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1.
Increase in circulating vascular endothelial growth factor (VEGF) is suggested as a prognostic indicator in human patients with malignant tumors. The purpose of this study was to evaluate the clinical significance of circulating VEGF in dogs with mammary gland tumors (MGT). Both plasma and serum VEGF were significantly higher in dogs with MGT when compared with those in the healthy dogs. In dogs with MGT, the plasma and serum VEGF of the malignant group increased significantly compared with those of the benign group. Additionally, there was a significant difference between the plasma and serum VEGF in the groups with postoperative metastasis and no metastasis. Circulating VEGF is expected to be clinically available for the determination of prognosis in canine MGT.  相似文献   

2.
Mammary gland tumours (MGT) are the third most common tumours in the cat. At least 85% are malignant and metastasis is common. The HER‐2/neu protooncogene encodes a 185‐kDa transmembrane tyrosine receptor kinase protein. Approximately 25–30% of human MGT demonstrate HER‐2/neu protein overexpression in the malignant cells, and overexpression has been associated with an increased metastatic propensity and a decreased prognosis. No reports have been published, to date, investigating the expression of Her‐2/neu in cats or cats with spontaneous mammary tumours. Based on the increased percentage of malignant mammary cancers in cats, compared to that in dogs, and the correlation of an increased malignancy and a decreased prognosis with Her‐2 overexpression in human mammary cancer, we hypothesized that cats with spontaneous malignant mammary adenocarcinoma overexpress Her‐2/neu in the neoplastic mammary epithelial cells. Thirty cats with MGT were assayed for Her‐2/neu immunohistochemical expression. The median percentage of cells from feline MGT expressing Her‐2/neu by utilizing the Dako polyclonal and CB11 monoclonal antibodies was 85 and 92.5, respectively. Her‐2/neu expression intensity grades 2 and 3 consistent with the overexpression by utilizing the Dako polyclonal and CB11 monoclonal antibodies were observed in 90 and 76.7% of cats with MGT, respectively. The level of overexpression concordance across the two antibodies was 70%. The results from this study suggest that Her‐2/neu overexpression is common in cats with spontaneous MGT, and therefore appears to represent an excellent model for Her‐2/neu‐overexpressing human breast cancer.  相似文献   

3.
Since gamma-glutamyl transpeptidase (GGT) is highly and locally expressed in human breast cancer, a GGT-enzymatically activatable fluorescent probe, gamma-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), has been developed to detect the human breast cancer area with high performance. In this study, GGT expression and the efficacy of gGlu-HMRG on visualization were investigated in canine mammary gland tumors (MGT). Seventeen non-fixed fresh-frozen MGT specimens and each peritumoral control tissue were utilized. The GGT mRNA levels were highly observed in the tumor specimens compared with the control. GGT immunostaining was mostly observed on the cell membrane and cytosol of the alveolar and duct mammary epithelium of MGT tissues. These signals were strongly positive in several cases while they were mild to not observed in other cases. When gGlu-HMRG solution was dropped to the non-fixed tissue pieces of MGT or control tissues, the fluorescence intensities (FIs) were measured using Maestro in-vivo imaging device. FIs in MGT tissues were significantly higher than each control tissue 20 min after treatment. Based on Youden index method said that the maximum sensitivity and specificity of FI was 82.4% and 82.4%. These findings suggest that GGT is highly expressed in several MGTs in dogs and gGlu-HMRG could visualize at least a part of MGT tissues in dogs. Nevertheless, it should be needed to assess the false-negative areas more carefully in canine than human cases.  相似文献   

4.
Somatostatin receptor 2 (SSTR2) is a negative regulator of cell proliferation in human breast cancer. Since there is little information about SSTR2 in canine mammary gland tumor (MGT), we clarified its distribution and expression level in normal mammary gland, benign MGT and malignant MGT. SSTR2 expression determined by immunohistochemical staining was observed in the cytoplasm of luminal epithelial cells. The intensity was negatively correlated with malignancy: normal tissues and some of the benign tumors had the highest levels, while the malignant tumors had little or no SSTR2 expression. As for the Western blotting, SSTR2 protein level in benign tumors was significantly lower than the normal mammary gland. On the other hand, SSTR2 protein levels in two of three malignant tumors were higher than the other groups. These results suggest that SSTR2 expression alters according to the malignancy of canine MGT.  相似文献   

