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1.
Metastases are the crucial factor for the prognosis of canine mammary tumours (CMTs). In women, the peptide hormone relaxin is linked with metastatic breast cancer. Therefore, the impact of relaxin and its receptors on matrix metalloproteinase (MMP) expression, metastatic disease and survival was analysed using qRT‐PCR and immunohistochemistry of CMT samples from 59 bitches. The expression of relaxin and its receptor RXFP1 (relaxin family peptide receptor 1) was discovered on gene and protein levels. Intratumoural relaxin mRNA expression and relaxin plasma levels had no prognostic value. High mRNA levels RXFP1 were an independent marker of metastatic potential, with a more than 15‐fold risk increase, and a predictor for shorter survival. Also, MMP‐2 expression was associated with early death because of CMT. The mRNA expressions of relaxin, RXFP1 and MMP‐2 were positively correlated indicating a common pathogenetic linkage. Thus, RXFP1 is proposed as a new early marker of metastatic potential in CMT and a possible therapeutic target.  相似文献   

2.
The biological implication of the growth hormone/insulin like growth factor-I (GH/IGF-I) axis in canine mammary tumours (CMT) has been recently demonstrated, however its clinical and prognostic implications are unknown. Our aim was to investigate its prognostic significance.Hormonal determinations were done by enzyme immunoassays techniques validated for canine species in serum and tumour tissue from 32 bitches with CMT and in serum and normal mammary tissue from 10 controls. Serum and tissular GH and IGF-I concentrations were significantly higher in the case of malignant tumour compared with benign and controls. GH and IGF-I elevated concentrations were significantly associated with tumour relapse and/or metastases during follow-up and in dogs with reduced survival times; however these parameters were not independent prognostic factors in multivariate analysis. This association demonstrates a link between high serum and intratumoural GH and IGF-I concentrations and a worse prognosis and opens the possibility to new anticancer endocrine therapies in dogs.  相似文献   

3.
The involvement of epidermal growth factor receptor (EGFR) is well established in human breast cancer, however, in canine mammary tumours (CMT), including inflammatory mammary carcinomas (IMC), still needs to be clarified. Enzyme immune assay techniques were used for EGFR determinations in tumour tissue from 45 bitches with CMT and in normal mammary glands from eight control dogs. Higher tissue EGFR levels were found in CMT compared with controls (P < 0.05). In malignant CMT, tissue EGFR elevated concentrations were statistically significantly associated with tumour relapse and/or distant metastasis during follow‐up and with reduced disease‐free and overall survival times. The IMC cases had the highest tissue EGFR levels compared with other malignant non‐IMC tumours (P < 0.001). The results support the hypothesis that EGFR levels influence prognosis in malignant CMT, suggesting that EGFR may represent a therapeutic target in cases of high histological aggressiveness and especially in cases of metastatic phenotype and poor prognosis.  相似文献   

4.
The aim of this study was to evaluate the possible association between hormonal changes that occur during oestrus and biomarkers related with glucose metabolism (glucose and insulin), lipid metabolism (lipidic profile and BChE) and adipokines (adiponectin and ghrelin) in healthy bitches. For this purpose, we measured these analytes in serum of bitches, at two times: before (T1) and after (T2) the LH peak that were established according to progesterone concentrations. Increased levels of total cholesterol (p < 0.01), high density lipoprotein cholesterol (HDL‐C) (p < 0.01), low density lipoprotein cholesterol (LDL‐C) (p < 0.01), adiponectin (p < 0.01) and ghrelin (p < 0.05) were observed at T2 in comparison with T1. No statistically significant changes were observed in serum glucose, insulin, homoeostasis model assessment for insulin sensitivity (HOMA), triglycerides and BChE. When all data of T1 and T2 were pooled, serum adiponectin showed positive correlation with progesterone (r = 0.353; p = 0.022) and HDL‐C (r = 0.307; p = 0.048), and negative with insulin (r = ?0.429; p = 0.005), HOMA (r = ?0.446; p = 0.003) and BChE (r = ?0.522; p < 0.001). Ghrelin showed negative correlation with estradiol (r = ?0.701; p = 0.004). BChE was negatively correlated with estradiol (r = ?0.441; p = 0.018) and glucose (r = ?0.343; p = 0.028), and positively with insulin (r = 0.460; p = 0.003) and HOMA (r = 0.505; p < 0.001). In conclusion, changes in metabolic biomarkers occur in bitches after LH peak, characterized by increased lipids (total cholesterol, HDL cholesterol and LDL cholesterol) without changes in BChE activity, and increased adiponectin and ghrelin concentrations, without significant changes in glucose and insulin.  相似文献   

