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1.
Klopfleisch R Hvid H Klose P da Costa A Gruber AD 《Veterinary and comparative oncology》2010,8(4):293-301
Insulin receptor (INSR) or insulin-like growth factor (IGF) signalling is speculated to be involved in mammary tumour development. Expression levels of members of the insulin receptor family (INSR, IGF1R, IGF2R, GHR) and their ligands IGF1and IGF2 were quantified in macro- and microdissected tissue samples of normal canine mammary gland, adenomas, carcinomas and their lymph node metastases to evaluate their potential impact on the carcinogenesis of canine mammary tumours. Normal mammary gland and adenomas had strong INSR expression, while carcinomas and metastases had significantly decreased expression. No differences were observed for IGF1R expression. IGF1, IGF2 and GHR mRNA expressions were strongly decreased in adenomas, carcinomas and metastases. INSR and IGF1R are therefore expressed in normal gland and adenomas and an increased stimulus by their ligands may be a proliferative stimulus in those tissues. However, decreased INSR expression carcinomas and their metastases render questionable its impact at late stages of carcinogenesis. 相似文献
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Canine mammary gland tumours (CMTs) are the most common malignancies in female dogs. The receptor tyrosine kinase EGFR (erbb1), a receptor for epidermal growth factor (EGF) and related factors, mediates multiple oncogenic functions in human epithelial neoplasms. While previous studies have demonstrated EGFR expression in canine tumours, its function has not been studied in canine cancer. The purpose of this study was to determine the in vitro effects of EGF and vandetanib (ZD6474), a small molecule inhibitor of VEGFR-2, EGFR and RET tyrosine kinases, on proliferation, invasion, survival and chemosensitivity in CMT cells. In low serum, EGF enhanced proliferation and chemotaxis, attenuated apoptosis, and stimulated vascular endothelial growth factor (VEGF) production. Vandetanib dose-dependently inhibited EGFR phosphorylation as well as PI3K/Akt activation, and inhibited all EGF-induced phenotypic effects. In conclusion, EGF stimulates multiple features promoting the malignant phenotype in CMT. Thus, CMT may be an important translational model for the investigation of novel EGFR-directed therapies. 相似文献
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A. K. Marr D. H. Thamm I. D. Kurzman D. M. Vail E. G. MacEwen 《Veterinary and comparative oncology》2003,1(3):159-167
The in vitro antiproliferative, apoptotic and cell‐cycle effects of 2‐methoxyestradiol (2ME2), an endogenous oestrogen metabolite, were investigated using a variety of canine tumour cell lines. The cells were cultured under standard conditions and incubated with varying concentrations of 2ME2. Inhibition of tumour cell proliferation was evaluated using a tetrazolium‐based colorimetric assay. DNA content analysis was performed using propidium iodide staining and flow cytometry. Cytologic analysis with Leukostat staining solution and Hoechst 33342 staining and Annexin V‐fluorescein isothiocyanate (FITC) fluorescence were used to quantify cell‐cycle distribution and apoptosis induction. Tumour cell proliferation was inhibited by 50% at concentrations of 2ME2 ranging from 0.88 to 7.67 µM, depending on the cell line tested. Profound G2/M phase arrest, an increase in binucleate cells and induction of apoptosis were observed in all cell lines tested, in a dose‐dependent manner. Based on these results, this compound has potential as an agent for the treatment of canine cancer and warrants further investigation. The canine lymphoma cell line, 1771, was inhibited at concentrations that may be achievable in vivo. 相似文献
4.