5.
Canine mammary gland tumour (MGT) is the most common neoplasm in female dogs and has similar biological characteristics to human MGT. Spontaneous canine MGT is a more attractive clinical model in oncological research than that of the murine experimental model. Tumour‐associated antigens (TAAs), which are produced in tumour cells, are applied as tumour markers, tumour vaccine antigens and molecular targets of therapeutic drugs. In this study, we have primarily identified 13 different TAAs of canine MGT by serological immunoscreening of cDNA expression library. The results of serological mini‐arrays of identified antigens showed that CCDC41 antigen specially reacted with 35% of sera from MGT‐dogs and did not react with control sera. We also found that HSPH1 mRNA expression levels increased significantly in MGT tissues. These findings will contribute to the development of diagnostic technologies and translational target therapies for dogs. Clinical relevance : HSPH1, which is strongly expressed in the tumour tissue, will be a possible vaccine antigen of canine MGT.  相似文献   

6.
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7.
The Prognostic Significance of Angiogenesis in Canine Mammary Tumors   总被引：1，自引：0，他引：1  
The purpose of the study was to determine if neovascularization, a measure of angiogenesis, is correlated with metastasis of mammary tumors in dogs. Forty-six paraffin-embedded tissue blocks of benign and malignant canine mammary tumors obtained from 42 clinical cases at the Iowa State University Veterinary Teaching Hospital were retrieved from the archives of the Department of Veterinary Pathology. Of the dogs with malignant tumors, cases with and without lymph node metastasis were chosen. Neovascularization was quantified by light microscopy on formalin-fixed, paraffin-embedded sections of canine mammary tumors using an avidin biotin immunoperoxidase assay for factor VIII-related antigen. Mean microvessel counts for each group were statistically evaluated using analysis of variance. The mean number of microvessels was highest in the malignant tumors of dogs with lymph node metastasis (44). This number was significantly different from the mean number of microvessels in the benign tumors (28; P = .03) and a trend occurred toward higher microvessel counts in malignant tumors with lymph node metastasis versus malignant tumors of dogs without metastasis (32; P = .1). No significant difference was found between the number of microvessels found in malignant tumors without metastasis versus benign tumors. The trend toward higher microvessel counts in mammary tumors that have metastasized supports the premise that angiogenesis may be an independent and significant prognostic indicator in dogs with malignant mammary tumors, as it is in women with breast cancer.  相似文献   

8.
5‐Aminolevulinic acid (5‐ALA) is widely used in photodynamic detection (PDD) and therapy. We evaluated the pharmacokinetics of 5‐ALA‐induced porphyrins and its effectiveness in PDD in dogs with mammary gland tumours (MGTs) following oral administration. Healthy dogs and those with MGTs (nine each) were orally administered 4 mg kg?1 5‐ALA. Protoporphyrin IX (PpIX) was not detected in the plasma of healthy dogs but it peaked in dogs with MGT at 2 h after 5‐ALA administration. In the PDD study, 16 dogs with MGT were orally administered 40 mg kg?1 5‐ALA, and MGT but not normal tissue showed red fluorescence after 2–4 h. Photon counts were 6635–63 890 and 59–4011 (median, 19 943 and 919) for MGT and non‐tumour tissues, respectively. Cell density strongly correlated with PpIX photon counts of MGT tissue of the dogs (R = 0.743, P = 0.0009). We suggest that 5‐ALA‐PDD might be an effective diagnostic tool for MGTs.  相似文献   

9.
A mammary gland tumour (MGT) was clinically diagnosed in 136 dogs. Histologically 71% were malignant and 29% benign. Intrathoracic metastatic disease was noted or suspected radiographically in 13.5% of the dogs with malignant and in 2.5% of the dogs with benign MGT. Six dogs with malignant MGT were necropsied, 5 had pulmonary metastases but only 1 had radiographic signs of intrathoracic metastatic disease. We conclude that radiographs are not very sensitive for detection of early intrathoracic metastatic disease of MGT.  相似文献   

10.
Two canine nm-23 cDNAs, designated as nm23-C1 and -C2, were isolated and characterized. Both have a putative open reading frame consisting of 459-bp encoding 152 amino acids and are highly similar to human, mouse and rat homologues. To understand the potential role of nm23-C1 and -C2 in the development of mammary gland tumors (MGT), we analyzed the mRNA expression in 14 MGT samples by RT-PCR. The samples were divided into categories according to their histopathology (benign/malignant) and metastasis. No significant difference in the mRNA expression levels of either nm23-C1 or -C2 were observed between the benign and malignant groups or the metastatic and non-metastatic groups. These results suggest that nm23-C1 and -C2 are not related to the establishment of malignancy and metastatic lesions in canine MGT cases.  相似文献   