5.
A non-pharmaceutical, dietary option may be useful to manage clinical pseudopregnancy (PSP). To describe the effect of short-term food restriction on canine PSP, 16 privately owned, overtly pseudopregnant bitches were randomly assigned to one of the following groups: Limit-fed (increasing amounts of a restricted maintenance: 50%, 40%, 30% restriction for 2, 3 and 2 days respectively) during 7 days (n = 8) or Maintenance-fed of the same food and period (n = 8). The bitches were physically examined and blood samples were taken for prolactin and progesterone determinations on days 2, 5 and 8. By day 8, none of the bitches had completely regressed the condition although all (8/8) the animals of the Limit-fed and two (25%) of the Maintenance-fed group improved in condition decreasing mammary size and secretion (p < 0.05). No day or group effects were observed for serum prolactin and progesterone concentrations (>0.05). It is concluded that although an 8-day food restriction did not cure PSP, it seemed to hasten PSP signs involution in these bitches. No endocrine change was related to these clinical findings.  相似文献   

6.
The aim of this study was to describe the changes in the resistance index (RI) and systolic/diastolic ratio ( S / D ) of the uterine arteries during mid-pregnancy abortion induction in the dog. Sixteen 30–35 day pregnant bitches were randomly assigned to either a pharmacological protocol to interrupt gestation (n = 8) or were used as untreated control group (n = 8). Doppler assessments of uterine arteries blood flow were carried out before the initiation of the protocol and then every other day up to abortion (treated group) or parturition (control group). All treated bitches aborted 6 ± 1.2 days after initiation of the treatment (while none of the non-treated bitches aborted). Pre-treatment RI and S / D did not differ between groups (p > 0.2) while average post-treatment indexes were (mean ± SD): 0.62 ± 0.1 vs 0.53 ± 0.1 (p < 0.01) and 2.96 ± 0.9 vs 2.23 ± 0.3 (p = 0.01), for the treated and non-treated group respectively. Correlations between days to abortion and RI or S / D were 0.75 (p < 0.01) and 0.79 (p < 0.01) and, −0.78 (p < 0.01) and −0.73 (p < 0.01) for the treated and non-treated groups respectively. In the treated group, correlations between serum progesterone (P4) concentrations and RI and S / D were −0.76 (p < 0.01) and −0.59 (p < 0.01) respectively. It is concluded that, during induction of abortion, RI and S / D of uterine arteries progressively increased while P4 decreased.  相似文献   

7.
In this study, we have determined the prognostic value of the presence of the micrometastases and metastases greater than 2 mm in the regional lymph nodes for bitches with mammary carcinomas. The study involved 51 dogs diagnosed with a single malignant epithelial tumour in the 4th or 5th mammary gland. All animals underwent regional mastectomy; the 4th and 5th mammary glands were removed together with the inguinal lymph node. The lymph nodes were examined immunohistochemically using the anti-cytokeratin antibody, clone AE1/AE3. The bitches were followed up every 6 months for 2 years after surgery to determine the disease-free survival (DFS) and overall survival (OS). The Kaplan-Meier analysis showed a statistically significant difference in DFS and OS only between the group of bitches without metastases and the group with lymph node metastases greater than 2 mm. No significant differences between these two groups versus bitches with lymph node micrometastases were found.  相似文献   

8.
Gonadotropin-releasing hormone (GnRH) antagonists are particularly useful when a rapid inhibitory effect on the gonadal axis is required. The aim of this study was to test the efficacy and clinical safety of a low and high dose of the third generation GnRH antagonist, acyline, on pregnancy termination in female dogs. The effect of the antagonist on the progesterone (P4) serum concentration was also described. Twenty-one mid-pregnant bitches were randomly assigned to a single subcutaneous (SC) dose of a placebo (PLACE; n = 7), a low (ACY-L; 110 μg/kg; n = 6) or high (ACY-H; 330 μg/kg; n = 8) dose of acyline. The animals were followed up for 15 days. All ACY treated but no placebo-treated animals terminated their pregnancy by abortion (p < 0.01). The ACY-L and ACY-H groups interrupted their pregnancy 7 ± 1.9 and 6.4 ± 1.3   days after treatment, respectively (p = 0.7). A significant interaction between treatment and day was found (p < 0.01) for P4 serum concentrations when PLACE was compared with both ACY groups. No difference was found for this hormone between both ACY groups (p > 0.05) where P4 diminished throughout the study. The decreasing rate varied among animals and was closely related to the time of abortion when P4 reached basal concentrations. In PLACE animals, gestation progressed normally and P4 did not change throughout the study (p > 0.05). None of the bitches presented side effects. It was concluded that acyline safely terminated mid-pregnancy by permanently decreasing P4 serum concentrations.  相似文献   