Hiro HORIKIRIZONO Kumiko ISHIGAKI Keigo IIZUKA Kei TAMURA Naoki SAKURAI Kazuyuki TERAI Tatsuya HEISHIMA Orie YOSHIDA Kazushi ASANO 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2022,84(5):720
Angiogenesis plays an important role in the proliferation and metastasis mechanisms of malignant tumors. Vascular endothelial growth factor (VEGF), a group of cytokines that contribute to angiogenesis and vasculogenesis. This study aimed to investigate the serum VEGF-A concentrations in dogs with various proliferative diseases. A total of 202 dogs that were histopathologically diagnosed with proliferative diseases were included in the study. Serum VEGF-A concentrations were measured using enzyme-linked immunosorbent assay. Median serum VEGF-A concentrations in dogs were as follows: healthy dogs, 4 pg/ml [0–21 pg/ml]; hepatocellular carcinoma, 30 pg/ml [0–158 pg/ml, P=<0.001]; hepatocellular adenoma, 32 pg/ml [0–49 pg/ml, P=0.003]; hepatic nodular hyperplasia, 18 pg/ml [0–51 pg/ml, P=0.595]; adrenal pheochromocytoma, 32 pg/ml [0–187 pg/ml, P=<0.001]; adrenocortical carcinoma, 32 pg/ml [3–161 pg/ml, P=0.002]; adrenocortical adenoma, 27 pg/ml [0–106 pg/ml, P=0.005]; colorectal adenocarcinoma, 36 pg/ml [0–75 pg/ml, P=0.002]; colorectal adenoma, 43 pg/ml [0–48 pg/ml, P=0.144]; inflammatory colorectal polyps, 37 pg/ml [0–111 pg/ml, P=<0.001]; pulmonary adenocarcinoma, 35 pg/ml [4–107 pg/ml, P=0.002]; pulmonary histiocytic sarcoma, 35 pg/ml [0–131 pg/ml, P=0.016]; and follicular thyroid carcinoma, 35 pg/ml [0–106 pg/ml, P=0.009]. The serum VEGF-A concentrations were significantly higher in dogs with neoplastic lesions compared to healthy dogs, except for colorectal adenoma. High serum VEGF-A concentrations were observed in dogs with proliferative diseases. The present study suggests that angiogenesis-inhibiting therapy, which targets VEGF-A, may be useful for canine neoplastic diseases. 相似文献
5.
V. J. Poirier M. K. Huelsmeyer I. D. Kurzman D. H. Thamm D. M. Vail 《Veterinary and comparative oncology》2003,1(4):207-215
Bisphosphonates (BPs) are a class of non‐hydrolysable analogues of pyrophosphate that have high affinity for bone mineral and are inhibitors of bone resorption. The in vitro effects of two nitrogen‐containing BPs, alendronate (ALE) and zoledronate (ZOL), on growth, induction of apoptosis and effects on cell‐cycle distribution in two canine and two human osteosarcoma (OSA) cell lines are investigated here. Both significantly (P < 0.001) reduced cell growth in all cell lines, as assessed by a colorimetric assay with IC50 values in the range of 7.3–61.4 µM and 7.9–36.3 µM for ALE and ZOL, respectively. Both BPs caused a significant (P < 0.001) dose‐dependent increase in the proportion of cells undergoing apoptosis, as assessed both by cell‐cycle analysis and by annexin‐V binding. Both ALE and ZOL altered the proportion of cells in each phase of the cell cycle, but the extent and proportion was both drug and cell line dependent. These data indicate that the nitrogen‐containing BPs have direct anti‐tumour activity against canine and human OSA cells. 相似文献
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K. E. Morrison-Collister K. M. Rassnick N. C. Northrup O. Kristal J. D. Chretin L. E. Williams S. M. Cotter A. S. Moore 《Veterinary and comparative oncology》2003,1(4):180-190
A chemotherapy protocol using a consolidation phase of alkylating agents was used for treating 94 dogs with lymphoma. Fifty‐seven percent of dogs were in stage V, 63% were ill and 38% had T‐cell lymphoma. The complete remission (CR) rate was 70% and is comparable to results achieved with previously published chemotherapy protocols. Anorexia predicted the remission; of the 40 dogs without anorexia, 35 (88%) achieved CR whereas of 52 dogs with anorexia, 30 (58%) achieved CR. Median first CR duration was 168 days and 1‐ and 2‐year CR rates were 17.4 and 15.5%, respectively. Platelet count affected length of first CR, with a 53.2% reduced chance of coming out of remission with each log increase in platelet count. Median survival time was 302 days. One and 2‐year survival rates were 44 and 13%, respectively. Anorexia and no dose reduction of any drug were independent negative variables. Of 93 dogs with toxicity data, 65 dogs (70%) required a dose reduction. Cyclophosphamide was most commonly reduced with reductions in 31 (38%) of 82 dogs. A dose reduction was significantly more likely in dogs with B‐cell lymphoma than in those with T‐cell lymphoma. 相似文献
8.