11.
BACKGROUND: Genomic instability is a hallmark of cancer and may be required for the accumulation of cancer-causing mutations within cells. One form of genomic instability occurs in tandem nucleotide repeats and is known as microsatellite instability (MSI). HYPOTHESIS: We hypothesized that MSI can be observed in canine mammary gland tumors (MGT) and represents a potential carcinogenic mechanism in dogs. ANIMALS: Thirty-five dogs with MGTs and 9 dogs with other tumors were recruited from the University of Minnesota Veterinary Medical Center and referring veterinary clinics. METHODS: A panel of 21 canine microsatellite (MS) markers was amplified by polymerase chain reaction (PCR) from deoxyribonucleic acid obtained from blood and from fresh or formalin-fixed, paraffin-embedded tumor tissues. PCR products were evaluated by using capillary electrophoresis, and the chromatograms were analyzed by using genotyping software. MS genotypes obtained from fresh and formalin-fixed tumor tissues were compared, as were MS genotypes from normal tissue and tumor tissue. RESULTS: Genotypes obtained from formalin-fixed and fresh tissues were identical for all MS in 9 tumors evaluated, suggesting excellent concordance between the 2 sample types. For the 35 canine mammary tumors evaluated, 13 (37%) had stable genotypes; 22 (63%) exhibited aberrations in 1 or 2 MS; and 4 tumors (11%) demonstrated high-level instability, with aberrations in 29 to 61% of MS. CONCLUSIONS AND CLINICAL IMPORTANCE: Although some low-level MSI often is observed, high-level MSI is an infrequent finding in canine mammary tumors. Further evaluations are required to better characterize this phenomenon and to determine its relevance to canine carcinogenesis.  相似文献   

12.
Background: Mammary tumors are the most common neoplasms in female dogs. Malignant tumors may carry a poor prognosis and necessitate surgery. Few data are available on the value of cytologic examination as a diagnostic or prognostic tool for mammary tumors in dogs. Objectives: The objectives of this study were to determine whether cytologic findings in fine‐needle aspirate specimens of canine mammary tumors correlate with histopathologic results and whether the cytologic diagnosis is associated with postoperative outcome. Methods: In this prospective study, fine‐needle aspirate samples were obtained from 50 mammary tumors in 50 dogs. Results of cytologic and histopathologic examination were compared, using the histologic diagnosis as the reference method. Kaplan–Meier log rank analysis was used to evaluate univariate association of the cytologic diagnosis with duration of survival, local control, and metastasis‐free interval. Results: Adequate cytologic samples were obtained in 43/50 (86%) cases. The cytologic diagnosis correlated with the histologic diagnosis for benign and malignant tumors in 40/43 (93%) and 35/43 (81%) cases, respectively. Cytologic examination had a sensitivity of 88% and a specificity of 96% for the diagnosis of malignancy. The cytologic diagnosis had significant univariate association with duration of survival (P=.016), recurrence‐free interval (P=.003), and metastasis‐free interval (P=.014). Conclusions: Cytologic examination of mammary tumors in the dog has satisfactory accuracy, sensitivity, and specificity for the diagnosis of malignancy and is associated with postoperative outcome. Further studies on the diagnostic accuracy of cytology as well as multivariate analysis of its preoperative prognostic value in mammary tumors in the dog are warranted.  相似文献   

13.
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14.
Mammary gland tumors in female dogs are an excellent model for the clinic-pathological, diagnostic and prognostic investigation of mammary neoplasias. Prognostic and predictive markers are effective in research and routine diagnosis. Interleukins play a fundamental role in cancer, with a particular function in tumor growth, invasion and metastatic potential. Interleukin-8 (IL-8) is known to possess tumorigenic and pro-angiogenic properties, and its overexpression is seen in a number of human tumors. IL-8 serum levels were determined and correlated with the clinic-pathological features and clinical evolution of mammary gland neoplasias in female dogs. IL-8 was measured by an immunoenzymatic assay in 30 female dogs with mammary neoplasias within a 12 month follow-up and in 50 control animals. The correlation between IL-8 concentration and clinical parameters was investigated. A statistically significant difference in the IL-8 serum levels was found in tumor-bearing dogs compared to the controls. In addition, when the individual parameters were evaluated, IL-8 content showed a positive correlation with the tumor progression, lymph node involvement, recurrence and death. Single and multivariate analyses showed associations between tumor recurrence, metastasis, high clinical staging and high IL-8, and also with the death risk. This was also consistent with the high IL-8 content in dogs showing tumor recurrence and metastasis. IL-8 superexpression has been detected in a number of human tumors, usually associated with a poor prognostic. Besides promoting angiogenesis, IL-8 is strongly related with the metastatic phenotype of mammary tumor cells. High IL-8 concentration was found in mammary gland cancer patients with advanced disease stages. Our results show that IL-8 can be used as a non-invasive prognostic marker for mammary gland cancer, and can be useful for the prediction of disease progression and recurrence in dogs with mammary neoplasias. The increased level of this cytokine acts as an independent prognostic marker of survival and the identification of animals with the poor prognostic.  相似文献   