9.
Hormonal dependency of canine mammary tumours (CMT) has been studied over the last few decades. However, studies assessing the prognostic and predictive potential of serum and/or tissue steroid hormone levels are still scarce in CMT. To the best of our knowledge, this is the first report relating serum and tissue levels of steroid hormones and prognosis in dogs. Serum and tumour tissue from 45 female dogs with spontaneous CMT were included in the study. Moreover, serum and normal mammary tissue from 13 healthy female dogs were also included as controls. Steroid hormones were determined by competitive enzyme immunoassay. Overall, levels of steroid hormones in serum and tissue homogenates were significantly different between malignant and benign mammary tumours (p < 0.01), except for progesterone (P4) serum levels that revealed no statistical differences between groups. In malignant tumours, oestrone sulphate (SO4E1), dehydroepiandrosterone (DHEA), androstenedione (A4), testosterone (T) and P4 elevated tissue concentrations were significantly associated with tumour relapse and/or distant metastasis during follow‐up. A significant association was found between elevated tissue SO4E1 (p = 0.003), 17β‐oestradiol (E2) (p = 0.036), DHEA (p = 0.022), A4 (p = 0.001) and P4 (p = 0.013) concentrations and shorter disease‐free survival and overall survival in female dogs with malignant mammary tumours. The high levels of tissue steroids found in cases of poor prognosis open the possibility of additional new therapeutic approaches. Future clinical trials will be needed to clarify the usefulness of targeting steroid hormones in the treatment of this neoplastic disease.  相似文献   

10.
Follicle blood flow, follicular-fluid and plasma hormone concentrations, and oocyte quality were studied 30 h after an ovulation-inducing hCG treatment when the pre-ovulatory follicle was 32 mm. Mares were grouped as positive (n = 16) and negative (n = 44) for hCG antibodies before the experimental hCG treatment. Percentage of the follicle wall with blood flow signals was less (p < 0.05) in the antibody positive group than in the negative group. The concentrations of follicular-fluid oestradiol and free IGF1, and plasma oestradiol were greater (p < 0.001), and follicular-fluid progesterone (p < 0.001) and plasma LH (p < 0.02) were less in the antibody-positive group than in the negative group. For recovered oocytes at 30 h (n = 37), the antibody-positive group had fewer (p < 0.001) mature (MII) oocytes than the antibody-negative group. Results were attributable to highly effective neutralization of the hCG in the antibody-positive group.  相似文献   

11.
The aim of the study was to investigate the expression of major histocompatibility complex (MHC)-I and -II in uterine tissues from pregnant and non-pregnant bitches, taken at different time periods after mating. The pregnant bitches were ovariohysterectomized during the pre-implantation (group 1, n = 4), implantation (group 2, n = 7) and placentation stage (group 3, n = 7). Non-pregnant animals in diestrus served as controls (group 4, n = 7). The expression of MHC- I and -II in salpinx, apex, middle horn, corpus uteri and at implantation sites was investigated by immunohistochemistry as well as qualitative and quantitative RT-PCR; MHC-I mRNA was detected in all tissues and with quantitative RT-PCR, and no significant changes were detected until placentation. Immunohistologically, at the apex and corpus site, the average number of MHC-II positive cells increased from the pre-implantation to the post-implantation stage (apex: 1.54 ± 1.21 to 3.82 ± 2.93; corpus: 1.62 ± 1.9 to 5.04 ± 4.95; p < 0.05). The greatest numbers of MHC-II positive cells were observed at placentation sites (6.64 ± 5.9). In parallel, a marked increase in the relative mRNA expression of MHC-II in uterine tissues was assessed from the pre-implantation to the placentation stage (relative to Glycerinaldehyd-3-phosphate-Dehydrogenase (GAPDH): 6.9 ± 9.5, 8.4 ± 5.8, p > 0.05). Immunohistologically, in the salpinx, significantly greater numbers of MHC-II positive cells were found in the tissues of pregnant animals than in the control group (p < 0.05). It is proposed that the increase in MHC-II is pregnancy-related, even though the impact on maintenance of canine pregnancy is still unclear.  相似文献   