Shohei YOKOTA Tomohiro YONEZAWA Yasuyuki MOMOI Shingo MAEDA 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2022,84(5):666
Canine transitional cell carcinoma (cTCC) is the most common naturally occurring bladder cancer and accounts for 1–2% of canine tumors. The prognosis is poor due to the high rate of invasiveness and metastasis at diagnosis. Sorafenib is a multi-kinase inhibitor that targets rapidly accelerated fibrosarcoma (RAF), vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor-β (PDGFR-β), and KIT. In previous studies, a somatic mutation of B-rapidly accelerated fibrosarcoma (BRAF) and expressions of VEGFR-2 and PDGFR-β were observed in over 80% of patients with cTCC. Therefore, in this study, we investigated the anti-tumor effects of sorafenib on cTCC. Five cTCC cell lines were used in the in vitro experiments. All five cTCC cell lines expressed VEGFR-2 and PDGFR-β and sorafenib showed growth inhibitory effect on cTCC cell lines. Cell cycle arrest at the G0/G1 phase and subsequent apoptosis were observed following sorafenib treatment. In the in vivo experiments, cTCC (Sora) cells were subcutaneously injected into nude mice. Mice were orally administered with sorafenib (30 mg/kg daily) for 14 days. Sorafenib inhibited tumor growth compared to vehicle control. The necrotic area in the tumor tissues was increased in the sorafenib-treated group. Sorafenib also inhibited angiogenesis in the tumor microenvironment. Thus, sorafenib may be potential therapeutic agent for cTCC via its direct anti-tumor effect and inhibition of angiogenesis. 相似文献
9.
表皮生长因子对水牛胚胎体外发育及凋亡的影响 总被引:1,自引:0,他引:1
为了探讨表皮生长因子(EGF)对水牛早期胚胎体外发育及凋亡的影响,通过收集屠宰场卵巢卵母细胞进行体外成熟和体外受精,将假定的受精卵置于含不同浓度EGF(0,25,50和100 ng/mL)的培养液中培养,检查分裂率和囊胚发育率,用细胞凋亡试剂盒(Annexin-V-FluosStaining kit)试剂染色,统计囊胚细胞凋亡率和坏死率。结果表明:50 ng/mL EGF组的孵化囊胚率显著高于对照组(P<0.05),该组细胞凋亡率和坏死率显著低于对照组(P<0.05)。100 ng/mL EGF的卵裂率、囊胚率、D7囊胚率和孵化囊胚率显著低于对照组和其他试验组(P<0.05)。细胞凋亡率和坏死率显著高于其他各组(P<0.05)。提示:一定浓度的EGF可提高囊胚孵化率,并可抑制胚胎细胞的凋亡。 相似文献
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Dog reproductive cycle is unique among other mammals in that females experience long and variable periods of ovarian inactivity. Neuroendocrine controls of the reproductive cycle have been thoroughly studied in the dog. However, there is little information regarding endocrine, paracrine and autocrine controls of dog ovarian folliculogenesis. Advancements in the understanding of mechanisms regulating dog ovarian follicle development will be helpful in the establishment of an approach to control cyclicity in this species. Furthermore, such information will likely be useful for the establishment of an in vitro follicle culture system to preserve fertility of genetically valuable disease models or endangered canids. This review highlights current knowledge on dog folliculogenesis with emphasis on endocrine, paracrine and autocrine controls of follicular development. 相似文献
12.