15.
As part of a study of the effects of low-level radiation, 1,343 Beagles, including 671 males and 672 females, were evaluated over their full lifetime for the occurrence of mammary neoplasia; there were 139 control males and 138 control females and 532 irradiated males and 534 irradiated females. All nodules found in surgical specimens or at necropsy were evaluated histologically. The overall incidence, metastasis and recurrence rates, and contribution to mortality of mammary neoplasms were determined. Based on this unique opportunity to correlate morphologic characteristics with ultimate biological behavior of all mammary tumors in a defined canine population, we propose a histogenetically based reclassification of epithelial mammary tumors. Of the 672 female dogs, 70.8% (476) had at least one mammary neoplasm; 60.7% (408) had more than one. Two male dogs had mammary neoplasms. Of 1,639 mammary carcinomas in the 672 females, 18.7% (307) were classified as ductular carcinomas (arising from the small interlobular or intralobular ductules), whereas 80.7% (1,322) were classified as adenocarcinomas of other histogenetic origin. Of 73 fatal carcinomas, ductular carcinomas accounted for 48 fatalities (65.8%), whereas other adenocarcinomas accounted for only 20 fatalities (27.4%). Radiation had no effect on this ratio. Ductular carcinomas also had a higher rate of metastasis than did adenocarcinomas. Existing classifications of mammary carcinomas do not recognize the characteristic morphologic features, the degree of malignancy, and the prognostic importance of these ductular carcinomas. Metastasis rates did not differ between simple and complex carcinomas or between those lesions and adenocarcinomas in mixed tumors. True carcinosarcomas metastasized more frequently (100%, or 5/5) than did adenocarcinomas in mixed tumors (34.4%, or 22/64), emphasizing the importance of not lumping these tumors under the classification of malignant mixed tumors.  相似文献   

16.
This is the first report describing the expression of canine calreticulin (cCRT) in canine mammary gland tumour (MGT). Using cDNA subtraction method, it is found that mRNAs of CRT, cathepsin A, ovostatin, and lactotransferrin were differentially expressed in mammary adenocarcinoma as compared to hyperplasia, both of which were obtained from the dog. Furthermore, the mRNA expression levels of CRT and cathepsin A were significantly higher in canine MGT samples than in nontumour samples. In contrast, immunohistochemical studies have indicated that the expression of cCRT protein found to be detected in most of mammary gland tissues and was not correlated to the types of canine MGTs. Furthermore, cCRT was molecularly cloned, and the amino acid sequence of cCRT was found to be very similar to those of other species. Further studies are required to elucidate additional roles of cCRT in canine MGT.  相似文献   

17.
Background: In veterinary medicine, there is increasing interest in measuring acute phase proteins as a tool in the diagnosis and monitoring of neoplastic diseases. Although mammary neoplasms are the most common type of cancer in dogs, acute phase proteins have not been extensively evaluated in dogs with mammary tumors. Objectives: The aim of this study was to evaluate serum haptoglobin (Hp) and C‐reactive protein (CRP) concentrations in the dogs with mammary tumors and assess their potential association with malignancy. Methods: A retrospective study of dogs with mammary tumors was performed. Serum concentrations of CRP and Hp were determined in healthy control dogs (n=20) and dogs with mammary tumors before surgery (n=41). Mammary tumors were grouped as carcinomas (n=24), fibrosarcoma (n=1), malignant mixed tumors (n=7), benign mixed tumors (n=6), and adenomas (n=3). CRP and Hp concentrations were compared in dogs with different tumor types and were also compared based on tumor size, lymph node infiltration, skin ulceration, fixation to underlying tissue, and time between tumor identification and removal. Results: Hp concentration was significantly (P<.043) higher in dogs with mammary tumors (median 2.03 g/L, range 0.09–2.94 g/L) compared with controls (1.38 g/L, range 0.08–3.00 g/L), but the range of values overlapped considerably. CRP concentration was higher in dogs with carcinomas (4.70 mg/L, range 0.63–128.96 mg/L) vs controls (2.11 mg/L, range 0.25–6.57 mg/L) (P=.0008) and in dogs with ulcerated skin (14.8 mg/L, range 5.7–128.9 mg/L, n=3) compared with those without ulceration (2.4 mg/L, range 0.11–30.3 mg/L, n=38) (P=.048). Conclusions: Serum Hp and CRP do not appear to have value in diagnosing or predicting malignancy of mammary tumors in dogs. Higher CRP concentrations in dogs with mammary carcinoma suggest a role for inflammation in this tumor type.  相似文献   