12.
Introduction:  Inverse associations have been shown between E‐cadherin expression and degree of differentiation in canine mammary tumours and with the acquisition of malignancy in human epithelial cancers. The purpose of this study was to examine whether there was an association between prognosis, and the distribution or intensity of immunohistochemical staining for E‐cadherin in anal sac adenocarcinoma.
Methods:  Formalin‐fixed paraffin‐wax embedded canine anal sac adenocarcinoma specimens were obtained for 36 patients for whom clinical data, including survival statistics, were available. Canine mammary adenoma tissue was employed as the positive and negative controls with antibody diluent replacing the primary antibody in the latter. Samples were scored according to proportion of cells showing positive cytoplasmic membranous staining, intensity of cytoplasmic membranous staining and proportion of nuclei staining. As quality control, a sample of 10 slides was randomly selected for repeat evaluation; results exactly matched those obtained in the first assessment.
Results:  All anal sac adenocarcinoma cells expressed E‐cadherin to varying degrees. There was no evidence of an association between survival time and the intensity of staining or the proportion of nuclei staining. Patients whose tumours exhibited >75% positive cytoplasmic membranous staining survived significantly longer than those exhibiting <75% staining with median survival times of 1100 and 479 days respectively (log rank test: χ2 = 3.89, 1 DF, p = 0.049).
Conclusion:  Immunohistochemical evaluation of the proportion of cells in anal sac adenocarcinoma samples exhibiting positive cytoplasmic membranous staining for E‐cadherin may allow improved determination of prognoses and could aid clinical decision making.  相似文献   

13.
This study was conducted to evaluate clinical efficacy of deslorelin for inhibiting reproduction in the bitch. Ten adult healthy bitches or bitches with mammary neoplasia for which owners were requesting suppression of cyclicity without performing gonadectomy were administered a 4.7- or a 9.4-mg deslorelin implant subcutaneously. The first implant of deslorelin was administered in anoestrus (n = 5) or in dioestrus (n = 5). Treatment was repeated every 5 months for as long as necessary based on the clinical situation of the dog and owner's desires. Some of the bitches implanted in anoestrus came in heat within 4–15 days after treatment, while none of the bitches implanted in dioestrus showed heat during treatment. Suppression of reproductive cyclicity was successfully achieved in 6/10 bitches for 1–4 years. No behavioural and local/general side-effects were observed in any of the treated bitches. The 4.7-mg deslorelin implant may work well for suppression of cyclicity provided that it is administered in dioestrus and at intervals of 4.5 months. A 9.4-mg implant may be more suitable for this use although its efficacy may also be shorter than 12 months. Owner compliance is an important limiting factor.  相似文献   

14.
This study was conducted in order to evaluate effects on prolactin (PRL) concentration and mammary milk secretion of an injectable cabergoline formulation administered to five lactating Beagle bitches during early postpartum (PP). Bitches were bled twice daily (from PP day 3 to PP day 12) and then daily (from PP day 13 to PP day 16) to assay serum PRL. On PP day 6, a subcutaneous (SC) injection of 0.1 ml/kg of placebo was administered. On PP day 9, a SC 0.1 ml/kg dose of injectable cabergoline was administered. All bitches were checked for milk production, using a clinical scoring in order to quantify milk expression from each teat. A circadian variation of serum PRL was evident during the 6 days of pre-treatment monitoring. The day after cabergoline injection, an 80% decrease of PRL serum concentration was observed (p < 0.05). The circadian oscillatory pattern of PRL secretion disappeared after administration of cabergoline, and PRL values remained significantly lower than in the previous days for the first 60 h following treatment (p < 0.001). Milk production was drastically reduced when comparing pre-treatment to post-treatment scores (p < 0.001). A single dose of injectable cabergoline caused a significant reduction in serum PRL concentration and a significant reduction in milk flow. The injectable formulation of cabergoline appeared to be safe and well tolerated.  相似文献   

15.
Canine mammary tumours (CMTs) are a very heterogeneous group of neoplasms with variable prognosis. Their aggressiveness is mainly due to their ability to invade locally and to metastasize. The degradation of extracellular matrix components is an important determinant of the invasive phenotype. The aims of this study were to analyse by immunohistochemistry and double immunofluorescence the expression of metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) in eight normal canine mammary glands and 118 CMTs (24 benign, 94 malignant) and to investigate relationships with metastatic disease and survival.MMP-2 and TIMP-2 expression was higher in malignant tumours than in normal canine mammary tissue and benign tumours. The main difference between benign and malignant CMTs was the pattern of expression of both molecules: benign tumours presented TIMP-2 and MMP-2 immunoreactivity in the myoepithelial cells lining the basement membrane of tubuloalveolar structures, while malignant tumours showed mainly diffuse expression in neoplastic cells. In malignant tumours, increased TIMP-2 expression was significantly associated with the development of distant metastases, lower overall survival and lower disease-free survival. MMP-2 expression was not significantly associated to any of these parameters. These results suggest that the immunohistochemical expression of TIMP-2 is a useful prognostic factor in CMTs.  相似文献   