兰忠岐;李鹏;沈爽;蒋金凤;秦鸿灯;向钰婷;王家乡 《中国畜牧兽医》2025,52(5):2035-2044
【目的】试验旨在研究饲粮中添加不同剂量表皮生长因子(epidermal growth factor;EGF)对蛋鸡卵巢形态学、激素含量及凋亡因子表达的影响;为探明EGF促进蛋鸡卵巢的生长发育提供一定的理论依据。【方法】选用240只260日龄体重相近、健康的白来航高产蛋鸡;随机分为4个处理组;每组5个重复;每个重复12只鸡。对照组(Con)蛋鸡饲喂不添加EGF的基础饲粮;3个试验组(LG、MG、HG)蛋鸡分别在基础饲粮中添加200、400及800 mg/kg EGF。预试期7 d;正试期42 d。每个重复取2只蛋鸡;采集血液和组织样品;测量卵巢、输卵管、卵泡的重量;统计卵泡分级的数量;测定血清中促黄体激素(LH)、促卵泡素(FSH)、雌二醇(E2)和孕酮(P4)含量;并利用实时荧光定量PCR和Western blotting测定卵巢中凋亡因子Bcl-2和Caspase-3的表达量。【结果】与Con组相比;①饲粮中添加不同剂量EGF对蛋鸡卵巢重、卵巢指数和白卵泡数量均有显著影响(P<0.05);但各组卵巢在形态上无明显变化。②LG、MG、HG组蛋鸡血清中LH、FSH和E2水平均显著升高(P<0.05);LG、MG组蛋鸡血清中P4水平显著升高(P<0.05)。③LG、MG组蛋鸡卵巢中Bcl-2基因相对表达量均显著升高(P<0.05);LG、MG、HG组蛋鸡卵巢中Bcl-2蛋白相对表达量均显著升高(P<0.05);LG、MG组蛋鸡卵巢组织中Caspase-3基因相对表达量均显著降低(P<0.05);MG、HG组蛋鸡卵巢组织中Caspase-3蛋白相对表达量均显著降低(P<0.05)。【结论】在本试验条件下;饲粮中添加不同剂量EGF在一定程度上可促进卵巢生殖激素分泌和卵泡发育;有效抑制细胞凋亡进而改善蛋鸡生产性能。EGF在白来航高产蛋鸡饲粮中的推荐添加量为400 mg/kg。 相似文献
13.
G. Hartley E. Faulhaber A. Caldwell J. Coy J. Kurihara A. Guth D. Regan S. Dow 《Veterinary and comparative oncology》2017,15(2):534-549
Expression of programmed cell death receptor ligand 1 (PD‐L1) on tumor cells has been associated with immune escape in human and murine cancers, but little is known regarding the immune regulation of PD‐L1 expression by tumor cells and tumor‐infiltrating macrophages in dogs. Therefore, 14 canine tumor cell lines, as well as primary cultures of canine monocytes and macrophages, were evaluated for constitutive PD‐L1 expression and for responsiveness to immune stimuli. We found that PD‐L1 was expressed constitutively on all canine tumor cell lines evaluated, although the levels of basal expression were very variable. Significant upregulation of PD‐L1 expression by all tumor cell lines was observed following IFN‐γ exposure and by exposure to a TLR3 ligand. Canine monocytes and monocyte‐derived macrophages did not express PD‐L1 constitutively, but did significantly upregulate expression following treatment with IFN‐γ. These findings suggest that most canine tumors express PD‐L1 constitutively and that both innate and adaptive immune stimuli can further upregulate PD‐L1 expression. Therefore the upregulation of PD‐L1 expression by tumor cells and by tumor‐infiltrating macrophages in response to cytokines such as IFN‐γ may represent an important mechanism of tumor‐mediated T‐cell suppression in dogs as well as in humans. 相似文献
14.