18.
The oncolytic effects of reovirus in various cancers have been proven in many clinical trials in human medicine. Oncolytic virotherapy using reovirus for canine cancers is being developed in our laboratory. The objective of this study was to examine the synergistic anti-cancer effects of a combination of reovirus and low doses of various chemotherapeutic agents on mammary gland tumors (MGTs) in dogs. The first part of this study demonstrated the efficacy of reovirus in canine MGTs in vitro and in vivo. Reovirus alone exerted significant cell death by means of caspase-dependent apoptosis in canine MGT cell lines. A single injection of reovirus impeded growth of canine MGT tumors in xenografted mice, but was insufficient to induce complete tumor regression. The second part of this study highlighted the anti-tumor effects of reovirus in combination with low doses of paclitaxel, carboplatin, gemcitabine, or toceranib. Enhanced synergistic activity was observed in the MGT cell line treated concomitantly with reovirus and in all the chemotherapeutic agents except toceranib. In addition, combining reovirus with paclitaxel or gemcitabine at half dosage of half maximal inhibitory concentration (IC50) enhanced cytotoxicity by activating caspase 3. Our data suggest that the combination of reovirus and low dose chemotherapeutic agents provides an attractive option in canine cancer therapy.  相似文献   

19.

Background

Accurate early diagnosis of lung metastases is important for establishing therapeutic measures. Therefore, the present study aimed to compare survey thoracic radiographs and computerized tomography (CT) scans to specifically identify lung metastases in female dogs with mammary tumors.

Methods

Twenty-one female dogs, weighing 3 to 34 kg and aged from 5 years to 14 years and 10 months, with mammary tumors were studied. In all dogs before the imaging examinations, fine-needle aspiration cytology of the mammary tumors was performed to confirm the diagnosis. Three-view thoracic radiographs were accomplished: right lateral, left lateral and ventrodorsal views. Sequential transverse images of the thorax were acquired on a spiral Scanner, before and after intravenous bolus injection of nonionic iodine contrast. Soft-tissue and lung windows were applied. All the mammary tumors were surgically removed and examined histologically.

Results

The correlation between the cytological and histological results regarding presence of malignancy was observed in only 17 cases. In radiographic examinations, no dog displayed signs of lung metastases or thorax chest lesions. CT detected lung metastasis in two cases, while small areas of lung atelectasis located peripherally were found in 28.57% of the dogs.

Conclusion

In this study population, spiral CT showed higher sensitivity than chest radiographies to detect lung metastasis; this indicates that CT should be performed on all female dogs with malignant mammary tumors.  相似文献   

20.
BACKGROUND: Treatment outcome after surgery alone is unsatisfactory in dogs with invasive malignant mammary gland tumors. HYPOTHESIS: Adjuvant doxorubicin or docetaxel will improve the treatment outcome in dogs with high-risk malignant mammary gland tumors, and the use of docetaxel will be feasible in affected dogs. ANIMALS: Thirty-one dogs with malignant mammary gland tumors of histologic stages II and III (vascular or lymphatic invasion, regional lymph node metastasis, or distant metastasis) were used. METHODS: A prospective clinical trial in which dogs were treated with surgery alone (n = 19) or also received adjuvant chemotherapy (n = 12) with doxorubicin or docetaxel was conducted. Docetaxel was given as an IV infusion at a dose of 30 mg/m2 preceded by dexamethasone and diphenhydramine administration. RESULTS: The recurrence-free interval ranged from 13 to 2,585 days (median not reached); the median metastasis-free interval and overall survival were 294 days and 370 days, respectively. Dogs treated with chemotherapy had a tendency toward higher long-term local control and survival rates, but there was no significant difference in the recurrence-free interval (P = .17), time to metastasis (P = .71), and overall survival (P = .12). Factors found to influence the time to metastasis and overall survival included lymph node metastasis (P = .009) and tumor fixation to underlying structures (P = .043, time to metastasis), as well as age (P = .018) and histologic stage (P < .001, survival). Mild allergic skin reactions were the most frequently observed complications of docetaxel treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Chemotherapy did not lead to an improved outcome in this population. Docetaxel treatment was well tolerated. Additional investigations of adjuvant chemotherapy in dogs with high-risk mammary cancer are warranted.  相似文献   

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