (CNS), 80% (n = 1474 udder-half samples); within this group, Staphylococcus epidermidis was the most-prevalent species (38%). Other prevalence were Staphylococcus aureus 6% (n = 112 udder-half samples) and environmental pathogens 14% of infected udder-half samples (n = 251) with a diverse mixture of species, none of which had a frequency of >4%. Enterococcus faecalis was the most-frequently isolated among this group. Neither Salmonella spp. nor Listeria monocytogenes were detected. The risk (sample level) of infection differed across herds, parities, and stage of lactation according to results from logistic multiple regression. Infection was more common among goats in third and fourth parities and during the later stages of lactation. Of the 2734 samples from uninfected udder halves, the mean log2 SCC was 3.9 cell/ml; of the 1837 bacteriological positive samples, the mean log2 SCC was 5.6 cell/ml. According to results from a linear mixed model, concentrations of somatic cells tended to increase with increasing age and days in milk and with the presence of bacteria. Infection with S. aureus was associated with the highest SCS.  相似文献   

14.
This investigation aims to classify, describe and evaluate the sustainability of dairy goat production systems (GPS) in South Spain Sierra de Cadiz. The research took place throughout 25 goat farms during the 2001–2002 campaigns, with the method posed by Masera et al. (1999) [Masera, O., Astier, M., S., López-Ridaura. 1999. Sustentabilidad y manejo de recursos naturales. El marco de evaluación MESMIS (Sustainability and natural resource management. The MESMIS evaluation framework). Mundi-Prensa, S.A., Gira, IE-UNAM, México. 109 pp.] and adapted to animal production systems, as the guideline and framework to evaluate sustainability.

The principal component, namely energy input from grazing (eigenvalue 1.329) which comprises the indicators total area per goat (factorial value 0.664) together with net energy obtained from grazing (factorial value 0.903) allowed to differentiate significantly between semi extensive (SES), semi intensive (SIS) and intensive (IS) goat production systems.

Intensification of the GPS tends to be inefficient, especially in terms of net margin per litre of milk produced (p < 0.05). A higher degree of adaptability of IS (64.8%) derives from a higher investment on new production strategies. Likewise, higher self-management capacity of SES (60.9%) fosters standards of productivity (76.0%) and stability (42.9%). The SIS presented the highest equity values (67.8%).

On the whole, sustainability of GPS tends to decrease as the degree of intensification increases: SES = 57.3%; SIS = 55.7% and IS = 53.1%. The reduction of the dependency on external input alongside with the optimization of natural resources management would surely improve the standard of sustainability.  相似文献   


15.
目的通过给SD大鼠灌喂石榴汁,研究其体重增加和粪便及盲肠内容中鞣花酸及尿石素A含量,为深层次研究鞣花酸及尿石素A的生物学作用提供数据支持。方法选择24只平均体重为(169.08±7.88)g的雄性SD大鼠,随机分为3组,每组8只,分别为对照组、试验Ⅰ组和试验Ⅱ组。在相同日粮基础上,试验Ⅰ组大鼠每天每只灌喂1.5 mL石榴汁,试验Ⅱ组大鼠每天每只灌喂3.0 mL石榴汁,并获取大鼠体重数据及采集粪便及盲肠内容物样品。结果①试验Ⅱ组大鼠日增重显著(P<0.05)高于对照组,比对照组高36.32%;②灌喂石榴汁显著(P<0.05)增加大鼠粪便鞣花酸和尿石素A的含量;③灌喂石榴汁后,试验Ⅰ组和试验Ⅱ组大鼠盲肠中鞣花酸和尿石素A的含量均极显著(P<0.01)高于对照组。结论给大鼠灌喂石榴汁可以显著提高大鼠体重,显著或极显著提高大鼠粪便和盲肠内容中鞣花酸和尿石素A的含量,且灌喂3 mL/(只·d)效果最佳。  相似文献   

16.
Introduction:  Canine malignant melanoma (CMM) is an aggressive neoplasm treated with surgery and/or fractionated RT; however, metastatic disease is common and chemoresistant. Preclinical and clinical studies by our laboratory and others have shown that xenogeneic DNA vaccination with tyrosinase family members can produce immune responses resulting in tumor rejection or protection and prolongation of survival. The potency of DNA vaccines can be further enhanced by adding DNA encoding cytokine genes. We have shown in preclinical mouse models that GM‐CSF DNA enhances immune responses and tumor protection. These studies provided the impetus for murine tyrosinase (muTyr) ± human GM‐CSF (huGM‐CSF) DNA vaccination in CMM.
Materials & Methods:  Two groups of five dogs each with advanced (WHO stage II‐IV) CMM received four biweekly IM injections (100 ug or 500 ug, respectively/vaccination) of plasmid DNA encoding muTyr via the Biojector2000 jet delivery device. Subsequently, three groups of nine dogs each with advanced CMM received four biweekly IM injections of plasmid DNA encoding muTyr (50 ug), huGM‐CSF (3 dogs each at 100/400/800 ug) or both.
Results:  Minimal to mild pain was noted on vaccination and no toxicity or induction of autoimmunity was seen. The KM median survival time was 224 days (100/500 ug muTyr), 278 days (50 ug muTyr), 140 days (huGM‐CSF) and >265 days (muTyr & huGM‐CSF; 6 dogs still alive).
Conclusions:  The results of these trials demonstrate that xenogeneic DNA vaccination continues to be a safe and potentially therapeutic modality for CMM. These results also warrant further evaluation of this novel therapeutic in a Phase II setting.  相似文献   