H. Ballestero Fêo L. Montoya Flórez R. S. Yamatogi A. Prado Duzanski J. P. Araújo Jr. R. A. Oliveira N. S. Rocha 《Veterinary and comparative oncology》2018,16(3):370-378
The canine transmissible venereal tumour (CTVT) is a transmissible cancer that is spread naturally between dogs, with the ability to develop and evade the immune system, despite strict immune surveillance of the host. Furthermore, molecular signalling between cells of the immune system and the tumour microenvironment appear to influence the behaviour and development of the tumour. Thus, this study aimed to quantify the expression of genes related to the immune system such as IL‐6, IFN‐γ, and TGF‐β, as well as angiogenic factors (VEGF, CXCR4), in CTVT cells in vivo and in vitro (primary culture), correlating with the clinical response of the animals treated with vincristine. As expected, the most prevalent subtype was plasmacytoid cells, although lymphocytic cells were also found, indicating the possibility of polyclonality. When we compared the gene expressions of IFN‐γ and IL‐6, we mostly found low expression, concluding that MHC expression was probably not occurring in tumour cells, and no activation of immune cells to eliminate the tumour. The TGF‐β gene was normal in the majority of animals but demonstrated decreased expression in vincristine resistant animals, leading to the hypothesis that the concentration of tumour‐derived TGF‐β was affecting and even suppressing the real TGF‐β expression, favouring tumour proliferation and progression in these cases. VEGF expression was extremely high, demonstrating its angiogenic role in tumour growth, while CXCR4 was decreased, possibly because of CTVT’s low metastatic potential. Thus, we concluded that the tumour microenvironment, together with the immune system of the host, influences CTVT, presumably altering its tumorigenesis and the animal’s clinical response to treatment. 相似文献
15.
B. Dobenecker V. Endres E. Kienzle 《Journal of animal physiology and animal nutrition》2013,97(1):190-196
To ensure an optimal growth is crucial in raising healthy dogs, especially in large and giant breeds. Dogs with a moderate growth velocity tend to have lesser problems with developmental orthopaedic diseases than those with forced or maximum weight gain. In this study, the energy needs of growing dogs from two different breeds (Beagles as a medium‐size breed and Foxhound crossbreds as a large‐size breed) to ensure a growth development as recommended by the National Research Council (NRC) were determined at the age of 6–28 weeks. After weaning at the age of 6 weeks, the food rations sufficient to meet the energy requirements of each individual puppy were adjusted every other day according to growth level, guaranteeing a development consistent with the recommended weight curve for the respective breed size. The food and therefore energy intake of the puppies was registered daily; it ranged from 0.72 to 2.34 times the maintenance requirements with little effect of age. During the whole period, however, there was a consistent breed difference: Foxhound‐Boxer‐Ingelheim Labrador crossbreds (FBIs) had higher energy intakes expressed as multiples of maintenance than Beagles, suggesting that during the major period of growth, the energy requirement is not a function of age. Adult Beagles and FBIs showed similar differences in energy requirements as already during growth as shown in this study. This indicates that breed differences in energy requirements have already to be taken into account during growth. On the other hand, the results showed clearly lower energy needs for growth in these two different breeds than recommended in the NRC. 相似文献
16.
孕激素诱导的生长激素与犬的乳腺肿瘤 总被引:1,自引:0,他引:1
乳腺肿瘤是犬的最常见的肿瘤,约占母犬肿瘤总数的一半;乳腺肿瘤约有一半是恶性肿瘤,发生转移的比率很高。犬乳腺肿瘤的发病原因还不很明确,它的形成都受哪些因子调节还未完全确定。孕激素能够诱导乳腺组织生成并蓄积生长激素,使乳腺增生,最终导致犬乳腺肿瘤的形成。在此过程中,雌激素受体、孕激素受体、生长激素结合蛋白和生长激素受体在乳腺癌的形成、发展中起关键作用。从内分泌的角度对犬乳腺肿瘤发病机理作了简单综述,以期为激素治疗乳腺肿瘤提供一些理论依据。 相似文献
17.
R. Finotello L. Ressel M. Arvigo G. Baroni V. Marchetti G. Romanelli R. Burrow D. Mignacca L. Blackwood 《Veterinary and comparative oncology》2016,14(2):170-180
Insulin‐like growth factor type II (IGF‐II) is the main cause of non‐islet cell tumour hypoglycaemia (NICTH) and insulin is thought to be the only factor causing hypoglycaemia in insulinomas. However, two case reports of pancreatic neuroendocrine tumours (PNETs) producing IGF‐II have been previously published: a human and a canine patient. In this study, we investigated clinical, histopathological, immunohistochemical and ultrastructural features, and biological behaviour of canine pancreatic IGF‐II‐omas, a subgroup of PNETs that has not been previously characterized. Case records of 58 dogs with confirmed PNETs and hypoglycaemia were reviewed: six patients were affected by IGF‐II‐omas. Surgery was performed in all cases and two dogs had metastases. Four patients remained alive and in remission at 370, 440, 560 and 890 days post‐diagnosis; two died of non‐tumour‐related causes. IGF‐II‐omas can be differentiated from insulinomas through hypoinsulinaemia, IGF‐II positive and insulin negative immunostaining. The prevalence of this neoplasia is low, accounting for just 6% of PNETs. 相似文献
18.