16.
The two-year prognosis for malignant mammary tumours seen in 175 bitches in the Tokyo metropolitan area was assessed based on the extent of mastectomy and on whether an ovariectomy was carried out at the time of mastectomy. The prognosis for the bitches was not influenced by the excision size of the affected mammary glands. Ovariectomy had no effect on the two-year survival rate of the dogs that underwent the tumour excision. There was no significant difference in the two-year survival rate between the dogs ovariectomised prior to mastectomy and those ovariectomised at the time of mastectomy. These results suggest that ovariectomy at the time of mastectomy has no effect on the prognosis in dogs with established neoplasms of the mammary gland.  相似文献   

17.
The aim of the present study was to describe some of the oxidative stress parameters in bitches suffering from spontaneously occurring mammary gland tumours. The experiment involved 28 bitches which had mammary gland tumours removed surgically (15 bitches with malignant tumour and 13 with benign tumour) as well as 10 clinically healthy bitches. The activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were determined in haemolysates of erythrocytes derived from the animals. The concentrations of thiobarbituric acid reactive substances (TBARS), as well as -SH groups, were determined in blood plasma. GSH-Px activity was significantly higher in the malignant tumour group than in healthy animals. SOD activity was significantly higher in animals with tumours compared with the control group. Activities of both enzymes were higher in animals with malignant tumours than in benign groups, but the differences were not statistically significant. The concentrations of TBARS and -SH groups were similar in all examined groups. The increase of antioxidative enzyme activities in these animals may suggest the activation of antioxidative defence mechanisms in mammary gland carcinogenesis. Moreover, it might indicate the participation of oxidative stress in malignancies. Further experiments involving more animals, with more frequent sample collection and the use of other oxidative stress markers are necessary.  相似文献   

18.
Leptin and its receptor (ObR) expression were investigated by immunohistochemistry in normal, hyperplastic and neoplastic canine mammary tissues and related to clinical-pathological features. Leptin expression was detected in healthy mammary tissues, adenosis and in benign mammary tumours and was lower in ductal hyperplasias and malignant tumours. A high percentage of ObR-positive cells were present in adenosis, benign tumours and in complex carcinomas, while ObR expression was lower in healthy mammary tissues, in ductal hyperplasias and in a large part of invasive mammary carcinomas. Our data demonstrated that cancer cells expressed at low level leptin and ObR in canine mammary tumours with a more aggressive behaviour, as well as in lymph node metastases. Consequently, leptin and ObR expressions in this species resulted to be not associated with a reduced overall survival.  相似文献   

19.
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20.
Neutrophil gelatinase‐associated lipocalin (NGAL) is a new biomarker for renal injury. It is also involved in tumorigenesis of different human cancer types. The oncogenic role of NGAL is related to its molecular forms, and heterodimer formation with matrix metalloproteinase 9 (MMP9) promotes human breast cancer (HBC) invasion and metastasis. To date, the levels of NGAL and NGAL/MMP9 complex have not yet been explored in canine mammary tumours (CMTs). Hence, this study aimed to investigate whether NGAL and its molecular forms could be the biomarker for CMT diagnosis. To this end, expression profile of NGAL and MMP9 in mammary epithelial cells as well as in urine samples were detected. By immunohistochemistry staining, NGAL was expressed at variable levels. Unlike HBC, a significant reduction in NGAL expression was demonstrated in benign and malignant CMTs as compared with normal controls. Additionally, NGAL expression was significantly reduced in dogs with metastatic CMTs. By contrast, the mean score of MMP9 expression in ascending order was normal groups, benign, and malignant CMTs. Interestingly, analysis of the molecular form revealed the NGAL/MMP9 complex presents in most mammary tissues and urine of dogs with benign or malignant CMTs, whereas the complex was absent in samples from dogs without CMTs. In conclusion, NGAL and MMP9 are ubiquitously expressed in canine mammary epithelial cells in normal and cancerous status. However, the NGAL/MMP9 complex exclusively presents in mammary tissues and urine of dogs with tumours.  相似文献   

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