17.
Energy balance of conjugated linoleic acid-treated pigs   总被引:2,自引:0,他引:2  
The term conjugated linoleic acid (CLA) refers to a group of linoleic acid derivatives whose conjugated double-binding system begins at the carbon atom 8 to 11. This means that including the cis-trans geometry, 16 isomers are possible in theory. CLA occurs primarily in lipids of ruminants because polyunsaturated fatty acids can be converted to CLA in the rumen of these animals through the action of bacterial enzymes (Kepler et al. 1966). The most widely occurring isomer is C18 : 2 c 9, t 11, which is present in milk and dairy products in concentrations of 0.4–1.7% (Fritsche and Steinhart 1998). But CLA was also generated in the colon of rats fed a diet containing free linoleic acid (Chin et al. 1994b). In animal experiments CLA inhibits carcinogenesis and reduces the development of arteriosclerosis (Ip et al. 1994; Belury 1995; Jahreis and Bochmann 1998), and was found to have a specific influence on body composition. In experiments with mice, pigs and chicks a negative effect of CLA on the accumulation of body fat was observed (Pariza et al. 1996; Dugan et al. 1997; Park et al. 1997; West et al. 1998). The effective dose in those experimental diets was 0.5 to 1.5% CLA. In contrast, CLA may also act as a growth factor and increased daily weight gains of rats (Chin et al. 1994a). However, in these trials on changes in body composition the feed intake was not controlled and the observed effects may be due at least partially to differences in feed intake between the control group and the CLA animals. The objective of the present study was to investigate the influence of CLA on thermogenesis and energy balance in animals with an isoenergetic feed intake by using the methodology of the calorimetric balance technique. The animals used in the model were adult sows with a nutritional status approaching equilibrium.  相似文献   

18.
Two experiments were conducted to assess whether feeding level in the period from weaning to puberty can affect the amount of mammary tissue at puberty. Four female pigs from eight (exp. 1) to ten (exp. 2) litters were allocated to four treatment groups within litter. From day 28 to 90 of age (period 1) and from day 90 to slaughter, at approximately 5 1/2 months of age (period 2), the gilts were given either ad libitum or restrictive access to feed in a 2 × 2 factorial arrangement. Neither the amount of dissected mammary tissue nor the amounts of DNA or RNA were affected by feeding regime in period 1. However, ad libitum feeding in period 2 gave rise to more dissected mammary tissue (52%, P < 0.0001), RNA (37%, P = 0.006) and DNA (28%, P = 0.005) compared to restricted feeding. Cyclicity gave rise to increases in mammary DNA (P = 0.05) and RNA (P = 0.02). There were no clear correlations between mammary measures and plasma IGF-I or IGF-binding proteins. It is concluded that a high feeding level from three months of age to puberty has a stimulatory effect on mammary development in prepubertal gilts.  相似文献   

19.
Of the 120 cases of mammary cancer occurring in 117 female dogs (15 spayed), 2 male dogs, and 1 dog of undetermined sex, 107 (nearly 90%) were observed in dogs 8 to 15 years old. Mammary tumors occurred in nearly 14% of 875 female dogs with neoplasms. Nearly 60% of 128 neoplasms were located in the 4th and 5th mammary glands. Of the 128 cancers in these 120 dogs, 85 were classified as duct carcinoma, 38 as lobular carcinoma, 3 as malignant mixed tumor, and 2 as duct and lobular carcinomas. Most duct carcinomas originated in the epithelial cells of ducts at all levels, and a few arose in previously benign duct papillomas. The lobular carcinomas arose in alveoli and developed into progressively larger lobules. A negative factor in the development of mammary cancer is ovariectomy before or shortly after the first estrous cycle in the dog and before the age of 40 in women. In both dog and man, aging is a positive factor in the development of mammary cancer. In women, other positive factors are nulliparity and inheritance; e.g., a high rate of breast cancer in close female relatives of Jewish extraction. An epidemiologic study of breast cancer in man and dog in high-risk countries(e.g., United States) and low-risk countries (e.g., Japan) is indicated.  相似文献   

20.
Growth is a very complex physiological process and is controlled by many genes and therefore easy to manipulate by selective breeding. Such manipulation of growth was realized by long-term selection of laboratory mice for different growth parameters (body weight, total protein amount in the carcass and an index combining body weight and endurance fitness) resulting in a high phenotypic and genetic differentiation compared to the nonselected control (Bünger et al. 1983, 1992, 1994; Renne et al. 1995). After 70 generations the 42-day body weights increased from 28 g at the start of selection to 58.3 g, 51.9 g and 47.4 g in these lines, respectively (Bünger et al. 1994). At the same time the carcass protein content increased from 2.92 to 5.23 g in the line selected for protein mass without an increase of fat percentage up to the age of 42 days (Renne et al. 1995). In comparison with that, selection for body weight was accompanied by a marked increase of fat percentage up to this age as reported in literature for many long-term selection experiments. Because of the different chemical composition of the body gain at relatively small differences in growth rate, these selected lines seemed to be suitable models for studying some aspects of energetic efficiency of growth. The results of a former experiment conducted in generations 32–42 suggested a higher efficiency of energy utilization in the line selected for body weight than in the other selected lines (Bünger et al. 1987). The objective of the present study was to characterize the energy metabolism of these different selected lines complementary to the studies on protein metabolism given by Schadereit et al. (1997, 1998).  相似文献   

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