E. B. Andreasen O. L. Nielsen M. Tranholm T. Knudsen A. T. Kristensen 《Veterinary and comparative oncology》2016,14(2):191-201
Tissue factor (TF) expression in human cancers has been associated with a procoagulant state and facilitation of metastasis. This study was conducted in order to evaluate if TF was expressed in canine mammary tumours. Forty epithelial mammary tumours from 28 dogs were included. TF expression of the tumours was evaluated by immunohistochemistry using a polyclonal antibody against recombinant canine TF. In addition, thromboelastography, haemostatic and inflammatory parameters were evaluated in the patients. TF was recognized in 44% of benign and 58% of malignant tumours. TF localized to the cytoplasmic membrane of neoplastic luminal epithelial cells and/or diffusely in the cytoplasm. No association was found between TF expression and stage or grade of disease. A significant association between TF expression and antithrombin and plasminogen was found, and extensive TF expression was seen in a lymph node metastasis classified as anaplastic mammary carcinoma from a dog with concomitant disseminated intravascular coagulation (DIC). 相似文献
19.
Median survival times (STs) for doxorubicin‐treated canine lymphoma range from 5.7 to 9 months. Because dogs treated with multi‐agent protocols have longer STs, we sought to evaluate whether adding cyclophosphamide would improve outcome in canine lymphoma patients while maintaining an acceptable level of toxicity. Thirty‐two dogs with stage III–V multicentric lymphoma were treated with doxorubicin every 3 weeks for five total cycles and prednisone at a tapering dose for the first 4 weeks. Dogs were randomized to receive either cyclophosphamide or placebo concurrently. Seventeen dogs received doxorubicin and placebo, while 15 dogs received doxorubicin and cyclophosphamide. Response, toxicity, progression‐free interval (PFI) and ST were evaluated. The combination of doxorubicin and cyclophosphamide was well tolerated, causing no increase in adverse events over doxorubicin alone. Despite a numeric improvement in outcome in cyclophosphamide treated dogs, the addition of cyclophosphamide did not result in statistically improved response rate, PFI or ST. 相似文献
20.
Douglas H. Thamm Kristen M. Weishaar Joseph B. Charles E. J. Ehrhart 《Veterinary and comparative oncology》2020,18(2):169-175
Canine cutaneous mast cell tumour (MCT) is the most common malignant skin tumour in dogs and can exhibit variable biologic behaviour. Dysregulated signalling through the receptor tyrosine kinase (RTK) KIT can promote cell proliferation and survival, and assessment of its dysregulation via detection of activating c‐kit gene mutations or assessment of KIT protein localization is associated with multiple features of malignancy. The aim of the current study was to use a previously validated immunohistochemical (IHC) assay to directly measure phosphorylated KIT (pKIT) in order to investigate its association with other established prognostic markers, response to therapy, progression free interval (PFI) and overall survival time (OST) in dogs treated medically for measurable MCT. Tumour tissue from 74 dogs enrolled in a prospective study comparing toceranib and vinblastine for MCT treatment were evaluated for pKIT immunoreactivity. pKIT was variably expressed, with some degree of positivity observed in 49/74 cases (66%). pKIT immunoreactivity was significantly associated with aberrant KIT localization, high mitotic index and high histologic grade. On univariate analysis, pKIT immunoreactivity predicted shorter PFI and OST in the entire patient population as well as shorter PFI in the toceranib treated group, and was the sole predictive factor for OST upon multivariate analysis, while mitotic index was the sole independent predictive factor for PFI. These results demonstrate that IHC detection of pKIT correlates with several features of aggressive behaviour, and may confer information that is complementary to other prognostic factors. However, the role of pKIT in predicting outcome needs to be studied further before recommendations can be made for its routine use. 相似文献